Room-temperature Palladium-catalyzed Direct 2-alkenylation Of Azole Derivatives With Alkenyl Bromides

Azoles are found in a myriad of natural products and bioactive molecules.The therapeutic potential of azole scaffold has pushed it to the forefront of metal-catalyzed development.There are diverse direct C2-functionalizations of benzene-fused derivatives,such as arylation,and other transformations.Of these reactions,the most widely accepted is arylation,while much less attention has been given to alkenylation.In addition,azole derivatives bearing alkenyl substituents at the 2-position are widely used in numerous organic functional materials,such as liquid crystals and fluorescent agents.Therefore,there is a demand for metal-catalyzed methodologies to efficiently synthesize C2-alkenylated azole derivatives.Efforts have been devoted to the method development of alkenylation of benzo-fused azole derivatives.For instance,four strategies have been established to synthesize heterocyclic compounds in the presence of a C2-alkenyl group.Three existing strategies employing copper(Cu),allyl halides or alkenes can compensate shortcoming of coupling between heterocycles and alkenyl halides,but they are still limited in substrate scope.The metal-catalyzed alkenylation with alkeny halides is still the major strategy for synthesis of C2-alkenylated azole derivatives.However,these protocols all require high temperature(over 100 ?)where low-boiling-point and temperature sensitive alkenyl halides are restricted.Under some high-temperature conditions,alkenyl reagents were merely used with the help of autoclave,making it inappropriate to scale up.Besides,reactions performed in high boiling solvents,such as DMF,are complicated in product isolation.Thus,the development of general and mild catalyst systems for this type of transformation is strongly desired.Pd-catalyzed direct C2-alkenylation of azole derivatives proceeds efficiently under mild conditions,and the reaction of substituted benzoxazoles,oxazole and benzothiazole occurred even at room temperature.The substrate scope of the reaction was turned out to include mono-,di-and trisubstituted alkenyl bromides.To validate the scalability of this method,5-Methyl-2-(prop-1-en-2-yl)benzoxazole(3c)was prepared on one-gram scale at room temperature.This thesis is involved with the research background,condition optimization,scope exploration and gram test.