美国普林斯顿大学MacMillan, David W. C.团队报道了金属光氧化还原α-消去法解锁卡宾的反应性。相关研究成果发表在2024年6月6日出版的《自然》。

驾驭高能中间体的能力对于合成化学至关重要，其能够构建复杂分子并推动合成领域的进步。沿着这些路线，卡宾和类卡宾中间体是特别有吸引力的，但往往难以捉摸的高能中间体。获取金属卡宾中间体的经典方法利用双电子化学形成关键的碳-金属键。然而，由于试剂安全问题，这些方法往往令人望而却步，限制了它们在合成中的广泛应用。

从机制上讲，一种可以绕过这些陷阱的卡宾中间体的替代方法将涉及两个单电子步骤：向金属中添加自由基以形成初始的碳-金属键，然后氧化还原促进的α-消除以产生所需的金属卡宾中间体。

该文中，这一策略是通过金属马达氧化平台实现的，该平台利用铁-卡宾反应性，使用现成的化学原料作为自由基来源，并从六类先前未充分开发的离去基团中消除α。这些发现能够从丰富且稳定的羧酸、氨基酸和醇中环丙烷化和σ键插入N–H、S–H和P–H键，从而为卡宾介导的化学多样化的挑战提供了一个通用的解决方案。

附：英文原文

Title: Unlocking carbene reactivity by metallaphotoredox α-elimination

Author: Boyle, Benjamin T., Dow, Nathan W., Kelly, Christopher B., Bryan, Marian C., MacMillan, David W. C.

Issue&Volume: 2024-06-06

Abstract: The ability to tame high-energy intermediates is critical for synthetic chemistry, enabling the construction of complex molecules and propelling advances in the field of synthesis. Along these lines, carbenes and carbenoid intermediates are particularly attractive, but often elusive, high-energy intermediates.1,2 Classical methods to access metal carbene intermediates exploit two-electron chemistry to form the critical carbon–metal bond. However, these methods are often prohibitive due to reagent safety concerns, limiting their broad implementation in synthesis.3–6 Mechanistically, an alternative approach to carbene intermediates that could circumvent these pitfalls would involve two single-electron steps: radical addition to a metal to forge the initial carbon–metal bond followed by redox-promoted α-elimination to yield the desired metal carbene intermediate. Herein, this strategy is realized through a metallaphotoredox platform that exploits iron carbene reactivity using readily available chemical feedstocks as radical sources and α-elimination from six classes of previously underexploited leaving groups. These discoveries permit cyclopropanation and σ-bond insertion into N–H, S–H, and P–H bonds from abundant and bench-stable carboxylic acids, amino acids, and alcohols, thereby providing a general solution to the challenge of carbene-mediated chemical diversification.

DOI: 10.1038/s41586-024-07628-1

Source: https://www.nature.com/articles/s41586-024-07628-1