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Synlett 2008(4): 578-582  
DOI: 10.1055/s-2008-1032089
LETTER
© Georg Thieme Verlag Stuttgart · New York

Ruthenium-Catalyzed Cyclotrimerization of 1,6- and 1,7-Azadiynes: New Access to Fluorinated Bicyclic Amino Acids

Grigorii T. Shchetnikova, Sergey N. Osipov*a, Christian Bruneaub, Pierre H. Dixneuf*b
a A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov str. 28, 119991 Moscow, Russian Federation
Fax: +7(495)1355085; e-Mail: osipov@ineos.ac.ru;
b Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
e-Mail: pierre.dixneuf@univ-rennes1.fr;
Further Information

Publication History

Received 29 November 2007
Publication Date:
12 February 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

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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.

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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.