Study On The Highly Selective Cyclization Of Alkynone

As a special kind of internal alkyne,ynones can be conveniently synthesized by the Sonogashira coupling of terminal alkynes with acyl chlorides.Due to connecting the carbon-carbon triple bond and the carbonyl group,ynones possess high reactivity and can provide multiple active sites to participate in the cyclization reaction for preparing functionalized cyclic compounds.In this paper,inspired by the previous works of ynones as double or four active sites involving the cyclization reaction,the [2+4] and [4+3] cyclization reactions involving ynones were investigated to construct various cyclic compounds.An effective base-controlled divergent synthesis of 5?cyanobenzoxepines and benzofuro[2,3?b] pyridines from 2?bromophenylacetonitriles and ynones has been developed.The corresponding 5-cyanobenzoxepines were prepared with high efficiency and high selectivity using Li OtBu as a base,and the highest yield could reach 96%.Using DBU as a base,a series of benzofuran[2,3-b]pyridines can be delivered with high selectivity and the highest yield could reach 84%.The plausible reaction mechanism study implied that ynones underwent the [4+3] cyclization reaction to construct corresponding 5?cyanobenzoxepines,and underwent O-rearrangement reaction to offer benzofuran[2,3-b]pyridines.On the basis of the reaction between ynones and 2-bromophenylacetonitriles,the [2+4] cyclization reaction of ynones with 2?(2-alkynylphenyl)acetonitriles was further developed,and a library of polysubstituted naphthalenes were successfully constructed.This protocol was characterized by mild conditions,excellent functional group tolerance,complete regioselectivity and atom economy,which provided a simple and effective access to prepare polysubstituted naphthalenes.On the basis of the reaction between ynones and methyl 2-bromophenylacetonitriles,the cyclization reaction of ynones with 2-bromobenzyl ester was also further developed.A decarboxylation reaction occurred at high temperature and a series of benzoxepines were efficiently synthesized.