Palladium-Catalyzed Amination and Amidation of Benzo-Fused Bromine-Containing Heterocycles

Abstract

Amination and amidation of bromoindole, 6-bromo-1,2,3,4-tetrahydrocarbazol-1-one, and 8-bromo-2,4,5,6-tetrahydro-1H-pyrazino[3,2,1-jk]carbazole derivatives was effected in the presence of palladium complexes. The use of the catalytic system Pd 2 dba 3 · CHCl 3 -2-[di(tert-butyl)phosphino]biphenyl in the amination and of Pd 2 dba 3 · CHCl 3 -Xantphos [or 3,5-(CF 3 ) 2 Xantphos] in the amidation ensured moderate to high yields of the corresponding products.

Update 1 of: Synthesis and Functionalization of Indoles Through Palladium-Catalyzed Reactions

“…The amination and amidation of N-protected bromoindoles were reported to occur in moderate to high yields by using, respectively, Pd 2 (dba) 3 ·CHCl 3 /2-[di( tert -butyl)phosphino]biphenyl and Pd 2 (dba) 3 ·CHCl 3 /Xantphos [or 3,5-(CF 3 ) 2 Xantphos] . N-Protected 5-bromo-3-[2-(diethylamino)ethoxy]indoles were subjected to amination reactions in the presence of Pd(OAc) 2 , 1-phenyl-2-[di(1-adamantyl)phosphanyl]pyrrole as ligand, and LiHMDS (or Cs 2 CO 3 ) at 100 °C for 20 h in toluene .…”

The Role of Bidentate Fluorenylphosphines in Palladium-Catalyzed Cross-Coupling Reactions

“…[81][82][83][84] As an example, the amination of 9-benzyl-6-bromo-1,2,3,4-tetrahydrocarbazol-1-one with 4-methylbenzamide results in 82% yield with 1 mol % of a Pd/Xantphos catalyst; under the same reaction conditions biphenyl-di-tert-butylphosphine affords only 16% conversion. 85 Notoriously difficult substrates such as nucleosides are efficiently aminated with 3-methylindole using 5 mol % PdOAc/ Xantphos, affording 69% yield, whereas 2-(dicyclohexylphosphinyl)-2′-(N,N-dimethylamino)-1,1′-biphenyl ligands proved to be inefficient. 82 BINAP was reported to be a useful ligand for the amination of 1,8-dichloroanthracene, while sterically demanding monophosphines tBu 3 P and Cy 3 P are poor performers.…”

“…Despite the popularity of monodentate phosphines, there are numerous examples where bidentates appear to perform better than monodentates. – As an example, the amination of 9-benzyl-6-bromo-1,2,3,4-tetrahydrocarbazol-1-one with 4-methylbenzamide results in 82% yield with 1 mol % of a Pd/Xantphos catalyst; under the same reaction conditions biphenyl-di -tert -butylphosphine affords only 16% conversion . Notoriously difficult substrates such as nucleosides are efficiently aminated with 3-methylindole using 5 mol % PdOAc/Xantphos, affording 69% yield, whereas 2-(dicyclohexylphosphinyl)-2′-( N,N -dimethylamino)-1,1′-biphenyl ligands proved to be inefficient …”