Isocyanides: Anionic Methods for Dearomatization to Complex Cyclohexadienes

Abdullah Bilal Altundas

doi:10.17918/00001325

Isocyanides are powerful functionalities by virtue of the carbene-like terminal carbon that imparts unique reactivity. Capable of functioning as electrophiles, nucleophiles, radical acceptors, and in transition metal-catalyzed insertions, isocyanides engage in a plethora of methodologies that generate complex molecules from relatively simple starting materials. Despite their reactivity, only a handful of isocyanides are commercially available. Relatively few methods access isocyanides with even less providing di- or tri-substituted isocyanides. The challenge has been to develop a general method to prepare variously substituted isocyanides through a simple general method. The focus of this dissertation is to address the deficiency of methods to rapidly, generate complex isocyanides and to demonstrate their unique chemistry through the synthesis of highly functionalized cyclohexadienes. As such, the thesis is a collection of six published articles focused on different aspects of isocyanide chemistry. As a prelude to much of the chemistry, the first chapter describes the formation, structure, and reactivity of metalated isocyanides. The summary provides the broad reactivity patterns to understand the isocyanide chemistry of Anisylsulfanylmethylisocyanide (Asmic) that features in chapter 2. Initially developed as an isocyanide building block, chapter 2 describes the discovery of the first-ever low-temperature isomerization of isocyanides to nitriles from Asmic. Asmic has proven to be a particularly valuable precursor, not only to complex isocyanides, but also to a variety of heterocycles which has led to the development of a large-scale synthesis, the subject of chapter 3. The demonstrated utility of Asmic was summarized as a useful reagent for building functionalized isocyanides and nitriles in chapter 4. Rapid access to diverse Asmic derivatives led to the discovery and development of a novel dearomatization method that rapidly assembles complex cyclohexadienes which is described in detail in chapter 5. The dearomatization was rigorously explored through both computational and experimental investigations that have shed light onto a new avenue for isocyanide chemistry. The concluding chapter describes a practical synthesis and purification of sulfonium salts that was developed during the development of the dearomatization of Asmic derivatives. Collectively, the thesis demonstrates the highly versatile nature of isocyanides and their excellent potential for accessing complex scaffolds that are otherwise extremely challenging to prepare.

Isocyanides: Anionic Methods for Dearomatization to Complex Cyclohexadienes

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Isocyanides: Anionic Methods for Dearomatization to Complex Cyclohexadienes

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