Journal Article

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

Nguyen, Thach T., Zhang, Hanmo, Hoveyda, Amir H., Schrock, Richard R., Koh, Ming Joo

2016

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 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