A free-radical design featuring an intramolecular migration for a synthetically versatile alkyl-(hetero)arylation of simple olefins

Dylan J. Babcock, Andrew J. Wolfram, Jaxon L. Barney, Santino M. Servagno, Ayush Sharma, Eric D. Nacsa

Research output: Contribution to journalArticlepeer-review

Abstract

A free-radical approach has enabled the development of a synthetically versatile alkyl-(hetero)arylation of olefins. Alkyl and (hetero)aryl groups were added concurrently to a full suite of mono- to tetrasubstituted simple alkenes (i.e., without requiring directing or electronically activating groups) for the first time. Key advances also included the introduction of synthetically diversifiable alkyl groups featuring different degrees of substitution, good diastereocontrol in both cyclic and acyclic settings, the addition of biologically valuable heteroarenes featuring Lewis basic nitrogen atoms as well as simple benzenes, and the generation of either tertiary or quaternary benzylic centers. The synthetic potential of this transformation was demonstrated by leveraging it as the key step in a concise synthesis of oliceridine, a new painkiller that received FDA approval in 2020.

Original languageEnglish (US)
Pages (from-to)4031-4040
Number of pages10
JournalChemical Science
Volume15
Issue number11
DOIs
StatePublished - Feb 2 2024

All Science Journal Classification (ASJC) codes

  • General Chemistry

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