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Volumn 64, Issue 2, 1999, Pages 611-617

Prototype Pictet-Spengler reactions catalyzed by superacids. Involvement of dicationic superelectrophiles

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CATALYSIS; CHEMICAL REACTION; CHEMICAL REACTION KINETICS; CHEMICAL STRUCTURE; CYCLIZATION;

EID: 0033593374     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo982019e     Document Type: Article
Times cited : (108)

References (73)
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    • 0) of the TFSA-TFA system is described in Saito et al. (Saito, S.; Saito, S.; Ohwada, T.; Shudo, K. Chem. Pharm. Bull. 1991, 39, 2718-2720). See also: Saito, S.; Sato, Y.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1994, 116, 2312-2317, footnote 8.
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    • footnote 8
    • 0) of the TFSA-TFA system is described in Saito et al. (Saito, S.; Saito, S.; Ohwada, T.; Shudo, K. Chem. Pharm. Bull. 1991, 39, 2718-2720). See also: Saito, S.; Sato, Y.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1994, 116, 2312-2317, footnote 8.
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    • Saito, S.1    Sato, Y.2    Ohwada, T.3    Shudo, K.4
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    • 0).
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    • note
    • The yield of the cyclized product was calculated after conversion to the corresponding benzoyl derivative by benzoylation of the crude amine products to allow convenient purification of the compound. Under the same reaction conditions (in 90% w/w TFSA-10% w/w TFA, 50°C, 1 h), N-benzoyl-1,2,3,4-tetrahydroisoquinoline was formed in 74% yield, along with the N-benzoyl derivative of 2-phenethylamine (5% yield), which was generated through decomposition of the starting imine 1a. This decomposition of the starting imine partially accounts for the limiting conversion (for example, 1b) particularly under a longer reaction time and a higher reaction temperature. The yield of the cyclized product after benzoylation is comparable with that obtained by the direct separation of 2a Benzoylation of the crude reaction mixture obtained in the cyclization reaction of the imine 1a allows convenient isolation of the crude amines, and also affords good separation of a small amount of an undefined polar byproduct.
  • 39
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    • note
    • 1H NMR spectrum of 1a in TFA at -18°C, the two methylene signals are observed at 8.10 ppm (J = 8.5 Hz) and 7.87 ppm (J = 8.3 and 17.8 Hz) as a triplet and a quartet signal, respectively. The splittings of these signals are due to the geminal coupling (J = 8 Hz) and the coupling with the NH signal.
  • 41
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    • Tomaszewski, M. J.; Warkentin, J.; Werstiuk, N. H. Aust. J. Chem. 1995, 48, 291-321. Sakamoto, M.; Tomimatu, Y. Yakugaku Zasshi 1970, 90, 1339-1346; Chem. Abstr. 1971, 74, 53468t.
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    • note
    • 0 = -12.7) gave essentially the same pattern as that in TFA, and therefore, the concentration of the diprotonated imine (4c) seems to be too low to allow for detection by NMR. This conclusion is consistent with the Zucker-Hammett criteria which postulate that such a linear relationship between the rates and the acidities (Figure 1) can be obtained only when the concentration of the diprotonated species is very small.
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    • (d) Long, F. A.; Paul, M. A. Chem. Rev. 1957, 57, 935-1010. If the reactive electrophile in the cyclization is the monoprotonated imine, the rates of the reaction will be saturated because the imine 1 is fully monoprotonated even in TFA.
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    • footnote 24
    • e (the ionization constant of the carbodication 4) at the different temperatures. See: Ohwada, T.; Suzuki, T.; Shudo, K. J. Am. Chem. Soc. 1998, 120, 4629-4637, footnote 24. Therefore the activation parameters obtained from the kinetic data should represent the thermal parameters in the rate-determining cyclization process. A similar situation is also expected in the case of the monocationic cyclization, i.e., the cyclization of the imine 1a in TFA.
    • (1998) J. Am. Chem. Soc. , vol.120 , pp. 4629-4637
    • Ohwada, T.1    Suzuki, T.2    Shudo, K.3
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    • We noted a slight curvature of the plot in the highest acidity region
    • We noted a slight curvature of the plot in the highest acidity region.
  • 52
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    • note
    • The facile deuterium exchange of the phenyl protons of the 2-phenethylamine moiety of 1c even at 23°C indicates a facile formation of dicationic species such as 5i-5iii matrix presented and probably ipso-protonated 5iv. Nevertheless, they are not substrates for the cyclization due to positive charge repulsion between the benzenium cation and the iminium cation. A more facile ring protonation is expected in the imines 1f and 1g.
  • 53
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    • note
    • 1 at 23°C, we could not exclude as contribution of C,N-diprotonated species such as 6i-6iii matrix presented as well as ipso-protonated 6iv which might be activated electrophiles due to conjugate positive ion centers. Relevant dications can also be formed in the cases of the imines 1f and 1g.
  • 54
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    • note
    • The electrophilic reactivity of imines is known to be increased by N-acylation or N-sulfonylation, so-called amidoalkylation. The proposed intermediates of the amidoalkylation are N-acyliminium ions or N-sulfonyliminium ions, which are activated to react with nitrobenzene. The ammonium group of the dication 4 acts as an acyl-nitrogen atom or a sulfonyl-nitrogen atom.
  • 57
  • 66
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    • note
    • 1 of the monocations 3c, 3f, and 3g would be similar to each other. If the N,C-protonation process is rate-determining, the cyclization rates of 1c, 1f, and 1g would not be modified. This is in disagreement with the observed acceleration, 1g > 1f > 1c.
  • 67
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    • note
    • The reaction of 1h in TFA at 72°C is significantly faster than those of 1a, 1f, and 1g under the same reaction conditions (Table 1). Thus, in the monocationic cyclization in TFA, the cyclization process is also involved in the rate-determining process.
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    • Reduction of nitriles to the corresponding amines was carried out in the presence of a Lewis acid. See: Nystrom, R. B. J. Am. Chem. Soc. 1955, 77, 2544-2545.
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