Synthesis of 1,3-Teraryls Through Carbanion Induced Ring Transformation of Functionalised Pyran-2-ones

Abstract

1,3-Teraryls 2 were synthesised by reaction of 6-aryl-3-methoxycarbonyl-4-(methylthio)-2H-pyran-2-ones 1a with aryl methyl ketones. An analogous reaction with 6-aryl-3-cyano-4-(methylthio)-2H-pyran-2-ones 1b and aryl methyl ketones failed to yield cyano-substituted 1,3-teraryls, but afforded (4,6-diarylpyran-2-ylidene)acetonitriles 4 in poor yields.The marvel of the specificity in biological systems of recognising tailor-made synthetic molecules which imitate the working features of naturally occurring compounds led to the design and synthesis of molecular hosts, guests and their complexes. Recently, the chemistry of synthetic hosts for selective complexation has received extraordinary attention 1,2 due to their pharmacological potential as carriers of ions and molecules. The presence of specific cavities in the molecular makeup of host molecules is responsible for the molecular recognition resulting in the desired bioresponses. Here, we address our synthetic efforts towards functionalised symmetrical and unsymmetrical 1,3-teraryls as intermediates for the synthesis of host compounds 3-7 in a single step through ring-transformation reactions.The principal methods for the synthesis of 1,3-teraryls are largely based on the metal-assisted, 8 aryllithium 9 and arylboric acid 10 arylation of 1,3-dihalobenzene, decomposition 11 of 3-(nitrosoacetamido)biphenyls or 1,3-bis(nitrosoacetamido)benzene, and the action of arylmagnesium halides on 3-pheenylcyclohexanone, 12 alkyl 3-chlorophenyl sulfides, 13 and 4,6-diarylpyran-2-ones 14 separately. The Diels-Alder reaction of the latter with methyl propiolate 15 also led to the formation of the title compound. A circuitous multistep synthesis 16 of 1,3-teraryls has also been reported in poor yield. Our approach to synthesise 1,3-teraryls is based on the carbanion induced ring transformation of 6-aryl-3-methoxycarbonyl-4-(methylthio)-2H-pyran-2-ones 17 1a. However, the symmetrical 1,3-teraryls were also obtained directly as a side product from the reaction of methyl 2-methoxycarbonyl-3,3-bis(methylthio)acrylate with aryl methyl ketones, possibly through the intermediacy of pyran-2-ones 1a. To establish the course of the reaction, an independent reaction of 1a with aryl methyl ketones was carried out which resulted in the formation of the respective 1,3-teraryls. However, under similar reaction conditions, reaction of aryl methyl ketones with 6-aryl-3-cyano-4-(methylthio)-2H-pyran-2-ones 1b yielded 4, a minor product analogous to 3, through an enolised intermediate and a decomposed material as a major constituent. 6-Aryl-3-methoxycarbonyl-4-(methylthio)-2H-pyran-2-ones 1a and 6-aryl-3-cyano-4-(methylthio)-2H-pyran-2-ones 1b used as precursors were synthesised by basecatalysed condensation-cyclization of aryl methyl ketones with methyl 2-methoxycarbonyl-3,3-bis(methylthio)acry 1 late 18 and ethyl 2-cyano-3,3-bis(methylthio)-acrylate, 8 respectively. During the synthesis of 1a, a new minor product was also isolated and characterised as the 1,3-teraryl 2 (Scheme 1). The formation of...