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DOI: 10.1055/s-0030-1259569
Synthesis of trans-4-Triazolyl-Substituted 3-Hydroxypiperidines
Publication History
Publication Date:
03 February 2011 (online)
Abstract
The synthesis of tert-butyl trans-4-ethynyl-3-hydroxypiperidine-1-carboxylate is described via regioselective ring-opening of a racemic N-Boc-protected 7-oxa-3-azabicyclo[4.1.0]heptane, and serves as a new scaffold for the preparation of substituted piperidines. The terminal alkyne is converted into 1,4- and 1,5-disubstituted 1,2,3-triazoles through 1,3-dipolar cycloaddition reactions with organic azides.
Key words
piperidine - epoxide - alkyne - azide - triazole
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Evans BE.Rittle KE.Bock MG.Freidinger RM.Whitter WL.Lundell GF.Veber DF.Anderson PS.Chang RSL.Lotti VJ.Cerino DJ.Chen TB.Kling PJ.Kunkel KA.Springer JP.Hirshfield J. J. Med. Chem. 1988, 31: 2235 - 2a
Mason JS.Morize I.Menard PR.Cheney DL.Hulme C.Labaudiniere RF. J. Med. Chem. 1999, 42: 3251Reference Ris Wihthout Link - 2b
Costantino L.Barlocco D. Curr. Med. Chem. 2006, 13: 65Reference Ris Wihthout Link - 3
Eicher T.Hauptmann S. The Chemistry of Heterocycles: Structure, Reactions, Syntheses and Applications 2nd ed.: Wiley-VCH; Weinheim: 2003. - 4a
Buffat MGP. Tetrahedron 2004, 60: 1701Reference Ris Wihthout Link - 4b
De Risi C.Fanton G.Pollini GP.Trapella C.Valente F.Zanirato V. Tetrahedron: Asymmetry 2008, 19: 131Reference Ris Wihthout Link - 5a
Schramm H.Pavlova M.Hoenke C.Christoffers J. Synthesis 2009, 1659Reference Ris Wihthout Link - 5b
Schramm H.Saak W.Hoenke C.Christoffers J. Eur. J. Org. Chem. 2010, 1745Reference Ris Wihthout Link - 6
Wang D.Nugent WA. J. Org. Chem. 2007, 72: 7307 - 7
Kim BJ.Pyun DK.Jung HJ.Kwak HJ.Kim JH.Kim EJ.Jeong WJ.Lee CH. Synth. Commun. 2001, 31: 1081 - 8
Marquis RW.Yamashita DS.Ru Y.LoCastro SM.Oh H.-J.Erhard KF.DesJarlais RL.Head MS.Smith WW.Zhao B.Janson CA.Abdel-Meguid SS.Tomaszek TA.Levy MA.Veber DF. J. Med. Chem. 1998, 41: 3563 - 9a
Alexakis A.Jachiet D.Normant JF. Tetrahedron 1986, 42: 5607Reference Ris Wihthout Link - 9b
Alexakis A.Jachiet D. Tetrahedron 1989, 45: 6197Reference Ris Wihthout Link - 9c
Skrydstrup T.Bénéchie M.Khuong-Huu F. Tetrahedron Lett. 1990, 31: 7145Reference Ris Wihthout Link - 10a
Yamaguchi M.Hirao I. Tetrahedron Lett. 1983, 24: 391Reference Ris Wihthout Link - 10b
Eis MJ.Wrobel JE.Ganem B. J. Am. Chem. Soc. 1984, 106: 3693Reference Ris Wihthout Link - 11a
Zhao H.Pagenkopf BL. Chem. Commun. 2003, 2592Reference Ris Wihthout Link - 11b
Zhao H.Engers DW.Morales CL.Pagenkopf BL. Tetrahedron 2007, 63: 8774Reference Ris Wihthout Link - 13
Huisgen R. In 1,3-Dipolar Cycloaddition ChemistryPadwa A. Wiley; New York: 1984. p.1-176 - 14
Tornøe CW.Christensen C.Meldal M. J. Org. Chem. 2002, 67: 3057 - 15
Rostovtsev VV.Green LG.Fokin VV.Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596Reference Ris Wihthout Link - 16
Zhang L.Chen X.Xue P.Sun HHY.Williams ID.Sharpless KB.Fokin VV.Jia G. J. Am. Chem. Soc. 2005, 127: 15998 - 17
Aucagne V.Berná J.Crowley JD.Goldup SM.Hänni KD.Leigh DA.Lu sby PJ.Ronaldson VE.Slawin AMZ.Viterisi A.Walker DB. J. Am. Chem. Soc. 2007, 129: 11950 - 18a
Appukkuttan P.Dehaen W.Fokin VV.Van der Eycken E. Org. Lett. 2004, 6: 4223Reference Ris Wihthout Link - 18b
Feldman AK.Colasson B.Fokin VV. Org. Lett. 2004, 6: 3897Reference Ris Wihthout Link - 19
Chittaboina S.Xie F.Wang Q. Tetrahedron Lett. 2005, 46: 2331 - 20
Smith NW.Polenz BP.Johnson SB.Dzyuba SV. Tetrahedron Lett. 2010, 51: 550 - 21
Krasiński A.Fokin VV.Sharpless KB. Org. Lett. 2004, 6: 1237 - 22 Epoxide 2 was
prepared according to a reported procedure, see:
Zhao S.Ghosh A.D’Andrea SV.Freeman JP.VonVoigtlander PF.Carter DB.Smith MW.Blinn JR.Szmuszkovicz J. Heterocycles 1994, 39: 163 - 23 Azide 5 was
prepared according to a reported procedure, see:
Alvarez SG.Alvarez MT. Synthesis 1997, 413 - 24 The bromide was prepared according
to a reported procedure, see:
Fürstner A.Domostoj MM.Scheiper B. J. Am. Chem. Soc. 2006, 128: 8087
References
Crystal data for compound 3: C15H27NO3Si, MW = 297.47, triclinic, a = 5.7413(15), b = 11.872(3), c = 14.437(5) Å, α = 112.127(15), β = 97.874(14), γ = 98.495(10), V = 881.4(4) ų, d (calcd) = 1.121 g cm-³, T = 123(2) K, space group P-1, Z = 2. Data collected, 15714, R (int) 0.0185. The structure was solved by direct methods, and least-squares refinement of the model based on 5471 independent data [4982 reflections with I>2σ(I)] converged to a final R1 = 0.0321 and wR2 = 0.0885, respectively, S = 1.067. Selected geometric parameters (Å, ˚); N1-C1 1.4562(10), N1-C5 1.4646(10), N1-C11 1.3505(10), C1-C2 1.5242(11), C2-O2 1.4201(10), C2-C3 1.5432(11), C3-C4 1.5370(12), C3-C6 1.4706(12), C4-C5 1.5247(12), C6-C7 1.2068(13), C7-Si1 1.8339(11), C11-O2 1.2254(10), C11-O3 1.3441(10), O3-C12 1.4675(10), C11-N1-C1 118.77(7), C11-N1-C5 123.83(7), C1-N1-C5 114.35(6), N1-C1-C2 110.96(6), O1-C2-C1 111.74(6), O1-C2-C3 107.16(6), C1-C2-C3 111.00(6), C11-O3-C12 120.39(7), C6-C3-C4 112.00(7), C6-C3-C2 109.45(7), C4-C3-C2 109.88(6), C5-C4-C3 111.30(6), N1-C5-C4 109.66(6), C7-C6-C3 176.62(9), C6-C7-Si1 172.82(8), O2-C11-O3 123.90(7), O2-C11-N1 124.53(7), O3-C11-N1 111.54(7). CCDC 793221 contains the supplementary crystallographic data for 3. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.