The research investigations presented herein are concerned with the syntheses and applications of arylboronic acids and their derivatives; with a particular focus on their accessibility or utility in certain of the most significant modern transition metal-catalysed reactions to involve organoborons. Chapter 1 provides an introduction to the field of organoboron chemistry, from its roots employing borane and related highly reactive derivatives for uncatalysed hydroboration of olefins and acetylenes, to the modern classes of organoboron reagents of the greatest significance to the related contemporary transition metal-catalysed methodologies. Furthermore particular emphasis is placed on the discussion of arylboronic acids, their synthesis, and application to transition metal catalysis as a result of their propensity to undergo useful transmetallation events. Chapter 2 details the use of a commercially available sulfonated monophosphine ligand in the rhodium-catalysed 1,2-addition reaction employing aryl aldehydes and arylboronic acids in aqueous media. The high and continued activity of the catalytic complex is demonstrated by it being successfully recycled five consecutive times in the arylation reaction of an aryl aldehyde; as well as being active for the arylations of more sterically demanding aryl methyl ketone substrates. Chapter 3 details the design and synthesis of a novel bench-stable azidomethylene substituted arylboronate ester. The reactivity of this compound and a related analogue in both the coppercatalysed azide alkyne cycloaddition reaction and the Suzuki coupling reaction are detailed, culminating in the proof-of-concept use of such versatile synthetic building blocks in the synthesis of a drug-substance derivative. Chapter 4 details alternative synthetic approaches to that used in Chapter 3 in order to access bifunctional azidomethylene substituted arylboronate esters. In particular the application of Miyaura borylation of arylhalides bearing benzylic azides is addressed as a means to rapidly access substrates which are otherwise shown to be incompatible with classical s-block synthetic intermediates.

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23734号 / 理博第4824号 / 新制||理||1690(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 依光 英樹, 教授 若宮 淳志, 教授 時任 宣博 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Boronic acids are attractive synthetic intermediates and have been shown to be effective as inhibitors of various enzymes. In this project, the overarching goal is the selective inhibition of a protease present in the mitochondria known as human ClpXP. To study the potential selective inhibition of Human ClpXP using N-terminal peptidic boronic acid, we have designed a synthetic scheme that includes?-borylation of °,?-unsaturated carbonyl compounds using Cu(I) as catalyst, °-alkylation, saponification/hydrogenation, amidation, and oxidative removal of pinacolyl group with sodium periodate. A simple amidoboronic acid was also synthesized for stability studies. This compound, synthesized in 44% overall yield, could be used as a surrogate for N-terminal peptidic boronic acid to provide basic understanding of the stability of more elaborate N-terminal peptidic boronic acids. During the synthesis of this compound, published deprotection methods were not suitable to deprotect the pinacol group. A two-step protocol for pinacolyl boronic ester deprotection via a diethanolamine protected intermediate was successfully developed with the advantages of mild reaction conditions, tolerance to various functional groups, short reaction time and ease of product isolation. The current results will be useful for the deprotection of other boronic esters, such as pinanediol protected compounds, which are being used extensively in stereoselective synthesis. / Master of Science