Metal-free Hydrohalogenation Of Alkynes Promoted By H-bonding Networks And Its Mechanistic Studies

Vinyl halides are among the most significant functional groups as they are at a core structure of many natural products,pharmaceuticals,and agrochemicals.They are also versatile synthetic intermediates in organic synthesis,especially used as coupling partners for a range of transition-metal-mediated cross-coupling reactions,and also used as precursors to a variety of organometallic reagents.Therefore,the preparation of alkenyl halides has aroused great interest among researchers in organic synthesis.The preparation of alkenyl halides can not only use the traditional methods of carbonyl as well as hydrometallation-electrophilic halogenation,halogen exchange,but also use the new process based on olefin metathesis and C-H bond activation.Compared with these methods,although hydrohalogenation of alkynes by direct addition of HX remains the most direct and most atom-economical synthetic method to access vinyl halides,it has low yield and low selectivity.On the one hand,the transition metal catalysis activate the alkyne carbon-carbon triple bond and HX insertion,which can provide alkenyl halides with high efficiency and high selectivity.However,there are few reports on non-activated alkyne,and there is a problem of narrow substrate range and low selectivity for internal alkyne.On the other hand,in metal-free reaction systems,the hydrohalogenation of alkynes is typically restricted to activated substrates,in order to achieve high efficiency and excellent selectivity;as for non-activated alkynes,it is difficult.Therefore,a hydrohalogenation method that produces a variety of vinyl halides in high efficiency and high regio-and diastereoselectivity remains a worthwhile pursuit.Many studies have shown that HFIP(hexafluoro-2-propanol,CF3CHOHCF3)is a solvent capable of forming strong hydrogen bonds networks or aggregates;linear aggregates can stabilize cations well and serve as better H bond donors than monomers and cyclic aggregates.It can be speculated that HFIP linear aggregates can not only serve as proton donors,but also activate hydrohalogenating reagents to achieve slow release of nucleophilic halide anions and complete the hydrohalogenation reaction.Therefore,it is worth considering using the unique properties of HFIP to realize the transition metal-free hydrogen halide reaction of alkyne to develop an innovative metal-free hydrogen halogenation system.In this paper,a highly regioselective trans-hydrohalogenation reaction of terminal aromatic alkynes and unactivated internal alkynes is described,using organic bases Et3N or DMPU,TMSX as different halogen sources and HFIP as solvents to activate TMSX through a hydrogen bonding network.The strategy can efficiently preparate alkenyl chloride,alkenyl bromide and alkenyl iodide,and has diverse functional group tolerance;Advantages lie in metal-free catalysis,safe and convenient operation,a wide range of substrates and high stereoselectivity,etc.It is a environmentally friendly synthesis strategy,which solves the problem of hydrohalogenation of internal alkynes and provides a new approach for the efficient synthesis of alkenyl halides form non-activated alkynes without metal-catalysis.The reported methods for the preparation of vinyl halides involve two main categories sharing the same step-wise mechanism.The first category involves an initial activation of alkynes by metals,followed by the nucleophilic halide addition to the activated alkyne,and the protodemetallation of the resultant vinyl-metal intermediate in an anti-manner.The second category involves the initial proton addition to alkynes,followed by the halide nucleophile capture of the ensuing vinyl carbocation intermediate.We also propose a relatively novel reaction mechanism on the basis of our experimental results and theoretical calculations.This reaction relies on the hydrogen bond network aggregates of HFIP and organic bases Et3N or DMPU to activate TMSCI;and it achieves the one-step hydrohalogenation reaction of alkynes via a synergistic anti-addition reaction mode.This provides a new idea for further research on the hydrogenation of unsaturated carbon-carbon bonds.This mechanism is markedly distinct from any previously reported stepwise mechanism for hydrohalogenation of alkynes under metal-or metal-free catalysis.DFT computations also provide the rationale supporting a concerted regio-and stereoselectivity.This provides a new theoretical idea for further research on the hydrogen halogenation of unsaturated carbon-carbon bonds.