Mukaiyama-Michael reaction, iminium

Scheme 71 Iminium ion catalysed Mukaiyama-Michael reaction in the synthesis of compactin...

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

In the total synthesis of (+)-Greek tobacco lactone (14SL1888), the authors utilized the previously reported asymmetric Mukaiyama—Michael reaction of acrolein with a 2-siloxyfuran to prepare the key aldehyde intermediate in one step (14CEJ5983). This process was catalyzed by tmns-2,5-diphenylpyrrolidine via an iminium intermediate, with high enantioselectivity. The natural product was obtained from the aldehyde intermediate in a remarkable 34% overall yield in only four steps. 

In addition, sUyl enol ethers of substituted acetophenones [93] or thioesters [94] react with a,P-unsaturated aldehydes under iminium-catalysis conditions in the sense of a Mukaiyama-Michael reaction (Scheme 4.24). Apphcations of this transformation can be found in the total syntheses of compactin [95] and ho mod trie acid lactone and its homolog [96]. 

Chiral imidazolidinones like 20 serve as chiral organocatalysts for the enantioselective reactions of 2-siloxyfuran with a y9-unsaturated aldehydes through oc,fi-unsaturated iminium species (Scheme 3-83)J The Mukaiyama-Michael reaction with nitroolefines provides an access to 1,3-dicarbonyl compounds... 

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. 

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