Angelw: the Reisman group of Caltech converted enol trifluoromethylsulfonate to haloalkene under the catalysis of nickel

Haloalkenes, as functional groups, are often used to construct C-C and C-X (x = O, N, s) bonds, and also exist in some natural products and active molecules Haloalkenes are not only common substrates of transition metal catalyzed cross coupling reactions, but also can be converted into nucleophiles through metal halide exchange to participate in the 1,2-addition of carbonyls (scheme 1) Noncyclic halogenated alkenes are usually prepared from corresponding alkynes or aldehydes, while most cyclic halogenated alkenes are synthesized from corresponding ketones Under the control of kinetics or thermodynamics, CYCLOKETONE can be directly converted into trifluoromethylsulfonate enol ester, but it can not be directly converted into alkenyl lithium or alkenyl magnesium commonly used in 1,2-addition reaction Therefore, it is necessary to develop a multi-step alternative method to 1) convert ketone to trifluoromethylsulfonate enol ester; 2) convert trifluoromethylsulfonate to stantane; 3) convert stantane to halide Under mild conditions, the synthesis route can be simplified by directly converting trifluoromethylsulfonate to haloalkene without organotin intermediate In the first time, Buchwald group converted alkenyl trifluoromethylsulfonate into bromide or chloride under the catalysis of PD, but did not form iodide, and the expensive ligands, high temperature and additives involved in the reaction limited its application Recently, Hayashi's group has converted enol trifluoromethylsulfonate into iodide, bromide or chloride at room temperature under Ru catalysis, but the Ru catalyst needed is not suitable for commercial production, and there are limited examples of iodoene formation Recently, Sarah E Reisman group of Caltech developed a nickel catalyzed enol trifluoromethylsulfonate halogen exchange reaction, which can be used for the synthesis of alkenyliodide, bromide and chloride (scheme 1) The results were recently published in angelw Chem Int ed (DOI: 10.1002 / anie 201906815) (picture source: angelw Chem Int ed.) firstly, the author used enol trifluoromethylsulfonate 1A as model substrate and Ni (COD) 2 as catalyst to prepare alkenyl iodide, bromide or chloride (Table 1) in DMA / THF (1:3) mixed solvent system by changing brine preparation Then, the author screened a variety of Ni (II) pre catalysts and found that when Ni (OAC) 2.4h 2O was used, the three reactions had good yields; when Ni (OAC) 2.4h 2O (5 mol%) and 10 mol% cod (method B) were used, the brominated and chlorinated olefins could be obtained in good yields, but only in medium yields In order to improve the yield of iodide, the author selected additives The results show that the yield of 2A can be increased by adding 20 mol% DMAP and increasing the loading amount of catalyst (10 mol% Ni (OAC) 4, 10 mol% COD) However, the exact role of DMAP in the process of iodization is not clear In addition, when 5 mol% Ni was used, many substrates were not completely transformed (entry 10) Therefore, the increase of Ni loading to 10 mol% can not only improve the conversion rate, shorten the reaction time, but also reduce the formation of reduction products (methoda) (picture source: angelw Chem Int ed.) after determining the best reaction conditions, the author investigated the substrate range of nickel catalyzed halogenation reaction (Table 2) The reaction can tolerate a variety of common functional groups, including amines, carbamates, pyridines, olefins, dienes, esters, ketones and ketenes In the chemical selective halogenation reaction, alkenyl trifluoromethylsulfonate is superior to aryl trifluoromethylsulfonate, aryl acyl chloride and aryl borate; however, in the presence of aryl bromide and iodide, competitive halide exchange will occur The performance of iodization, Bromination and chlorination reactions are different: the method a is the best for about half of the substrates; after the iodization reaction slows down, the reaction time needs to be extended and 5.0 equivalent Nai needs to be added to improve the conversion rate; however, the improved reaction conditions are often accompanied by dehalogenation, which makes it difficult to separate olefins from iodinated olefins For the above substrates, the competitive reduction can be eliminated by using Ni (COD) 2 and enol non three fluoromethanesulfonate to obtain the pure iodoene Bromination and chlorination are generally efficient and more stable For most substrates, the complete conversion can be achieved by using 5 mol% Ni without DMAP In order to prove that the reaction can be amplified, the author has carried out a 1 mmol scale reaction at room temperature to obtain bromide 13b (yield 95%) (photo source: angelw Chem Int ed.) at present, the mechanism of this reaction is not clear The preliminary study on the iodination reaction with Ni (COD) 2 as catalyst shows that the reaction of 1A presents the induction period (scheme 2a) at low [Ni] The V max / [Ni] curve shows that the reaction is positively dependent on [Ni] When the amount of Nai is more than 1 equivalent, the iodination rate of 1A does not change, but its dependence on [1A] is more complex One possibility is that induction period is needed to form active Ni I catalyst In the reaction, EPR spectrum shows that there is a signal consistent with Ni-x complex, but it only accounts for 2% of the total [Ni], while other experiments for the determination of non catalytic catalysts have not been determined Finally, the reversibility of the exchange of trifluoromethylsulfonate and halogens was evaluated by cross experiments: at 23 ℃, DMA / THF (1:3), the mixed solution of 24-otf / 25-br (1:1) was treated with Ni (COD) 2 (10 mol%), and the formation of 25-otf or 24-br (scheme 2b) was not detected; when 1.0 equivalent LiBr was added, 24-br (90% yield) was obtained ）, but 25 - OTF was not detected Through 1H NMR monitoring, it is found that 24 OTF does not occur oxidation addition when there is no halogen in the system When iodoene 25-i is placed in Ni (COD) 2 (10 mol%) and metal salt of trifluoromethylsulfonate (such as naotf), it will not form scheme 2C The above experiments show that the oxidation addition of trifluoromethylsulfonate alkenyl ester is irreversible, or the exchange of trifluoromethylsulfonate halogen in the oxidation addition complex is fast and irreversible In these two cases, the irreversible consumption of trifluoromethylsulfonate enol ester enables the reaction to generate corresponding haloalkenes, which is in sharp contrast to the nickel catalyzed halogen exchange reaction, which is a thermodynamic driven equilibrium process Conclusion: Sarah E Reisman group has developed a nickel catalyzed exchange reaction of enol trifluoromethylsulfonate with halogen, which can produce enol iodide, bromide and chloride in good yield The reaction condition is mild and has good functional group tolerance.