BF₃·OEt₂-Promoted Propargyl Alcohols Rearrangement/[1,5]-Hydride Shift/Cyclization Reaction

As one of the most valuable skeletons and building blocks,tetrahydroquinolines can be found in lots of natural products and drugs.In the past few decades,tandem[1,5]-hydride shift(HT)/cyclization reactions proved synthetically powerful for the construction of structurally diverse complicated molecules,especially tetrahydroquinoline derivatives.In the most of[1,5]-HT/cyclization reactions,substrates usually requires to contain both hydride donors and hydride acceptors.The typical hydride donors are C(sp³)–H moiety adjacent to heteroatom.Activated alkenes,aldehydes,ketones,and imines are common as hydrogen acceptors,but alkynes are rarely reported as hydrogen acceptors.Up to now,tetrahydroquinoline compounds containing alkenyl fluoride moiety have never been reported by[1,5]-HT/cyclization/fluorination.Thus,developing a novel approach to synthesize complex tetrahydroquinoline derivatives still has potential application value.In this dissertation,an efficient BF₃·OEt₂-mediated cascade propargyl alcohol rearrangement/[1,5]-HT/cyclization reaction for the synthesis of tetrahydroquinoline derivatives has been described.The optimal reaction conditions were determined by screening of the reaction parameters,such as Lewis acids,Br?nsted acids,solvents,temperature,and the ratio of the reactants.The optimal conditions were chosen as:2.5equivalent of BF₃·OEt₂ can be used as both Lewis acid and fluorine source,1,2-dichloroethane as solvent at 60 ? for 2 h.First,for the class of tertiary amines:cyclic or chain tertiary amines can be carried out smoothly under standard conditions;Second,the substituents directly linked to triple bonds have great impact on the results.The ketones can be obtained in a single manner when the aryl or alkenyl are bonded to the triple bond,but alkenyl fluorides can be obtained when alkyl or TMS are attached to the triple bond.This protocol not only can obtain a various of tetrahydroquinoline derivatives with good-to-execllent yields,and different types of target products can be synthesized by changing the substituents.Therefore,this article provides a convenient method to synthesis the tetrahydroquinolines.