Mukaiyama-Michael lactonization

Scheme 7.80 Asymmetric synthesis of 3,4-dihydropyran-2-ones by cascade Mukaiyama Michael/lactonization.

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

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. 

Mukaiyama et al. have productively employed chiral quaternary ammonium phe-noxides derived from Cinchona alkaloids as catalysts in a new and efficient method for the preparation of optically active 3,4-dihydropyran-2-one derivates via tandem Mukaiyama-Michael addition/lactonization between a, 3-unsaturated ketones and the silyl enolate derived from phenyl isobutyrate (Scheme 2.51) [150]. In this... 

The enantioselective vinylogous Mukaiyama—Michael addition of 2-silyloxyfurans to cyclic unsaturated oxo esters afforded a variety of compounds bearing a y-butenolide or y-lactone connected to a cycloalkane or cycloalkene moiety (13JOC2289). The reaction of siloxyfurans with aromatic aldimines could be catalyzed efficiently by silver(I) complexes of the Ar-BlNMOL-derived chiral monophosphine (13T8777). 

A reported diastereoselective synthesis of precursor A of vitamin D3 involved the use of 2-methylcyclopent-2-enone as starting material. The Mukaiyama-Michael conjugate addition of ketene acetal 269 in the presence of trityl hexachloroaniimonate afforded the adduct 270. The lateral chain was introduced, according the procedure of Tsuji, by the treatment of crude 270 with allyl carbonate and palladium dibenzylideneacetone " (Scheme 63). The expected product 271 was obtained in 63% yield from 269. Reduction of 271 with LAH afforded a mixture of diols that was selectively tosylated at the primary hydroxy group. The secondary hydroxy group was protected with the methoxymethyl group and further functional modifications afforded the lactone 272. The reaction of lithium dimethyl methylphosphonate with the lactone 272 completed the synthesis of the AB-des-cholestane derivative 273. 

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]. 

Silyl enolates are useful carbon nucleophiles in the asymmetric tandem Michael addition and lactonization (Scheme 3.3). Mukaiyama recently reported that cinchona-derived ammonium phenoxides act as activators (nucleophilic catalysis), to give highly stereocontrolled products [18-20]. In a typical PTC manner, most of the... 

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]. 

The monographs (8,9) also present clear expositions of methods of synthesis. A recent communication addressing a short approach to both symmetrical and unsymmetrical tetrahydrofurofuran lignans is outlined in Scheme 32 (149). Michael addition of the sodium salt of the silyl monoprotected diol (155) to the a-sulfonylcinnamate (156) gave the ether (157) which on desulfurization and hydrolysis gave the hydroxy acid (158). Lactonization of (158) by the Mukaiyama method... 

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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