ADDITION OF TERT-BUTYLDIMETHYLSILYL 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-degrees-C) or bases (KCN, 18-crown-6, CH2Cl2, 25-degrees-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 dithioketal-protected 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'-[(di-methyl(1,1-dimethylethyl)silyl)oxy]-4a'-methylspiro[1,3-dithiolane-2,2'(3'H)-naphthalene]-5'-car-bonitrile (+)-(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.