Chemical Synthesis

Cyclopropane Reagent

Potassium Cyclopropyltrifluoroborate:
Cyclopropyl groups are found in a numerous natural products and are increasingly incorporated into pharmaceuticals such as the broad-spectrum antibiotic ciprofloxacin (Figure 1). A common method for installation of a pre-formed cyclopropane ring is through the use of cyclopropane-containing organometallic reagents such as cyclopropylmagnesium bromide (526797).

Cyclopropane rings may also be affixed to haloarenes and haloolefins via cross-coupling methods, with the Suzuki coupling of cyclopropylboronic acid, cyclopropylboronic acid pinacol ester, or potassium cyclopropyltrifluoroborate being the most explored (Figure 2).

Researchers at Merck reported the successful cross-coupling of cyclopropylboronic acid with a variety of substituted bromobenzene electrophiles, as well as with heteroarylbromides in the presence of Pd(OAc)2, PCy3, and K3PO4 (Figure 3).1

Unfortunately, cyclopropylboronic acid suffers from several drawbacks including: a non-trivial synthesis, a limited and variable shelf-life, and an uncertain stoichiometry due to anhydride formation (necessitating that large excesses of the reagent be used). While use of the corresponding pinacol ester avoids these issues, two-thirds of the carbon content of the molecule ultimately ends up as pinacol waste that requires extra effort to remove upon completion of the cross-coupling reaction. Addressing these issues, the Charette and Deng groups have reported success in the cross-coupling of substituted potassium cyclopropyltrifluoroborates with aryl bromides in the presence of common palladium catalysts (Scheme 1).2,3 The organotrifluoroborates exhibit enhanced stability and more certain stoichiometry relative to their boronic acid counterparts. Generally they can be handled in open air, and are stable to the presence of moisture. Additionally, post-reaction byproducts (salts) are easily removed from the crude reaction mixture by a simple aqueous wash.

Sigma-Aldrich is delighted to add the new “parent” potassium cyclopropyltrifluoroborate reagent to our expanding portfolio of nucleophiles for Suzuki cross-coupling.

   Product Information


Product #  Product Name/Description Add To Cart
662984 Potassium cyclopropyltrifluoroborate
  • Aldrichimica Acta review on trifluoroborate reagents (Click here to view).
  • Cheminar™ 1.2: Potassium Organotrifluoroborates on-line seminar (Click here to view).
  • Boron Reagents for Suzuki Coupling Product Directory (Click here to view).


References:

  1. Wallace, D. J.; Chen, C.-y. Tetrahedron Lett. 2002, 43, 6987.
  2. Charette, A. et al. Synlett 2005, 11, 1779.
  3. Fang, G.-H. et al. Org. Lett. 2004, 6, 357.