ASYMMETRIC SYNTHESIS OF CDP840 BY JACOBSEN EPOXIDATION. AN UNUSUAL SYN SELECTIVE REDUCTION OF AN EPOXIDE

An asymmetric synthesis of the PDE IV inhibitor, CDP840 (3) is reported. The absolute stereochemistry was controlled by a Jacobsen epoxidation of the Z triaryl olefin 8 (89% ee) or the E triaryl olefin 9 (48% ee). The disparate results in stereocontrol were interpreted in terms of the “skewed side-on approach model” proposed by Jacobsen. LiBH4·BH3 reduction of the epoxides was found to proceed with retention of configuration.