Microwave-Assisted Tandem Nucleophilic Substitution-Wittig Reaction of α-Hypervalent Iodine Functionalized Phosphonium Ylide

Abstract

Under microwave irradiation conditions the tandem nucleophilic substitution-Wittig reaction of α-hypervalent iodine functionalized phosphonium ylide can occur readily to afford α-heteroatom substituted-α,β-unsaturated enoates in good yields stereoselectively.

microwave irradiation conditions - α-hypervalent iodine functionalized phosphonium ylide - umpolung ylides - tandem reaction

References

1a Gedye R. Smith F. Westaway K. Humera A. Baldisera L. Laberge L. Roussel J. Tetrahedron Lett.  1986,  27:  279 

1b Giguere RJ. Bray TL. Duncan SM. Majetich G. Tetrahedron Lett.  1986,  27:  4945 

For reviews, see:

2a Majetich G. Wheless K. In Microwave-Enhanced Chemistry Fundamentals, Sample Preparation, and Applications   Kingston HM. Haseell SJ. American Chemical Society; Washington DC: 1997.  p.455-505  

2b Caddick S. Tetrahedron  1995,  51:  10403 

3a Xu CD. Chen GY. Huang X. Chinese Chem. Lett.  1995,  6:  467 

3b Xu CD. Chen GY. Huang X. Org. Prep. Proc. Int.  1995,  27:  559 

3c Xu CD. Chen GY. Huang X. Synth. Commun.  1995,  25:  2229 

4a Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 

4b Cristan H. Chem. Rev.  1994,  94:  1299 

4c Li AH. Dai LX. Aggarwal VK. Chem. Rev.  1997,  97:  2341 

5a Johnson AW. Kaska WC. Starzewsky KAO. Dixon D. Ylides and Imines of Phosphorus   Wiley; New York: 1993. 

5b Speziale AJ. Ratts W. J. Am. Chem. Soc.  1963,  85:  2790 

5c Seyferth D. Singh G. J. Am. Chem. Soc.  1965,  87:  4156 

5d Gosney I. Lloyd D. Tetrahedron  1973,  29:  1697 

5e Huang ZZ. Huang X. Huang YZ. Tetrahedron Lett.  1995,  36:  425 

5f Kayer MM. Zhu J. Hooper DL. Can. J. Chem.  1997,  75:  1315 

For recent review see:

6a Varvoglis A. Chem. Soc. Rev.  1981,  10:  377 

6b Varvoglis A. Synthesis  1984,  709 

6c Moriarty RM. Prakash O. Acc. Chem. Res.  1986,  19:  244 

6d Stang PJ. Angew. Chem. Int. Ed. Engl.  1992,  31:  274 

6e Stang PJ. Zhdankin VV. Chem Rev.  1996,  46:  1123 

7 Ochiai M. J. Organomet. Chem.  2000,  611:  494 

8 Moriarty RM. Prakash I. Prakash O. Freeman W. J. Am. Chem. Soc.  1984,  106:  6082 

9

Typical procedure for the synthesis of α-bromo-substituted phosphonium ylide 3 under microwave irradiation conditions:
To a solution of α-hypervalent iodine functionalized phosphonium ylide in DMF was added Bu₄NBr, and the mixture was irradiated in a modified domestic microwave oven (National, power max. 750 W) for 3 min. The reaction mixture was poured into ice-cold water and extracted with benzene (4 × 20 mL), the organic layer was dried with Na₂SO₄. The solvent was evaporated to obtain a solid. Crystallization of this solid from acetone-hexane gave the pure α-bromosubstituted phosphonium ylide 3. mp155-156 °C (lit. [13] Mp 157-158 °C)

10

General procedure for the synthesis of product under microwave irradiation conditions:
To a solution of α-hypervalent iodine functionalized phosphonium ylide (2.0 mmol) and aldehyde (2.0 mmol) in anhydrous DMF was added the anions of nuleophiles (2.5 mmol), and the mixture was irradiated in a modified domestic microwave oven for a few minutes. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (3 × 20 mL), the organic layer was dried with Na₂SO₄. Removal of the solvent followed by column chromatography (ethyl acetate/hexane) of the crude product yielded (Z)-α-heteroatom-α,β-unsaturated enoates.
General procedure under conventional conditions: Under N₂, to a solution of α-hypervalent iodine functional-ized phosphonium ylide (2.0 mmol) (2.5 mmol) and aldehyde (2.0 mmol) in anhydrous DMF was added the anions of nuleophiles, the mixture was reacted under room temperature for 8-32 hours. After completion of the reaction, the following procedure was the same as above. [14]

11

The ratio of Z/E was determined by the ¹H NMR spectra. It was reported that the signal of vinyl and the methyl proton in ester of Z-type α-heteroatom substituted-α,-unsaturated enoates were in lower field than that of the corresponding E compounds. For example, ¹H NMR spectrum shows that the chemical shifts of vinyl and the methyl in ester proton of
Z-type ethyl 2-bromo-3-(4-methoxyphenyl)-2-propenoate are 7.80 ppm and 1.35 ppm, respectively. While the corresponding chemical shifts of the E-type ethyl 2-bromo-3-(4-methoxyphenyl)-2- propenoate compound are 7.07 ppm and 1.23 ppm, respectively. [12] The result is in accordance with our research.

12a Ohno A. Oae S. Organic Chemistry of Sulfur   Oae S. Plenum; New York: 1976. 

12b Metzner P. Thuillier A. Sulfur Reagents in Organic Synthesis   Academic Press; London, U.K.: 1994. 

13 Denny DB. Ross KW. J. Org. Chem.  1962,  27:  998 

14 Le Menn J.-C. Sarrazin J. Tallec A. Can. J. Chem.  1989,  67:  1332