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Synlett 2008(3): 351-354  
DOI: 10.1055/s-2008-1032043
LETTER
© Georg Thieme Verlag Stuttgart · New York

RCM-Mediated Synthesis of Fluorinated Cyclic Hydrazines

Valeria De Matteisa, Floris L. van Delfta, Jörg Tiebesb, Floris P. J. T. Rutjes*a
a Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Fax: +31(24)3653393; e-Mail: F.Rutjes@science.ru.nl;
b Bayer CropScience AG, Industrial Park, 65926 Frankfurt am Main, Germany
Further Information

Publication History

Received 11 October 2007
Publication Date:
16 January 2008 (online)

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Abstract

A series of fluorinated cyclic hydrazine derivatives has been prepared in a straightforward manner using ring-closing me­tathesis (RCM) of fluorinated- and trifluoromethylated olefins as the key step.

Key words

cyclic hydrazines - ring-closing metathesis - fluorinated heterocycles - trifluoromethylated heterocycles

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Representative Procedures N ′-(1-Phenylbut-3-enyl)hydrazinecarboxylic Acid tert -Butyl Ester (31)Allylmagnesium bromide (4.57 mL of a 1.0 M solution in Et2O, 4.57 mmol) was added at -78 °C to a well-stirred solution of 13 (336 mg, 1.53 mmol) in THF (2 mL). The mixture was stirred at -78 °C for 1 h and allowed over 12 h to reach r.t. It was poured into aq sat. NH4Cl and the aqueous layer was extracted with Et2O (3 × 6 mL). The ether layers were dried (MgSO4), evaporated, and the crude product 31 (135 mg, 40%) was obtained as a colorless oil. IR (neat): 3403, 3283, 3067, 3028, 2980, 2928, 1709, 1455, 1368, 1282, 1243, 1156, 1022, 919, 759, 698 cm-1. 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ = 7.31-7.24 (m, 5 H, Ph), 6.22, (s, 1 H, BocNH), 5.83-5.69 (m, 1 H, CH=CH2), 5.13-5.03 (m, 2 H, CH=CH 2), 4.32 (br s, 1 H, PhCH), 4.11 (br s, 1 H, BocNHNH), 2.42-2.37 (m, 2 H, PhCHCH 2), 1.41 (s, 9 H, 3 CH 3). 13C NMR (75 MHz, CDCl3, 25 °C): δ = 156.6, 141.9, 134.7, 128.4, 127.8, 127.5, 117.9, 80.3, 63.3, 40.3, 28.4. ESI-HRMS: m/z calcd for C15H22N2O2Na [M+ + Na]: 285.1579; found: 285.15766.N ′-Phenylacetyl- N ′-(1-phenylbut-3-enyl)hydrazine­-carboxylic Acid tert -Butyl Ester (32)To a solution of phenylacetylchloride (64.8 µL, 0.5 mmol) in THF (2 mL), Et3N (69.7 l, 0.5 mmol) was added at 0 °C and the mixture was stirred at 0 °C for 30 min. At the same temperature compound 31 (130 mg, 0.51 mmol) was added and the mixture was allowed to reach r.t. over 12 h. The solvent was evaporated and the residue was purified using column chromatography (heptane-EtOAc, 10:1 to 6:1) to give 32 (166 mg, 89%) as a white solid; mp 107-109 °C. IR (neat): 3278, 3028, 2980, 2933, 1705, 1658, 1493, 1455, 1394, 1368, 1251, 1156, 707, 607 cm-1. 1H NMR (300 MHz, CDCl3, 25 °C, TMS, some signals appear as rotamers): δ = 7.40-7.14 (m, 10 H, Ar), 6.10 (br s, 1 H, NH), 5.88-5.52 (m, 2 H, CHPh, CH2=CH), 5.14-5.85 (m, 2 H, H 2C=CH), 3.72-3.63 (m, 2 H, CH2Ph), 2.73-2.50 (m, 2 H, PhCHCH 2), 1.50 and 1.30 (s, 9 H, 3 CH3). 13C NMR (75 MHz, CDCl3, 25 °C): δ = 165.2, 150.6, 145.2, 134.7, 130.8, 129.3, 129.1, 128.0, 127.8, 127.3, 126.9, 117.4, 81.9, 58.8, 49.2, 40.6, 28.4. HRMS (CI): m/z calcd for C23H29N2O3 [M+ + H]: 381.2178; found: 381.2188.N -(2-Fluoroallyl)- N ′-phenylacetyl- N ′-(1-phenylbut-3-enyl)hydrazinecarboxylic Acid tert -Butyl Ester (33)To a suspension of NaH (14 mg, 0.57 mmol) in DMF (5 mL) was added at 0 °C compound 32 (166 mg, 0.44 mmol). After stirring for 15 min at r.t., 1-chloro-2-fluoroprop-2-ene (18, 42 mg, 0.44 mmol) was added slowly. The reaction was stirred for 12 h, quenched with H2O (5 mL) and extracted with Et2O (3 × 5 mL). The ether layers were dried (MgSO4), evaporated, and the residue was purified using column chromatography (heptane-EtOAc, 10:1) to give 33 (104 mg, 54%) as a colorless oil. IR (neat): 3062, 3032, 2976, 2928, 1718, 1679, 1497, 1450, 1364, 1251, 1156, 1031, 914, 854, 763, 698 cm-1. 1H NMR (300 MHz, CDCl3, 25 °C, TMS, some signals appear as rotamers): δ = 7.41-7.25 (m, 10 H, Ar), 5.65-5.43 (m, 3 H, CH 2=CH, CH2=CH), 5.07-4.35 (m, 6 H, CH 2=CH, FC=CH 2, CHPh, NCH2), 4.00-3.91 (m, 1 H, NCH2), 3.72-3.54 (m, 2 H, CH2Ph), 2.92 (br s, 2 H, PhCHCH 2), 1.42 and 1.22 (s, 9 H, 3 CH3). 13C NMR (75 MHz, CDCl3, 25 °C, some signals appear as rotamers): δ = 173.8, 160.3 (d, J = 260.1 Hz, CF), 169.0, 134.3, 134.2, 133.8, 129.2, 129.1, 128.2, 127.8, 127.2, 126.3, 122.9, 95.5-95.2 (m, CH2=CF), 82.2, 62.8, 39.8, 38.5, 37.5 (d, J = 48.8 Hz, CH2CF), 27.8 and 27.3, HRMS (CI): m/z calcd for C26H32N2O3F [M+ + H]: 439.2397; found: 439.2389.6-Fluoro-3-phenyl-2-phenylacetyl-2,3,4,7-tetrahydro[1,2]diazepine-1-carboxylic Acid tert -Butyl Ester (34)To a solution of compound 33 (90 mg, 0.2 mmol) in anhyd toluene (40 mL) Grubbs II catalyst (20 mol%) was added at 100 °C in small portions over 2 h. The mixture was then evaporated and the product was purified using column chromatography (heptane-EtOAc, 10:1) to give 34 (52 mg, 64%) as a white solid; mp 110-113 °C. IR (neat): 3058, 3028, 2967, 2898, 2859, 1722, 1689, 1493, 1450, 1368, 1260, 1230, 1161, 1117, 1096, 1027, 858, 806, 698, 659, 517 cm-1. 1H NMR (300 MHz, CDCl3, 25 °C, TMS, some signals appear as rotamers): δ = 7.37-7.08 (m, 10 H, Ar), 5.48 and 5.30 (br s, 1 H, CHPh), 5.30-4.86 (m, 1 H, CF=CH), 4.74 and 4.41 (d, J = 18.3, 1 H, NCH2), 3.74-3.61 (m, 2 H, CH2Ph), 3.22-3.12 (m, 1 H, NCH2), 2.74-2.65 (m, 1 H, CH 2CHPh), 2.19-2.10 (m, 1 H, CH 2CHPh), 1.56 and 1.51 (s, 9 H, 3 CH3). 13C NMR (75 MHz, CDCl3, 25 °C, some signals appear as rotamers): δ = 173.7 and 173.4, 156.3 and 155.9 (d, J = 254.7 Hz, CF), 155.5 and 154.6, 141.5 and 141.3, 134.9 and 134.4, 129.2, 128.8, 128.7, 128.4, 127.3, 127.1, 126.9, 125.7, 101.2 and 100.6 (d, J = 18.9 Hz, C=CF), 83.5, 65.3 and 64.8, 50.2 and 48.6 (d, J = 42.8 Hz, NCH2), 42.2 and 41.9, 28.3. HRMS (CI): m/z calcd for C24H28FN2O3 [M+ + H]: 411.2084; found: 411.2075.

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Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 666813.