Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405, USA.
Current address: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, P. R. China.
Angew Chem Int Ed Engl. 2022 Jun 20;61(25):e202201753. doi: 10.1002/anie.202201753. Epub 2022 Apr 20.
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.
天然产物的生物学和治疗意义是开发有效方法促进其构建的强大动力。因此，反映了β-氧羰基模体的普遍性，已经发展出了一系列复杂的基于醛醇缩合的策略，这些策略取决于单烯醇化物异构体的生成。由于这有可能降低基于试剂的方法的效率，基于直接催化的解决方案将是可行的。为了补充基于底物的策略，并在催化剂水平上调节烯醇化物的几何形状，已经开发出了酯与氧杂环戊二烯的直接催化烷基化反应。金属氢化物反应性与路易斯碱催化协同作用，导致反应范围广泛，具有有用的立体控制水平（高达＞99%ee）。这些两性关键中间体的易于衍生化得到了证明，为高价值的含有相邻立体中心的模体提供了途径，包括 1,2-氨基醇。
