ChemInform Abstract: Desymmetrization of 3-Dimethyl(phenyl)silyl Glutaric Anhydride with Evans′ Oxazolidinone: An Application to Stereocontrolled Synthesis of the Antifungal Agent (+)-Preussin

A stereoselective total synthesis of (+)-preussin (1) has been achieved from the σ-symmetric 3-dimethyl(phenyl)silyl substituted glutaric anhydride 4 featuring its desymmetrization using Evans’ oxazolidinone 10. The first homochiral intermediate, the glutarate half-ester 9 was obtained from both the diastereoisomeric acids 11a and 12a in a convergent fashion. The dimethyl(phenyl)silyl group is not only acting as a masked hydroxy group but also restricts elimination reactions and facilitates Curtius reaction. It also stereodirects ester enolate alkylation of 18 and hydrogenation of intermediate Δ1-pyrroline 5.