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Published on: August 22, 2018
C(sp3)-H arylation to construct all-syn cyclobutane-based heterobicyclic systems: a novel fragment collection
Thomas J Osberger1, Sarah L Kidd2, Thomas A King2
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. spring@ch.cam.ac.uk and Department of Chemistry and Biochemistry, California State Polytechnic University, Pomona, CA, USA.
Abstract:
All-syn fused cyclobutanes remain an elusive chemotype and thus present an interesting synthetic challenge. Herein, we report the successful application of Pd-catalysed C(sp3)-H arylation of cyclobutane compounds to generate all-syn heterobicyclic fragments using an innovative 'inside-out' approach. Through this strategy we generate a virtual collection of 90 fragments, which we demonstrate to have enhanced three-dimensionality and superior fragment-like properties compared to existing collections.
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