Enantioselective Palladium‐Catalyzed Hydrophosphinylation of Allenes with Phosphine Oxides: Access to Chiral Allylic Phosphine Oxides

The biological and therapeutic significance of natural products is a powerful impetus for the development of efficient methods to facilitate their construction. Accordingly, and reflecting the prevalence of β‐oxy‐carbonyl motifs, a sophisticated arsenal of aldol‐based strategies has evolved that is contingent on the generation of single enolate isomers. Since this has the potential to compromise efficiency in reagent‐based paradigms, direct catalysis‐based solutions would be enabling. To complement the array of substrate‐based strategies, and regulate enolate geometry at the catalyst level, a direct catalytic alkylation of esters with oxyallenes has been developed. Synergizing metal hydride reactivity with Lewis base catalysis has resulted in a broad reaction scope with useful levels of stereocontrol (up to >99 % ee). Facile derivatization of these ambiphilic linchpins is demonstrated, providing access to high‐value vicinal stereocenter‐containing motifs, including 1,2‐amino alcohols.

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A Pd−H/Isothiourea Cooperative Catalysis Approach to anti‐Aldol Motifs: Enantioselective α‐Alkylation of Esters with Oxyallenes**

Lin

Knox

Pearson

et al. 2022

Angewandte Chemie

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Enantio‐ and Regioselective Construction of 1,4‐Diamines via Cascade Hydroamination of Methylene Cyclopropanes

et al. 2022

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Despite the widespread existence of chiral 1,4‐diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long‐standing challenge. Here, we report a Cu‐catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4‐diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4‐diamine structures. The desired products could be easily transformed into chiral 1,4‐diamines and chiral NH2‐Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring‐opening and cascade hydroamination sequence.

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

et al. 2022

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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.

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Enantioselective Palladium‐Catalyzed Hydrophosphinylation of Allenes with Phosphine Oxides: Access to Chiral Allylic Phosphine Oxides

Cited by 14 publications

References 125 publications

A Pd−H/Isothiourea Cooperative Catalysis Approach to anti‐Aldol Motifs: Enantioselective α‐Alkylation of Esters with Oxyallenes**

A Pd−H/Isothiourea Cooperative Catalysis Approach to anti‐Aldol Motifs: Enantioselective α‐Alkylation of Esters with Oxyallenes**

Enantio‐ and Regioselective Construction of 1,4‐Diamines via Cascade Hydroamination of Methylene Cyclopropanes

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

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