Organocatalytic alkylation of carbohydrate‐containing aldehydes with dihydroquinoline N,O‐acetals: Absolute configuration of 1,2‐dihydroquinolines

Abstract

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.

Direct enantioselective vinylogous Mannich‐type reactions of acyclic enals: New experimental insights into the E/Z‐dilemma

“…Using a combined experimental and computational procedure, the ECD spectra of 2c-syn and 2c-anti were recorded in acetonitrile and compared with those calculated by density functional theory (DFT) on a truncated model of 2c (benzyl of Cbz replaced by methyl). 26,27 As SCHEME 2 Stereochemical models for main facial selectivity observed FIGURE 3 Transition states leading to (R,R) and (S,S)-anti diastereoisomers recently observed for other 1,2-dihydroquinoline derivatives, 28 the ECD spectra of 2c is dominated by the configuration of the endocyclic stereocentre. The configuration of the endocyclic stereocentre depends on the attack of the dienamine with either Re or Si face of the N-acyl quinolinium ion (Scheme 2).…”

Conjugation of Carbohydrates with Quinolines: A Powerful Synthetic Tool

“…Menichetti et al reported the organocatalytic asymmetric amidoalkylation of C-2 in dihydroquinolines (113), as shown in Scheme 21. [60] They used the organocatalyst 115 under In(OTf) 3 promotion to form an intermediate N-acylquinolinium ion, capable of undergoing the subsequent nucleophilic addition of the carbohydrate aldehyde 114. Subsequent reduction of the unstable aldehyde provide the diasteroisomeric mixture 116-117.…”