Rh(iii)-catalyzed 7-azaindole synthesis via C–H activation/annulative coupling of aminopyridines with alkynes

Abstract

An efficient Rh(iii)-catalyzed 7-azaindole synthesis was developed via C-H activation/annulative coupling of aminopyridines with alkynes. The reaction was highly regioselective and tolerated various functional groups, permitting the construction of various 7-azaindoles.

Rh-catalyzed aerobic oxidative cyclization of anilines, alkynes, and CO

“… 2 – 6 In the past decades, N-monosubstituted secondary (2° amine) anilines and alkynes have been extensively used in this field with the assistance of stoichiometric oxidants in most cases (i, Scheme 1a ). 3 , 4 However, despite this significance, the preparation of 2° anilines often requires tedious multi-steps because the tertiary (3°) amines would be mainly obtained by a traditional substitution reaction. In addition, the difficulty in removing the R group from the formed N-heterocycles also limits their further transformation.…”

“…(2) O 2 is successfully utilized as the sacrificial oxidant for the aerobic oxidative cyclizations in efficient ways to fulfill the requirements of green chemistry. 10 , 11 (3) In contrast to the well-known two component aerobic oxidative cyclizations for N-heterocycles such as indoles, 3 this chemistry provides a three component cyclization approach to N-heterocycles with CO, which has been used as a prominent C1 synthon in organic synthesis. 14 , 15 …”

Electrochemical C−H/N−H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles

“…Traditional methods including the Fischer indole synthesis often fail or are inefficient when electron‐deficient pyridine‐derived substrates are employed . In contrast, preparation of azaindoles by annulation of alkynes with aminopyridines has been reported only once, in which a series of 7‐azaindoles were constructed using a rhodium‐based catalyst and a stoichiometric amount of silver oxidant …”

Metal-Catalyzed Cross-Coupling Reactions on Azaindole Synthesis and Functionalization

“…This approach was based in the use of aminopyridines and alkynes. Since the aminopyridine ring can be considered a Lewis base, a Lewis acid (Ag 2 CO 3 ) was strategically used to coordinate with the N atom of the pyridine ring, facilitating the annulation process ( Scheme 21 ) [ 34 ].…”