Koh Ming Joo, Nguyen Thach T, Lam Jonathan K, Torker Sebastian, Hyvl Jakub, Schrock Richard R, Hoveyda Amir H
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature. 2017 Feb 2;542(7639):80-85. doi: 10.1038/nature21043. Epub 2017 Jan 23.
The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations.
催化剂控制的立体选择性烯烃复分解反应过程的发展是近年来化学领域的一项关键进展。在基于钼、钨和钌的配合物中引入合适的配体，已实现了以前无法达到的反应活性和选择性水平。在此，我们表明，单芳氧基氯化钼配合物通过与市售、廉价且通常惰性的Z-1,1,1,4,4,4-六氟-2-丁烯发生交叉复分解反应，可提供三氟甲基取代烯烃的高能（Z）异构体。此外，与Z-1,2-二氯乙烯和1,2-二溴乙烯进行的原本低效且无立体选择性的转化反应，可在效率和Z选择性方面得到显著提高。使用此类单芳氧基氯化钼配合物能够合成具有代表性的生物活性分子以及药用相关化合物的三氟甲基类似物。借助密度泛函理论计算，阐明了所观察到的活性和选择性水平的起源，这些起源与先前提出的原理相矛盾。
