Department of Chemistry, Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, USA.
Department of Biochemistry and Biophysics, EPR Laboratory, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nat Chem. 2017 Oct;9(10):997-1004. doi: 10.1038/nchem.2760. Epub 2017 Apr 17.
Direct C(sp)-C(sp) bond formation under transition-metal-free conditions offers an atom-economical, inexpensive and environmentally benign alternative to traditional transition-metal-catalysed cross-coupling reactions. A new chemo- and regioselective coupling protocol between 3-aryl-substituted-1,1-diphenyl-2-azaallyl derivatives and vinyl bromides has been developed. This is the first transition-metal-free cross-coupling of azaallyls with vinyl bromide electrophiles and delivers allylic amines in excellent yields (up to 99%). This relatively simple and mild protocol offers a direct and practical strategy for the synthesis of high-value allylic amine building blocks that does not require the use of transition metals, special initiators or photoredox catalysts. Radical clock experiments, electron paramagnetic resonance studies and density functional theory calculations point to an unprecedented substrate-dependent coupling mechanism. Furthermore, an electron paramagnetic resonance signal was observed when the N-benzyl benzophenone ketimine was subjected to silylamide base, supporting the formation of radical species upon deprotonation. The unique mechanisms outlined herein could pave the way for new approaches to transition-metal-free C-C bond formations.
在无过渡金属条件下直接形成 C(sp)-C(sp)键，为传统过渡金属催化交叉偶联反应提供了一种原子经济性、廉价且环境友好的替代方法。本文开发了一种 3-芳基取代的 1,1-二苯基-2-氮杂烯丙基衍生物与溴代乙烯基之间的新型化学和区域选择性偶联方案。这是首例无过渡金属的氮杂烯丙基与溴代乙烯基亲电试剂的交叉偶联反应，以优异的收率（高达 99%）得到烯丙基胺。该相对简单温和的方案为合成高价值的烯丙基胺砌块提供了一种直接实用的策略，该策略不需要使用过渡金属、特殊引发剂或光氧化还原催化剂。自由基钟实验、电子顺磁共振研究和密度泛函理论计算表明存在一种前所未有的底物依赖性偶联机制。此外，当 N-苄基二苯甲酮亚胺经受硅酰胺碱时，观察到电子顺磁共振信号，支持在去质子化时形成自由基物种。本文概述的独特机制可能为无过渡金属 C-C 键形成开辟新途径。
