Selective synthesis of ferrocenes

Abstract

We have developed a new one pot procedure for the selective functionalization of the 1′ position in ferrocenecarbaldehyde, with fair yields (up to 70%) and good regioselectivity (>90/10). Our method uses lithium N-methylpiperazide as a temporary protecting group of the aldehyde function and directing group for lithiation on the unsubstituted cyclopentadienyl ring of ferrocene. The extension of this new method with enantiomerically pure 2-substituted ferrocenecarbaldehydes provides an easy access to various enantiomerically pure 1,2,1′-trisubstituted ferrocenes with three different groups. Finally, when applying our method for the lithiation of 1,1′-ferrocenedicarbaldehyde with a chiral amine, we found a one pot synthesis of 1,2,1′,2′-tetrasubstituted C 2-symmetrical ferrocenes with very high enantiomeric excesses (>99%). Furthermore, changing the experimental conditions allows us to obtain 1,2,1′-trisubstituted ferrocenes with a very good enantioselectivity (up to 96%). The first chiral enantiomerically pure 2-substituted 1,1′-( β- oxa-trimethylene)ferrocenes and the first chiral enantiomerically pure C 2-symmetrical-disubstituted 1,1′-( β- oxa-trimethylene)ferrocene were also synthesized.