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.
Keywords: Allenes; C1-Ammonium Enolates; Enantioselectivity; Isothioureas; Palladium Catalysis.
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