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Volumn 129, Issue 2, 2007, Pages 441-449

Organocatalytic asymmetric direct α-alkynylation of cyclic β-ketoesters

Author keywords

[No Author keywords available]

Indexed keywords

ALKYNYLATING REAGENTS; CYCLIC Β-KETOESTERS; ENANTIOSELECTIVITIES; NUCLEOPHILIC ACETYLENIC SUBSTITUTION;

EID: 33846220324     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja067289q     Document Type: Article
Times cited : (143)

References (93)
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    • For additions to aldehydes catalytic in metal see: a
    • For additions to aldehydes catalytic in metal see: (a) Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687.
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    • For additions to imines catalytic in metal see: (h) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638.
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    • For procedures stoichiometric in metal, see ref 5a. For catalytic conjugate alkyne addition, see: (i) Knöpfel, T. F, Zarotti, P, Ichikawa, T, Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 9682
    • For procedures stoichiometric in metal, see ref 5a. For catalytic conjugate alkyne addition, see: (i) Knöpfel, T. F.; Zarotti, P.; Ichikawa, T.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 9682.
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    • Diederich, F, Stang, P. J, Tykwinski, R. R, Eds, VCH: Weinheim, Germany, Chapter 3, pp
    • (k) Aschwanden, P.; Carreira, E. M. in Acetylene Chemistry; Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; VCH: Weinheim, Germany, 2005, Chapter 3, pp 101-138.
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    • Asymmetric synthesis of propargylic stereocenters can also be achieved through the Nicholas reaction, for a review see: (a) Teobald, B. J. Tetrahedron 2002, 58, 4133
    • Asymmetric synthesis of propargylic stereocenters can also be achieved through the Nicholas reaction, for a review see: (a) Teobald, B. J. Tetrahedron 2002, 58, 4133.
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    • By asymmetric reduction of ynones (propargylic alcohols): (b) Helal, C. J.; Magriotis, P. A.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 10938.
    • By asymmetric reduction of ynones (propargylic alcohols): (b) Helal, C. J.; Magriotis, P. A.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 10938.
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    • By resolution of racemic propargylic alcohols: (c) Birman, V. B. M.; Guo, L. Org. Lett. 2006, 8, 4859 and references herein.
    • By resolution of racemic propargylic alcohols: (c) Birman, V. B. M.; Guo, L. Org. Lett. 2006, 8, 4859 and references herein.
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    • For reviews see: (a) Stang, P. J. J. Org. Chem. 2003, 68, 2997.
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    • (b) Stang, P. J. In Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim, Germany, 1995; Chapter 3, pp 67-98.
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    • For a review: a, 2nd ed, Ojima I, Ed, Wiley-VCH: Weinheim, Germany
    • For a review: (a) O'Donnell, M. J. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima I., Ed.: Wiley-VCH: Weinheim, Germany, 2000; p 727.
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    • For recent examples of phase-transfer catalyzed asymmetric reactions, see: b
    • For recent examples of phase-transfer catalyzed asymmetric reactions, see: (b) Ooi, T.; Uematsu, Y.; Maruoka, K. J. Am. Chem. Soc. 2006, 128, 2548.
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    • The allyloxycarbonyl (alloc) group can be removed from an alkyne by palladium(0)-catalyzed deallylation-decarboxylation. See: (a) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic Synthesis, 3rd ed.; Wiley: New York, 1999; p 409.
    • The allyloxycarbonyl (alloc) group can be removed from an alkyne by palladium(0)-catalyzed deallylation-decarboxylation. See: (a) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic Synthesis, 3rd ed.; Wiley: New York, 1999; p 409.
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    • 3 (10 mol%) to the reaction mixture in acetone we observed the immediate formation of a greyish precipitate. This precipitate is presumed to originate from a reaction between the silver(I) and allyl propiolate resulting in irreversible removal of catalyst from the catalytic cycle.
    • 3 (10 mol%) to the reaction mixture in acetone we observed the immediate formation of a greyish precipitate. This precipitate is presumed to originate from a reaction between the silver(I) and allyl propiolate resulting in irreversible removal of catalyst from the catalytic cycle.
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    • Klunder, A. J. H.; Zhu, J.; Zwanenburg, B. Chem. Rev. 1999, 99, 1163. See also ref 12.
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    • The only described synthesis of 1e proceeds through a Pd-catalyzed carbonylation reaction from the corresponding bromo derivative: Raju, P. V. K.; Adapa Srinivas, R. Indian J. Chem., Sect. B 1992, 31, 363. In our hands, the transesterification from the methyl ester in the conditions used for indanones 1a-d (ref 22) proceeded only sluggishly (conversion <50% after several days), though providing the expected product.
    • The only described synthesis of 1e proceeds through a Pd-catalyzed carbonylation reaction from the corresponding bromo derivative: Raju, P. V. K.; Adapa Srinivas, R. Indian J. Chem., Sect. B 1992, 31, 363. In our hands, the transesterification from the methyl ester in the conditions used for indanones 1a-d (ref 22) proceeded only sluggishly (conversion <50% after several days), though providing the expected product.
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    • Apparently, the present catalytic system does not accommodate relatively flexible substrates: for example, a noncyclic β-ketoester such as tert-butyl 2-methyl-3-oxo-3-phenylpropanoate could be alkynylated only with low enantioselectivities (<20% ee).
    • Apparently, the present catalytic system does not accommodate relatively flexible substrates: for example, a noncyclic β-ketoester such as tert-butyl 2-methyl-3-oxo-3-phenylpropanoate could be alkynylated only with low enantioselectivities (<20% ee).
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    • The parent 3-acyl oxindole was obtained by acylation of N-Me-oxindole with tert-butyl cyanoformate 6. These compounds are inherently unstable towards isolation by chromatography on silica gel. To facilitate isolation, the 3-acyl oxindole was converted to the 2-silyl ether indole 11 (see Supporting Information for details).
    • The parent 3-acyl oxindole was obtained by acylation of N-Me-oxindole with tert-butyl cyanoformate 6. These compounds are inherently unstable towards isolation by chromatography on silica gel. To facilitate isolation, the 3-acyl oxindole was converted to the 2-silyl ether indole 11 (see Supporting Information for details).
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    • For recent total syntheses of compounds possessing this structural feature, see for example: a
    • For recent total syntheses of compounds possessing this structural feature, see for example: (a) Reisman, S. E.; Ready, J. M.; Hasuoka, A.; Smith, C. J.; Wood, S. L. J. Am. Chem. Soc. 2006, 128, 1448.
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    • For a very nice study on the protonation of allenic enols and enolates, see
    • For a very nice study on the protonation of allenic enols and enolates, see: Zimmerman, H. E.; Pushechnikov, A. Eur. J. Org. Chem. 2006, 3491.
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    • For the haloalkynes employed in this study, attack at C2 must be considered unlikely because the electron withdrawing group strongly stabilizes the incipient anion resulting from attack at C3, undergoes nucleophilic attack
    • For the haloalkynes employed in this study, attack at C2 must be considered unlikely because the electron withdrawing group strongly stabilizes the incipient anion resulting from attack at C3. No such stabilization is possible when C2 undergoes nucleophilic attack.
    • No such stabilization is possible when , Issue.C2
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    • 2-phenolate in MeOH for 2 h followed by aqueous work-up.
    • 2-phenolate in MeOH for 2 h followed by aqueous work-up.
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    • By searching of the Cambridge Crystallographic Data Centre
    • By searching of the Cambridge Crystallographic Data Centre.
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    • It is worth noting that the overall conformation of our catalyst and the one described by Corey et al. in ref 40 is to a very large extent the same in the solid state by comparison of the X-ray structures
    • It is worth noting that the overall conformation of our catalyst and the one described by Corey et al. in ref 40 is to a very large extent the same in the solid state (by comparison of the X-ray structures).


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