One Pot Synthesis Of β-methylstyrene Via Palladium-catalyzed Dearomatization/isomerization

The development of simple and efficient synthesis methods ofβ-methylstyrene compounds has always been an important research direction in the fields of drug development and organic synthesis.These compounds can be used as intermediates to synthesize complex natural products and are widely used in industrial production.The method of synthesizingβ-methylstyrene is the cross-coupling reaction of an aryl metal reagent with a vinyl boronate or vinyl halide.Another conventional method is isomerization of allylbenzene to obtainβ-methylstyrene,and the catalyst includes bases（KF/Al₂O₃ and K₂CO₃）or transition metal complexes（Rh,Ru,Ir,Pt,Ni and Pd,etc.）.Although these methods are effective,these reactions have many disadvantages,such as the need for pre-functionalization,harsh reaction conditions,poor resistance to functional groups,and incapability of completely obtaining a single product,which is generally contains a mixture containing a cis-trans structure.How to obtain a single product is a difficult problem in the synthesis of such important compounds.In this thesis,a series ofβ-methylstyrene compounds were synthesized by one-pot method using benzyl chloride and allyltributylstannane as substrates via dearomatization/isomerization strategy.The effects of catalyst,solvent and acid on the reaction were systematically investigated.The optimal reaction conditions were determined as follows:Pd₂（dba）₃（5 mol%）,PPh₃（10 mol%）,p-toluenesulfonic acid（2.0 equiv）,DCM（2 mL）,and acidified at room temperature for 12 h.Under the optimal reaction conditions,we investigated 16 kinds of benzyl chlorides with different substituents in the yield of 60%-84%.It was found that the benzyl chloride with electron donating groups or an electron withdrawing groups all showed higher reactivity.By this method,β-methylstyrene compounds containing different functional groups can be synthesized in high yield and high selectivity.Finally,the reaction mechanism was discussed.It is speculated that the reaction has undergone oxidation reaction,transmetalation,andβ-H elimination.All the substrates obtained were characterized by ¹H NMR,¹³C NMR,IR and HRMS.