Reactions of Heterocumulenes with Organometallic Reagents: XXV. Quantum Chemical Study of the Substituent Effects in Alkyl [(Buta-2,3-dienimidoyl)sulfanyl]acetates on Their Cyclization to Thiophene Derivatives

Abstract

Base-catalyzed low-temperature transformation of alkyl [(buta-2,3-dienimidoyl)sulfanyl]acetates [1-aza-1,3,4-trienes generated from lithiated alkoxy(or 1H-pyrrol-1-yl)allenes, isothiocyanates, and alkyl 2-bromoacetates] to tetrasubstituted thiophenes has been studied by B3LYP/6-311+G(d,p) quantum chemical calculations. Structural reorganization of 1-aza-1,3,4-trienes to thiophene derivatives involves deprotonation of the SCH₂ group, followed by intramolecular addition of the resulting carbanion to the β-carbon atom of the allene fragment. Gradient paths leading to sulfur heterocycles have been analyzed assuming participation of most stable 1-aza-1,3,4-triene isomers with trans-gauche orientation of the N=C and C=C=C fragments that are conformationally favorable for thiophene ring closure. The nature of substituents on the allene carbon atom and nitrogen atom is the main factor responsible for the ability of 1-aza-1,3,4-trienes to rearrange to thiophene derivatives. In going from 3-methoxy- to 3-(1H-pyrrol-1-yl)-1-aza-1,3,4-triene, the barrier to the cyclization decreases more than twice (from 5.6 to 2.5 kcal/mol). A comparable effect is observed on replacement of methyl group on the nitrogen atom by phenyl: the barrier decreases from 5.6 to 3.1 kcal/mol. Change of substituent in the allene fragment from methoxy to ethoxy group reduces the barrier by 1.0 kcal/mol (from 5.6 to 4.6 kcal/mol). Variation of the alkyl group in the ester moiety almost does not affect the cyclization barrier.