A C ₂-Symmetric Metallocene-Pyrrolidinopyridine Nucleophilic Catalyst for Asymmetric Synthesis

Abstract

A C ₂-symmetric nucleophilic catalyst, (R,R)-3,5-diferrocenyl-4-(2′,5′-dimethylpyrrolidino)pyridine, was synthesised in three steps from commercially available (S,S)-hexane-2,5-diol. ­Application to the kinetic resolution of secondary alcohols (0.5 mol% loading) resulted in selectivity factors (s) of up to 6.

Key words

alcohols - asymmetric catalysis - kinetic resolution - metallocenes - nucleophiles

References and Notes

• For reviews on achiral 4-aminopyridine nucleophilic catalysts, see:
• 1a Scriven EFV. Chem. Soc. Rev.  1983,  12:  129 
• 1b Grondal C. Synlett  2003,  1568 
• 1c Murugan R. Scriven EFV. Aldrichimica Acta  2003,  36:  21 
• For reviews on chiral 4-aminopyridine nucleophilic catalysts, see:
• 2a Fu GC. Acc. Chem. Res.  2004,  37:  542 
• 2b Spivey AC. Maddaford A. Redgrave A. Org. Prep. Proced. Int.  2000,  32:  331 
• 2c Connon SJ. Lett. Org. Chem.  2006,  3:  333 
• 3 Nguyen HV. Butler DCD. Richards CJ. Org. Lett.  2006,  8:  769 
• 4a Whitesell JK. Chem. Rev.  1989,  89:  1581 
• 4b Najdi S. Kurth MJ. Tetrahedron Lett.  1990,  31:  3279 
• 5a Naraku G. Shimomoto N. Hanamoto T. Inanaga J. Enantiomer  2000,  5:  135 
• 5b Spivey AC. Maddaford A. Fekner T. Redgrave AJ. Frampton CS. J. Chem. Soc., Perkin Trans. 1  2000,  3460 
• 6 Lieser JK. Synth. Commun.  1983,  13:  765 
• 7 Canibano V. Rodríguez JF. Santos M. Sanz-Tejedor MA. Carreno MC. González G. García-Ruano JL. Synthesis  2001,  2175 
• 8 Guillaneux D. Kagan HB. J. Org. Chem.  1995,  60:  2502 
• 9 Mee SPH. Lee V. Baldwin JE. Angew. Chem. Int. Ed.  2004,  43:  1132 
• 12 Hassner A. Krepski LR. Alexanian V. Tetrahedron  1978,  34:  2069 
• Toluene has frequently been found to be one of the best solvents for this reaction, for example see:
• 13a Ruble JC. Tweddell J. Fu GC. J. Org. Chem.  1998,  63:  2794 
• 13b Priem G. Pelotier B. Macdonald SJF. Anson MS. Campbell IB. J. Org. Chem.  2003,  68:  3844 
• 14a Spivey AC. Arseniyadis S. Angew. Chem. Int. Ed.  2004,  43:  5436 
• 14b Xu S. Held I. Kempf B. Mayr H. Steglich W. Zipse H. Chem. Eur. J.  2005,  11:  4751 

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Nguyen, H. V.; Motevalli, M.; Richards, C. J. manuscript in preparation.

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Crystal data of 2.
C₃₂H₃₃Cl₃Fe₂N₂, M = 663.65, orthorhombic, a = 7.3563(2), b = 17.9280(6), c = 21.8849(7) Å, α = 90°, β = 90°, γ = 90°, V = 2886.26(15) ų, space group P2₁2₁2₁, Z = 4, D _c = 1.527 mg/m³, µ = 1.309 mm^-1, reflections measured 21200, reflections unique 6560 with R _int = 0.0495, T = 120 (2) K, final R indices [F² >2σ(F²)] R1 = 0.0370, wR2 = 0.0670 and for all data R1 = 0.0457, wR2 = 0.0701 (CCDC 619938).