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Volumn 74, Issue 14, 2009, Pages 5107-5110

New strategy for the synthesis of substituted morpholines

Author keywords

[No Author keywords available]

Indexed keywords

ALKENYL; AMINO ALCOHOLS; CHEMICAL EQUATIONS; ETHANOLAMINE; FOUR-STEP SYNTHESIS; GOOD YIELD; MORPHOLINE; MORPHOLINES; NEW STRATEGY;

EID: 67650351948     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9007223     Document Type: Article
Times cited : (78)

References (41)
  • 2
    • 27644585300 scopus 로고    scopus 로고
    • For selected examples of biologically active cis-3,5-disubstituted morpholines, see: (a) O'Neil, S. V.; Wang, Y.; Laufersweiler, M. C.; Oppong, K. A.; Soper, D. L.; Wos, J. A.; Ellis, C. D.; Baize, M. W.; Bosch, G. K.; Fancher, A. N.; Lu, W.; Suchanek, M. K.; Wang, R. L.; De, B.; Demuth, T. P., Jr. Bioorg. Med. Chem. Lett. 2005, 15, 5434.
    • For selected examples of biologically active cis-3,5-disubstituted morpholines, see: (a) O'Neil, S. V.; Wang, Y.; Laufersweiler, M. C.; Oppong, K. A.; Soper, D. L.; Wos, J. A.; Ellis, C. D.; Baize, M. W.; Bosch, G. K.; Fancher, A. N.; Lu, W.; Suchanek, M. K.; Wang, R. L.; De, B.; Demuth, T. P., Jr. Bioorg. Med. Chem. Lett. 2005, 15, 5434.
  • 4
    • 67650457376 scopus 로고    scopus 로고
    • Josien, H. B, Clader, J. W, Bara, T. A, Xu, R, Li, H, Pissarnitski, D, Zhao, Z. Chem. Abstr. 2006, 144, 129004 PCT Int. Appl. WO 2006004880 A2, January 12, 2006;
    • (c) Josien, H. B.; Clader, J. W.; Bara, T. A.; Xu, R.; Li, H.; Pissarnitski, D.; Zhao, Z. Chem. Abstr. 2006, 144, 129004 PCT Int. Appl. WO 2006004880 A2, January 12, 2006;
  • 5
    • 61449177950 scopus 로고    scopus 로고
    • For recent approaches to the synthesis of C-substituted morpholines, see: a
    • For recent approaches to the synthesis of C-substituted morpholines, see: (a) Yar, M.; McGarrigle, E. M.; Aggarwal, V. K. Org. Lett. 2009, 11, 257.
    • (2009) Org. Lett , vol.11 , pp. 257
    • Yar, M.1    McGarrigle, E.M.2    Aggarwal, V.K.3
  • 10
    • 47049098712 scopus 로고    scopus 로고
    • For stereoselective syntheses of trans-3,5-disubstituted morpholines, see: (a) Leijondahl, K.; Boren, L.; Braun, R.; Bäckvall, J.-E. Org. Lett. 2008, 10, 2027.
    • For stereoselective syntheses of trans-3,5-disubstituted morpholines, see: (a) Leijondahl, K.; Boren, L.; Braun, R.; Bäckvall, J.-E. Org. Lett. 2008, 10, 2027.
  • 13
    • 0000758313 scopus 로고    scopus 로고
    • For non-stereoselective syntheses of 3,5-disubstituted morpholines, see
    • (d) Takahata, H.; Takahashi, S.; Kouno, S.-i.; Momose, T. J. Org. Chem. 1998, 63, 2224. For non-stereoselective syntheses of 3,5-disubstituted morpholines, see:
    • (1998) J. Org. Chem , vol.63 , pp. 2224
    • Takahata, H.1    Takahashi, S.2    Kouno, S.-I.3    Momose, T.4
  • 20
    • 4544265647 scopus 로고    scopus 로고
    • For related syntheses of pyrrolidines, imidazolidin-2-ones, isoxazolidines, and pyrazolidines via Pd-catalyzed carboamination reactions, see: (a) Ney, J. E.; Wolfe, J. P. Angew. Chem., Int. Ed. 2004, 43, 3605.
    • For related syntheses of pyrrolidines, imidazolidin-2-ones, isoxazolidines, and pyrazolidines via Pd-catalyzed carboamination reactions, see: (a) Ney, J. E.; Wolfe, J. P. Angew. Chem., Int. Ed. 2004, 43, 3605.
  • 25
    • 33846644502 scopus 로고    scopus 로고
    • For reviews on Pd-catalyzed carboamination reactions, see: a
    • For reviews on Pd-catalyzed carboamination reactions, see: (a) Wolfe, J. P. Eur. J. Org. Chem. 2007, 571.
    • (2007) Eur. J. Org. Chem , pp. 571
    • Wolfe, J.P.1
  • 27
    • 67650472024 scopus 로고    scopus 로고
    • For a representative reaction sequence, chiral HPLC analysis indicated complete retention of enantiomeric purity (99% ee) during the preparation of substrate 2a from 1a. The Pd-catalyzed carboamination reaction of 2a to 3b also proceeded with no erosion of ee.
    • For a representative reaction sequence, chiral HPLC analysis indicated complete retention of enantiomeric purity (99% ee) during the preparation of substrate 2a from 1a. The Pd-catalyzed carboamination reaction of 2a to 3b also proceeded with no erosion of ee.
  • 28
    • 67650476939 scopus 로고    scopus 로고
    • Use of other ligands provided greater amounts of 5a, led to formation of side products resulting from Heck arylation of the starting material, or both. See the Supporting Information for a table of results obtained with other phosphines.
    • Use of other ligands provided greater amounts of 5a, led to formation of side products resulting from Heck arylation of the starting material, or both. See the Supporting Information for a table of results obtained with other phosphines.
  • 29
    • 67650476938 scopus 로고    scopus 로고
    • Side products of general structure 5 were also observed in crude reaction mixtures. NMR analysis indicated these side products were formed as ca. 10-35% of the mixture. See the Supporting Information for further details.
    • Side products of general structure 5 were also observed in crude reaction mixtures. NMR analysis indicated these side products were formed as ca. 10-35% of the mixture. See the Supporting Information for further details.
  • 30
    • 67650472027 scopus 로고    scopus 로고
    • In some instances side products resulting from sequential N-arylation and Heck arylation of the substrate were also isolated.
    • In some instances side products resulting from sequential N-arylation and Heck arylation of the substrate were also isolated.
  • 31
    • 41849088108 scopus 로고    scopus 로고
    • The known trans-2-(N-phenylamino)cycloalkanols were prepared in one step from aniline and cyclohexene oxide or cyclopentene oxide. See: (a) Wang, Z.; Cui, Y.-T.; Xu, Z.-B.; Qu, J. J. Org. Chem. 2008, 73, 2270.
    • The known trans-2-(N-phenylamino)cycloalkanols were prepared in one step from aniline and cyclohexene oxide or cyclopentene oxide. See: (a) Wang, Z.; Cui, Y.-T.; Xu, Z.-B.; Qu, J. J. Org. Chem. 2008, 73, 2270.
  • 32
    • 34447117685 scopus 로고    scopus 로고
    • Arai, K.; Lucarini, S.; Salter, M.; Ohta, K.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2007, 129, 8103. The cis-2-(N-phenylamino)cycloalkanols were prepared in three steps from the epoxides. See the Supporting Information for further details.
    • (b) Arai, K.; Lucarini, S.; Salter, M.; Ohta, K.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2007, 129, 8103. The cis-2-(N-phenylamino)cycloalkanols were prepared in three steps from the epoxides. See the Supporting Information for further details.
  • 35
    • 67650498156 scopus 로고    scopus 로고
    • Chair-like transition states for intramolecular syn-aminopalladation reactions that generate six-membered rings appear to be less favorable than boatlike transition states due to poor overlap between the alkene π-system and the Pd-N bond. For additional discussion of boat-like vs. chair-like transition states in Pd-catalyzed carboamination reactions that afford piperazine products, see ref 6b
    • Chair-like transition states for intramolecular syn-aminopalladation reactions that generate six-membered rings appear to be less favorable than boatlike transition states due to poor overlap between the alkene π-system and the Pd-N bond. For additional discussion of boat-like vs. chair-like transition states in Pd-catalyzed carboamination reactions that afford piperazine products, see ref 6b.
  • 36
    • 67650506675 scopus 로고    scopus 로고
    • The modest diastereoselectivities observed in the reactions of 8 and 10 are presumably due to relatively small differences in the energies of transition states in which the substrate R-group is oriented in a psueduoaxial vs. pseudoequatorial position. For further discussion, see ref 6b
    • The modest diastereoselectivities observed in the reactions of 8 and 10 are presumably due to relatively small differences in the energies of transition states in which the substrate R-group is oriented in a psueduoaxial vs. pseudoequatorial position. For further discussion, see ref 6b.
  • 39
    • 12344337689 scopus 로고    scopus 로고
    • The rate of reductive elimination from Pd(II) decreases as ligand basicity increases and ligand size decreases. However, steric effects can outweigh electronic effects, as electron-rich ligands that are sterically bulky are known to promote reductive elimination. For reviews, see: (a) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.
    • The rate of reductive elimination from Pd(II) decreases as ligand basicity increases and ligand size decreases. However, steric effects can outweigh electronic effects, as electron-rich ligands that are sterically bulky are known to promote reductive elimination. For reviews, see: (a) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.
  • 41
    • 33846797894 scopus 로고    scopus 로고
    • IPr = 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene. Although this electron-rich ligand is also sterically bulky, it appears that ligand electronic properties play a larger role than steric properties in this particular reaction. For further discussion on the steric and electronic properties of NHC ligands, see: Diez-Gonzalez, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251, 874.
    • IPr = 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene. Although this electron-rich ligand is also sterically bulky, it appears that ligand electronic properties play a larger role than steric properties in this particular reaction. For further discussion on the steric and electronic properties of NHC ligands, see: Diez-Gonzalez, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251, 874.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.