Studies On The Reaction Of Aryl Alkyl Grignard Reagent With Enol Esters

A series of 1,3-diol and 1,3,5-triol compounds were synthesized by cascade reactions of aryl alkynyl Grignard reagents with three enol esters.The reaction mechanism of the cascade reaction was further speculated.The effect of weak interaction in the crystals of 1,3,5-triol on molecular conformation and packing was investigated.The thesis main consists of the following three parts:?1?About sixty of 1,3-diols and 1,3,5-triol compounds were obtained by the non-classical cascade 1,2-addition/rearrangement/retro-O-acylation/C-acylation reaction of aryl alkynyl Grignard reagents with isopropyl acetate,vinyl acetate and vinyl benzoate.The products were characterized by ¹H NMR,¹³C NMR and ER-MS.The reaction yield and the proportion of isomers were determined by HPLC.The results showed that the reactivity and stereoselectivity of aryl alkynyl Grignard reagents with isopropenyl acetate were higher than the other reactions.In addition,the yield of 1,3-diol in isopropyl acetate was higher,vinyl benzoate 1c provided a higher yield of 1,3,5-triols.Further measurements revealed that symmetrical 1,3,5-triol possesses anti-and syn-two configurations,and the asymmetric of1,3,5-triol has(anti,anti,syn_C?C)-,(syn,anti,syn_C?C)-,(syn,syn,anti_C?C)-three configurations.?2?Based on the experimental results,the universality of the cascading reaction mechanism of 1,2-addition/rearrangement/retro-O-acylation/C-acyl group was verifiedy by DFT theoretical calculation,used the reaction of phenylacetylene Grignard reagent with isopropenyl acetate,vinyl acetate and vinyl benzoate as a template.The results showed that the reaction mechanism was applicable to the reaction of phenylacetylene Grignard reagent with isopropenyl acetate and vinyl acetate,while vinyl benzoate undergoed two rearrangement reactions.The energy level diagram of theoretically calculated showed that,unlike the reaction of isopropenyl acetate and vinyl acetate,the retro-O-acylation process in the reaction of vinyl benzoate with phenylacetylene Grignard reagent was endothermic.The reaction mechanism of the 1,3,5-triol was speculated base on the mechanism of the1,3-diol.It was proposed that the formation of 1,3-diol and 1,3,5-triol experienced a common six-membered ring intermediate.It was presumed that the formation of a nucleophilic enol intermediateis which by O-Mg cleavage of intermediate was the key to the formation of the1,3,5-triol.Comparing the structures of 1,3-diol with 1,3,5-triol,it was proposed that other six-membered ring intermediate was formed by the aldol reaction of six-membered ring intermediate with the enol intermediate,extending the carbon chain.Then this six-membered ring continued to react with the aryl alkynyl Grignard reagent to form 1,3,5-triol with different configurations.With the experimental result,it could be seen that the steric hindrance was not conducive to the reverse-O-acylation reaction,thereby affecting the relative yield of 1,3-triol and 1,3,5-triol.?3?Five crystals of 1,9-bis?X-phenyl?-1,8-diyne-3,5,7-triols?X=p-Cl,p-F,p-H,p-CH₃?compounds were obtained by solvent evaporation.Single crystal diffraction indicates that they were all monoclinic crystal systems with different spatial groups.The intramolecular and intermolecular interactions in the 1,3,5-triol molecules were analyzed,as well as the effects on molecular conformation and three-dimensional packing.It was observed that the hydrogen bonding patterns were formed between each of single-molecule,whereas H-bonding dimers multimers were formed in the crystal lattice of compounds 2,4,and 5.All of the structures were stabilized by classical intra-and intermolecular hydrogen bonding and some other weak interactions.The OH all facing the same direction was beneficial to the formation of intramolecular O-H···O hydrogen bond,and the pattern set S?6?.The intra-and intermolecular O-H···O hydrogen bonded aggregated to form one-dimensional?1D?infinite ribbons,allowing molecules to form infinitely along the chain to form 2D layers.Adjacent layers were connected by different weak intermolecular interactions to form 3D supramolecular structure.The difference in intermolecular interactions leaded to different dihedral angles.