Regioselective lithiation and functionalization of 3-(benzyloxy)isothiazole: Application to the synthesis of thioibotenic acid
Regioselective lithiation and functionalization of 3-(benzyloxy)isothiazole: Application to the synthesis of thioibotenic acid
复制标题
DOI：
10.1021/jo0162134
复制
发表时间：
2002-04-05
影响因子：
3.6
通讯作者：
Madsen, U
中科院分区：
文献类型：
--
作者：
Bunch, L;Krogsgaard-Larsen, P;Madsen, U
3-含氧异噻唑杂芳烃母体体系的直接官能化还没有文献报道。在这里，我们首次报道了在乙醚中用LDA对3-(苄氧基)异噻唑(4)的5-位进行区域选择性锂化合反应。通过用各种亲电剂淬灭，以54-68%的产率得到所需的产物7a，b，d-g，探索了该方法的通用性。只有以合成7c为目标的苯甲酰化反应不成功。此外，还进行了神经毒性天然产物鹅膏酸的硫磺类似物--硫代鹅膏酸(1)的高收敛合成。
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.