Total synthesis of tubastrine and 3-dehydroxy tubastrine by microwave-assisted cross-coupling reactions

Abstract

The first syntheses of tubastrine and 3-dehydroxy tubastrine are described. The target compounds were prepared in four consecutive steps from commercially available starting materials. The central scaffold was formed by a microwave-assisted C–N cross-coupling reaction between 1,3-bis(<i>tert</i>-butoxycarbonyl)-guanidine and (<i>E</i>)-((4-(2-iodovinyl)-1,2-phenylene)bis(oxy))bis(<i>tert</i>-butyldimethylsilane) and (<i>E</i>)-<i>tert</i>-butyl(4-(2-iodovinyl)phenoxy)–dimethylsilane, respectively. The aryl vinyl iodides were obtained by a Hunsdiecker–Borodin-type reaction of aryl acrylic acids, which were easily available from <i>trans</i>-caffeic acid or <i>trans-p</i>-coumaric acid.