CATALYTIC ASYMMETRIC KETENE [2 + 2] AND [4 + 2] CYCLOADDITIONS

摘要

Among the denning characteristics of organic cumulenes is their propensity to undergo thermal [2 + 2] cycloadditions despite the formally "forbidden" nature of these reactions. Ketenes are among the cumulenes that are particularly reactive partners for [2 + 2] cycloaddition reactions. For example, ketenes dimerize under ambient conditions to generate cyclobutane-1,3-dione, cyclobutenone, or β-lactone structures depending on the C2 ketene substituents (Scheme 1); ketene itself rapidly dimerizes to generate diketene (4-methylideneoxetan-2-one), a shelf-stable, commercially available precursor to ketene. Both Lewis acid and Lewis base catalysts are effective in diverting ketene reactivity away from dimer-ization processes to enable efficient intermolecular [2 + 2] cycloadditions with electrophilic ketenophiles. As both Lewis acidic and Lewis basic catalysts for the ketene-dependent [2 + 2] cycloadditions are involved in the stereochemistry-defining step, enantioenriched variants of these catalysts have been effective in developing highly enantioselective cycloadditions involving carbonyl- and imine-derived ketenophiles (Scheme 2). Ketenes also engage alkenes in facile, thermally allowed [2 + 2] cycloadditions that share many of the features associated with the imine- and carbonyl-dependent cycloaddition reactions. However, alkene cycloadditions wherein ketene ostensibly functions as the electrophilic reaction component, rather than the electron-rich cycloaddition partner for car-bonyls and imines, have not, thus far, proven amenable to the development of catalytic asymmetric reaction variants.