This thesis discusses interactions of Lewis base and CO2 for CO2 utilization and functionalization reactions from the following two aspects: 1) Chiral base-CO2 adducts were investigated as electrophiles or nucleophiles for enantioselective CO2-functionalization; and 2) reactive nucleophiles and anionic transient species might be trapped by CO2 in accelerated cyanation and transamidation reactions.
Chapter 1 will discuss the most relevant CO2 utilization and functionalization methods, with an emphasis on base CO2 interactions. Endeavors towards stabilized base CO2 adducts, characterized by NMR, IR, and single crystal X-ray diffraction, promoted a better understanding of CO2 activation and utilization. This contributes to the applications of CO2 in organic synthesis to access value added chemicals and following new methodologies in chapters 2, 3, and 4.
Chapter 2 will present experimental data on chiral base CO2 interactions. I attempted to analyze of the chiral chemical environment with CO2 incorporated crystal. The in situ generated chiral base-CO2 adducts were investigated as electrophiles or nucleophiles respectively in the imine umpolung carboxylation and the four component Ugi reaction. As hydrogen bonding donors to stabilize the CO2 adduct, the active N-H proton might be problematic since it can protonate reactive 2-azaallyl anion species. The nucleophilic activation of CO2 by a base was supported by the increased isolated yields of α-amino amide products.
Chapter 3 will describe achiral base CO2 interactions. Various bases were screened in the carboxylation of Grignard reagents. While the negligible role of DBU in CO2-(de)activation was observed , the positive DBU CO2 interaction led to a higher effective concentration of CO2 in the reaction mixture, and therefore higher carboxylation yield. As for cyanide CO2 interaction, multiple roles of CO2 were discussed along with the possible mechanism in stereoselective cyanation of coumarins. Endeavor toward enantioselective cyanation was not successful by
employing cinchona alkaloid derived cyanid e sources. However, significant ee (20%) was detected when thiourea was used for the cyanation of coumarins, indicating an accelerated cyanation process would minimize the racemic background reaction.
Chapter 4 will present Lewis acidic CO2 catalyzed transamidation reactions. A broad scope of primary, secondary and tertiary amide donors was tolerated for amide exchange reactions. The Hammett plot study indicated that transient anionic species was stabilized by the electrophilic CO2. This methodology was preliminarily investigated in peptide modification, showing promising
outcomes. I then extended the concept of Lewis acidic CO2 catalysis to synthesize amide from esters, nitriles, aldehydes, and carboxylic acids.
Conclusion and perspective will summarize CO2-base interactions and stabilization factors on base-CO2 adducts . A discussion will be delivered on electrophilic/nucleophilic activation of CO2 for functionalization reactions. Perspectives on future work will be highlighted.