Directing Group Guided Site-Selective Diversification of Indoles by Aziridine: Synthesis of β-Indolylethylamines.

A palladium catalyzed directing group assisted cross-coupling of aliphatic aziridines with indole, indoline, tetrahydroquinoline, and aniline has been developed to furnish the corresponding β-arylethylamine derivatives. The substrate scope was very general, and the protocol was also tolerated in the presence of various external additives. Control experiments suggested that the C-H cleavage step is the rate-determining step.

Ru-Catalyzed C-H alkenylation on the arene ring of pirfenidone using pyridone as a directing group.

A method to functionalize the arene ring of pirfenidone has been demonstrated using pyridone as a directing group. Unlike the functionalization of the pyridone nucleus, the method demonstrated here is the alkenylation of the -aryl ring of pirfenidone with internal alkynes using ruthenium catalyst. High functional group tolerance, simple reaction conditions and site-selective functionalization permit the synthesis of new analogues of drugs in a step-economical manner.

Diastereoselective [3 + 2] Cycloaddition of Quinoxalin-2(1)-ones with Donor-Acceptor Cyclopropanes: Efficient Synthesis of Tetrahydro pyrrolo[1,2-]quinoxalin-4(5)-ones.

A ytterbium triflate-catalyzed diastereoselective [3 + 2] cycloaddition of quinoxalinones with donor-acceptor cyclopropanes and cyclobutanes is described. A series of tetrahydropyrrolo-quinoxalinone derivatives were obtained in high yields (up to 96%) with excellent diastereoselectivities (up to 46:1). Other medicinally important heterocycles like benzoxazinone, isoquinoxalinone, and dibenzoxazepine derivatives were also suitable for the desired annulation reaction.

Cu(II)-Catalyzed C-N, C-O, C-Cl, C-S, and C-Se Bond Formation via C(sp)-H Activation Using 7-Azaindole as an Intrinsic Directing Group.

A general protocol has been developed for the construction of carbon-heteroatom (C-N, C-Cl, C-O, C-S, and C-Se) bonds using the bench stable, earth-abundant, and environmentally benign copper catalyst. Only oxygen is sufficient to regenerate the copper catalyst. Control experiments suggested that the proto-demetalation step is reversible.

Pd-Catalyzed C-H Halogenation of Indolines and Tetrahydroquinolines with Removable Directing Group.

Pd-catalyzed directing-group-assisted regioselective halogenations to C7 of indolines and C8 of tetrahydroquinolines were achieved in good to excellent yields. The practicality and utility of the developed method have been illustrated by various functional group transformations such as arylation, alkenylation, cyanation, and silylation utilizing the installed synthetic handle. The concise synthesis of primaquine, an antimalarial drug, and formal syntheses of two bioactive natural products, hippadine and pratosine, have also been demonstrated.

Cu(II)-Catalyzed Ortho C(sp)-H Diarylamination of Arylamines To Synthesize Triarylamines.

A copper-catalyzed, directed C-H diarylamination of indoles, indolines, anilines, and -aryl-7-azaindoles has been established. Only copper salt as the catalyst and oxygen as the terminal oxidant are used to synthesize triarylamines using various diarylamines including carbazole and phenothiazine. Mechanistic interrogation reveals that copper plays a dual role.

Cu(II)-Mediated Cross-Dehydrogenative Coupling of Indolines with Sulfonamides, Carboxamides, and Amines.

A facile and efficient Cu-mediated protocol for the cross-dehydrogenative coupling of indoline with sulfonamides, carboxamides, and anilines is reported. The reaction takes place through Cu-mediated C7-H activation via a 6-membered metallacycle to afford the amide and amine derivatives in good yields with a wide range of functional group tolerance. The importance of the protocol has been demonstrated by synthesizing the antiproliferative agent, ER-67836.