Date of Award

2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Gary A. Molander

Second Advisor

Amos B. Smith, III

Abstract

The Suzuki–Miyaura cross-coupling reaction is one of the most efficient methods to form new carbon-carbon bonds, allowing a rapid increase in complexity among target molecules of interest. Among a variety of boron reagents utilized in Suzuki–Miyaura reactions, potassium organotrifluoroborates are of great interest because they have many advantages over other boron reagents. Organotrifluoroborates, which are tetracoordinate boron species, show better stability and reactivity, and they are much less prone to protodeboronation.

α-Chiral β-arylated carbonyl compounds are important substructures in organic chemistry, and their preparations, such as benzylations, asymmetric hydrogenations, and conjugate additions, have been studied. However, these methods have limitations in terms of selectivity and functional group tolerance. We developed a more direct method that could overcome the problems. Enantiomerically enriched potassium α-chiral β-trifluoroboratoamides were prepared, and the general conditions were found to couple successfully with various aryl and hetaryl chlorides to afford the corresponding α-chiral β-arylated carbonyl compounds. Moreover, the diastereoselectivities were greater than 95:5, and retained throughout the coupling reactions.

Aminomethyl moieties are readily encountered in biologically active compounds as well as in organic intermediates. Even though several synthetic methods have been reported, the means of preparation of these subunits are still limited. We developed a more efficient method to access aminomethyl substructures by preparation of air stable potassium Boc-protected primary and secondary aminomethyltrifluoroborates. The Suzuki–Miyaura cross-coupling reaction was investigated with these new aminomethylating boron reagents to provide the corresponding aminomethyl moieties. Aryl and hetaryl chlorides, mesylates, and sulfamates were proved to be effective electrophilic coupling partners under developed conditions. These methods provide a complementary way to access important building blocks that is more direct and general than currently available methods.

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