Catalytic Asymmetric Alkylation of Substituted Isoflavanones

The asymmetric alkylation of isoflavanones (3-aryl-chroman-4-ones) and protected 3-phenyl-2,3-dihydroquinolin-4(1H)-ones catalyzed by a novel cinchonidine-derived phase transfer catalyst E is reported. This functionalization occurs at the unactivated C3 methine to afford novel products that can easily be functionalized to generate more complex fused ring systems. The process accommodates a variety of isoflavanones and activated electrophiles and installs a stereogenic quaternary center in high yield and with good-to-excellent selectivity. Isoflavanones are a privileged class of natural products with a broad spectrum of biological activities including insecticidal, antimicrobial, antibacterial, estrogenic, antitumor, and anti-HIV activity. Isoflavanones are also precursors for more complex natural products such as pterocarpans and rotenones. Given their therapeutic promise, selective strategies to access new classes of isoflavanones and related structures has high value. The functionalization of the C3 position could promote beneficial interactions with biological targets of interest. Specifically, an alkylation at C3 can rapidly access new members of the general class of biologically active homoisoflavanones.