Mandelic Acid as Synthetic Equivalent of Benzoyl Carbanion. Synthesis of Nitrobenzophenones

Abstract

Nitrobenzophenones are prepared from a mandelic acid dioxolanone. The sequence starts with the aromatic nucleophilic substitution of the enolate of the dioxolanone onto p-fluoronitrobenzenes, followed by hydrolysis of the acetal moiety and oxidative decarboxylation of the resulting α-hydroxyacids. The whole sequence involves the use of mandelic acid as synthetic equivalent of the benzoyl carbanion.

acetals - nucleophilic aromatic substitutions - ketones - oxygen - oxidations - decarboxylation

References

1 Wiesner J. Kettler K. Jomaa H. Schlitzer M. Bioorg. Med. Chem. Lett.  2002,  12:  543 

2 Palomer A. Pascual J. Cabré M. Borràs L. González G. Aparici M. Carabaza A. Cabré F. García ML. Mauleón D. Bioorg. Med. Chem. Lett.  2002,  12:  533 

3 Schlitzer M. Böhm M. Sattler I. Bioorg. Med. Chem.  2002,  10:  615 

4 Nilsson JP. Andersson C.-M. Tetrahedron Lett.  1997,  38:  4635 

5a Langer P. Holtz E. Synlett  2003,  402 

5b Kaiser F. Schwink L. Velder J. Schmalz HG. Tetrahedron  2003,  59:  3201 

5c Vidya R. Eggen M. Georg GJ. Himes RH. Bioorg. Med. Chem. Lett.  2003,  13:  757 

5d Denieul MP. Laursen B. Hazell R. Skrydstrup T. J. Org. Chem.  2000,  65:  6052 

5e Karrer F. Meier H. Pascual A. J. Fluor. Chem.  2000,  103:  81 

6a Friedel-Crafts and Related Reactions   Vol I-IV:  Olah G. Wiley-Interscience; New York: 1962-1964. 

6b Heaney H. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  Chap. 3.2. p.733 

7a Blay G. Fernández I. Formentín P. Pedro JR. Roselló AL. Ruiz R. Journaux Y. Tetrahedron Lett.  1998,  39:  3327 

7b Blay G. Fernández I. Formentín P. Monje B. Pedro JR. Ruiz R. Tetrahedron  2001,  57:  1075 

7c Blay G. Fernández I. Monje B. Pedro JR. Ruiz R. Tetrahedron Lett.  2002,  43:  8463 

8a Künding EP. Desobry V. Simmons DP. Wegner E. J. Am. Chem. Soc.  1989,  111:  1804 

8b Rose-Munch F. Rose E. Semra A. J. Chem. Soc., Chem. Commun.  1987,  942 

8c Rose-Munch F. Rose E. Semra A. Jeannin Y. Rober F. J. Organomet. Chem.  1988,  353:  53 

8d Rose-Munch F. Rose E. Semra A. Mignon L. Garcia-Oricain J. Knobler C. J. Organomet. Chem.  1989,  363:  297 

9a Zhang TY. Zhang H. Tetrahedron Lett.  2002,  43:  1363 

9b Ahman J. Wolfe JP. Troutman MV. Palucki M. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  1918 

9c Freund R. Mederski WWKR. Helv. Chim. Acta  2000,  83:  1247 

9d Palucki M. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  11108 

9e Littke AF. Fu GC. Angew. Chem. Int. Ed.  1998,  37:  3387 

10a Lawrence NJ. Liddle J. Jackson DA. Synlett  1996,  55 

10b Makosza M. Synthesis  1991,  103 

11a Selvakumar N. Azhagan AM. Srinivas D. Krishna GG. Tetrahedron Lett.  2002,  43:  9175 

11b Selvakumar N. Reddy BY. Kumar GS. Iqbal J. Tetrahedron Lett.  2001,  42:  8395 

11c Gurjar M. Reddy DS. Murugaiah A. Murugaiah S. Synthesis  2000,  1659 

12 Comprehensive Carbanion Chemistry, Part A   Durst T. Elsevier; Amsterdam: 1980.  Chap. 5.

13 Handbook of Reagents for Organic Synthesis. Acidic and Basic Reagents   Reich JH. Rigby JH. John Wiley and Sons; Chichester: 1999. 

14a Katritzky AR. Chassaing C. Toader D. Gill K. J. Chem. Res., Synop.  1999,  504 

14b Davis RB. Benigni JB. J. Org. Chem.  1962,  27:  1605 

15 Steglich W. Kübel B. Gruber P. Chem. Ber.  1976,  106:  2870 

Stereochemistry of compounds 3 was determined by NOE experiments and it is in good agreement with the results reported by Seebach:

16a Seebach D. Naef R. Calderari G. Tetrahedron  1984,  40:  1313 

16b Seebach D. Sting AR. Hoffmann M. Angew. Chem., Int. Ed. Engl.  1996,  35:  2708 

17 Bull DJ. Fray MJ. Mackenny MC. Malloy KA. Synlett  1996,  647 

18

All prepared compounds gave satisfactory spectroscopic and HRMS data.