Synthesis of enantiomerically pure all cis-2,3,6-trisubstituted piperidine: a silicon mediated total synthesis of (+)-carpamic acid

A stereoselective total synthesis of (+)-carpamic acid 1 has been achieved from the σ-symmetric 3-[dimethyl(phenyl)silyl]glutaric anhydride 11 featuring its asymmetric desymmetrisation using oxazolidinone 12. The dimethyl(phenyl)silyl group is not only acting as a masked hydroxy group but also stereodirects ester enolate methylation and facilitates the Curtius reaction of the β-silyl-amide 23. A highly stereoselective hydrogenation of the imine 10 is the key step in the construction of the all cis-2,3,6-trisubstituted piperidine.