Department of Medicinal Chemistry, Biocon Bristol Myers Squibb R&D Centre, Biocon Park, Bommasandra IV Phase, Jigani Link Road, Bangalore, Karnataka 560099, India.
Department of Chemistry, Bharathidasan University, Palkalaiperur, Thiruchirapalli, Tamil Nadu 620024, India.
J Org Chem. 2022 Nov 4;87(21):14778-14792. doi: 10.1021/acs.joc.2c02107. Epub 2022 Oct 26.
Synthetically important α-oxoketene aminal intermediates can now be accessed from readily available and inexpensive carbodiimides as starting materials via the nucleophilic addition of palladium enolates derived from enol silane precursors. This operationally simple method features mild reaction conditions, including open air atmosphere, ligand-free metal catalysis, broad substrate scope, and multi-gram scalability. Select synthetic applications that take advantage of the enamine character of α-oxoketene aminals and involve C-nucleophilic additions to electrophilic systems, including an α,β-unsaturated ester, an azo dicarboxylate, an aralkyl halide, and an aldehyde, are demonstrated.
现在可以从易得且廉价的碳二亚胺起始原料出发，通过钯烯醇化物的亲核加成，来合成具有重要合成意义的α-氧代烯酮亚胺中间体，这些钯烯醇化物是由烯醇硅烷前体制得的。该方法操作简单，反应条件温和，包括在开放空气氛围中、无配体的金属催化、底物适用范围广、可实现多克规模放大。展示了一些利用α-氧代烯酮亚胺的烯胺特性的合成应用，包括 C-亲核加成到亲电体系，涉及α,β-不饱和酯、偶氮二羧酸酯、芳基卤代物和醛。
