Samarium(II) folding cascades involving hydrogen atom transfer for the synthesis of complex polycycles

• DOI: 10.1038/s41467-018-07194-x
• Publication Date: 2018-11-09T15:06:30Z
• Authors: Mateusz P. Plesniak; Monserrat H. Gard...; Philipp Lenz; Xavier Just-Baringo; David J. Procter
• Keywords: Folding (DSP implementation); Natural product; Hydrogen atom

The expedient assembly of complex, natural product-like small molecules can deliver new chemical entities with the potential to interact biological systems and inspire development drugs probes for biology. Diversity-oriented synthesis is a particularly attractive strategy delivery complex in which 3-dimensional architecture varies across collection. Here we describe folding cascade approach polycyclic bearing multiple stereocentres mediated by reductive single electron transfer (SET) from SmI2. Simple, linear substrates undergo three different pathways triggered SET. Two radical involve activation functionalization otherwise inert secondary alkyl benzylic groups 1,5-hydrogen atom (HAT). Combination SmI2, privileged reagent reactions, 1,5-HAT lead complexity-generating sequences that unlock access diverse structures not readily accessible other means.