Novel synthetic approaches to Aza-heterocycles, Oxo-α-Amino Acids and (E)-α,β-Unsaturated Carboxylic Acids/Esters

Abstract

A two step on-pot synthesis of disubstituted piperidone and piperidines (only trans configuration) starting from α,β-unsaturated ketoesters has been developed. Cascade type reaction using BF3.OEt2 or one-pot deprotection of tBoc group by TFA then TEA facilated the intramolecular aza-Michael addition of α,β-unsaturated ketoesters to afford trans-2,3-disubstituted piperidines. Also, initial synthetic study of 5-membered heterocyclic β-enamino esters has been established using catalytic amount of B(C6F5)3. Few 5-membered heterocyclic β-enamino esters have synthesized by optimizing the reaction conditions. This procedure gives an easy access to the chiral and non-chiral 5-membered heterocyclic β-enamino esters in good yields under mild reaction condition. Further, a Short and concise synthesis of enantiopure side chain-modified α-amino acids such as 4-oxo-L-norvaline, 6-oxo-L-homonorleucine, and 5-cis-alkyl prolines is described. Meldrum’s acid has been employed for the preparation of aminocarboxylate-derived β-ketoesters. Knoevenagel condensation of L-aminocarbo-xylate-derived β-ketoesters with aldehydes followed by reductive decarboxylation afforded unnatural α-amino acids. Application of the method has been illustrated by the synthesis of a fluorescent amino acid. In another study novel and expedient syntheses of α,β-unsaturated carboxylic acids/esters has been described by exploring the reactivity of alkylidene Meldrum’s acids with water/alcohols in presence of FeCl3•6H2O. Application of this method has been extended to biomass derived aldehydes and synthesis of sunscreen filters.