Synthesis of N-Heteroarenemethyl Esters via C-C Bond Cleavage of Acyl Cyanides Under Transition Metal-Free Conditions

Abstract

A practical method to synthesize N-heteroaryl esters from N-heteroaryl methanols with acyl cyanides via C-C bond cleavage without using any transition metal is demonstrated here. The use of Na₂CO₃/15-crown-5 couple enables access to a series of N-heteroaryl esters in high efficiency. This protocol is operationally simple and highly environmentally benign producing only cyanides as byproducts.

Keywords: C-C bond cleavage; N-heteroaryl esters; N-heteroaryl methanols; acyl cyanides; transition-metal free synthesis.

SCHEME 1

Strategies toward the synthesis of esterification products.

SCHEME 2

Substrate scope of heteroaryl methanols for the acylation reactions. ^a,b Reaction conditions: ^a heteroaryl methanols 1 (0.5 mmol), benzoylacetonitrile 2 (0.2 mmol), Na₂CO₃ (0.2 mmol), 15-crown-5 (0.2 mmol), and toluene (1 ml) at 140°C for 24 h, under N₂ atmosphere. ^b Isolated yields.

SCHEME 3

Substrate scope of benzoylacetonitriles for the acylation reactions. ^a,bReaction conditions: ^a heteroaryl methanols 1 (0.5 mmol), benzoylacetonitrile derivatives 2 (0.2 mmol), Na₂CO₃ (0.2 mmol), 15-crown-5 (0.2 mmol), and toluene (1 ml) at 140°C for 24 h, under N₂ atmosphere. ^b Isolated yields.

SCHEME 4

Substrate scope of benzoyl cyanides for the acylation reactions. ^a,b Reaction conditions: ^a heteroaryl methanols 1 (0.5 mmol), benzoyl cyanides 2 (0.2 mmol), Na₂CO₃ (0.2 mmol), 15-crown-5 (0.2 mmol), and toluene (1 ml) at 140°C for 24 h, under N₂ atmosphere. ^b Isolated yields.

SCHEME 5

Gram-scale reaction of 1a and 2k.

SCHEME 6

Mechanistic experiments.

SCHEME 7

Plausible reaction mechanism.