Stereoselective synthesis of ( E)-4-(imidazo[1,2- a]pyrid-2-yl)-3-(4-methylphenylsulfonyl)but-3-en-2-one. X-ray crystal structure and conformational analysis

• Published in: Journal of molecular structure 1998-06, Vol.447 (1), p.135-140
• Main Authors: Roche, D., Force, L., Carpy, A., Gardette, D., Madesclaire, M.
• Format: Article
• Language: English
• Subjects: Conformational analysis; Stereoselective synthesis; X-ray crystal structure
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/S0022-2860(98)00316-0

The title compound, gem-ketovinylsulfone 3, was obtained stereoselectively (de > 98%) by the action of the α-anion from p-tolylsulfonylacetone 1 on imidazol[1,2- a]pyridine-2-carbaldehyde 2 in chelation-controlled conditions in the presence of a Lewis acid (ZnCl 2). The X-ray crystal structure of 3 [C 18H 16N 2O 3S: M t = 340.4, orthorhombic, Pbca, a = 12.208(3) A ̊ , b = 18.848(4) A ̊ , c = 14.566(11) A ̊ , V = 3.351(3) A ̊ 3 , Z = 8, D calc = 1.349 g cm −3, λ( CuKα) = 1.54178 A ̊ , μ = 1.83 mm −1, F(000) = 1424, T = 293 K, R = 0.061 for 2.046 observed reflections] was determined, and confirmed the ( E) configuration. Despite the conjugate position of the vinyl double bond, quasi-coplanar with the imidazopyridine heterocycle, there is no evidence of p-electron delocalization. The crystal cohesion is ensured by a dense network of van der Waals contacts. The conformational analysis of the ( E) and ( Z) stereoisomers was performed by molecular dynamics simulation, and showed the ( E) isomer to be 9.1 kJ mol −1 more stable than the ( Z) isomer.