Synergistic Catalysis with Azomethine Ylides

Abstract

What is the most favorite and original chemistry developed in your research group? Developing new catalysts and catalytic system for the asymmetric transformation of azomethine ylides. How do you get into this specific field? Could you please share some experiences with our readers? 1,3-Dipolar cycloaddition of azomethine ylides is one of the most powerful methods for the construct of chiral pyrrolidines, which are ubiquitous in the cores of natural products and bioactive molecules. Initially, we designed a new type of chiral ligand, TF-BiphamPhos, which not only coordinates with Lewis acids to activate azomethine ylides, but also serves as an H-bond donor to increase the reactivity of dipolarophiles with significantly enhanced stereochemical control. Using the Cu(I) or Ag(I)/TF-BiphamPhos complex as the catalyst, we achieved highly stereoselective (3+2) cycloadditions of glycinate and non-glycinate-derived azomethine ylides with diverse dipolarophiles, producing a variety of enantioenriched pyrrolidines with multiple stereocenters. To further expand the synthetic utility of azomethine ylides, we successfully developed higher order (3+6)-/(3+3)-type cycloadditions to generate enantioenriched six-membered N-heterocycles. In mechanistic studies, we uncovered that N-metallated azomethine ylides could be utilized as viable nucleophiles to furnish an array of unnatural α-amino acids, which is the base of the research work summarized in this article. Keep doing what you love best is the criteria that I am encouraged to follow. What is the most important personality for scientific research? Curiosity and persistence. How do you supervise your students? Encourage them to think independently and explore bravely. What's your hobbies? Reading, walking and listening to Chinese national music.

Doubly stereoconvergent construction of vicinal all-carbon quaternary and tertiary stereocenters by Cu/Mg-catalyzed propargylic substitution

“…We first considered strategies to restrict the rotational flexibility of the nucleophile 11a . Along this line, we investigated the use of various Brønsted bases that contain Lewis acidic metal counterions 44 – 46 , with the expectation that they would deprotonate 11a to form cyclic metal enolate intermediates such as 13 . Among the bases screened (entries 2–6), Mg(O t Bu) 2 afforded 12 in best yield (84%) but still with moderate diastereoselectivity (entry 6).…”

Mechanistic Origins of Stereodivergence in Asymmetric Cascade Allylation and Cyclization Reactions Enabled by Synergistic Cu/Ir Catalysis

“…Despite the great progress the synthesis of one chiral center has made, the catalyst-controlled creation of two or more continuous chiral centers in one-pot conditions still remains a challenge . In recent years, the cooperative catalysis strategy (such as metal–organic cooperative catalysis and metal–metal cooperative catalysis) has emerged as a powerful method toward assembling continuous chiral centers in a one-pot protocol. − In 2013, Carreira’s group made a breakthrough in this strategy by employing two distinct chiral catalysts (a chiral iridium complex and a chiral cinchona amine) to create two contiguous chiral carbon atoms in the α-allylation of aldehydes. , Furthermore, great advances have been achieved in the creation of stereospecific multichiral centers catalyzed by two distinct chiral metal catalysts. ,− In 2016, Zhang et al disclosed the stereodivergent reaction by cooperative bimetallic catalysis, wherein the enantio- and diastereodivergent α-allylation of α-hydroxyketones was realized by a chiral zinc complex and a chiral iridium complex . By simply regulating the combination of chiral catalysts, all four stereoisomers could be easily gained .…”

“…On the basis of experiments and previous reports by Wu, You, Zhang, Sunoj, etc., ,, a dual catalytic cycle is pictured in Scheme to depict synergistic catalysis. On the one hand, nucleophilic Cu­(I)/ L1 -azomethine ylide could be formed via the coordination and deprotonation of aldimine ester 1a .…”

Stereodivergent synthesis via iridium-catalyzed asymmetric double allylic alkylation of cyanoacetate

“…4 To overcome the diastereoselective bias in the chiral induction process, diverse methodologies, such as the modulation of the structure of the catalyst and substrate, changing the reaction conditions (solvent, temperature, pressure, and additives) or using an entirely different catalytic system, have been developed in the past twenty years. 5,6 Despite many important advances, serendipity is the most important factor in these findings and such strategies cannot be readily extended to the development of other stereodivergent transformations.…”