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for a recent review on the asymmetric synthesis of pipecolic acids and its derivatives, see: k
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38849144569
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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.
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35
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2942555626
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for a review on the stability and reactivity of lactam-derived vinyl triflates, see: b
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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.
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38
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0034719260
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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;
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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;
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M. K. S. Vink, C. A. Schortinghuis, J. Luten, J. H. van Maarseveen, H. E. Schoemaker, H. Hiemstra, F. P. J. T. Rutjes, J. Org. Chem. 2002, 67, 7869-7871.
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42
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38849098367
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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.
-
-
-
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43
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0029926182
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C. Herdeis, C. Kaschinski, R. Karla, H. Lotter, Tetrahedron: Asymmetry 1996, 7, 867-884.
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45
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38849163544
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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
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[21]).
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46
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0000311627
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S. Cacchi, E. Morera, G. Ortar, Tetrahedron Lett. 1985, 26, 1109-1112.
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Cacchi, S.1
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47
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38849108087
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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;
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0033609875
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d) N. Toyooka, M. Okumura, H. Takahata, H. Nemoto, Tetrahedron 1999, 55, 10673-10684;
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0030961411
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e) T. Luker, H. Hiemstra, W. N. Speckamp, J. Org. Chem. 1997, 62, 3592-3596.
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Luker, T.1
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38849111223
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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.
-
-
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53
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0025730945
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a) P. M. Esch, R. F. de Boer, H. Hiemstra, I. M. Boska, W. N. Speckamp, Tetrahedron 1991, 47, 4063-4076;
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Esch, P.M.1
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0025754760
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b) P. M. Esch, I. M. Boska, H. Hiemstra, R. F. de Boer, W. N. Speckamp, Tetrahedron 1991, 47, 4039-4062.
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Esch, P.M.1
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de Boer, R.F.4
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55
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38849106842
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-
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
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38849142559
-
-
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.
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57
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0003463148
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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
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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.
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