Enantioselective Organocatalysis Using SOMO Activation
2011,07,16 M2 Masafumi Ando
Typical Organocatalysts and the Advantages of Using Organocatalysts
N
MacMillan, D. W. C. Nature, 2008, 455, 304-308.
Characterization of Organocatalysis
Ac<va<on mode
HOMO ac<va<on
SOMO ac<va<on
➡Enamine catalysis
Ac<va<on mode
LUMO ac<va<on ➡Counterion catalysis
Substrate
Catalyst
Example of new reaction variation
Reference
S
NNN
HH
X R''
R''
• Strecker reaction
First application:
• Mannich reaction
1996-1999
• Ketone cyanosilylation First use as a
Ac<va<on mode
LUMO ac<va<on ➡Hydrogen-­‐bonding catalysis
Substrate
Catalyst
X R R'
tBu S H N
NNN HH O
RR
X = O, NR R, R', R'' = alkyl, aryl
Activation mode
COOH
H
tBu S H N
NNN HH O
RR
Stable in air and water Available from biological materials Inexpensive and easy to prepare Simple to use Both enan<oseries available Non-­‐toxic
O N
Bn
N tBu
Nu R LUMO activation
Example of new reaction variation
Reference
• Conjugate Friedel-Crafts reaction • Ketone Diels-Alder reaction • exo-Selective Diels-Alder reaction • Mukaiyama-Michael reaction • Conjugate hydride reduction • Conjugate amination • Conjugate oxygenation • Conjugate sulphenylation • Cyclopropanation • Epoxidation, aziridination
Characterization of Organocatalysis
Ac<va<on mode
HOMO ac<va<on ➡Enamine catalysis
Substrate
O R
Z
Catalyst
N
COOH
H
XY
R = any organic chain or ring system
First application: 1971 First use as a generic mode of activation: 2000
MacMillan, D. W. C. Nature, 2008, 455, 304-308.
Characterization of Organocatalysis
• Biginelli reaction
generic mode of
• Pictet–Spengler reaction activation: 2002
• Reductive amination
R R' Nu
LUMO activation
MacMillan, D. W. C. Nature, 2008, 455, 304-308.
➡SOMO catalysis
LUMO ac<va<on
➡Hydrogen-­‐bonding catalysis ➡Iminium catalysis ➡Counterion catalysis
MacMillan, D. W. C. Nature, 2008, 455, 304-308.
First application and first use as a generic mode of activation: 2000
MacMillan, D. W. C. Nature, 2008, 455, 304-308.
Characterization of Organocatalysis
X = C, N, O, S Y = generic organic atom Z = Alkyl, H
Activation mode
N R
X
Y Z
H
OOΒιβλιοθήκη HOMO activation
Example of new reaction variation
Reference
• Aldehyde-aldehyde cross aldol coupling • Intramolecular !-alkylation • Mannich reaction • Michael reaction • !-Amination • !-Oxygenation • !-Halogenation • !-Sulphenylation
Characterization of Organocatalysis
Ac<va<on mode
LUMO ac<va<on ➡Iminium catalysis
Substrate O
H
R R = alkyl, aryl
Catalyst
O N
Bn
N tBu
H
Activation mode