Scope of the palladium-catalyzed aryl borylation utilizing bis-boronic acid

Abstract

The Suzuki-Miyaura reaction has become one of the more useful tools for synthetic organic chemists. Until recently, there did not exist a direct way to make the most important component in the coupling reaction, namely the boronic acid. Current methods to make boronic acids often employ harsh or wasteful reagents to prepare boronic acid derivatives and require additional steps to afford the desired boronic acid. The scope of the previously reported palladium-catalyzed, direct boronic acid synthesis is unveiled, which includes a wide array of synthetically useful aryl electrophiles. It makes use of the newly available second generation Buchwald XPhos preformed palladium catalyst and bis-boronic acid. For ease of isolation and to preserve the often sensitive C-B bond, all boronic acids were readily converted to their more stable trifluoroborate counterparts.

Figure 1

Buchwald’s First (1) and Second (2) Generation Preformed Catalysts. XPhos (A) Ligand (L).

Figure 2

Kinetics Experiments Comparing 4-Bromo and 4-Chloroanisole Under Reaction Conditions Using Catalyst 1A or 2A (Figure 1).

Figure 3

Color Change Indicating Completion of the Boryla-tion Reaction: left to right: air stable solids during degassing; colorless reaction solution; completion of reaction [aryl chlorides turn yellow (left), aryl bromides turn orange (right)].

Figure 4

New Catalyst System for Heteroaryl Borylation

Scheme 1

Current Methods to Synthesize Boronic Acids.

Scheme 2

Competing Catalytic Cycles

Scheme 3

Aldehyde-Containing Trifluoroborate Synthesis.

Scheme 4

Proposed Mechanism of Observed Palladium-Hydride Reduction of Aldehydes