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Photochemistry and Applications in Synthesis Jason M. Rohde September 1, 2004
Transcript of Photochemistry and Applications in Synthesis - Home | · PDF file ·...
Photochemistryand
Applications in Synthesis
Jason M. Rohde
September 1, 2004
Photochemistry
-chemical reactions initiated by light-energy is absorbed or emitted by matter in discrete quanta called photons -absorption of light leads to an electronic excitation (ground state→excited state)-promote an e- like n→π∗ or π→π∗
-most chemistry takes place from S1 and T1 excited states
E = hν = hc/ λshort λ light corresponds to high energy
S1 have a shorter lifetimeand higher E (10-9 to 10-5)
T1 have a longer lifetimeb/c spin flip req. (10-5 to 10-3)
Photochemistry-If a molecule absorbs energy, it can undergo a reaction or undergo loss of energy by two methods: •radiative processes-involve emission of a photon -phosphorescence-relaxation to a lower state with different multiplicity, such as T1→S0 (spin forbidden) -fluorescence-relaxation to lower state of same multiplicity, such as S1→S0 (spin allowed) •non-radiative processes-no emission -internal conversion-involves no spin change, such as S1→S0 -intersystem crossing-involves change in spin multiplicity •one way competes with phophorescent decay of the lowest triplet state to the ground state •another way converts the lowest excited singlet state to the lowest triplet state (competes with fluorescence and IC)[gives access to triplet state]-Excitation by E transfer is Sensitization (deactivation is Quenching)
Geometrical Isomerism
R
R R
Rhν
-cis/trans (E / Z) isomerism under photochemical conditions commonly leads to thermodynamically less stablecis-isomer -cis-isomer typically absorbs at a lower λ due to decreased conjugation b/c of non-bonded interactions-reactions come to photostationary state unless optical pumping is performed (irradiation of just 1 isomer to drive the equilibrium)
hν
w/o sensitizer photostationary state: E / Z : 8/92w sensitizer photostationary state: E / Z :50/50
Geometrical Isomerism
α-pyran: G. Büchi and N.C. Yang J. Am. Chem. Soc. 1957, 79, 2318.
OO
O
β-ionone
hν, quartz
EtOH
α-pyran
5% 95%
hν
2-C10H7COMe
Ph Phhν
toluene
Ar ArAr
Ar
hν
λ>180nm6π-elec.
∆
Geometrical Isomerism
O O
OO
hν hν
O
H
H
HH
O
H
H
HH
O
O
O
H
HH
O
O
H
HH
O
O
hν, pyrex
cyclohexane70%
hν, uranium
DCM, -75°C77%
10:1
5:1
H. Dorr, V. Rawal J. Am. Chem. Soc. 1999, 121, 10229
λ>285nm
λ>340nm
Electrocyclizations
-reactions generate a new σ-bond between the termini of the conjugated π-system-concerted process-bond breaking occurs at the same time as bond formation-reactions also come to photostationary state based on absorption coefficient at the λ of irradiation
Thermal Reactions -occur via HOMO4n - conrotatory4n + 2 - disrotatory
Photochemical Reactions -occur via LUMO4n - disrotatory4n + 2 - conrotatory
4π-Electrocyclizations
H
H
hν
hν
OO
O
O
OO
HH
hν
hν
4π-electrocyclizationsoccur with disrotatoryring closure under photochemical conditions
95%
59%
254nm
hνFe
OCCO
COFe(CO)5
8 and 6π-Electrocyclizations
hν
hν
8π-electrocyclizationsoccur with disrotatoryring closure under photochemical conditions and 6π-systems undergo conrotatory ringclosure
C9H17
HOH
Ergosterol(provitamin D)
C9H17
HO
H
Precalciferol(previtamin D)
C9H17
HOVitamin D2(calciferol)
hν
6π
>20°C
1,7 H-shift
6π-Electrocyclization in Synthesis
H H
H H HO
HNO
HNO
OH
H
Ikarugamycin
H HH H OH
OH
OH
OH
H
H
H
HO
O
H
H
Wittig Reaction
1. hν, -78°C, hex.2. HCl
50%
4:1
J. Whitesell and M. Minton J. Am. Chem. Soc. 1987, 109, 6403
retro-6π-Electrocyclization
OO
dihydrocostunolide
E. Corey and A. Hortmann J. Am. Chem. Soc. 1963, 85, 4033
OO
OO
H
hν
1:1
MeOH-18°C
H2Raney Ni
MeOH-15°C
Di-π-methane rearrangement
-Howard E. Zimmerman has studied this reaction extensively-Reaction takes 1,4-dienes or 3-phenylalkenes to vinyl or phenyl cyclopropanes
barrelene semibullvalene
61%
hν
hν
O O
66%
hν
Oxa-di-π-methane rearrangement
O
pyrext-BuOH
50%
hν
hν
acetone70%
hν
R1
R5R4
R3R2
OR1 R4
R5
R3R2O
R1
R3R2
R4R5
O
R1
R3R2
R4R5
OO
O
O
Di-π-methane rearrangement in Natural Products
S. Look, W. Fenical, D. Van Engen, J. Clardy J. Am. Chem. Soc. 1984, 106, 5026.
O
O
AcO
H
AcO O
OH
O
Cl
OAc
AcO
H
AcOO
OHCl
OAc
O
erythrolide Aerythrolide B
hν
quartz PhH
87% convin 3 hr
or5% methanolic
seawater(glass)
with sunlight
37% convin 8 days
Oxa-di-π-methane vs. 1,3-Acyl Migration
T. Uyehara, Y. Kabasawa, T. Kato Bull. Chem. Soc. Jpn. 1986, 59, 2521
O
OO
hν
300nmhexane
254nmacetone
hν
50%
O
62%
OOMe
MeOO
O
X
hν
pyrexTHF59%
steps
X = O pinguisone X = H2 deoxypinguisone
1,3-Acyl Migration in Natural Products
J. Shin, W. Fenical J. Org. Chem. 1991, 56, 1227
O
O O
O O
hν
quartzPhH3h
cembratriene 10.6% cembratriene 11.5%
calyculone D back 8.8%calyculone E 6.2%
calyculone F up 10.6%calyculone G 15.9%
[2 + 2] Cycloaddition-[2+ 2] photocycloadditon is the cyclization of two olefinic units to provide a cyclobutane (generate 2 new C-C bonds and up to four new stereocenters)-1908 Ciamician observed the first [2 + 2] reaction when exposure to Italian sunlight for 1 year generated carvone camphor from carvone
O
O
carvone carvone camphor
hν
-photochemical conditions create charge like umpolung of enone (β-carbon is electron rich)-intermolecular variants also well known, but regioselec. can be highly dependent on both olefinic partners-this [2 + 2] follows the "rule of 5" and none of the other regioisomer is observed
O
not observed
"Rule of 5"
O
O
H
O
O
O O
hν
70%
O
O
notobserved
O
O
hν
O
O
[2 + 2] Cycloaddition in Synthesis
O
H•
HH
HH
H
O
H
H
Ohν
Et2O72% 2:1
O
OO
periplanone B
periplanone: S. Schreiber, C. Santini Tetrahedron Lett. 1981, 22, 4651saudin: J. Winkler, E. Doherty J. Am Chem. Soc. 1999, 121, 7425
O
O
OO
H
O
O
saudin
O
O
O
OO
O
O
H
O
OO
O
O
O
O
hν
0°CCH3CN/acetone
(9:1)80%
steps
de Mayo Reaction
O
OH
CO2Me
O
O
CO2MeOH
CO2MeO
hν
[2 + 2]
retro-aldol
-[2 + 2] cycloaddition involving double bond of an enol and another olefin and the retro-aldol reaction
Paterno-Büchi Reaction
-Paterno and Chieffi observed the first example of a [2 + 2] cycloaddition between a carbonyl and an olefin to make an oxetane
OO*
T1
O Ohν
-many examples of intermolecular reaction, but regioselectivity and product distributions are highly case dependent-many synthetic examples of intramolecular variant
OH
AcOAcOO AcO
O
hν
acetone42%
HI
AcOH82%
vitamin D3 analogs: M. Mihailovic, L. Lorenc, V. Pauolvic, J. Kalvoda Tetrahedron 1977, 33, 441
Paterno-Büchi Reaction in Synthesis
Oobtained viaDiels-Alder
O
hν
corexλ>250nm
PhH90%
O
1. i-Pr2NMgI, ∆2. PDC, DMF
65%
O H H
H
LDBBTHF
-78°C66%
H
H
H
endo-hirsutene
NaBH4TFA
DCM, CH3CN69%
V. Rawal, A. Fabré, S. Iwasa Tetrahedron Letters 1995, 36, 6851
Furan-Carbonyl Variant of the Paterno-Büchi Reaction
OPhCHO
hν
O O
PhH
OH
OH
Ph
O
O O
PhH
wet celite
O
OH
Ph
O
0.01N HCl
THF
H25% Rh/ Al2O3
S. Toki, K. Shima, H. Sakurai Bull. Chem. Soc. Jpn. 1965, 38, 760K. Shima, H. Sakurai Bull. Chem. Soc. Jpn. 1966, 39, 1806S. Schreiber, A. Hoyveda, H. Wu J. Am. Chem. Soc. 1983, 105, 660
-this variant of the [2 + 2] offers a photochemical variant of the aldol reaction through transformations of the photoadduct
Furan-Carbonyl Variant of the Paterno-Büchi Reaction
O
hν
S. Schreiber, K. Satake J. Am. Chem. Soc. 1983, 105, 6723S. Schreiber, K. Satake J. Am. Chem. Soc. 1984, 106, 4186
O OO
OH
H
OH
O
asteltoxin
H
O
OBn
O OH
OBn
PhH, Et2O63%
establishes 2 sterocenters present inasteltoxin (architecture used to install
remaining stereocenters in next few steps)
Arene-Olefin Cycloadditions
-cycloadditions between arenes and an olefin •ortho cycloadditions-[2 + 2] •para cycloadditions-[4 + 2] •meta cycloadditions-[3 + 2]
R1 R2R1 R2hν R1 = OMe R2 = CN
R1 = CN R2 = OAcR1 = H R2 = CN
O
O
O
O
O
O
O
O
O
O
O
O
hν ∆
ORTHO CYCLOADDITIONS
Para Cycloadditions
hν•
CNCN
hν
R
Meta Cycloadditions
hν
H H H
H R
RR
R
hνBryce-Smith and Blair dispelledthe long standing myth that arenesare photochemically inert
In 1966, Wilzbach and Kaplan and Bryce-Smith, Gilber and Orger codiscovered the meta arene olefin cycloaddition
R
Meta Cycloadditions in Synthesis
MeO
H OMe H OMe
hν
1. Br22. R3SnH 59%
H
cedreneH
O
H2NNH2KOH
Wender pioneered the use of [3 + 2]
arene/olefin cyc loadditions in
synthesis
P. Wender, J. Howbert J. Am. Chem. Soc. 1981, 103, 688
vycorpentane
65%
200°C
Meta Cycloadditions in Synthesis
hν
H2Pd/C
P. Wender, G. Dreyer Tetrahedron 1981, 37, 4445
isocomene
∆
vycorcyclohexane
85-90%∆
toluene230-244°C
90%
hexane98%
Photoinduced Electron Transfer
Acceptor Donor A•- D•+hν
chemistry
polar solvents facilitate the generation of radical ions and subsequent chemical reactions
Witkop Cyclization
NH
HN
OCO2H
NH
HN
OCO2H
Cl
NH
HN
HOCO2H
Clhν -HCl
H2O40%after
esterification
O. Yonemitsu, P. Cerutti, B. Witkop J. Am. Chem. Soc. 1966, 88, 3941
Witkop Cyclization in Synthesis
A. Burgett, Q. Li, Q. Wei, P. Harran Angew. Chem. Int. Ed. 2003, 42, 4961
O NH
NH
N
O
NO
HN
O
HN
O
HO
Cl
Cl
diazonamide A
O NH
NH
N
O
NO
HN
OTeocHN
OAcBr
O NH
NH
N
O
NO
HN
OTeocHN
OH
hν (300nm)
CH3CN/aq. LiOH
72%
NHBr
NH
N
O
O
Li+
steps
(32-40% in initialsynthesis of the
nominal diazonamides)
Additional Photochemical Reactions
-Norrish Type I and II (α-cleavage of carbonyl and H-abstraction and fragmentation)-nitrogen extrusion (generate carbenes such as the Wolff rearrangment or to give diradical)-sigmatropic rearrangements such as (1,3), (1,5), and (1,7)-1O reactions-deprotections (such as cleavage of nitroarenes)-many other PET reactions •isomerizations •rearrangements •fragmentations •arene substitutions and reductions •photooxygenations •and many more reactions
Problem 1 (Were you paying attention to the last slide?)
R. Danheiser, A. Helgason J. Am. Chem. Soc. 1994, 116, 9471
Br
N2 O
Br
ON2
OTIPShν
vycorClCH2CH2Cl
rt then80°C
60-71%
OTIPSHO
Br
either substrate can be usedto generate the product and
both give essentially the sameyield of tricycle
reaction sequence usedin Danheiser's synthesis
of salvilenone
Problem 1 Solution
R. Danheiser, A. Helgason J. Am. Chem. Soc. 1994, 116, 9471
Br
N2 OBr
ON2
OTIPShν
vycorClCH2CH2Cl
rt then80°C
60-71%
OTIPSHO
Br
BrO
Br
O
O
•Br Br
O OTIPS
OTIPS
BrO •
-N2 -N2
Wolff rearr.
[2 + 2]4π
electro.
6π electro.(tautomer.)
Problem 2
Y. Kwak, J. Winkler J. Am. Chem. Soc. 2001, 123, 7429
O
NBoc
NBoc
O
1. hν, 87%2. EtOH, reflux3. cat. PPTS EtOH 87% 2 steps
Problem 2 Solution
Y. Kwak, J. Winkler J. Am. Chem. Soc. 2001, 123, 7429
O
NBoc
NBoc
O
1. hν, 87%2. EtOH, reflux3. cat. PPTS EtOH 87% 2 steps
hν
NBocO
BocN
OEtOH, reflux
cat. PPTS EtOH
retro-Mannich
Mannich
