Dissertation
Sulfuranide methods for preparing azoles from the isocyanide asmic
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2022
DOI:
https://doi.org/10.17918/00001324
Abstract
As a sulfide and an isocyanide, anisylsulfanylmethylisocyanide (Asmic) has enabled the development of new methods for synthesizing heterocycles through the marriage of sulfuranide chemistry and isocyanide chemistry. Sulfides, typically thought of as unreactive functional groups, can be rendered reactive by addition of organometallics leading to their transformation into hypervalent sulfuranides. Isocyanides like Asmic, driven by the reactivity of their terminal carbene-like carbon, are prized for their ability to prepare nitrogen-containing heterocycles as well as peptidomimetic scaffolds. This dissertation describes the development of methods that employ the isocyanide functional group in Asmic to prepare oxazoles and imidazoles while increasing the complexity of the heterocycles by use of sulfuranide chemistry. The foundation for the chemistry developed in this dissertation is the rich history of sulfuranide chemistry, which is reviewed in the 1st Chapter. The review discusses patterns of reactivity and key features of sulfuranide chemistry such as the effect of directing groups. Chapter 2 describes an Asmic-based oxazole synthesis which utilizes sulfuranide chemistry in the key transformation. Asmic was condensed with esters to give anisylsulfanyl oxazoles that were then elaborated by transformation into sulfuranides which underwent smooth alkylation. The method was showcased in a three-step synthesis of the natural product streptochlorin. Chapter 3 briefly discusses a method for preparing imidazoles from Asmic. Asmic was condensed with nitriles to give anisylsulfanyl imidazoles that undergo smooth desulfurization when treated with Raney nickel. Finally, the project described in Chapter 4 evolved from Chapters 2 and 3 as a modified method for preparing oxazoles and imidazoles from Asmic. Here, monoalkyl Asmic derivatives are condensed with acid chlorides (for oxazoles) and nitriles (for imidazoles). An extremely facile sulfuranide formation-desulfurization is the key step in the formation of the end azole. The combined methods of this dissertation highlight the utility of Asmic in oxazole and imidazole synthesis.
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Details
- Title
- Sulfuranide methods for preparing azoles from the isocyanide asmic
- Creators
- Louis Gregory Mueller
- Contributors
- Fraser F. Fleming (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, 209 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991019104705304721