A Short Synthesis of (±)-3-Demethoxyerythratidinone by Ligand-Controlled Selective Heck Cyclization of Equilibrating Enamines

Angewandte Chemie - International Edition

5 years ago

A Short Synthesis of (±)-3-Demethoxyerythratidinone by Ligand-Controlled Selective Heck Cyclization of Equilibrating Enamines

Kevin I. Booker-Milburn, Emma E. Blackham

A short, 5-step total synthesis of (±)-3-demethoxyerythratidinone from a simple pyrrole derivative is described. Features include the formation of gram quantities of a key tricylic aziridine from a challenging photochemical cascade reaction through the use of flow photochemistry. The final step involved a highly unusual Heck cyclization whereby ligand control enabled efficient formation of the natural product in 69 % yield from the minor isomer present in an equilibrating mixture of labile enamines. Five steps to success: A short total synthesis of (±)-3-demethoxyerythratidinone (1) has been completed using a combination of photochemistry and Pd-catalyzed Heck cyclization. A key feature was the ability to control the outcome of the Heck cyclization onto an equilibrating mixture of labile enamines by ligand choice.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201701775