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Volumn 127, Issue 24, 2005, Pages 8817-8825

Combined ruthenium(II) and lipase catalysis for efficient dynamic kinetic resolution of secondary alcohols. Insight into the racemization mechanism

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSIS; COMPLEXATION; ENZYMES; ETHANOL; KETONES; SYNTHESIS (CHEMICAL); X RAY ANALYSIS;

EID: 21044443212     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja051576x     Document Type: Article
Times cited : (277)

References (102)
  • 3
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    • Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin
    • (c) Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999.
    • (1999) Comprehensive Asymmetric Catalysis
  • 20
    • 21044459921 scopus 로고    scopus 로고
    • See ref 5a
    • (e) See ref 5a.
  • 22
    • 0001079960 scopus 로고    scopus 로고
    • For a related DKR of amines see: Reetz, M. T.; Schimossek, K. Chimia 1996, 50, 668-669.
    • (1996) Chimia , vol.50 , pp. 668-669
    • Reetz, M.T.1    Schimossek, K.2
  • 64
    • 21044442051 scopus 로고    scopus 로고
    • note
    • A slightly modified method was employed for the synthesis of 4 (R = Ph, R′ = Me). See Supporting Information for details.
  • 65
    • 0001531956 scopus 로고
    • In the case of Cp and Cp* complete transformation to the corresponding ruthenium dimers occurs after only 3 h. See for example: (a) Nelson, G. O.; Sumner, C. E. Organometallics 1986, 5, 1983-1990.
    • (1986) Organometallics , vol.5 , pp. 1983-1990
    • Nelson, G.O.1    Sumner, C.E.2
  • 68
    • 21044441115 scopus 로고    scopus 로고
    • note
    • Complete details of the X-ray analysis are given in the crystal structure analysis report in the Supporting Information.
  • 70
    • 21044434425 scopus 로고    scopus 로고
    • note
    • Immobilized and commercially available as Novozym-435.
  • 71
    • 21044453256 scopus 로고    scopus 로고
    • note
    • To control the water activity, the enzyme was stored in a sealed container with a saturated solution of LiCl for a minimum of 24 h.
  • 76
    • 21044445404 scopus 로고    scopus 로고
    • note
    • Reduction of 2-hexanone using catalytic hydrogenation gives 96% yield of the alcohol in 75% ee, and reduction of 2-nonanone gives the alcohol in 100% yield, 1% ee. See ref 36.
  • 83
    • 0034720945 scopus 로고    scopus 로고
    • DKR of allylic alcohols at room temperature has been previously reported, but longer reaction times (48 h) were needed: Lee, D.; Huh, E. A.; Kim, M.-J.; Jung, H. M.; Koh, J. H.; Park, J. Org. Lett. 2000, 2, 2377-2379.
    • (2000) Org. Lett. , vol.2 , pp. 2377-2379
    • Lee, D.1    Huh, E.A.2    Kim, M.-J.3    Jung, H.M.4    Koh, J.H.5    Park, J.6
  • 85
    • 4644221820 scopus 로고    scopus 로고
    • (b) For a recent synthesis of (R)-sulcatol and (2S,5R)-pityol see: Chen, S.-L.; Hu, Q.-Y.; Loh, T.-P. Org. Lett. 2004, 6, 3365-3367.
    • (2004) Org. Lett. , vol.6 , pp. 3365-3367
    • Chen, S.-L.1    Hu, Q.-Y.2    Loh, T.-P.3
  • 87
    • 21044451372 scopus 로고    scopus 로고
    • Ru-alkoxide complexes: (a) ref 28
    • Ru-alkoxide complexes: (a) ref 28
  • 90
    • 21044459440 scopus 로고    scopus 로고
    • (c) Ru-alcohol complex: See ref 27a
    • (c) Ru-alcohol complex: See ref 27a.
  • 91
    • 2942544978 scopus 로고    scopus 로고
    • and references therein
    • W-alcohol and Mo-alcohol complexes: Bullock, R. M. Chem. Eur. J. 2004, 10, 2366-2374 and references therein.
    • (2004) Chem. Eur. J. , vol.10 , pp. 2366-2374
    • Bullock, R.M.1
  • 92
    • 21044456421 scopus 로고    scopus 로고
    • note
    • The mixture was analyzed by chiral GC.
  • 93
    • 21044459763 scopus 로고    scopus 로고
    • note
    • 13C NMR spectra in Supporting Information.
  • 94
    • 21044446339 scopus 로고    scopus 로고
    • note
    • See Experimental Section for details.
  • 95
    • 21044437003 scopus 로고    scopus 로고
    • note
    • The possible pathways for alkoxide exchange include: (i) ring slippage, (ii) alkoxide loss, (iii) CO loss, (iv) alkoxide attack at CO followed by alkoxide loss.
  • 96
    • 21044443698 scopus 로고    scopus 로고
    • note
    • As shown in Figure 3, the racemization of (S)-9 catalyzed by complexes 3a-c can be performed by the use of only 0.5 mol % of catalyst with short reaction times. In sharp contrast, the racemization of (S)-9 catalyzed by 1 mol % of ruthenium hydride 8 (in the presence of 1 mol % acetophenone) required very long reaction times (1.5 days). Only when 5 mol % of ruthenium hydride 8 was used (in the presence of 5 mol % of acetophenone) could shorter reaction times be realized but still with an induction period of 2.5 h (Figure 5).
  • 100
    • 21044433534 scopus 로고    scopus 로고
    • note
    • Other conceivable mechanisms are hydride migration to the cyclopentadienyl ring and hydride migration to CO to give a formyl intermediate. We are currently investigating the mechanism of this remarkable C-H bond cleavage in our laboratories.
  • 101
    • 21044453255 scopus 로고    scopus 로고
    • note
    • If the ketone from β-elimination were only π-bonded no racemization could take place, since the hydride would readd to the same enantioface from which it was eliminated.
  • 102
    • 21044442469 scopus 로고    scopus 로고
    • note
    • An interesting question is why the ring slippage readily occurs for the alkoxide in β-elimination and not for the hydride in its reaction with a ketone. This is probably due to that the ketone is not nucleophilic enough to induce a ring slip. In the alkoxide the C-H can interact with ruthenium and induce a push of electrons to favor the ring slip.


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