One-Pot, Two-Step Conversion of Aldehydes to Phosphonyl- and Sulfonylpyrazoles Using Bestmann–Ohira Reagent

Abstract

A one-pot, two-step, three-component method for the conversion of commercially available aldehydes to phosphonylpyrazoles has been developed, demonstrating, for the first time, the dual reactivity of the Bestmann-Ohira reagent (BOR) in a single-pot transformation. This method, extended to the synthesis of sulfonylpyrazoles by employing BOR in the first step and a diazomethyl sulfone in the second step, is complementary, with regard to regioselectivity, to the previous methods for the synthesis of such functionalized pyrazoles.

Synthesis of Functionalized Pyrazoles via 1,3‐Dipolar Cycloaddition of α‐Diazo‐β‐ketophosphonates, Sufones and Esters with Electron‐Deficient Alkenes

“…This procedure worked well to produce functionalized pyrazoles in high yields. More importantly, the pyrazole derivative formed by this method is regioisomerically different from pyrazole obtained from nitroalkenes …”

“…In 2012, our group reported a one‐pot synthetic strategy towards the synthesis of phosphonylpyrazoles starting from aldehyde and BOR . As previously discussed, synthesis of homologated alkynes from aldehydes is a well‐established method from BOR by generating Horner‐Wadsworth‐Emmons (HWE) reagent.…”

“…In the preliminary experimental study, we attempted the reaction of p ‐nitrobenzaldehyde 51 with two equivalents of BOR under basic reaction conditions. In the presence of Cs 2 CO 3 , complete conversion of aldehyde to alkyne was observed, but the cycloaddition product was not formed . Ready and co‐worker reported the [3+2] cycloaddition of terminal alkynes and diazo carbonyl compounds in 2007 .…”

“…Aromatic aldehydes possessing electron withdrawing group reacted with BOR and provided the corresponding phosphonylpyrazoles 53a‐e in good yields, whereas aldehydes possessing strongly electron donating substituents furnished the products 53j‐n in lower yields (Scheme ). An aliphatic aldehyde such as isovaleraldehyde and α , β ‐unsaturated aldehyde such as cinnamaldehyde were not compatible for the transformation to pyrazoles …”

Exploiting Palladium-Catalyzed Cross-Coupling for the Synthesis of 2-Aryl-Substituted 1-Aminocyclopropylphosphonates

“…14 The pyrazole ring is virtually planar, bond distances and angles being within normal ranges. 15,16 Concerning the tautomerism, the characteristic feature of the geometry of 1H-pyrazoles allowing the discrimination between the tautomers is the angle centered at N1 atom always being significantly larger than the one centered at N2. 16 The corresponding values for pyrazole 5 were found equal to 114.0° and 103.6°, respectively.…”