Methyl trichlorosilyl ketene acetal

Methyl trichlorosilyl ketene acetal reacts with aromatic and aliphatic ketones (the former enantioselectively), using chiral pyridine bis-N-oxide catalysts.134 Computations and an X-ray crystal structure of a catalyst-SiCU complex have helped to elucidate the mechanism. 

Preparative Methods two different routes have been developed for the preparation of methyl trichlorosilyl ketene acetal. One route is through bis(tributyltin) oxide-catalyzed transmetala-tion of methyl tributylstannyl acetate (2) with silicon tetrachloride (eq 1).3 When the reaction is complete, excess silicon tetrachloride is removed and the product is purified by fractional distillation under reduced pressure. 

Handlings Storage, and Precautions methyl trichlorosilyl ketene acetal is a thermally unstable and hydrolytically labile... 

Aldol Additions to Ketones. Traditionally, cerium enolates or the Reformatsky-type reaction have been employed to achieve high-yielding aldol additions to enolizable ketones. In this regard, methyl trichlorosilyl ketene acetal provides a reliable alternative for the synthesis of tertiary -hydroxy esters. In the absence of a Lewis base promoter, the aldol additions of 1 to ketones are too slow to be synthetically useful. On the contrary, with pyridine A-oxide as catalyst, methyl trichlorosilyl ketene acetal reacts smoothly with nearly all classes of ketones (7) (Scheme 1). Good yields of the tertiary alcohol products (8) are obtained (eq 4), table 2 from aromatic (entries 1-2 and 4—6), hetereoaromatic (entry 3), olefinic (entries 7-8), acetylenic (entries 9-10), and aliphatic (entries 11-14) ketones. The only poorly performing substrate is 2-tetralone (7o), which affords a 45% yield of the addition product and returns 45% of unreacted starting material, most likely from competitive enolization. 

Ester Enolate Aldol Additions to Aldehydes. Among the first examples of aldol additions employing chiral Lewis bases as catalysts were the additions of trichlorosilyl ketene acetals to aldehydes. Silyl ketene acetal 7 could be generated by metathesis of methyl tributylstannylacetate with SiCL. Treatment of 7 with benzaldehyde and 10 mol % of a phosphoramide in CH2CI2 at —78°C afforded aldol products in good to high yields with moderate enantioselectivities for all phosphoramides employed. Reaction of 7 with pivalaldehyde provided aldol products in similar yields and with slightly improved enantioselectivities. The increase in stereoselection is presumably attributed to a less com-... 

In a novel departure from the traditional approach to the asymmetric Mukaiyama aldol, Denmark has reported a Lewis base-catalyzed aldol addition reaction of enol trichlorosilanes and aldehydes. These unusual silyl ketene acetals are readily prepared by treatment of the tributylstannyl enolates 246 with SiC (Eq. 51). In the initial ground-breaking studies, the methyl acetate-derived trichlorosilyl ketene acetal 247 was shown to add rapidly to a broad range of aldehydes at -80 C to give adducts (89-99% yield, Eq. 52). 

This class of chiral Lewis base catalysts was also applicable to the enantioselective aldol reactions of trichlorosilyl enol ethers (Scheme 7.14) [24, 25). As included in Scheme 7.14, Denmark devised chiral bipyridine N.N -dioxide 8 and demonstrated that it smoothly catalyzed the aldol addition of methyl acetate-derived trichlorosilyl ketene acetal to a series of ketones with good to high enantioselectivi-ties [25],... 

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