MKG LECTURE 15

17/04/2023
Enamine catalysis with SOMO photoredox catalysis

SET = single electron transfer

A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 60-77. 2

 Brönsted acid/base

Aminocatalysis Lewis Base

Cooperative Reactions:

Transition Metal
+
Organocatalyst

NHC organocatalyst Bifunctional catalyst

3
Chiral Brönsted-acid/base with metal activated substrates

Chiral Brönsted acid/base catalyst: a powerful strategy.

In combination with transition-metal, 3 approaches:

4
Chiral Brönsted-acid/base with metal activated substrates

Chiral Brönsted acid/base catalyst: a powerful strategy.

In combination with transition-metal, 3 approaches:

5
Asymmetric Counter-Anion-directed catalysis
Strategy (ACDC)
First example proposed by Toste et al,

G. L. Hamiltion, E. J. Kang, M. Mba, F. D. Toste, Science 2007, 317, 496-499. 6

Enantioselective α-allylation of aldehyde
via ACDC strategy
List et al.,

G. Jiang, B. List, Angew. Chem. Int. Ed. 2011, 50, 9471-9474. 7

Chiral Brönsted-acid/base with metal activated substrates

Chiral Brönsted acid/base catalyst: a powerful strategy.

In combination with transition-metal, 3 approaches:

8
Chiral Brönsted acid activation

Asymmetric alkynylation of α-imino esters proposed by Chan et al.:

Limited scope!

J.-X. Ji, J. Wu, A. S. C. Chan, Proc. Natl. Acad. Sci. USA 2005, 102, 11196-11200. 9
 Chiral Brönsted acid activation: sp carbon nucleophile

Rueping et al. 2007,

Arndtsen et al.,

- Inexpensive catalyst
- Large scope
- Excellent ee

M. Rueping, A. P. Antonchick, C. Brinkmann, Angew. Chem. Int. Ed. 2007, 46, 6903-6906.
Y. Lu, T. C. Johnstone, B. A. Arnsdtsen, J. Am. Chem. Soc. 2009, 131, 11284-11285. 10
Chiral Brönsted acid activation:
Rh mediated-carbene nucleophile

11
W.-H. Hu, X.-F. Xu, J. Zhou, W.-J. Liu, H.X. Huang, J. Hu, L. P. Yang, L.-Z. Gong, J. Am. Chem. Soc. 2008, 130, 7782-7783.
Enantioselective hydrogenation of imine
Beller’s group in 2011,

An alternative to the Hantzsch dihydropyridine

S. Zhou, S. Fleisher, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2011, 50, 5120-5124. 12
Chiral Brönsted-acid/base with metal activated substrates

Chiral Brönsted acid/base catalyst: a powerful strategy.

In combination with transition-metal, 3 approaches:

13
 Chiral Brönsted base and transition-metal Lewis acid

Enantioselective aza-Henry reaction,

K. R. Knudsen, K. A. Jorgensen, Org. Biomol. Chem. 2005, 3, 1362-1364. 14

Heck Coupling Reaction
Negishi Cross-Coupling Reaction
Suzuki Cross-Coupling Reaction
Sonagashira Cross-Coupling Reaction
Stile Coupling Reaction