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DOI: 10.1055/s-2008-1032089
Ruthenium-Catalyzed Cyclotrimerization of 1,6- and 1,7-Azadiynes: New Access to Fluorinated Bicyclic Amino Acids
Publikationsverlauf
Publikationsdatum:
12. Februar 2008 (online)
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Abstract
An efficient access to a variety of trifluoromethyl-substituted cyclic α-amino acid derivatives based on ruthenium-catalyzed cyclotrimerization of appropriate 1,6- and 1,7-diynes with terminal and internal alkynes has been developed.
Key words
fluorinated diynes - amino acids - ruthenium catalysis - cyclotrimerization - alkynes
-
1a
Salomon CJ.Breuer E. J. Org. Chem. 1997, 62: 3858 -
1b
Breuer E.Frant J.Reich R. Exp. Opin. Ther. Patents 2005, 15: 3 -
2a
Sewald N.Burger K. Synthesis of Fluoro-Containing Amino AcidsKukhar VP.Soloshonok VA. John Wiley and Sons Ltd.; New York, Brisbane, Toronto: 1995. p.139 ; and references cited therein -
2b
Burger K.Muetze K.Hollweck W.Koksch B. Tetrahedron 1998, 54: 5915 -
2c
Sutherland A.Willis CL. Nat. Prod. Rep. 2000, 621 -
2d
Koksch B.Sewald N.Hofmann H.-J.Burger K.Jakubke H.-D. J. Pept. Sci. 1997, 3: 157 -
2e
Horng J.-C.Raleigh DP. J. Am. Chem. Soc. 2003, 125: 9286 - 3
Banks RE.Taltow JC.Smart BE. Organofluorine Chemistry: Principles and Commercial Applications Plenum Press; New York: 1994. -
4a
Biligicer B.Kumar K. Tetrahedron 2002, 58: 4105 -
4b
Wang P.Tang Y.Tirrell DA. J. Am. Chem. Soc. 2003, 125: 6900 - 5
Carosati E.Sciabola S.Cruciani G. J. Med. Chem. 2004, 47: 5114 -
6a
Osipov SN.Golubev AS.Sewald N.Burger K. Tetrahedron Lett. 1997, 38: 5965 -
6b
Moroni M.Koksch B.Osipov SN.Crucianelli M.Triderio M.Bravo P.Burger K. J. Org. Chem. 2001, 66: 130 -
6c
Osipov SN.Tsouker P.Hennig L.Burger K. Tetrahedron 2004, 60: 271 - 7
Osipov SN.Golubev AS.Sewald N.Michel T.Kolomiets AF.Fokin AV.Burger K. J. Org. Chem. 1996, 61: 7521 -
8a
Osipov SN.Bruneau C.Picquet M.Kolomiets AF.Dixneuf PH. Chem. Commun. 1998, 2053 -
8b
Semeril D.Le Notre J.Bruneau C.Dixneuf PH.Kolomiets AF.Osipov SN. New J. Chem. 2001, 16 -
8c
Osipov SN.Artyushin OI.Kolomiets AF.Bruneau C.Dixneuf PH. Synlett 2000, 1031 -
8d
Osipov SN.Kobel’kova NM.Shchetnikov GT.Kolomiets AF.Bruneau C.Dixneuf PH. Synlett 2001, 621 -
8e
Osipov SN.Artyushin OI.Kolomiets AF.Bruneau C.Picquet M.Dixneuf PH. Eur. J. Org. Chem. 2001, 3891 -
8f
Osipov SN.Dixneuf P. Russ. J. Org. Chem. 2003, 39: 1211 -
8g
Eckert M.Monnier F.Shchetnikov GT.Titanyuk ID.Osipov SN.Dérien S.Dixneuf PH. Org. Lett. 2005, 7: 3741 - 9
Bird CW. Transition Metal Intermediates in Organic Synthesis Logos Press; London: 1967. - 10 For a review on synthetic applications of transition-metal-catalyzed acetylene cyclization, see:
Vollhardt KPC. Acc. Chem. Res. 1977, 10: 1 - 11
Vollhardt KPC. Angew. Chem. Int. Ed. Engl. 1984, 23: 53 ; Angew. Chem. 1984, 96, 525 - 12
Neeson SJ.Stevenson PJ. Tetrahedron Lett. 1988, 29: 813 -
13a
Kotha S.Sreenivasachary N. Eur. J. Org. Chem. 2001, 3375 -
13b
Kotha S.Sreenivasachary N. Bioorg. Med. Chem. Lett. 2000, 10: 1413 -
13c
Kotha S.Brahmachary E. Bioorg. Med. Chem. 2002, 10: 2291 -
14a
Yamamoto Y.Hata K.Arakawa T.Itoh K. Chem. Commun. 2003, 1290 -
14b
Yamamoto Y.Okuda S.Itoh K. Chem. Commun. 2001, 1102 -
14c
Yamamoto Y.Hata K.Ogawa R.Itoh K. J. Am. Chem. Soc. 2001, 123: 6189 -
14d
Yamamoto Y.Takagishi H.Itoh K. J. Am. Chem. Soc. 2002, 124: 28 -
14e
Yamamoto Y.Takagishi H.Itoh K. J. Am. Chem. Soc. 2002, 124: 6844 -
14f
Yamamoto Y.Takagishi H.Itoh K. Org. Lett. 2001, 3: 2117 -
14g
Yamamoto Y.Kitahara H.Ogawa R.Kawaguchi H.Tatsumi K.Itoh K. J. Am. Chem. Soc. 2000, 122: 4310 -
14h
Yamamoto Y.Kinpara K.Saigoku T.Takagishi H.Okuda S.Nishiyama H.Itoh K. J. Am. Chem. Soc. 2005, 127: 605 -
14i
Yamamoto Y.Arakawa T.Ogawa R.Itoh K. J. Am. Chem. Soc. 2003, 125: 12143 -
15a
Albers MO.de Waal DJA.Liles DC.Robinson DJ.Singleton E.Wiege MB. J. Chem. Soc., Chem. Commun. 1986, 1680 -
15b
Yamamoto Y.Kitahara H.Ogawa R.Itoh K. J. Org. Chem. 1998, 63: 9610 -
15c
Kirchner K.Calhorda MJ.Schmid R.Veiros LF. J. Am. Chem. Soc. 2003, 125: 11721 -
15d
Paih JL.Monnier F.Dérien S.Dixneuf PH.Clot E.Eisenstein O. J. Am. Chem. Soc. 2003, 125: 11964 -
15e
Le Paih J.Dérien S.Demerseman B.Bruneau C.Dixneuf PH.Toupet L.Dazinger G.Kirchner K. Chem. Eur. J. 2005, 11: 1312 - 16
Sewald N.Gaa K.Burger K. Heteroat. Chem. 1993, 4: 253 - 17
Shchetnikov GT.Peregudov AS.Osipov SN. Synlett 2007, 136 - 19
Peters J.-U.Blechert S. Chem. Commun. 1997, 1983 - 20
Das SK.Roy R. Tetrahedron Lett. 1999, 40: 4015 - 21
Witulski B.Stengel T.Fernández-Hernández JM. Chem. Commun. 2000, 1965
References and Notes
General Procedure for Ru-Catalyzed Cyclotrimerization: The catalyst RuCl(Cp*)(cod) (2 mol%) was added to the solution of diyne (0.15 mmol) and alkyne (0.6 mmol) in degassed DCE under an argon atmosphere. The resulting mixture was stirred at r.t. until the reaction completion (TLC control). The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel (eluent: EtOAc-PE).
Data for Compound 6a: oil. 1H NMR (400 MHz, DMSO-d
6, 80 ºC): δ = 3.61 (br s, 3 H, OMe), 4.84 (d, J
AB = 15.2 Hz, 1 H, NCH2), 5.03 (d, J
AB = 15.2 Hz, 1 H, NCH2), 5.23 (s, 2 H, OCH2), 7.34-7.56 (m, 9 H, Ar). 19F NMR (282 MHz, DMSO-d
6, TFA, 80 °C): δ = 5.3 (s, 3 F, CF3). Anal. Calcd for C19H16F3NO4: C, 60.16; H, 4.25; N, 3.69. Found: C, 60.21; H, 4.35; N, 3.67.
Data for Compound 7a: oil. 1H NMR (400 MHz, DMSO-d
6, 80 °C): δ = 3.33 (d, J
AB = 15.4 Hz, 1 H, CH2), 3.39 (d, J
AB = 15.4 Hz, 1 H, CH2), 3.50 (s, 3 H, OMe), 4.49 (d, J
AB = 15.1 Hz, 1 H, NCH2), 4.87 (d, J
AB = 15.1 Hz, 1 H, NCH2), 5.15 (s, 2 H, OCH2), 7.29 (m, 4 H, Ar), 7.33-7.43 (m, 5 H, Ph). 19F NMR (282 MHz, CDCl3, TFA, 80 °C): δ = 6.32 (s, 3 F, CF3). 13C NMR (150.9 MHz, DMSO-d
6, 80 ºC): δ = 32.51, 45.15, 56.21, 68.18, 70.10 (q, 2
J
C-F = 28.4 Hz), 122.23 (q, 1
J
C-F = 288.2 Hz), 127.88, 127.91, 128.04, 134.70, 136.51, 139.18, 156.32, 165.81. Anal. Calcd for C20H18F3NO4: C, 61.07; H, 4.61; N, 3.56. Found: C, 60.99; H, 4.55; N, 3.67.
Data for Compound 10: mp 234 °C (dec.). 1H NMR (300 MHz, DMSO-d 6): δ = 3.35 (d, J AB = 15.4 Hz, 1 H, CH2), 3.39 (d, J AB = 15.4 Hz, 1 H, CH2), 3.86 (d, J AB = 15.5 Hz, 1 H, NCH2), 4.06 (d, J AB = 15.5 Hz, 1 H, NCH2), 7.23 (m, 4 H, Ar). 19F NMR (282 MHz, DMSO-d 6): δ = 3.07 (s, 3 F, CF3). 13C NMR (150.9 MHz, DMSO-d 6): δ = 31.03, 45.12, 64.01 (q, 2 J C-F = 29.9 Hz), 120.91 (q, 1 J C-F = 281.3 Hz), 127.31, 128.01, 128.41, 129.21, 133.81, 138.14, 168.41. Anal. Calcd for C12H12F3NO2: C, 53.88; H, 4.11; N, 5.71. Found: C, 53.61; H, 4.32; N, 5.34.