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Volumn 132, Issue 6, 2010, Pages 1828-1830

Practical and highly selective sulfur ylide mediated asymmetric epoxidations and aziridinations using an inexpensive, readily available chiral sulfide. Applications to the synthesis of quinine and quinidine

Author keywords

[No Author keywords available]

Indexed keywords

ALIPHATIC ALDEHYDES; ASYMMETRIC EPOXIDATION; AZIRIDINES; CHIRAL SULFIDE; CINCHONA ALKALOID; DIASTEREOISOMERS; DIASTEREOSELECTIVITIES; ELEMENTAL SULFUR; HIGH YIELD; HOMOCHIRAL; NATURALLY OCCURRING; ONE STEP SYNTHESIS; SCALEABLE; STEREOSELECTIVE SYNTHESIS; SULFONIUM SALTS;

EID: 77249084687     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja9100276     Document Type: Article
Times cited : (154)

References (59)
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    • We are aware of just one report of the application of a chiral sulfur ylide by a group not involved in the development of chiral sulfides: Morales-Serna, J. A, Llaveria, J, Díaz, Y, Matheu, M. I, Castillón, S. Org. Biomol. Chem. 2008, 6, 4502
    • We are aware of just one report of the application of a chiral sulfur ylide by a group not involved in the development of chiral sulfides: Morales-Serna, J. A.; Llaveria, J.; Díaz, Y.; Matheu, M. I.; Castillón, S. Org. Biomol. Chem. 2008, 6, 4502.
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    • Weitkamp, A. W. Chem. Abs. 1962, 57, 4706g U.S. Patent 3,026,315, Mar 20, 1962
    • (b) Weitkamp, A. W. Chem. Abs. 1962, 57, 4706g (U.S. Patent 3,026,315, Mar 20, 1962).
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    • Although the original procedure by Weitkamp had been optimized and operated on a >100 gallon scale, it still resulted in low yield and erosion in er and required a difficult separation of the product isothiocineole from various side products. By adding γ-terpinene a much improved synthesis was achieved without erosion of er and with simple isolation. Full details on its role will be reported in due course
    • Although the original procedure by Weitkamp had been optimized and operated on a >100 gallon scale, it still resulted in low yield and erosion in er and required a difficult separation of the product isothiocineole from various side products. By adding γ-terpinene a much improved synthesis was achieved without erosion of er and with simple isolation. Full details on its role will be reported in due course.
  • 25
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    • (R)-Limonene is an extremely cheap chiral pool material, available in bulk quantities. Sulfide (-)-1 costs <$1/g to synthesize based on Aldrich's current UK prices. (S)-Limonene is also available in bulk but is normally available as a 90:10 mixture of enantiomers. In this case, two successive low temperature (-50 °C) recrystallizations from pentane furnished enantiopure (+)-isothiocineole.
    • (R)-Limonene is an extremely cheap chiral pool material, available in bulk quantities. Sulfide (-)-1 costs <$1/g to synthesize based on Aldrich's current UK prices. (S)-Limonene is also available in bulk but is normally available as a 90:10 mixture of enantiomers. In this case, two successive low temperature (-50 °C) recrystallizations from pentane furnished enantiopure (+)-isothiocineole.
  • 26
    • 77249172702 scopus 로고    scopus 로고
    • We have scaled up the reaction uneventfully to an ∼1 mol scale. This material is commercially available from TCI T2578 and T2579
    • We have scaled up the reaction uneventfully to an ∼1 mol scale. This material is commercially available from TCI (T2578 and T2579).
  • 27
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    • This was prepared by alkylation of the sulfide with BnBr and required 24 h at 20 °C. The alkylation of sulfides with flanking gem-dimethyl groups, e.g. 1,4-oxathianes (see 4k) or 1,3-thioacetals [Solladié- Cavallo, A, Diep-Vohuule, A, Šunjiç, V, Vinkovic, V. Tetrahedron: Asymmetry 1996, 7, 1783, is usually difficult. In the event, alkylation proved to be facile, presumably because of the lack of heteroatoms within the ring which, in the case of 1,4-oxathianes or 1,3-thioacetals, reduce the nucleophilicity of the sulfide through inductive effects
    • This was prepared by alkylation of the sulfide with BnBr and required 24 h at 20 °C. The alkylation of sulfides with flanking gem-dimethyl groups, e.g. 1,4-oxathianes (see 4k) or 1,3-thioacetals [Solladié- Cavallo, A.; Diep-Vohuule, A.; Šunjiç, V.; Vinkovic, V. Tetrahedron: Asymmetry 1996, 7, 1783. ] is usually difficult. In the event, alkylation proved to be facile, presumably because of the lack of heteroatoms within the ring which, in the case of 1,4-oxathianes or 1,3-thioacetals, reduce the nucleophilicity of the sulfide through inductive effects.
  • 28
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    • See page S14 in the SI for a comparison with sulfide 2.
    • See page S14 in the SI for a comparison with sulfide 2.
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    • Zanardi, J, Lamazure, D, Minière, S, Reboul, V, Metzner, P. J. Org. Chem. 2002, 67, 9083. For a review on vinyl epoxides see ref 3b
    • Zanardi, J.; Lamazure, D.; Minière, S.; Reboul, V.; Metzner, P. J. Org. Chem. 2002, 67, 9083. For a review on vinyl epoxides see ref 3b.
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    • For reviews see: a
    • For reviews see: (a) Müller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905.
    • (2003) Chem. Rev , vol.103 , pp. 2905
    • Müller, P.1    Fruit, C.2
  • 46
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    • For recent discussion surrounding Woodward's synthesis see: b
    • For recent discussion surrounding Woodward's synthesis see: (b) Seeman, J. I. Angew. Chem., Int. Ed. 2007, 46, 1378.
    • (2007) Angew. Chem., Int. Ed , vol.46 , pp. 1378
    • Seeman, J.I.1
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    • Kobayashi used this protecting group on the piperidine ring in his synthesis of quinine. Ref 16c.
    • Kobayashi used this protecting group on the piperidine ring in his synthesis of quinine. Ref 16c.
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    • Although aldehyde 6 has been prepared by total synthesis (ref 16c, we obtained it more directly from quinine (5 steps) using procedures described previously see SI, Martinelli, M. J, Peterson, B. C, Khau, V. V, Hutchison, D. R, Sullivan, K. A. Tetrahedron Lett. 1993, 34, 5413
    • Although aldehyde 6 has been prepared by total synthesis (ref 16c), we obtained it more directly from quinine (5 steps) using procedures described previously (see SI): Martinelli, M. J.; Peterson, B. C.; Khau, V. V.; Hutchison, D. R.; Sullivan, K. A. Tetrahedron Lett. 1993, 34, 5413.
  • 58
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    • Clark, J. S.; Townsend, R. J.; Blake, A. J.; Teat, S. J.; Johns, A. Tetrahedron Lett. 2001, 42, 3235. Many syntheses of quinine adopt this strategy, i.e. are relay syntheses.
    • Clark, J. S.; Townsend, R. J.; Blake, A. J.; Teat, S. J.; Johns, A. Tetrahedron Lett. 2001, 42, 3235. Many syntheses of quinine adopt this strategy, i.e. are relay syntheses.
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    • For microwave aminolysis of epoxides see ref 16a and: Lindstrom, U. M, Olofsson, B, Somfai, P. Tetrahedron Lett. 1999, 40, 9273
    • For microwave aminolysis of epoxides see ref 16a and: Lindstrom, U. M.; Olofsson, B.; Somfai, P. Tetrahedron Lett. 1999, 40, 9273.


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