Lombardo’s Reagent

Introduction

The reagent combination Zn/CH₂Br₂/TiCl₄ gives rise to an organometallic reagent which is known as Lombardo’s reagent. It converts ketones into methylene groups. [¹] The active reagent is presumed to be a dimetalated species (1) which adds to the ketone under the influence of the Lewis acidity of titanium to give a β-oxymetal-substituted organometallic compound (2). Following β-elimination generates the methylene group (3) [²] (Scheme  [¹] ).

Ketones are not enolized by the reagent and as an important consequence adjacent enolizable chiral centers are not epimerized. The reagent is compatible with a wide ­variety of functional groups, e.g., THP and tert-butyldi­methylsilyl ethers, acetals, esters, carboxylic acids, alcohols, and lactones. [³] Such selectivity makes it a valuable procedure in organic synthesis and appreciably augments Wittig methodology.

References

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• 1b Lombardo L. Tetrahedron Lett.  1982,  23:  4293 
• 2 Okazoe T. Takai K. Utimoto K. J. Am. Chem. Soc.  1987,  109:  951 
• 3a Lombardo L. Org. Syn.  1993,  Coll Vol. 8:  386 
• 3b Lombardo L. Org. Syn.  1987,  Coll Vol. 65:  81 
• 4 Liu B. Zhou W.-S. Tetrahedron  2003,  59:  3379 
• 5 Piers E. Orellana A. Synthesis  2001,  2138 
• 6 Scott ME. Lautens M. Org. Lett.  2005,  7:  3045 
• 7 Marsden PS. Ducept PC. Beilstein J. Org. Chem.  2005,  1:  5