The hydroformylation of Delta 4 - and Delta 5 -steroids, namely cholest-4-ene (1), 3 eta-acetoxycholest-4-ene (2), 3 beta-acetoxycholest-5-ene (3), and 3 beta-acetoxypregn-5-en-20-one (4), was studied using rhodium catalysts modified with beta-donor ligands containing electron withdrawing substituents, such as tris(o-tert-butylphenyl)phosphite, tris(o-trifluoromethylphenyl)phosphine and tris(p-trifluoromethylphenyl)phosphine. The effect oftemperature, pressure and ligand/Rh molar ratios on the regio- and stereoselectivity of the reaction were studied. Under the reaction conditions assayed, only the Delta(4) -steroids 1 and 2 are hydroformylated, producing the 4-formyl derivatives with 100 % regioselectivity and 70 and 60 % stereoselectivity for the P isomer, respectively. Delta(5) -Steroids 3 and 4 either did not react or produced traces of products from the isomerization of the double bond. Among the three catalysts used, only the Rh/tris(o-tert-butylphenyl)phosphite was able to catalyze the hydroformylation of A4 -steroids. The two new formyl steroids obtained from 1, 4-formyl-5 alpha-H-cholestane (6) and 4-formyl-5 beta-H-cholestane (7), were isolated as their acetal derivatives and fully characterized by 2D NMR techniques. The structure of the acetal arising from the minor aldehyde product of the reaction was further corroborated byX-ray analysis. The mechanism of there action-for the conversion of 3p-acetoxycholest-4-ene2 into 7 was investigated, through the hydroformylation of (1 R)-(-)-myrtenyl acetate (5) as a cyclic allylic acetate model. The results show that the reaction does not take place through an allylic intermediate, but that the major aldehyde obtained from 2 undergoes AcOH elimination followed by stereoselective hydrogenation of the alpha,beta-unsaturated aldehyde, leading to 7. (c) 2007 Elsevier B.V. All rights reserved.