Access to Triazolopiperidine Derivatives via Copper(I)‐Catalyzed [3+2] Cycloaddition/Alkenyl C−N Coupling Tandem Reactions

Abstract

A copper‐catalyzed [3+2] cylcoaddition/ alkenyl C−N coupling tandem reaction was demonstrated. It provided a method for the formation of triazolopiperidine skeletons.

Syntheses and Applications of 1,2,3-Triazole-Fused Pyrazines and Pyridazines

“…Primary Applications : Primarily c-Met inhibition [ 1 , 2 , 25 , 96 ] and use as fluorescent probes in optical and/or cellular imaging [ 20 , 23 , 99 ]. 1,2,3-Triazolo[1,5-a]pyrazines : For non-fused derivatives, the most common methods are: intramolecular cyclization of pyrazinyl hydrazones [ 36 , 42 ], formation of 1,2,3-triazolo[1,5- a ]pyrazinium-5-olates from cyano and amide groups [ 37 , 40 ], or reaction of iodopropiolamides to form triazolopiperazine [ 43 ]. For benzo-fused derivatives (i.e., those containing quinoxaline or quinoxalinone), the most common methods are: cyclization of a ring-bound 1,2,3-triazole with an ortho -substituted amine [ 52 ] or nitro [ 45 ] group (if a nitro group, either PBu 3 to give a quinoxaline [ 45 ] or FeCl 3 [ 48 ] to give a quinoxalinone), cyclization of 1-azido-2-isocyanoarenes or 1-triazolyl-2-isocyanoarenes [ 54 , 55 ], or intramolecular cyclization of alkynes [ 53 , 57 ].…”

“…Copper-catalyzed [3 + 2] cycloaddition of propiolamide 53 , followed by halide displacement to form a fused product, was utilized in the synthesis of saturated derivatives of 1,2,3-triazolo[1,5- a ]pyrazine (i.e., triazolopiperazines) 54 in 80% yield [ 43 ] ( Scheme 12 ). Koguchi and coworkers used ynones and β-amino azides to afford 6,7-dihydro-1,2,3-triazolo[1,5- a ]pyrazines.…”

“…Xiao and coworkers [ 43 ] and Chen and coworkers [ 57 ] used in situ conversion of N-propargyl-N-(2-iodoaryl)amides 88 to azides, which underwent 1,3-dipolar cycloaddition with the adjacent alkyne to form substituted 1,2,3-triazolo[1,5- a ]quinoxalines 89 ( Scheme 23 ) in yields in the range 58–91%. Chen and coworkers suggested that cycloaddition might occur first.…”

Base-Promoted Tandem SNAr/Boulton–Katritzky Rearrangement: Access to [1,2,4]Triazolo[1,5-a]pyridines

“…Recently, we reported a cascade Michael addition/Boulton–Katritzky rearrangement process for the preparation of ( E )-5-tetrasubstituted ylidene-3,5-dihydro-4 H -imidazol-4-ones . As part of our continuing interest in developing practical methodologies for the synthesis of heterocycles, herein, we would like to report a base-promoted tandem S N Ar/Boulton–Katritzky rearrangement process for the straightforward formation of functionalized [1,2,4]­triazolo­[1,5- a ]­pyridines from simple 1,2,4-oxadiazol-3-amines or 3-aminoisoxazoles and 2-fluoropyridines (Scheme b).…”