Expeditious diastereoselective synthesis of elaborated ketones via remote Csp<sup>3</sup>-H functionalization.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28082736.
- Also identified by DOI 10.1038/ncomms13832 and PMC identifier 5241786.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The quest for selective C-H functionalization reactions, able to provide new strategic opportunities for the rapid assembly of molecular complexity, represents a major focus of the chemical community. Examples of non-directed, remote Csp<sup>3</sup>-H activation to forge complex carbon frameworks remain scarce due to the kinetic stability and thus intrinsic challenge associated to the chemo-, regio- and stereoselective functionalization of aliphatic C-H bonds. Here we describe a radical-mediated, directing-group-free regioselective 1,5-hydrogen transfer of unactivated Csp<sup>3</sup>-H bonds followed by a second Csp<sup>2</sup>-H functionalization to produce, with exquisite stereoselectivity, a variety of elaborated fused ketones. This study demonstrates that aliphatic acids can be strategically harnessed as 1,2-diradical synthons and that secondary aliphatic C-H bonds can be engaged in stereoselective C-C bond-forming reactions, highlighting the potential of this protocol for target-oriented natural product and pharmaceutical synthesis.