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Volumn 50, Issue 27, 2011, Pages 6123-6127

Dual hydrogen-bond/enamine catalysis enables a direct enantioselective three-component domino reaction

Author keywords

domino reactions; enamine catalysis; hydrogen bond catalysis; nitroolefins; organocatalysis

Indexed keywords

DOMINO REACTIONS; ENAMINES; HYDROGEN-BOND CATALYSIS; NITROOLEFINS; ORGANOCATALYSIS;

EID: 79959522610     PISSN: 14337851     EISSN: 15213773     Source Type: Journal    
DOI: 10.1002/anie.201101835     Document Type: Article
Times cited : (43)

References (77)
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    • As the enantiomeric ratios have not been calibrated, ratios higher than 200:1 are reported as >99.5:<0.5. The actual observed ratios were: for Table2, entry1 (with (S)- 3): 99.90:0.10, and for Table2, entry3 (with (R)- 3): 0.02:99.98. In addition, we have also prepared ent- 17 ((S)- 17), which gives 99.98:0.02 e.r. with (S)- 3). These are, to the best of our knowledge, the highest enantioselectivities reported for these conjugate addition processes. These results also indicate that catalyst 3 appears to be almost solely responsible for the sense of enantioinduction. Although 17 is chiral, the results indicate that achiral versions of 17 could also be conceived
    • For kinetic evidence of the involvement of iminium intermediates in pyrrolidine-catalyzed aldehyde condensation reactions, see Ref.[9b]. For a full description of the solvents and alternative amine catalysts screened, see the Supporting Information. As the enantiomeric ratios have not been calibrated, ratios higher than 200:1 are reported as >99.5:<0.5. The actual observed ratios were: for Table2, entry1 (with (S)- 3): 99.90:0.10, and for Table2, entry3 (with (R)- 3): 0.02:99.98. In addition, we have also prepared ent- 17 ((S)- 17), which gives 99.98:0.02 e.r. with (S)- 3). These are, to the best of our knowledge, the highest enantioselectivities reported for these conjugate addition processes. These results also indicate that catalyst 3 appears to be almost solely responsible for the sense of enantioinduction. Although 17 is chiral, the results indicate that achiral versions of 17 could also be conceived.
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    • Step1 (formation of 4) proceeds faster with unbranched aliphatic aldehydes than with branched aliphatic or aromatic aldehydes, thus precluding the addition of all three components at once.
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    • -1 have also been identified and they are presented in the Supporting Information. The reported binding energies were obtained from the gas-phase electronic energies
    • -1 have also been identified and they are presented in the Supporting Information. The reported binding energies were obtained from the gas-phase electronic energies.
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    • 1HNMR analysis. A slight upfield shift for the vinylic protons of 4 g (Δδ=-0.017ppm for the α and -0.020ppm for the βproton) was observed in presence of 17 (see the Supporting Information). Further binding studies are in progress
    • 1HNMR analysis. A slight upfield shift for the vinylic protons of 4 g (Δδ=-0.017ppm for the α and -0.020ppm for the βproton) was observed in presence of 17 (see the Supporting Information). Further binding studies are in progress.


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