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

The title compound, gem-ketovinylsulfone 3, was obtained stereoselectively (de > 98%) by the action of the oc-anion from p-tolylsulfonylacetone 1 on imidazo[1,2-a]pyridine-2-carbaldehyde 2 in chelation-controlled conditions in the presence of a Lewis acid (ZnCl2). The X-ray crystal structure of 3 [C18H16N2O3S: M-I = 340.4, orthorhombic, Pbca, a = 12.208(3) Angstrom, b = 18.848(4)Angstrom, c = 14.566(11)Angstrom, V = 3.351(3)Angstrom(3), Z = 8, D-calc = 1.349 g cm(-3), <(lambda)over bar>(CuK alpha) = 1.54178 Angstrom, mu = 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. (C) 1998 Elsevier Science B.V. All rights reserved.