Chemoselectivity in the Reactions Between Ethyl 4,4,4-Trifluoro-3-oxobutanoate and Anilines: Improved Synthesis of 2-Trifluoromethyl-4- and 4-Tri­fluoromethyl-2-quinolinones

Abstract

Chemoselectivity in the reactions between ethyl 4,4,4-trifluoroacetoacetate (ethyl 4,4,4-trifluoro-3-oxobutanoate) and various anilines was systematically studied as a function of the reaction conditions used (solvent/temperature, catalyst). The results obtained allowed chemoselective (>90%) synthesis of the corresponding ethyl 3-arylamino-4,4,4-trifluorobut-2-enoates and N-aryl-4,4,4-trifluoro-3-oxobutyramides, which were cyclized to afford 2-trifluoromethyl-4-quinolinones and 4-trifluoromethyl-2-quinolinones, respectively.

chemoselectivity - enamino esters - keto amides - quinolines - fluorine

References

<A NAME="RM01103SS-1">1</A> Marull M. Schlosser M. Eur. J. Org. Chem  2003,  1576 ; and references cited therein

<A NAME="RM01103SS-2">2</A> Lefebvre O. Marull M. Schlosser M. Eur. J. Org. Chem.  2003,  2115 ; and references cited therein

<A NAME="RM01103SS-3">3</A> Schlosser M. Marull M. Eur. J. Org. Chem.  2003,  1569 

<A NAME="RM01103SS-4">4</A> Cottet F. Marull M. Lefebvre O. Schlosser M. Eur. J. Org. Chem.  2003,  1559 

<A NAME="RM01103SS-5">5</A> Soloshonik VA. Ono T. J. Org. Chem.  1997,  62:  3030 

<A NAME="RM01103SS-6">6</A> Soloshonik VA. Ono T. Soloshonik IV. J. Org. Chem.  1997,  62:  7538 

<A NAME="RM01103SS-7">7</A> Soloshonok VA. Kukhar VP. Tetrahedron  1997,  53:  8307 

<A NAME="RM01103SS-8">8</A> Soloshonok VA. Ohkura H. Uneyama K. Tetrahedron Lett.  2002,  43:  5449 

<A NAME="RM01103SS-9">9</A>

Ohkura, H.; Berbasov, D. O.; Soloshonok, V. A. Tetrahedron 2003, in press.

<A NAME="RM01103SS-10">10</A>

In the reported procedure (see Ref. [2] )the starting keto ester 3 and anilines 4 were used in a ratio of 2:1; accordingly, the corresponding yields of the products 2 are calculated based on 4. Despite the fact that keto ester 3 is a cheap technical bulkware, it is still more expensive than most of the anilines 4, therefore, we believe that the chemical yields, as one of the criteria of synthetic efficiency, should be calculated on 3 to make an economical sense.

<A NAME="RM01103SS-11">11</A> Kobayashi Y. Kumadaki I. Taguchi S. Chem. Pharm. Bull.  1969,  17:  2335 

<A NAME="RM01103SS-12">12</A> Liu J. LU HJ. J. Fluorine Chem.  2001,  111:  207 

For additional references on the synthesis of trifluoromethyl-containing compounds of type 5 and 6, see the following papers suggested by a referee:

<A NAME="RM01103SS-13A">13a</A> Latham EJ. Stanforth SP. J. Chem. Soc., Perkin Trans. 1  1997,  2059 

<A NAME="RM01103SS-13B">13b</A> Combs DW. Reed MS. Klaubert DH. Synth. Commun.  1992,  22:  323 

<A NAME="RM01103SS-13C">13c</A> Bajwa GS. Joullie MM. J. Heterocycl. Chem.  1972,  9:  1403 

<A NAME="RM01103SS-13D">13d</A> Fustero S. Pina B. Salavert E. Navarro A. Ramires de Arrellano MC. Fuentes AS. J. Org. Chem  2002,  67:  4667 

<A NAME="RM01103SS-13E">13e</A> Stanforth SP. Tetrahedron  2002,  57:  1833 

<A NAME="RM01103SS-14A">14a</A> Gildemeister H. Knorr H. Mildenberger H. Salbeck G. Liebigs Ann. Chem.  1982,  1656 

<A NAME="RM01103SS-14B">14b</A> Staskun B. Israelstam SS. J. Org. chem.  1961,  26:  3191