Synthesis Of Spiroketals By Au(?)/Sc(?)Bimetallic Catalysis

Transition metals exhibit a variety of bond formation and diverse chemical properties.Combined two transition-metal catalytic strategy is an important and efficient synthetic method by using multiple catalysts in one reaction system,which can break through the limitation of single catalyst system for avoiding the separation of intermediates and building complex target molecules in a single step.This strategy can develop a new type of reaction that can not be achieved by a single catalyst system,and improve the efficiency and selectivity of the reaction,which follows up with the requirements of green chemistry.Spiroketals are an important structural unit within a wide variety of bioactive natural products as well as pharmaceuticals.Its unique molecular structure and good biological activity have attracted the attention of many research groups.The synthetic methods of spiroketals all require preparation of complicated functionalized precursors in advance.Thus,the development of a simple and effective approach to spiroketals from easily available fragments is highly desirable.Based on this research background,we have developed a novel and ultrafast reaction to access a range of spiroketals in high yields and excellent diastereoselectivities from alkyne alcohol and o-quinone methide precursors by a bimetallic ? acid gold(I)complex/Lewis acid Sc(OTf)3 catalytic system.This method has ultrafast reaction rate(less than 5 min)under mild condition.Even if the loading of catalysts decrease tenfold,this reaction still remain very high activity.General scope and good scalability are also attractive features of this method.Two reaction pathways are proposed according to controlled experiments:Cationic gold and lewis acid Sc(OTf)3 synergistically catalyzed 5-exo-dig cyclization of the alkynyl alcohol and dehydration of o-hydroxybenzhydryl alcohol,generate two key reactive intermediates electron-rich vinyl ether M2 and electrophilic o-QMs Ml,subsequent the direct[4 + 2]cycloaddition between Ml and M2 would form the expected spiroketals.The Michael reaction of alkynyl alcohol with M1 forms adduct 4,which undergoes 5-exo-dig cyclization,and C-O bond cleavage cascade in the presence of gold catalyst could also generate intermediate Ml and M2 at the same time.At the same time,the catalytic asymmetric version of this reaction was also explored,however the enatioselectivities are not good at current stage.It still provides the data and possibility for the asymmetric synthesis of spiroketal derivatives although no excellent results have been obtained.