Total facial selectivity in 2π+4π reactions of (2R,4S,5R)-4-((E)-((4-Methoxyphenyl)imino)methyl)-2-phenyl-1,3-dioxan-5-ol to electron-rich dienophiles

Tetrahydroquinoline (THQ) is an important structural unit present in various natural products and pharmaceutical agents having a large range of biological activities. Many approaches have been developed for the construction of THQ scaffold. Among these, the inverse electron demand hetero-Diels-Alder reaction1 or its ionic version2 is regarded as a powerful tool. The imine 3 is generated in situ from D-erythrose and p-methoxy-aniline. When the reaction is finished dienophiles were added at – 78 ºC giving products in moderate to high yields, with formation of a single diastereoisomer. In this work BF3·Et2O3 used as catalyst is supposed to help to induce facial selectivity in 2π+4π reactions. The boron atom is able to form a bridge between the oxygen and nitrogen atoms, neighbor in space. In this way rotation around bound a would be avoided, and the structure would obtain some rigidity. According to X-ray crystallography of product 4a, dienophiles approach the imine by the re face. It is likely that the packing of the dienophile hydrogens with diene’s H-4 explains the si face impediment. Reactions of the imine with vinyl ether and (E)-5-bromopenta-1,3-diene occurred in the absence of catalyst, but a single product was also formed. This was rationalized by an intramolecular hydrogen bond between the alcohol and the nitrogen atom that would confer to the structure the same rotational restriction. When 2,3-dimethylbutadiene was used as dienophile a mixture of inverse and normal polarity 2π+4π reaction product occurred in a 1:2 ratio.The FCT for financial support PTDC/EQF-MED/1671/2012, the national network of NMR (PTNMR, Bruker Avance III 400-Univ. Minho) and FEDER-COMPETE-QREN-EU funding the Department Chemistry-UM.