Carbonyl Catalysis: Hydrolysis of Organophosphorus Compounds and Application in Prebiotic Chemistry

Title: Carbonyl Catalysis: Hydrolysis of Organophosphorus Compounds and Application in Prebiotic Chemistry
Authors: Li, Binjie
Date: 2019-11-08
Abstract: Since late 1990s, organocatalysis has been widely explored in many aspects and achieved various difficult transformations. In this field, carbonyl catalysis, which could be traced back to 1860 has been developed with impressive progress including asymmetric variants. Over the years, major activation modes were developed for carbonyl catalysis including exploiting temporary intramolecularity to form catalytic tethers and transient intramolecular nucleophiles, dioxirane formation and imine formation. On the other hand, electrophilic activation is also an important area of organocatalysis where impressive progress has been achieved. However, limited examples were reported to achieve the electrophilic activation via carbonyl catalysis. Organophosphorus compounds are crucially important in many aspects in organic chemistry. Many approaches were developed for asymmetric organophosphorus compounds. In this work, different types of organophosphorus compounds were used as the substances for aldehyde-catalyzed hydrolysis reactions. The first part of this thesis illustrated the strategy to combine carbonyl catalysis and electrophilic activation. The hydrolysis of organophosphorus compounds containing P(=O)-N bond were investigated based on Jencks and Gilchrist’s preliminary results with formaldehyde as the catalyst to promote the hydrolysis of one inorganic substance, phosphoramidate. This Chapter describes a systematic research to identify a superior catalyst, o-phthalaldehyde, and develop catalytic hydrolyses of various organophosphorus compounds containing P(=O)-NHR subunits. Gratifyingly, the reaction proved efficient with phosphinic amides and phosphoramidates. Moreover, chemoselectivity was also studied and selective hydrolysis of the P(=O)-N bonds in the presence of P(=O)-OR bonds could be accomplished. The second part of this thesis demonstrated the further development of one of the major modes of carbonyl catalysis. Formaldehyde was identified as the efficient catalyst to react with α-amino phosphonates to form the transient intramolecular nucleophile, which facilitated the subsequent hydrolysis reactions. In this Chapter, different primary and secondary α-amino phosphonates with phenol as the leaving group, were tested in the reaction conditions. As a result, a vast of mono esters of α-amino phosphoric acids could be formed as the products. Finally, the last portion of this thesis applied the methodologies developed in Chapter 2 to prebiotic chemistry. A prebiotic-related aldehyde, glycolaldehyde was studied as the catalyst for the hydrolysis of organophosphorus compounds containing P(=O)-N bond, including phosphinic amides and phosphoramidates. Additionally, other prebiotic important substances, diamidophosphate (DAP) and monoamidophosphate (MAP) were also investigated for potential glycolaldehyde-catalyzed phosphorylation reaction under aqueous conditions. In the presence of catalytic amount of glycolaldehyde, 1) when water was used as the nucleophile, the hydrolysis of DAP and MAP were significantly improved; 2) when other phosphate nucleophiles were added to compete with water, DAP could act as a phosphorylating reagent to phosphorylate other phosphate nucleophiles. Overall, the results presented in this thesis investigated two different activation modes, electrophilic activation and transient intramolecular nucleophiles, for carbonyl catalysis to hydrolyze different organophosphorus compounds, phosphinic amides, phosphoramidates and α-amino phosphonates. The application of carbonyl catalysis to prebiotic chemistry was also achieved especially with the phosphorylation reaction with DAP.
CollectionThèses, 2011 - // Theses, 2011 -