Reaction of 2-Polyfluoroalkylchromones with 1,3,3-Trimethyl-3,4-dihydroisoquinolines and Methylketimines as a Direct Route to Zwitterionic Axially Chiral 6,7-Dihydrobenzo[a]quinolizinium Derivatives and 2,6-Diaryl-4-polyfluoroalkylpyridines

Abstract

[reaction: see text] 2-Polyfluoroalkylchromones react with 1,3,3-trimethyl-3,4-dihydroisoquinolines to give zwitterionic axially chiral 6,7-dihydrobenzo[a]quinolizinium derivatives in high yields. In addition, performing this reaction with aromatic methylketimines is a simple and convenient synthesis of 2,6-diaryl-4-polyfluoroalkylpyridines.

Synthesis and Transformation of Halochromones

“…During the last decade Sosnovskikh [128,[194][195][196][197][198][199][200][201] and his group continued to devote great attention to the chemistry of 2-(polyhaloalkyl)chromones (2-R F -chromones) 185, particularly 2-(polyfluoromethyl)chromones (2-CF 3 -chromones) [52]. Some of their possible reactions are depicted in (Scheme 60): the reaction with ketimines leading to compounds 186-189 [194,196,198]; with acetophenones in the presence of lithium diisopropylamide to give 2-aroylmethyl-2-R F -chromanones 190 [197]; and a novel annulation reaction with salicylaldehydes in the presence of piperidine that constituted a direct route to chromeno [2,3-b]chromen-11-ones 191 by a tandem intermolecular oxa-Michael addition and subsequent intramolecular Mannich condensation [195].…”

A Simple One-Pot Synthesis of 2,6-Disubstituted 4-(Polyfluoroalkyl)pyridines and -pyrimidines by Reaction of 2-Polyfluoroalkylchromones with Aromatic Methyl Ketimines and Amidines

“…We demonstrated that chromones 1 react with dihydroisoquinolines and methyl ketimines to give 2,6-diaryl-4-trifluoromethylpyridines (preliminary communication, see Ref. 5 ). This result and the literature data 4k clearly showed that the present approach could be also applicable to chromones 1 and amidines (1,3-N,N-dinucleophiles), providing the corresponding 4-polyfluoroalkylpyrimidines.…”

“…Recently, 5 in continuation of our studies on the chemical properties of 2-polyfluoroalkylchromones 1, which turned out to be highly reactive substrates in the reactions with N-, 6a,b S-, 6c,d and C-nucleophiles, 6e,f we investigated the reactions of these compounds with 1,3,3-trimethyl-3,4-dihydroisoquinolines and aromatic N-substituted methyl ketimines capable of reacting with electrophilic substrates as 1,3-C,N-dinucleophiles due to the enamine tautomeric form. We demonstrated that chromones 1 react with dihydroisoquinolines and methyl ketimines to give 2,6-diaryl-4-trifluoromethylpyridines (preliminary communication, see Ref.…”

“…Most likely, the reaction includes the nucleophilic attack of the enamine tautomer of methyl ketimine 2 at C2 atom of 2-R F -chromone 1 followed by the opening of pyrone ring and intramolecular cyclization at the keto group (Scheme 1). Taking into account the results of the reaction of chromones 1 with 1,3,3-trimethyl-3,4-dihydroisoquinolines, 5 we could propose that the first step involves the formation of the zwitterionic intermediate 4, bearing an isopropyl group at the nitrogen atom, followed by elimination of propylene. In fact, in the case of compound 3e, the zwitterionic compound 4e (R F = CF 3 , Ar = Ph) was isolated as red crystals (at ca.…”

Reaction of 2-(trifluoromethyl)chromones with pyridoxal: Formation of 1-benzopyranooxepino- and 1-benzopyranopyranopyridines

“…Calcd for C 18 H 13 ClF 3 NO 4 Á1.5H 2 O: C, 50.66; H,3.78; N, 3.28. Found: C, 50.45;H, 3.80; N, 3.19.…”