Enantioselective, Vinylogous Mannich Reactions

Vinylogous Mannich products have proven to be extremely valuable synthetic 

Chiral Amine Synthesis Methods, Developments and Applications. Edited by Thomas C. Nugent Copyright 2010 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32509-2 

In this review we will attempt to highlight the most important contributions toward the realization of a catalytic, enantioselective, vinylogous Mannich reaction and show the current state of the art. This chapter is organized in such a way that vinylogous Mannich reactions of preformed silyl dienolates in Mukaiyama type reactions will be discussed first followed by direct vinylogous Mannich reactions of unmodified substrates. 

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In 2008 our group reported the first example of a catalytic, enantioselective, vinylogous Mannich reaction of acyclic silyl dienolate 30 with imines (Table 5.5) [14]. 

Scheme 5.10 Enantioselective, vinylogous Mannich reaction of silyl dienolate 30 catalyzed by...

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

Giera DS, Sickert M, Schneider C (2008) Brfmsted Acid-Catalyzed, Enantioselective, Vinylogous Mannich Reaction of Vinylketene Silyl N,0-Acetals. Org Lett 10 4259... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

The enantioselective vinylogous Mannich reaction of siloxyfurans with ketimines catalyzed by a cinchona alkaloid amide/Cu(OAc)2 combination afforded furan-2(5fJ)-one containing contiguous tetra- and trisubstituted stereocenters with high selectivity (13AGE5557). 

M. Sickert, F. Abels, M. Lang, J. Sieler, C. Birkemeyer, C. Schneider, Chem.-Eur. J. 2010,16, 2806-2818. The Brpnsted acid catalyzed, enantioselective vinylogous Mannich reaction. 

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