Enantioselective Construction of Aryl‐Substituted All‐Carbon Quaternary Stereocenters by Using Tertiary Amine–Thiourea‐Catalyzed Michael Additions

Abstract

A catalytic enantioselective synthetic strategy for the aryl-substituted all-carbon quaternary stereocenters of bioactive hydrodibenzofuran alkaloids was achieved by the Michael addition reaction of α-cyano ketones and acrylates using a chiral tertiary amine-thiourea catalyst. This method can tolerate steric bulkiness and multiple functional groups, and 32 Michael adducts were prepared in good to excellent yields with

Asymmetric Conjugate Addition of α-Cyanoketones to Enones Using Diaminomethylenemalononitrile Organocatalyst

“…However, catalytic asymmetric conjugate additions using α-cyanoketones as Michael donors are scarce. In particular, asymmetric conjugate additions of α-cyanoketones using organocatalysts are relatively rare . Chiral 1,5-dicarbonyl-2-cyano derivatives obtained by the asymmetric conjugate addition of α-cyanoketones to aromatic vinyl ketones are valuable building blocks because they can be easily transformed to enantioenriched spiro-piperidine and bicycle[3.3.0]­octane motif; however, there has been only one pioneering example of the asymmetric conjugate addition using a chiral yttrium catalyst for access to chiral 1,5-dicarbonyl-2-cyano compounds, as reported by Shibasaki et al (Scheme ).…”

Construction of Acyclic All-Carbon Quaternary Stereocenter Based on Asymmetric Michael Addition of Chiral Amine

“…Effective methods that use the nucleophilicity of enolates have been reported. 4,[35][36][37][38][39][40][41][42][43][44] We have developed an asymmetric Michael addition reaction of chiral amine 1 having a bornyl group as a chiral auxiliary, 45) in which the construction of multiple contiguous chiral centers has been achieved by taking advantage of the enolate intermediate derived from the asymmetric Michael addition of 1 in a tandem reaction or a one-pot reaction, i.e., the Michaelaldol reaction, the double Michael reaction, the double Michael-aldol reaction, and the quadruple Michael reaction. 46,47) We have recently reported two contiguous chiral centers generated by the face-selective protonation of enolate intermediates A, which were formed by the asymmetric Michael addition reaction of 1 with trisubstituted (E)-α,β-unsaturated esters 2, and the asymmetric synthesis of β 2,3 -amino esters utilizing this protocol 48) (Chart 1).…”