Cuomo Valentina D, Romano Ciro, Procter David J
Department of Chemistry, University of Manchester, Oxford Road, Manchester, M139PL, U K.
Angew Chem Int Ed Engl. 2025 Aug 11;64(33):e202509244. doi: 10.1002/anie.202509244. Epub 2025 Jun 18.
The sulfide motif is distributed widely across chemical and biological space. In synthesis, its installation often marks the end point of a sequence, due to its relative inertness; sulfides typically require direct oxidation of sulfur before they are receptive toward transformation. Unfortunately, selective S-oxidation is not always straightforward, with the need for oxidants lacking chemoselectivity in the presence of functionality and delivering mixtures of oxidation products. This multistep manipulation of the sulfide motif, initiated by direct S-oxidation, limits the use of sulfides as synthetic handles for downstream manipulation. Herein, we describe a direct activation of sulfides by C-H oxidation alpha to sulfur-rather than traditional oxidation at sulfur-that facilitates efficient formal C─S bond manipulation. The mild nature of the photo-induced anaerobic oxidation protocol enables its merger with high-value transformations in telescoped or one-pot protocols that deliver branched amines, secondary alcohols, and alkenes from aldehyde and ketone intermediates. The method expands the chemistry of sulfides by diverting reactivity away from sulfur (oxidation, alkylation) and instead targeting directly the alpha position, resulting in formal manipulation of the C─S bond, and redefining sulfides as latent synthetic handles to be "switched on" at will.
硫化物基序广泛分布于化学和生物领域。在合成过程中，由于其相对惰性，硫化物的引入往往标志着一个序列的终点；硫化物通常需要先将硫直接氧化，才能进行转化。不幸的是，选择性S-氧化并不总是那么直接，因为在存在官能团的情况下需要缺乏化学选择性的氧化剂，并且会生成氧化产物的混合物。由直接S-氧化引发的硫化物基序的这种多步操作，限制了硫化物作为下游操作的合成手柄的使用。在此，我们描述了一种通过硫α位的C-H氧化直接激活硫化物的方法，而不是传统的硫氧化，这有助于高效地进行形式上的C-S键操作。光诱导厌氧氧化方案的温和性质使其能够与高价值转化合并，在串联或一锅法方案中，从醛和酮中间体生成支链胺、仲醇和烯烃。该方法通过将反应性从硫（氧化、烷基化）转移开，转而直接靶向α位，从而扩展了硫化物的化学性质，实现了形式上的C-S键操作，并将硫化物重新定义为可随意“开启”的潜在合成手柄。
