s3-eu-west-1.amazonaws.com › itempdf...doi.org/10.26434/chemrxiv.12931703.v1 π-Extended Helical...

of 108/108
doi.org/10.26434/chemrxiv.12931703.v1 π-Extended Helical Nanographenes: Synthesis and Photophysical Properties of Naphtho[1,2-a]pyrenes Paban Sitaula, Ryan Malone, Giovanna Longhi, Sergio Abbate, Eva Gualtieri, Andrea Lucotti, Matteo Tommasini, Roberta Franzini, Claudio Villani, Vincent J. Catalano, Wesley Chalifoux Submitted date: 08/09/2020 Posted date: 09/09/2020 Licence: CC BY-NC-ND 4.0 Citation information: Sitaula, Paban; Malone, Ryan; Longhi, Giovanna; Abbate, Sergio; Gualtieri, Eva; Lucotti, Andrea; et al. (2020): π-Extended Helical Nanographenes: Synthesis and Photophysical Properties of Naphtho[1,2-a]pyrenes. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12931703.v1 A mild and efficient synthesis of a broad scope of substituted naphtho[1,2-a]pyrene derivatives was accomplished in good yields using an InCl 3 /AgNTf 2 -mediated two-fold alkyne benzannulation reaction. HPLC enantiomeric separation was achieved and the interconversion barriers have been determined. The ECD spectra of two derivatives were recorded and interpreted through TD-DFT calculations. Raman spectra were also recorded and predicted through DFT calculations. File list (2) download file view on ChemRxiv chalifoux-manuscript-preprint.pdf (1.12 MiB) download file view on ChemRxiv chalifoux-SI-preprint.pdf (6.00 MiB)
  • date post

    30-Jan-2021
  • Category

    Documents

  • view

    1
  • download

    0

Embed Size (px)

Transcript of s3-eu-west-1.amazonaws.com › itempdf...doi.org/10.26434/chemrxiv.12931703.v1 π-Extended Helical...

  • doi.org/10.26434/chemrxiv.12931703.v1

    π-Extended Helical Nanographenes: Synthesis and PhotophysicalProperties of Naphtho[1,2-a]pyrenesPaban Sitaula, Ryan Malone, Giovanna Longhi, Sergio Abbate, Eva Gualtieri, Andrea Lucotti, MatteoTommasini, Roberta Franzini, Claudio Villani, Vincent J. Catalano, Wesley Chalifoux

    Submitted date: 08/09/2020 • Posted date: 09/09/2020Licence: CC BY-NC-ND 4.0Citation information: Sitaula, Paban; Malone, Ryan; Longhi, Giovanna; Abbate, Sergio; Gualtieri, Eva; Lucotti,Andrea; et al. (2020): π-Extended Helical Nanographenes: Synthesis and Photophysical Properties ofNaphtho[1,2-a]pyrenes. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12931703.v1

    A mild and efficient synthesis of a broad scope of substituted naphtho[1,2-a]pyrene derivatives wasaccomplished in good yields using an InCl3/AgNTf2-mediated two-fold alkyne benzannulation reaction. HPLCenantiomeric separation was achieved and the interconversion barriers have been determined. The ECDspectra of two derivatives were recorded and interpreted through TD-DFT calculations. Raman spectra werealso recorded and predicted through DFT calculations.

    File list (2)

    download fileview on ChemRxivchalifoux-manuscript-preprint.pdf (1.12 MiB)

    download fileview on ChemRxivchalifoux-SI-preprint.pdf (6.00 MiB)

    http://doi.org/10.26434/chemrxiv.12931703.v1https://chemrxiv.org/authors/Wesley_Chalifoux/9354782https://chemrxiv.org/ndownloader/files/24615515https://chemrxiv.org/articles/preprint/_-Extended_Helical_Nanographenes_Synthesis_and_Photophysical_Properties_of_Naphtho_1_2-a_pyrenes/12931703/1?file=24615515https://chemrxiv.org/ndownloader/files/24615521https://chemrxiv.org/articles/preprint/_-Extended_Helical_Nanographenes_Synthesis_and_Photophysical_Properties_of_Naphtho_1_2-a_pyrenes/12931703/1?file=24615521

  • π-Extended Helical Nanographenes: Synthesis and Photophysical Properties of

    Naphtho[1,2-a]pyrenes

    Paban Sitaula,† Ryan J. Malone,† Giovanna Longhi,‡ Sergio Abbate,‡ Eva Gualtieri,§

    Andrea Lucotti,§ Matteo Tommasini,§ Roberta Franzini,# Claudio Villani,# Vincent

    J. Catalano,† and Wesley A. Chalifoux*†

    †Department of Chemistry, University of Nevada-Reno, 1664 North Virginia Street, Reno, Nevada 89557, United

    States.

    ‡Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy

    §Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica “G. Natta,” Piazza Leonardo da

    Vinci 32, 20133 Milano, Italy

    #Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Universitá di Roma “La

    Sapienza”, 00185 Roma, Italy

    Abstract: A mild and efficient synthesis of a

    broad scope of substituted

    naphtho[1,2-a]pyrene derivatives

    was accomplished in good yields

    using an InCl3/AgNTf2-mediated

    two-fold alkyne benzannulation

    reaction. HPLC enantiomeric separation was achieved and the interconversion barriers have been

    determined. The ECD spectra of two derivatives were recorded and interpreted through TD-DFT

    calculations. Raman spectra were also recorded and predicted through DFT calculations.

    Introduction:

    Nanographenes are substructures of the graphene and have gained significant interest in the

    physical sciences because of the synthetic challenges they pose as well as their interesting

    structure-property relationships.1 There is a lot of recent interest in using nanographenes in various

    optical and electronic devices.2 Helicenes are an important class of nanographene having ortho-

    fused benzene rings that results in fascinating structures that make them useful variety of

    applications.3 Incorporation of pyrene substructures into helicenes not only results in lateral

    extension of the 𝜋-system but also leads to unique structural as well as photophysical properties.4 Naphtho[1,2-a]pyrenes are examples of small nanographene structures that derive from laterally

    -extended [4]helicenes. There are limited synthetic methods for the synthesis of these pyrene-

    helicene hybrids. Desai and co-workers demonstrated that a Brønsted acid-catalyzed alkene-

    benzannulation reaction could be used for the synthesis of naphtho[1,2-a]pyrene (Figure 1a).5 In

    2020, Alabugin and coworkers synthesized naphtho[1,2-a]pyrenes using an elegant three-point

    double annulation via a radical cascade reaction (Figure 1b).6 This methodology was extended to

    other interesting nanographenes such as naphtho[3,4-a]pyrenes, pyreno[1,2-a]pyrenes, and

    peropyrenes. Methods that incorporate substituents into the cove region of the [4]helicene core has

    also been achieved. For example, Collins and coworkers reported the synthesis of an electron-rich

    cove-substituted naphtho[1,2-a]pyrene using a photoredox flow-chemistry approach (Figure 1c).7

    The same methodology was applicable to the synthesis of -extended [5]helicenes. Our group has

  • been interested in harnessing the potential of high-energy alkyne-containing compounds in multi-

    fold benzannulation reactions to arrive at various achiral8 and chiral nanographenes,8a, 8c, 9 as well

    as soluble graphene nanoribbons.10 For example, we recently reported a Brønsted acid-catalyzed

    four-fold alkyne benzannulation reaction to fuse a second naphthyl group onto a naphtho[1,2-

    a]pyrene core as well as two aryl groups within the cove to arrive at chiral pyreno[a]pyrene-based

    helicene hybrids (Figure 1d).11 We have found that switching from Brønsted acids to Lewis acids

    allows us to synthesize a broader scope of substituted nanographenes.8a, 8c Here, we report the use

    of Lewis acid catalysis for the synthesis of broadly functionalized naphtho[1,2-a]pyrenes (Figure

    1e). The reaction features a double alkyne benzannulation reaction that results in an aryl substituent

    within a newly formed cove region of a [4]helicene. We envisioned that this design feature would

    increase the inversion barrier of the [4]helicene core and allow for enantiomeric separation for

    spectroscopic studies.

    Figure 1: Synthesis of pyrene-helicene hybrids via (a) Brønsted acid catalyzed alkene-benzannulation, (b)

    radical cascade three-point double annulation, (c) photoredox chemistry, (d) Brønsted acid-catalyzed four-

    fold alkyne benzannulations, and (e) Lewis acid catalyzed two-fold alkyne benzannulations (this work).

    Result and discussion:

    Synthesis: Our strategy for the synthesis of naphtho[1,2-a]pyrenes 1 starts with a Suzuki

    crosscoupling reaction between boronic esters 28a, 8c, 8d and 3-bromophenanthrenes 312 to afford

    our key diyne intermediate 4. The diyne was then subjected to a two-fold InCl3/AgNTf2-catalyzed

    alkyne benzannulation reaction8a, 8c to afford the naphtho[1,2-a]pyrene products 1 (Scheme 1). The

    reaction works well with various electron-rich aryl (Ar) groups and R1 as an alkyl group to improve

    solubility (1a-d). Electron withdrawing groups such as R1 = CF3 (1e and 1f) or and ester group

    (1g) resulted in good to excellent yields, respectively. Cyclization of both alkynes on to an

  • electron-rich phenanthrene moiety (4h) worked well to give 1h in good yield. The reaction on an

    electron-poor phenanthrene (4i) to give 1i also worked, albeit with slightly lower yield. We found

    that reactions with less electron-rich aryl groups, such as Ar = 4-tert-butylphenyl and 4-

    chlorophenyl, stalled at the monocyclization products 5 and 6, respectively. Interestingly, the

    alkyne benzannulation reaction occurred regioselectively to give the helical benzo[c]chrysene

    products with the structure of compound 6 being unambiguously confirmed by X-ray

    crystallographic analysis. Cyclization on the more sterically crowded side to produce a new cove

    region, as seen in 5 and 6, has been observed in similar systems.11 It should be noted that carrying

    out the reaction at higher temperatures only resulted in decomposition.

  • Scheme 1: Two-fold alkyne benzannulation reaction yielding naphtho[1,2-a]pyrenes 1a-i and

    monocyclized benzo[c]chrysene products 5 and 6. aCompound 4h was synthesized using an alternate method. See SI for details.

    Chiral Separation: The conformation from the twisted -system in compounds 1a-i, 5, and 6 renders these molecules chiral, and their M-P enantiomers are amenable to HPLC separation,

    provided the enantiomers are separated by a sufficiently high energy barrier. The M-P

    interconversion barriers of the complete set of naphtho[1,2-a]pyrenes 1b-i and of the partially

    cyclized 5 (Scheme 1) were investigated. We used variable temperature dynamic high-

    performance liquid chromatography (DHPLC)13 on a chiral stationary phase (CSP) for the

    determination of the enantiomerization barriers. Preliminary experiments showed that single

    enantiomers of 1b-i and of 5 are prone to racemization at room temperature. However, excellent

    enantioseparations were achieved by lowering the column temperature between 0 °C and 10 °C,

    using a single enantioselective HPLC column packed with an immobilized amylose derivative

    CSP,14 and a single mobile phase consisting of hexane/dichloromethane/methanol 90/10/1. Low-

    temperature HPLC separations of the enantiomers of 1h and 1i using ultraviolet and circular

    dichroism detections clearly demonstrate the enantiomeric relationship of the two species observed

    in each plot, showing equal intensity and opposite chiroptical signals (Figure 2).

    Figure 2. Enantioselective HPLC of 1h (a) and 1i (b) using UV (280 nm, red traces) and CD (300 nm, blue

    traces) detections.

    When the HPLC column temperature was set to 0 °C, little or no on-column interconversion was

    detected for 1b-i and 5, as judged from the absence of a plateau between the resolved peaks. At

    column temperatures between 10 °C and 20 °C, we observed temperature dependent deformations

    of the elution profiles and peak coalescence due to fast on-column M-P enantiomer interconversion

    for the majority of the examined compounds. For compounds 1h, 1i and 5, the dynamic behavior

    was shifted to higher temperatures, with peak coalescence observed between 40 °C and 60 °C (see

    supporting information). We used computer simulation of the exchange broadened chromatograms

    to extract the apparent rate constants for the on-column M-P interconversion process,15 and from

    these values we calculated the corresponding free energy barriers of enantiomerization (Table 1).

  • Compd. k’1[a]

    Tcol = 0 °C

    G‡ (T)[b]

    (kcal/mol)[c]

    T[b]

    (°C)

    1b 0.52 19.39 10

    1c 1.06 19.53 10

    1d 1.19 19.51 10

    1e 0.26 19.61 10

    1f 0.86 19.63 10

    1g 1.92 19.72 10

    1h 0.41 20.48 10

    1i 0.13 21.36 20

    5 0.05 20.04 10

    Table 1: Rate constant and free energy barriers of enantiomerization.

    [a]Retention factor of the 1st eluted enantiomer, defined as (t1-t0)/t0 where t1 is the elution time of the 1st eluted

    enantiomer and t0 is the elution time of a non-retained compound. [b]Column temperature for the DHPLC experiments,

    T ±0.1°C. [c]Gibbs free activation energy for the on-column enantiomerization (conversion of the 1st into the 2nd eluted

    enantiomer) at column temperature T, error ±0.02 kcal/mol.

    The experimental Gibbs free energy of enantiomerization (G‡) for 1b-i and 5 are gathered in

    Table 1, together with the retention factor of the first eluted enantiomer on the CSP. As expected,

    for the structurally similar 1b-i naphtho[1,2-a]pyrene series, enantiomerization barriers span a

    narrow range between 19.39 and 21.36 kcal/mol. The naphtho[1,2-a]pyrenes derived from

    unsubstituted phenanthrene (R2 = H) show interconversion barriers between 19.39 and 19.72

    kcal/mol, that correspond to half-life times between 20 and 30 s at 25 °C. Conversely, 1h and 1i

    (R2 = methoxy and trifluoromethyl, respectively) have slightly higher interconversion energy

    barriers of 20.48 and 21.36 kcal/mol, respectively, and their M-P enantiomers have half-lives in

    the minutes range at 25 °C. Clearly, M-P interconversion barriers in 1b-i are mainly dependent on

    the presence of substituents at the terminal rings of the helix. Remote functionalization at the

    pyrene rings with methyl, tert-butyl, trifluoromethyl or ester groups has no effect on the

    interconversion barrier. The partially cyclized benzo[c]chrysene 5 shows a barrier equal to 20.04

    kcal/mol, suggesting the stereochemical stability of the whole set of compounds is controlled by

    the number of ortho‐condensed rings in the benzo[c]chrysene skeleton, by the size of the group on

    the terminal ring (R2), and by the presence of a substituted aryl ring in the cove region.

    CD spectra and configuration assignment of compounds 1h and 1i: Discrete amounts of the

    single enantiomers of 1h and 1i were obtained by low-temperature HPLC on a semipreparative

    column packed with the same CSP of the analytical separations. Wet fractions containing the

    individual enantiomers were used for the acquisition of their circular dichroism (CD) spectra. For

    these two compounds, comparison between experimental CD spectra and calculated ones is

    possible despite the low racemization barrier, as done for other [5]helicenes that racemize at

    room temperature.16 Calculations have been performed considering on the P-form of compounds

    1h and 1i. Conformational analysis has been conducted considering just the most significant

  • dihedral angles (Scheme SI-3), assuming for simplicity that the aliphatic chains are transplanar

    and also substituting methoxy groups for hexyloxy chains. The orientation of the phenyl group in

    the cove region is dictated by steric hindrance due to the [4]helicene moiety (1 dihedral angle,

    Scheme SI-3), while the phenyl substituent on the opposite side (K region) shows two possible

    orientations. The hexyloxy/methoxy groups also exhibit two different orientations, giving a total

    of eight possible conformers for 1i and sixteen for 1h (due to the two possible conformers of

    methoxy group). Substitution of hexyloxy chains with methoxy groups seems to have a marginal

    influence on the conformer populations. The results of the conformational analysis of the

    compounds with methoxy groups is reported in Table SI-1 and Table SI-2 with the dihedral

    angles of only the significantl

    y populated conformers reported. The reported values refer to IEFPCM calculations in hexane

    and are quite similar to the ones obtained in vacuo.

    For all reported conformers, ECD spectra have been calculated. The phenyl and hexyloxy/methoxy

    orientations have some influence on the calculated ECD spectra, particularly considering the

    higher energy bands. Calculations for all conformers for the solvated case are reported in Figure

    SI-1 and SI-2. Similar effects of substituents on the high energy bands had been already observed

    in other helicene hybrids despite the quite extended and distorted π-system.11 Substitution of

    hexyloxy with methoxy seems to play a minor role on the calculated ECD spectra. The final results

    for the two molecules are reported in Figure 3 after applying a wavelength red-shift as indicated

    in the caption, analogous to the one used with a similar level of calculations. The correspondence

    with the experimental spectra of the first eluted fraction is quite good for the two compounds,

    permitting a safe assignment of the configuration, namely the P form for the two molecules. We

    notice that the succession of band signs is correctly predicted, the lowest energy bands are well

    reproduced and are the ones also showing low sensitivity to conformational changes. We find that

    the wavelength difference among the observed features is better reproduced by the calculations

    based on the presence of solvent (we considered hexane for simplicity). The low sensitivity of the

    lowest energy CD band to the pendant conformation is strictly connected to the laterally extended

    -system in comparison with carbohelicene: in this last case it is well known that the lowest energy

    bands correspond to forbidden transitions,17 a fact that limits their use for optoelectronic

    applications as opposed to the cases with helicene or helicenoid compounds with heteroatoms.18 In the two compounds herein considered, the extended carbon-atom backbone gives rise to dipole

    and rotational strength of the lowest energy transition, which are non-negligible due to the pyrene

    moiety. From the calculations, we conclude that the electric dipole moment of the lowest energy

    transition (HOMO-LUMO) is nearly parallel to the pyrene long axis, while the magnetic dipole

    transition moment forms an angle of about 80°, pointing out of the pyrene plane, which is enough

    to give good rotational strength. In Figure SI-3, one may consider the HOMO and LUMO orbitals

    for the most populated conformer of the two molecules 1h and 1i, which are localized on the

    pyrene-helicene backbone, justifying their sensitivity to configuration.

  • Figure 3. Comparison of calculated and experimental ECD and absorption spectra of compounds

    1h (left) and 1i (right). Calculations have been performed considering all transplanar aliphatic

    chains and methoxy substitution (model compounds) in the gas phase and at the IEFPCM level, in

    all cases a Boltzmann weighted average has been performed. Red-shift has been applied to

    calculated spectra by 40 nm for the gas phase and by 35 nm when implicit solvent model has been

    considered.

    IR and Raman spectroscopy: The analysis of the IR spectra of 1b-i, fostered by DFT

    calculations, reveals several characteristic features that can be associated to the different functional

    groups attached to the helical nanographene core (detailed assignments are provided in Supporting

    Information). Compounds 1b, 1c, 1f, and 1g can be put together in a first group of similar

    molecules (group I) because of their common and extended substructure (i.e., the nanographene

    core functionalized by two p-methoxyphenyl groups). As shown in Figure 4, within group I,

    compounds 1b (R1 = tert-butyl) and 1c (R1 = methyl) display the most similar IR spectra. This is

    expected based on the structure similarity between the tert-butyl and the methyl group. The former

    can be roughly seen as the union of three methyl groups. Like the common pattern of the IR spectra

    of 1b and 1c, in the spectra of 1g (R1 = ethyl ester) and 1f (R1 = trifluoromethyl) one can spot

    characteristic bands which, supported by DFT calculations, we can associate to the specific R1

    functional groups. For instance, the C=O stretching band (box 1 in Figure 4) is evidence of the

    ethyl ester functionalization of 1g. The peaks belonging to boxes 6, 11 and 15 in Figure 4 are

    evidence of the trifluoromethyl functionalization of 1e and 1f (which bears the same R1

  • functionalization). Remarkably, the different position of the trifluoromethyl group in the helical

    nanographenes produces different patterns in the IR spectra (Figure 4, box 6 and 7): R1 substitution

    (1e, 1f) is associated to IR signals in box 6, whereas R3 substitution (1i) is associated to IR signals

    in box 7.

    The markers of the methoxy functional group are found in boxes 12 and 13 (Figure 4) and are

    assigned by DFT calculations to CO stretching. Compounds 1e, 1h and 1i (all bearing R2 =

    hexyloxy functionalities) show broad features in the same region as boxes 12 and 13, which DFT

    calculations assign to several normal modes involving CO stretching and hexyl CC stretching. The

    broadening observed in the experimental spectra can be ascribed to conformational effects of the

    alkyl chains (not accounted for in present DFT simulations of the vibrational spectra).

    The markers of the phenyl functional groups are found in the regions highlighted by boxes 3, 5, 9

    and 10 (Figure 4). The CO stretching vibrations from the alkoxy groups couple with phenyl

    vibrations in the region highlighted by box 9 in Figure 4. The naphthyl functionalization of

    compound 1d is evidenced by the markers observed in the regions labelled by 2, 4, and 8. Similarly

    to modes in box 9, in box 8 the vibrations of naphthyl groups are coupled with those of the methoxy

    functional group, as well as contributions of tert-butyl R1 group. Collective CC stretching

    vibrations, coupled with in-plane CH bending vibrations of naphthyl and phenyl are assigned to

    boxes 2 and 3. The IR bands found in region 4 involve both naphthyl and tert-butyl groups (see

    Supporting Information for details).

    Methyl bending modes are found in the region between 1490 and 1360 cm-1, but they do not yield

    evident IR signals (group I compounds exhibit the antisymmetric methyl bending at ~1464 cm-1,

    and the umbrella (symmetric) bending at ~1440 cm-1). CH2 scissoring in 1g (R1 = ethyl ester), and

    1e, 1h, and 1i (bearing hexyl groups), is found roughly in the same region as the methyl

    antisymmetric bending. CH2 wagging is found in the same molecules between 1425 and 1100 cm-

    1, whereas CH2 twisting is found between 1305 and 1240 cm-1. As expected, CH2 rocking modes

    are found at lower wavenumber, in the out-of-plane bending region. Since their signal is quite

    weak, it is difficult to assign them to any experimental feature of the IR spectra.

    Finally, we found a series of collective out-of-plane CH bending markers in the region highlighted

    by box 14 (Figure 4). These bands form a pattern which is remarkably similar across the series of

    compounds 1b, 1c, 1e, 1f and 1g. This is because such molecules share the same topology of CH

    bonds at the edge of the helical nanographene core. Interestingly, 1h and 1i deviate slightly from

    the previous pattern because of their functionalization at the tail of the nanographene core (R3). As

    expected, the naphthyl groups on compound 1d add significant signals in this wavenumber region,

    so that the pattern of the IR spectrum changes quite dramatically.

    Interestingly, as documented by the tables found in Supporting Information, it is not possible to

    find a single IR marker of the nanographene core. The vibrations of this part of the molecule are

    always coupled with vibrations of the functional groups. Essentially, only the CH out-of-plane

    wavenumber region can be considered, as a whole, a fingerprint of the nanographene shape.

  • Figure 4. The experimental micro FT-IR spectra of compounds 1b-i across the fingerprint region.

    The contributions from specific functional groups are highlighted with numbered boxes (see text).

    With Raman spectroscopy, the situation is quite different. The comparison of Figure 5 with Figure

    4 highlights the complementarity of IR and Raman: the expected G and D bands of such

    nanographenes are markers of the structure of the extended π-conjugated core. We do not observe

    obvious Raman markers of the functional groups, with the only exception of the weak CO

    stretching feature observed for compound 1g (slightly above 1700 cm-1, Figure 5). However, the

    pattern of the G band and the position of the D peak are remarkably sensitive to the functional

    groups attached to the nanographene core. Compounds 1b and 1c essentially share the same

    substituents [the difference between a tert-butyl (1b) and methyl (1c) substituent is not much from

    the point of view of the effect on π-conjugation]. By consequence, the position of the D peak in

    the two compounds is essentially the same (1314 cm-1) as is the pattern of the G band. Compared

    with 1b and 1c, the ethyl-ester substituent of 1g very slightly changes the pattern of the G band

    and the position of the D peak (1317 cm-1). Compounds 1e and 1f share the trifluoromethyl

    functionalization at R1, and the p-methoxy-phenyl/p-hexyloxy-phenyl functionalization at R2 has

    the same influence on π-conjugation. Therefore, as expected, 1e and 1f exhibit the same G band

    pattern and the same position of the D peak (1321 cm-1). The Raman spectra of 1h and 1i are rather

    close, from which we infer that the inductive effect caused by the methoxy and trifluoromethyl R3

    substituents on the nanographene core are rather close. This observation is consistent with the

    similarity of the position of the π-π* electronic transitions of 1h and 1i (see CD spectroscopy

    section). Finally, the G and D band of compound 1d appear significantly different from the

    previous compounds given the sizeable contributions from the π-conjugated naphthyl substituents

    to the Raman spectrum.

  • Figure 5. The experimental micro FT-Raman spectra of compounds 1b-i across the G and D-band

    regions. The grey boxes identify similar patterns and positions of the G and D bands (see text).

    Conclusion:

    In summary, we have developed a successful and efficient synthesis of functionalized

    naphtho[1,2-a]pyrenes by utilizing a two-fold alkyne benzannulation reaction. The reaction is

    catalyzed by a mixture of indium chloride and silver bistriflimide to afford the products in

    moderate to excellent yields. The separation of enantiomers can be done at low temperatures and

    analysis of the enantiomerization process shows a higher barrier than regular [4]helicenes. This

    is due to steric repulsion in the cove region due to substitution. Adding substituents to the

    backbone of the nanographene, near the cove region, further increases the inversion barrier of

    these molecules and could serve as a design element to arrive at persistently chiral [4]helicene-

    like nanographenes. The lifetime of the enantiopure substrates is long enough to allow for

    analysis by CD spectroscopy. The ECD spectra were consistent with calculated values, which

    assisted in the assignment of absolute stereochemistry. Functionality around the nanographene

    core is discernable by IR spectroscopy while Raman spectroscopy serves as a great

    complimentary tool for looking at the extended π-conjugated backbone structure. Further studies

    on extending this methodology to the synthesis of larger π-extended helicene-like structures is

    ongoing in our lab.

    Acknowledgements

  • Research was carried out with the support of resources of Big&Open Data Innovation Laboratory (BODaI-Lab), University of Brescia, granted by Fondazione Cariplo and Regione Lombardia and of Computing Center CINECA (Bologna), Italy. Support from the Italian MIUR (PRIN 2017, project “Physico-chemical Heuristic Approaches: Nanoscale Theory of Molecular Spectroscopy” (PHANTOMS), prot. 2017A4XRCA) is acknowledged. M.T., E.G., A.L. acknowledges that this research was partly funded by the Italian Ministry of Education, University and Research (MIUR) through the PRIN 2017 program (Project No. 2017PJ5XXX “Magic Dust”); part of this work was realized at the ‘CD Lab’, which is an inter-Departmental laboratory financed and supported by the Politecnico di Milano. W.A.C. acknowledges the National Science Foundation for supporting this work through a CAREER Award (CHE-1555218).

    References:

    1. (a) Narita, A.; Wang, X.-Y.; Feng, X.; Müllen, K., New advances in nanographene chemistry.

    Chem. Soc. Rev. 2015, 44, 6616; (b) Magiera, K. M.; Aryal, V.; Chalifoux, W. A., Alkyne

    benzannulations in the preparation of contorted nanographenes. Org. Biomol. Chem. 2020, 18,

    2372; (c) Senese, A. D.; Chalifoux, W. A., Nanographene and Graphene Nanoribbon Synthesis

    via Alkyne Benzannulations. Molecules 2018, 24, 118; (d) Muzammil, E. M.; Halilovic, D.;

    Stuparu, M. C., Synthesis of corannulene-based nanographenes. Commun. Chem. 2019, 2, 58.

    2. (a) Wu, J.; Pisula, W.; Müllen, K., Graphenes as Potential Material for Electronics. Chem. Rev.

    2007, 107, 718; (b) Mei, J.; Diao, Y.; Appleton, A. L.; Fang, L.; Bao, Z., Integrated Materials

    Design of Organic Semiconductors for Field-Effect Transistors. J. Am. Chem. Soc. 2013, 135,

    6724; (c) Sergeyev, S.; Pisula, W.; Geerts, Y. H., Discotic liquid crystals: a new generation of

    organic semiconductors. Chem. Soc. Rev. 2007, 36, 1902; (d) Ball, M.; Zhong, Y.; Wu, Y.;

    Schenck, C.; Ng, F.; Steigerwald, M.; Xiao, S.; Nuckolls, C., Contorted Polycyclic Aromatics.

    Acc. Chem. Res. 2015, 48, 267.

    3. (a) Shen, Y.; Chen, C.-F., Helicenes: Synthesis and Applications. Chem. Rev. 2012, 112, 1463;

    (b) Gingras, M., One hundred years of helicene chemistry. Part 1: non-stereoselective syntheses

    of carbohelicenes. Chem. Soc. Rev. 2013, 42, 968; (c) Gingras, M.; Félix, G.; Peresutti, R., One

    hundred years of helicene chemistry. Part 2: stereoselective syntheses and chiral separations of

    carbohelicenes. Chem. Soc. Rev. 2013, 42, 1007; (d) Gingras, M., One hundred years of helicene

    chemistry. Part 3: applications and properties of carbohelicenes. Chem. Soc. Rev. 2013, 42, 1051.

    4. (a) Hu, Y.; Paternò, G. M.; Wang, X.-Y.; Wang, X.-C.; Guizzardi, M.; Chen, Q.; Schollmeyer,

    D.; Cao, X.-Y.; Cerullo, G.; Scotognella, F.; Müllen, K.; Narita, A., π-Extended Pyrene-Fused

    Double [7]Carbohelicene as a Chiral Polycyclic Aromatic Hydrocarbon. J. Am. Chem. Soc. 2019,

    141, 12797; (b) Buchta, M.; Rybáček, J.; Jančařík, A.; Kudale, A. A.; Buděšínský, M.;

    Chocholoušová, J. V.; Vacek, J.; Bednárová, L.; Císařová, I.; Bodwell, G. J.; Starý, I.; Stará, I. G.,

    Chimerical Pyrene-Based [7]Helicenes as Twisted Polycondensed Aromatics. Chem. Eur. J. 2015,

    21, 8910.

    5. (a) Desai, D.; Sharma, A. K.; Lin, J.-M.; Krzeminski, J.; Pimentel, M.; El-Bayoumy, K.;

    Nesnow, S.; Amin, S., Synthesis, in Vitro Metabolism, Cell Transformation, Mutagenicity, and

    DNA Adduction of Dibenzo[c,mno]chrysene. Chem. Res. Toxicol. 2002, 15, 964; (b) Sharma, A.

    K.; Krzeminski, J.; Desai, D.; Amin, S., Synthesis of Dihydrodiol Metabolites of Naphtho[8,1,2-

    GHI]Chrysene and Dibenzo[C,MNO]Chrysene. Polycyclic Aromat. Compd. 2003, 23, 297.

    6. Kawade, R .K.; Hu, C.; Dos Santos, N. R.; Watson, N.; Lin, X.; Hanson, K.; Alabugin, I.,

    Phenalenannulations: Three‐Point Double Annulation Reactions that Convert Benzenes into

    Pyrenes. Angew. Chem. Int. Ed. 2020, Accepted Author Manuscript, doi:10.1002/anie.202006087.

  • 7. Bédard, A.-C.; Vlassova, A.; Hernandez-Perez, A. C.; Bessette, A.; Hanan, G. S.; Heuft, M. A.;

    Collins, S. K., Synthesis, Crystal Structure and Photophysical Properties of Pyrene–Helicene

    Hybrids. Chem. Eur. J. 2013, 19, 16295.

    8. (a) Yang, W.; Bam, R.; Catalano, V. J.; Chalifoux, W. A., Highly Regioselective Domino

    Benzannulation Reaction of Buta-1,3-diynes To Construct Irregular Nanographenes. Angew.

    Chem. Int. Ed. 2018, 57, 14773; (b) Yang, W.; Chalifoux, W. A., Rapid π-Extension of Aromatics

    via Alkyne Benzannulations. Synlett 2017, 28, 625; (c) Yang, W.; Kazemi, R. R.; Karunathilake,

    N.; Catalano, V. J.; Alpuche-Aviles, M. A.; Chalifoux, W. A., Expanding the scope of peropyrenes

    and teropyrenes through a facile InCl3-catalyzed multifold alkyne benzannulation. Org. Chem.

    Front. 2018, 5, 2288; (d) Yang, W.; Monteiro, J. H. S. K.; de Bettencourt-Dias, A.; Catalano, V.

    J.; Chalifoux, W. A., Pyrenes, Peropyrenes, and Teropyrenes: Synthesis, Structures, and

    Photophysical Properties. Angew. Chem. Int. Ed. 2016, 55, 10427; (e) Yang, W.; Monteiro, J. H.

    S. K.; de Bettencourt-Dias, A.; Catalano, V. J.; Chalifoux, W. A., Synthesis, Structure,

    Photophysical Properties, and Photostability of Benzodipyrenes. Chem. Eur. J. 2019, 25, 1441; (f)

    Yang, W.; Monteiro, J. H. S. K.; de Bettencourt-Dias, A.; Chalifoux, W. A., New thiophene-

    functionalized pyrene, peropyrene, and teropyrene via a two- or four-fold alkyne annulation and

    their photophysical properties. Can. J. Chem. 2016, 95, 341.

    9. Yang, W.; Longhi, G.; Abbate, S.; Lucotti, A.; Tommasini, M.; Villani, C.; Catalano, V. J.;

    Lykhin, A. O.; Varganov, S. A.; Chalifoux, W. A., Chiral Peropyrene: Synthesis, Structure, and

    Properties. J. Am. Chem. Soc. 2017, 139, 13102.

    10. Yang, W.; Lucotti, A.; Tommasini, M.; Chalifoux, W. A., Bottom-Up Synthesis of Soluble

    and Narrow Graphene Nanoribbons Using Alkyne Benzannulations. J. Am. Chem. Soc. 2016, 138,

    9137.

    11. Bam, R.; Yang, W.; Longhi, G.; Abbate, S.; Lucotti, A.; Tommasini, M.; Franzini, R.; Villani,

    C.; Catalano, V. J.; Olmstead, M. M.; Chalifoux, W. A., Four-Fold Alkyne Benzannulation:

    Synthesis, Properties, and Structure of Pyreno[a]pyrene-Based Helicene Hybrids. Org. Lett. 2019,

    21, 8652.

    12. (a) Mallory, F. B.; Mallory, C. W., Photocyclization of stilbenes. VII. Unusual fluorine atom

    rearrangement in the photocyclization of 1-fluoro [5] helicenes. J. Org. Chem. 1983, 48, 526; (b)

    Talele, H. R.; Gohil, M. J.; Bedekar, A. V., Synthesis of Derivatives of Phenanthrene and Helicene

    by Improved Procedures of Photocyclization of Stilbenes. Bull. Chem. Soc. Jpn. 2009, 82, 1182.

    13. (a) Casarini, D.; Lunazzi, L.; Alcaro, S.; Gasparrini, F.; Villani, C., Atropisomerism in

    Hindered Naphthyl Sulfones Investigated by Dynamic NMR and Dynamic HPLC Techniques. J.

    Org. Chem. 1995, 60, 5515; (b) Villani, C.; Pirkle, W. H., Chromatographic resolution of the

    interconverting stereoisomers of hindered sulfinyl and sulfonyl naphthalene derivatives.

    Tetrahedron: Asymmetry 1995, 6, 27; (c) D’Acquarica, I.; Gasparrini, F.; Pierini, M.; Villani, C.;

    Zappia, G., Dynamic HPLC on chiral stationary phases: A powerful tool for the investigation of

    stereomutation processes. J. Sep. Sci. 2006, 29, 1508; (d) Trapp, O.; Schurig, V., Stereointegrity

    of Tröger's Base:  Gas-Chromatographic Determination of the Enantiomerization Barrier. J. Am.

    Chem. Soc. 2000, 122, 1424; (e) Maier, F.; Trapp, O., Effects of the Stationary Phase and the

    Solvent on the Stereodynamics of biphep Ligands Quantified by Dynamic Three‐Column HPLC.

    Angew. Chem. Int. Ed. Engl. 2012, 51, 2985; (f) Mortera Levi, S.; Sabia, R.; Pierini, M.;

    Gasparrini, F.; Villani, C., The dynamic chromatographic behavior of tri-o-thymotide on HPLC

    chiral stationary phases. Chem. Commun. 2012, 48, 3167; (g) Trapp, O., Interconversion of

    stereochemically labile enantiomers (enantiomerization). Topics in Current Chemistry 2013, 341,

    231; (h) Sabia, R.; Ciogli, A.; Pierini, M.; Gasparrini, F.; Villani, C., Dynamic high performance

  • liquid chromatography on chiral stationary phases. Low temperature separation of the

    interconverting enantiomers of diazepam, flunitrazepam, prazepam and tetrazepam. J.

    Chromatogr A 2014, 1362, 144; (i) Viglianisi, C.; Biagioli, C.; Lippi, M.; Pedicini, M.; Villani,

    C.; Franzini, R.; Menichetti, S., Synthesis of Heterohelicenes by a Catalytic Multi‐Component

    Povarov Reaction. Eur. J. Org. Chem. 2019, 164.

    14. Zhang, T.; Kientzy, C.; Franco, P.; Ohnishi, A.; Kagamihara, Y.; Kurosawa, H., Solvent

    versatility of immobilized 3,5-dimethylphenylcarbamate of amylose in enantiomeric separations

    by HPLC. J. Chromatogr. A, 2005, 1075, 65.

    15. (a) Schurig, V., Contributions to the theory and practice of the chromatographic separation of

    enantiomers. Chirality 2005, 17, S205; (b) Wolf, C., Stereolabile chiral compounds: analysis by

    dynamic chromatography and stopped-flow methods. Chem. Soc. Rev. 2005, 34, 595; (c) Trapp,

    O., Unified Equation for Access to Rate Constants of First-Order Reactions in Dynamic and On-

    Column Reaction Chromatography. Anal. Chem. 2006, 78, 189; (d) Trapp, O., A novel software

    tool for high throughput measurements of interconversion barriers: DCXplorer. J. Chromatogr. B,

    2008, 875, 42; (e) Cirilli, R.; Costi, R.; Di Santo, R.; La Torre, F.; Pierini, M.; Siani G., Perturbing

    Effects of Chiral Stationary Phase on Enantiomerization Second-Order Rate Constants Determined

    by Enantioselective Dynamic High-Performance Liquid Chromatography: A Practical Tool to

    Quantify the Accessible Acid and Basic Catalytic Sites Bonded on Chromatographic Supports.

    Anal. Chem. 2009, 81, 3560.

    16. (a) Lebon, F.; Longhi, G.; Gangemi, F.; Abbate, S.; Priess, J.; Juza, M.; Bazzini, C.; Caronna,

    T.; Mele, A., Chiroptical Properties of Some Monoazapentahelicenes. J. Phys. Chem. A 2004, 108,

    11752; (b) Abbate, S.; Bazzini, C.; Caronna, T.; Fontana, F.; Gangemi, F.; Lebon, F.; Longhi, G.;

    Mele, A.; Natali Sora, I., Experimental and Calculated Circular Dichroism Spectra of

    Monoaza[5]helicenes. Inorg. Chim. Acta 2007, 360, 908.

    17. (a) Weigang, O. E. Jr.; Turner, J. A.; Trouard, P. A., Emission Polarization and Circular

    Dichroism of Hexahelicene. J. Chem. Phys. 1966, 45, 1126; (b) Nakai, Y.; Mori, T.; Inoue, Y.,

    Theoretical and Experimental Studies on Circular Dichroism of Carbo[n]helicenes. J. Phys. Chem.

    A 2012, 116, 7372; (c) Abbate, S., Longhi, G., Lebon, F., Castiglioni, E., Superchi, S., Pisani, L.,

    Fontana, F., Torricelli, F., Caronna, T., Villani, C., Sabia, R., Tommasini, M., Lucotti, A.,

    Mendola, D., Mele, A., Lightner, D. A., Helical sense-responsive and substituent-sensitive features

    in vibrational and electronic circular dichroism, in circularly polarized luminescence and in Raman

    spectra of some simple optically active hexahelicenes. J. Phys. Chem. C 2014, 118, 1682; (d) Liu,

    Y., Cerezo, J., Mazzeo, G., Lin, N., Zhao, X., Longhi, G., Abbate, S., Santoro, F., Vibronic

    coupling explains the different aspect of electronic circular dichroism and of circularly polarized

    luminescence spectra of hexahelicenes. J. Chem. Theor. Comput. 2016, 12, 2799.

    18. Dhbaibi, K., Favereau, L., Crassous. J., Enantioenriched Helicenes and Helicenoids Containing

    Main-Group Elements (B, Si, N, P). Chem. Rev. 2019, 119, 8846.

  • download fileview on ChemRxivchalifoux-manuscript-preprint.pdf (1.12 MiB)

    https://chemrxiv.org/ndownloader/files/24615515https://chemrxiv.org/articles/preprint/_-Extended_Helical_Nanographenes_Synthesis_and_Photophysical_Properties_of_Naphtho_1_2-a_pyrenes/12931703/1?file=24615515

  • Supporting Information for

    π-Extended Helical Nanographenes: Synthesis and Photophysical

    Properties of Naphtho[1,2-a]pyrenes

    Paban Sitaula,† Ryan J. Malone,† Giovanna Longhi,‡ Sergio Abbate,‡ Eva Gualtieri,§

    Andrea Lucotti,§ Matteo Tommasini,§ Roberta Franzini,# Claudio Villani,# Vincent

    J. Catalano,† and Wesley A. Chalifoux*†

    †Department of Chemistry, University of Nevada-Reno, 1664 North Virginia Street, Reno, Nevada 89557, United

    States.

    ‡Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy

    §Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica “G. Natta,” Piazza Leonardo da

    Vinci 32, 20133 Milano, Italy

    #Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Universitá di Roma “La

    Sapienza”, 00185 Roma, Italy

    Table of content

    1. General experimental section………………………………………………………….. 2. Synthesis and characterization…………………………………………………………. 3. Chromatographic HPLC separations and dynamic HPLC experiments……………….. 4. Computational details for compounds 1h and 1i……………………………………….. 5. FTIR and Raman spectroscopy………………………………………………………… 6. References……………………………………………………………………………… 7. X-ray structure of compound 6…………………………………….. 8. Crystal parameters and refinement metrics of compound 6………………………..

    9. 1HNMR and 13CNMR spectra of new compounds……………………………………..

  • 1. General experimental:

    All reactions dealing with air- or moisture-sensitive compounds were carried out in a dry reaction

    vessel under nitrogen. All reagents and solvents were commercially obtained and used without prior

    purification, unless otherwise noted. Anhydrous toluene and tetrahydrofuran (THF) were obtained

    by passing the solvent (HPLC grade) through an activated alumina column on a PureSolv MD 5

    solvent drying system. 1H and 13C NMR spectra were recorded on Varian 400 MHz or Varian 500

    MHz NMR Systems Spectrometers. Spectra were recorded in deuterated chloroform (CDCl3).

    Chemical shifts are reported in parts per million (ppm) relative to the solvent residual peak (7.26

    ppm for 1H and 77.16 ppm for 13C NMR, respectively). Coupling constants (J) are reported in Hz.

    The multiplicity of 1H signals are indicated as: s = singlet, d = doublet, t = triplet, m = multiplet.

    High resolution ESI/APPI mass spectrometry was recorded using an Agilent 6230 TOF MS. TLC

    information was recorded on Silica gel 60 F254 glass plates. Purification of reaction products was

    carried out by flash chromatography using Silica Gel 60 (230-400 mesh). A suitable crystal was

    mounted on a glass fiber and placed in the low-temperature nitrogen stream. Data was collected

    on a Bruker Apex CCD area detector diffractometer equipped with a low-temperature device,

    using graphite-mono-chromated Mo K radiation (λ= 0.71073 Å) and a full sphere of data was

    collected. Integration, data reduction and scaling were carried out with the programs SAINT and

    SADABS1 in the Bruker APEX32 suite of software. The structure was solved using intrinsic

    phasing methods and refined using full‐matrix least‐squares refinement using SHELXL.3,4

    Compounds S2abj and 2abj were synthesized using known procedures.5,6

  • 2. Synthesis and characterization:

    S2c: To the solution of 1-bromo-4-methyl-2,5-diiodobenzene (2.22 g, 5.26 mmol) and 4-methoxy-

    1-ethynylbenzene (1.73 g, 13.1 mmol) in Et3N (30 mL) and THF (80 mL) were added Pd(PPh3)2Cl2

    (369 mg, 0.525 mmol) and CuI (200 mg, 1.05 mmol). The resulting mixture was stirred under a

    N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration.

    The solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane 2:3) to afford 1.50 g (66%) of S2c. Rf = 0.32

    (DCM:hexane, 2:3); FTIR (neat) 2964, 2933, 2837, 2209, 1604, 1508, 1245 cm-1; 1H NMR (400

    MHz, CDCl3) δ 7.57 – 7.51 (m, 4H), 7.30 (s, 2H), 6.93 – 6.87 (m, 4H), 3.82 (s, 6H), 2.29 (s, 3H);

    13C NMR (400 MHz, CDCl3) δ 160.0, 136.8, 133.3, 133.0, 126.3, 124.9, 115.1, 114.1, 93.9, 87.2,

    55.4, 20.7; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for [C25H19BrO2Na]+ 453.0461, found

    453.0426.

  • S2e: To the solution of 1-bromo-2,5-diiodo-4-(trifluoromethyl)benzene (6.00 g, 12.6 mmol) and

    4-hexyloxy-1-ethynylbenzene (6.36 g, 31.4 mmol) in Et3N (30 mL) and THF (80 mL) were added

    Pd(PPh3)2Cl2 (885 mg, 1.26 mmol) and CuI (480 mg, 2.52 mmol). The resulting mixture was stirred

    under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by

    filtration. The solvent was removed under reduced pressure and the residue was purified by

    column chromatography (silica gel, DCM:hexane 1:3) to afford 7.10 g (90%) of S2e. Rf = 0.41

    (DCM:hexane, 1:4); FTIR (neat) 2839, 2263, 1605, 1571, 1510 cm–1; 1H NMR (400 MHz, CDCl3) δ

    7.67 (s, 2H), 7.55 – 7.50 (m, 4H), 6.93 – 6.86 (m, 4H), 3.99 (t, J = 6.6 Hz, 4H), 1.85 – 1.75 (m, 4H),

    1.52 – 1.42 (m, 4H), 1.40 – 1.30 (m, 8H), 0.95 – 0.88 (m, 6H); 13C NMR (400 MHz, CDCl3) δ 160.2,

    133.5, 131.7, 129.8 (q, 2J(C, F) = 33.6 Hz), 128.2 (q, 1J(C, F) = 3.5 Hz), 127.8, 123.4 (q, 3J(C, F) =

    272.4 Hz), 114.8, 114.1, 96.2, 86.1, 68.3, 31.7, 29.3, 25.8, 22.7, 14.2; HRMS (ESI-TOF) m/z:

    [M+Na]+ for [C35H36BrF3O2Na]+ 647.1743, found 647.1774.

    S2f: To the solution of 2-bromo-1,3-diiodo-5-(trifluoromethyl)benzene (4.00 g, 8.39 mmol) and

    4-methoxy-1-ethynylbenzene (2.22 g, 16.8 mmol) in Et3N (30 mL) and THF (80 mL), were added

    Pd(PPh3)2Cl2 (589 mg, 0.84 mmol) and CuI (320 mg, 1.68 mmol). The resulting mixture was

    stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed

  • by filtration. The solvent was removed under reduced pressure and the residue was purified by

    column chromatography (silica gel, DCM:hexane, 1:3) to afford 2.84 g (70%) of the product S2f.

    Rf = 0.31 (DCM:hexane, 1:3); FTIR (neat) 2839, 2215, 1605, 1510 cm–1; 1H NMR (400 MHz,

    CDCl3) δ 7.67 (s, 2H), 7.57 – 7.52 (m, 4H), 6.94 – 6.89 (m, 4H), 3.85 (s, 6H); 13C NMR (400 MHz,

    CDCl3) δ 160.5, 133.6, 131.7, 129.8 (q, J = 33.4 Hz), 128.2 (q, J = 3.8 Hz), 127.8, 123.4 (q, J =

    272.8 Hz), 114.4, 114.3, 96.1, 86.2, 55.5; HRMS (ESI-TOF) m/z: [M+H]+ calcd for

    [C25H17BrF3O2]+ 485.0359, found 485.0114.

    S2g: To the solution of ethyl-(2-bromo-3,5-diiodo)benzoate (2.00 g, 4.42 mmol) and 4-methoxy-

    1-ethynylbenzene (1.37 g, 10.4 mmol) in Et3N (30 mL) and THF (80 mL), were added

    Pd(PPh3)2Cl2 (146 mg, 0.208 mmol) and CuI (79 mg, 0.42 mmol). The resulting mixture was

    stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed

    by filtration. The solvent was removed under reduced pressure and the residue was purified by

    column chromatography (silica gel, DCM:hexane, 1:2) to afford 1.29 g (63%) of the product S2g.

    Rf = 0.41 (DCM:hexane, 1:2); FTIR (neat) 3070, 2959, 2836, 2209, 1718, 1603 cm–1; 1H NMR

    (500 MHz, CDCl3) δ 8.08 (s, 2H), 7.56 – 7.52 (m, 4H), 6.92 – 6.87 (m, 4H), 4.38 (q, J = 7.1 Hz,

    2H), 3.82 (s, 6H), 1.41 (t, J = 7.2 Hz, 3H); 13C NMR (500 MHz, CDCl3) δ 165.0, 160.3, 133.4,

    132.8, 132.5, 129.5, 127.1, 114.6, 114.2, 95.2, 86.5, 61.6, 55.4, 14.4; HRMS (ESI-TOF) m/z:

    [M+Na]+ for [C27H21BrO4Na]+ 511.0515, found 511.0494.

  • S2k: To the solution of 1-bromo-4-(t-butyl)-2,5-diiodobenzene (3.00 g, 6.45 mmol) and 4-chloro-

    1-ethynylbenzene (2.20 g, 16.1 mmol) in Et3N (30 mL) and THF (80 mL), were added

    Pd(PPh3)2Cl2 (453 mg, 0.645 mmol) and CuI (246 mg, 1.29 mmol). The resulting mixture was

    stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed

    by filtration. The solvent was removed under reduced pressure and the residue was purified by

    column chromatography (silica gel, hexane) to afford 2.21 g (71%) of the product S2k. Rf = 0.55

    (hexane); FTIR (neat) 2961, 2868, 2214, 1563, 1488 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.55 –

    7.51 (m, 6H), 7.37 – 7.33 (m, 4H), 1.34 (s, 9H) ppm. 13C NMR (400 MHz, CDCl3) δ 150.5, 134.9,

    133.1, 130.5, 128.9, 125.7, 125.4, 121.5, 92.5, 89.5, 34.8, 31.1 ppm. HRMS (ESI-TOF) m/z:

    [M+Na]+ calcd for [C26H19BrCl2Na]+ 502.9939, found 502.9938.

    2c: To a solution of S2c (1.10 g, 2.55 mmol) in THF (120 mL) at -78 °C was added a solution of

    n-butyllithium in hexanes (1.3 mL, 2.5 M, 3.12 mmol). After stirring for 1 h at -78 °C,

    isopropoxyboronic acid pinacol ester (712 mg, 3.82 mmol) was added, the reaction was removed

    from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was

    quenched by the addition of H2O, and then extracted with DCM. The extract was washed with

    water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash

    column chromatography (silica gel, DCM:hexane, 1:1) and yielded 485 mg (40%) of 2c as a white

    solid. Rf = 0.46 (DCM:hexane, 1:1); FTIR (neat) 2980, 2253, 1605, 1509 cm–1; 1H NMR (400

    MHz, CDCl3) δ 7.47 – 7.42 (m, 4H), 7.29 (s, 2H), 6.88 – 6.84 (m, 4H), 3.82 (s, 6H), 2.31 (s, 3H),

  • 1.37 (s, 12H); 13C NMR (400 MHz, CDCl3) δ 159.7, 139.0, 133.1, 132.2, 127.1, 115.8, 114.1, 90.2,

    88.6, 84.3, 55.4, 25.1, 21.2; HRMS (ESI-TOF) m/z: [M+H]+ for [C31H32BO4]+ 479.2394, found

    479.2399.

    2d: To a solution of S2d (774 mg, 1.35 mmol) in THF (60 mL) at -78 °C was added a solution of

    n-butyllithium in hexanes (0.65 mL, 2.5 M, 1.62 mmol). After stirring for 1 hour at -78 °C,

    isopropoxyboronic acid pinacol ester (400 mg, 2.15 mmol) was added, the reaction was removed

    from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was

    quenched by the addition of H2O, and then extracted with DCM. The extract was washed with

    water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash

    column chromatography (silica gel, DCM:hexane, 1:1) and yielded 600 mg (72%) of 2d as a

    reddish-yellow solid. Rf = 0.30 (DCM:hexane, 1:1); FTIR (neat) 2964, 2202, 1628, 1600 cm–1; 1H

    NMR (500 MHz, CDCl3) δ 7.99 (s, 2H), 7.72 (d, J = 5.6 Hz, 2H), 7.70 (d, J = 4.8 Hz, 2H), 7.57

    (s, 2H), 7.56 (d, J = 8.4, 1.7 Hz, 2H), 7.17 (dd, J = 8.9, 2.5 Hz, 2H), 7.13 (d, J = 2.5 Hz, 2H), 3.94

    (s, 6H), 1.39 (s, 12H), 1.35 (s, 9H); 13C NMR (500 MHz, CDCl3) δ 158.5, 152.5, 134.2, 131.4,

    129.5, 129.2, 129.1, 128.7, 126.9, 126.8, 119.5, 118.6, 106.0, 90.5, 90.0, 84.4, 55.5, 34.8, 31.2,

    25.2 (one peak not detected due to coincidental overlap); HRMS (ESI-TOF) m/z: [M+H]+ calcd

    for [C42H42BO4]+ 621.3171, found 621.3181.

  • 2e: To a solution of S2e (2.00 g, 3.19 mmol) in THF (120 mL) at -78 °C was added a solution of

    n-butyllithium in hexanes (1.6 mL, 2.5 M, 4.0 mmol). After stirring for 1 h at -78 °C,

    isopropoxyboronic acid pinacol ester (1.19 g, 6.40 mmol) was added, the reaction was removed

    from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was

    quenched by the addition of H2O, and then extracted with DCM. The extract was washed with

    water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash

    column chromatography (silica gel, DCM:hexane, 1:4) and yielded 1.16 g (yield 55%) of 2e as a

    white solid. Rf = 0.2 (DCM:hexane, 1:4). FTIR (neat) 2930, 2210, 1604, 1553, 1467cm–1. 1H NMR

    (500 MHz, CDCl3) δ 7.66 (s, 2H), 7.46 – 7.43 (m, 4H), 6.88 – 6.86 (m, 4H), 3.97 (t, J = 6.6 Hz,

    4H), 1.81 – 1.77 (m, 4H), 1.50 – 1.42 (m, 6H), 1.38 (s, 12H), 0.93 – 0.89 (m, 6H) ppm. 13C NMR

    (500 MHz, CDCl3) δ 159.7, 133.2, 131.7(q, 2J(C, F) = 33.5 Hz), 128.1, 127.4 (q, 1J(C, F) = 3.8

    Hz), 123.5(q, 3J(C, F) = 272.6 Hz), 114.72, 114.66, 92.3, 87.0, 84.8, 68.3, 31.7, 29.3, 25.9, 25.1,

    22.7, 14.2 ppm. HRMS (ESI-TOF) m/z: [M+H]+ calcd for [C41H49BF3O4]+ 673.2676, found

    673.3765.

    2f: To a solution of S2f (835 mg, 1.73 mmol) in THF (80 mL) at -78 °C was added a solution of

    n-butyllithium in hexanes (0.92 mL, 2.5 M, 2.30 mmol). After stirring for 1 hour at -78 °C,

  • isopropoxyboronic acid pinacol ester (387 mg, 2.07 mmol) was added, the reaction removed from

    the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched

    by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried

    with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column

    chromatography (silica gel, DCM:hexane, 1:3) and yielded 598 mg (yield 65%) of 2f as a white

    solid. Rf = 0.15 (DCM:hexane, 1:3). FTIR (neat) 2982, 2210, 1602, 1569, 1553 cm-1. 1H NMR

    (400 MHz, CDCl3) δ 7.67 (s, 2H), 7.48 – 7.45 (m, 4H), 6.90 – 6.87 (m, 4H), 3.83 (s, 6H), 1.38 (s,

    12H) ppm. 13C NMR (400 MHz, CDCl3) δ 160.1, 133.2, 131.7(q, 2J(C, F) = 32.8 Hz), 128.1,

    127.5(q, 1J(C, F) = 3.8 Hz), 127.4, 123.4(q, 3J(C, F) = 272 Hz), 114.9, 114.2, 92.2, 87.1, 84.8,

    55.4, 25.1 ppm. HRMS (ESI-TOF) m/z: [M+H]+ calcd for [C31H29BF3O4]+ 533.2111, found

    531.2115.

    2k: To a solution of S2k (1.21 g, 2.51 mmol) in THF (120 mL) at -78 °C was added a solution of

    n-butyllithium in hexanes (1.3 mL, 2.5 M, 3.1 mmol). After stirring for 1 hour at -78 °C,

    isopropoxyboronic acid pinacol ester (700 mg, 3.80 mmol) was added, the reaction was removed

    from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was

    quenched by the addition of H2O, and then extracted with DCM. The extract was washed with

    water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash

    column chromatography (silica gel, DCM:hexane, 1:4) and yielded 800 mg (yield 61%) of 2k as

    a white solid. Rf = 0.21 (DCM:hexane, 1:4). FTIR (neat) 2963, 2869, 2216, 1563 cm–1. 1H NMR

    (400 MHz, CDCl3) δ 7.53 (s, 2H), 7.46 (d, J = 8.2 Hz, 4H), 7.32 (d, J = 8.2 Hz, 4H), 1.35 (s, 12H),

    1.32 (s, 9H) ppm. 13C NMR (400 MHz, CDCl3) δ 152.6, 134.4, 132.9, 129.3, 128.8, 126.5, 122.1,

    91.1, 88.9, 84.4, 34.8, 31.1, 25.1 ppm. HRMS (ESI-TOF) m/z: [M+H]+ calcd for [C32H32BCl2O2]+

    529.1872, found 529.1877.

  • 4a: 3-Bromophenanthrene (78 mg, 0.30 mmol), 2a (200 mg, 0.303 mmol) and K2CO3 (84 mg,

    0.61 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed

    by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.030 mmol) was added and the

    resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was

    complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The

    solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, diethyl ether:hexane, 1:15) to give 118 mg (yield 55%) of 4a as a

    spongy white solid. Rf = 0.37 (diethyl ether : hexane, 1:15). FTIR (neat) 2953, 2206, 1604, 1567,

    1554 cm-1. 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1H), 8.75 – 8.70 (m, 1H), 7.99 – 7.94 (m, 2H),

    7.94 – 7.90 (m, 1H), 7.84 – 7.76 (m, 2H), 7.67 (s, 2H), 7.60 – 7.56 (m, 2H), 7.06 – 7.00 (m, 1.3

    Hz, 4H), 6.63 – 6.56 (m, 4H), 3.84 (t, J = 6.4 Hz, 4H), 1.74 – 1.67 (m, 4H), 1.43 (s, 9H), 1.38 –

    1.27 (m, 12H), 0.91 – 0.85 (m, 6H) ppm. 13C NMR (400 MHz, CDCl3) δ 159.2, 150.3, 142.7,

    137.3, 132.9, 132.2, 131.4, 130.8, 129.7, 129.6, 129.5, 128.6, 127.3, 127.05, 126.96, 126.7, 126.5,

    125.2, 123.4, 123.0, 115.1, 114.4, 92.6, 88.4, 68.1, 34.8, 31.7, 31.3, 29.2, 25.8, 22.7, 14.2 ppm.

    HRMS (APPI-TOF) m/z: [M]+ calcd for [C52H54O2]+ 740.4124, found 740.4124.

    4b: 3-Bromophenanthrene (124 mg, 0.482 mmol), 2b (250 mg, 0.480 mmol) and K2CO3 (131 mg,

  • 0.948 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was

    degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (56 mg, 0.048 mmol) was added and

    the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was

    complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The

    solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane, 1:15) to give 213 mg (yield 78%) of 4b as a spongy

    white solid. Rf = 0.3 (DCM:hexane, 1:3) FTIR (neat) 2960, 2205, 1604, 1585, 1543, 1508, cm–1.

    1H NMR (400 MHz, CDCl3) δ 9.08 (s, 1H), 8.78 – 8.71 (m, 1H), 8.01 – 7.91 (m, 3H), 7.86 – 7.78

    (m, 2H), 7.70 (s, 2H), 7.63 – 7.56 (m, 2H), 7.10 – 7.04 (m, 4H), 6.67 – 6.59 (m, 4H), 3.70 (s, 6H),

    1.46 (s, 9H) ppm. 13C NMR (400 MHz, CDCl3) δ 159.6, 150.4, 142.8, 137.3, 133.0, 132.3, 131.4,

    130.8, 129.7, 129.5, 128.6, 127.4, 127.1, 126.9, 126.7, 126.5, 125.1, 123.4, 123.0, 115.4, 113.9,

    92.5, 88.5, 55.3, 34.8, 31.3 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C42H34O2]+ 570.2559,

    found 570.2550.

    4c: 3-Bromophenanthrene (134 mg, 0.521 mmol), 2c (250 mg, 0.522 mmol) and K2CO3 (144 mg,

    1.05 mmol) were dissolved in THF (50 mL) and distilled water (10mL). The solution was degassed

    by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (61 mg, 0.052 mmol) was added and the

    resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was

    complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The

    solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane, 1:3) to give 334 mg (yield 63%) of 4c as a spongy

    white solid. Rf = 0.12 (DCM:hexane, 1:3). FTIR (neat) 2953, 2206, 1604, 1567, 1554 cm–1. 1H

    NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.76 – 8.72 (m, 1H), 8.00 – 7.91 (m, 3H), 7.82 (m, 2H),

    7.61 – 7.57 (m, 2H), 7.50 (s, 2H), 7.05 – 7.01 (m, 4H), 6.64 – 6.60 (m, 4H), 3.70 (s, 6H), 2.44 (s,

  • 3H) ppm. 13C NMR (400 MHz, CDCl3) δ 159.6, 142.8, 137.3, 137.1, 132.95, 132.88, 132.3, 131.4,

    130.8, 129.7, 129.6, 128.6, 127.3, 127.1, 126.9, 126.7, 126.5, 125.1, 123.6, 123.0, 115.3, 113.9,

    92.8, 88.1, 55.3, 20.9 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C39H28O2]+ 528.2089, found

    528.2123.

    4d: 3-Bromophenanthrene (55 mg, 0.21 mmol), 2d (132 mg, 0.21 mmol) and K2CO3 (59 mg, 0.42

    mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by

    bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (25 mg, 0.16 mmol) was added and the resulting

    mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the

    mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was

    removed under reduced pressure and the residue was purified by column chromatography (silica

    gel, DCM:hexane, 1:1) to give 90 mg (63%) of 4d as a spongy white solid. Rf = 0.37 (DCM:hexane,

    1:1). FTIR (neat) 2961, 2205, 1629, 1600 cm–1. 1H NMR (500 MHz, CDCl3) δ 9.19 (s, 1H), 8.82

    (d, J = 8.0 Hz, 1H), 8.06 – 8.01 (m, 2H), 7.99 (dd, J = 7.8, 1.6 Hz, 1H), 7.87 (d, J = 8.9 Hz, 2H),

    7.77 (s, 2H), 7.62 – 7.56 (m, 2H), 7.51 (s, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.24 (d, J = 8.9 Hz, 2H),

    7.17 (dd, J = 8.5, 1.6 Hz, 2H), 7.04 – 6.97 (m, 4H), 3.87 (s, 6H), 1.48 (s, 9H) ppm. 13C NMR (500

    MHz, CDCl3) δ 158.3, 150.5, 143.2, 137.3, 134.1, 132.4, 131.6, 131.4, 130.9, 129.9, 129.75,

    129.71, 129.4, 128.8, 128.7, 128.4, 127.7, 127.5, 127.2, 127.0, 126.8, 126.6, 123.3, 119.2, 118.1,

    105.7, 93.3, 89.5, 55.3, 34.8, 31.4 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C50H38O2]+

    670.2872, found 670.2874.

  • 4e: 3-Bromophenanthrene (76 mg, 0.29 mmol), 2e (200 mg, 0.297 mmol) and K2CO3 (83 mg, 0.60

    mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by

    bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.03 mmol) was added and the resulting

    mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the

    mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was

    removed under reduced pressure and the residue was purified by column chromatography (silica

    gel, DCM:hexane, 1:4) to give 194 mg (yield 90%) of 4e as a spongy white solid. Rf = 0.36

    (DCM:hexane, 1:4). FTIR (neat) 2930, 2859, 2211, 1605, 1509 cm–1. 1H NMR (400 MHz, CDCl3)

    δ 9.07 (s, 1H), 8.73 (dd, J = 6.3, 3.1 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.98 – 7.89 (m, 2H), 7.88

    (s, 2H), 7.84 (s, 2H), 7.65 – 7.58 (m, 2H), 7.06 – 6.99 (m, 4H), 6.66 – 6.58 (m,, 4H), 3.84 (t, J =

    6.6 Hz, 4H), 1.75 – 1.65 (m, 4H), 1.44 – 1.26 (m, 12H), 0.96 – 0.85 (m, 6H) ppm. 13C NMR (400

    MHz, CDCl3) δ 159.6, 148.2, 136.2, 133.1, 132.3, 131.9, 130.7 (q, 2J(C, F) = 33.4 Hz),, 129.9,

    129.7, 129.0, 128.7, 128.3 (q, 1J(C,F) = 3.2 Hz),, 127.7, 127.6, 126.9, 126.84, 126.78, 125.0, 124.9,

    123.7 (q, 3J(C,F) = 272.6 Hz),, 123.0, 114.5, 114.3, 94.9, 86.7, 68.1, 31.7, 29.2, 25.8, 22.7, 14.1

    ppm. HRMS (APPI-TOF) m/z: [M]+calcd for [C49H45F3O2]+ 722.3371, found 722.3372.

    4f: 3-Bromophenanthrene (72 mg, 0.28 mmol), 2f (150 mg, 0.223 mmol) and K2CO3 (78 mg, 0.56

    mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by

    bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (32 mg, 0.027 mmol) was added and the resulting

  • mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the

    mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was

    removed under reduced pressure and the residue was purified by column chromatography (silica

    gel, DCM:hexane, 1:1) to give 131 mg (80%) of 4f as a spongy white solid. Rf = 0.38

    (DCM:hexane, 1:1). FTIR (neat) 2964, 2206, 1604, 1554, 1506, cm–1. 1H NMR (500 MHz,

    CDCl3) δ 9.05 (s, 1H), 8.73 – 8.70 (m, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.95 – 7.91 (m, 2H), 7.88 (s,

    2H), 7.86 – 7.83 (m, 2H), 7.62 – 7.60 (m, 2H), 7.04 – 7.01 (m, 4H), 6.64 – 6.61 (m, 4H), 3.71 (s,

    6H). 13C NMR (500 MHz, CDCl3) δ 160.0, 148.2, 136.1, 133.2, 133.0, 132.3, 131.9, 130.6, 130.1,

    129.8, 129.7, 128.8, 128.4, 128.2, 127.8, 126.9, 126.8, 125.1, 124.9, 124.8, 122.9, 114.2, 94.8,

    86.8, 55.9, 55.4 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C39H25F3O2]+ 582.1807, found

    582.1807.

    4g: Phenanthryl-3-borolane7 (374 mg, 1.12 mmol), S2g (300 mg, 0.613 mmol) and K2CO3 (340

    mg, 2.45 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was

    degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (142 mg, 0.123 mmol) was added and

    the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was

    complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The

    solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane, 3:2) to give 210 mg (58%) of 4g as a spongy white

    solid. Rf = 0.28 (DCM:hexane, 3:2). FTIR (neat) 2964, 2206, 1714, 1602, 1554 cm–1. 1H NMR

    (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.78 – 8.69 (m, 1H), 8.29 (s, 2H), 8.01 (d, J = 8.2 Hz, 1H), 7.96

    – 7.91 (m, 2H), 7.83 (d, J = 2.8 Hz, 2H), 7.63 – 7.58 (m, 2H), 7.09 – 6.99 (m, 4H), 6.68 – 6.56 (m,

    4H), 4.47 (q, J = 7.1 Hz, 2H), 3.71 (s, 6H), 1.48 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (400 MHz,

    CDCl3) δ 165.6, 159.8, 149.0, 136.5, 133.1, 132.9, 132.3, 131.9, 130.7, 129.75, 129.69, 129.0,

  • 128.7, 127.6, 126.89, 126.87, 126.7, 125.0, 124.4, 123.0, 114.9, 114.0, 94.0, 87.2, 61.6, 55.4, 14.5

    ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C41H30O4]+ 586.2144, found 586.2205.

    4h: 6-Methoxy-3-bromophenanthrene (86 mg, 0.30 mmol), 2a (200 mg, 0.303 mmol) and K2CO3

    (83 mg, 0.60 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was

    degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (58 mg, 0.050 mmol) was added and

    the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction

    was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4.

    The solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane, 1:4) to give 150 mg (yield 67%) of 4h as a spongy

    white solid . Rf = 0.15 (DCM:hexane, 1:4). FTIR (neat) 2953, 2205, 1621, 1507 cm-1. 1H NMR

    (400 MHz, CDCl3) δ 9.02 (s, 1H), 8.06 (s, 1H), 7.97 (s, 2H), 7.82 (d, J = 8.7 Hz, 1H), 7.73 – 7.69

    (m, 3H), 7.25 – 7.19 (m, 2H), 7.12 – 7.02 (m, 4H), 6.66 – 6.60 (m, 4H), 3.84 (t, J = 6.6 Hz, 4H),

    3.79 (s, 3H), 1.75 – 1.67 (m, 4H), 1.45 (s, 9H), 1.40 – 1.26 (m, 12H), 0.94 – 0.86 (m, 6H) ppm.

    13C NMR (400 MHz, CDCl3) δ 159.2, 158.6, 150.3, 142.6, 136.7, 132.9, 132.1, 130.6, 130.0,

    129.6, 129.5, 129.1, 127.8, 127.4, 126.7, 125.1, 124.5, 123.5, 117.5, 115.0, 114.5, 103.5, 92.8,

    88.5, 68.1, 55.4, 34.7, 31.7, 31.3, 29.2, 25.8, 22.7, 14.2 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd

    for [C53H56O3]+ 640.4229, found 640.4250.

  • 4i: 6-Trifluoromethyl-3-bromophenanthrene (98 mg, 0.30 mmol), 2a (200 mg, 0.297 mmol) and

    K2CO3 (84 mg, 0.61 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The

    solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.03 mmol) was

    added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the

    reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over

    Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, EtOAc:hexane, 1:20) to give 151 mg (yield 64%) of 4i as a spongy

    white solid. Rf = 0.32 (EtOAc:hexane, 1:20). FTIR (neat) 2930, 2859, 2211, 1605, 1508 cm-1. 1H

    NMR (500 MHz, CDCl3) δ 9.10 (s, 1H), 9.00 (s, 1H), 8.04 – 8.00 (m, 2H), 7.94 (d, J = 8.8 Hz,

    1H), 7.84 – 7.75 (m, 2H), 7.70 (s, 2H), 7.57 (s, 1H), 7.37 – 7.32 (m, 1H), 7.06 – 7.02 (m, 4H), 6.75

    – 6.73 (m, 1H), 6.63 – 6.60 (m, 3H), 3.91 (t, J = 6.4 Hz, 2H), 3.84 (t, J = 6.6 Hz, 2H), 1.75 – 1.68

    (m, 4H), 1.53 – 1.47 (m, 9H), 1.39 – 1.29 (m, 12H), 0.91 – 0.87 (m, 6H) ppm. 13C NMR (500

    MHz, CDCl3) δ 159.3, 150.7, 142.1, 138.1, 134.1, 133.0, 132.9, 131.6, 130.5, 130.3, 129.7, 129.4,

    129.3, 128.2, 127.6, 126.3, 125.1, 123.4, 122.4, 114.9, 114.7, 114.51, 114.46, 92.9, 88.2, 68.1,

    34.8, 31.7, 31.3, 29.2, 25.8, 22.7, 14.1 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C53H53F3O2]+

    778.3998, Found 778.3966.

    4j: 3-Bromophenanthrene (65 mg, 0.25 mmol), 2j (144 mg, 0.252 mmol) and K2CO3 (70 mg, 0.50

    mmol) were dissolved in THF (50 mL) and distilled water (10 ml). The solution was degassed by

    bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (29 mg, 0.025 mmol) was added and the resulting

    mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the

    mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was

    removed under reduced pressure and the residue was purified by column chromatography (silica

    gel, DCM:hexane, 1:5) to give 123 mg (yield 79%) of 4j as a spongy white solid. Rf = 0.43

  • (DCM:hexane, 1:5). FTIR (neat) 2961, 2252, 1512 cm–1. 1H NMR (500 MHz, CDCl3) δ 9.07 (s,

    1H), 8.78 – 8.72 (m, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.97 – 7.93 (m, 2H), 7.87 – 7.79 (m, 2H), 7.73

    (s, 2H), 7.63 – 7.57 (m, 2H), 7.16 – 7.10 (m, 4H), 7.10 – 7.04 (m, 4H), 1.46 (s, 9H), 1.23 (s, 18H)

    ppm. 13C NMR (500 MHz, CDCl3) δ 151.4, 150.4, 143.2, 137.2, 132.3, 131.5, 131.3, 131.1, 130.8,

    130.0, 129.7, 128.7, 127.2, 127.1, 127.0, 126.8, 126.6, 126.4, 125.2, 125.2, 123.3, 120.2, 92.7,

    89.1, 34.8, 34.8, 31.4, 31.3 ppm. HRMS (APPI-TOF) m/z: [M]+calcd for [C48H46]+ 622.36, found

    622.3606.

    4k: 3-Bromophenanthrene (97 mg, 0.38 mmol), 2k (200 mg, 0.378 mmol) and K2CO3 (104 mg,

    0.753 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was

    degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (44 mg, 0.038 mmol) was added and

    the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was

    complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The

    solvent was removed under reduced pressure and the residue was purified by column

    chromatography (silica gel, DCM:hexane, 1:5) to give 131 mg (yield 60%) of 4k as a spongy white

    solid. Rf = 0.37 (DCM:hexane, 1:5). FTIR (neat) 3384, 2963, 2248, 1584 cm–1. 1H NMR (500

    MHz, CDCl3) δ 9.02 (s, 1H), 8.72 – 8.67 (m, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.95 – 7.92 (m, 1H),

    7.90 (dd, J = 8.2, 1.6 Hz, 1H), 7.86 – 7.78 (m, 2H), 7.72 (s, 2H), 7.64 – 7.54 (m, 2H), 7.08 – 7.04

    (m, 4H), 7.03 – 6.99 (m, 4H), 1.44 (s, 9H) ppm. 13C NMR (500 MHz, CDCl3) δ 150.6, 143.5,

    136.9, 134.2, 132.7, 132.3, 131.6, 130.6, 130.3, 130.2, 130.1, 129.7, 129.3, 128.7, 128.6, 127.5,

    126.9, 126.82, 126.76, 125.1, 122.9, 121.6, 91.5, 90.5, 34.8, 31.3 ppm. HRMS (APPI-TOF) m/z:

    [M]+ calcd for [C40H28Cl2]+ 578.1568, found 578.1590.

  • 1a: Compound 4a (82 mg, 0.11 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. InCl3 (2.6 mg, 0.011 mmol) and silver bistriflimide (4.5 mg, 0.11 mmol) was added

    inside a glovebox. Then the reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After the reaction was complete, it was quenched with 5 mL of a saturated solution

    of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:DCM, 2:1) to give 52

    mg (63%) of 1a as faintly yellow spongy solid. Rf = 0.3 (hexane:DCM, 2:1). FTIR (neat) 2953,

    2929, 1605 cm–1. 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.36 (d, J = 15.8 Hz, 2H), 8.27 (s,

    1H), 8.15 (d, J = 8.1 Hz, 1H), 8.01 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.76

    – 7.7.66 (m, 4H), 7.32 – 7.7.26 (m, 1H), 7.16 (d, J = 7.0 Hz, 3H), 7.00 – 7.08 (m, 1H), 6.95 – 5.66

    (br, 3H), 4.13 (t, J = 6.5 Hz, 2H), 3.83 (q, J = 6.2, 5.6 Hz, 2H), 1.91 (m, J = 7.5 Hz, 2H), 1.73 –

    1.69 (m, 2H), 1.64 (s, 9H), 1.52 – 1.30 (m, 12H), 1.02 – 0.92 (m, 6H) ppm. 13C NMR (400 MHz,

    CDCl3) δ 158.9, 157.8, 149.8, 139.44, 139.38, 136.7, 133.4, 131.3, 131.2, 131.1, 130.6, 130.4,

    129.6, 129.5, 129.2, 127.9, 127.5, 126.8, 126.7, 126.1, 125.62, 125.59, 125.1, 125.0, 124.3, 124.0,

    122.9, 122.2, 114.6, 68.3, 68.1, 35.4, 32.0, 31.8, 31.7, 29.5, 29.2, 26.0, 25.8, 22.83, 22.76, 14.3,

    14.2 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C52H54O2]+ 710.2124, found 710.2124.

  • 1b: Compound 4b (213 mg, 0.373 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-

    dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the

    solution for 30 min. InCl3 (8.2 mg, 0.037 mmol) and silver bistriflimide (15 mg, 0.037 mmol) was

    added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After reaction was complete, it was quenched with 5 mL of saturated solution of

    sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 163

    mg (76%) of 1b as faint yellow spongy solid. Rf = 0.32 (hexane:DCM, 1:1). FTIR (neat) 2960,

    1608 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.36 (d, J = 1.9 Hz, 1H), 8.32 (s, 1H), 8.25

    (d, J = 1.8 Hz, 1H), 8.13 (m, J = 8.3, 1.3, 0.7 Hz, 1H), 7.99 (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.86

    – 7.80 (m, 1H), 7.76 – 7.67 (m, 3H), 7.31 – 7.25 (m, 1H), 7.19 – 7.15 (m, 2H), 7.04 (m, J = 8.3,

    7.0, 1.4 Hz, 1H), 6.90 – 6.15 (br, 4H), 3.98 (s, 3H), 3.69 (s, 3H), 1.64 (s, 9H) ppm. 13C NMR (400

    MHz, CDCl3) δ 159.4, 158.3, 149.9, 139.4, 139.3, 136.9, 133.7, 131.4, 131.3, 131.2, 131.1, 130.6,

    130.4, 129.7, 129.5, 129.2, 128.0, 127.5, 126.9, 126.7, 126.2, 125.7, 125.1, 125.0, 124.4, 124.0,

    122.9, 122.2, 121.9, 114.1, 55.6, 55.4, 35.4, 32.0 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for

    [C42H34O2]+ 570.2559, found 570.2567.

    1c: Compound 4c (334 mg, 0.63 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. InCl3 (13.9 mg, 0.0631 mmol) and AgNTf2 (24.5 mg, 0.0631 mmol) was added inside

    glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After

    reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate,

    extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and

    purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 257 mg (77%) of

    1c as faint yellow spongy solid. Rf = 0.32 (hexane:DCM, 1:1). FTIR (neat) 2926, 1739, 1620, 1506

  • cm-1. 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.23 (s, 1H), 8.12 (s, 2H), 8.00 (s, 1H), 7.96 –

    7.90 (m, 2H), 7.83 (d, J = 8.7 Hz, 1H), 7.75 – 7.65 (m, 3H), 7.31 – 7.26 (m, 1H), 7.16 (d, J = 8.8

    Hz, 2H), 7.30 – 7.26 (m, 1H), 6.85 – 6.12 (br, 4H), 3.98 (s, 3H), 3.68 (s, 3H), 2.84 (s, 3H) ppm.

    13C NMR (400 MHz, CDCl3) δ 159.4, 158.3, 139.5, 139.4, 136.9, 136.5, 133.7, 131.41, 131.36,

    131.25, 131.3, 130.3, 130.1, 129.7, 129.4, 129.2, 127.54, 127.52, 126.8, 126.7, 126.3, 126.2, 125.8,

    125.7, 125.2, 124.9, 124.4, 124.1, 121.9, 114.2, 55.6, 55.4, 22.2 ppm. HRMS (APPI-TOF) m/z:

    [M]+ calcd for [C39H28O2]+ 528.2089, found 528.2114.

    1d: Compound 4d (87 mg, 0.13 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. InCl3 (3.1 mg, 0.013 mmol) and AgNTf2 (5.0 mg, 0.013 mmol) was added inside

    glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After

    reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate,

    extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and

    purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 55 mg (77%) of 1d

    as faint yellow spongy solid. Rf = 0.26 (hexane:DCM 1:1). FTIR(neat) 3026, 2920, 1604 cm-1. 1H

    NMR (500 MHz, CDCl3) δ 8.62 (s, 1H), 8.48 (s, 1H), 8.42 (d, J = 1.8 Hz, 1H), 8.30 (d, J = 1.8 Hz,

    1H), 8.22 – 8.18 (m, 2H), 8.11 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.93 – 7.85 (m, 4H), 7.81 (d, J =

    8.7 Hz, 1H), 7.63 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 2.6 Hz, 1H), 7.30 – 7.27 (m, 1H), 7.08 – 7.03

    (m, 2H), 6.95 (d, J = 13.1 Hz, 2H), 6.83 (s, 2H), 4.03 (s, 3H), 3.88 (s, 3H), 1.65 (s, 9H) ppm. 13C

    NMR (500 MHz, CDCl3) δ 158.2, 157.5, 150.0, 139.84, 139.78, 136.7, 134.2, 133.2, 131.4, 131.3,

    131.2, 131.1, 130.4, 129.9, 129.6, 129.4, 129.3, 129.24, 129.18, 128.8, 128.4, 127.64, 127.56,

    126.9, 126.8, 126.7, 126.1, 125.7, 125.3, 125.0, 124.2, 124.1, 123.2, 122.5, 122.1, 119.4, 118.6,

    106.0, 105.6, 55.6, 55.3, 35.5, 32.1 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for [C50H38O2]+

    670.2872, found 670.2874.

  • 1e: Compound 4e (194 mg, 0.268 mmol) was dissolved in dry toluene (25 mL) in a 50 mL flame-

    dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the

    solution for 30 min. InCl3 (5.9 mg, 0.027 mmol) and AgNTf2 (10 mg, 0.0258 mmol) was added

    inside glovebox. The reaction mixture was heated to reflux for 15 h under nitrogen environment.

    After reaction was complete, it was quenched with 5 mL of saturated solution of sodium

    bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation

    and purification by column chromatography (silica gel, hexane:DCM, 1:4) to give 180 mg (92%)

    of 1e as faint yellow spongy solid. Rf = 0.07 (hexane:DCM, 1:4). FTIR (neat) 2930, 1607, 1508

    cm-1. 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.52 (s, 1H), 8.38 – 8.29 (m, 2H), 8.10 (d, J =

    7.8 Hz, 1H), 8.00 (d, J = 4.6 Hz, 1H), 7.96 – 7.92 (m, 1H), 7.90 – 7.85 (m, 1H), 7.75 (d, J = 7.8

    Hz, 1H), 7.77 – 7.72 (m, 2H), 7.334 – 7.28 (m, 1H), 7.26 (s, 1H), 7.18 – 7.13 (m, 2H), 7.09 – 7.03

    (m, 1H), 6.55 (s, 3H), 4.13 (t, J = 6.6 Hz, 2H), 3.85 – 3.75 (m, 2H), 1.95 – 1.86 (m, 2H), 1.75 –

    1.65 (m, 2H), 1.60 – 1.54 (m, 2H), 1.46 – 1.38 (m, 6H), 1.37 – 1.30 (m, 4H), 1.00 – 0.90 (m, 6H)

    ppm. 13C NMR (400 MHz, CDCl3) δ 159.3, 158.2, 158.1, 141.0, 140.7, 136.0, 132.7, 131.54,

    131.51, 131.49, 131.3, 131.1, 131.0, 130.0, 129.7, 129.7, 129.0, 128.4, 127.2, 126.6, 126.3, 126.13,

    126.09, 125.9, 125.6, 125.2, 124.9, 124.7, 121.30, 121.26, 120.8, 120.7, 114.8, 68.4, 68.2, 31.8,

    31.7, 29.5, 29.2, 26.0, 25.8, 22.83, 22.76, 14.2, 14.2 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for

    [C49H45F3O2]+ 722.3372, found 722.3372.

  • 1f: Compound 4f (186 mg, 0.319 mmol) was dissolved in toluene (30 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. catalytic mixture of InCl3 (7.1 mg, 0.032 mmol) and AgNTf2 (12 mg, 0.031 mmol)

    was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After reaction was complete, it was quenched with 5 mL of saturated solution of

    sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 134

    mg (72%) of 1f as faint yellow spongy solid. Rf = 0.38 (hexane:DCM, 1:1). FTIR (neat) 3026.27,

    2919.55, 1604.32, 1495.09 cm-1. 1H NMR (500 MHz, CDCl3) δ 8.63 (s, 1H), 8.52 (s, 1H), 8.35

    (d, J = 1.7 Hz, 1H), 8.33 (s, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.98 (s, 1H), 7.94 (d, J = 8.6 Hz, 1H),

    7.87 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 6.6 Hz, 1H), 7.65 (d, J = 7.9 Hz, 2H), 7.33 – 7.29 (m, 1H),

    7.16 (d, J = 8.8 Hz, 3H), 7.07 – 7.04 (m, 1H), 6.92 – 6.16 (br, 3H), 3.98 (s, 3H), 3.69 (s, 3H). 13C

    NMR (500 MHz, 3) δ 159.7, 158.6, 140.9, 140.6, 136.2, 132.9, 131.5, 131.4, 131.1, 131.0, 130.0,

    129.8, 129.6, 129.0, 128.5, 128.4, 128.2, 127.2, 126.6, 126.3, 126.12, 126.06, 125.9, 125.5, 125.1,

    124.9, 124.7, 123.9, 121.3, 120.8, 114.3, 55.62, 55.60, 55.4 ppm. HRMS (APPI-TOF) m/z: [M]+

    calcd for [C39H25F3O2]+ 582.1807, found 582.1807.

    1g: Compounds 4g (170 mg, 0.289 mmol) was dissolved in toluene (30 mL) in a 50 mL flame

    dried-round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the

  • solution for 30 min. catalytic mixture of InCl3 (7.1 mg, 0.032 mmol) and AgNTf2 (11 mg, 0.028

    mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under

    nitrogen environment. After reaction was complete, it was quenched with 5 mL of saturated

    solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by

    rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 3:2) to

    give 152 mg (89%) of 1g as faint yellow spongy solid. Rf = 0.38 (hexane:DCM 3:2). FTIR (neat)

    2917.23, 2848.98, 1714.61, 1608.06, 1245.65, 1221.56, 1210.14, 1176.83, 1034.46, 833.67 cm-1.

    1H NMR (400 MHz, CDCl3) δ 8.98 (s, 1H), 8.82 (s, 1H), 8.62 (s, 1H), 8.37 (s, 1H), 8.11 (d, J =

    8.2 Hz, 1H), 8.04 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.74 (d, J = 7.9 Hz,

    1H), 7.69 (d, J = 8.1 Hz, 2H), 7.33 – 7.27 (m, 1H), 7.18 (d, J = 8.3 Hz, 2H), 7.09 – 7.03 (m, 1H),

    6.55 (s, 4H), 4.58 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 3.69 (s, 3H), 1.54 (s, 3H). 13C NMR (400 MHz,

    CDCl3) δ 167.3, 159.6, 158.5, 140.2, 140.1, 136.4, 133.1, 131.44, 131.40, 131.2, 131.1, 130.9,

    130.6, 130.0, 129.7, 129.1, 128.4, 128.2, 127.8, 126.6, 126.4, 126.32, 126.29, 126.2, 126.0, 125.8,

    125.5, 125.3, 124.69, 124.67, 114.2, 61.5, 55.6, 55.4, 14.7 ppm. HRMS (APPI-TOF) m/z: [M]+

    calcd for [C41H30O4]+ 586.2144, found 586.2158.

    1h: Compound 4h (68 mg, 0.092 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. InCl3 (2.1 mg, 0.0092 mmol) and AgNTf2 (3.5 mg, 0.0092 mmol) was added inside a

    glovebox. Then the reaction mixture was heated to reflux for 15 h under nitrogen environment.

    After the reaction was complete, it was quenched with 5 mL of a saturated solution of sodium

    bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation

    and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 45 mg (66%)

    of 1h as light yellow spongy solid. Rf = 0.33 (hexane:DCM, 1:1). FTIR (neat) 2953.07, 1608.66,

    12043.31, 1174.56, 830.41 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.32 (d, J = 8.3 Hz,

  • 2H), 8.22 (s, 1H), 7.96 (s, 1H), 7.82 – 7.76 (m, 2H), 7.71 – 7.63 (m, 3H), 7.57 (d, J = 2.5 Hz, 1H),

    7.18 – 7.12 (m, 2H), 6.94 (m, 1H), 6.57 (br, 4H), 4.16 – 4.10 (m, 2H), 3.88 – 3.75 (m, 5H), 0.99 –

    0.87 (m, 2H), 1.74 – 1.67 (m, 2H), 1.62 (s, 9H), 1.49 – 1.28 (m, 12H), 0.99 – 0.87 (m, 6H) ppm.

    13C NMR (400 MHz, CDCl3) δ 159.0, 157.9, 156.6, 149.8, 139.5, 139.0, 136.5, 133.5, 131.4,

    131.2, 131.16, 131.15, 130.8, 130.3, 129.6, 129.2, 127.9, 127.8, 127.1, 126.5, 126.4, 125.0, 124.8,

    124.5, 124.0, 122.9, 122.1, 121.9, 116.0, 114.7, 112.8, 68.4, 68.2, 55.2, 35.4, 32.1, 31.83, 31.75,

    29.6, 29.3, 26.0, 25.8, 22.83, 22.81, 14.24, 14.20 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for

    [C53H56O3]+ 640.4229, found 640.4225.

    1i: Compound 4i (199 mg, 0.256 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. A catalytic mixture of InCl3 (5.6 mg, 0.02 mmol) and AgNTf2 (10 mg, 0.026 mmol)

    was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After the reaction was complete, it was quenched with 5 mL of a saturated solution

    of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:EtOAc, 1:20) to give

    98 mg (49%) of 1i as faint yellow spongy solid. Rf = 0.30 (hexane:EtOAc, 1:20). FTIR (neat) 2953,

    1608, 1509 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 8.45 – 8.35 (m, 3H), 8.28 (s, 1H),

    8.08 – 8.00 (m, 2H), 7.87 – 7.81 (m, 2H), 7.68 (d, J = 6.7 Hz, 2H), 7.46 (d, J = 8.4 Hz, 1H), 7.16

    (d, J = 7.3 Hz, 2H), 6.12 (br, 4H), 4.13 (t, J = 6.5 Hz, 2H), 3.86 (t, J = 6.2 Hz, 2H), 1.96 – 1.87

    (m, 2H), 1.75 – 1.69 (m, 2H), 1.65 (d, J = 1.3 Hz, 9H), 1.56 – 1.28 (m, 12H), 1.02 – 0.90 (m, 6H)

    ppm. 13C NMR (400 MHz, CDCl3) δ 159.0, 158.0, 150.3, 139.3, 139.0, 135.8, 133.2, 132.9,

    131.34, 131.27, 131.1, 131.0, 130.5, 130.2, 129.7, 129.3, 129.0, 128.5, 128.1, 127.2, 126.9, 126.6,

    126.0, 125.9, 125.6, 125.2, 124.8, 124.0, 123.3, 122.6, 121.7, 114.7, 68.3, 68.2, 35.5, 32.0, 31.8,

  • 31.7, 29.5, 29.2, 26.0, 25.8, 22.83, 22.77, 14.25, 14.20 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd

    for [C53H53F3O2]+ 778.3998, Found 778.3998.

    5: Compound 4j (123 mg, 0.197 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. catalytic mixture of InCl3 (4.4 mg, 0.019 mmol) and AgNTf2 (7.6 mg, 0.019 mmol)

    was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After reaction was complete, it was quenched with 5 mL of saturated solution of

    sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:EtOAc, 20:1) to give

    82 mg (67%) of 5 as faint yellow spongy solid. Rf = 0.31 (hexane:EtOAc, 20:1). FTIR (neat) 3026,

    2919, 2224, 1604 cm-1. 1H NMR (400 MHz, CDCl3) δ 10.22 (d, J = 8.4 Hz, 1H), 8.10 (s, 1H), 8.02

    (d, J = 8.7 Hz, 2H), 7.93 (s, 1H), 7.91 – 7.80 (m, 4H), 7.72 – 7.61 (m, 3H), 7.50 – 7.45 (m, 2H),

    7.21 – 7.12 (m, 1H), 7.11 – 6.78 (m, 4H), 1.55 (s, 9H), 1.39 (s, 9H), 1.19 (s, 9H) ppm. 13C NMR

    (400 MHz, CDCl3) δ 151.8, 149.3, 148.8, 140.8, 139.8, 133.0, 132.9, 132.3, 131.33, 131.31, 130.6,

    130.1, 129.9, 128.8, 127.8, 127.7, 127.4, 127.2, 126.3, 125.7, 125.5, 125.3, 125.08, 125.05, 124.7,

    124.4, 121.0, 119.5, 94.2, 92.0, 35.0, 34.8, 34.4, 31.5, 31.4, 31.3 ppm. HRMS (APPI-TOF) m/z:

    [M]+ calcd for [C48H46]+ 622.3599, found 622.3601.

  • 6: Compound 4k (138 mg, 0.238 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried

    round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution

    for 30 min. catalytic mixture of InCl3 (5.3 mg, 0.024 mmol) and AgNTf2 (9.3 mg, 0.024 mmol)

    was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen

    environment. After reaction was complete, it was quenched with 5 mL of saturated solution of

    sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory

    evaporation and purification by column chromatography (silica gel, hexane:DCM, 4:1) to give 68

    mg (50%) of 6 as faint yellow spongy solid. Rf = 0.37 (hexane:DCM, 4:1). FTIR (neat) 2962, 2234,

    1602, 1489 cm-1. 1H NMR (400 MHz, CDCl3) δ 10.07 (d, J = 8.7 Hz, 1H), 8.08 (s, 1H), 8.00 (d, J

    = 10.5 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H), 7.88 – 7.81 (m, 3H), 7.71 (d, J = 7.9 Hz, 1H), 7.61 (d, J

    = 8.3 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 14.6 Hz, 2H), 7.06 – 6.82 (m, 4H), 1.53 (s,

    9H) ppm. 13C NMR (400 MHz, CDCl3) δ 149.1, 142.4, 138.8, 134.6, 133.3, 133.2, 132.80, 132.75,

    132.2, 131.6, 131.4, 130.5, 130.4, 130.1, 129.7, 129.0, 128.9, 128.1, 127.5, 127.01, 127.0, 126.8,

    125.85, 125.64, 125.6, 125.3, 125.2, 124.8, 122.3, 119.0, 93.4, 92.9, 34.9, 31.4 ppm. HRMS

    (APPI-TOF) m/z: [M]+ mass calcd for [C40H28Cl2]+ 578.1568, found 578.1574.

    3. Chromatographic HPLC separations and dynamic HPLC experiments

    The HPLC unit was composed by a binary pump, a 20 μL loop injector, and two UV and UV/CD

    detectors connected in series. HPLC analytical runs were performed at flow rates of 1.0 mL/min

    and monitored by simultaneous UV and CD detections. Column temperature was controlled within

    ± 0.1 °C using a home-made cooling/heating device. Samples were dissolved in CH2Cl2