title: Regioselective lithiation and functionalization of 3-(benzyloxy)isothiazole: application to the synthesis of thioibotenic acid.
abstract: Direct functionalization of the 3-oxygenated isothiazole heteroaromatic parental system has not yet been reported in the literature. Here, we report the first regioselective lithiation of the 5-position of 3-(benzyloxy)isothiazole (4) using LDA in diethyl ether. The versatility of the methodology was explored by quenching with a variety of electrophiles to give the desired products 7a,b,d-g in 54-68% yield. Only benzoylation aiming at the synthesis of 7c was unsuccessful. Furthermore, a highly convergent synthesis of thioibotenic acid (1), the sulfur analogue of the neurotoxic natural product ibotenic acid, was carried out.
authors.affiliation: Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Lennart
authors.initials: L
authors.lastname: Bunch
authors.forename: Povl
authors.initials: P
authors.lastname: Krogsgaard-Larsen
authors.forename: Ulf
authors.initials: U
authors.lastname: Madsen