Department of Chemistry and FRQNT Center for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A 0B8, Canada.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Road, Lanzhou, Gansu, 730000, China.
Nat Commun. 2019 Feb 12;10(1):715. doi: 10.1038/s41467-019-08631-1.
Alkenes are fundamental functionalities in nature and highly useful intermediates in organic synthesis, medicinal chemistry and material sciences. Transition-metal-catalyzed Heck couplings with organic halides as electrophiles have been established as a powerful protocol for the synthesis of this valuable building block. However, the requirement of organic halides and the generation of stoichiometric hazardous halide wastes may cause significant sustainable concerns. The halide-free oxidative Heck alkenylations involving organometallics or arenes as the coupling partners provide a facile and alternative pathway. Nonetheless, stoichiometric amounts of extra oxidant are essential in most cases. Herein, we present a direct dehydrogenative alkyl Heck-coupling reaction under oxidant-free conditions, liberating hydrogen, nitrogen and water as the side products. Excellent regioselectivity is achieved via neighboring oxygen atom coordination. Broad substrate scope, great functional group (ketone, ester, phenol, free amine, amide etc) tolerance and modification of pharmaceutical candidates and biological molecules exemplified its generality and practicability.
烯烃是自然界中的基本官能团，也是有机合成、药物化学和材料科学中非常有用的中间体。过渡金属催化的 Heck 偶联反应以有机卤化物作为亲电试剂，已被确立为合成这一有价值构建块的有力方法。然而，有机卤化物的需求以及产生的化学计量有害卤化物废物可能会引起重大的可持续性问题。涉及有机金属或芳基作为偶联伙伴的无卤化物氧化 Heck 烯基化提供了一种简单的替代途径。尽管如此，在大多数情况下仍需要化学计量的额外氧化剂。在此，我们提出了一种在无氧化剂条件下直接脱氢烷基 Heck 偶联反应，释放氢气、氮气和水作为副产物。通过相邻氧原子的配位实现了优异的区域选择性。广泛的底物范围、对酮、酯、酚、游离胺、酰胺等官能团的良好耐受性以及对药物候选物和生物分子的修饰证明了其通用性和实用性。
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