Bian Kang-Jie, Nemoto David, Chen Ying, Lu Yen-Chu, Kao Shih-Chieh, Chen Xiao-Wei, Martí Angel A, West Julian G
Department of chemistry, Rice University, Houston, TX, USA.
Department of Materials Science and Nanoengineering, Rice University, Houston, TX, USA.
Nat Synth. 2025 Mar;4(3):314-326. doi: 10.1038/s44160-024-00698-z. Epub 2025 Jan 2.
Hydrochlorination of unsaturated hydrocarbons is a fundamental reaction scheme in organic synthesis, with the traditional acid-mediated approaches proceeding in Markovnikov selectivity and direct access to anti-Markovnikov hydrochlorination products being a longstanding pursuit. Previous efforts were restricted to multistep syntheses, stoichiometric chlorine and hydride sources, and/or highly oxidative photocatalysis, resulting in limited scope, and low regioselectivity in some cases. Thus, the development of redox-neutral hydrochlorination with high anti-Markovnikov regioselectivity compatible with both alkenes and alkynes remains important. Here we report a photocatalytic anti-Markovnikov hydro- and deuterochlorination of unsaturated hydrocarbons enabling access to diverse alkyl and alkenyl chlorides regio- and stereo-selectively. Broad scope (125 examples), mild conditions and regio- and isotopo-divergent syntheses are demonstrated. Critical to success is leveraging ligand-to-metal charge transfer (LMCT) photoreactivity of earth-abundant iron and hydrogen atom transfer (HAT) reactivity of redox-active thiol. This cooperative system offers a powerful strategy for anti-Markovnikov hydrofunctionalization of unsaturated hydrocarbons.
不饱和烃的氢氯化反应是有机合成中的一个基本反应路径，传统的酸介导方法按马氏规则选择性进行，而直接获得反马氏规则氢氯化产物一直是人们长期追求的目标。以往的努力局限于多步合成、化学计量的氯和氢化物源，以及/或者高氧化性光催化，导致适用范围有限，且在某些情况下区域选择性较低。因此，开发具有高反马氏规则区域选择性、与烯烃和炔烃均兼容的氧化还原中性氢氯化反应仍然很重要。在此，我们报道了一种光催化的不饱和烃反马氏规则氢氯化和氘氯化反应，能够区域和立体选择性地得到各种烷基和烯基氯化物。展示了广泛的适用范围（125个实例）、温和的条件以及区域和同位素发散性合成。成功的关键在于利用地壳丰富的铁的配体到金属电荷转移（LMCT）光反应性和氧化还原活性硫醇的氢原子转移（HAT）反应性。这种协同体系为不饱和烃的反马氏规则氢官能化提供了一种强大的策略。
