General Method for the Synthesis of Phthalaldehydic Acids and Phthalides from o-Bromobenzaldehydes via Ortho-Lithiated Aminoalkoxides

Article abstract of DOI:10.1021/jo00162a011

A general method for the synthesis of phthalaldehydic acids and phthalides, many of which are key intermediates in natural product synthesis, has been developed. o-Bromobenzaldehydes 1a-f were first protected in situ as α-morpholinoalkoxides by reaction with lithium morpholide.Treatment of the α-morpholinoalkoxides 3a-f with n-butyllithium (to exchange bromine with lithium) followed by sequential treatment with solid CO2 and dilute acid afforded the phthalaldehydic acids 6a-f, respectively.Reduction of 6a-f with NaBH4 in EtOH furnished the phthalides 7a-f, respectively, in nearly quantitative yields.Efficient methods for the synthesis of the o-bromobenzaldehydes 1a-d, which were not readily available, are also described.