Radical Conjugated Addition:
Addition of Dialkyl Phosphonodifluoromethyl Radical onto Unsaturated
Ketones

Aboubacary Sène; Sonia Diab; Antje Hienzsch; Dominique Cahard; Thierry Lequeux

doi:10.1055/s-0028-1088207

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2009(6): 981-985
DOI: 10.1055/s-0028-1088207

LETTER

Radical Conjugated Addition: Addition of Dialkyl Phosphonodifluoromethyl Radical onto Unsaturated Ketones

Aboubacary Sène^a, Sonia Diab^a, Antje Hienzsch^a, Dominique Cahard^b, Thierry Lequeux*^a
^a Laboratoire de Chimie Moléculaire et Thioorganique, CNRS UMR 6507 & FR3038, Université de Caen Basse-Normandie, ENSICAEN 6 Boulevard du Maréchal Juin, 14050 Caen Cedex, France
Fax: +33(2)31452865; e-Mail: Thierry.Lequeux@ensicaen.fr;
^b Chimie Organique et Bioorganique: Réactivité et Analyse, CNRS UMR 6014 & FR3038, Université de Rouen, INSA de Rouen, Rue Tesnière, 76130 Mont Saint Aignan, France

Further Information

Publication History

Received 22 December 2008
Publication Date:
16 March 2009 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

The free radical addition of phosphonodifluoromethyl radical is reported from iodophosphonate and sodium dithionite, triethylborane, or dilauroyl peroxide as initiator. Triethylborane promoted the radical conjugated addition onto enones.

Key words

radical reaction - fluorine - enone - phosphonate - alkene

References and Notes

1a Blackburn GM. England DA. Kolkmann F. J. Chem. Soc., Chem. Commun. 1981, 930

Google Scholar
1b Blackburn GM. Kent DE. Kolkmann F. J. Chem. Soc., Perkin Trans. 1 1984, 1119

Google Scholar
1c Thatcher GR. Campbell AS.
J. Org. Chem. 1993, 58: 2272

Google Scholar
1d Chambers RD. O’Hagan D. Lamont RB. Jain SC. J. Chem. Soc., Chem. Commun. 1990, 1053

Google Scholar
1e Kim CU. Luh BY. Misco PF. Bronson JJ. Hitchcock MJM. Ghazoulli I. Matin JC. J. Med. Chem. 1990, 33: 1207

Google Scholar
1f Smyth MS. Ford H. Burke TR. Tetrahedron Lett. 1992, 33: 4137

Google Scholar
1g Jakeman DL. Ivory AJ. Williamson MP. Blackburn GM. J. Med. Chem. 1998, 41: 4439

Google Scholar
1h Berkowitz DB. Bose M. Pfannenstiel TJ. Doukov T. J. Org. Chem. 2000, 65: 4498

Google Scholar
1i Berkowitz DB. Bose M. J. Fluorine Chem. 2001, 112: 13

Google Scholar
1j O’Hagan D. Rzepa HS. Chem. Commun. 1997, 645

Google Scholar
2a Yang Z.-Y. Burton DJ. J. Org. Chem. 1991, 56: 5125

Google Scholar
2b Julià L. Bosch MP. Rodriguez S. Guerrero A.
J. Org. Chem. 2000, 65: 5098

Google Scholar
2c Sato K. Nakazato S. Enko H. Tsujita H. Fujita K. Yamamoto T. Omote M. Ando A. Kumadaki I. J. Fluorine Chem. 2003, 121: 105

Google Scholar
2d Sato K. Omote M. Ando A. Kumadaki I. J. Fluorine Chem. 2004, 125: 509

Google Scholar
2e Xiao F. Wu F. Shen Y. Zhou L. J. Fluorine Chem. 2005, 126: 63

Google Scholar
2f Ghattas W. Hess CR. Iacazio G. Hardré R. Klinman JP. Réglier M.
J. Org. Chem. 2006, 71: 8618

Google Scholar
2g Moreno B. Quehen C. Rose-Hélène M. Leclerc E. Quirion J.-C. Org. Lett. 2007, 9: 2477

Google Scholar
2h Yang X. Yuan W. Gu S. Yang X. Xiao F. Shen Q. Wu F. J. Fluorine Chem. 2007, 128: 540

Google Scholar
2i Godineau E. Schenk K. Landais Y. J. Org. Chem. 2008, 73: 6983

Google Scholar
2j Leung L. Linclau B. J. Fluorine Chem. 2008, 129: 986

Google Scholar
3a Yang Z. Burton DJ. Tetrahedron Lett. 1991, 32: 1019

Google Scholar
3b Yang Z. Burton DJ. J. Org. Chem. 1992, 57: 4676

Google Scholar
4 Hu C. Chen J. J. Chem. Soc., Perkin Trans. 1 1993, 327

Crossref Google Scholar
5a Lequeux T. Lebouc F. Lopin C. Yang H. Gouhier G. Piettre S. Org. Lett. 2001, 3: 185

Google Scholar
5b Pignard S. Lopin C. Gouhier G. Piettre SR. J. Org. Chem. 2006, 71: 31

Google Scholar
5c Murakami S. Kim S. Ishii H. Fuchigami T. Synlett 2004, 815

Google Scholar
6a Huang B. Wu F. Zhou C. J. Fluorine Chem. 1995, 75: 1

Google Scholar
6b Wu F. Huang B. Lu L. Huang W. J. Fluorine Chem. 1996, 80: 91

Google Scholar
6c Petrik V. Cahard D. Tetrahedron Lett. 2007, 48: 3327

Google Scholar
6d Li Y. Li H. Hu J. Tetrahedron 2009, 65: 478

Google Scholar
7 Li A. Chen Q. Synthesis 1996, 606

Article in Thieme Connect Google Scholar
8 Yang X. Zhu Y. Fang X. Yang X. Wu F. Shen Y.
J. Fluorine Chem. 2007, 128: 174

Google Scholar
9 Nair KD. Guneratne RD. Modak AS. Burton DJ.
J. Org. Chem. 1994, 59: 2393

Crossref Google Scholar
10 Henry-dit-Quesnel A. Toupet L. Pommelet J.-C. Lequeux T. Org. Biomol. Chem. 2003, 1: 2486

Crossref Google Scholar
12 Xu Y. Prestwich GD. Org. Lett. 2002, 4: 4021

Crossref Google Scholar
13 Li Y. Liu J. Zhang L. Zhu L. Hu J. J. Org. Chem. 2007, 72: 5824

Crossref Google Scholar
14 Chambers RD. Jaouhari R. O’Hagan D. Tetrahedron 1989, 45: 5101

Crossref Google Scholar
15a Quiclet-Sire B. Zard SZ. J. Am. Chem. Soc. 1996, 118: 9190

Google Scholar
15b Studer A. Amrein S. Synthesis 2002, 835

Google Scholar
15c Jean-Baptiste L. Yemets S. Legay R. Lequeux T.
J. Org. Chem. 2006, 71: 2352

Google Scholar
16a Buttle LA. Motherwell WB. Tetrahedron Lett. 1994, 35: 3995

Google Scholar
16b Dolbier WR. Chem. Rev. 1996, 96: 1557

Google Scholar
17 Srikanth GSC. Castle SL. Tetrahedron 2005, 61: 10377

Crossref Google Scholar
18a Lequeux TP. Percy JM. J. Chem. Soc., Chem. Commun. 1995, 2111

Google Scholar
18b Kawamoto AM. Campbell MM. J. Chem. Soc., Perkin Trans. 1 1997, 1249

Google Scholar
18c Murano T. Muroyama S. Yokomatsu T. Shibuya S. Synlett 2002, 1657

Google Scholar
18d Hikishima S. Isobe M. Koyanagi S. Soeda S. Shimeno H. Sibuya S. Yokomatsu T. Bioorg. Med. Chem. 2006, 14: 1660

Google Scholar

11

The elimination of HI was also observed when crude 5b was treated with DBU in CH₂Cl₂ over 2 h at 20 ˚C.

19

Typical Procedure for the Synthesis of Phosphonate 12a
To a solution of the 2-cyclohexenone (0.073 mL, 0.76 mmol) and iodo-difluoromethylphosphonate 2 (200 mg, 0.58 mmol) in CH₂Cl₂ (5 mL) at 20 ˚C under N₂ was slowly added a solution of Et₃B (0.058 mL, 1 M in n-hexane). Addition of Et₃B (5 × 0.058 mL) was realized every 1 h until complete consumption of the iodophosphonate. After 6 h under stirring, the solvents were evaporated under reduced pressure, and the crude mixture was purified by flash column chromatography (n-C₅H₁₂-EtOAc, 3:2) to afford the phosphonoketone 12a (125 mg, 69%). ^¹H NMR (250 MHz, CDCl₃): δ = 1.30 (d, ^³ J _HH = 6.2 Hz, 12 H), 1.53-1.67 (m, 2 H), 2.05-2.61 (m, 7 H), 4.78 (dsept, ^³ J _HH = ^³ J _HP = 6.2 Hz, 2 H). ^¹9F NMR (235 MHz, CDCl₃): δ = -115.7 (ddd, ^² J _FF = 299 Hz, ^² J _FP = 108 Hz, ^³ J _FH = 13 Hz), -118.14 (ddd, ^² J _FF = 299 Hz, ^² J _FP = 108 Hz, ^³ J _FH = 13 Hz). ^³¹P NMR (101 MHz, CDCl₃): δ = 4.64 (t, ^² J _PF = 108 Hz). ^¹³C (63 MHz, CDCl₃):
δ = 23.7 (m, i-Pr and CH₂), 24.0 (d, ^³ J _CP = 2.5 Hz, i-Pr), 24.2 (s, CH₂), 39.8 (dt, ^³ J _CF = ^³ J _CP = 4.6 Hz, CH₂), 40.9 (s, CH₂), 42.8 (dt, ^² J _CF = 20.6 Hz, ^² J _CP = 15.3 Hz, CH), 73.8 (d, ^² J _CP = 3.0 Hz, i-Pr), 73.9 (d, ^² J _CP = 3.0 Hz, i-Pr), 121.9
(dt, ^¹ J _CF = 263.0 Hz, ^¹ J _CP = 214.0 Hz, CF₂), 208.9 (s, CO). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₃H₂₄F₂O₄P: 313.1380; found: 313.1366.
Phosphonate 12b: ^¹H NMR (250 MHz, CDCl₃): δ = 1.31 (d, ^³ J _HH = 6.2 Hz,12 H), 1.97-2.38 (m, 6 H), 2.84-2.91 (m, 1 H), 4.80 (dsp, ^³ J _HH = ^³ J _HP = 6.2 Hz, 2 H). ^¹9F NMR (235 MHz, CDCl₃): δ = -119.04 (ddd,^² J _FF = 298 Hz, ^² J _FP = 101 Hz, ^³ J _FH = 15 Hz), -117.10 (ddd, ^² J _FF = 298 Hz, ^² J _FP = 101 Hz, ^³ J _FH = 17 Hz). ^³¹P NMR (101 MHz, CDCl₃): δ = 4.79 (t, ^² J _PF = 108 Hz). ^¹³C (63 MHz, CDCl₃): δ = 22.1 (dt, ^³ J _CF = ^³ J _CP = 5.1 Hz, CH₂), 23.7 (d, ^³ J _CP = 4.2 Hz, i-Pr), 24.0 (d, ^³ J _CP = 3.3 Hz, i-Pr), 37.5 (s, CH₂), 38.1 (dt, ^³ J _CF = ^³ J _CP = 3.0 Hz, CH₂), 40.5 (dt, ^² J _CF = 21.4 Hz, ^² J _CP = 15.2 Hz, CH), 73.8 (d, ^² J _CP = 7.2 Hz, i-Pr), 73.81 (d, ^² J _CP = 7.1 Hz, i-Pr), 119.9 (dt, ^¹ J _CF = 262.0 Hz, ^¹ J _CP = 217.0 Hz, CF₂), 215.8 (s, CO). ESI-HRMS: m/z [M + H]⁺ calcd for C₁₂H₂₂F₂O₄P: 299.1224; found: 299.1213.