Homo-Favorskii rearrangement explained

The homo Favorskii rearrangement is the rearrangement of β-halo ketones and cyclobutanones, which in ring systems may yield ring contraction.[1] This rearrangement takes place in the presence of a base, yielding a carboxylic acid derivative corresponding to the nucleophile (most often the base itself). E1cb will occur if α-carbon adjacent to the halogen atom has hydrogens on it.

Reaction mechanism

The reaction proceeds in an analogous manner to that of the Favorskii rearrangement. The major difference is that the cyclopropanone intermediate is replaced by a cyclobutanone intermediate, and therefore the intermediate's formation cannot be viewed as a 2-electron electrocyclization reaction.The selectivity is similar to the Favorskii rearrangement in that the most stable carbanion is formed.

Examples

The homo-Favorskii rearrangement is a key step in the synthesis of Kelsoene, constructing its four-membered ring. In this particular example, the nucleophile is absent and the base, t-BuOK, is very bulky. Therefore, the cyclobutanone intermediate can be isolated and is further reacted to yield the product.[2] [3]

See also

Notes and References

  1. Book: Kurti 1 Czako 2, Laszlo 1 Barbara 2 . Strategic Applications of Named Reactions in Organic Synthesis . 15 September 2005 . . 0-12-429785-4 . 164–165.
  2. Zhang . Liming . Koreeda . Masato . 2002-10-01 . Stereocontrolled Synthesis of Kelsoene by the Homo-Favorskii Rearrangement . Organic Letters . en . 4 . 21 . 3755–3758 . 10.1021/ol026739q . 12375936 . 1523-7060.
  3. Web site: Homo-Favorskii rearrangement - Big Chemical Encyclopedia . 2024-06-02 . chempedia.info.