Organic catalysis Conjugate addition

P. Perlmutter, Conjugate Addition Reactions in Organic Synthesis, Tetrahedron Organic Chemistry Series Vol. 9, Pergamon Press, Oxford, 1992 B. E. Rossiter and N. M. Swingle, Chem. Rev., 92, 111 (1992) J. Leonard, E. Dtez-Barra and S. Merino, Ear. J. Org. Chem., 2051 (1998) M. P. Sibi and S. Manyem, Tetrahedron, 56, 8033 (2000) N. Krause and A. Hoffmann-Roder, Synthesis, 171 (2001) K. Tomioka and Y. Nagaoka, in Comprehensive Asymmetric Catalysis (Eds. E. N. Jacobsen, A. Pfaltz and H. Yamamoto), Vol. Ill, Chap. 31.1, Springer, Berlin, 1999 K. Tomioka, in Modem Carbonyl Chemistry (Ed. J. Otera), Chap. 12, Wiley-VCH, Weinheim, 2000. 

This is an important area with many available methods. We shall look first at organic catalysis and then change to catalysis by metal complexes. The same type of intermediate 117 used for conjugate addition is clearly also suitable for Diels-Alder reactions with the same proviso it must be more reactive then the a,(5-unsaturated carbonyl compound as that too can do Diels-Alder reactions. And of course the first formed product 118 must hydrolyse rapidly to release the catalyst 102. 

Abstract In this chapter, the asymmetric organocatalytic conjugate addition of nucleophiles to Michael acceptors is covered. This report presents an overview of the most important developments and concepts of this area of catalysis organized by the type of nucleophile involved in the process. 

Metal-catalyzed reactions have been of major importance in synthetic organic chemistry. Over the past decade, enantio- and diastereoselective metal-mediated domino catalysis has emerged as an effective tool to construct really highly complex molecules in one-pot processes [2, 4b,d]. Among them, enantioseletcive metal-catalyzed conjugate additions (in particular, Cu-catalyzed 1,4-addition to a,P-unsaturated carbonyl compounds) have been useful components of domino reactions [4d, 5]. The generated metal enolates 2 after the additions of nucleophiles readily react with a variety of electrophiles (Scheme 11.1). Enantioselectivity of 3 depends on the first addition of nucleophiles to the P-position of the unsaturated carbonyl compounds 1. 

This work represents a landmark in the area of stereoselective metal-free (i.e., aminocatalysis) alkylation of benzenes based on Michael-type condensation via covalent catalyst-substrate interaction [22]. Subsequently, asymmetric acid catalysis based on hydrogen bond catalyst-substrate recognitions has found elegant applications in 1,4-conjugated additions and direct condensation of arenes with carbonyl compounds. The following sections will be organized based on the reactivity exploited in the arene functionalization. 

Conjugate Addition. Catalytic asymmetric conjugate addition of acetylenes to a. -unsaturated carbonyl confounds is one of the most challenging tasks in organic chemistry and TIPS-acetylene has been used as a useful tool reagent to confirm the viability of the developed protocols. Rh(I)-catalyzed conjugate alkynylation has been extensively developed by Hayashi and coworkers. Asymmetric conjugate addition of TIPS-acetylene was accomplished via a Rh(T) catalysis (eq 28) and the effects of the alkyl substituents on the sUylacetylenes were examined for their... 

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