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

Abstract 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 18 H 16 N 2 O 3 S: 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( Cu Kα) = 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.