Asymmetric Photochemistry
Liu-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.
O
O
O
O Ph
O
RCOOH
O
R1O
t-Bu
t-Bu
R2
R3
O
O
O
O
O
N
N
O
O
O
Et
OH
OH
R
O
N
PhCH2
R
O
Ph
PhCH3
R
OMe
SiMe3
H
Ph
N
Et
OMe
H2N
O
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
Why few Examples in Enantioselective Photochemical
Transformations
 Short excited lifetime
 low activation energy for reactions in excited states
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 Photochemistry
2.1 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
Glycol-Metal Cation
JOC, 1995, 60, 7984
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
DNA
RNA
T
G
U
G
A
C
A
C
CR, 2006, 106, 5413-5430
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.
Cyclodextrin
• 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
Self-Assembled Molecular Cage
3.2.5 Templates Containing a Shield
Coumarin group (香豆素）
Thymine (胸腺嘧啶）
Mori and Nakamura, TL, 1996, 37, 8523-8526
dr: 95/5
yield: 56%
Bach, T. JACS, 1999, 121, 10650-10651
Bach, T. ACIE, 2000, 39, 2302-2304
dr: up to 95/5
ee: up to 98
Bach, T. JACS, 2000, 122, 11525-11526
dr: up to 95/5
ee: up to 97
Bach, T. ACIE, 2003, 42, 3693-3696
Bach, T. OL, 2001, 3, 601-603
Bach, T. CC, 2001, 607
Bach, T. CEJ, 2002, 8, 2464
Catalytic Enantioselective Photochemical Reaction
Krische, J. JOC, 2003, 68, 15-21
Catalyst 30%, dr: 85/15
Bach, T. Nature, 2005, 436, 1139-1140
Bach, T. ACIE, 2009, 48, 1-4
Polymer-Bound Chiral Temple
dr: up to 96/4
ee: up to 99%
Bach, T. ACIE, 2008, 47, 7957-7959
3.3 Chiral Sensitizer
 Photosensitized ant-Markovnikov methanol additiong to 1,1-diphenylpropene
Inoue JCS CC, 1993, 718
 [4+2] cycloaddition between electron-rich diene and electron-rich dienophile
Schuster, JACS, 1990, 112, 9635
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
Ph
O
Ph
N
Ph
BF4
HO
O
hv (>300 nm)
O
O
O
Sens*
7% ee
Garcia, JOC, 2002, 67, 5184-5189
3.3 Activation of Substates by Chiral Catalysts (Organocatalysis)
3
O2
Ph
hv, TPP
O
N
H
COOH
N
COOH
1O
2
Ph
O
BF4
Ph
N
COO
HOO
R
R
R
OH
NaBH4
HO
O
HOO
R
R
R
O
i-Pr
Yield
CH2Ph
77%
ee
66%
75%
n-Pent
77%
n-Bu
73%
57%
54%
57%
NH2
O 20%
OH
O
HO
87% yield, 56% ee
Cordova, JACS, 2004, 126, 8914
ACIE, 2004, 43, 6532
O
H
Y
Br
O
fluorenscent light
R
FG
organocatalyst
Ru(bpy)3Cl2
R
FG
H
Y
N
N
BPY
MacMillan
Science, 2008, 322, 77
JACS, 2009, 131, 10875
4 Photecatalysts
A: Via electron transfer
CN
CO2Me
O
Cl
Cl
NC
CN
Cl
Cl
NC
CN
Chloranil
CN
CN
DCN
O
DMT
TCB
Ph
DCB
O
Ph
TPP
CN
O
CN
O
Anthraquinone
OMe
OMe
BP
BF4
CN
CO2Me
O
Ph
DMN
DCA
MeO2C
CO2Me
MeO2C
CO2Me
TMPM
B: Via H abstraction
O
NaO3S
O
SO3Na
BPSS
UO22+ (Uranyl)
BP
(Bu4N)4W10O32 (TBADT)
O
O
5. Conclusion
 Solid-Phase asymmetric photochemistry can work very well, but has limited.
 Solution-phase photochemistry is more attractive for the catalytic enantioselective photochemistry. More excellent catalysts as Bach’ catalysts and assymmetric inducing model will be developed.
 Asymmetric photochemistry using chiral sensitizers is usually poorly selective.