PDF icon Download PDF
Synlett 2004(7): 1199-1202  
DOI: 10.1055/s-2004-825586
LETTER
© Georg Thieme Verlag Stuttgart · New York

Iron(II)-Catalyzed Chlorolactamization of γ,δ-Unsaturated Carboxylic Acids

Jan Klueggea, Eberhardt Herdtweckb, Thorsten Bach*a
a Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
b Lehrstuhl für Anorganische Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Further Information

Publication History

Received 11 February 2004
Publication Date:
10 May 2004 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

A one-pot chlorolactamization of γ,δ-unsaturated carboxylic acids is presented. Substrates like carboxylic acid 1 were transformed into the acyl azides which upon treatment with FeCl2 and TMSCl in i-PrOH cyclized to yield lactams such as 2 (75% yield). The reaction yielded exclusively the syn-addition product as proven by the crystal structure of chlorolactam 2. The acyclic alkenoic acids 3-6 reacted equally well to the products 7-10 (57-81% yield). The reaction proceeded not stereospecifically but yielded a mixture of erythro- and threo-products.

Key words

aminations - homogenous catalysis - iron - lactams - radical reactions

9

General Procedure for the One-Pot Chloro-lactamization: To 141 mg (1.0 mmol) of 2-(cyclohex-2-enyl)acetic acid (1) [8] dissolved in 5 mL CH2Cl2 were added 94 µL (1.1 mmol) of oxalyl chloride and one drop of DMF. The reaction mixture was stirred at r.t. for 20 min. CH2Cl2 and the excess oxalyl chloride were removed in vacuum. The remaining acyl chloride was dissolved in 5 mL of acetone and a solution of 130 mg NaN3 (2.0 mmol) in 300 µL H2O was added at -15 °C. The reaction mixture was stirred for 1.5 h at -15 °C and the solvent was removed at this temperature in vacuum. The acyl azide was dissolved in 10 mL i-PrOH. A solution of 25.3 mg (0.2 mmol) FeCl2 and 252 µL (2.0 mmol) TMSCl in 5 mL i-PrOH was added. The reaction mixture was stirred for 5 h at -15 °C and for 8 h at r.t.. After evaporation of the solvent in vacuo 40 mL of EtOAc were added. The organic layer was washed with H2O (3 × 20 mL) and brine (2 × 20 mL) and dried over MgSO4. After filtration the solvent was evaporated and the crude product was purified by flash chromatography. (silica 60, pentane-CH2Cl2-MeOH-NH3 ( aq) = 65:30:5:0.25) to give 130 mg (75%) of lactam 2. 1H NMR (500 MHz, CDCl3): δ = 1.23-1.36 (m, 2 H, CH2CHHCH2CHCl, CHHCH2CH2CHCl), 1.60-1.70 (m, 1 H, CHHCH2CH2CHCl), 1.73-1.85 (m, 2 H, CH2CH2CHHCHCl, CH2CHHCH2CHCl), 1.93-2.01 (m, 1 H, CH2CH2CHHCHCl), 2.05 (d, J = 16.3 Hz, 1 H, CHCHHCO), 2.35-2.45 (m, 1 H, CHCH2CO), 2.45 (dd, J = 16.3 Hz, J = 6.5 Hz, 2 H, CHCHHCO), 3.98-4.07 (m, 2 H, CH2CH2CH2CHCl, CHClCHNH), 5.91 (br s, 1 H, NH). 13C NMR (90.6 MHz, CDCl3): δ = 23.9 (CH2 CH2CH2CHCl), 26.6 (CH2CH2 CH2CHCl), 30.1 (CH2CH2CH2CHCl), 35.9 (CHCH2CO), 40.3 (CHCH2CO), 58.2 (CH2CH2CH2 CHCl), 59.7 (CHClCHNH), 177.2 (CO). Anal. Calcd for C8H12ClNO (173.64): C, 55.34; H, 6.97; N, 8.07. Found: C, 55.31; H, 6.92; N, 7.98.

10

Crystal structure analysis of lactam 2: C8H12ClNO, M r = 173.64, colorless prism (0.56 × 0.64 × 0.97 mm3), monoclinic, P21/c (No.: 14), a = 10.1739 (1), b = 6.5823 (1), c = 12.4662 (2) Å, β = 94.0723 (5)°, V = 832.72 (2) Å3, Z = 4, dcalc = 1.385 gcm-3, F000 = 368, µ = 0.398 mm-1. Preliminary examination and data collection were carried out on a kappa-CCD device (NONIUS MACH3) at the window of a rotating anode (NONIUS FR591) with graphite monochromated Mo-Kα radiation (λ = 0.71073 Å). Data collection were performed at T = 173 K within the Θ range of 2.01°<Θ<25.36°. A total of 19024 reflections were integrated and corrected for Lorentz and polarization effects. A correction for absorption effects and/or decay was applied during the scaling procedure. After merging (R int = 0.035), 1525 [1462: I o>2σ(I o)] independent reflections remained and all were used to refine 149 parameters. The structure was solved by a combination of direct methods and difference-Fourier syntheses. All non-hydrogen atoms were refined with anisotropic displacement parameters. All hydrogen atoms were found and refined freely. Full-matrix least-squares refinements were carried out by minimizing Σw(F o 2-F c 2) [2] and converged with R1 = 0.0248 [I o>2σ(I o)], wR2 = 0.0609 [all data], GOF = 1.087, and shift/error <0.001. The final difference-Fourier map shows no striking features (Δe min/max = +0.25/-0.19 eÅ-3). A correction for extinction was applied ε = 0.066 (3). Crystallographic data (excluding structure factors) for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-234 589. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk]. For references see ref. 12b-g.