Scope of the two-step, one-pot palladium-catalyzed borylation/Suzuki cross-coupling reaction utilizing bis-boronic acid

Abstract

The use of bis-boronic acid for the direct synthesis of boronic acids has greatly facilitated the two-step, one-pot borylation/Suzuki cross-coupling reaction between aryl and heteroaryl halides. With use of Buchwald's second-generation XPhos preformed catalyst, high yields of cross-coupled products were obtained for most substrates. The method also allows an efficient two-step, one-pot synthesis, providing access to three distinct cross-coupled products after column chromatography. The method also provides a rapid and convenient route to teraryl compounds.

Figure 1

Buchwald’s First Generation XPhos Preformed Catalyst XPhos-Pd-G1 (1), Second Generation XPhos Preformed Catalyst XPhos-Pd-G2 (2), and Ligands XPhos (A) and CataCXium A (B).

Figure 2

Color Change Indicating Completion of Borylation Reaction. From Left to Right: Completion of Borylation on an Aryl Chloride, and Completion of Borylation of an Aryl Bromide.

Scheme 1

Diboron Reagents. Comparison of Current and Newly Developed One-Pot Miyaura Borylation/Suzuki Cross-Coupling Reaction Methods

Scheme 2

Proposed Mechanisms of the Two-Step, One-Pot Borylation/Suzuki Reaction with BBA and XPhos-Pd-G2

Scheme 3

One Pot Borylation/Suzuki Reaction Utilizing BBA and XPhos-Pd-G2 Yielding Three Distinct Products

Scheme 4

Efficient Teraryl Synthesis Utilizing Alcohols as Masked Halides and Boronic Acids