The reduction of α-silyloxy ketones using phenyldimethylsilyllithium

Abstract

Phenyldimethylsilyllithium reacts with acyloin silyl ethers RCH(OSiMe3)COR 8 to give regiodefined silyl enol ethers RCHC(OSiMe2Ph)R 9, and hence by hydrolysis ketones RCH2COR 10. The yields can be high but are usually moderate. The mechanism of this reduction is established to involve a Brook rearrangement (Scheme 6) rather than a Peterson elimination (Scheme 1). Although the mechanism appears to be the same in each case, the stereochemistries of the silyl enol ethers 9 are opposite in sense in the aromatic series (R = Ph, Scheme 7) and the aliphatic series (R = cyclohexyl, Scheme 8), with the major aromatic silyl enol ether being the thermodynamically less stable isomer E-PhCHC(OSiMe2Ph)Ph E-9aa, and the major aliphatic silyl enol ether being the thermodynamically more stable isomer Z-c-C6H11CH C(OSiMe2Ph)-c-C6H11Z-9ba. This is a consequence of anomalous anti-Felkin attack in the aromatic series. The reaction with the silyl ether ButCH(OSiMe3)COPh 13b is normal in giving Z-ButCH C(OSiMe2Ph)Ph Z-38 (Scheme 11), but reduction of the silyl ether 8a with lithium aluminium hydride is also anti-Felkin giving with high selectivity the meso diol PhCH(OH)CH(OH)Ph 39. The reaction between phenyldimethylsilyllithium and the acyloin silyl ether 8d (R = But) does not give the ketone ButCH2COBut, but gives instead the anti-Felkin meso diol ButCHOHCHOHBut 40 also with high selectivity (Scheme 12). Silyllithium and some related reagents react with trifluoromethyl ketones 46 and 48 to give α,α-difluoro silyl enol ethers 47 and 49 (Scheme 14).