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 Bu^tCH(OSiMe₃)COPh 13b is normal in giving Z-Bu^tCH 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 = Bu^t) does not give the ketone Bu^tCH₂COBu^t, but gives instead the anti-Felkin meso diol Bu^tCHOHCHOHBu^t 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).