Lombardo methylenation

What is Lombardo methylenation?

The reaction known as the Lombardo methylenation, Lombardo olefination, or Lombardo reaction was first reported in 1982 by Lombardo as a modification of the Takai-Nozaki methylenation (or Nozaki-Hayashe Methylenation). This method involves the conversion of ketones/aldehydes into alkenes using the carbenoid reagent generated from zinc, dibromomethane, and titanium tetrachloride TiCl4.

The combination of Zn/CH2Br2/TiCl4 is known as the Lombardo reagent or Lombardo’s reagent.

Lombardo methylenation - general reaction scheme - Lombardo-Oshima methylenation - Lombardo-Takai olefination - Takai/Oshima-Lombardo methylenation - Lombardo olefination - Lombardo reaction
Lombardo methylenation
  • R1 = alkyl, aryl
  • R2 = H, alkyl, aryl

The Lombardo reagent is usually prepared by adding TiCl4 to a precooled suspension of zinc dust in a solution of dibromomethane in dry THF at a very low temperature, and aged for two days at 4 ºC before the methylenation.

Unlike the Wittig reaction, the Lombardo methylenation is highly selective and occurs under nonbasic conditions. This reaction is especially valuable for the methylenation of keto esters, for which the Wittig reaction fails, and for the olefination of β,γ-unsaturated enones without enolization.

However, this reaction also has some disadvantages, such as the lengthy preparation of the reagent, the heterogenous nature of the reaction condition, the need for a large excess of reagent, and the low yield in conversion of ketene into allene. An excess amount of reagent makes the workup and isolation very difficult. This reaction is closely related to the condition reported by Takai, Oshima, and co-workers in 1978 and is also referred to as the Lombardo-Oshima methylenation, Lombardo-Takai olefination, or Takai/Oshima-Lombardo methylenation.

The Lombardo reagent is also referred to as the Lombardo-Oshima reagent. The Lombardo methylenation is an alternative olefination method when the Wittig reaction or Tebbe olefination is not applicable.

References

Lombardo, L. (1982). Methylenation of carbonyl compounds with Zn/CH2Br2/TiCl4. Application to gibberellins. Tetrahedron Letters, 23(41), 4293-4296. https://doi.org/10.1016/S0040-4039(00)88728-6

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