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Volumn , Issue 3, 2008, Pages 524-531

Stereoselective synthesis of (2S,4R)-4-hydroxypipecolic acid

Author keywords

Amino acids; Carbonylation; Hydrogenation; Lactams; Natural products

Indexed keywords


EID: 38849090679     PISSN: 1434193X     EISSN: 10990690     Source Type: Journal    
DOI: 10.1002/ejoc.200700849     Document Type: Article
Times cited : (22)

References (64)
  • 23
    • 23944496414 scopus 로고    scopus 로고
    • for a recent review on the asymmetric synthesis of pipecolic acids and its derivatives, see: k
    • for a recent review on the asymmetric synthesis of pipecolic acids and its derivatives, see: k) C. Kadouri-Puchot, S. Comesse, Amino Acids 2005, 29, 101-130;
    • (2005) Amino Acids , vol.29 , pp. 101-130
    • Kadouri-Puchot, C.1    Comesse, S.2
  • 32
    • 38849144569 scopus 로고    scopus 로고
    • As both the enantiomers (96 % ee) of ethyl 4-chloro-3- hydroxybutanoate are commercially available, the synthesis can be extended to the (2R,4S) enantiomer of 4-hydroxypipecolic acid.
    • As both the enantiomers (96 % ee) of ethyl 4-chloro-3- hydroxybutanoate are commercially available, the synthesis can be extended to the (2R,4S) enantiomer of 4-hydroxypipecolic acid.
  • 35
    • 2942555626 scopus 로고    scopus 로고
    • for a review on the stability and reactivity of lactam-derived vinyl triflates, see: b
    • for a review on the stability and reactivity of lactam-derived vinyl triflates, see: b) E. G. Occhiato, Mini-Rev. Org. Chem. 2004, 1, 149-162.
    • (2004) Mini-Rev. Org. Chem , vol.1 , pp. 149-162
    • Occhiato, E.G.1
  • 38
    • 0034719260 scopus 로고    scopus 로고
    • 2 catalyst and other catalysts has been employed to create the C-2 stereocenter in the enantioselective synthesis of unsubstituted pipecolic acids. For examples, see: a) T. J. Wilkinson, N. W. Stehle, P. Beak, Org. Lett. 2000, 2, 155-158;
    • 2 catalyst and other catalysts has been employed to create the C-2 stereocenter in the enantioselective synthesis of unsubstituted pipecolic acids. For examples, see: a) T. J. Wilkinson, N. W. Stehle, P. Beak, Org. Lett. 2000, 2, 155-158;
  • 42
    • 38849098367 scopus 로고    scopus 로고
    • Compound 14 has the following 1H NMR (CDCl3, 200 MHz) data: δ, 3.82 (s, 3 H, OCH3, 4.38 (dd, J, 4.1, 1.5 Hz, 2 H, CH2N, 5.74 (d, J, 5.5 Hz, 1 H, 3-H, 5.77-5.83 (m, 1 H, 4-H, 5.99-6.04 (m, 1 H, 5-H) ppm. In compounds 15a and 15b 3-H is strongly shielded (4.60 and 4.93 ppm, respectively) as a silyloxy group is at C-2 in place of the electron-withdrawing OTf group. Accordingly, in the 13C NMR spectrum of 15b, C-3 is shifted upfield and resonates at δ, 94.0 ppm. Compound 15b has the following 1H NMR (CDCl3, 200 MHz) data: δ, 0.20 [s, 6 H, Si(CH3)2, 0.95 [s, 9 H, SiC(CH3)3, 3.74 (s, 3 H, OCH 3, 4.23 (dd, J, 4.4, 1.0 Hz, 2 H, CH2N, 4.93 (d, J, 5.5 Hz, 1 H, 3-H, 5.39-5.47 (m, 1 H, 4-H, 5.88-5.97 (m, 1 H, 5-H) ppm
    • 2N), 4.93 (d, J = 5.5 Hz, 1 H, 3-H), 5.39-5.47 (m, 1 H, 4-H), 5.88-5.97 (m, 1 H, 5-H) ppm. The formation of 15a and 15b represents quite an anomalous migration of the silyl-protecting group which could have occurred intermolecularly.
  • 45
    • 38849163544 scopus 로고    scopus 로고
    • An electron-withdrawing group is necessary to confer stability to the triflate (see ref.[9, We chose the methoxycarbonyl group as the final product before exhaustive hydrolysis is known in racemic form see ref.[21
    • [21]).
  • 47
    • 38849108087 scopus 로고    scopus 로고
    • It is known that in piperidines that bear an alkoxycarbonyl or a tosyl group on the N atom, 2-alkyl substituents are preferentially pseudoaxially oriented in order to reduce the allylic strain with the N-protecting group. Much chemistry has been based on this feature which strongly affects the stereochemical outcome of additions to the enamine double bond: a D. L. Comins, S. P. Joseph in Advances in Nitrogen Heterocycles (Ed.: C. J. Moody), JAI Press, Greenwich, CT, 1996, 2, pp. 251-294;
    • It is known that in piperidines that bear an alkoxycarbonyl or a tosyl group on the N atom, 2-alkyl substituents are preferentially pseudoaxially oriented in order to reduce the allylic strain with the N-protecting group. Much chemistry has been based on this feature which strongly affects the stereochemical outcome of additions to the enamine double bond: a) D. L. Comins, S. P. Joseph in Advances in Nitrogen Heterocycles (Ed.: C. J. Moody), JAI Press, Greenwich, CT, 1996, vol. 2, pp. 251-294;
  • 52
    • 38849111223 scopus 로고    scopus 로고
    • A small amount of trans-24 was obtained by selective protection as the TBDPS ether (TBDPSCl, imidazole, DMF, 45°C, 2 h) of the less hindered OH group of the minor trans isomer 21 present in the mixture (with the cis compound) obtained after hydrogenation of (R)-20. 1H NMR (CDCl3, 400 MHz, δ, 1.04 [s, 9 H, SiC(CH3)3, 1.50-1.57 (m, 1 H, 5ax-H, 1.71 (ddd, J, 17.6, 11.1, 6.1 Hz, 1 H, 3ax-H, 1.72-1.84 (m, 1 H, 5eq-H, 2.21-2.30 (br. m, 1 H, 3eq-H, 2.81-3.00 (m, 1 H, 6ax-H, 3.49 (s, 3 H, C-CO2CH3, 3.57-3.65 (m, 1 H, 4-H, 3.66 and 3.69 (s, 3 H, two rotamers, N-CO 2CH3, 3.90 (br. d, J, 13.2 Hz, major rotamer, 6eq-H) and 4.08 (br. d, J, 12.1 Hz, minor rotamer, 6eq-H, 4.75 (br. s, minor rotamer, 2eq-H, 4.90 br. s, major r
    • arom) ppm.
  • 55
    • 38849106842 scopus 로고    scopus 로고
    • 3, 200 MHz) are diagnostic of the trans isomer: δ = 1.33-1.47 (m, 1 H), 2.96-3.11 (m, 1 H), 4.11-3.98 (m, 1 H), 5.04 and 4.88 (br. s, two rotamers) ppm.
    • 3, 200 MHz) are diagnostic of the trans isomer: δ = 1.33-1.47 (m, 1 H), 2.96-3.11 (m, 1 H), 4.11-3.98 (m, 1 H), 5.04 and 4.88 (br. s, two rotamers) ppm.
  • 56
    • 38849142559 scopus 로고    scopus 로고
    • This was demonstrated by treating the diastereomeric 2.4:1 mixture of cis- and trans-21 with TBAF in THF at room temperature. After 24 h the trans isomer was the major component of the mixture the cis/trans ratio was 1:1.5, Deprotection of 24 with HF-pyridine in THF left the starting material unaltered after 24 h at room temperature
    • This was demonstrated by treating the diastereomeric 2.4:1 mixture of cis- and trans-21 with TBAF in THF at room temperature. After 24 h the trans isomer was the major component of the mixture (the cis/trans ratio was 1:1.5). Deprotection of 24 with HF-pyridine in THF left the starting material unaltered after 24 h at room temperature.
  • 64
    • 0026637008 scopus 로고    scopus 로고
    • Reported spectroscopic and analytical data for cis-(±, 1·HCl: m.p. 203°C (dec, 1H NMR (CD3OD, 200 MHz, δ, 1.60-1.78 (m, 2 H, 3ax-H and 5ax-H, 2.10 (m, J, 13.9 Hz, 1 H, 5eq-H, 2.38 (m, J, 13.5Hz, 1 H, 3eq-H, 3.08 (td, J, 12.9, 3.2 Hz, 1 H, 6ax-H, 3.49 (td, J, 12.9, 3.9 Hz, 1 H, 6eq-H, 3.92 (m, 1 H, 4 ax-H, 4.06 (dd, J, 12.0, 3.5 Hz, 1 H, 2ax-H) ppm. 13C NMR (CD3OD) δ, 31.66 (t, C-5, 35.54 (t, C-3, 42.58 (t, C-6, 56.55 (d, C-2, 65.83 (d, C-4, 170.77 (s, C=O) ppm. C. Herdeis, W. Engel, Arch. Pharm. 1992, 325, 419-423
    • 3OD) δ = 31.66 (t, C-5), 35.54 (t, C-3), 42.58 (t, C-6), 56.55 (d, C-2), 65.83 (d, C-4), 170.77 (s, C=O) ppm. C. Herdeis, W. Engel, Arch. Pharm. 1992, 325, 419-423.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.