1,2,4-Oxadiazole are compounds that have attracted the attention of many researchers due to their wide range of biological activities. Methods used for the synthesis of 3,5-substituted 1,2,4-oxadiazoles are reviewed in this works, as well as their applications. The syntheses are based mostly on the use of primary amidoximes and acylating agents as the initial reactants. In the last years, numerous reports concerning new methods of synthesis of 1,2,4-oxadiazoles have been reported. The use of microwave irradiation and ultrasound in chemical synthesis has many advantages with consequent impacts on the economy and the environment.

This work describes the total synthesis of raputindole A ( 1 ) through a convergent approach that features (1) an iridium-catalyzed cyclization to assemble the tricyclic core of the northern part, (2) enzymatic resolution to secure the preparation of an enantiomerically pure benzylic alcohol intermediate, and (3) the installation of the isobutenyl side chain via methallylation of the corresponding benzylic carbocation and coupling of the northern and southern parts via the Heck reaction. (+)-Raputindole A ( 1 ) was prepared in 10 steps (longest linear sequence) in 3.3% overall yield.

This work describes the total synthesis of Raputindole A <b>(1)</b> through a convergent approach which features: 1) an iridium-catalyzed cyclization to assembly the tricyclic core of the northern part, 2) enzymatic resolution to secure the preparation of enantiomerically pure benzylic alcohol, 3) installation of the butenyl substituent via methallylation of the corresponding benzylic carbocation and coupling of the northern and southern parts via Heck reaction. (+)-Raputindole A <b>(1)</b> was prepared in 10 steps (LLS) and 10% overall yield.