福州大学宋秋玲/郑州大学李世俊ACS Catal.:铜催化烯基环丙烷的化学发散性、区域选择性开环双硼化反应
图1. TOC (图片来源于ACS Catal.)Diboron compounds have become indispensable synthetic building blocks in organic chemistry due to their chemoselective reactivity, transformational potential, and structural versatility. While synthetic methods for 1,1-, 1,2-, 1,3-, and 1,4-diboronates are well established, general and efficient access to more distal 1,5-diboronates remains scarce. Here, we report a copper-catalyzed ring-opening diborylation of vinylcyclopropanes that is controlled synergistically by the ligand and activator, providing a practical route to access diverse 1,5-diboronates via distal alkene difunctionalization. This method uses readily available starting materials and inexpensive copper catalysts under mild conditions, with broad substrate compatibility and good chemo-, regio-, and stereoselectivity. When PCy3 replaces dcpe, an unusual deboronation/isomerization/protonation/hydroboration sequence is observed. Mechanistic studies involving control experiments and density functional theory calculations reveal a plausible reaction pathway and demonstrate that thermodynamic factors and the availability of reductants account for the divergent selectivity. The synthetic utility of the method is demonstrated through late-stage modification of bioactive molecules; downstream transformations to diols, dihalides, dienes, and heterocycles; and expeditious gram-scale synthesis.图2. 研究背景及本策略 (图片来源于ACS Catal.)图3. CuH/CuBpin接力催化体系条件优化 (图片来源于ACS Catal.)图4. VCPs的三组分双硼化反应底物拓展 (图片来源于ACS Catal.)图4. CuBpin催化体系条件优化 (图片来源于ACS Catal.)图6. 涉及CuBpin介导VCPs的开环双硼化反应底物拓展 (图片来源于ACS Catal.)图7. 流水线应用和修饰反应 (图片来源于ACS Catal.)图8. 机理研究 (图片来源于ACS Catal.)图9. 可能的反应机理 (图片来源于ACS Catal.)图10. DFT计算启动步骤 (图片来源于ACS Catal.)图11. DFT计算关键中间体7到产物48步骤 (图片来源于ACS Catal.)In conclusion, we have unlocked a synergistically ligand- and activator-controlled copper-catalyzed diborylation protocol, which allows the divergent synthesis of two distinct organoboron products from the readily available VCPs as starting materials and bis(pinacolato)diboron (B2pin2) as the commercial borylating agent in the presence of cheap copper catalysts, thus addressing the long-standing challenge of the more distal 1,5-diboronate diversification in boron chemistry. These presented reactions feature inexpensive metal catalysts, excellent functional operational simplicity, exceptional catalytic efficiency, and excellent chemo-, regio-, and stereochemical control. Mechanistic studies and DFT calculations demonstrate that the product generated by the CuH/CuBpin relay catalytic system could serve as the reaction intermediate for the remaining two 1,5-diboronates. To the best of our knowledge, no existing report has delineated the capacity of copper-boron species cat alyzed to enable the concurrent formation of both sp2 and sp3 C−B bonds in a one-pot transformation. The synthetic methodologies presented herein will substantially expand the applica bility of alkenylcyclopropane toward structurally diverse classes of organboron scaffolds. Moreover, the resulting diborylated compounds serve as versatile synthetic intermediates, enabling a diverse array of downstream transformations to deliver many structurally diversified molecules, such as distal diborons, dihalides, diols, dienes, β-substituted six-membered heterocycles, and so on. Current efforts are focused on exploring diverse asymmetric reaction modes for the synthesis of a series of remote chiral diboron compounds from accessible VCPs. At the same time, further studies the on ring-opening reaction of vinylcyclobutane and vinylcyclopentane bearing lower ring strain and their asymmetric ring-opening borylation reaction having greater challenges will be further investigated by our research group in the future.
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