Michael Addition of Ketone Enolates to α,β-Unsaturated Esters or Amides in a One-Pot Procedure: Highly Efficient Effect of Lithium Salt Generated in situ on Organotin Enolate

Abstract

Michael addition of a metal ketone enolate to an α,β-unsaturated ester is thermodynamically disfavored, and thus, isolated metal enolates with an equimolar amount of Lewis acids or additives are usually required. This work describes the methodology of one-pot Michael addition from the parent ketones and unsaturated esters to the products directly. The treatment of a parent ketone with sec-butyllithium and Bu₃SnBr gives a highly coordinated tin enolate that is complexed with LiBr generated in situ. The species is reactive and affords the Michael adducts, δ-keto esters and amides, in the reaction with α,β-unsaturated esters and amides, respectively.

tin enolates - ligand - Michael addition - unsaturated ester - high coordination

References

<A NAME="RF12104SS-1">1</A> Trost BM. Comprehensive Organic Synthesis   Vol. 3:  Pergamon; Oxford: 1991.  p.1-63  

<A NAME="RF12104SS-2">2</A> Yasuda M. Chiba K. Ohigashi N. Katoh Y. Baba A. J. Am. Chem. Soc.  2003,  125:  7291 

<A NAME="RF12104SS-3">3</A> Hashimoto Y. Machida S. Saigo K. Inoue J. Hasegawa M. Chem. Lett.  1989,  943 

Examples for types A-C:

<A NAME="RF12104SS-4A">4a</A> Oare DA. Heathcock CH. J. Org. Chem.  1990,  55:  157 

<A NAME="RF12104SS-4B">4b</A> Yamaguchi M. Tsukamoto M. Hirao I. Chem. Lett.  1984,  375 

<A NAME="RF12104SS-5A">5a</A> For classical examples using a strong base for cycloalkanones, see: House HO. Roelofs WL. Trost BM. J. Org. Chem.  1966,  31:  646 

<A NAME="RF12104SS-5B">5b</A> For reactions involving a subsequent step such as cyclization after Michael addition, see: Miller JJ. de Benneville PL. J. Org. Chem.  1957,  22:  1268 

<A NAME="RF12104SS-5C">5c</A> See also: Lee R. A.; Tetrahedron Lett.; 1973, 3333

<A NAME="RF12104SS-5D">5d</A> For reactions using intramolecular strong interaction between Li and F, see: Yamazaki T., Haga J., Kitazume T., Nakamura S.; Chem. Lett.; 1991, 2171

<A NAME="RF12104SS-5E">5e</A> See also: Yamazaki T. Hiraoka S. Kitazume T. J. Org. Chem.  1994,  59:  5100 

<A NAME="RF12104SS-6">6</A>

A similar result was also observed when LDA was used instead of s-BuLi.

<A NAME="RF12104SS-7A">7a</A> Narasaka K. Soai K. Mukaiyama T. Chem. Lett.  1974,  1223 

<A NAME="RF12104SS-7B">7b</A> Narasaka K. Soai K. Aikawa Y. Mukaiyama T. Bull. Chem. Soc. Jpn.  1976,  49:  779 

<A NAME="RF12104SS-8A">8a</A> The keto-enol tautomerization of the tin species of the Michael adduct causes thermodynamic stabilization: Yasuda M. Ohigashi N. Shibata I. Baba A. J. Org. Chem.  1999,  64:  2180 

<A NAME="RF12104SS-8B">8b</A> Yasuda M. Ohigashi N. Baba A. Chem. Lett.  2000,  1266 

<A NAME="RF12104SS-9">9</A>

LiCl generated in situ as a side product would not be a strong enough Lewis acid for type D reaction.

<A NAME="RF12104SS-10A">10a</A> Yasuda M. Chiba K. Baba A. J. Am. Chem. Soc.  2000,  122:  7549 

<A NAME="RF12104SS-10B">10b</A> Yasuda M. Hayashi K. Katoh Y. Shibata I. Baba A. J. Am. Chem. Soc.  1998,  120:  715 

<A NAME="RF12104SS-10C">10c</A> Yasuda M. Katoh Y. Shibata I. Baba A. Matsuda H. Sonoda N. J. Org. Chem.  1994,  59:  4386 

<A NAME="RF12104SS-11A">11a</A> Zapata A. Acuna CA. Synth. Commun.  1984,  14:  27 

<A NAME="RF12104SS-11B">11b</A> Shimada E. Inomata K. Mukaiyama T. Chem. Lett.  1974,  689 

<A NAME="RF12104SS-12">12</A> Hiroi K. Yamada S. Chem. Pharm. Bull.  1973,  21:  47 

<A NAME="RF12104SS-13">13</A> Pereyre M. Bellegarde B. Mendelsohn J. Valade J. J. Organomet. Chem.  1968,  11:  97