Thequestforhighly$ enanoselecve $$ chiral$hypervalentarylλ ...€¦ · type 3 as electrophilic...

The quest for highly enan2oselec2ve chiral hypervalent aryl-‐λ3-‐iodane reagents

Salinda Wijeratne

CEM 958

12/7/11

Chiral aryl-‐λ3-‐iodanes

IOR

OMeO OR

OI(OAc)2

OO

OMe

I(OAc)2O

O

MeO

1

OO

OMe

I(OAc)2O

O

MeO

IOR

OMeO OR

OI(OAc)2

O OR

OI(OAc)2

OO

OMe

I(OAc)2O

O

MeO

The versa2lity & demand for aryl-‐λ3-‐iodanes

•  Chemical proper.es and reac.vity: similar to the heavy metal reagents such as Hg(III), Ti(III), Pb(IV)

•  No toxicity and environmental issues

•  Mild reac.on condi.ons and easy handling

•  Commercial availability of key precursors

– e.g PhI(OAc)2 2

hJp://onlinelibrary.wiley.com/doi/10.1002/anie.v49:12/issuetoc Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523-‐2584

•  “Hypervalent”: exceeding octet rule

•  Aryl-‐λ3-‐iodanes

−  10 valence electrons

−  Important hypervalent aryl-‐λ3-‐iodanes

Hypervalent aryl-‐λ3-‐iodanes

Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523-‐2584 3

I

L

Ar

L!"

!+

!"

#3-Iodanes (10-I-3)

IOTs

OTs

Koser'sReagent

I OF3C

CH3

CH3

Togni'sReagent

ICl

Cl

(Dichloroiodo)benzeneWillgerodt, Germany, 1886

Bonding orbital

nonbonding orbital

Antibonding orbital

I LL

Three centered four electron bonding

IOTs

OTs

Koser'sReagent

I OF3C

CH3

CH3

Togni'sReagent

ICl

Cl


IOTs

OTs

Koser'sReagent

I OF3C

CH3

CH3

Togni'sReagent

ICl

Cl


Classifica2on & reac2vity of aryl-‐λ3-‐iodanes

4 Wirth, T. Topics in Current Chemistry: Hypervalent Iodine Chemistry. Vol. 224. Springer. 2003, p 8-‐9

I

Ar

Ar

Cl

Two carbon-one heteroatom ligands systems (Ar2IL)

Pseudotrigonalbipyramid

R

O

R

O

Ar

1) base

2)Ar* I

Ar

X * Ar* I

reoxidize

I

OAc

Ar

OAc

Pseudotrigonalbipyramid

One carbon-two heteroatom ligands systems (ArIL2)

PhI

PhIOAc

OAc

R

O

I

R'

OAcPh

mCPBA

mCBA

R

OHR' R

OR'

R

OR'

OAc

Ligand exchange

Reductive elemination

OAc

(AcOH)

Asymmetric induc2ons using aryl-‐λ3-‐iodanes

5

O

O

O

OI

R!

R!

S!

H O

O

I

RO

O X XX

X = I, I(OAc)2

II

O

OAc

OAc

Type 1 Type 2 Type 4 Type 5

O !

O

ORR'

I(OAc)2I

OR'

R"'

R"

Type 3

R''

One carbon-two heteroatom ligands systems

IL*

Ar*IL

Type 2Type 1

Two carbon-one heteroatom ligandsystems

A -‐ Iodoaryl moiety B -‐ Chiral linker

One carbon-‐two heteroatom ligands systems

Two carbon-‐one heteroatom ligands systems

Outline

•  Introduc.on

•  Asymmetric induc.on using chiral aryl-‐λ3-‐iodane reagents

–  Chiral aryl-‐λ3-‐iodanes with one carbon and two heteroatom ligands & their applica.ons in oxida2ve addi2on reac2ons

–  Chiral aryl-‐λ3-‐iodanes with two carbon and one heteroatom ligands & their applica.ons in aryla.on reac.ons

6

One carbon and two heteroatom ligands chiral aryl-‐λ3-‐iodanes

7

O !

O

XRR'

I(OAc)2

I

OR'

R"'

R"Type 3

R''

O

O

O

OI

R!

R!

Type 1

S!

H O

O

I

RO

O

Type 2

X XX

X = I, I(OAc)2

Type 4

II

O

OAc

OAc

Type 5

R S R' R S R'

O

Oxidation of sulfide

R R'O

R R'O

OR"

! -

Oxy

gena

tion

of k

eton

es

R

R'

R

R'OR"

OR"

OH

R'

OH

R'

Nu

Dearomatization

O

O

O

OI

R"

R"

Type 1

S"

HO

O

I

RO

O

Type 2

Catalyst

Diox

ygen

atio

n &

diam

inat

ion

of a

lken

es

Flexible

Rigid

Type 1 chiral aryl-‐λ3-‐iodanes in oxida2on of sulfide

8

Type 2 chiral aryl-‐λ3-‐iodanes in α-‐oxygena2on of ketone

Imamoto, T.; Koto, H. Chem. LeD. 1886, 967-‐968 Hatzigrigoriou, E.; Varvoglis, A.; Chris.anopoulou, M. Org. Chem. 1990, 55, 315-‐318

O S OO

OIPh

OH

Ph

O OPh

O O

RHPh

O O

HR

O S OO

OR =

10-(+)-camphoryl

PhI

H2OMeCN, 45 min, 80 °C

(1 equiv) 5

90%, (S)-6 : (R)-6 = 1:1

4

o-CH3C6H4S CH3

O

Acetone, 3 h, r.t

O

O

t-BuCOOH

Ht-BuCOO

OO

I

o-CH3C6H4S CH3

(2 mmol) 2

75%, 53% ee,(S)-3

(1 mmol) 1

R S R' R S R'

O


R R'O

R R'O

OR"

! -

Oxy

gena

tion

of k

eton

es

R

R'

R

R'XR"

XR"

Diox

ygen

atio

n &

diam

inat

ion

of a

lken

es

OH

R'

OH

R'

Nu

Dearomatization

Catalyst

I

OR'

R"'

R"

O "

O

XRR'

I(OAc)2R''

Type 3

9

O !

O

XRR'

I(OAc)2

I

OR'

R"'

R"Type 3

R''

O

O

O

OI

R!

R!

Type 1

S!

H O

O

I

RO

O

Type 2

X XX

X = I, I(OAc)2

Type 4

II

O

OAc

OAc

Type 5


Flexible

Rigid

Type 3 aryl-‐λ3-‐iodanes with ether moiety

10

O

O

O

O

I

R!

R!

S!

H O

O

I

RO

O

Chiral center faraway from reaction center

Liberation ofthe chiral ligand

Liberation ofthe chiral ligand

Type 1

Type 2

Results and Discussion

Hypervalent iodine compounds are electrophilic speciesand can attack double bonds as shown in Scheme 1. Weconfirmed this mechanism by converting either (E)- or(Z)-2-pentene with the hypervalent iodine compounds 3into syn- or anti-2,3-bis(tosyloxy)pentane selectively. Aclean SN2 type mechanism is the prerequisite for thedevelopment of asymmetric reactions with chiral hyper-valent iodine compounds. For these investigations wechose the dioxytosylation of styrene and the R-oxytosy-lation of propiophenone as test reactions (Scheme 2). Inthese reactions new stereocenters are created and theproducts of these reactions, 1,2-bis(tosyloxy)phenylethane(4) and R-(tosyloxy)propiophenone (5), are compoundscontaining asymmetric carbon atoms.

Employing chiral hypervalent iodine compounds oftype 3 as electrophilic reagents, we observe a facialselectivity upon reaction with alkenes and ketones andenantiomerically enriched products 4 and 5 are gener-ated. With compound 3a (R ) Et, R! ) Me, R!! ) H) wereported asymmetric reactions yielding 4 and 5 with 21%ee and 15% ee, respectively.10 Because of the lowstereoselectivities we tried to optimize the chiral hyper-valent iodine compounds of type 3. First we focused ourinterest on the substituents R and R! in the chiral moietyof 3. In a second step we then varied the substituent R!!to understand its influence on the electronic propertiesof the reagent. A further target was the optimization ofthe reaction conditions to obtain better yields and ste-reoselectivities.

We chose to synthesize the most simple compound 3bwith R ) R! ) Me and R!! ) H. The synthesis of thiscompound starts with an ortho-deprotonation of (S)-1-phenylethanol (6) with n-BuLi followed by introductionof iodine yielding compound 7a. The hydroxy group wasmethylated, and the precursor 7b was oxidized withsodium perborate in glacial acetic acid.12 Subsequenttreatment with p-toluenesulfonic acid monohydrate leadsto the hypervalent iodine compound 3b. An alternativeway to obtain 3b is chiral reduction13 of 2-bromoac-etophenone (8) followed by methylation. After the bro-mine-iodine exchange compound 7b can be oxidized asdescribed above. Because of the inefficent ortho-depro-

tonation of 6, the second route leads to a higher overallyield of 3b (43%) (Scheme 3).

The hypervalent iodine compound 3b can be purifiedonly by recrystallization. The X-ray structural analysisshows a strong interaction between the oxygen of themethoxy group and the iodine (Figure 1). The distancebetween these two atoms (2.47 Å) is much less than thedistance from the iodine to the oxygen of the tosyloxygroup (2.82 Å). Because the hydroxy group is tightlybound to the iodine (1.94 Å), we prefer writing thestructures of these hypervalent iodine compounds as saltsof p-toluenesulfonic acid.

Compound 3b shows a similar T-shaped structure likethe Koser reagent.14 Interestingly, the oxygen of themethoxy group is now replacing the tosylate leading toan oxygen-iodine-oxygen angle of 166° (Koser reagent:179°).14 Compared with the X-ray structural analysis of3a, the hypervalent iodine compound 3b shows a verysimilar geometry at the iodine atom. With 3b theproducts 4 and 5 were obtained with 33% ee and 15%ee, respectively.

Compared to 3a, the smaller substituent R ) Me in3b shows a higher enantiomeric excess in the product 4.If R! is changed into a larger substituent in 3c (R ) Me,R! ) Et), the product 4 is obtained with only 21% ee.

With the optimized chiral moiety in 3b (R ) R! ) Me),we started to synthesize derivatives with methoxy groups(R!! ) OMe) in the ortho-, meta-, and para-positions withrespect to iodine.

Two synthetic routes to the chiral hypervalent iodinecompound 3d with an ortho-methoxy substituent have

(12) McKillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299-3306.(13) Resnick, S. M.; Torok, D. S.; Gibson, D. T. J. Org. Chem. 1995,

60, 3546-3549.(14) Koser, G. F.; Wettach, R. H.; Troup, J. M.; Frenz, B. A. J. Org.

Chem. 1976, 41, 3609-3611.

Chart 1

Scheme 2

Scheme 3a

a Key: (a) N,N,N!,N!-TMEDA, n-BuLi, I2, 22%; (b) NaH, MeI,72%; (c) (-)-Ipc2BCl, 92%; (d) NaH, MeI, 92%; (e) t-BuLi, I2, 74%;(f) (i) NaBO3‚4H2O, AcOH, 73%, (ii) p-TsOH‚H2O, 95%.

Figure 1. X-ray structure of 3b.

Chiral Hypervalent Iodine Compounds J. Org. Chem., Vol. 63, No. 22, 1998 7675

Stabilizing interaction

n !*

O

IY

Orbital overlap for I---O interaction

Wirth, T.; Hirt, U. H. Tetrahedron Asymm. 1997, 8, 23

I+

OR'

-OTs

OH

R

Type 3 with ether moiety

Crystal structure of compound (S)-‐2

2.47 Å

I

EtOMe

OH

-OTs I

MeOMe

OH

-OTs

(S)-1 (S)-2

11

Type 3 chiral aryl-‐λ3-‐iodanes in α-‐oxygena2on of ketones

Ph

O

CH2Cl2, 0 °C Ph

O

OTsI

EtOMe

OH

(0.5 mmol) (S)-2 or 4(0.6 mmol) p-TsOH

(1.2 mmol) 1

-OTs

3(S)-2 =>10% ee(S)-4 =>15% ee

I

MeOMe

OH

-OTs

(S)-2 (S)-4

Hirt, U. H.; Spingler, B.; Wirth, T. J. Org. Chem. 1998, 63, 7674.

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1

(0.5 mmol) 2,3 or 4, (0.6 mmol) p-TsOH

(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

12

Op2miza2on of condi2ons for high enan2oselec2vity

1. Steric influence of chiral moiety

Results and Discussion

Hypervalent iodine compounds are electrophilic speciesand can attack double bonds as shown in Scheme 1. Weconfirmed this mechanism by converting either (E)- or(Z)-2-pentene with the hypervalent iodine compounds 3into syn- or anti-2,3-bis(tosyloxy)pentane selectively. Aclean SN2 type mechanism is the prerequisite for thedevelopment of asymmetric reactions with chiral hyper-valent iodine compounds. For these investigations wechose the dioxytosylation of styrene and the R-oxytosy-lation of propiophenone as test reactions (Scheme 2). Inthese reactions new stereocenters are created and theproducts of these reactions, 1,2-bis(tosyloxy)phenylethane(4) and R-(tosyloxy)propiophenone (5), are compoundscontaining asymmetric carbon atoms.

Employing chiral hypervalent iodine compounds oftype 3 as electrophilic reagents, we observe a facialselectivity upon reaction with alkenes and ketones andenantiomerically enriched products 4 and 5 are gener-ated. With compound 3a (R ) Et, R! ) Me, R!! ) H) wereported asymmetric reactions yielding 4 and 5 with 21%ee and 15% ee, respectively.10 Because of the lowstereoselectivities we tried to optimize the chiral hyper-valent iodine compounds of type 3. First we focused ourinterest on the substituents R and R! in the chiral moietyof 3. In a second step we then varied the substituent R!!to understand its influence on the electronic propertiesof the reagent. A further target was the optimization ofthe reaction conditions to obtain better yields and ste-reoselectivities.

We chose to synthesize the most simple compound 3bwith R ) R! ) Me and R!! ) H. The synthesis of thiscompound starts with an ortho-deprotonation of (S)-1-phenylethanol (6) with n-BuLi followed by introductionof iodine yielding compound 7a. The hydroxy group wasmethylated, and the precursor 7b was oxidized withsodium perborate in glacial acetic acid.12 Subsequenttreatment with p-toluenesulfonic acid monohydrate leadsto the hypervalent iodine compound 3b. An alternativeway to obtain 3b is chiral reduction13 of 2-bromoac-etophenone (8) followed by methylation. After the bro-mine-iodine exchange compound 7b can be oxidized asdescribed above. Because of the inefficent ortho-depro-

tonation of 6, the second route leads to a higher overallyield of 3b (43%) (Scheme 3).

The hypervalent iodine compound 3b can be purifiedonly by recrystallization. The X-ray structural analysisshows a strong interaction between the oxygen of themethoxy group and the iodine (Figure 1). The distancebetween these two atoms (2.47 Å) is much less than thedistance from the iodine to the oxygen of the tosyloxygroup (2.82 Å). Because the hydroxy group is tightlybound to the iodine (1.94 Å), we prefer writing thestructures of these hypervalent iodine compounds as saltsof p-toluenesulfonic acid.

Compound 3b shows a similar T-shaped structure likethe Koser reagent.14 Interestingly, the oxygen of themethoxy group is now replacing the tosylate leading toan oxygen-iodine-oxygen angle of 166° (Koser reagent:179°).14 Compared with the X-ray structural analysis of3a, the hypervalent iodine compound 3b shows a verysimilar geometry at the iodine atom. With 3b theproducts 4 and 5 were obtained with 33% ee and 15%ee, respectively.

Compared to 3a, the smaller substituent R ) Me in3b shows a higher enantiomeric excess in the product 4.If R! is changed into a larger substituent in 3c (R ) Me,R! ) Et), the product 4 is obtained with only 21% ee.

With the optimized chiral moiety in 3b (R ) R! ) Me),we started to synthesize derivatives with methoxy groups(R!! ) OMe) in the ortho-, meta-, and para-positions withrespect to iodine.

Two synthetic routes to the chiral hypervalent iodinecompound 3d with an ortho-methoxy substituent have

(12) McKillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299-3306.(13) Resnick, S. M.; Torok, D. S.; Gibson, D. T. J. Org. Chem. 1995,

60, 3546-3549.(14) Koser, G. F.; Wettach, R. H.; Troup, J. M.; Frenz, B. A. J. Org.

Chem. 1976, 41, 3609-3611.

Chart 1

Scheme 2

Scheme 3a

a Key: (a) N,N,N!,N!-TMEDA, n-BuLi, I2, 22%; (b) NaH, MeI,72%; (c) (-)-Ipc2BCl, 92%; (d) NaH, MeI, 92%; (e) t-BuLi, I2, 74%;(f) (i) NaBO3‚4H2O, AcOH, 73%, (ii) p-TsOH‚H2O, 95%.

Figure 1. X-ray structure of 3b.

Chiral Hypervalent Iodine Compounds J. Org. Chem., Vol. 63, No. 22, 1998 7675

Ph

O

CH2Cl2, 0 °C Ph

O

OTsI

EtOMe

OH


(1.2 mmol) 1

-OTs

3(S)-2 =>10% ee(S)-4 =>15% ee

I

MeOMe

OH

-OTs

(S)-2 (S)-4


Crystal structure of compound (S)-‐4

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

13

Op2miza2on of condi2ons for high enan2oselec2vity

1. Steric influence of chiral moiety


2. Steric influence at ortho posi2on

Ph

O

CH2Cl2, 0 °C Ph

O

OTsI

MeOMe

OH

(0.5 mmol) (S)-5,6 or 7(0.6 mmol) p-TsOH

(1.2 mmol) 1

-OTs

3(S)-5 =>10% ee(S)-6 =>40% ee(S)-7 =>0% ee

I

MeOMe

OH

-OTs

(S)-5 (S)-6

I

MeOMe

OH

-OTs

(S)-7

Me Et i-Pr

Ph

O

CH2Cl2, 0 °C Ph

O

OTsI

EtOMe

OH


(1.2 mmol) 1

-OTs

3(S)-2 =>10% ee(S)-4 =>15% ee

I

MeOMe

OH

-OTs

(S)-2 (S)-4

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

Type 3 chiral aryl-‐λ3-‐iodanes in dioxygena2on of alkenes

14

Proposed mechanism for dioxygena2on of styrene

H

Ph H

H H

Ph H

H

IAr!

HO

OTsH

Ph H

HOTs

IHO Ar

!

H

Ph H

HTsOOTs OTs

Ar*I(OH)OTs =

I

OR'

OTs

OH

RAr*I(OH)OTs2 OTs -IAr

-OH

R''1

3 4 (R)-3

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

Hirt, U. H.; Schuster, M. F. H.; French, A. N.; Wiest, O. G.; Wirth, T. Eur. J. Org. Chem. 2001, 1569

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

I

MeOMe

OH

-OTs

(S)-3

MeO

I

MeOMe

OH

-OTs

(S)-4

Et

Ph Ph OTsOTs

CH2Cl2, -30 °C

0.6 mmol 1


(R)-5(S)-2 =>33% ee(S)-3 =>53% ee(S)-4 =>55% ee

I

MeOMe

OH

-OTs

(S)-2

15

Why R-‐configura2on ?

PhA

B

A face addition

of Ar*I(OH)OTs

B face addition

of Ar*I(OH)OTs

OMe

MeI

HHH Ph

OMe

MeI

HHPh H

TsOH

TsOH

H

Ph

TsO(R)-3

H

H

OTs

3a+

3b+

H

H

TsO(S)-3

H

Ph

OTs

1


Ra2onale for Stereoselec2vity

16

H

Ph

HO

SeAr!

(R)-2

CF3SO3H

MeOH

OH

EtSe

HHPh H H

Ph

OMe

SeAr!

(R)-3

H

Ph

HO

ArSe!

(S)-2

CF3SO3H

MeOH

OH

EtSe

HHH Ph H

Ph

MeO

ArSe!

(S)-3

H

Ph

OMe

SeAr!

(R)-3

Ph

A face addition

B face addition

3a+

3b+

1

Se)2

OH

Et

Br2

Se

OH

Et

TfO

Ph

MeOHAgOTfH

Ph

OMe

SeAr!

(R)-3

Wirth, T.; Fragale, G.; Spichty, M. J. Am. Chem. Soc. 1998, 120, 3376


17

Se)2

OH

Et

Br2

Se

OH

Et

TfO

Ph

MeOHAgOTfH

Ph

OMe

SeAr!

(R)-3

H

Ph

HO

SeAr!

(R)-2

CF3SO3H

MeOH

OH

EtSe

HHPh H H

Ph

OMe

SeAr!

(R)-3

H

Ph

HO

ArSe!

(S)-2

CF3SO3H

MeOH

OH

EtSe

HHH Ph H

Ph

MeO

ArSe!

(S)-3

3a+

3b+

Ph+ ArSe

!


Ra2onale for Stereoselec2vity: Stability of transi2on states

18

OH

MeSe

HHPh H

OH

MeSe

PhHH H

OH

MeSe

HPhH H

OH

MeSe

HHH Ph

3a+0.0 kcal/mol

3b+2.8 kcal/mol

3c+5.4 kcal/mol

3d+7.4 kcal/mol

bipyramidal structure resulting from an selenium-oxygenin-teraction can alternatively also be obtained by the conformationshown in 21+. Due to the strong steric interaction between themethyl group and the alkene, we focused our investigations onthe conformations of the diastereoisomers 20a+-20d+.The optimized geometries of the seleniranium ions 20a+-

20d+ are shown in Scheme 9. In all structures the alkene isbonded slightly asymmetrically to the selenium atom reflectingthe asymmetry of the highest occupied molecular orbital(HOMO) of styrene which is involved in the selenium-alkenebonding. The bond lengths vary from 2.03 to 2.10 Å for theshorter Se-C2 bond and from 2.13 to 2.17 Å for the Se-C1bond (Table 1). These bonds are longer than the selenium-aryl bond (Se-Caryl), which varies between 1.93 and 1.97 Å.There is a remarkable correlation between the Se-O distance

and the O-Se-alkene angle (see Table 1). In the structures20c+ and 20d+ the alkene and the oxygen are arranged in analmost T-shaped manner with an O-Se-alkene angle close to180°. This facilitates the interaction of the oxygen lone pairwith the antibonding molecular orbital of the selenium-alkene

bonding. Therefore stronger selenium-oxygen interactions andweaker selenium-alkene bondings are found for 20c+ and 20d+than for 20a+ and 20b+. That is expressed in the respectivebond lengths shown in Scheme 9 and Table 1.The natural population analysis (NPA) predicts a higher

charge of about 0.25 for atom C1 than for atom C2 in alldiastereomers (Table 1). This confirms the preference of carbonatom C1 over carbon atom C2 for a nucleophilic attack. Thisfact was also observed in all our methoxyselenenylationexperiments. For the structures 20c+ and 20d+, the charge ofthe selenium is less positive than for 20a+ and 20b+. This isin agreement with the stronger selenium-oxygen interactionin the diastereoisomers 20c+ and 20d+.Due to the reversibility of the seleniranium formation from

the selenium electrophile and the alkene, the stereoselectivityshould be influenced by the relative stabilities of the selenira-nium ions 20a+-20d+. The lowest energy is found for thediastereoisomer 20a+, which corresponds to the re attack ofthe selenium electrophile to styrene leading to the methoxyse-lenenylated product with the (R)-configuration at the newstereocenter. Diastereoisomer 20b+ is yielding the methoxy-selenenylated product with opposite configuration and is foundto be more than 2.5 kcal/mol (see Scheme 9) higher in energy.For the diastereoisomers 20c+ and 20d+ which cannot gain from!-stacking, energy differences of 5.4 and 7.4 kcal/mol arecalculated.

Conclusions

The asymmetric methoxyselenenylation reaction has beeninvestigated in detail. It was shown that the formation of theseleniranium ion intermediates is reversible. For the first timethe diastereomeric seleniranium ions, which are the intermediatesin the addition of chiral selenium electrophiles to alkenes, havebeen prepared independently. Therefore it was possible to detailby experiment the different stabilities of the seleniranium ionsinvolved in the asymmetric methoxyselenenylation. Further-

Scheme 9

Table 1. Geometry Parameters for the MP2/3-21G*-OptimizedSeleniranium Ions 20a+-20d+a

20a+ 20b+ 20c+ 20d+

Se-C1 2.13 2.13 2.15 2.17Se-C2 2.06 2.03 2.08 2.10Se-O 2.66 2.71 2.54 2.46Se-Caryl 1.94 1.93 1.96 1.97!O-Se-alkeneb 130.6 120.0 156.8 175.2!Caryl-Se-alkeneb 96.5 98.8 98.7 98.5atomic chargesSe +0.883 +0.904 +0.839 +0.813C1 -0.269 -0.306 -0.248 -0.255C2 -0.550 -0.523 -0.533 -0.505a Distances are in angstroms; angles are in degrees. The atomic

charges were determined by NPA using the MP2/6-31G*//MP2/3-21G*density. b Se-alkene stands for the bisector of the angle C1-Se-C2.

Asymmetric Methoxyselenenylation Reaction J. Am. Chem. Soc., Vol. 120, No. 14, 1998 3379







Conclusions


Scheme 9


20a+ 20b+ 20c+ 20d+










Conclusions


Scheme 9


20a+ 20b+ 20c+ 20d+










Conclusions


Scheme 9


20a+ 20b+ 20c+ 20d+





R-‐configura2on through A face addi2on

19

PhA

B

A face addition

of Ar*I(OH)OTs

B face addition

of Ar*I(OH)OTs

OMe

MeI

HHH Ph

OMe

MeI

HHPh H

TsOH

TsOH

H

Ph

TsO(R)-3

H

H

OTs

3a+

3b+

H

H

TsO(S)-3

H

Ph

OTs

1More stable Major enan2omer

OH

MeSe

HHPh H

OH

MeSe

PhHH H

OH

MeSe

HPhH H

OH

MeSe

HHH Ph

3a+0.0 kcal/mol

3b+2.8 kcal/mol

3c+5.4 kcal/mol

3d+7.4 kcal/mol

OH

MeSe

HHPh H

OH

MeSe

PhHH H

OH

MeSe

HPhH H

OH

MeSe

HHH Ph

3a+0.0 kcal/mol

3b+2.8 kcal/mol

3c+5.4 kcal/mol

3d+7.4 kcal/mol


Type 3 aryl-‐λ3-‐iodanes with ester moiety

20

I+

OR'

-OTs

OH

R


Influence of ester binding moiety in α-‐oxygena2on of ketones

Altermann, S. M. et al, T. Eur. J. Org. Chem. 2008, 5315

I+O

ORR

OH

-OTs

Type 3 with ester moiety

Ph

OPh

O

OTs(0.5 mmol) 1 4

(R)-2 =>39% ee(R)-3 =>12% ee

(S)-2

IO

O10 mol% 2 or 33 equiv m-CPBA,3 equiv p-TsOH

MeCN, r.t

MeI

MeOMe

(S)-3

•  Strong interac.on between I-‐-‐-‐O

•  Greater distance between two alkyl groups

21

Ra2onale for improved enan2oselec2vity

Ochiai, M.; Sueda, T.; Miyamoto, K.; Kiprof, P.; Zhdankin, V. Angew. Chem. Int. Ed. 2006, 45, 8203

I OHO

OR

I OHO

CH3

CH3

2.47 Å 2.30 Å1.94 Å 2.00 Å

IO

OMe

Bulky menthylgroup

Greater distance

Altermann, S. M. et al, T. Eur. J. Org. Chem. 2008, 5315

Type 3 aryl-‐λ3-‐iodanes with lactate & lac2c amide moie2es

22

I+

OR

-OTs

OH

R'


I+O

ORR

OH

-OTs

Type 3 with ester moiety

OO

ORR'

I(OAc)2

Type 3 with lactatemoiety

I(OAc)2O NR

O

R'

Type 3 with lactic amide moiety

IO XR'

R''R

O

Large groups possible

Longer distance

Non-C2-symmetric

IOXR'

OO XR'

O

R''R R

C2-symmetric

Steric at ortho position

Type 3 chiral aryl-‐λ3-‐iodanes in Woodward reac2on

Fujita, M.; Wakita, M.; Sugimura, T. Chem. Commun. 2011, 47, 3983

Ar*I(OAc)2 =

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

Ar

(0.5 mmol) Ar*I(OAc)2 (0.5 mmol) BF3•OEt2 Ac2O

Ar

OAc

OHOMe

(0.2 ml) AcOHCH2Cl2

-80 to -40 °C

OMe

Ar

OH

OAcOMe

pyridine Ar

OAc

OAcOMe

(1S,2S) syn-2(0.4 mmol)1a

2'

2"3a=> 55%, 88% ee, (syn:anti = 98:2)3b=> 49%, 95% ee, (syn:anti = 98:2)

3a

3b

Ar*I(OAc)2 =

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

Ar

(0.5 mmol) Ar*I(OAc)2 (0.5 mmol) BF3•OEt2 Ac2O

Ar

OAc

OHOMe

(0.2 ml) AcOHCH2Cl2

-80 to -40 °C

OMe

Ar

OH

OAcOMe

pyridine Ar

OAc

OAcOMe

(1S,2S) syn-2(0.4 mmol)1a

2'

2"3a=> 55%, 88% ee, (syn:anti = 98:2)3b=> 49%, 95% ee, (syn:anti = 98:2)

3a

3b

Ar*I(OAc)2 =

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

OO

MeO

3a

3b

3c

Type 3 chiral aryl-‐λ3-‐iodanes in Pre ́vost reac2on

Ar OMe (0.2 ml) AcOH, (0.2 ml) TMSOAc, CH2Cl2

-80 C° to rt

Ar

OAc

OAcOMe

(0.4 mmol)1

(0.5 mmol) Ar*I(OAc)2 (0.5 mmol) BF3•OEt2

(1R,2S) anti-2

3a=> 70%, 88% ee, (syn:anti = 2:98)3b=> 53%, 96% ee, (syn:anti = 2:98)

Type 3 chiral aryl-‐λ3-‐iodanes in diamina2on of alkenes

24

NMs2

NMs2

H(2.4 equiv) HNMs2 ,

(1.2 equiv) 1

CH2Cl2, 0 °C

O

Me

MeO2CI(OAc)2

O CO2Me

Me

O

iPr

MeO2CI(OAc)2

O CO2Me

iPr

1a

1b

2 (S)-31a=> 86% yield, 85% ee, (99%)1b=> 30% yield, 84% ee

Roben, C.; Souto, J. A.; Gonzalez, Y.; Lishchynskyi, A.; Muniz, K. Angew. Chem. Int. Ed. 2011, 50, 9478

Non-‐C2 or C2-‐symmetry ?

25

NMs2

NMs2

H(2.4 equiv) HNMs2 ,

(1.2 equiv) 1

CH2Cl2, 0 °C

O

Me

MeO2CI(OAc)2

O CO2Me

Me

O

iPr

MeO2CI(OAc)2

O CO2Me

iPr

1a

1b

2 (S)-31a=> 86% yield, 85% ee, (99%)1b=> 30% yield, 84% ee

Roben, C.; Souto, J. A.; Gonzalez, Y.; Lishchynskyi, A.; Muniz, K. Angew. Chem. Int. Ed. 2011, 50, 9478

Ar*I(OAc)2 =

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

OO

OMe

I(OAc)2

OO

MeO

3a

3b

3c

Ar OMe (0.2 ml) AcOH, (0.2 ml) TMSOAc, CH2Cl2

-80 C° to rt

Ar

OAc

OAcOMe

(0.4 mmol)1

(0.5 mmol) Ar*I(OAc)2 (0.5 mmol) BF3•OEt2

(1R,2S) anti-2

3a=> 70%, 88% ee, (syn:anti = 2:98)3b=> 53%, 96% ee, (syn:anti = 2:98)

Dearoma2za2on of phenol using internal nucleophile

26

IO OMe

O 3a

24% yield, 13% ee, (R)-2

IO N

H

O3b

42% yield, 32% ee, (R)-2

IOEtO

OO OEt

O

Me Me3c

23% yield, 27% ee, (R)-2

ION

H

OO N

H

O

Me Me3d

55% yield, 92% ee (CHCl3), (R)-2

C2-‐symmetry C2-‐symmetry

Binding moiety

OH

HO O

O

OO

1

(15 mol%) 3 (a-d)(1.3 equiv) mCPBA

CH2Cl2, 0 °C, 3 h

(R)-2

Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem. Int. Ed. 2010, 49, 2175

Dearoma2za2on of phenol using internal nucleophile

27

IO OMe

O 3a

24% yield, 13% ee, (R)-2

IO N

H

O3b

42% yield, 32% ee, (R)-2

IOEtO

OO OEt

O

Me Me3c

23% yield, 27% ee, (R)-2

ION

H

OO N

H

O

Me Me3d

55% yield, 92% ee (CHCl3), (R)-2

IOX

OO X

O

R'R R

[O]in situ

IO

OX

O

O XL1

L2

R'

X = YH or YR"

aa

Binding moiety

OH

HO O

O

OO

1

(15 mol%) 3 (a-d)(1.3 equiv) mCPBA

CH2Cl2, 0 °C, 3 h

(R)-2

Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem. Int. Ed. 2010, 49, 2175

Binding moiety

Type 4 & 5 aryl-‐λ3-‐iodanes

28

X X IX I

OY

Y

X = I, I(OAc)2 Y = OAc, OCOCF3

II

O

OAc

OAc

Conformationally rigid systems

Type 4 Type 5

I+

OR

-OTs

OH

R'

I+OR

OR

OH

-OTs

Type 3 with ether moiety Type 3 with ester

moiety

Form conformationally flexible iodoarane

OO

ORR'

I(OAc)2 I(OAc)2O NR

O

R'



Form conformationally rigid iodoarane

29

O !

O

XRR'

I(OAc)2

I

OR'

R"'

R"Type 3

R''

O

O

O

OI

R!

R!

Type 1

S!

H O

O

I

RO

O

Type 2

X XX

X = I, I(OAc)2

Type 4

II

O

OAc

OAc

Type 5

R S R' R S R'

O


R R'O

R R'O

OR"

! -

Oxy

gena

tion

of k

eton

es

R

R'

R

R'OR"

OR"

OH

R'

OH

R'

Nu

Dearomatization

Catalyst

Diox

ygen

atio

n &

diam

inat

ion

of a

lken

esII OOAc

OAc

Type 5

X

X = I(OAc)2Type 4


Flexible

Rigid

Quideau, S.; Lyvinec, G.; Marguerit, M.; Bathany, K.; Ozanne-‐Beaudenon, A.; Buffeteau, T.; Cavagnat, D.; Chenede, A. Angew. Chem. Int. Ed. 2009, 48, 4605

Dearoma2za2on using external nucleophile

30

O

OHI

* O

OHI

*

CO2H

IOMe

(+)-2a70% yield, 21% ee, 3

(-)-2b72% yield,23% ee, 3

(R)-2c70% yield,47% ee, 3

OH O

OH

(1 equiv) 2(a-c)

(1 equiv) m-CPBA,CH2Cl2, r.t

1 (S)-3

*Ar IOH

O

*Ar IO

O

OH*Ar I

OO

OHO

[O]

m-CPBA

[O]

ArOH-H2O

H+ cat.ligandexchanges

* = chirality*Ar I

OH

OArCO2H

*Ar IO

O

OArO

(R)-2c 4 5

5'4'

ArOHH+ cat.

General mechanism proposal: aryl-‐λ3-‐iodane pathway

31


O IMe

HO

OO

O

HMe

R

rotatingbonds

Unfavored face for ArOH approach

O IMe

HO

OO

O

R

MeH

syn

OOH

S

OOH

R

minor major

Via ligand coupling (LC)

*Ar IOH

O

*Ar IOH

O

4'

(R)-3 (S)-3

General mechanism proposal: aryl-‐λ5-‐iodane pathway

32


O IMe

O

O OO

R

Hypervalent twist

O IMe

OO

O

R

Mesyn

OOH

S

major

5'

(S)-3

MeO

Same facial discriminating orientation as for iodine (III) path

OO

S

I O

O*Ar IO

O

OH3

Evidence for aryl-‐λ5-‐iodane pathway

33 Quideau, S.; Lyvinec, G.; Marguerit, M.; Bathany, K.; Ozanne-‐Beaudenon, A.; Buffeteau, T.; Cavagnat, D.; Chenede, A. Angew. Chem. Int. Ed. 2009, 48, 4605

[5+H]+

*Ar IOH

O

*Ar IO

O

OH*Ar I

OO

OHO

[O]

m-CPBA

[O]

(R)-2c 4 5

ArOH-H2O

H+ cat.*Ar I

OO

OArO

5'

[(R)-‐2C + H] +

S47

a)

S48

34


*Ar IOH

O

*Ar IO

O

OH*Ar I

OO

OHO

[O]

m-CPBA

[O]

(R)-2c 4 5

ArOH-H2O

H+ cat.*Ar I

OO

OArO

5'

[5’+H]+ [(R)-‐2C + H] +

Evidence for aryl-‐λ5-‐iodane pathway

Dearoma2za2on using internal nucleophile

35

II

O

OAc

OAc

OMe

I(OAc)2

O

O

BzOH

HBzO

OO

I

3a40% yield,

3% ee, (R)-2

3b66% yield,

1% ee, (R)-2 3c

65% yield, 59% ee, (R)-2

Dohi, T.; Maruyama, A.; Takenaga, N.; Senami, K.; Minamitsuji, Y.; Fujioka, H.; Caemmerer, S. B.; Kita, Y. Angew. Chem. Int. Ed. 2008, 47, 3787

OH

HO O

O

OO

1

(0.55 equiv) 3 (a-c)

CH2Cl2, 0 °C, 3 h

(R)-2

O

2a

O

HO O

IOAc

Ar*

OO

O

HO O

Associative

Dissociative

Racemic

O

2a

OO

O

HO O

IOAc

Ar*

OH

HO O

1

OH

HO O

O

OO

1

(0.55 equiv) 3 (a-c)

CH2Cl2, 0 °C, 3 h

(R)-2

Evidence for associa2ve pathway

Entry Solvent ee (%) 2 Yields (%)

1 CHCl3 72 64

2 CH2Cl2 59 65

3 CH3CN 20 50

4 (CF3)2CHOH 0 87

36

OH

HO O

1

(0.55 equiv) 3c

0 °C, 3 h

O

(R)-2

O

HO O

IOAc

Ar*

OO

O

HO O

Associative

Dissociative

Racemic

O

2

OO

Non-polar solvent

Polar solvent

II

O

OAc

OAc


Evidence for associa2ve pathway

37

O

HO O

IOAc

Ar*

Associative

Br

OH

HO O

1a

(0.15 equiv) 3c

CH2Cl2, 0 °C, 3 h

O

70% yield,69% ee, (R)-2a

OO

II

O

OAc

OAc

Br Br

OH

HO O

1

(0.55 equiv) 3cO

30% yield,0% ee, 2

OO

O

HO O

DissociativeII

O

OAc

OAc

OMe OMeOMeCH2Cl2, -50 °C,

2 h



38

IIO

OAc

OAc I

IO

AcO

OAc

=

I

IO

AcO

OAcI

IO

AcO

O

OHO

rotatingbonds

HOO

I

IO

AcO

O

OH

HO O

1

O

(R)-2

O

Outline

•  Introduc.on

•  Asymmetric induc.on using chiral aryl-‐λ3-‐iodane reagents

–  Chiral aryl-‐λ3-‐iodanes with one carbon and two heteroatom ligands & their applica.ons in oxida.ve addi.on reac.ons

–  Chiral aryl-‐λ3-‐iodanes with two carbon and one heteroatom ligands & their applica.ons in aryla2on reac2ons

39

Two carbons and one heteroatom ligands chiral aryl-‐λ3-‐iodanes

40

R

OR

O

Ar*

Asymmetric !"arylation

Catalyst

IL

Ar*

Type 1

IL

Ar*

IL*

Ar

Type 1

Type 2

Asymmetric α-‐aryla2on with unsymmetric aryl-‐λ3-‐iodanes

41 Ochiai, M.; Kitagawa, Y.; Takayama, N.; Takaoka, Y.; Shiro, M. J. Am. Chem. Soc. 1999, 121, 9233

IBn

Ar

BF4CO2Me

O (0.20 mmol) (S)-3 (0.20 mmol) tBuOK

(0.20 mmol) 1

CO2MeO

Ar(R)-2

(4 ml) tBuOHr.t, 1 h

37% yield, 53% ee(S)-3

Possible pathways for α-‐aryla2on

42 Chen, K. C.; Koser, G. F. J. Org. Chem. 1991, 56, 5764 Ochiai, M.; Kitagawa, Y.; Toyonari, M. ARKIVOC 2003, 6, 43

IO

CO2MeIO

CO2Me

O-

CO2Me

K+

IO

CO2Me

IX

and/or

I O

MeO2C

!-

!+

and/orI!-

O

MeO2C !+

OCO2MeAryl radicals pathway

Ligand exchange-ligand coupling pathway

Evidence for ligand exchange-‐ligand coupling pathway

43

O O

No evidence forformation of 3-substituted

dihydrobenzofuran

Ochiai, M.; Kitagawa, Y.; Toyonari, M. ARKIVOC 2003, 6, 43

O-

CO2Me

K+ O

I+ BF4-

(2 ml) t-BuOH, 25 °C

OCO2Me

OCO2Me

O

IO

OCO2Me

OH

(0.09 mmol) 1

(0.09 mmol) 2

(61%) 3 (7%) 4

5 6

Ligand exchange-‐ligand coupling pathway

44 Ochiai, M.; Kitagawa, Y.; Toyonari, M. ARKIVOC 2003, 6, 43

O-

CO2Me

K+

O

I+Ph

BF4-

IO

O

MeO2C

I O

MeO2C

O

Ligand exchange Pseudo rotation

IO

O

MeO2C

!-

!+

I O

MeO2C

O

!-

!+

Ligand coupling

OCO2Me

OCO2Me

O

IO

!-

O

MeO2C!+

1

23 4

5 6

O-

CO2Me

K+ O

I+ BF4-


OCO2Me

OCO2Me

O

IO

OCO2Me

OH

(0.09 mmol) 1

(0.09 mmol) 2

(61%) 3 (7%) 4

5 6

O-

CO2Me

K+ O

I+ BF4-


OCO2Me

OCO2Me

O

IO

OCO2Me

OH

(0.09 mmol) 1

(0.09 mmol) 2

(61%) 3 (7%) 4

5 6

45

R

OR

O

Ar*

Asymmetric !"arylation

Catalyst

IL*

Ar

Type 2

IL

Ar*

IL*

Ar

Type 1

Type 2

Two carbons and one heteroatom ligands chiral aryl-‐λ3-‐iodanes

46

C

D

I

O

A

I

OOSO

O

OSOO

B

OCO2Et

2, 3

1, 2

O-I bondforms

C-I bondforms

O

CO2Et

I

O

OEt

O

I

O

OEt

O

4

Norrby, P. O.; Petersen, T. B.; Bielawski, M.; Olofsson, B. Chem-‐Eur. J. 2010, 16, 8251

O

OEt

O

(0.19 mmol) 2(0.17 mmol) CsOH,

(2 mL) toluene,

I

2

OO3S

O

OEt

O

racemic(0.15 mmol) 3

42

α-‐aryla2on using aryl-‐λ3-‐iodanes with chiral heteroatom ligand

Energy level diagram of aryla2on of acetaldehyde

good agreement with the lack of selectivity observed in theexperimental work (Scheme 2 and Supporting Information).

Thus, asymmetric induction in the arylation of enolates bydiaryliodonium salts could either be obtained by influencingthe neutral, prochiral complex C,[6] by differentiation of theenantiotopic faces irreversibly during the enolate forma-tion,[7] or by increasing the barrier to interconversion of theO!I and C!I intermediates. Ionic species are not expectedto have any beneficial interactions with neutral C. ChiralLewis bases could coordinate to the iodine in a similarmanner to chiral anions and give complexes like E and F,but rearrangements of those species have too high barriersto be competitive. Potentially fruitful approaches couldeither be based on covalently linked auxiliaries, or on chiral

Lewis acids that could associate with and favor reactions viaC-linked intermediate D. We are currently investigatingsuch systems[27] and will report the results in due time.

Experimental Section

Experimental procedures, analytical data, and computational details areavailable in the Supporting Information.

Acknowledgements

This work was financially supported by the Swedish Research Council,Carl Trygger Foundation, and K&AWallenberg Foundation.

Keywords: arylation · density functional calculations ·hypervalent compounds · iodanes · reaction mechanisms

[1] a) R. E. Gawley, J. Aub!, Principles of Asymmetric Synthesis, Perga-mon, Oxford, 1996 ; b) T. Ooi, K. Maruoka, Angew. Chem. 2007,119, 4300–4345; Angew. Chem. Int. Ed. 2007, 46, 4222–4266.

[2] A. C. B. Burtoloso, Synlett 2009, 0320–0327.[3] E. A. Merritt, B. Olofsson, Angew. Chem. 2009, 121, 9214–9234;

Angew. Chem. Int. Ed. 2009, 48, 9052–9070.[4] a) M. Bielawski, M. Zhu, B. Olofsson, Adv. Synth. Catal. 2007, 349,

2610–2618; b) M. Bielawski, D. Aili, B. Olofsson, J. Org. Chem.2008, 73, 4602–4607; c) E. A. Merritt, J. Malmgren, F. J. Klinke, B.

Figure 2. Energy levels (in kJmol!1) of possible intermediates and TS structures in the reaction of acetaldehyde enolate with Ph2ICl in THF. Dotted linesindicate rapid association/dissociation equilibria.

Figure 3. Favored [2,3] rearrangement TS in the arylation of enolate 1with Ph2ICl (hydrogen atoms are hidden).

Chem. Eur. J. 2010, 16, 8251 – 8254 " 2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim www.chemeurj.org 8253

COMMUNICATIONa-Arylation by Rearrangement

47 Norrby, P. O.; Petersen, T. B.; Bielawski, M.; Olofsson, B. Chem-‐Eur. J. 2010, 16, 8251

Ener

gy (k

J/m

ol)

48

O

O

O

OI

R!

R!

Type 1

S!

H O

O

I

RO

O

Type 2

O

o-CH3C6H4S CH3

53% ee

Ph

O O

RHRacemic

OI

OSOO

Ar2IL O

OEt

O

Racemic

1) Aryl-‐λ3-‐iodanes with chiral hetero atom ligands: no chiral induc.on

Summary

Summary

49

I+

OR

-OTs

OH

R'

I+OR

OR

OH

-OTs

Type 3 with ether moiety Type 3 with ester

moiety

Form conformationally flexible iodoarane

OO

ORR'

I(OAc)2 I(OAc)2O NR

O

R'



Form conformationally rigid iodoarane

2) Type 3 Aryl-‐λ3-‐iodanes: Binding moiety plays major role in asymmetric induc.on

3) Type 3 Aryl-‐λ3-‐iodanes: C2-‐Symmetry plays major role in asymmetric induc.on

IOXR'

OO XR'

O

R''R R

C2-symmetric

Steric at ortho position

Summary

50

4) Type 4 & 5 Aryl-‐λ3-‐iodanes: Rigidity plays major role in asymmetric induc.on

X XX

X = I, I(OAc)2

Type 4

II

O

OAc

OAc

Type 5O

OO

59% ee

O

OH

47% ee

Acknowledgement

•  Dr. Baker & Dr. Smith

•  Dr. Borhan

•  Dr. Jackson

•  Dr. Maleczka

•  Baker’s Group: Gina, Greg, Hui, Heyi, Quanxuan, Wen & Zhe

•  Friends: Kumar, Uday, Ruth, Mark, Irosha & Damith

•  Dilini

51

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