JACS: stereospecific synthesis of e-alkenes from Terminal Alkynes by anti Markovian addition

Hydroalkylation of alkynes has recently become an effective new method for olefin synthesis The z-substituted arylalkenes can be prepared by the free radical hydroalkylation of arylalkynes (scheme 1a) Fu and Macmillan team have developed the conversion method of terminal alkynes to 1,1-disubstituted alkenes (scheme 1b) by nickel catalysis and photo oxidation reduction / nickel co catalysis, respectively However, the hydroalkylation methods which can effectively synthesize disubstituted e-alkenes are rarely reported In 2015, Gojko lalic group reported the copper catalyzed hydrogenation of terminal alkynes (scheme 1c) using alkyltrifluoromethylsulfonate as electrophilic reagent, providing an effective method for the synthesis of e-alkenes However, this method has some obvious limitations, for example, it is highly sensitive to the space properties of electrophilic reagents, and it is only suitable for the linear primary alkyl trifluoromethylsulfonate without α - branch chain In addition, the high reactivity of alkyltrifluoromethylsulfonate and reagents further limits the reaction range, and introduces practical problems related to the preparation, purification and stability of initial electrophilic reagents (source: J am Chem SOC.) recently, Gojko lalic group of Washington University developed a new method of hydroalkylation of terminal alkynes on this basis, which solved the key shortcomings of the previous original hydroalkylation reaction, while retaining its main advantages It is proved that the Cu / Ni double catalyst system allows the use of primary and secondary alkyl iodine as coupling mate and can synthesize a wide range of e-olefins from terminal alkynes Relevant research results were published in j.am Chem SOC (DOI: 10.1021/jacs.9b04800) Inspired by the pioneering work of Nakao and brown, the author plans to use nickel catalyst to promote the cross coupling of organic copper intermediates with alkyl iodine (scheme 2C) In the initial experiment, the author found that the common cross coupling catalyst (dtbpy) NiCl2 promoted the effective cross coupling of the separated alkenyl copper intermediate 5 and cyclohexyl iodine (scheme 3a) However, the same nickel catalyst can only obtain the required e-olefin (scheme 3b) in 23% yield in the catalytic hydrogenation alkylation reaction, which is also not successful with various single and bidentate phosphine and nitrogen ligands (source: J am Chem SOC.) contrary to the author's expectation, the product of Ma hydroalkylation is not an important by-product in these reactions, on the contrary, the main problem is to form a mixture of high molecular weight products It is concluded that the byproducts of high molecular weight may be formed by trimerization of Reppe and related tetramerization of alkynes promoted by nickel (0) complex Considering the mechanism of Reppe trimerization, tridentate ligands should inhibit this side reaction by preventing two alkyne molecules from coordinating at the same time It is found that the reaction of terminal alkyne 12 and cyclohexyl iodide can be optimized by using iprcucl as catalyst, tridentate TPY ligand supported nickel (I) as cocatalyst, pH 3sih as hydride source and lioi PR as conversion reagent of copper catalyst (Table 1) (source: J am Chem SOC.) further, the scope of the reaction was studied As shown in Table 2, all products are obtained as a single regional isomer and a single diastereomer The reaction has excellent functional group tolerance, including nitriles (19), esters (20), arylethers (15), methylsilyl ethers (13, 17, 21 and 27), alkenes (15), alkylchlorines (26), sulfonamides (31), dialkyanilines (25) and arylbromides (18) The new reaction can also tolerate a variety of heteroaromatics, including furan (23), 2-chloropyridine (24), pyridazine (30), thiazole (28), pyrimidine (29), tetrazole (33) and benzoxazole (34) However, the reaction can not tolerate proton functional groups such as hydroxyl and amino groups Reducible functional groups such as aldehydes and activated olefins are also incompatible with the reaction conditions Tert alkyl iodide, aryl substituted alkynes and disubstituted alkynes also do not participate in the hydroalkylation reaction (source: J am Chem SOC.) as shown in scheme 4, based on the typical mechanism of copper catalyzed hydrofunctionalization of alkynes and nickel catalyzed cross coupling reaction, the author proposed the mechanism of hydroalkylation reaction (source: J am Chem SOC.) further, the feasibility of the nickel catalyzed cross coupling of alkenyl copper intermediates with alkyl iodide (scheme 5) was proved by experiments Finally, the relationship between metal transfer reaction and the activation of alkyl halides is discussed The results show that the metal transfer (VI → VIII) may occur before the activation of alkyl iodine (VIII → IX) (source: J am Chem SOC.) conclusion: Gojko lalic et al Of the University of Washington developed a stereospecific method for the synthesis of e-alkenes from terminal alkynes and alkyliodides The hydroalkylation reaction is realized by the synergistic catalysis of copper and nickel, and has excellent anti martensitic addition selectivity The reaction has a wide range The mechanism study provides evidence for the activation of Alkynes by hydrogenation of copper catalyst, which is the key to control the regioselectivity and enantioselectivity of the whole reaction.