Zhao Fei, Mattana Ariane, Alam Ruqaiya, Montgomery Sarah L, Pandya Akash, Manetti Fabrizio, Dominguez Beatriz, Castagnolo Daniele
Department of Chemistry, University College London, London, UK.
Johnson Matthey, Cambridge, UK.
Nat Commun. 2024 Sep 27;15(1):8332. doi: 10.1038/s41467-024-52608-8.
Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp)-S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp)-S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp)-S and C(sp)-O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee). Notably, this biocatalytic strategy allows to overcome the long-standing shortcomings of catalyst poisoning and C(sp)/C(sp)-S bond cleavage faced in transition-metal-catalyzed hydrogenation of vinyl sulfides. Finally, the potential of this methodology is also exemplified by its broader application in the stereoconvergent assembly of chiral C(sp)-N/O/Se bonds with good to excellent enantioselctivities.
生物催化已被广泛用于构建碳-碳/杂原子立体中心，然而其在手性C(sp)-S键构建中的应用却很少，且仅限于酶促动力学拆分。在此，我们描述了通过烯还原酶生物催化前手性乙烯基硫醚的共轭还原对映选择性构建手性C(sp)-S键。已开发出一系列协同的顺序/并行化学酶促和生物催化级联反应，以立体汇聚的方式获得多种手性硫化物，包括带有两个相邻C(sp)-S和C(sp)-O立体中心的有价值的β-羟基硫化物，产率良好至优异（高达96%），对映选择性高达>99% ee。值得注意的是，这种生物催化策略能够克服在乙烯基硫醚的过渡金属催化氢化中面临的催化剂中毒和C(sp)/C(sp)-S键断裂这一长期存在的缺点。最后，该方法的潜力还体现在其在手性C(sp)-N/O/Se键的立体汇聚组装中的更广泛应用，对映选择性良好至优异。
