The Development Of Novel Tandem Reactions From Conjugated Enynals And Application In The Construction Of Polycyclic Compounds

Polycyclic compounds are the core structures widely existed in the natural and biologically active compounds. Tandem reaction strategies, which could generate multiple rings and chemical bonds in one pot, have been considerated as the most powerful and efficient methods for the synthesis of these polycyclic structures. Conjugated enynals are highly active substrates with several reaction sites and have attracted immense attention in the realization of varities of transformations in the past decades, nevertheless, the reactions commonly proceed through benzopyryl salt intermediates. Therefore much more novel reactive properties would be desirable to be explored. Hence we would like to describe the achievements in the construction of polycyclic compounds by designing novel tandem strategies derived from conjugated enynals. During the cascade reactions, intermediates being different from typical benzopyryl salts were uncovered, providing potential synthetic methodologies for the total synthesis of natural or bioactive compounds. This dissertation was divided into four parts as follow:（1） Silver-catalyzed 1,3-dipolar cycloaddition/cyclopropanation of conjugated enynals with alkenes. The reaction proceeded through a key intermediate of 1,3-dipolar/silver carbene tautomerized from benzopyryl salt intermediate to access a series of polyoxacyclic compounds. The stability of the key intermediate was determinated by introducing an electron-withdrawing group on the alkyne to disperse the negative charge of 1,3-dipolar. The premilinary asymmetric exploration revealed that chiral bisphosphine ligand could reach polyoxacyclic compounds employing 5-6 chiral centers, including 1-2 chiral quaternary carbon centers with moderate enatioselectivity.（2） Metal-catalyzed tandem cyclizations of electron-withdrawing conjugated enynals with alkynes. On the one hand, in the presence of indium catalysis, the reaction proceed via an indanone intermediate formed by sequential hydrolysis and Knoevenagel condensation from enynals, which could be captured by kinds of alkynes through [2+2] cyclization to furnish indanone-fused cyclobutenes. Alkynes including diaryl acetylenes, aryl-alkyl acetylenes, aryl alkynyl bromides and phenylacetylene derivatives were all tolerated. On the other hand, in the presence of the silver catalysis, fluorenol derivatives were obtained by cascade procedures of [4+2] cycloaddition and intramolecular Friedel-Crafts reaction of benzopyryl salts with diarylacetylenes; besides, electron-withdrawing conjugated enynals could react with aryl-alkyl acetylenes or phenylacetylene derivatives to yield the corresponding fluorenol derivatives by stepwise with naphthalene derivatives as the intermediates.（3） Indium-catalyzed reactions of electron-withdrawing conjugated enynals with propynols. The reactions proceeded through four-step tandem process, including hydrolysis, Knoevenagel condensation, Michael addition and Conia-ene, to produce indanone-fused 2-methylene tetrahydrofurans and γ-lactones. Indanone-fused γ-lactones could be readily obtained under the oxdative conditions of Cr O₃/pyridine resulting from indanone-fused 2-methylene tetrahydrofurans.（4） Zinc-catalyzed cyclization of electron-withdrawing conjugated enynals with 1,3-conjugated dienes. The activated indanone intermediates were captured by 1,3-conjugated dienes to offer indanone-fused cyclohexenes. Besides, N,N-dimethyl aniline could also attack the indanone intermediate to form deesterified 3-substituted dihydroindanone. And also, In the absence of attacking reagents, electron-withdrawing conjugated enynals could be dimerized under the catalyst of zinc via the indanone intermediates.