Forming Tertiary Organolithiums and Organocuprates from Nitrile Precursors and their Bi molecular Reactions with Carbon Electrophiles to Form Quaternary Carbon Stereocenters

摘要

The stereoselective formation of quaternary carbons is one of the most demanding challenges in organic synthesis. An especially direct way to construct such stereocenters would be to combine a prochiral tertiary organometallic and a carbon-centered electrophile (Scheme 1 A). However, this strategy is not mentioned in the numerous reviews of stereoselective synthesis of chiral quaternary carbons, and to our knowledge has never been employed in target-directed organic synthesis. This omission undoubtedly derives from the challenge in generating tertiary organometallic intermediates, particularly those containing three alkyl substituents. We were recently drawn to explore this undeveloped approach for forming quaternary carbon stereocenters in the context of fashioning the demanding C8-C14 bond and the C8 quaternary stereocenter of rearranged spongian diterpenes such as aplyviolene (4) and dendrillolide A (5) by the reaction of tertiary organocuprate 1 and cyclopentenone 2. This coupling was anticipated to take place from the convex face of nucleophile 1 and from the face of 2 opposite the branched side chain (Scheme 1 B).