posted on 2024-02-13, 22:30authored bySubhabrata Dutta, Yi-Lin Lu, Johannes E. Erchinger, Huiling Shao, Emanuel Studer, Felix Schäfer, Huamin Wang, Debanjan Rana, Constantin G. Daniliuc, K. N. Houk, Frank Glorius
In pursuit of potent pharmaceutical candidates and to
further improve
their chemical traits, small ring systems can serve as a potential
starting point. Small ring units have the additional merit of loaded
strain at their core, making them suitable reactants as they can capitalize
on this intrinsic driving force. With the introduction of cyclobutenone
as a strained precursor to ketene, the photocycloaddition with another
strained unit, bicyclo[1.1.0]butane (BCB), enables the reactivity
of both π-units in the transient ketene. This double strain-release
driven [2π+2σ]-photocycloaddition promotes the synthesis
of diverse heterobicyclo[2.1.1]hexane units, a pharmaceutically relevant
bioisostere. The effective reactivity under catalyst-free conditions
with a high functional group tolerance defines its synthetic utility.
Experimental mechanistic studies and density functional theory (DFT)
calculations suggest that the [2π+2σ]-photocycloaddition
takes place via a triplet mechanism.