Pd(0)-Catalyzed Intramolecular Heck reaction of 2/3-Aryl(amino)methyl-3/2-bromoindoles: Syntheses of 3,4-Benzo[c]-β-carbolines, Benzo[4,5]isothiazolo[2,3-a]indole 5,5-Dioxides, and 1,2-Benzo[a]-γ-carbolines

One-pot synthesis of 3,4-benzo[c]-beta-carbolines was achieved from 2-aryl(tosylamino)methyl-3-bromoindoles via 10 mol % Pd(OAc)(2)/PPh3-mediated intramolecular Heck coupling using K2CO3 as a base in DMF at 110 degrees C with concomitant aromatization through an elimination of tosylsulfinic acid. Under identical conditions, the isomeric 3-aryl(tosylamino)methyl-2-bromoindoles upon intramolecular Heck reaction furnished benzo[4,5]isothiazolo[2,3-a]indole 5,5-dioxides instead of the expected gamma-carbolines. However, synthesis of the expected gamma-carboline framework, 3-tosyl-6,9-dihydro-1,2-benzo[a]-gamma-carbolines, could be achieved from 3-aryl(tosylamino)methyl-2-bromoindoles containing a mesitylene sulfonyl unit as a protecting group on the indole nitrogen.

Automated summary

The one-pot synthesis of 3,4-benzo[c]-beta-carbolines and related compounds was successfully achieved through intramolecular Heck coupling reaction, with the ability to control product formation by employing specific protecting groups on different parts of the molecule.