Enantioselective Diels-Alder reactions: novel constrained bis(oxazoline) ligand-metal triflate catalysts

Asymmetric copper-catalyzed Diels–Alder reaction revisited: control of the structure of bis(oxazoline) ligands

“…We also decided to test N-crotonyloxazolidinone 8b as a substrate to compare our results with those previously reported. 13 In our hands, the endo-cycloadduct 9…”

“…35 X-ray diffraction analysis shows that the two chiral oxazoline rings are slightly twisted pushing the two oxazolinyl phenyl towards the metal centre. In contrast, X-ray structure of the other diastereomer ligand 4e' (using the (R)-phenyl glycinol and trans-(11R,12R)-dicarboxylic acid 1), 13 showed that the two oxazolinyl phenyl are far away from the metal centre in the complex.…”

“…The 1 H NMR analysis confirmed the presence of the desired product as a single diastereomer. It should be noted that some epimerization occurs with the previously requisited procedure 13 in forming the diamide intermediate.…”

“…Besides the central chirality element in the oxazoline moiety, these ligands possess an additional chirality element in the backbone such as 1,3-dioxolane I, [10][11][12] bicyclo [2,2,1] II, [2,2,2] III, 13 cyclohexane IV, 14,15 and cyclopentane V. Although the Diels-Alder reaction between acrylimide dienophiles and cyclopentadiene was the most successful application of the Cu(II)-bis(oxazoline) catalytic system with enantiomeric excess up to 99%, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] its application with the ligands I, II, III, IV and V was less effective in enantioselectivity. In particular, the ligand III, previously introduced by Takacs et al, 13 has particularly focused our attention since the best enantioselectivity (75%) in the Diels-Alder reaction surprisingly involves the meso-backbone and poor results were obtained with the other chiral configurations. Moreover, the authors 13 indicated that a phenomenon of epimerization was observed during the synthesis of these ligands.…”

“…In particular, the ligand III, previously introduced by Takacs et al, 13 has particularly focused our attention since the best enantioselectivity (75%) in the Diels-Alder reaction surprisingly involves the meso-backbone and poor results were obtained with the other chiral configurations. Moreover, the authors 13 indicated that a phenomenon of epimerization was observed during the synthesis of these ligands. These results inspired us to reinvestigate the synthesis of these ligands with more convenient routes to better control the stability of their relative configuration.…”