Design And Research Of A New Cyclization Reaction Based On O-alkynylbenzaldehyde Substrates

Ortho-alkynylbenzaldehydes are one class of important organic intermeidates,which can be converted into various cyclic skeletons under transition-metal catalysis and non-metal catalysis conditions,such as isochromenes,indanones,isoquinolines,naphthalenes,isobenzofurans and other polycycles.These skeletons which could be found in a large number of natural products and pharmaceutically compounds thus have potential application for drug discovery.Therefore the construction of these cyclic skeletons by developing new ways is vitally important.In this project,some new studies on the reaction of ortho-alkynylbenzaldehydes were carried out for achieving the synthesis of a variety of compounds with cyclic structure.It includes as follows:In part one,the synthesis of a series of highly strained tetracyclic bridgehead olefins by gold-catalyzed reaction of ortho-alkynylbenzaldehydes with conjugated dienes was achieved with high chemo-and stereo-selectivity.This reaction could involve tandem gold-catalyzed[3+2]cycloaddition and Prins type ring-closing reaction,thus generating complex structures in a straightforward manner.It has several advantages such as simple operation,mild conditions,good substrate scope,high stereoselectivity and high yields.Moveover,the reaction of ortho-carbonylated alkynyl-substituted benzaldehydes with conjugated dienes by siliver catalysis was also developed,and a variety of indanone-fused cyclohexenes were obtained with high stereoselectivity and good yields.The reaction mechanism was provided as a domino hydrolysis/Knoevenagel condensation/Diels-Alder reaction process.In part two,the reaction of ortho-alkynylbenzaldehydes with low-active thiophenes by gold catalysis was introduced in detail.Many thienyl-substituted isochromene derivatives could be provided in good yield.It could go through tandem heteroarylation/cycloisomerization reaction.This reaction provides a new method for synthesis of isochromene comnpounds containing thiophene sub-structure with protential bioactivivty.In part three,by tuning the size of substituent of primary amines,ortho-carbonylated alkynyl-substituted benzaldehydes with primary amines can reaction smoothly under catalyst-free conditions,giving functionalized 3-hydroxylindenamine and isoindolinone derivatives,respectively.In particular,the use of Et₃N could change completely the reaction route to afford 3-hydroxylindenamine products in good yields,and the mechanism of base-promoted Petasis-Ferrier type rearrangement was proposed.These reactions are simple,green and efficient for synthesis of isoindolinone and 3-hydroxylindenamine derivatives.Furthermore,the reaction of ortho-carbonylated alkynyl-substituted benzaldehydes with phenols under arylsulfonic acid conditions was performed,thus the indeno[2,1-c]chromen-7-one derivatives conld be obtained in moderate yield.The sulfonyl-functionalized indanone products could be provided in high yield when the reaction of ortho-carbonylated alkynyl-substituted benzaldehydes with arylsulfinic acids was carried out without extra catalyst.The two reactions could undergo similarly a domino ynone hydrolysis/Knoevenagel condensation sequence.