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

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.

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

References

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16

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

17 Hubert J. Moniotte P. Goebbels G. Warin R. Teyssié P. J. Chem. Soc., Perkin Trans. 2  1973,  1954 

Boc₂NH represents an exellent alternative to the classical Gabriel method for preparation of amines from halides:

18a Grehn L. Ragnarson U. Synthesis  1987,  285 

18b Grehn L. Ragnarson U. Acc. Chem. Res.  1991,  24:  285 ; and references cited therein

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]

20

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]⁺.

21

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]⁺).

22

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).

23

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]

24

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

25 N-Allylphthalimide afforded N-(prop-1-enyl)-phthalimide (E/Z 10: 1) in 99% yield after 15 h at 100 °C. Interestingly, our results were in disagreement with those of Rossi and Barola, reporting only partial conversion of some N-allylimides with Fe(CO)₅: Rossi P. Barola PF. Ann. Chim.  1969,  59:  762 

26

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