Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis

• Published in: Nature (London) 2016-03, Vol.531 (7595), p.459-465
• Main Authors: Koh, Ming Joo, Nguyen, Thach T., Zhang, Hanmo, Schrock, Richard R., Hoveyda, Amir H.
• Format: Article
• Language: English
• Subjects: 140/131; 140/146; 639/638/403; 639/638/77; Alkenes - chemical synthesis; Alkenes - chemistry; Ambient temperature; Biological Products - chemical synthesis; Biological Products - chemistry; Bromides; Bromides - chemical synthesis; Bromides - chemistry; Catalysis; Catalysts; Chemical properties; Chemical synthesis; Chlorides - chemical synthesis; Chlorides - chemistry; Fluorides; Fluorides - chemical synthesis; Fluorides - chemistry; Halides; Halogenation; Humanities and Social Sciences; Identification and classification; Methods; Molybdenum; Molybdenum - chemistry; multidisciplinary; Observations; Olefins; Organic chemistry; Production processes; Reagents; Ruthenium; Science; Structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature17396

One shortcoming of olefin metathesis has been that acyclic alkenyl halides could not be generated efficiently and stereoselectively; but now halo-substituted molybdenum alkylidene species are shown to be able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z -alkenyl halides. Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z -alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules. Catalytic olefin metathesis Olefins with a halide substituent are a mainstay in synthetic chemistry. However, the scope for the efficient stereoselective synthesis of acyclic alkenyl halides — a class of compound common that includes many biologically active natural products — has been limited. Amir Hoveyda and colleagues show here that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and can participate in high-yielding olefin metathesis reactions that produce acyclic 1,2-disubstituted Z -alkenyl halides. Many alkenyl chlorides, bromides and fluorides can be obtained in up to 91% yield and complete Z selectivity.