Mukaiyama-type Michael addition

The Mukaiyama-type Michael addition of sUyl enol ether to enoate catalyzed by EtAlCl2 affords the corresponding silyl ketene acetal, and then successively to the intramolecular silyl oxonium carbon to provide a cyclobutane... 

Michael Reactions. Several reports highlighting utilization of the title reagent in Mukaiyama-type Michael reactions have now appeared. 3,4-Dihydro-Q -pyrones are obtained in quantitative yield from the reagent and a, -unsaturated ketones via a two-step sequence comprising conjugate addition followed by mercuric ion mediated cycUzation (eq 11). ... 

The elfectiveness of imidazolidinone of type 11 was confirmed by successful application to a broad range of chemical transformations, including cycloadditions, conjugate additions, Friedel-Crafts alkylations, Mukaiyama-Michael additions, hydrogenations, cyclopropanations, and epoxidations. A summary of these enantio-selective iminium catalyzed processes is provided by reaction subclass. 

Intermolecular Michael addition [4.1] Intermolecular aldol reaction [6.2.1] Intramolecular aldol reaction [6.2.2] Aldol-related reactions (e.g. vinylogous Mukaiyama-type aldol) [6.2.3]... 

The third part of this chapter reviews previously described catalytic asymmetric reactions that can be promoted by chiral lanthanoid complexes. Transformations such as Diels-Alder reactions, Mukaiyama aldol reactions, several types of reductions, Michael addition reactions, hydrosilylations, and hydroaminations proceed under asymmetric catalysis in the presence of chiral lanthanoid complexes. 

Mechanistically, enamine and Lewis-acid-mediated conjugate additions are complex. The opportunity exists for the product-determining step to occur at a number of points and, without further study, the precise nature of the manifold is not entirely clear. In some enamine cases where the stereoselectivity likely results from the conjugate addition, a synclinal type transition state seems to be involved. With the Mukaiyama-Michael addition, some processes implicate an open-extended pathway. Despite the mechanistic uncertainties that remain, sufficient data are now available so that the stereochemistry in many cases can be anticipated by extrapolation. 

Kitazume and coworkers used microreactors with microchaimels 100 pm wide and 40 pm deep for the synthesis of a series of organofluorine compounds [19,20]. The silylation of4,4,4-trifluorobutan-2-one and the Mukaiyama-type aldol reaction of the resulting enol silyl ether with acetals gave good yields of the desired products [20]. They also described nitro-aldol reactions of 2,2-difluoro-l-ethoxyethanol and Michael additions of nitroalkanes to ethyl 4,4,4-trifluorocrotonate and ethyl 4,4-difluorocrotonate [19,20]. Reactions were carried out at room temperature, and... 

By 1989 Mukaiyama had already explored the behaviour of phosphonium salts as Lewis acid catalysts. It was possible to show that the aldol-type reaction of aldehydes or acetals with several nucleophiles and the Michael reaction of a,j3-unsatu-rated ketones or acetals with silyl nucleophiles gave the products in good yields with a phosphonium salt catalyst [116]. In addition, the same group applied bisphosphonium salts as shown in Scheme 45 in the synthesis of ]3-aminoesters [117]. High yields up to 98% were obtained in the reaction of A-benzylideneaniline and the ketene silyl acetal of methyl isobutyrate. Various analogues of the reaction parteers gave similar results. The bisphosphonium salt was found to be superior to Lewis acids like TiCl and SnCl, which are deactivated by the resulting amines. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

The conditions used for the Mukaiyama-aldol type reactions employing InCh (see Section 8.2) were found by Loh et al. to be useful in Michael-type additions of silyl enol ethers to a,P-unsaturated carbonyl compounds [49] (Figure 8.25). 

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