Formal fusion of a pyrrole ring onto 2-pyridyl and 2-pyrimidyl cations: One-step gas-phase synthesis of indolizine and its derivatives

Two ortho-hetarynium ions, the 2-pyridyl and 2-pyrimidyl cations, react pro mptly with 1,3-dienes in the gas phase by annulation, formally by fusion, o nto the ions of a pyrrole ring. This novel reaction proceeds through an ini tial polar [4 + 2(+)] cycloaddition across the C=N+ bond, followed by fast ring opening, a [1,4-H] shift, and finally a recyclization that results in a contraction of a six- to a five-membered ring and dissociation by the los s of a methyl radical. For the 2-pyridyl cation. this reaction yields ioniz ed indolizines (pyrrolo[1,2-a]pyridines), while for the 2-pyrimidyl cation, it gives ionized pyrrolo[1,2-a]pyrimidines. The annulation reaction, perfo rmed in the rf-only collision quadrupole of a pentaquadrupole (QqQqQ) mass spectrometer, occurs readily with both 1,3-butadiene and isoprene, and is t hermodynamically and kinetically favored as predicted by ab initio calculat ions. Ortho-hetarynium ions and 1,3-dienes provide, therefore, the two buil ding blocks for the efficient one-step gas-phase synthesis of ionized bicyc lic pyrrolo[1,2-a]pyridine (indolizine) and pyrrolo[1,2-a] pyrimidine, as w ell as their analogues and derivatives.