1,3-Dipolar Cycloadditions to Unsymmetrical Ketone-Derived Chiral Stabilized Azomethine Ylides: Strategies for the Synthesis of Highly Substituted Amino Acids

Abstract

We report herein, the first generation of unsymmetrical ketone-derived chiral stabilized azomethine ylides. Intramolecular and intermolecular cycloaddition strategies have been utilized to synthesize both an enantiomerically pure bicyclic proline derivative and an enantiomerically pure β-hydroxy-α-amino acid.

azomethine ylide - β-hydroxy-α-amino acid - proline - intramolecular - cycloaddition

References

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For examples of the synthesis of substituted prolines, see:

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X-ray Crystal Data: 6 C₁₇H₂₁NO₂, M = 271.35, orthorhombic, space group P212121, Z = 4, a = 6.715 (10), b = 13.502 (8), c = 16.73 (2), V = 1517 ų, d = 1.188 Mg/m³, 1545 independent reflections were collected with MoKα radiation on the MAR research Image Plate system. Data analysis was carried out with the XDS program [8] the structure was solved by direct methods using Shelx86 [9] and refined on F2 using Shelx [10] to R1 0.0686, wR2 0.1937. 8a C₂₃H₂₂N₂O₄, M = 390.43, orthorhombic, space group P212121-, Z = 4, a = 9.510 (12), b = 9.934 (14), c = 21.23 (2), V = 2006 ų, d = 1.293 Mg/m³, 3554 independent reflections were collected. The structure was solved by direct methods and refined on F2 to R1 0.0834, wR2 0.2490. 9c C₂₈H₂₄N₂O₄, M = 452.49, monoclinic, space group P21-, Z = 2, a = 10.857 (12), b = 8.120 (10), c = 28.75 (3), β = 96.895 (i1)°, V = 2516 ų, d = 1.194 Mg/m³, 4541 independent reflections were collected. The structure was solved by direct methods and refined on F2 to R1 0.1749, wR2 0.4199. 10c C₂₄H₂₅NO₆, M = 423.45.31, orthorhombic, space group P212121, Z = 4, a = 11.389 (15), b = 13.320 (14), c = 15.080 (17), V = 2272 ų, d = 1.238 Mg/m³, 2480 independent reflections were collected. The structure was solved by direct methods and refined on F2 to R1 0.0488, wR2 0.1277. 11c C₂₄H₂₅NO₆, M = 423.45.31, orthorhombic, space group P212121, Z = 4, a = 6.212 (10), b = 16.72 (2), c = 20.33 (3), V = 2111 ų, d = 1.332 Mg/m³, 6680 independent reflections were collected. The structure was solved by direct methods and refined on F2 to R1 0.1078, wR2 0.2857. 15 C₂₅H₂₂N₂O₅, M = 430.45, orthorhombic, space group P212121, Z = 4, a = 7.481 (10), b = 13.464 (17), c = 21.72 (3), V = 2188 ų, d = 1.307 Mg/m³, 6487 independent reflections were collected. The structure was solved by direct methods and refined on F2 to R1 0.0996, wR2 0.2057. Atomic co-ordinates, bond lengths and angles and thermal parameters have been deposited with the Cambridge Crystallographic Service.

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