Mild Stereoselective Hydrohalogenation Leading to (Z)-Halopropenamides at Room Temperature

Abstract

Hydroiodination of 2-propynamides leading stereoselectively to (Z)-iodopropenamides was achieved under mild conditions at room temperature by the combined use of zinc iodide and tert­butyl iodide. Similarly, the use of zinc bromide in the presence of tert-butyl bromide enabled the synthesis of (Z)-bromopropen­amides. (Z)-Halopropenoic esters were also prepared in high yields.

hydrohalogenation - (Z)-halopropenamides - (Z)-halopropenoic esters - tert-butyl halide - zinc halide

References and Notes

For Sonogashira coupling reaction, see:

1a Eichberg MJ. Dorta RL. Grotjahn DB. Lamottke K. Schmidt M. Vollhardt KPC. J. Am. Chem. Soc.  2001,  123:  9324 

1b Fiandanese V. Babudri F. Marchese G. Punzi A. Tetrahedron  2002,  58:  9547 

1c Cherry K. Thibonnet J. Duchêne A. Parrain J.-L. Abarbri M. Tetrahedron Lett.  2004,  45:  2063 

1d Cramer N. Laschat S. Baro A. Schwalbe H. Richter C. Angew. Chem. Int. Ed.  2005,  44:  820 

1e Cramer N. Buchweitz M. Laschat S. Frey W. Baro A. Mathieu D. Richter C. Schwalbe H. Chem. Eur. J.  2006,  12:  2488 

For Stille coupling reaction, see:

1f Mcdonald G. Alcaraz L. Wei X. Lewis NJ. Taylor RJK. Tetrahedron  1998,  54:  9823 

1g Cherry K. Abarbri M. Parrain J.-L. Duchêne A. Tetrahedron Lett.  2003,  44:  5791 

1h Cherry K. Duchêne A. Thibonnet J. Parrain J.-L. Abarbri M. Synthesis  2005,  2349 

For coupling reaction with organozirconocenes, see:

1i Crombie L. Hobbs AJW. Horsham MA. Tetrahedron Lett.  1987,  28:  4875 

1j Rossi R. Carpita A. Lippolis V. Synth. Commun.  1991,  21:  333 

For annulation of allenes, see:

1k Larock RC. He Y. Leong WW. Han X. Refvik MD. Zenner JM. J. Org. Chem.  1998,  63:  2154 

2a Grigg R. Sridharan V. Stevenson P. Sukirthalingam S. Tetrahedron  1989,  45:  3557 

2b Kiewel K. Tallant M. Sulikowski GA. Tetrahedron Lett.  2001,  42:  6621 

2c Mori M. Nakanishi M. Kajishima D. Sato Y. J. Am. Chem. Soc.  2003,  125:  9801 

3 Ikoma M. Oikawa M. Sasaki M. Tetrahedron  2008,  64:  2740 

4 Han C. Shen R. Su S. Porco JA. Org. Lett.  2004,  6:  27 

5a Bey P. Vevert JP. J. Org. Chem.  1980,  45:  3249 

5b Ge CS. Hourcade S. Ferdenzi A. Chiaroni A. Mons S. Delpech B. Marazano C. Eur. J. Org. Chem.  2006,  4106 

For the preparation of (E)-3-bromopropenamides via the reaction of 3-aminopropynal with HBr followed by rearrangement, see:

6a Neuenschwander M. Hafner K. Angew. Chem., Int. Ed. Engl.  1968,  7:  460 

6b Gais H.-J. Hafner K. Neuenschwander M. Helv. Chim. Acta  1969,  52:  2641 

6c Niederhauser A. Neuenschwander M. Helv. Chim. Acta  1973,  56:  1318 

For the synthesis of (E)- or (Z)-iodopropenamides via peptide coupling reaction between the corresponding (E)- or (Z)-iodopropenoic acids and an amine, see refs. 1d, 3, 4. For aminolysis of acyl chlorides prepared from 3-bromo- or 3-iodopropenoic acids leading to a mixture of Z- and E-isomers, see:

6d Wilson RM. Commons TJ. J. Org. Chem.  1975,  40:  2891 

6e Wojcik J. Witanowski M. J. Mol. Struct.  1978,  49:  249 

7 Fujisawa T. Tanaka A. Ukaji Y. Chem. Lett.  1989,  1255 

8a Ma S. Lu X. Tetrahedron Lett.  1990,  31:  7653 

8b Ma S. Lu X. Li Z. J. Org. Chem.  1992,  57:  709 

8c For the use of NaI in AcOH, see: Marek I. Alexakis A. Normant J.-F. Tetrahedron Lett.  1992,  33:  5329 

9

The reactions were generally performed at 90 ˚C over 22-48 h. At 70 ˚C lower yields were obtained (see ref. 8b).

10 Feray L. Bertrand MP. Eur. J. Org. Chem.  2008,  3164 

11

Using only 2 equivalents of tert-butyl iodide led to lower yields.

12 De la Pradilla RF. Morente M. Paley RS. Tetrahedron Lett.  1992,  33:  6101 

13

This might be correlated to the relative basicity of amides and sulfoxides.

14

( Z )- N , N -Diallyl-3-iodoacrylamide(2d); Typical Procedure To a solution of N,N-diallyl-3-propynamide (50 mg, 0.335 mmol) in CH₂Cl₂ (1.7 mL) were added t-BuI (200 µL, 1.67 mmol, 3 equiv) and ZnI₂ (214 mg, 0.67 mmol, 2 equiv) at r.t. After 18 h, H₂O (5 mL) was added, and the reaction mixture was extracted twice with CH₂Cl₂. The organic layers were dried over MgSO₄, filtered, and concentrated under reduce pressure. Flash chromatography on SiO₂ (100% pentane then 100% Et₂O) afforded 2d (81 mg, 0.293 mmol, 87%). ^¹H NMR (300 MHz): δ = 3.85 (br d, J = 5.1 Hz, 2 H), 4.05 (br d, J = 5.9 Hz, 2 H), 5.11-5.28 (m, 4 H), 5.68-5.89 (m, 2 H), 6.85 (d, J = 8.8 Hz, 1 H), 7.10 (d, J = 8.8 Hz, 1 H). ^¹³C NMR (75 MHz): δ = 47.4 (CH₂), 49.9 (CH₂), 87.6 (=CHI), 117.9 (=CH₂), 118.4 (=CH₂), 132.9 (=CH), 133.1 (=CH), 134.5 (=CH), 167.1 (C=O). HRMS: m/z calcd for C₉H₁₂NOI [MH]⁺: 278.0036; found: 278.0035.

15 Taniguchi M. Kobayashi S. Nakagawa M. Hino T. Tetrahedron Lett.  1986,  27:  4763 

16

Owing to complexation of the product to zinc salts, the olefinic protons are more deshielded in the crude reaction mixture - before aqueous treatment - than in the pure isolated product 2d (δ = 7.0 ppm and 7.4 ppm with a coupling constant equal to 9.1 Hz: 6.85 ppm and 7.10 ppm with a coupling constant equal to 8.8 Hz, respectively).

17

Using zinc bromide led to degradation of benzylic and propargylic esters.