Phenyl-indolyl ether

The Bartoli indole synthesis has found utility in medicinal chemistry despite its infancy. For instance, the nitro-diarylether ketone was protected as a ketal and treated with vinylmagnesium bromide to afford the indole derivative. The resulting phenyl-indolyl ether is an intermediate for preparing serotonin (5HT) receptor ligands for treatment of nervous system disorders. Specifically, the diphenyl ether ligands exhibited activity as 5HT2 antagonists. 

Meanwhile, an efficient procedure for the sequential catalysis of olefin cross-metathesis and AFC alkylation was developed (Scheme 6.58). Two distinct catalytic processes were involved in this procedure, olefin crossmetathesis of 135 and 136 catalyzed by a Ru complex and intramolecular AFC alkylation catalyzed by a chiral phosphoric acid. In the presence of 5 mol% Ru complex and 5 mol% chiral phosphoric acid (S )-13b, the reaction of indolyl allyl ether or amine 135 and phenyl enone 136 proceeded smoothly to afford the desired products 134 in good to excellent yields (43-97%) with good enantioselectivity (80-94% ee). 

Scheme 6.58 Cross-metathesis/AFC cascade reaction of indolyl allyl ether or amine 135 and phenyl enone 136 reported by You.

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