Diastereodivergent Aldol‐Type Coupling of Alkoxyallenes with Pentafluorophenyl Esters Enabled by Synergistic Palladium/Chiral Lewis Base Catalysis

Abstract

As a fundamental and synthetically useful C−C bond formation reaction, the aldol reaction is one of the most versatile transformations in organic synthesis. However, despite extensive research on asymmetric versions of the reaction, a unified method for stereoselective access to the complementary syn and anti diastereomeric products remains to be developed. In this study, we developed a synergistic palladium/chiral Lewis base system that overcomes the inherent diastereoselectivity bias of aldol reactions and, as a result, allowed us to achieve the first diastereodivergent coupling reactions of alkoxyallenes with pentafluorophenol esters. Computational studies suggest a mechanism involving an intermolecular protonative hydropalladation pathway rather than a palladium‐hydride migratory insertion pathway. The origin of the stereochemistry for this synergistic catalysis system is rationalized by DFT calculations.

Diastereodivergent Desymmetric Annulation to Access Spirooxindoles: Chemical Probes for Mitosis

“…Enantiomerically enriched spirooxindole frameworks play a vital role in bioscience, medicine, and chemistry. , As one of the most attractive subtypes, highly substituted spirooxindole lactones are among the most prevalent structural units in biologically active natural products, pharmaceuticals, and agrochemicals (Figure A). , As structurally diverse compound collections with different absolute and relative configurations would potentially possess distinct biological activities, the ubiquity of spirooxindole-containing natural products makes the development of an efficient stereodivergent synthetic methodology , highly desirable . Since the seminal work reported by Carreira and co-workers, stereodivergent construction of vicinal stereocenters via organo/metal, − metal/metal, − and organo/organo cooperative catalysis has frequently appeared. − Despite the remarkable progress made in the area, the diastereodivergent synthesis of spirooxindole skeletons with full control of continuous chiral centers including a spiro quaternary carbon stereocenter , remains largely elusive, presumably arising from their rigid three-dimensional structure that requires each individual member of the combined chiral catalyst system to exhibit excellent stereocontrol ability for stereodivergent synthesis.…”

Stereodivergent Construction of Csp3−Csp3Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase‐Transfer Catalysis

“…The past few years have witnessed tremendous success in this field with the establishment of organo/metal, [4] metal/metal, [5] and organo/organo [6] catalyst systems. Nucleophilic substrates, such as aldehydes, [2, 4g] aldimine esters, [5c–e] pentafluorophenyl esters, [4c, i, 6] α‐hydroxy ketones, [5a] and azaaryl acetamides [5b, j] have been used for these catalyst systems. One common feature of these substrates is that they are non‐stabilized nucleophiles, which cannot react with the Cat 2 ‐El complex (Δ G ≠ single is too large) until they have been activated by Cat 1 (the Cat 1 ‐Nu+Cat 2 ‐El reaction has a small Δ G ≠ syner ) (Figure 1b).…”

Cooperative Isothiourea/Iridium-Catalyzed Asymmetric Annulation Reactions of Vinyl Aziridines with Pentafluorophenyl Esters

“…Recently, chiral isothioureas (ITUs) have been shown to serve as effective Lewis base catalysts combined with transition metals in the discovery of new reaction manifolds and the development of elegant asymmetric processes (Scheme C) . Since the seminal work established by the Snaddon group in 2016, the discovery of efficient ITU/TM cooperative catalytic systems to access chiral molecules continues to attract the attention of organic chemists, and many achievements have been accomplished. − Since 1997, the development of iridium-catalyzed asymmetric allylic substitution reactions has emerged as a powerful methodology for the construction of complex molecules or natural products . In 2021, we disclosed that the iridium catalyst and N-heterocyclic carbene organocatalyst could be merged in the [4 + 3] annulation reaction involving vinyl aziridines .…”