Recent years, catalytic cascade reactions using CO2 as a reagent have gained interest as they can lead to more complex structures resembling pharma-relevant compounds. Another observation in the area of CO2 catalysis is the privileged nature of Ag-catalysis to convert propargylic alcohols and CO2 into activated -alkylidene carbonates which have potential to undergo further reactions provided that suitable nucleophiles are present that can induce isomerization of the heterocyclic structure. In view of these features and notions, so this doctoral thesis will introduce the development of novel Ag-catalyzed cascade conversions of carbon dioxide into new types of heterocycles with a high level of functionality, substitution degree and further extending these procedures to larger ring carbonates and carbamates.
In first part (Chapter 2) a new Ag-catalyzed process is reported for the cascade conversion of synthetically modular alkyne-1,n-diols and carbon dioxide allowing for the selective formation of keto-functionalized cyclic carbonates. The protocol is characterized by operational simplicity, excellent scope of carbonate-based heterocycles, and mild reaction conditions. In situ IR studies, control experiments, and detailed computational analysis of these manifolds support the intermediacy of an α-alkylidene carbonate that can be intercepted by an intramolecular alcohol pro-nucleophile. The inherent synthetic potential of this conceptually attractive CO2 transformation is demonstrated in the preparation of larger ring carbonates and their thermal rearrangement to sterically crowded, five-membered bicyclic carbonate products.
Inspired by the work discussed in chapter 2 of this thesis, the research described in second part (Chapter 3) focused on a conceptually novel catalytic cascade approach towards the formation of highly functional 1,4-dihydro-2H-1,3-benzoxazine-2-one derivatives is presented. In particular, the chemo-selectivity was greatly influenced by the structure of the substrate precursor. We finally found that the presence of a tertiary propargylic carbonate in the precursor is key to override parasitic cyclization processes while empowering the formation of the desired product through Thorpe–Ingold (angle-compression) effects. The isolation of one of the reaction intermediates and its separately studied conversion into the final product supports an unusual ring-expansion sequence from an α-alkylidene, five-membered cyclic carbonate to a six-membered cyclic carbamate by N-induced isomerization.
In conclusion, some new Ag-catalyzed cascade processes have been developed, in which propargylic alcohols are highly versatile substrates for the design of multi-step synthetic sequences based on CO2. This does not only expand the repertoire of functional heterocyclic compounds, but also showcases that more complex compounds are accessible through a judicious combination of cyclizative carboxylation and intramolecular isomerization by a nucleophilic present in the intermediate species.
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