Recent advances in the chemistry of bicyclo- and 1-azabicyclo[1.1.0]butanes

• Published in: Pure and applied chemistry Vol. 92; no. 5; pp. 751 - 765
• Main Author: Fawcett, Alexander
• Format: Journal Article
• Language: English
• Published: Berlin De Gruyter 01.05.2020; Walter de Gruyter GmbH
• Subjects: 1-azabicyclo[1.1.0]butane; 2019 IUPAC-Solvay Prize; azetidines; bicyclo[1.1.0]butane; Butanes; carbopalladation; Chemistry; cyclobutanes; C–C bond reactivity; nucleophilic addition; organic synthesis; ring-opening reactions
• ISSN: 0033-4545; 1365-3075
• DOI: 10.1515/pac-2019-1007

Bicyclo[1.1.0]- and 1-azabicyclo[1.1.0]butanes are structurally unique compounds that exhibit diverse chemistry. Bicyclo[1.1.0]butane is a four-membered carbocycle with a bridging C(1)-C(3) bond and 1-azabicyclo[1.1.0]butane is an analog of bicyclo[1.1.0]butane featuring a nitrogen atom at one bridgehead. These structures are highly strained, allowing them to participate in a range of strain-releasing reactions which typically cleave the central, strained bond to deliver cyclobutanes or azetidines. However, despite these molecules being discovered in the 1950s and 1960s, and possessing a myriad of alluring chemical features, the chemistry and applications of bicyclo[1.1.0]- and 1-azabicyclo[1.1.0]butanes remain underexplored. In the past 5 years, there has been a resurgent interest in their chemistry driven by the pharmaceutical industry’s increasing desire for new methods to access cyclobutanes and azetidines. This short review intends to provide a timely summary of the most recent developments in the chemistry of bicyclo[1.1.0]- and 1-azabicyclo[1.1.0]butane to highlight the diverse chemistry they can access, their value as synthetic precursors to cyclobutanes and azetidines, and to identify areas for future research.