Synthesis and reactions of 1,2‐fused 3‐cyanoindolizines

Abstract

With the intention that annulation of carbo‐ or heteroaromatic rings at the 1,2‐positions can activate 3‐cyanoindolizines as 1,3‐dipolar species, 6‐cyanobenz[a]indolizines, pyridazino[4,5‐a]indolizines and 5‐cyano‐1,3‐diphenylthiopheno[3,4‐a]indolizine were prepared. 6‐Cyanobenz[a]indolizines smoothly ‐underwent 1,3‐dipolar cycloaddition on to dibenzoylacetylene and diacetylacetylene to afford the corresponding indolizino[3,4,5‐ab]isoindoles, whereas 5‐cyano‐1,4‐diphenylpyridazino[4,5‐a]indolizine reacted with dimethyl acetylenedicarboxylate to give the 1:2 adduct. Only a 3% yield of 5‐cyano‐1,3‐diphenylthiopheno[3,4‐a]indolizine formed upon phosphorus pentasulfide treatment of 1,2‐dibenzoyl‐3‐cyanoindolizine.

Indolizines and Their Hetero/Benzo Derivatives in Reactions of [8+2] Cycloaddition

“…Cyano-derivative of benzo[a]indolizine is easily available from pyridinium-dicyanmethylide and dehydrobenzene. Matsumoto first published the results of cycloaddition of dibenzoylacetylene to the structures 40a – d ( Scheme 18 , Table 9 ) [ 62 , 63 ]. Again, the reaction required a catalyst.…”

Pyrido- and pyrimidoisoindoles: methods of synthesis and properties

“…Comparative data on the NMR spectra for six 2-R-6-cyanopyrido[2,1-a]isoindoles 43 are available. 29 Detailed assignment of signals in the 1 H and 13 C NMR spectra of benzo [1,2]pyrrolizino [3,4,5-a,b]isoquinolines (112) 65 and indolizino [3,4,5-a,b]isoindoles (113) was carried out based on the results of COSY, HMQC and HMBC experiments and the nuclear Overhauser effects. 66 Matsumoto et al 67 have measured the ESR spectra of the radical cations derived from benzo[a]isoindolo [1,2,3-cd ]indolizine (1,2,3,4-dibenzocyclo[2,2,3]azine) 114 (R = H) upon its oxidation with AgClO 4 in dichloromethane at room temperature.…”

“…Although the yields of the latter did not exceed 4% and no corresponding compounds were isolated in the case of R = CO 2 Me, it is evident that 6-cyanopyrido[2,1-a]isoindole 43 was further coupled with dehydrobenzene with the elimination of HCN. 29,30 It is of interest that the change in the mode of generation of dehydrobenzene (the reaction of anthranilic acid with isoamyl nitrite was used instead of pyrolysis of diphenyliodonium-2carboxylate) and the decrease in the reaction temperature increase the yield of the corresponding benzoyl derivative of benzo[a]isoindolo [1,2,3-cd ]indolizine 114 (R = PhCO) (up to 17%) without any significant changes in the yields of the products with other substituents. 30 If compounds 43 isolated in the individual state reacted with dehydrobenzene generated by pyrolysis of diphenyliodonium-2-carboxylate, the yields of the products 114 were 18% ± 39%.…”

Pyrrolizidine and Indolizidine Syntheses Involving 1,3-Dipolar Cycloadditions

“…Pyridinium N-ylides are the most easily available cyclic azomethine ylides. However, their cycloaddition to acetylenes (or to synthetic equivalents of the latter) originates aromatic indolizidines, [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99] which do not reflect exactly the structure of indolizidine alkaloids. More challenging…”