Date of Award

2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Gary A. Molander

Abstract

ABSTRACT

PALLADIUM-CATALYZED BORYLATION AND CROSS-COUPLING OF ARYL AND HETEROARYL HALIDES UTILIZING DIBORA DERIVATIVES

Sarah Little Jane Trice

Professor Gary A. Molander

Although much current research focuses on developing new boron reagents and identifying robust catalytic systems for the cross-coupling of these reagents, the fundamental preparations of the nucleophilic partners (i.e., boronic acids and derivatives) has been studied to a lesser extent. Most current methods to access boronic acids are indirect and require harsh conditions or expensive reagents. Therefore, we sought to provide a simple, efficient, and direct synthesis of arylboronic acids. Utilizing aryl halides and an underutilized reagent, tetrahydroxydiboron B2(OH)4, we developed a palladium-catalyzed method that now provides access to boronic acids in high yield. The method eliminates the necessity to employ the extremely wasteful and most commonly used source of boron, bis(pinacolato)diboron.

The first method developed focused on the borylation of the less expensive and more commercially available aryl chlorides. We demonstrated that most functional groups are well tolerated under the mild reaction conditions, providing the corresponding trifluoroborate in good to excellent yield for most subtrates. We also demonstrated that the crude boronic acid could be easily and efficiently converted to a myriad of boronate esters. The method was later extended to include aryl and heteroaryls bromides, chlorides, and triflates.

We went on to demonstrate that we could achieve similar results with the synthetic precursor to B2(OH)4, tetrakis(dimethylamino)diboron.

We also demonstrated that we could perform a one-pot, two-step borylation/Suzuki cross-coupling reaction.

And Finally, through the use of ethylene glycol as an additive to the borylation reaction with B2(OH)4, we were able to access heteroaryl substrates that were difficult to obtain in good yield with our optimized methods. Using this strategy, we were able to access one-pot borylation/Suzuki cross-coupled products between two heteroaryls in high yield.

Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS