Expeditious approach to pyrrolophenanthridones, phenanthridines, and benzo[c]phenanthridines via organocatalytic direct biaryl-coupling promoted by potassium tert-butoxide.
A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KO(t)Bu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).
Department of Chemistry, Indian Institute of Science Education and Research (IISER), Bhopal MP-462 023, India.
Subhadip
S
De
Sourabh
S
Mishra
Badrinath N
BN
Kakde
Dhananjay
D
Dey
Alakesh
A
Bisai
D053119:Benzophenanthridines / Q000138:chemical synthesis* / Q000737:chemistry; D000440:Butanols / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
D053119:Benzophenanthridines; D000440:Butanols; D010617:Phenanthridines; D011758:Pyrroles; C077664:tert-butoxide, potassium