Transition metal-catalyzed isocyanide insertions

Ondertitel:from noble to base metal catalysis

Isocyanides are versatile compounds, and are used as powerful reagents in a plethora of chemical conversions. Their use in organic reactions such as the Nef-, Ugi- and Passerini reactions is well documented. More recently, the isoelectronic nature of isocyanides to CO has also allowed them to be inserted in metal-catalyzed cross-coupling reactions, opening up broader synthetic avenues towards nitrogen-containing products. Chapter 1 provides an updated summary of all currently known palladium-catalyzed isocyanide insertion reactions. This chapter clearly illustrates the versatility of palladium in metal-catalyzed imidoylations. However, while palladium has shown itself to be a highly useful metal in these transformations, it is limited by its inherent tendency to only undergo two-electron processes. By replacing palladium with more abundant base metals, novel reactivities are unearthed. A complete overview of the catalytic activities of row IV metals is provided in Chapter 2, and show the propensity of these metals to react with isocyanides in ways the noble metals are unable to. Chapter 3 and 4 illustrate our efforts to elaborate on palladium-catalyzed isocyanide insertion processes by providing imidoylation/cyclization cascades. In chapter 3 we show novel reactivities of the known imidoylative Sonogashira reaction. We were able to greatly increase the isocyanide tolerance of this transformation, and provide a one-pot cascade reaction that generates 4-aminoquinolines. Although the 4-aminoquinolines are generally formed in good yields, when electron withdrawing substituents are present, yields are typically moderate. This reactivity was extended in chapter 4, in a novel 3-component reaction between haloarenes, isocyanides and cyanates to form 4-aminobenzoxazin-2-ones and 4- aminoquinazolin-2-ones. These products are obtained in moderate yields, and more optimization is required to provide a reliable and robust insertion pathway to these structures. In chapter 5, we move from palladium towards nickel catalysis. This chapter shows the nickel(II)-catalyzed isocyanide insertion in amidinouracils. This oxidative imidoylation affords the corresponding, underinvestigated bicyclic pyrimidouracils in up to quantitative yields. Further work investigating base metal-catalyzed isocyanide insertions is reported in chapter 6, where we use copper(II) as a Lewis acid. With this catalyst, we were able to subject o-isocyanobenzoates to amination and subsequent lactamization to afford quinazoline-4-ones under mild conditions, in high yields. Finally, chapter 7 reflects on the possibilities of using the chemistry in this thesis to further expand the synthetic applicability of isocyanide insertions.

ISBN:978-94-6423-367-4

Jaar van publicatie:2021

Trefwoorden:Doctoral thesis

Toegankelijkheid:Open