Chemoenzymatic synthesis of optically active 1,2-disubstituted ferrocenes with planar chirality

A new pathway for the synthesis of 2-substituted ferrocenyl compounds with planar chirality using a chemoenzymatic resolution as the key step is described. The kinetic resolution of racemic 2-hydroxy-methyl phenylthioferrocene 4 has been optimised and carried Out on a multi-gram scale using CAL-B lipase, giving the resulting acetate and remaining alcohols in ee's >99%. The enantiomerically enriched sulfides have been transformed via a two-step sequence, in a new family of 2-substituted ferrocenyl alcohol by using a sulfoxide-lithium exchange/electrophilic trapping sequence; this gives straightforward access to non-racemic ferrocenyl alcohols with planar chirality. (C) 2009 Elsevier Ltd. All rights reserved.