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. LiBH 4 ·BH 3 reduction of the epoxides was found to proceed with retention of configuration.