Direct Synthesis Of β,γ-Unsaturated α-Keto Esters And Its Application In Two Annulation Reactions

Herein,we developed and investigated two direct and efficient methods to synthesize β,γ-unsaturated α-Keto esters from aldehyde and pyruvate.Initially,this thesis gives a comprehensive description of the research and development of β,γ-unsaturated α-Keto esters in recent years.We later focus on the synthesis of β,γ-unsaturated α-Keto esters from aromatic aldehyde and pyruvate promoted by BF₃.Et₂O and acetic anhydride as a dehydrant.This one pot reaction protocol afforded good to excellent yield under mild conditions with aromatic and some branched aliphatic g substitutedβ,γ-unsaturated α-Keto esters.Moreover,we explored a similar protocol to synthesize the linear alkyl β,γ-unsaturated α-Keto esters from linear aliphatic aldehyde and pyruvate with tetraethyl titanate Ti（OEt）₄ acting as both the promoter and dehydrant.This direct synthetic method is based on the Aldol condensation of ethyl pyruvate in the appropriate Lewis acid condition.The synthetic route has certain advantages compared to the reported synthetic methods,in that,the reaction is one pot,the conditions favorable,afforded moderate to excellent yield,and more importantly,the reaction is effective for both aliphatic and aromatic aldehydes.Furthermore,Huisgen zwitterions are generally known to effect special and efficient routes to aza-heterocycles therefore this thesis explored and investigated the application of β,γ-unsaturated α-Keto esters with respect to Huisgen zwitterion.The method includes intercepting the Huisgen zwitterion derived from triphenyl phosphine and diisopropyl azodicarboxylate DIAD with β,γ-unsaturated α-Keto esters,to form 1,2,3-tricarboxlate pyrazole.The protocol was successful with both electron withdrawing and donating groups substituted β,γ-unsaturated α-Keto esters and afforded the desired products in excellent yields.Finally,we also investigated the application of β,γ-unsaturated α-Keto esters with 4-phenylbut-3-yn-2-one promoted by various catalyst through Michael addition Annulation reaction to synthesize 3,4-dihydro-2H-pyran-2-carboxylate derivatives under mild reaction condition.Several catalysts could be applied in this protocol.Chiral and Racemic catalysts could be employed to promote the reaction in good yield.This protocol afforded us the advantages of a broad substrate scope of substituted aromatic β,γ-unsaturated α-Keto esters and helps us to avoid the use of expensive transition metals as catalyst in the synthesis of pyran derivatives.