Base-mediated chemo- and stereoselective addition of 5-aminoindole/tryptamine and histamines onto alkynes.
Transition-metal-free chemo- and stereoselective addition of 5-aminoindole (1a), tryptamine (1b), and histamine (1c) to alkynes 2a-s to synthesize the indolyl/imidazolyl enamines 3a-p, 5a-o, and 6a-e using superbasic solutions of alkali-metal hydroxides in DMSO is described. The addition of N-heterocycles onto alkynes takes places chemoselectively without affecting the 1° amino groups (aromatic and aliphatic) of 5-aminoindole, tryptamine, and histamine. The stereochemistry of the products was found to be dependent upon reaction time; an increase in reaction time leads to the formation of a mixture of E/Z isomers and the thermodynamically stable E addition product. The chemoselective addition of N-heterocycle 1a onto alkyne over thiophenol 7 and phenol 8 is supported by control experiments. Competitive experiments showed that 5-aminoindole was more reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient chemoselective method to synthesize a variety of (Z)-enamines of 5-aminoindole, tryptamine, and histamine without affecting the 1° amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which proved to be highly advantageous for structural and biological activity assessments.
Synthetic Organic Chemistry Research Laboratory, Department of Chemistry, University of Delhi , Delhi 110007, India.
Akhilesh K
AK
Verma
Monika
M
Patel
Megha
M
Joshi
Pravin R
PR
Likhar
Rakesh K
RK
Tiwari
Keykavous
K
Parang
D000480:Alkynes / Q000737:chemistry*; D006632:Histamine / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D013237:Stereoisomerism; D014363:Tryptamines / Q000737:chemistry*
D000480:Alkynes; D007211:Indoles; D014363:Tryptamines; C030820:tryptamine; D006632:Histamine; C512101:5-aminoindole