(E) - selective cross dimerization of terminal alkynes catalyzed by angelw: Co

Conjugated 1,3-enyne is a kind of important synthesis unit in organic synthesis It can be used to prepare multi substituted π - conjugated compounds and natural products It is also an important group in medicine Therefore, chemists have developed many effective and practical methods to prepare 1,3-alkyne, including: 1) coupling reaction between terminal alkyne and alkenyl halides or activated alkenes; 2) Wittig reaction of conjugated alkynaldehyde compounds; 3) dehydration reaction of alkynpropanol However, these reactions have some disadvantages, such as severe reaction conditions, difficult to obtain raw materials, high catalyst consumption Under mild conditions, the catalytic dimerization of two terminal alkynes is an economic and direct way to prepare such compounds Since the study group of Trost reported PD catalyzed alkyne dimerization, many metal catalyzed (mostly noble metal catalysts) alkyne dimerization have been reported one after another In this respect, chemists are more and more inclined to use the first row of cheap metals to catalyze such reactions, such as CO, Fe, etc., which are rich in content, cheap and easy to obtain, and less toxic In 2005, hengst group reported the co catalyzed self polymerization of terminal alkynes, which has good regioselectivity and stereoselectivity However, after adding two different terminal alkynes, not only the selectivity will be reduced, but also the selectivity of self coupling and cross coupling will be difficult to control In 2016, Milstein research group reported the Fe catalyzed (z) - selective cross dimerization of terminal alkyne, which requires three times the amount of trimethylsilylene to obtain the intermediate yield cross dimerization product, and it will inevitably produce the end alkyne self polymerization product Recently, the Kazushi mashima group of Osaka University in Japan reported the co catalyzed (E) - selective cross dimerization of terminal alkynes to synthesize a series of 1,3-enynes The reaction has good functional group tolerance and no self dimerization product The related research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201913835) It is worth mentioning that the team of Collins recently reported the photocatalytic end alkyne dimerization, but it needs a large amount of silylene to achieve a high yield, and the author thinks that the mechanism of the reaction through CO (Ⅲ) intermediate is different from that in this paper (source: angel Chem Int ed.) firstly, the author used 4-phenyl-1-butyne 2a and trimethylsilylene 3 as template substrate to optimize the conditions (Table 1) By optimizing the reaction conditions of ligands, solvents and reducing agents, the author determined that the optimal conditions for the reaction were: 1A as catalyst, ethyl magnesium bromide as reducing agent, THF Finally, the target product was obtained in 98% yield It is worth noting that ligands not only affect the activity of the reaction, but also the selectivity of self dimerization and cross dimerization (source: angelw Chem Int ed.) after determining the optimal reaction conditions, the author expanded the substrate range of the reaction (Table 2) Among them, the terminal alkynes with phenyl, naphthyl, thiophene, pyridine and alkyl substitution can get the target product in good yield, but tert butylphenylene can not get the corresponding product, which may be due to the effect of steric hindrance The reaction has good functional group tolerance, hydroxyl group, silicon ether, amino group, ester group, acetal, phthalimide, cyano group, halogen and other functional groups can be compatible with the reaction conditions (source: Angew Chem Int Ed.) subsequently, the authors extended the alkyne donors in the reaction (Table3) Among them, dimethyltert butyl silacetylene, trisisopropylsilacetylene and diphenylsiloxyacetylene can all be obtained in high yield However, tert butyl acetylene can only be obtained in 61% yield, which may be due to its higher steric hindrance (source: angelw Chem Int ed.) finally, the mechanism of the reaction was studied by in-situ capture and deuterium generation experiments, and the scheme 1 of the reaction was proposed: firstly, the co catalyst precursor was reduced to zero valent co active intermediate a in situ under the action of reductant, and then the C-H bond of silylacetylene was oxidized and added to form intermediate C Secondly, C metallizes another alkyne to form intermediate D or e finally, D or E is eliminated by reduction In this cycle, large steric ligands are very important for the activity and selectivity of the reaction (source: angel Chem Int ed.) Summary: Kazushi mashima research group has developed a series of 1,3-enynes synthesized by CO catalyzed (E) - selective cross dimerization of terminal alkynes The mechanism of the reaction was studied through the separation of CO (0) active intermediates and deuterium experiments, and the importance of large steric ligands was emphasized.