Recent advances in benzylic and heterobenzylic lithiation

Yuk Fung Wong, Graeme Barker

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Aryl and heteroaryl rings are omnipresent in small molecule drugs, and examples bearing multiple substitutions at benzylic positions are ubiquitous across a range of pharmaceutical families. The comparative acidity of α-aryl protons makes organolithium mediated deprotonation-substitution protocols an attractive strategy for effecting substitutions at benzylic positions. In this review, we survey recent advances in benzylic lithiation chemistry, including 1) lithiations facilitated by heteroatom-appended directing groups, 2) lateral lithiations enabled by directing groups attached in the aryl ortho-position, as well as 3) examples remote from any Lewis basic group. Recent 4) heterobenzylic and 5) stereoselective benzylic lithiations are also summarized.
Original languageEnglish
Article number131704
JournalTetrahedron
Volume76
Issue number50
Early online date26 Oct 2020
DOIs
Publication statusPublished - 11 Dec 2020

Keywords

  • Benzylic substitution
  • C–H functionalisation
  • Lithiation
  • Organometallics
  • Pharmaceutical synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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