Tandem Chiral Cu(II) Phosphate‐Catalyzed Deoxygenation of Nitrones/Enantioselective Povarov Reaction with Enecarbamates

Abstract

A new catalytic enantioselective tandem deoxygenation/aza‐Diels‐Alder reaction of nitrones with enecarbamates was serendipitously discovered in the presence of chiral copper(II) diphosphate complexes. This process affords a wide range of 4‐aminotetrahydroquinolines in respectable yields under mild conditions with good to excellent ee values.

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

“…The TS that explains the stereochemistry observed in the product, presents electrostatic interactions and hydrogen bonding between the chiral phosphate anion and the iminium ion, making one side of the iminium ion prevented from addition, inducing endo diastereoselectivity, according to the literature [97] (Figure 16b). Following the same proposal, C. Gelis et al [98] enantioselective Mannich reaction occurs, followed by an intramolecular Friedel-Crafts reaction to form the (2S, 3R, 4S)-4-aminoTHQ 178.…”

Enantioselective synthesis and selective functionalization of 4‐aminotetrahydroquinolines as novel GLP‐1 secretagogues

“…A Suzuki coupling with compound 5d 8 was attempted with phenylboronic acid in the presence of Pd (OAc) 2 , P( o ‐Tol) 3 and K 2 CO 3 ; the desired product 9 was achieved in 94% yield (Figure 2).…”

Enamides and dienamides in phosphoric acid-catalysed enantioselective cycloadditions for the synthesis of chiral amines

“…Recently, an alternative strategy for a stereoselective synthesis of tetrahydroquinolines 11 was disclosed by our group. 32 During our study on the development of enantioselective (3 + 2) cycloadditions between enecarbamates 1 and nitrones 41, an unexpected result was observed when a copper-phosphate salt Cu II [(R)-4c] 2 was employed as catalyst. The only product formed was not the expected isoxazolidines 42 but, to our surprise, the 4-aminotetrahydroquinolines 11 in excellent enantio-and diastereoselectivity.…”