RESEARCH ARTICLE

 

Synthesis of novel 3-hydroxy-3-pyridylcamphor derivatives

 

 

Grant A. Boyle^I; Thavendran Govender^II; Hendrik G. Kruger^I; Glenn E.M. Maguire^I

^ISchool of Chemistry, University of KwaZulu-Natal, Durban, 4041, South Africa
^IISchool of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, 4041, South Africa

 

 

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ABSTRACT

The synthesis of a series of five novel precursor compounds derived from (R)-(+)-camphor is reported. From these precursors, a further four novel pyridyl alcohol ligands were synthesized. The molecules represent the first reported examples where the pyridyl and hydroxyl moieties are pendant on the C3 position of the camphor skeleton. The regioselective synthesis was investigated and an efficient method was identified. The final ligands were obtained in moderate yield with absolute regio- and stereoselective control. The molecules were screened as catalysts in the alkylation of aldehydes with diethylzinc in order to compare the new arrangement of donor groups with previously reported results obtained with C2 pendant ligands. The results demonstrated a significant improvement for the synthesized C3 pendant ligands over previous C2 examples with moderate yields and up to 85 % ee being obtained.

Key words: Chiral, camphor ligands, pyridyl alcohols, asymmetric alkylation reactions

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Acknowledgements

This work was supported by grants from the National Research Foundation, Gun 2046819 (South Africa), Aspen Pharmacare and the University of KwaZulu-Natal.

 

References

1 P.I. Arvidsson, T. Govender, H.G. Kruger, G.E.M. Maguire and T. Naicker, S. Afr. J. Chem., 2009, 62, 60-66.         [ Links ]

2 K.B. Sharpless, W. Amberg, M. Beller, H. Chen, J. Hartung, Y. Kawanami, D. Lubben, E. Manoury, Y. Ogino, T. Shibata and T. Ukita, J. Org. Chem., 1991, 56, 4585-4588.         [ Links ]

3 K.B. Sharpless, Angew. Chem, Int. Ed. Engl, 2002, 41, 2024-2032.         [ Links ]

4 J.S. Johnson and D.A. Evans, Acc. Chem. Res., 2000, 33, 325-335.         [ Links ]

5 D.A. Evans, G. Helmchen, M. Ruping and J. Wolfgang, Asymmetric Synthesis, 2007, 3-9.         [ Links ]

6 M. Kitamura, S. Suga, K. Kawai and R. Noyori, J. Am. Chem. Soc., 1986, 108, 6071-6072.         [ Links ]

7 G. Chelucci, Chem. Soc. Rev., 2006, 35, 1230-1243.         [ Links ]

8 G. Chelucci and F. Soccolini, Tetrahedron: Asymmetry, 1992, 3, 1235-1238.         [ Links ]

9 M. Genov, K. Kostova and V Dimitrov, Tetrahedron: Asymmetry, 1997, 8, 1869-1876.         [ Links ]

10 H.-L. Kwong and W.-S. Lee, Tetrahedron: Asymmetry, 1999, 10, 3791-3801.         [ Links ]

11 W.-S. Lee, H.-L. Kwong, H.-L. Chan, W.-W. Choi and L.-Y. Ng, Tetrahedron: Asymmetry, 2001, 12, 1007-1013.         [ Links ]

12 M. Nevalainen and V. Nevalainen, Tetrahedron: Asymmetry, 2001, 12, 1771-1777.         [ Links ]

13 Q. Xu, X. Wu, X. Pan, A.S.C. Chan and T.-K. Yang, Chirality, 2002, 14, 28-31.         [ Links ]

14 T. Bunlaksananusorn and P. Knochel, J. Org. Chem., 2004, 69, 4595-4601.         [ Links ]

15 H. Takeshita, T. Muroi and S. Ito, Bull. Chem. Soc. Japan, 1969, 42, 2068-2069.         [ Links ]

16 P.-F. Xu, Y.-S. Chen, S.-I. Lin and T.-J. Lu, J. Org. Chem., 2002, 67, 2309-2314.         [ Links ]

17 M.D. Evans and P.T. Kaye, Synth. Commun., 1999, 29, 2137-2146.         [ Links ]

18 M. Evans and P. Kaye, Synth. Commun., 2001, 31, 805-815.         [ Links ]

19 M.D. Evans, P.T. Kaye and L. Cook, S. Afr. J. Chem., 2000, 53, 90-95.         [ Links ]

20 H. Lachance, M. St-Onge and D.G. Hall, J. Org. Chem., 2005, 70, 4180-4183.         [ Links ]

21 I. Fleming and R.B. Woodward, J. Chem. Soc. C, 1968, 10, 1289-1291.         [ Links ]

22 G.A. Boyle, T. Govender, H.G. Kruger and G.E.M. Maguire, Acta Cryst., 2007, E63, o3765.         [ Links ]

23 V. Dimitrov, S. Bratovanov, S. Simova and K. Kostova, Tetrahedron Lett., 1994, 35, 6713-6716.         [ Links ]

24 V. Dimitrov, K. Kostova and M. Genov, Tetrahedron Lett., 1996, 37, 6787-6790.         [ Links ]

25 T. Herold, U. Schrott and R.W. Hoffmann, Chem. Ber., 1981, 114, 359-374.         [ Links ]

 

 

Received 19 February 2009
Revised 29 April 2009
Accepted 13 May 2009

 

 

* To whom correspondence should be addressed. E-mail: kruger@ukzn.ac.za