An Investigation in Oxidative Cation Formation: The Total Synthesis of Lactodehydrothyrsiferol and Synthetic Application for a Bimolecular Carbon–Carbon Bond Forming Reaction

The first total synthesis of lactodehydrothyrsiferol, a selective inhibitor of protein phosphatase 2A, was accomplished through the application of our electron-transfer-initiated cyclization reaction. Other highlights of our synthetic strategy include a novel method for the formation of 1,1-disubstuted vinyl iodides from a terminal alkyne, a Suzuki-Miyaura cross coupling reaction on a iodinated allylic carbonate, a one pot diepoxidation of a diene to generate two epoxides with opposite stereochemical identities, an asymmetric Nozaki-Hiyama-Kishi reaction, and the selective deoxygenation of a triol. This document will focus on the key epoxide cascade and completion of the synthesis. An oxidative method to form Carbon–Carbon bonds through Carbon–Hydrogen bond cleavage is described herein. Chromene and isochromene both form aromatically stabilized oxocarbenium ions in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reactivity of these cations was explored with a variety of nucleophiles. In addition, the electronic properties were altered on the benzopyran ring system to elucidate the substrate scope for this transformation

Aromatic Cations from Oxidative Carbon–Hydrogen Bond Cleavage in Bimolecular Carbon–Carbon Bond Forming Reactions

Chromenes and isochromenes react quickly with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to form persistent aromatic oxocarbenium ions through oxidative carbon–hydrogen cleavage. This process is tolerant of electron-donating and electron-withdrawing groups on the benzene ring and additional substitution on the pyran ring. A variety of nucleophiles can be added to these cations to generate a diverse set of structures