Asymmetric Synthesis of Remote Quaternary Centers by Copper-Catalyzed Desymmetrization: An Enantioselective Total Synthesis of (+)-Mesembrine

Abstract

Catalytic asymmetric syntheses of remote quaternary stereocenters have been developed by copper-catalyzed 1,4-hydrosilylation of γ,γ-disubstituted cyclohexadienones. A variety of cyclohexenones have been synthesized in good yield and excellent enantioselectivity. Versatile 2-silyloxy diene intermediates bearing γ,γ-disubstituted all carbon stereogenic centers can be isolated from the mild reaction conditions. The utility of this strategy is exemplified in a catalytic asymmetric total synthesis of (+)-mesembrine.

Silver-Catalyzed Asymmetric Desymmetrization of Cyclohexadienones via Van Leusen Pyrrole Synthesis

“…In particular, the use of cyclohexadienone derivatives tethered with alkene, alkyne, and allene moieties has been widely explored in the transition-metal-catalyzed asymmetric desymmetrization strategies (Scheme a) . While the direct reductions of the alkene moiety of cyclohexadienones and the conjugate addition reactions to the enone moiety have been achieved with a variety of nucleophiles, the catalytic asymmetric desymmetrization strategies of cyclohexadienones without the tethered functional groups have been limited to Wang group’s 1,3-dipolar cycloaddition reaction of spirocyclohexadienone lactones and Takagi group’s Diels–Alder reaction of cyclohexadienones . With the aim to explore the catalytic asymmetric desymmetrization of cyclohexadienones in the context of cycloaddition reactions, we envisioned the Van Leusen pyrrole synthesis using arylsulfonylmethyl isocyanides (Scheme b).…”

Asymmetric construction of densely functionalized three-dimensional aza-tetracyclic scaffolds for drug discovery

“…7 b The scaffold VIII 7 c was synthesized asymmetrically via Cu-catalyzed enantioselective desymmetrization of a dienone intermediate. 8 Thus, asymmetric construction of densely functionalized 3D scaffolds would provide an opportunity to discover novel bioactive compounds and lead optimization process.…”

Asymmetric Bromoaminocyclization and Desymmetrization of Cyclohexa-1,4-dienes through Anion Phase-Transfer Catalysis

“…On the other hand, the cis -3a-aryloctahydro­indole possessing an all-carbon quaternary stereocenter is a key structural motif found in alkaloid natural products and biologically active agents. We sought to apply this developed methodology to realize the total synthesis of (+)-Mesembrane, which is a well-known member of the Sceletium alkaloids . For this purpose, an enantioselective synthesis of (+)-Mesembrane is illustrated in Scheme b.…”