A Synthetic Pathway to the 1,4-Dihydro-2H-3-benzoxocine System from Morita-Baylis-Hillman Cinnamyl Alcohols with 2,5-Dimethoxy-2,5-dihydrofuran via the Heck Reaction

A new synthetic method for methyl 2-methoxy-1-(meth­oxycarbonylmethyl)-1,4-dihydro-2H-3-benzoxocine-5-carboxylates was developed using the Heck reaction between 2,5-dimethoxy-2,5-dihydrofuran and methyl 2-(hydroxymethyl)-3-(2-iodophenyl)propenoates as a key step. The latter were readily obtained from the Morita?Baylis?Hillman reaction of iodobenzaldehydes with methyl acrylate through acetylation, rearrangement, and hydrolysis. The methyl 2-methoxy-1-(methoxycarbonylmethyl)-1,4-dihydro-2H-3-benzoxocine-5-carboxylates were converted into methyl 2-oxo-1,2,5,11b-tetrahydro-3aH-furo[3,2-a][3]benzoxocine-6-carboxylates on exposure to excess trifluoroacetic acid.This work was supported in part by the Brain Korea 21 program, Republic of Korea