The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described.

Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3-4’)-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans-anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed.

Die Carbonsäuren (I) und (II) liefern bei der Elektrolyse in Acetonitril oder Methanol/Pyridin keine Dimeren, sondern laugelösliche Produkte.

Imines. -N-Methylimidazole is an efficient additive in the formal cycloaddition of aldimines with homophthalic anhydride to improve yields as well as the regioselectivity with regard to cyclization over elimination. -(LIU, J.; WANG, Z.; LEVIN, A.; EMGE, T. J.; RABLEN, P. R.; FLOYD, D. M.; KNAPP*, S.; J. Org. Chem. 79 (2014) 16, 7593-7599, http://dx.doi.org/10.1021/jo501316m ; Dep. Chem. Chem. Biol., Rutgers State Univ. N. J., Piscataway, NJ 08854, USA; Eng.) -Mais 08-227

Durch anodische Überkreuzkondensation von Gemischen aus einbasischen perfluorierten Säuren (I), (IV) und (VI) und Monomethyladipinat (II) erhält man die Perfluoralkylvaleriansäuremethylester (III), (V) und (VII) in Ausbeuten zwischen 10 und 19%.