Development of a Pseudo-Intramolecular Process

Abstract

A pseudo-intramolecular process is developed. Compounds having both an acidic hydrogen and a functionality serve as substrates in the present method, and immediately form an ammonium salt after the addition of an amine. When the amine is liberated under mild equilibrium conditions, both the nucleophilic amine and the electrophilic substrate are in proximity and react efficiently under mild reaction conditions. Although the reaction actually concerns an intermolecular process, it proceeds as if it were an intramolecular process. Thus, this method represents a novel procedure for synthesizing polyfunctionalized compounds that are not easily available via alternative methods. The transacylation using α-arylated or α-nitrated β-keto esters facilitates the chemoselective or regioselective acylation of amines. α-Nitro-δ-keto nitriles also serve as substrates for the present reaction to afford 1,4-dihydropyridines, diazepines, pyridazines, and diazabicyclic compounds, efficiently. 1 Introduction 2 Transacylation of an α-Arylated β-Keto Ester 3 Synthesis of Unsymmetrical Malonates 4 Transacylation of an α-Nitro-β-keto Ester 5 Reaction of an α-Nitro-δ-keto Nitrile with Amines 6 Reaction of an α-Nitro-δ-keto Nitrile with Hydrazines 7 Reactions of α-Nitro-δ-keto Nitriles with Diamines 8 Reactions of α-Nitro-δ-keto Esters with Diamines 9 Conclusion