Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Catalytic Asymmetric Lower-Rim Functionalization.

Abstract

We report herein an efficient approach for the enantioselective synthesis of inherently chiral calix[4]arenes (ICCs) via chiral phosphoric acid (CPA)-catalyzed lower-rim asymmetric functionalization. With vinylidene ortho-quinone methides (VQMs) as the key intermediates, a stepwise asymmetric halo-cyclization strategy was applied to construct diverse inherently chiral calix[4]arenes bearing multiple C─C axially stereogenic elements with high enantio- and diastereoselectivities (up to 96% ee, all d.r. > 20:1). The obtained lower-rim functionalized products underwent further photocatalytic transformations to access novel inherently chiral naphthofuran-based calix[4]arene architectures. Further synthetic modifications and analysis of their photophysical/chiroptical properties demonstrated their potential in optoelectronic materials and related fields. Mechanistic studies reveal that the reaction proceeds via a stepwise process, with the stereoselectivity-determining step occurring in the first VQMs-mediated cyclization, and the second step constituting a chiral transfer process.