Stereocontrol at the C-22 Position of Steroid Side Chain with the Aid of Organostannanes

Abstract

Treatment of the chiral steroidal acetal ([8], S-R, R isomer), prepared from the steroidal aldehyde [3] and (2 R, 4 R)-(-)-2, 4-pentanediol, with allyltrimethylsilane [12 a], 9-ally19-BBN [12 b], or allyltributylstannane [12 c] in the presence of TiC14 followed by the usual work-up gave the homoallyl alcohol ([14], S, S-isomer) either exclusively or highly predominantly. Although the corresponding reaction of the chiral acetal ([9], S-S, S isomer), prepared from [3] and (2 S, 4 S)-(+)-2, 4-pentanediol, with [12 a] or [12 b] gave again [14]predominantly, an isomeric homoallyl alcohol [16], 5, R-isomer, was obtained preferentially with [12 c]. Similarly, the reaction of stannylacetylenes ([11 a], [11 b]) with [ 8 ] produced the S, S-isomer [13], while an analogous reaction with [9] gave the S, R-isomer [15] predominantly. The reaction of [9]with [11 c] gave the S, S-isomer [13] with high stereoselectivity. These results clearly indicate that the enantiomer excess or even the direction of asymmetric induction strongly depends on the nucleophilicity of organometallic compounds, and provide for the first time evidence that the bond-formation and bond-cleavage are fully concerted to achieve the high asymmetric induction dictated by acetal templates.