Synthesis of 1, 3-disubstituted bicyclo[1.1.0]butanes via directed bridgehead functionalization. Issue 21 (30th April 2021)

• Record Type: Journal Article
• Authors: McNamee, Ryan E.; Haugland, Marius M.; Nugent, Jeremy; Chan, Rachel; Christensen, Kirsten E.; Anderson, Edward A.
• Is Part Of: Chemical science. Volume 12:Issue 21(2021)
• Page Start: 7480
• Page End: 7485
• Publication Date: 2021-04-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc01836a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Bicyclo[1.1.0]butanes (BCBs) are valuable precursors to four-membered rings and bicyclo[1.1.1]pentanes, and useful bioconjugation agents. We describe a versatile approach to access 1, 3-disubstituted BCBs, which are otherwise challenging to prepare. Abstract : Bicyclo[1.1.0]butanes (BCBs) are increasingly valued as intermediates in 'strain release' chemistry for the synthesis of substituted four membered rings and bicyclo[1.1.1]pentanes, with applications including bioconjugation processes. Variation of the BCB bridgehead substituents can be challenging due to the inherent strain of the bicyclic scaffold, often necessitating linear syntheses of specific BCB targets. Here we report the first palladium catalyzed cross-coupling on pre-formed BCBs which enables a 'late stage' diversification of the bridgehead position, and the conversion of the resultant products into a range of useful small ring building blocks.