Addition of tert-Butyldimethyl- or tert-Butyldiphenylsilyl Cyanide to Hindered Ketones

The addition of trimethylsilyl cyanide (TMSCN), tert-butyldimethylsilyl cyanide (TBDMSCN) or tert-butyldiphenylsilyl cyanide (TBDPSCN) to sterically hindered ketones proceeded in good yield under catalysis by Lewis acids (ZnI₂, CH₂Cl₂, 25 °C) or bases (KCN, 18-crown-6, CH₂Cl₂, 25 °C). For example, the ZnI₂-catalyzed addition of TBDMSCN to 2,2-dimethylcyclohexanone (3e), 2,2,6-trimethylcyclohexanone (3f), and 2,2,6,6-tetramethylcyclohexanone (3g) provided the protected cyanohydrins 4e, 4f, and 4g in 94, 83, and 92% yield, respectively. The C-1 ketone of C-6 dithioketalprotected Wieland-Miescher ketone ((4′aS)-4′,4′a,7′,8′-tetrahydro-4a′-methylspiro[1,3-dithiolane-2,2′(3′H)-naphthalen]-5′(6′H)-one (+)-(8)) provided (4′aS,5′S)-4′,4′a,5′,6′,7′,8′-hexahydro-5′-[(dimethyl(1,1-dimethylethyl)silyl)oxy]-4a′-methylspiro[1,3-dithiolane-2,2′(3′H)-naphthalene]-5′-carbonitrile (+)-(10b) in 94% yield. An X-ray crystallographic study established that the C-5 center in (+)-10b has the correct absolute stereochemistry needed for a projected synthesis of the C-1 center in the A ring of taxol using (+)-10b as a starting material.