Stereoselective reduction of the bioactive 19-nor-clerodane trans-dehydrocrotonin by using sodium borohydride and cerium (III) chloride as a catalyst

Abstract The bioactive 19- nor -clerodane trans -dehydrocrotonin ( t -DCTN) is herein used as starting material to afford an epimeric derivative mixture so called t -DCTN-α and β-OL, which is a diastereoisomeric pair. The stereoselective reduction of t -DCTN was performed in methanol medium by using NaBH 4 and CeCl 3 ·7H 2 O which react reducing the C2 carbonyl group on the t -DCTN decalin ring moiety. The t -DCTN-diastereoisomeric compounds were characterized by chromatographic HPLC analyses and by NMR data. The crystal structure of t -DCTN-α-OL was confirmed employing X-ray diffraction. Additionally, an experimental and theoretical NMR chemical shifts study applied to the t -DCTN diastereoisomeric derivatives lead favorable coefficients of correlation (R > 0.98) by using B3LYP combined with 6–311++G(d,p) basis set. Furthermore, a modified Gemal and Luche's mechanism in stepwise fashion is proposed. Agreement between theoretical and experimental higher reactivity of NaBH 4 /Ce 3+ towards NaBH 4 was found and the theoretical results explicit the participation of the reaction solvent (methanol) on transition state by using NaBH 4 unlike that involving NaBH 4 /Ce 3+ . It was found that the proposed modified mechanism only occurs in 0.8 eq. of Ce 3+ salt.