Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Amos B. Smith III

Abstract

Part 1: This work describes recent advances in Type II Anion Relay Chemistry (ARC), a three-component coupling tactic employing a bifunctional linchpin, developed by the Smith group to permit the rapid synthesis of natural product fragments. Our group has developed several novel linchpins and coupling tactics to achieve diastereoselective and stereoretentive transformations, but enantioselective methods remained elusive. By merging asymmetric [1,2]-additions of lithium acetylides with Type II ARC we have achieved an enantioselective three-component coupling ARC tactic. Additionally, we report here the development of a novel bifunctional Type II linchpin, employing fluorine as an Anion Stabilizing Group (ASG). The design of a synthetic route to access a variety of organofluorine linchpins, in conjunction with Type II ARC, has enabled access to diverse difluoromethylene scaffolds, which are of significant interest to the pharmaceutical and agrochemical industries.

Part 2: This work describes the design, synthesis, and application of a polystyrene supported siloxane transfer agent for use in transition metal-catalyzed cross-coupling reactions (CCRs) of organolithium reagents with aryl halides. Siloxane transfer agents, discovered during our investigation of Anion Relay Chemistry (ARC), permit cross-coupling reactions of organolithium reagents with high functional group tolerance with respect to the electrophile component. Organolithium reagents represent a convenient organometallic coupling component, as they can be generated from commercially available organohalides, and are in many cases used in the synthesis of other organometallic reagents. However, these reagents are often overlooked in synthesis due to their strong basicity, nucleophilicity, and tendency to afford homo-coupling products in transition metal catalyzed CCRs. Here we describe the development of a novel polystyrene supported siloxane transfer agent as a progression over previous generations of transfer agents, ultimately arriving at a highly efficient and recoverable transfer agent that can be used in iterative CCRs without loss in efficiency.

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