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Volumn 76, Issue 8, 2011, Pages 2635-2647

Asymmetric synthesis of 1,3-diamines. II: Diastereoselective reduction of atropisomeric N-tert -butanesulfinylketimines

Author keywords

[No Author keywords available]

Indexed keywords

ASYMMETRIC SYNTHESIS; ATROPISOMERS; DIASTEREOSELECTIVE REDUCTION; ENERGY OF ACTIVATION;

EID: 79953908279     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo1025767     Document Type: Article
Times cited : (26)

References (78)
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    • For preparation of ketones 3a - f, see the Experimental Section.
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    • Introduction of ortho-substituents in acetophenone imine results in a marked change in isomeric preference from E to Z form (with respect to the unsubstituted imine); see: Bjørgo, J.; Boyd, D. R.; Watson, C. G.; Jennings, W. B. J. Chem. Soc., Perkin Trans. 2 1974, 757
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    • Stabilization of the E -isomer of ortho-substituted diaryl sulfinylimines by the intramolecular hydrogen bond has been recently demonstrated: see ref 11.
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    • It is well-documented that in the solid state the rotational barriers are larger than in solutions. For selected examples, see: Riddell, F. G.; Arumagam, S.; Harris, K. D. M.; Rogerson, M.; Strange, J. H. J. Am. Chem. Soc. 1993, 115, 1881
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    • For NMR spectra see the Supporting Information, p S10.
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    • Configuration of (Z)-(M)- 4f was confirmed by X-rays analysis.
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    • For a list of chemical shifts see the Supporting Information (Table S1, p S9)
    • For a list of chemical shifts see the Supporting Information (Table S1, p S9).
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    • note
    • 3- d) = 0.6 ppm) confirms the absence of the intramolecular hydrogen bond in solutions. A relative energy of (P) and (M) atropisomers of (Z)- 4e was calculated by using the B3LYP/6-31G(d,p) basis set (see the Supporting Information for details).
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    • A series of 2D EXSY spectra were acquired by using the phase-sensitive NOESY pulse sequence to establish reasonable mixing times. A mixing time of 1 s at T = 258 K was subsequently chosen for all 2D EXSY experiments. The rate constants for chemical exchange were calculated from the ratio of diagonal and exchange cross peaks as described in: Perrin, C. L.; Dwyer, T. G. Chem. Rev. 1990, 90, 935
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    • 3 = 333 K). The Gibbs free energy of activation at T = 298 K was calculated from the Eyring plot of the atropisomerization rate constants vs inverse temperature (see the Supporting Information, pp S3-S4, for details)
    • 3 = 333 K). The Gibbs free energy of activation at T = 298 K was calculated from the Eyring plot of the atropisomerization rate constants vs inverse temperature (see the Supporting Information, pp S3-S4, for details).
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    • A cyclic six-membered transition state has been proposed in the reduction of sulfinylketimines with DIBAL: Hose, D. R. J.; Mahon, M. F.; Molloy, K. C.; Raynham, T.; Wills, M. J. Chem. Soc., Perkin Trans. 1 1996, 691
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    • 3ÂTHF at -78 °C (Conditions A: Table 3, entries 11 and 14)
    • 3ÂTHF at -78 °C (Conditions A: Table 3, entries 11 and 14).
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    • 8, 3 h) as evidenced by NMR (see the Supporting Information, p S7, for details)
    • 8, 3 h) as evidenced by NMR (see the Supporting Information, p S7, for details).
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    • The atropisomerization barrier of 97.9 kJ/mol at 25 °C (see Table 2) corresponds to an isomerization half-life (conversion of a pure atropisomer (Z)-(P)- 4f to a (P):(M)=75:25 mixture) of 4.3 h. In fact, the actual (P)(M) isomerization rate is higher because the backward (M)(P) transformation is suppressed due to the rapid reduction of the more reactive atropisomer (Z)-(M)- 4f immediate upon forming
    • The atropisomerization barrier of 97.9 kJ/mol at 25 °C (see Table 2) corresponds to an isomerization half-life (conversion of a pure atropisomer (Z)-(P)- 4f to a (P):(M)=75:25 mixture) of 4.3 h. In fact, the actual (P)(M) isomerization rate is higher because the backward (M)(P) transformation is suppressed due to the rapid reduction of the more reactive atropisomer (Z)-(M)- 4f immediate upon forming.
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    • 8 solution under the reduction conditions
    • 8 solution under the reduction conditions.
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    • S, S)- 7d was confirmed by X-ray analysis (see the Supporting Information)
    • S, S)- 7d was confirmed by X-ray analysis (see the Supporting Information).
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    • To avoid isomerization of individual atropisomers in eluate, collected fractions were cooled to -78 °C (dry ice-acetone bath)
    • To avoid isomerization of individual atropisomers in eluate, collected fractions were cooled to -78 °C (dry ice-acetone bath).


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