Asymmetric PhotochemistryLiu-Zhu Gong Group Meeting

September 12, 2009

Wei-Jun Liu

1. Fundemental Reaction

2. Solid-Phase

3. Solution-Phase Covalently-bound chiral auxilliaried Chiral complexing agents Chiral sensitizer

Review: Rau, H. Chem. Review. 1983, 83, 535-547. Inoue, Y. Chem. Review. 1992, 92, 741-770. Konig, B. Chem. Review. 2006, 106, 5413-5430. Fagnoni, M. Chem. Review. 2007, 107, 2725-2756. Hoffmann, N. Chem. Review. 2008, 108, 1052-1103.

1. Fundmental Reactions

1.1 [2+2] photocycloaddition

Synlett 2002, 1305

J. Am. Chem. Soc. 2009, 131, ASAP.

Paternò-Büchi Reaction (between a ketone and alkene)

J. Org. Chem. 2003, 68, 9899.

J. Org. Chem. 2004, 69, 33.

Ang. Chem., Int. Ed. 2003, 42, 1642

1.2 Photochemical Rearrangments (di-ПЛ

Synthesis 2001, 1175

The Herteroatom Variant Photochemical Rearrangments

Ang. Chem., Int. Ed. 2002, 41, 4090

1.3 Norrish-Yang Reaction

Synthesis 2001, 1253

1.4 Intermolecular Addition onto Double or Triple C-C Bonds

J. Org. Chem. 2001, 66, 7320.

OOOO

O

O Ph

t-Bu

t-Bu

RCOOH R

R3R1O

R

R2R

PhCH3PhCH2

OH OH

O O O

O

O O

O

ON N

PhN OMe

O

SiMe3Et

PhN OMe

O

EtH2N O

H

H2N O

1.5 Photo-oxygenation

Why Study Asymmetric Photochemistry?

Prebiotic photochemistry ---- enantiomeric excess of biomolecules may have been generated by circularly polarized light (CPL)

Environmentally benign processes ---- light is ubiquitous, generates no waste.

Different mode of reactivity ---- access to novel, strained compounds which are thermally inaccessible or diffcult to synthesize and low reaction temperature

Short excited lifetime

low activation energy for reactions in excited states

Why few Examples in Enantioselective Photochemical Transformations

A few energy difference of a few kilocalories per mole is sufficient to give >99% stereodifferentiation.

Inoue, Y. Chem. Review. 1992, 92, 741-770.

2. Enantioselective Solid-Phase Photochemistry2.1 Host-Gest Cocrystals

Toda, Chem. Comm. 1995, 621

100% ee Toda, Tanaka ACIE, 1999, 38, 3523

91-99.5% ee Tanaka OL, 2002, 4, 3255

2.2 Ionic Chiral Auxiliary

Scheffer ACR, 1996, 29, 203

2.3 Chiral Modified Supercages of Zeolites

Ramamurthy ACR, 2003, 36, 509

3. Enantioselective Solution-Phase Photochemistry

3.1 Covalently-bound chiral auxillaries

Meyer, JACS, 1986, 108, 306

Carreira, JACS, 1994, 116, 6622 JACS, 1997, 119, 2597

3.2 Chiral Complexing Agents (Templated Photochemsitry)

3.2.1 Noncovalent Asseemblies

EJOC, 2002, 2298

JOC, 1995, 60, 7984

Glycol-Metal Cation

Diaminotriazine-barbiturate(二氨基三唑－巴比妥酸盐）

CR, 2006, 106, 5413-5430

3.2.2 Complementary DNA Strands as Templates

CR, 2006, 106, 5413-5430

T

DNA RNA

A

G

C

U

A

G

C

3.2.3 Templates with a Covalently Bound Chromophore and Recognition Site

• The reaction did not proceed in the absence of the template

• As an artificial functional model of a photolyase

CR, 2006, 106, 5413-5430

3.2.4 Photochemical reaction in a molecular flask

The molecular flask is significantly larger than the guest and can therefore protect Substrates from the surrounding environment and thus controls the course of a Photochemical reaction.

• The syn isomers were the major.• The syn isomers changed to the minor.

Favorite temperate scaffolds Good availability Various sizes Inherent chirality CR, 2006, 106, 5413-5430

Cyclodextrin

Self-Assembled Molecular Cage

3.2.5 Templates Containing a Shield

Mori and Nakamura, TL, 1996, 37, 8523-8526

dr: 95/5yield: 56%

Bach, T. JACS, 1999, 121, 10650-10651

Bach, T. ACIE, 2000, 39, 2302-2304

dr: up to 95/5ee: up to 98

Bach, T. JACS, 2000, 122, 11525-11526

dr: up to 95/5ee: up to 97

Bach, T. ACIE, 2003, 42, 3693-3696

Bach, T. OL, 2001, 3, 601-603

Bach, T. CC, 2001, 607Bach, T. CEJ, 2002, 8, 2464

Catalytic Enantioselective Photochemical Reaction

Krische, J. JOC, 2003, 68, 15-21

Bach, T. Nature, 2005, 436, 1139-1140

Bach, T. ACIE, 2009, 48, 1-4

dr: up to 96/4ee: up to 99%

Polymer-Bound Chiral Temple

Bach, T. ACIE, 2008, 47, 7957-7959

3.3 Chiral Sensitizer

Inoue JCS CC, 1993, 718

Schuster, JACS, 1990, 112, 9635

Photosensitized ant-Markovnikov methanol additiong to 1,1-diphenylpropene

[4+2] cycloaddition between electron-rich diene and electron-rich dienophile

Sens* 2b : up to 70% ee

• Switching the product chiralty by solvent• lower temperature higher ee • The higheat ee ever reported for an enantiodifferentiating photosensitization.

Inoue, JACS, 2000, 122, 406-407

HO

O

O

O

O

O

hv (>300 nm)

7% ee

N

Ph

Ph Ph

BF4

Sens*

Garcia, JOC, 2002, 67, 5184-5189

3.3 Activation of Substates by Chiral Catalysts (Organocatalysis)

R

O NH

COOHN

R

COOH

3O2

1O2

hv, TPP

OPh Ph

Ph

BF4

N

R

COO

HOO

O

R

HOONaBH4OH

R

HO

R

Yield

ee

CH2Ph i-Pr n-Pent n-Bu

77% 75% 77% 73%

66% 57% 54% 57%

ONH2

O

OH

20%O

HO

87% yield, 56% ee Cordova, JACS, 2004, 126, 8914 ACIE, 2004, 43, 6532

O

H

YBr

R

FG

fluorenscent light

organocatalyst

Ru(bpy)3Cl2

H

O

FG

Y

R

MacMillan Science, 2008, 322, 77JACS, 2009, 131, 10875

N N

BPY

4 Photecatalysts

A: Via electron transfer

O

O

Cl Cl

Cl Cl

Chloranil

CO2Me

CO2Me

DMT

NC

NC CN

CN

TCB

CN

CN

DCB

O

Ph

Ph Ph

BF4

TPP

CN

CN

DCN

O

O

Anthraquinone

CN

CN

DCA

MeO2C

MeO2C CO2Me

CO2Me

TMPM

O

BP

OMe

OMe

DMN

B: Via H abstraction

O

NaO3S SO3Na

BPSS

O

BP

O O

UO22+ (Uranyl) (Bu4N)4W10O32 (TBADT)

5. Conclusion

Solid-Phase asymmetric photochemistry can work very well, but has limited.

Solution-phase photochemistry is more attractive for the catalytic enantiosele-ctive photochemistry. More excellent catalysts as Bach’ catalysts and assymme-tric inducing model will be developed.

Asymmetric photochemistry using chiral sensitizers is usually poorly selective.