Enantioselective Construction of α-Quaternary Cyclobutanones by Catalytic Asymmetric Allylic Alkylation

摘要

The asymmetric alkylation of enolates to generate a-quater-nary carbonyl compounds has become a mainstay transformation in organic synthesis.In this domain, cyclobutanones have received far less attention relative to their five-, six- and seven-membered congeners, despite the fact that these compounds and their derivatives are prevalent in important biologically active natural products (Figure 1 A). Additionally, cyclobutanes have been shown to serve as highly valuable synthetic intermediates for a variety of transformations. The dearth of reports describing the asymmetric alkylation of cyclobutanones may be attributed to the fact that these compounds possess an estimated 26-28.6 kcalmol~(-1) of ringstrain and, in turn, exhibit enhanced carbonyl electrophilicity The propensity of cyclobutanones to alleviate this strain through electrophilic ring opening is often a limiting challenge during their manipulation. Moreover, the energetic requirements for enolization of cyclobutanones are compounded by a concomitant increase in ringstrain to 31-34 kcalmol~(-1) (calculated for cyclobutene, Figure 1 B)as well as enforced deviation from the more favorable puckered conformation (Figure 1 C). In the case of a-substituted cyclobutanones, enolization is further impeded by the development of torsional strain between the putative enolate substituents (Figure 1C).