Iodolactonization

What is Iodolactonization?

The formation of lactones from β,γ- or γ,δ-unsaturated carboxylic acid derivatives using a positive iodine source with group and face selectivity is known as iodolactonization. This reaction was first reported by Bougault from 1904 to 1908 and is occasionally referred to as iodo cyclization. Similar reactions with bromine sources are called bromolactonization.

Iodolactonization - general reaction scheme
Iodolactonization
  • X = O, NH
  • R1, R2, R3 = H, alkyl, aryl

The iodine sources used for this reaction include:

  • I2 + NaHCO3 + H2O
  • KI + I2 + NaHCO3
  • I2 + AgOTF
  • cyanogen iodide (CNI)
  • ICl
  • IBr
  • N-iodosuccinimide (NIS)
  • iodonium dicollidine perchlorate
  • chalcogen iodine complex
  • etc

The unsaturated carboxylic acid derivatives can be acids, their esters, amides, or the phosphate. Although the unsaturated bonds are mostly double bonds, they could be triple bonds as well. The success of this reaction depends on the ability to form either a five- or six-membered ring and on the electron density on the unsaturated bond. The increase of electron density on the carbonyl group or the presence of substituents at the α position of carboxylic group facilitates this reaction and accelerates the reaction rate.

The stereochemistry of the products mostly depends on the substrates. However, in some cases, the reagents also control the outcome of the stereochemistry.

This reaction has broad applications in organic syntheses, including the synthesis of nucleosides and the change of stereochemistry of unsaturated carboxylic acids. In a special case, the iodolactonization is also competed by iodosultinization.

References

  • Stobbe, H., Ann., 1902, 321, 119
  • Fittig, R., Ann., 1904, 331, 142
  • Bougault, M. J., Compt. Rend., 1904, 139, 864
  • Bougault, M. J., Ann. Chim. Phys., 1908, 14, 145
  • Bougault, M. J., Ann. Chim. Phys., 1908, 15, 296
  • Haas, J.; Piguel, S. andWirth, T., Org. Lett., 2002, 4, 297
  • Chai,W.-G.; Ye, M.-C.; Yan, L. and Zhao, Y.-F., J. Org. Chem., 1987, 52, 1617
  • Van Tamelen, E. E. and Shamma, M., J. Am. Chem. Soc., 1954, 76, 2315
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