Addition of Ethyl Bromodifluoroacetate to Lactones: Reactivity and ­Stereoselectivity

Abstract

Reformatsky-type additions, under various metal­mediated activation, of ethyl bromodifluoroacetate toward a series of unactivated lactones and various sugar lactones proceeded with medium to good yields and in a completely diastereoselective ­manner.

addition reactions - fluorine - lactones - carbohydrates - stereoselectivity

References

For reviews on fluoro-containing compounds, see:

1a Hiyama T. Organofluorine Compounds: Chemistry Applications   Springer; Berlin: 2000. 

1b Iseki K. Tetrahedron  1998,  54:  13887 

Other publications related:

1c Kirsch P. Modern Fluoroorganic Chemistry   Wiley-VCH; Weinheim: 2004. 

1d Adejare A. Ojima I. McCarthy JR. Welch JT. J. Med. Chem.  1997,  40:  2967 

1e Hudlicky M. Ojima I. McCarthy JR. Welch JT. J. Nat. Prod.  1997,  60:  866 

1f Ojima I. McCarthy JR. Welch JT. Biomedical Frontiers of Fluorine Chemistry   ACS Symposium Series 639, American Chemical Society; Washington, DC: 1996. 

2 For a review on the synthesis of gem-difluoro-containing compounds, see: Tozer MJ. Herpin TF. Tetrahedron  1996,  52:  8619 

3a Nyffeler PT. Durón SG. Burkart MD. Vincent SP. Wong C.-H. Angew. Chem. Int. Ed.  2005,  44:  192 

3b Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 

3c Ma J.-A. Cahard D. Chem. Rev.  2004,  104:  6119 

3d Wilkinson JA. Chem. Rev.  1992,  92:  505 

4a Hallinan EA. Fried J. Tetrahedron Lett.  1984,  25:  2301 

4b Welch JT. Tetrahedron  1987,  43:  3123 

4c Doherty AM. Sicar IE. Kornberg B. Winters RT. Kaltenbronn JS. Taylor MD. Batley BL. Rapundalo SR. Ryan MJ. Painchaud CA. J. Med. Chem.  1992,  35:  2 

4d Schirlin D. Baltzer S. Altenburger JM. Tetrahedron Lett.  1988,  29:  3687 

4e Schirlin D. Baltzer S. Altenburger JM. Tetrahedron Lett.  1991,  32:  7255 

4f Robinson RP. Donahue K. J. Org. Chem.  1992,  57:  7309 

4g Thaisrivongs S. Pals DT. Kati WM. Turner SR. Thomasco LM. Watt W. J. Med. Chem.  1986,  29:  2080 

4h Thaisrivongs S. Pals DT. Kati WM. Turner SR. Thomasco LM. Watt W. J. Med. Chem.  1985,  28:  1555 

4i Peet NP. Burkhart JP. Angelastro MR. Giroux E. Mehdi S. Bey P. Kolb M. Neises B. Schirlin D. J. Med. Chem.  1990,  33:  394 

4j Hertel LW. Kroin JS. Misner JW. Tustin JM. J. Org. Chem.  1988,  53:  2406 

4k Witkowski S. Rao YK. Premchandran RH. Halushka PV. Fried J. J. Am. Chem. Soc.  1992,  114:  8464 

5 Term that was introduced by: Seebach D. Angew. Chem., Int. Ed. Engl.  1990,  29:  1320 

6 Marcotte S. Pannecoucke X. Feason C. Quirion JC. J. Org. Chem.  1999,  64:  8461 

For nucleophilic addition of simple lactones, see:

7a Hanessian S. Girard C. Synlett  1994,  865 

7b For a review on β-lactone chemistry, see: Pommier A. Pons JM. Synthesis  1993,  441 

For addition to the sugar lactones derivatives:

7c Csuk R. Franke U. Hu Z. Krieger C. Tetrahedron  2003,  59:  7887 

7d Orsini F. di Teodoro E. Tetrahedron: Asymmetry  2003,  14:  2521 

7e Hanessian S. Girard C. Synlett  1994,  865 

7f Grabberger V. Berger A. Dax K. Fechter M. Gradnig G. Stütz A. Liebigs Ann. Chem.  1993,  379 

7g Csuk R. Glänzer BI. J. Carbohydr. Chem.  1990,  9:  797 

7h Srivastava VK. Lerner LM. J. Org. Chem.  1979,  44:  3368 ; and references cited therein

8a Fürstner A. Synthesis  1989,  571 

8b Fürstner A. Organic Reagents, In The Reformatsky Reaction   Knochel P. Jones P. Oxford University Press; Oxford UK: 1999.  p.287-305  

9 Cintas P. Activated Metals in Organic Synthesis   CRC Press; Boca Raton: 1993.  p.172-183  

10a Burton DJ. Yang ZY. In Chemistry of Organic Fluorine Compounds II: A Critical Review   Hudlicky M. Pavlath AE. ACS Monograph 187, American Chemical Society; Washington, DC: 1995.  p.684 

10b Shen Y. Q’I M. J. Fluorine Chem.  1994,  67:  229 

11a Orsini F. Pelizzoni F. Pulici M. J. Org. Chem.  1994,  59:  1 

11b Ishihara T. Kuroboshi M. Chem. Lett.  1987,  1145 

11c Kagoshima T. Hashimoto L. Oguro D. Saigo K. J. Org. Chem.  1998,  63:  691 

11d Gabriel T. Wessjohann L. Tetrahedron Lett.  1997,  38:  1363 

11e Fukuzawa S. Matsuzawa H. Yoshimitsu S. J. Org. Chem.  2000,  65:  1702 

12a Parrish JD. Shelton DR. Little RD. Org. Lett.  2003,  5:  3615 

12b Ding Y. Zhao G. J. Chem. Soc., Chem. Commun.  1992,  941 

13

Method A. To a suspension of zinc [19] (7 equiv, 15.7 mmol) in anhyd THF (31 mL) warmed to reflux temperature were added ethyl bromodifluoroacetate (3 equiv, 6.7 mmol) and the desired lactone (1 equiv, 2.24 mmol) in anhyd THF (31 mL). The reaction was stirred at the same temperature under inert atmosphere during a variable period between 2.30-4 h depending of the substrate. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH₂Cl₂. The extracts were dried over anhyd MgSO₄. After removal of the solvent under reduced pressure, the crude mixture thus obtained was subjected to flash silica gel chromatography.
Method B.
To a suspension of zinc (7 equiv, 7 mmol) in anhyd THF (12 mL) was added Cp₂TiCl₂ (0.05 equiv, 0.05 mmol) at r.t. The initial reddish color was turned to easily identifiable green color after 2-3 min, the corresponding lactone (1 equiv, 1 mmol) was then added in anhyd THF (12 mL). Finally ethyl bromodifluoroacetate (5 equiv, 5 mmol) in anhyd THF (6 mL) was added. The reaction was stirred at the same temperature under inert atmosphere for 12 h. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH₂Cl₂. The extracts were dried over anhyd MgSO₄. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.
Method C.
To a mixture of (3.5 equiv, 1.33 mmol) of Zn and CeCl₃ (0.06 equiv, 0.023 mmol) in anhyd THF (3 mL) was added a solution of the required lactone (1 equiv, 0.38 mmol) in anhyd THF (6 mL) at r.t. Ethyl bromodifluoroacetate (3 equiv, 1.8 mmol) was added. The reaction mixture was stirred at the same temperature under inert atmosphere for 2-3 h. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH₂Cl₂. The extracts were dried over anhyd MgSO₄. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.
Method D.
To a solution of the required lactone (0.22 mmol, 1 equiv) in anhyd and degassed THF (20 mL) was added, at r.t. and under argon, ethyl bromodifluoroacetate (0.66 mmol, 3 equiv). At this moment, a 0.037 M solution of SmI₂ (50 mL, 8.40 equiv) was added, at r.t., until the blue color persisted. The reaction was stirred at the same temperature until the blue color disappeared and the mixture turned yellow. The resulting mixture was poured into a solution of NaHCO₃ (30 mL) and stirred for 10 min before extraction with CH₂Cl₂. The extracts were dried over anhyd MgSO₄. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.

14 Panev S. Dimitrov V. Tetrahedron: Asymmetry  2000,  11:  1517 

See also:

15a Ocampo R. Dolbier WR. Abboud KA. Zuluaga F. J. Org. Chem.  2002,  67:  72 

15b Machleidt H. Wessendorf R. Justus Liebigs Ann. Chem.  1964,  674:  1 

For recent reviews of samarium(II) iodide in organic synthesis, see:

16a Edmonds DJ. Johnston D. Procter DJ. Chem. Rev.  2004,  104:  3371 

16b Kagan HB. Tetrahedron  2003,  59:  10351 

16c Steel PG. J. Chem. Soc., Perkin Trans. 1  2001,  2727 

16d Molander GA. Harris CR. Tetrahedron  1998,  54:  3321 

16e Krief A. Laval AM. Chem. Rev.  1999,  99:  745 

For intermolecular reactions, see:

16f Girard P. Namy JL. Kagan HB. J. Am. Chem. Soc.  1980,  102:  2693 

16g Girard P. Namy JL. Kagan HB. Tetrahedron  1981,  37:  175 

16h Fukuzawa SI. Matsuzawa H. Yoshimitsu SI. J. Org. Chem.  2000,  65:  1702 ; and references cited therein

16i Reddy PP. Yen KF. Uang BJ. J. Org. Chem.  2002,  67:  1034 

For intramolecular processes, see:

16j Tabuchi T. Kawamura K. Inanaga J. Yamaguchi M. Tetrahedron Lett.  1986,  27:  3889 

16k Molander GA. Etter JB. J. Am. Chem. Soc.  1987,  109:  6556 

16l Moriya T. Handa Y. Inanaga J. Yamaguchi M. Tetrahedron Lett.  1988,  29:  6947 

17

Ethyl 2-{(2 R ,3 R ,4 S ,5 R ,6 R )-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]-tetrahydro-2-hydroxy-2 H -pyran-2-yl}-2,2-difluoroacetate ( 10). Procedure A: column chromatography (cyclohexane-EtOAc = 25:1) of the crude product gave a colorless syrup (73%); [α]_D ²⁰ +49.8 (c 0.616, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.23-7.17 (m, 18 H), 7.12-7.09 (m, 2 H), 4.80 (s, 1 H), 4.73 (m, 4 H), 4.55-4.37 (m, 3 H), 4.15 (q, 2 H, J = 7.17 Hz), 4.10 (m, 1 H), 3.95-3.90 (m, 3 H), 3.68-3.51 (m, 3 H), 1.16 (t, 3 H, J = 7.17 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 162.82 (t, ² J _CF = 30.8 Hz), 138.26, 138.16, 137.90, 137.45, 128.29, 127.82, 127.60, 127.52, 112.30 (dd, J _CF = 263.6 Hz, J _CF = 259.6 Hz), 96.08 (dd, J _CF = 28.17 Hz, J _CF = 26.4 Hz), 83.28, 78.12, 77.33, 75.88, 75.17, 74.97, 73.31, 72.54, 68.16, 63.21, 13.78. ¹⁹F NMR (282 MHz, CDCl₃): δ = -119.94 (d, 1 F, J _FF = 256.5 Hz), -117.63 (d, 1 F, J _FF = 256.5 Hz). MS (EI): 685.3 [M + Na]. Anal. Calcd for C₃₈H₄₀F₂O₈: C, 68.87; H, 6.08. Found: C, 68.56; H, 5.79.

18 Collins P. Ferrier R. Monosaccharides   John Wiley and Sons; New York: 1995. 

19 Tsuda K. Ohki E. Nogoe S. J. Org. Chem.  1963,  28:  783