近日，美国普林斯顿大学David W. C. MacMillan团队研究了"偶联-闭环"：半饱和循环支架的统一方法。相关论文于2026年1月22日发表在《科学》杂志上。

"偶联-闭环"作为一种合成范式，有望改变有机合成化学家构建环状骨架的传统方式。半饱和环状骨架作为一类环状分子正日益受到关注，其Csp²与Csp³杂化组分的特定组合赋予这类化合物独特的性质。然而，现有构建这类骨架的方法存在局限，往往依赖于芳环饱和化或需要冗长从头合成路线的成环反应。

研究组报道了一种统一且高度模块化的"偶联-闭环"策略，用于合成半饱和环状骨架。该策略通过一系列成键反应将双功能连接基团安装到芳环上，随后通过环化反应构建半饱和双环加合物。此方法的关键在于一种机制独特的钴催化脱氢自由基环化反应，该反应即使在电子性质未修饰的芳环上也能高效进行，从而在温和反应条件下实现广泛的底物适用性。

附：英文原文

Title: Couple-close: Unified approach to semisaturated cyclic scaffolds

Author: Jiaxin Xie, William Y. Zhao, Johnny Z. Wang, William L. Lyon, Noriyuki Takanashi, Alice Long, Taylor M. Sodano, Christopher B. Kelly, Marian C. Bryan, David W. C. MacMillan

Issue&Volume: 2026-01-22

Abstract: Couple-close as a synthetic paradigm has the potential to change the way that synthetic organic chemists approach cyclic scaffold construction. One class of cyclic molecules that has been increasingly sought after is semisaturated cyclic scaffolds, whose specific blend of Csp2- and Csp3-hybridized components confers distinct properties to these species. However, existing methods to construct these scaffolds are limited, often relying on arene saturation or annulations that require lengthy de novo syntheses. Herein, we describe a unified and highly modular couple-close strategy for the synthesis of semisaturated scaffolds. This approach installs bifunctional linkers onto aromatic rings through a range of bond-forming reactions, and subsequent cyclization furnishes semisaturated bicyclic adducts. Key to this approach is a mechanistically distinct cobalt-catalyzed dehydrogenative radical cyclization that proceeds efficiently even on electronically unbiased arenes, enabling a broad substrate scope under mild reaction conditions.

DOI: aec5748

Source: https://www.science.org/doi/10.1126/science.aec5748