An intramolecular coupling approach to alkyl bioisosteres for the synthesis of multisubstituted bicycloalkyl boronates

Yangyang Yang, Jet Tsien, Jonathan M.E. Hughes, Byron K. Peters, Rohan R. Merchant, Tian Qin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Bicyclic hydrocarbons, and bicyclo[1.1.1]pentanes (BCPs) in particular, are playing an emerging role as saturated bioisosteres in pharmaceutical, agrochemical and materials chemistry. Taking advantage of strain-release strategies, prior synthetic studies have featured the synthesis of bridgehead-substituted (C1, C3) BCPs from [1.1.1]propellane. Here, we describe an approach to access multisubstituted BCPs via intramolecular cyclization. In addition to C1,C3-disubstituted BCPs, this method also enables the construction of underexplored multisubstituted (C1, C2 and C3) BCPs from readily accessible cyclobutanones. The broad generality of this method has also been examined through the synthesis of a variety of other caged bicyclic molecules, ranging from [2.1.1] to [3.2.1] scaffolds. The modularity afforded by the pendant bridgehead boron pinacol esters generated during the cyclization reaction has been demonstrated through several downstream functionalizations, highlighting the ability of this approach to enable the programmed and divergent synthesis of multisubstituted bicyclic hydrocarbons. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)950-955
Number of pages6
JournalNature Chemistry
Volume13
Issue number10
DOIs
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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