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Synlett 2002(8): 1313-1317
DOI: 10.1055/s-2002-32962
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Convenient Method for the Preparation of Enamides from N-Allylamides

Sergey Sergeyev, Manfred Hesse*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Fax: +41(1)6356812; e-Mail: mtbohley@oci.unizh.ch;
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Publication History

Received 7 May 2002
Publication Date:
25 July 2002 (online)

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Abstract

Isomerization of various N-allylamides in the presence of Fe(CO)5 smoothly afforded the corresponding enamides in yields up to 95%. The reported procedure is compatible with various functional groups including protected amino and hydroxy groups. The possible mechanism of transformation is discussed.

Key words

enamides - N-allylamides - double bond shift - iron pentacarbonyl

16

This work is a part of the Ph.D. Thesis of S. Sergeyev, University of Zürich, 2002.

19

We have shown that the use of Cs2CO3 as the phase-transfer catalyst allows to avoid the preparation of Na or K salt of Boc2NH, see ref. [18a]

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Preparation of N -(2-Methylprop-2-enyl)-3-phenylpropanamide 9a (Typical Procedure for the Preparation of Substituted N -Allylamides 9a-d). A mixture of 6a (4.0 mL, 40 mmol), Boc2NH (4.34 g, 20 mmol), Cs2CO3 (6.52 g, 20 mmol), and DMF (20 mL) was stirred for 12 h at r.t., then the volatile materials were removed in vacuo. The residue was partitioned between CH2Cl2 (75 mL) and H2O (50 mL), the organic phase was separated and washed with H2O (2 × 50 mL), dried (MgSO4), and concentrated to afford crude 7a. It was dissolved in CH2Cl2 (20 mL) and treated with TFA (6.1 mL, 80 mmol) in one portion. After 4 h stirring at r.t. the mixture was concentrated and the residue was dried in vacuo to give crude 8a as TFA salt. It was dissolved in the mixture of CH2Cl2 (75 mL) and Et3N (8.3 mL, 60 mmol) and treated dropwise at 0 °C with 3-phenylpropanoyl chloride (2.83 mL, 19 mmol). The mixture was stirred for 1 h at 0 °C, then allowed to reach r.t., washed with H2O (25 mL), 10% aq citric acid (25 mL), again H2O (2 × 25 mL), and dried (MgSO4). Evaporation of the solvent in vacuo and crystallization of the residue from hexane/EtOAc afforded 9a (3.82 g, 94% total yield after 3 steps). Slightly yellow solid, mp 51-52 °C.
1H NMR (CDCl3): δ = 1.65 (s, 3 H, Me), 2.51 (t, 2 H, J = 7.7 Hz, CH2CO), 2.96 (t, 2 H, J = 7.7 Hz, CH 2Ph), 3.75 (d, 2 H, J = 6.0 Hz, CH2N), 4.68, 4.76 (2 s-like m, 2 H, CH2=C), 5.80 (br s, NH), 7.15-7.28 (m, 5 H, Ph). 13C NMR (CDCl3): δ = 20.1 (Me), 31.6 (CH2Ph), 38.3 (CH2CO), 44.9 (CH2N), 110.7 (CH2=C), 126.1 (arom. CH), 128.2 (2 arom. CH), 128.4 (2 arom. CH), 140.7 (C), 141.8 (C), 172.0 (C=O). CI-MS (NH3): m/z (%) = 407(29) [2 M + 1]+, 221(25) [M + NH4]+, 204(100) [2 M + 1]+.

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Preparation of 2a/2a′ (Typical Procedure for the Isomerization of N -Allylamides to N -Prop-1-enylamides). A mixture of 1a (945 mg, 5 mmol) and Fe(CO)5 (0.2 mL, 1 mmol) was stirred under Ar for 16 h at 100 °C. The mixture was allowed to reach r.t., then the catalyst was removed in vacuo and collected in a trap, cooled by liquid N2. Content of the trap was treated with 5% alcoholic FeCl3 solution to destroy toxic Fe(CO)5. The residue in the reaction flask was dissolved in CHCl3 and filtered through Celite. Evaporation of the solvent in vacuo and column chromatography of the residue on silica gel (CH2Cl2/EtOAc 10:1) afforded 2a (548 mg, 58%) and 2a′ (350 mg, 37%), total yield of 2a/2a′ 95%.
( E )-3-Phenyl- N -prop-1-enyl-propanamide(2a). Colorless solid, mp 113-114.5 °C.
1H NMR (CDCl3): δ = 1.62 (dd, 3 H, J = 1.7, 6.7 Hz, Me), 2.49 (t, 2 H, J = 7.8 Hz, CH2CO), 2.95 (t, 2 H, J = 7.8 Hz, CH 2Ph), 5.09 (qd, 1 H, J = 6.7, 14.2 Hz, CH=CHN), 6.71-6.78 (m, 1 H, CH=CHN), 7.15-7.28 (m, 5 H, Ph), 7.40 (br d, NH). 13C NMR (CDCl3): δ = 14.7 (Me), 31.4 (CH2Ph), 38.1 (CH2CO), 107.8 (CH=CHN), 123.1 (CH=CHN), 126.2 (arom. CH), 128.2 (2 arom. CH), 128.4 (2 arom. CH), 140.6 (arom. C), 169.2 (C=O). CI-MS (NH3): m/z (%) = 207(37)[M + NH4]+), 190(100) [M + 1]+).
( Z )-3-Phenyl- N -prop-1-enyl-propanamide (2a′). Colorless solid, mp 53.5-55 °C.
1H NMR (CDCl3): δ = 1.49 (dd, 3 H, J = 1.5, 7.0 Hz, Me), 2.57 (t, 2 H, J = 7.7 Hz, CH2CO), 2.96 (t, 2 H, J = 7.7 Hz, CH 2Ph), 4.73 (qd, 1 H, J = 7.0, 8.9 Hz, CH=CHN), 6.64-6.71 (m, 1 H, CH=CHN), 7.16-7.28 (m, 6 H, Ph, NH). 13C NMR (CDCl3): δ = 10.7 (Me), 31.4 (CH2Ph), 38.0 (CH2CO), 105.3 (CH=CHN), 121.8 (CH=CHN), 126.2 (arom. CH), 128.2 (2 arom. CH), 128.5 (2 arom. CH), 140.5 (arom. C), 169.5 (C=O). CI-MS (NH3): m/z (%) = 207(48) [M + NH4]+, 190(100) [M + 1]+).

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E/Z ratio was determined from the integral intensities of the signals of CH=CHN, (E)- or (Z)-configuration of double bond was assigned based on the value of coupling constants (typically 13.5-14.2 Hz for (E)- and 8.5-9.0 Hz for (Z)-enamides).

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It should be noted, that our findings are in contrast with those of Stille and Becker, reported decomposition of N-(3,3-dimethylallyl)acetamide upon the action of Fe(CO)5, see ref. [15]

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Prepared by alkylation of 1a with MeI in DMF in the presence of NaH.

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N-Tosylallylamine remained unchanged upon the action of Fe(CO)5.