Stereoselective synthesis of spiro and condensed pyrazolines of steroidal α,β-unsaturated ketones and nitrilimines by 1,3-dipolar cycloaddition

Effective syntheses of endo- and exocyclic alpha,beta-unsaturated ketones as C=C dipolarophiles were carried out in the 13 alpha-estrone series. The 1,3-dipolar cycloadditions of 15,16 alpha,beta-unsaturated ketones of 13 alpha-estrone 3-methyl and 3-benzyl ether with nitrilimines stereoselectively furnished two regioisomers of new condensed pyrazolines in a ratio of 2:1. The main product was the isomer obtained by the attack of the N-terminus of the 1,3-dipole on the carbon atom P to the carbonyl group of the dipolarophile. The nitrilimine cycloadditions to the 16-methylene-17-ketones of 13 alpha-estrone 3-methyl and 3-benzyl ether stereo- and regioselectively furnished spiropyrazolines. The attack of the N-terminus of the dipole occurred on the alpha-carbon of the alpha,beta-unsaturated ketones. The reactions were performed under both homogeneous and heterogeneous conditions. Silver acetate as a base proved more effective than its triethylamine counterpart. Changes in regio- and stereoselectivi ties were not observed on variation of the conditions of the cycloaddition reactions. The structures of the new products were determined by NMR (one- and two-dimensional) and MALDI TOF MS techniques. with C-70 fullerenes as matrix in the latter case. (C) 2009 Elsevier Inc. All rights reserved.