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Volumn 46, Issue 24, 2007, Pages 4534-4538

Efficient enantioselective synthesis of piperidines through catalytic asymmetric ring-opening/cross-metathesis reactions

Author keywords

Asymmetric catalysis; Molybdenum; Olefin metathesis; Piperidines; Ruthenium

Indexed keywords

CATALYSTS; CHIRALITY; ENANTIOMERS; FUNCTIONAL ANALYSIS; MOLYBDENUM; OLEFINS; RING OPENING POLYMERIZATION; SYNTHESIS (CHEMICAL);

EID: 34250718022     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200605130     Document Type: Article
Times cited : (79)

References (48)
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    • For catalytic asymmetric ring-closing metathesis processes that deliver N-containing heterocycles, see: a
    • For catalytic asymmetric ring-closing metathesis processes that deliver N-containing heterocycles, see: a) S. J. Dolman, E. S. Sattely, A. H. Hoveyda, R. R. Schrock, J. Am. Chem. Soc. 2002, 124, 6991-6997;
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    • For representative asymmetric ring-closing metathesis reactions promoted by chiral Mo complexes, see: a
    • For representative asymmetric ring-closing metathesis reactions promoted by chiral Mo complexes, see: a) J. B. Alexander, D. S. La, D. R. Cefalo, A. H. Hoveyda, R. R. Schrock, J. Am. Chem. Soc. 1998, 120, 4041-4042;
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    • For asymmetric ring-closing metathesis reactions promoted by Ru-based catalysts, see: a
    • For asymmetric ring-closing metathesis reactions promoted by Ru-based catalysts, see: a) T. J. Seiders, D. W. Ward, R. H. Grubbs, Org. Lett. 2001, 3, 3225-3228;
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    • For Mo-catalyzed AROM/CM reactions, see: a) G. S. Weatherhead, J. G. Ford, E. J. Alexanian, R. R. Schrock, A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 1828-1829;
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    • a recent report provides examples of catalytic AROM/CM of selected norbornene-derived substrates and styrene with chiral monodentate Ru-NHC complexes, albeit with little or no E:Z selectivity (1-1.4:1) and only up to 80% ee for the E product isomer (4-50% ee for Z isomers): f) J. M. Berlin, S. D. Goldberg, R. H. Grubbs, Angew. Chem. 2006, 118, 7753-7757;
    • a recent report provides examples of catalytic AROM/CM of selected norbornene-derived substrates and styrene with chiral monodentate Ru-NHC complexes, albeit with little or no E:Z selectivity (1-1.4:1) and only up to 80% ee for the E product isomer (4-50% ee for Z isomers): f) J. M. Berlin, S. D. Goldberg, R. H. Grubbs, Angew. Chem. 2006, 118, 7753-7757;
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    • For a review on olefin metathesis methods for synthesis of heterocycles, see
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    • For applications of catalytic olefin metathesis (non-asymmetric) to total synthesis of piperidine-containing natural products, see: a
    • For applications of catalytic olefin metathesis (non-asymmetric) to total synthesis of piperidine-containing natural products, see: a) S. Randl, S. Blechert, J. Org. Chem. 2003, 68, 8879-8882;
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    • Attempts to circumvent N-Ru complexation through protonation of the substrate's Lewis basic amine resulted in substrate decomposition (presumably due to cleavage of the allylic C-N bond).
    • Attempts to circumvent N-Ru complexation through protonation of the substrate's Lewis basic amine resulted in substrate decomposition (presumably due to cleavage of the allylic C-N bond).
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    • nMo=C} is converted to a terminal olefin) and another molecule of 7 (vs. reaction with styrene to afford 8).
    • nMo=C} is converted to a terminal olefin) and another molecule of 7 (vs. reaction with styrene to afford 8).
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    • Molecular models indicate that substrates bearing an exo heteroatom substituent (substrate corresponding to 20) can cause the amide group to be situated in a manner that hinders approach of the bulky Ru carbene from the exo face of the cyclic olefin.
    • Molecular models indicate that substrates bearing an exo heteroatom substituent (substrate corresponding to 20) can cause the amide group to be situated in a manner that hinders approach of the bulky Ru carbene from the exo face of the cyclic olefin.
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    • Preliminary experiments indicate that hydroalumination of 28 is directed by the hydroxyl (vs. the amine) group. Thus, subjection of piperidine 23 to the same reaction conditions only results in carbamate reduction, and the corresponding pyrans bearing the primary alcohol undergo hydroalumination. For a review of substrate-directed reactions, see: a) A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev. 1993, 93, 1307-1360;
    • Preliminary experiments indicate that hydroalumination of 28 is directed by the hydroxyl (vs. the amine) group. Thus, subjection of piperidine 23 to the same reaction conditions only results in carbamate reduction, and the corresponding pyrans bearing the primary alcohol undergo hydroalumination. For a review of substrate-directed reactions, see: a) A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev. 1993, 93, 1307-1360;
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    • for examples of hydroxyl-directed hydraoluminations, see: b
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    • In addition, primary alcohol 28 is obtained in 45% yield. Formation of 28 is not due to the presence of adventitious moisture. When the reaction (O2 quench) is worked up with MeOD, D 1]-28 is generated as the exclusive by-product. A portion of the alkylaluminum intermediate might exist in a less reactive oligomeric form
    • 1]-28 is generated as the exclusive by-product. A portion of the alkylaluminum intermediate might exist in a less reactive oligomeric form.
  • 48
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    • As reported previously, β-amino ketones such as 31 are subject to facile epimerization, presumably through an elimination/ intramolecular conjugate addition process; see: R. W. Bates, K. Sa-Ei, Tetrahedron 2002, 58, 5957-5978.
    • As reported previously, β-amino ketones such as 31 are subject to facile epimerization, presumably through an elimination/ intramolecular conjugate addition process; see: R. W. Bates, K. Sa-Ei, Tetrahedron 2002, 58, 5957-5978.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.