Cyclization by C(sp3)-H Arylation with a Transient Directing Group for the Diastereoselective Preparation of Indanes

Philip A. Provencher, Katherine L. Bay, John F. Hoskin, K. N. Houk, Jin Quan Yu, Erik J. Sorensen

Research output: Contribution to journalArticlepeer-review

Abstract

We report Pd(II)-catalyzed cyclative C(sp3)-H arylation of ketones with a transient directing group (TDG). Based on calculations, the oxidative addition step implicates a highly strained trigonal bipyramidal geometry around a Pd(IV) intermediate afforded by the bidentate TDG and the intramolecular arylation process. As a consequence, unproductive protodeiodination outcompetes the cyclative arylation Pd(II/IV) pathway under standard conditions. The desired selectivity was achieved by prudent selection of the TDG and the Ag(I) source. The reaction is accelerated by the inclusion of stoichiometric quantities of trifluoroacetic acid, which benefits both the palladium catalysis and the attachment of the TDG for the pivotal C(sp3)-H palladation. Critically, the use of the 2-pyridone ligand improves yields significantly and enables the cyclative arylation of both methyl and linear methylene C-H bonds. Mechanistically, the high energy barrier associated with the transition state of this cyclization type is sufficient to drive selective linear methylene C-H activation in the presence of a more reactive methyl C-H bond. The reaction is showcased in a two-step synthesis of a substituted indane using 3-iodoanisole as the linchpin in a formal [3 + 2] annulation concept featuring two C(sp3)-H arylations.

Original languageEnglish (US)
Pages (from-to)3115-3127
Number of pages13
JournalACS Catalysis
Volume11
Issue number5
DOIs
StatePublished - Mar 5 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • C-H activation
  • arylation
  • cyclization
  • diastereoselective
  • indane
  • palladium
  • transient directing group

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