ABSTRACT
Palladium-catalyzed cyclization of arylhydrazones of 2-bromoaldehydes and 2-bromoacetophenones to give 1-aryl-1H-indazoles has been studied in detail. The cyclization of arylhydrazone of 2-bromobenzaldehydes can be performed with good to high yields using Pd(dba)2 and chelating phosphines, of which the most effective are rac-BINAP, DPEphos, and dppf, in the presence of Cs2CO3 or K3PO4 as a base. Electron-rich, bulky ligands commonly employed for intermolecular amination such as PtBu3 and o-PhC6H4PtBu2 were shown to be ineffective for cyclization and to lead instead to extensive oligomerization and tarring. The method developed is applicable for preparation of a wide scope of indazoles bearing electron-donating or electron-withdrawing substituents, among them, unprotected carboxyl, as well as various indazole heteroanalogues. The cyclization of arylhydrazones of less reactive halides such as 2-chlorobenzaldehyde, as well as 2-bromoacetophenone and bromotetralone, has been achieved. The purity of the starting hydrazone has been shown to be a critical parameter, as various impurities inhibit the cyclization.
ABSTRACT
[reaction: see text] Vinylation of various azoles (pyrrole, indole, carbazole, and their derivatives) and phenothiazine with vinyl bromides catalyzed by palladium-phosphine complexes results in the respective N-vinylazoles in 30-99% yields. This reaction with cis- and trans-beta-bromostyrenes is stereospecific giving the respective products with full retention of configuration.