Bis(pyridine)iodonium Tetrafluoroborate Usage

(Ipy₂BF₄, Barluenga’s Reagent)

This mild iodinating and oxidizing reagent is capable of selectively reacting with a wide range of unsaturated substrates and tolerates a variety of functional groups. Ipy₂BF₄ reacts with acetonides derived from simple terpenes to accomplish selective iodofunctionalization with excellent regio- and diastereofacial control (Scheme 25).¹

Scheme 25.

When added to 2-alkynyl-substituted benzaldehydes, Ipy₂BF₄ produces substituted naphthalene products upon treatment with either an alkene or alkyne (Scheme 26).² Alternatively, subsequent treatment with primary alcohols affords oxygen containing heterocycles (Scheme 27).³

Scheme 26.

Scheme 27.

Recently, tetracyclic tetrahydrofurans were produced using Ipy₂BF₄ in a key step of the synthesis of a series of potential broad- spectrum psychotropic agents (Scheme 28).⁴

Scheme 28.

Additionally, Ipy₂BF₄ has been reported to be useful in general iodinations (Scheme 29)⁵ and oxidation of alcohols to carbonyls.⁶ Photolytic reactions of cycloalkanols produced ring-cleaved products, while thermal reactions left the ring intact during oxidation (Scheme 30). Thermal reactions of primary alcohols were capable of producing either aldehydes in dilute conditions or esters in more concentrated solutions (Scheme 31).

Scheme 29.

Scheme 30.

Scheme 31.

References

1. Barluenga J, Alvarez-Pérez M, Rodríguez F, Fañanás FJ, Cuesta JA, García-Granda S. 2003. Total Diastereofacial Selective Iodofunctionalization of Terpene Derivatives Based on Ipy2BF4. J. Org. Chem.. 68(17):6583-6586. https://doi.org/10.1021/jo034517f

2. Barluenga J, Vázquez-Villa H, Ballesteros A, González JM. 2003. Regioselective Synthesis of Substituted Naphthalenes:? A Novel de Novo Approach Based on a Metal-Free Protocol for Stepwise Cycloaddition ofo-Alkynylbenzaldehyde Derivatives with Either Alkynes or Alkenes. Org. Lett.. 5(22):4121-4123. https://doi.org/10.1021/ol035691t

3. Barluenga J, Vázquez-Villa H, Ballesteros A, González JM. 2003. Cyclization of Carbonyl Groups onto Alkynes upon Reaction with IPy2BF4and Their Trapping with Nucleophiles:  A Versatile Trigger for Assembling Oxygen Heterocycles. J. Am. Chem. Soc.. 125(30):9028-9029. https://doi.org/10.1021/ja0355372

4. Fernández J. et al. J. Med. Chem. in press. .

5. Campos PJ, Arranz J, Rodríguez MA. 1997. ?-Iodination of enaminones with bis(pyridine)iodonium(I) tetrafluoroborate. Tetrahedron Letters. 38(48):8397-8400. https://doi.org/10.1016/s0040-4039(97)10231-3

6. Barluenga J, González-Bobes F, Murguía MC, Ananthoju SR, González JM. 2004. Bis(pyridine)iodonium Tetrafluoroborate (IPy2BF4): A Versatile Oxidizing Reagent. Chem. Eur. J.. 10(17):4206-4213. https://doi.org/10.1002/chem.200400136