Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group

Jignesh J Patel; Marju Laars; Wei Gan; Johnathan Board; Matthew O Kitching; Victor Snieckus

doi:10.1002/anie.201805203

Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group

Angew Chem Int Ed Engl. 2018 Jul 20;57(30):9425-9429. doi: 10.1002/anie.201805203. Epub 2018 Jun 21.

Authors

Jignesh J Patel¹, Marju Laars¹, Wei Gan¹, Johnathan Board¹, Matthew O Kitching², Victor Snieckus¹

Affiliations

¹ Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, ON, K7L 3N6, Canada.
² Department of Chemistry, Durham University, South Rd, Durham, DH1 3LE, UK.

PMID: 29847003
DOI: 10.1002/anie.201805203

Abstract

A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt₂ or LiNiPr₂ into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3'-diaryl BINOL ligands is also reported.

Keywords: C−H activation; cyclization; lithiation; metalation; naphthols.