Studies On Phosphine-catalyzed Annulations Of Electron-deficient Conjugated Systems

Annulation reaction is one of the most powerful tools for rapid assembly of structurally diverse carbo-and hetero-cycles from readily available substrates. Besides the existing annulation protocols such as Diels-Alder reaction and transition-metal catalyzed ring-closure reactions, during the last decade, nucleophilic phosphine catalytic annulation reactions have provided a reliable platform for efficient construction of complicated molecular architectures. Since tertiary phosphine catalysis generally features mild condition and simplicity of operation, recently a great deal of effort has been poured into this field of phosphine-catalyzed annulation reactions. As a result, an array of various phosphine-triggered annulations has been developed, providing new synthetic methodology for cyclic structures with diversity.Phosphine-catalyzed annulation reactions depend on a range of peculiar substrates. It is known that, upon treatment with tertiary phosphines, the Morita-Baylis-Hillman (MBH) derivatives and electron-deficient allenes readily generate reactive dipoles which are entrapped with varied electrophiles, leading to a number of annulation reactions. Consequently, exploring electrophiles with proper reactivity has become a key to develop phosphine-catalyzed annulations. Electron-deficient conjugated systems are often involved in a variety of annulation reactions as electrophiles. However, the phosphine-catalyzed annulations of electron-poor conjugated systems are rarely touched. Thus, in this dissertation three novel phosphine-catalyzed annulation reactions of electron-deficient conjugated systems have been systematically investigated, and the following results have been achieved.1. For the first time, a PPh3-catalyzed [1+4] annulation of MBH acetates as a C1synthon with α,β-unsaturated imines derived from chalcones has been developed. Under mild conditions, a broad scope of substrates readily afforded the [1+4] annulation products in good diastereoselectivity and high yield. In contrast with the phosphine-catalyzed [3+2] annulations of MBH derivatives or allenoates, this [1+4] annulation produced2-pyrolines instead, providing a facile access to this kind of heterocycles. Mechanistic investigation unveiled this [1+4] annulation reaction represents the first example of the [1+4] cycloaddition of phosphorus ylides and1,3-azadienes.2. Following the [1+4] annulation mode between phosphorus ylides and1,3-azadienes, the phosphine-catalyzed annulations of in situ formed phosphorus ylides and polar conjugated dienes have been further explored. As a result, a novel phosphine-catalyzed [1+4] annulation reaction between MBH derivatives and1,1-dicyano-1,3-dienes has been developed, providing a new method to synthesize polysubstituted cyclopentenes. It was also found that the substituents of substrates impose significant influence on the annulation mode. Through choosing differently substituted substrates, highly chemoselective [1+4] annulation or regioselective [3+2] annulation could be readily achieved, which provide facile access to five-membered carbocycles.3. For the first time, a phosphine-catalyzed [3+2] annulation reaction of a-substituted allenoates and ester-activated α,β-unsaturated imines has been developed, which provides new and efficient access to highly functionalized cyclopentenes with one all-carbon quaternary center. This reaction also represents a novel variation of the famous Lu [3+2] cycloaddition reaction. Our findings in this study unveiled that the ester-activated alkene-assisted formal [1,2]-proton shift between β-and γ-carbon of the allenoate could serve as an alternative pathway to facilitate formation of the Lu [3+2] cycloaddition product. This reaction is the first example of α-alkyl substituted allenoates engaged [3+2] annulation under phosphine catalysis, illustrating a scope expansion in the famous Lu [3+2] cycloaddition reaction.