Difunctionalization of C–C σ Bonds Enabled by the Reaction of Bicyclo[1.1.0]butyl Boronate Complexes with Electrophiles: Reaction Development, Scope, and Stereochemical Origins

Steven Bennett, Alexander Fawcett, Elliott Denton, Tobias Biberger, Valerio Fasano, Nils Winter, Varinder K. Aggarwal*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Difunctionalization reactions of C-C σ bonds have the potential to streamline access to molecules that would otherwise be difficult to prepare. However, the development of such reactions is challenging because C-C σ bonds are typically unreactive. Exploiting the high ring-strain energy of polycyclic carbocycles is a common strategy to weaken and facilitate the reaction of C-C σ bonds, but there are limited examples of highly strained C-C σ bonds being used in difunctionalization reactions. We demonstrate that highly strained bicyclo[1.1.0]butyl boronate complexes (strain energy: ca. 65 kcal/mol), which were prepared by reacting boronic esters with bicyclo[1.1.0]butyl lithium, react with electrophiles to achieve the diastereoselective difunctionalization of the strained central CC -bond of the bicyclo[1.1.0]butyl unit. The reaction shows broad substrate scope, with a range of different electrophiles and boronic esters being successfully employed to form a diverse set of 1,1,3-trisubstituted cyclobutanes (>50 examples) with high diastereoselectivity. The high diastereoselectivity observed has been rationalized based on a combination of experimental data and DFT calculations, which suggests that separate concerted and stepwise reaction mechanisms are operating depending upon the migrating substituent and electrophile used.
Original languageEnglish
Pages (from-to)16766–16775
Number of pages10
JournalJournal of the American Chemical Society
Volume142
Issue number39
DOIs
Publication statusPublished - 4 Sep 2020

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