Application of an isomerization-ring-closing metathesis strategy to the synthesis of unsaturated seven-membered, benzo-fused heterocycles containing two heteroatoms

An isomerization-RCM approach was utilized to synthesize a number of seven-membered benzo-fused heterocycles containing two heteroatoms (N,O, N,S, and S,O). This approach utilized the ruthenium catalyst [RuClH(CO)(PPh3)3] for the isomerization of allyl groups, eventually followed by the use of the Grubbs second generation catalyst for the formation of the desired products. In most instances thermal RCM conditions were sufficient; however, in a number of cases where this methodology did not give the desired product a high temperature, short time microwave approach afforded the desired ring-closed products. In this manner, the following substituted benzo-fused scaffolds were successfully synthesized: 4,5-dihydro-1,5-benzoxazepine, 4,5- and 2,5-dihydro-1,5-benzothiazepine and 2H-1,5-benzoxathiepine.

Graphical abstractSynthesis of seven-membered benzo-fused heterocycles containing two heteroatoms and a carbon–carbon double bond were performed by the application of a sequential isomerization-ring-closing metathesis strategy. Figure optionsDownload full-size imageDownload as PowerPoint slide