Bian Kang-Jie, Yu Shijin, Chen Ying, Liu Qiming, Chen Xiaowei, Nemoto David, Kao Shih-Chieh, Martí Angel A, West Julian G
Department of Chemistry, Rice University, Houston, TX, USA.
Nat Commun. 2025 Aug 25;16(1):7906. doi: 10.1038/s41467-025-63203-w.
Hydroazidation of alkenes provides a direct entry to alkyl azides, which are prevalent structural motifs in medicine development and chemical biology probes. While direct access to anti-Markovnikov hydroazidation products has seen recent progress, these protocols are restricted to highly oxidative hypervalent iodine reagents or superstoichiometric metal salts under photochemical conditions with moderate olefin generality. Thus, the development of a mild, catalytic, redox-neutral hydroazidation with high anti-Markovnikov regioselectivity compatible with diverse classes of alkene remains challenging. Here we report a photocatalytic anti-Markovnikov hydroazidation of alkenes enabled by cooperative ligand-to-metal charge transfer (LMCT) and hydrogen atom transfer (HAT). Critical to this protocol is the use of ligand to achieve efficient visible-light induced homolysis of iron azide species and the cooperation with thiol catalysts to promote this redox-neutral process and address previous challenging substrates. Additionally, the photocatalytic system enables a regioselective haloazidation via a tandem LMCT/ halogen atom transfer (XAT) process with judicious choice of halogenating reagents. Preliminary mechanistic studies support a radical nature of this cooperative system and suggest it to be a powerful manifold in olefin hydro- and di-functionalization.
烯烃的氢叠氮化反应为直接合成烷基叠氮化物提供了一条途径，烷基叠氮化物是药物开发和化学生物学探针中常见的结构单元。虽然最近在直接获得反马氏规则的氢叠氮化产物方面取得了进展，但这些方法仅限于在光化学条件下使用高氧化性的高价碘试剂或化学计量过量的金属盐，且烯烃的通用性一般。因此，开发一种温和、催化、氧化还原中性的具有高反马氏规则区域选择性且适用于多种烯烃的氢叠氮化反应仍然具有挑战性。在此，我们报道了一种通过配体到金属的电荷转移（LMCT）和氢原子转移（HAT）实现的烯烃光催化反马氏规则氢叠氮化反应。该方法的关键在于使用配体实现叠氮化铁物种的高效可见光诱导均裂，并与硫醇催化剂协同作用以促进这种氧化还原中性过程并解决以前具有挑战性的底物。此外，通过明智地选择卤化试剂，光催化体系能够通过串联的LMCT/卤原子转移（XAT）过程实现区域选择性卤叠氮化反应。初步的机理研究支持了这种协同体系的自由基性质，并表明它是烯烃氢官能化和双官能化的一种强大方法。
