Development of Transition Metal-Catalyzed Borylation Protocols using Symmetrical and Unsymmetrical Diboron Reagents
Peck, Cheryl Lynne
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The versatility of organoboron compounds has been demonstrated by their use as synthetic intermediates and more recently in therapeutic applications since the FDA approval of Velcade©. As a result, transition metal-catalyzed protocols to incorporate boron reagents into unsaturated compounds have been extensively researched. While an abundance of literature protocols have been reported, the majority utilize harsh reaction conditions in combination with expensive reagents. This dissertation discloses the author’s contributions to the development of efficient, cost-effective, and operationally simple transition metal-catalyzed borylation protocols with alkynes and diboron reagents. An open-to-air copper(II)-catalyzed aqueous borylation protocol of alkynoates and a symmetrical diboron reagent is reported. Conjugate addition of the boryl-copper species to the electrophilic β-carbon provided β-boryl-α,β-unsaturated esters in moderate to excellent yields. Exclusive (Z)-stereochemistry was confirmed by nOe experiments. The resulting vinyl boronate esters are useful cross-coupling partners. The scope of the aqueous β-borylation protocol was extended to the unsymmetrical diboron reagent, pinB-Bdan. This alternative protecting group has emerged as an orthogonal protecting group and alters the reactivity of the boron moiety. Activation of the pinacol moiety to form the Lewis acid-base adduct allowed for the chemoselective transfer of the 1,8- diaminonapthalene moiety to the β-carbon. An alternative novel synthesis of vinyl, allyl diboronate esters from propargylic alcohols has also been described. Formation of a leaving group in-situ with a palladium- and coppercatalyzed protocol can lead to several competing reaction pathways and the formation of multiple products. Fortunately, the resulting vinyl, allyl diboronate esters were stereoselectively synthesized in moderate GC yields despite significate decomposition during purification, as confirmed by stability studies. The terminal diboration of allenes was previously the only reported method for the synthesis of vinyl, allyl diboronate esters.
- Doctoral Dissertations