Electrophilic Bicyclobutane Synthons

Bicyclo[1.1.0]butanes (BCBs) have emerged as versatile synthetic building blocks for the construction of multifunctionalized cyclobutanes and complex polycyclic frameworks at the core of modern medicinal chemistry. 1,3-Disubstituted BCBs are particularly useful to access highly functionalized building blocks, but access to these substrates is often limited by synthetic methodologies requiring long multi-step sequences. Late-stage modification of the BCB core constitutes an alternative strategy to access chemical diversity. However, this has been limited to the reaction of BCBs as nucleophiles with electrophilic partners. Herein, we report on the design, synthesis, and application of novel hypervalent iodine(III) reagents bearing a BCB motif acting as powerful BCB cation synthons. This unprecedented example of a thermally stable hypervalent iodine reagent bearing a carbon substituent linked to three alkyl groups enabled the first late-stage functionalization of the BCB core with sulfur- and carbon-centered nucleophiles, constituting a fundamentally different disconnection to access these key building blocks.