Additions of 1-(aminomethyl)benzotriazoles to enamines, enamides, and vinyl ethers: novel routes to 1,3-diamines and tetrahydroquinolines

Abstract

New methods for the synthesis of 1,3-diamines and of 4-substituted tetrahydroquinolines are described in which the key step is the addition of the condensation products derived from amines, aldehydes, and benzotriazole to enamines, enamides, and vinyl ethers.

3-(4-Chloroanilino)-5,5-dimethylcyclohex-2-en-1-one

“…For general background to enamines as versatile substrates for the preparation of bioactive alkaloids, see: Heller & Natarajan (2006); Katritzky et al (1993); Campaigine & Lake (1959). For bond-length data, see: Allen et al (1987).…”

“…Enamines are versatile substrates for the preparation of useful bioactive alkaloids, such as pyrazoles (Heller & Natarajan 2006), quinolines (Katritzky et al,1993) and carbazoles (Campaigine & Lake 1959). The compounds are generally prepared by heating aldehydes or ketones with primary amines in presence of strong acids.However, these methods are associated with the limitations of low yield, undesirable side reactions and polymerization.…”

Lewis Acid-Catalyzed Additions of (Benzotriazol-1-yl)diethoxymethane to Enol Ethers and Enamides. New Syntheses of β-Alkoxyalkanal and β-Aminoalkanal Acetals

“…Recent reports from our laboratory have described the additions of 1-(α-alkoxybenzyl)benzotriazoles to enol ethers which opened a new route to 1,3-diethers (Scheme ), of 1-(α-aminoalkyl)benzotriazoles to enol ethers leading to 1,3-amino-ethers, and of 1-(α-aminoalkyl)benzotriazoles to N -vinyl amides to give unsymmetrically substituted 1,3-diamines (Scheme ). , The benzotriazole-containing starting materials 1 and 5 (Schemes , ) can be considered as protected oxonium ( 2 ) or immonium ( 6 ) cations because of the easy heterolysis of the C−Bt bond under mild acidic catalysis ( p -toluenesulfonic acid) and consequently react with enol ethers and enamides to form the corresponding benzotriazolyl-substituted addition products ( c.f. 3 , 7 , 9 ).…”

Capture of benzotriazole-based Mannich electrophiles by CH-acidic compounds

“…A significant diversification is exemplified by the development of mild benzotriazole-mediated aminoalkylations and related reactions. [12][13][14][15] Benzotriazole-based aminoalkylating reagents have been readily utilized with various nucleophiles, including: enolates, 16 imidazolidine derivatives, 17 isonitriles, 18 enol ethers, [19][20][21][22] enamines, 20,22,23 and enamides. 22,23 Many active pharmaceutical ingredients (APIs) are obtained through a key Mannich step or display the typical core of a Mannich base.…”

“…[12][13][14][15] Benzotriazole-based aminoalkylating reagents have been readily utilized with various nucleophiles, including: enolates, 16 imidazolidine derivatives, 17 isonitriles, 18 enol ethers, [19][20][21][22] enamines, 20,22,23 and enamides. 22,23 Many active pharmaceutical ingredients (APIs) are obtained through a key Mannich step or display the typical core of a Mannich base. 24,25 The most famous include tropanone and derivatives, 26 rifamycin, 27 tramadol, 28-30 procyclidine, [31][32][33] falicain, 34 fluoxetine, 35,36 rolitetracycline 37,38 and tolmetin.…”