The tert-Amino Effect in the Synthesis of Hetaryl- and Arylsulfonyl-Substituted Pyrrolo- and Pyrido[1,2-a]quinoline Derivatives and their Pyrazolo Annulated Analogues

4-Hetaryl and 4-tosyl-1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-4-carbonitriles were prepared in two steps by the condensation of 2-(1-pyrrolidinyl)benzaldehydes with substituted acetonitriles XCH₂CN (X = hetaryl, tosyl), followed by the thermal cyclization of the corresponding arylidene derivatives. Similarly, starting from 2-(1-piperidinyl)benzaldehydes 5-hetaryl and 5-tosyl-2,3,4,4a,5,6-hexahydro-1H-pyrido[1,2-a]quinoline-5-carbonitriles were obtained. For the hetaryl-substituted derivatives the cyclization step was found to be assisted by protons. In addition 4,5,5a,6,7,8-hexahydro-1H-pyrazolo[3,4-e]indolizine and 1,4,5,5a,6,7,8,9-octahydro-pyrazolo[4,3-c]quinolizine derivatives were prepared by the same method starting from 5-(1-pyrrolidinyl)- and 5-(1-piperidinyl)-3-methyl-1-phenylpyrazole-4-carbaldehydes. The relative configuration between the bridgehead hydrogen and the cyano group was assigned as trans on the basis of x-ray crystallographic data.

Tverdokhlebov A. V.; Gorulya A. P.; Tolmachev A. A.; Kostyuk A. N.; Chernega A. N.; Rusanov E. B.
Synthesis 2005, 13, 2161-2170
DOI: 10.1055/s-2005-870004