Synthesis Of N-Containing Fused Heterocycles Through Carboxylation Of Terminal Alkynes With Carbon Dioxide

An increasing level of CO2 in atmosphere has tremendously influenced our perception on the observed climate fluctuations. Closely connected to the “CO2 issue” is the global energy consumption which increases by the year due to the use of large amounts of fossil fuels to fulfil our energy needs. Carbon dioxide is also a ubiquitous, nontoxic, safe and renewable C1 resource, and has recently proven to be of high value in the production of commercially attractive products such as urea, carbonates, polycarbonates and carboxylic acids.However, despite its increasing use, CO2 is not yet able to replace all fossil fuel based chemical synthesis and there is a clear demand for further amplification of its role as a raw material in organic chemistry. Closely associated to this is the need for improved technologies that will allow for the incorporation of CO2 into different organic scaffolds under low-energy-input conditions. Catalysis represents a powerful method that permits these “carbon-fixation” reactions to be carried out under low temperature/pressure conditions. Another practical process for CO2 transformation is using green, economic reaction pathway, such as multi-component reactions(MCRs) that could find broad applications in consecutive transformations of CO2 into value-added products.As electrophilic alkynes, propiolic acid esters have been ubiquitously employed in constructing five- or six-membered heterocycles with diverse biological properties and synthetic applications. This dissertation, on the bases of the preceding research of C-C bond construction by our group, focuses on the research field of CO2 transformation under mild conditions.1) An ionic liquid containing copper(I)([Cu(Im12)2][CuBr2])was proved to be an effective homogeneous catalyst for the carboxylation of terminal alkynes with ambient CO2 in the presence of Cs2CO3. This developed procedure needs no external ligands and terminal alkynes with electron-withdrawing groups or electron-donating groups proceeded smoothly at atmospheric CO2 pressure and room temperature(70-96% yield). Interestingly, the ILs containing copper(I) in both the anion and the cation showed much higher activity in comparison with the counterparts incorporating copper(I) solely in form of halocuprate i.e. copper(I) in the anion. Especially, activition effect of terminal alkyne by the ionic liquid was also validated by NMR technique.2) An efficient method for the synthesis of 3a-hydroxyisoxazolo [3,2-a] isoindol-8(3aH)-ones from CO2, terminal alkynes, EtBr, and NHPI(N-hydroxyphthalimide) was developed through the tandem carboxylation/annulation strategy catalyzed by copper(I)/phosphine system. This one-pot multicomponent reaction conducted at atmospheric CO2 pressure to afford the target products in good to excellent yields(65-96%) under mild conditions. Notably, a wide range of functional groups were tolerated in this procedure. This protocol with simultaneous formation of four novel bonds i.e. two C-C bonds and two C-O bonds represents an efficient methodology for upgrading CO2 into heterocycles.3) Cu(I)/Ag-catalyzed carboxylation of terminal alkynes with CO2 as a carbonylation reagent has emerged as an effective and greener method for the preparation of carboxylic acids and the corresponding esters. As high value-added compounds derived from CO2, propiolic acid esters was introduced to the simple base-catalyzed [3+2] annulation with NHPI. Only 10 mol% NaOAc·3H2O was needed for this transformation under room temperature for 6 h. Various of pharmaceutically attractive 3a-hydroxyisoxazolo [3,2-a] isoindol-8(3aH)-ones has been synthetised. Notably, a new base-promoted intermolecular “oxa-Michael-aldol type” mechanism has been proposed.