Date of Degree

6-2017

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor(s)

Mark R. Biscoe

Committee Members

George John

Shengping Zheng

Jack Norton

Subject Categories

Organic Chemistry

Keywords

Palladium, Stille, Cross-coupling, Stereospecific, Organometallic, Carbastannatranes

Abstract

Organic chemistry is present in all domains of everyday life, from polymer production to medicine. In order to synthesize complex compounds, it is often necessary to make new carbon-carbon bonds. Transition metal catalysts, particularly those derived from second and third row metals such as Pt, Pd, Rh, and Ir metals, display remarkable efficiency for the formation of carbon-carbon and carbon-heteroatom bonds. In the first chapter, introduction of transition metal-catalyzed cross-coupling reactions is given. While the formation of C(sp2)–C(sp2) bonds has been studied extensively, C(sp3)-C(sp2) bond formation still presents a challenge due to competitive β-hydride elimination and slow transmetallation of bulky secondary and tertiary alkyl organometallic nucleophiles. Palladium-catalyzed cross-coupling reactions (especially Stille and Suzuki cross coupling reactions) can tolerate a broad scope of reactants, and even proceed with high stereospecificity. The development of a general system that enables a broad scope of reactants to be employed in reactions with high sterespecificity would be transformative in the field of organic synthesis and drug development. Herein, in the second chapter, we present the development of a general Pd-catalyzed process for the stereospecific cross-coupling of secondary alkyl organotin reagents with aryl chlorides, bromides, iodides and triflates. The reaction proceeds with minimal isomerization of the secondary alkyl organometallic tin nucleophile, and tolerates a wide range of functional groups with absolute configuration. In the third chapter, this work has been extended to the use of acyl electrophiles, which undergo Pd-catalyzed cross-coupling reactions with secondary alkylcarbastannatranes with exceptional stereofidelity and with net retention of absolute configuration. Because the stereochemistry of the resulting products is entirely reagent-controlled, this process may be viewed as a general, alternative approach to the preparation of products typically accessed via asymmetric enolate methodologies. Additionally, we report a new method for the preparation of optically active alkylcarbastannatranes, which should facilitate their future use in stereospecific reactions.

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