Standard Article

Carbonyl Methylenation and Alkylidenation Using Titanium-Based Reagents

  1. Stanley H. Pine

Published Online: 15 OCT 2004

DOI: 10.1002/0471264180.or043.01

Organic Reactions

Organic Reactions

How to Cite

Pine, S. H. 2004. Carbonyl Methylenation and Alkylidenation Using Titanium-Based Reagents. Organic Reactions. 43:1:1–91.

Author Information

  1. California State University, Department of Chemistry and Biochemistry, Los Angeles, California

Publication History

  1. Published Online: 15 OCT 2004

Abstract

Alkylidenation of the carbonyl group of ketones and aldehydes is among the most useful reactions of organic synthesis. The Wittig reaction of phosphoranes is probably the most widely used method of alkylidenation, although a variety of other approaches have been developed to accomplish this transformation.

The observation that titanium-based reagents can accomplish such a transformation has provided a new approach to alkylidenation. Not only do these reagents accomplish alkylidenation of the carbonyl group of aldehydes and ketones, but they are also effective with esters, lactones, amides, thioesters, and certain other carboxylic acid derivatives. Alkylidenation of the carbonyl group of carboxylic acid derivatives cannot normally be accomplished by the Wittig reaction.

Initial interest in the reaction focused on methylenation using the titanium–aluminum complex known as the Tebbe reagent.

Reactions of the Tebbe reagent with carboxylic esters and observed their conversion to enol ethers in high yield.

Furthermore, the Tebbe reagent was also found to methylenate aldehydes and ketones, sometimes more effectively than the Wittig method. The related titanium metallacycles, which are prepared from the Tebbe reagent and an alkene in the presence of a Lewis base, accomplish similar alkylidenations.

During the same period a still undefined reagent was prepared from zinc, a dihalomethane, and titanium tetrachloride that was shown to methylenate aldehydes and ketones. Modification of this mixture provides a reagent that accomplishes methylenation and alkylidenation of carboxylic acid derivatives. An alternative preparation of this reagent has also received wide use.

Reagents for carbonyl alkylidenation involving titanium–magnesium, zirconium, tantalum, tungsten, molybdenum, boron, and chromium have also been studied, but none has found such broad use in synthesis.

Keywords:

  • carbonyl methylenation;
  • alkylidenation;
  • mechanism;
  • titanium catalysts;
  • carboxylic acid derivatives;
  • ketones;
  • aldehydes;
  • functional group selectivity;
  • Tebbe reagent;
  • experimental procedures;
  • esters;
  • amides;
  • amides;
  • experimental procedures;
  • scope;
  • limitations