Asymmetric Organocatalytic Synthesis of 3-Diarylmethine-Substituted Oxindoles Bearing a Quaternary Stereocenter via 1,6-Conjugate Addition to para-Quinone Methides

Abstract

A highly stereoselective organocatalytic 1,6-conjugate addition of 3-substituted oxindoles to para-quinone methides to construct all-carbon quaternary stereocenters is described. In the presence of 10 mol % of a bifunctional squaramide organocatalyst, this 1,6-addition reaction occurs with excellent yields, diastereoselectivities and very good enantioselectivities, providing an efficient approach to a series of oxindole derivatives containing the diarylmethine motif attached to an all-carbon quaternary stereogenic center.

Enantioselective Rauhut–Currier‐Type 1,6‐Conjugate Addition of Methyl Vinyl Ketone to para‐Quinone Methides

“…We envisioned that p ‐QMs could be a second Michael acceptor in an RC reaction (Scheme b). In the aforementioned pieces of work,,,– p ‐QMs could be activated by chiral Brønsted acid through an intermolecular H‐bonding interaction, resulting in remote stereocontrol. Notably, phosphines are also elegant catalysts for the RC reaction .…”

Complete diastereodivergence in asymmetric 1,6-addition reactions enabled by minimal modification of a chiral catalyst

“…In conjunction with our study on the development of chiral P -spiro iminophosphorane-catalysed regio-, diastereo- and enantioselective conjugate addition reactions, we herein report a complete inversion of diastereoselectivity in the 1,6-addition333435363738394041424344 of azlactones (oxazol-5(4 H )-ones) to δ-aryl dienyl carbonyl compounds enabled by the slight structural alteration of iminophosphorane catalyst 1 (Fig. 1)374546474849.…”

Recent Advances in the Catalytic Enantioselective Reactions of para‐Quinone Methides

“…An entirely different type of catalyst for the enantioselective 1,6‐conjugate addition of p ‐QMs was established by the Enders group (Scheme ) . They employed quinidine‐derived squaramide C11 as a bifunctional organocatalyst to activate and arrange p ‐QMs 41 and 3‐aryl oxindoles 42 synergistically to generate a variety of enantioenriched oxindole derivatives 43 , in which the diarylmethine motif was attached to an all‐carbon quaternary stereocenter, in 68–96 % yield with 84–92 % ee and 10:1 to >20:1 d.r.…”