Cycloaromatization of α-oxoketene dithioacetals with 5-lithiomethyl-3-methylisoxazole: a new general method for the synthesis of substituted and annulated 1,2-benzisoxazoles

Abstract

A new route to 6-substituted 4a-e and 5,6-annulated 4f-l 1,2-benzisoxazoles has been developed through regioselective 1,2-nucleophilic addition of 5-lithiomethyl-3-methylisoxazole (2) to a variety of α -oxoketene dithioacetals 1a-l and subsequent cycloaromatization of the resulting hydroxyacetals in the presence of boron trifluoride -diethyl ether complex. The corresponding 4-dethiomethylated benzisoxazoles 6a-d were also synthesized by cyclocondensation of β-methylthio-α,β-unsaturated ketones with 2 under identical conditions. The reaction was further extended for the synthesis of (6-benzisoxazolyl)-substituted ethylenes 9a-e, butadienes 9f-g and hexatriene 9h by subjecting α-cinnamoyl ketene dithioacetals 7a-e and their higher enyl analogs 7f-h to similar transformations.