Facile titanium(IV) chloride and TBD‐mediated synthesis of N‐aryl‐substituted azacycles from arylhydrazines

Abstract

A novel practical synthesis of N-aryl-substituted azacycles from arylhydrazines is described. In this method, target azacycles were prepared via reaction of arylhydrazines with cyclic ethers in the presence of both titanium(IV) chloride and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as key combined reagents. Using this synthetic protocol with titanium(IV) chloride and TBD, reaction of arylhydrazines with cyclic ethers successfully afforded various N-aryl-substituted azacycles in high yield. This facile synthetic method using arylhydrazines will be a promising guide for the synthesis of azacycles from arylhydrazines.

Recent Advances in Synthetic Routes to Azacycles

“…In 2022, Kim and co-workers used arylhydrazines to synthesize azacycles. The reactions were performed in xylene with TiCl 4 and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) at 120 °C, where a variety of arylhydrazines derivatives were converted into N -aryl pyrrolidines ( Scheme 21 ) [ 86 ]. It is noteworthy that N -arylhydrazine was nearly inactive when using solely TiCl 4 .…”

Construction of N-Aryl-Substituted Pyrrolidines by Successive Reductive Amination of Diketones via Transfer Hydrogenation

“…Additionally, the hydrogenation of N -heteroaromatics was employed as well for the construction of N -aryl-substituted pyrrolidines [ 24 , 25 , 26 ]. It is worth noting that other methods, including cross-coupling of aryl halides [ 27 ], reduction in tertiary amides [ 28 ] and lactams [ 29 , 30 ], intramolecular C-N coupling [ 31 ] or C-N amination [ 32 ], reactions of cyclic ether compounds with primary arylamines [ 33 , 34 , 35 , 36 , 37 ] or arylhydrazines [ 38 ], Mitsunobu cyclodehydration reaction [ 39 ], Prins cyclization [ 40 , 41 ], aminomercuration demercuration [ 42 ], as well as intramolecular carbonyl olefination of amides [ 43 ], were established to furnish N -aryl-substituted pyrrolidines. Furthermore, chiral-substituted pyrrolidines could be delivered via copper-catalyzed asymmetric 1,3-diploar cycloaddition [ 44 ].…”