Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China.
J Am Chem Soc. 2022 May 18;144(19):8870-8882. doi: 10.1021/jacs.2c03673. Epub 2022 May 9.
In contrast to the extensive but non-recyclable use of tetraalkoxydiboron(4) compounds as stoichiometric reagents in diverse reactions, this article reports an atom-economical reaction using a commercial diboron(4) as the catalyst. The key to success was designing a catalytic cycle for radical [3 + 2] cycloaddition involving a pyridine cocatalyst to generate from the diboron(4) catalyst and reversibly mediate the transfer of boronyl radicals. In comparison with known [3 + 2] cycloaddition with transition metal-based catalysts, the current reaction features not only metal-free conditions, inexpensive and stable catalysts, and simple operation but also remarkably broadened substrate scope. In particular, previously unusable cyclopropyl ketones without an activating group and/or alkenes with 1,2-disubstitution and 1,1,2-trisubstitution patterns were successfully used for the first time. Consequently, challenging cyclopentane compounds with various levels of substitution (65 examples, 57 new products, up to six substituents at all five ring atoms) were readily prepared in generally high to excellent yield and diastereoselectivity. The reaction was also successfully applied in concise formal synthesis of an anti-obesity drug and building natural product-like complex bridged or spirocyclic compounds. Mechanistic experiments and computational investigation support the proposed radical relay catalysis featuring a pyridine-assisted boronyl radical catalyst. Overall, this work demonstrates the first approach to use tetraalkoxydiboron(4) compounds as catalysts and may lead to the development of new, green, and efficient transition metal-like boron-catalyzed organic reactions.
与广泛但不可回收使用的四烷氧基二硼(4)化合物作为各种反应的化学计量试剂形成对比,本文报道了一种使用商业二硼(4)作为催化剂的原子经济反应。成功的关键是设计一种涉及吡啶共催化剂的自由基 [3+2] 环加成催化循环,以从二硼(4)催化剂生成并可逆地介导硼基自由基的转移。与已知的基于过渡金属的 [3+2] 环加成反应相比,目前的反应不仅具有无金属条件、廉价且稳定的催化剂和简单的操作,而且底物范围显著拓宽。特别是以前不能使用的无活化基团的环丙基酮和/或具有 1,2-取代和 1,1,2-三取代模式的烯烃首次被成功使用。因此,各种取代程度的挑战性环戊烷化合物(65 个实例,57 个新产物,所有五个环原子上最多有六个取代基)通常以高至优异的产率和非对映选择性轻易制备。该反应还成功地应用于抗肥胖药物的简洁形式合成和构建天然产物样复杂桥连或螺环化合物。机理实验和计算研究支持所提出的吡啶辅助硼基自由基催化剂的自由基接力催化。总的来说,这项工作展示了首次使用四烷氧基二硼(4)化合物作为催化剂的方法,并可能导致新的、绿色的和高效的类似过渡金属的硼催化有机反应的发展。