Ernst Schering Foundation Symposium Proceedings, Vol. 2, pp. 1–43
DOI 10.1007/2789_2008_084
© Springer-Verlag Berlin Heidelberg
Published Online: 30 April 2008
New Concepts for Organocatalysis
S.C. Pan, B. List
(u)
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1,
45470 Mülheim an der Ruhr, Germany
email: list@mpi-muelheim.mpg.de
1
Introduction: Organocatalysis . . . . . . . . . . . . . . . . . . . . 2
2
Enamine Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1
The Proline-Catalyzed Asymmetric Aldol Reaction: Scope,
Mechanism and Consequences . . . . . . . . . . . . . . . . . . . 5
2.2
Enamine Catalysis of Nucleophilic Addition Reactions . . . . . . 8
2.3
Enamine Catalysis of Nucleophilic Substitution Reactions . . . . . 10
2.4
The Proline-Catalyzed Asymmetric Mannich Reactions . . . . . . 10
3
Brønsted Acid Catalysis . . . . . . . . . . . . . . . . . . . . . . . 14
3.1
Catalytic Asymmetric Pictet–Spengler Reaction . . . . . . . . . . 15
3.2
Organocatalytic Asymmetric Reductive Amination . . . . . . . . . 17
4
Iminium Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . 22
4.1
Organocatalytic Conjugate Reduction of α,β-Unsaturated
Aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5
Asymmetric Counteranion Directed Catalysis . . . . . . . . . . . 26
5.1
Asymmetric Counteranion-Directed Catalysis: Application
to Iminium Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . 28
6
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Abstract. Organocatalysis, catalysis with low-molecular weight catalysts in
which a metal is not part of the catalytic principle or the reaction substrate, can
be as efficient and selective as metal- or biocatalysis. Important discoveries in
this area include novel Lewis base-catalyzed enantioselective processes and,
more recently, simple Brønsted acid organocatalysts that rival the efficiency
of traditional metal-based asymmetric Lewis acid-catalysts. Contributions to
DOI 10.1007/2789_2008_084
© Springer-Verlag Berlin Heidelberg
Published Online: 30 April 2008
New Concepts for Organocatalysis
S.C. Pan, B. List
(u)
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1,
45470 Mülheim an der Ruhr, Germany
email: list@mpi-muelheim.mpg.de
1
Introduction: Organocatalysis . . . . . . . . . . . . . . . . . . . . 2
2
Enamine Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1
The Proline-Catalyzed Asymmetric Aldol Reaction: Scope,
Mechanism and Consequences . . . . . . . . . . . . . . . . . . . 5
2.2
Enamine Catalysis of Nucleophilic Addition Reactions . . . . . . 8
2.3
Enamine Catalysis of Nucleophilic Substitution Reactions . . . . . 10
2.4
The Proline-Catalyzed Asymmetric Mannich Reactions . . . . . . 10
3
Brønsted Acid Catalysis . . . . . . . . . . . . . . . . . . . . . . . 14
3.1
Catalytic Asymmetric Pictet–Spengler Reaction . . . . . . . . . . 15
3.2
Organocatalytic Asymmetric Reductive Amination . . . . . . . . . 17
4
Iminium Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . 22
4.1
Organocatalytic Conjugate Reduction of α,β-Unsaturated
Aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5
Asymmetric Counteranion Directed Catalysis . . . . . . . . . . . 26
5.1
Asymmetric Counteranion-Directed Catalysis: Application
to Iminium Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . 28
6
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Abstract. Organocatalysis, catalysis with low-molecular weight catalysts in
which a metal is not part of the catalytic principle or the reaction substrate, can
be as efficient and selective as metal- or biocatalysis. Important discoveries in
this area include novel Lewis base-catalyzed enantioselective processes and,
more recently, simple Brønsted acid organocatalysts that rival the efficiency
of traditional metal-based asymmetric Lewis acid-catalysts. Contributions to