Studies On The Domino Reactions Of α-Functionalized Ketene-(S,S)-Acetals With Vilsmeier Reagents And Oxalyl Chloride

Since Kelber first synthesized theα-Benzoyl ketene-(S,S)-acetal in 1910,α-oxo ketene-(S,S)-acetals chemistry has become an important division in organic chemistry through the development of nearly one hundred years. Especially in the past three decades, quite amount of documents have been published in this field, and several reviews reported and summarized these findings. Generally speaking, the reaction types involvingα-oxoketene-(S,S)-acetals mainly include the regioselective addition-aromatization with organometallic reagents, conjugate addition-cyclization with nitrogen nucleophilicspecies, nucleophilic reactions ofα-carbon, acting as odorless dithiol equivalentsin thioacetalization, Michael additions and [5+1] annulation, as well as the synthetic applications based on the above reactions.Among the variousα-Oxo ketene-(S,S)-acetals,α-acetyl-α-carbamoyl ketene-(S,S)- acetals andα-alkenoyl ketene-(S,S)-acetals are easier to prepare and bear much more functionalities. We have had the extensive studies on theα-acetyl-α-carbamoyl ketene-(S,S)-acetals and its further applications, for example, their adols condensations with aldehydes giveα-alkenoyl-α-carbamoyl ketene-(S,S)-acetals which can be utilized as the 1,5-bielectronic five-carbon components to react with various binucleophlilic species in a [5+1] annulation. However, researches onα-acetyl-α-carbamoyl ketene-(S,S)-acetals with Vilsmeier reagents remained poorly explored. In addition,α-alkenoyl ketene-(S,S)-acetals mainly used as the synthons of 3C and 5C, theα-functionalized reactions of which just limited on some simple reactions, as bromination, nitration, acetylation. However, the understanding of the forming of C-C bond atα-position is far from enough. Therefore, studies and applications of the intramolecular cyclization betweenα-acetyl-α-carbamoyl ketene-(S,S)-acetals and Vilsmeier reagents, the C-C bond formation atα-position ofα-alkenoyl ketene-(S,S)-acetals are research projects of great significance.Developments of new basic reactions and new synthetic methods are the basis for the innovation and advancement of organic chemistry. Based on the research achievement of our group inα-oxo ketene-(S,S)-acetal chemistry in the past decades, my thesis starts from the synthesis ofα-acetyl-α-carbamoyl ketene-(S,S)-acetals andα-alkenoyl ketene-(S,S)-acetals through synthetic design, aiming to develop new basic reactions and new synthetic methods for interesting cyclic molecules and consequently found a new synthetic strategy to provide a general and simple route to halogenated pyridinones, bicycle[3.3.1]nonanes, pyrrolidinetriones. The thesis mainly includes the following four aspects.1. Investigate the reaction ofα-acetyl-α-carbamoyl ketene-(S,S)-acetals with Vilsmeier reagents and synthesis a rang of 4-halogenated N-substituted 2(1H)-pyridinones.2. The Domino reactions ofα-alkenoyl ketene-(S,S)-acetals and oxalyl chloride were carried out, and theγ-alkylidenebutenolides were obtained in good yield. These compounds can be potentially useful intermediates in organic synthesis due to the multifunctionality in the molecules.3. In the presence of BF3·Et2O, the intramolecular Michael addition ofγ-alkylidenebut- enolides were performed and generated the corresponding bicycle[3.3.1]nonanes compounds. The above experimental results revealed that the reactions have very high atom economical manner.4. By the reactions ofα-acylamino ketene-(S,S)-acetals and oxalyl chloride, a serie of pyrrolidinetriones were prepared. The simple procedure, mild condition,easy separation, high yield, make this protocol most attractive for synthesis of pyrrolidinetriones.