Samarium(II) Folding Cascades Involving Hydrogen Atom Transfer for the Synthesis of Complex Polycycles

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Nov 17

PMID 30442955

Citations 3

Authors

Mateusz P Plesniak

Monserrat H Garduno-Castro

Philipp Lenz

Xavier Just-Baringo

David J Procter

Affiliations

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Abstract

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

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