Lactonization, chiral ammonium phenoxide

Scheme 3.3 Tandem Michael addition and lactonization using chiral ammonium phenoxide.

Diastereo- and enantio-selective cascade of Michael addition and lactonization between various silyl enolates derived from phenyl carboxylates and -unsaturated ketones were successfully carried out by using an efficient organic catalyst, a cinchoni- dine-derived chiral quaternary ammonium phenoxide. In this asymmetric domino reaction, the corresponding tnms-3,4-dihydropyran-2-oncs were obtained in high yields with almost complete diastereoselectivities and good to excellent enantioselectivities.161... 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

In a paper that described a detailed preparation of air-stable cinchona alkaloid-derived chiral quaternary ammonium phenoxides, the Mukaiyama group also used these to enantioselectively prepare 3,4-dihydropyran-2-ones 160 [85]. A low loading of organocatalyst 159 at low temperatures, in a series of solvents, resulted in the formation of the optically active lactone products in high yields with excellent control of enantio- and diastereoselectivity. This process was proposed to go through a phenoxide-ion-catalyzed domino Michael addition and lactonization catalytic cycle as illustrated below. Many variations of the ketene silyl acetals and a, -unsaturated ketones were combined in this domino process (Scheme 7.32). Earlier,... 

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