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DOI: 10.1055/s-2008-1077984
Synthesis of (±)-Rhazinicine
Contributor(s):Philip Kocienski, Stewart EcclesUniversity of Cambridge and GlaxoSmithKline, Stevenage, UK
Synthesis of Rhazinicine by a Metal-Catalyzed C-H Bond Functionalization Strategy
Angew. Chem. Int. Ed. 2008, 47: 3004-3007
Publication History
Publication Date:
22 August 2008 (online)
Key words
C-H alkenylation - C-H functionalization - (±)-rhazinicine - palladium - iridium
Significance
Rhazinacine is a member of the rhazinilam family of natural products that mimic the cellular effects of paclitaxel. The synthesis of rhazinicine has two noteworthy steps: (1) the C-H functionalization of an N-protected pyrrole (A → C); (2) a palladium(II)-catalyzed intramolecular alkenylation to set up the tetrahydroindolizine ring system (E → F).
Comment
The C-H functionalization was achieved by an iridium-catalyzed borylation followed by Suzuki coupling, which was highly selective for the C-3 position. Intermolecular model studies of the alkenylation showed it was predisposed towards the C-5 position, so this was blocked resulting in the desired substitution exclusively.