The direct catalytic α-amidoalkylation of dihydroquinolines with aldehydes bearing oxygen functionalities at different positions in a Mannich-type reaction has been studied. β-Alkoxy-aldehyde 1d gave high enantioselectivity, albeit with an inherently poor diastereoselectivity, while the use of α-alkoxy aldehydes 1c was detrimental also to enantioselectivity. Mannich-type reactions have been studied for the first time using new chiral carbohydrate-derived aldehydes 1a,b showing a reactivity markedly influenced by the presence of water. The chiral glycidic backbone showed a slight but significant influence on the overall stereochemical outcome only when present in α-position of the aldehyde. The absolute stereochemistry of the products was studied by electronic circular dichroism (ECD) spectra and compared with theoretical calculations. ECD analysis easily provides the absolute configuration of 1,2-dihydroquinoline derivatives such as quinoline-1(2H)-carboxylates.
Keywords: Mannich reactions; Organocatalysis; TDDFT calculations; carbohydrate aldehydes; electronic circular dichroism; glycoconjugates.
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