CO₂-Promoted Hydration Of Propargylic Alcohols For α-hydroxy Ketones Synthesis And Application Research Of α-Hydroxy Ketones

α-Hydroxy ketone motifs are widely found in varieties of biological active compounds, synthetic drugs and natural products. Moreover, since its structural specificity, α-hydroxy ketones can be applied to the production of larger molecules and preparation of other important compounds. Thus, the approaches for the synthesis of α-hydroxy ketones have been extensively studied. In this thesis, we are going to presented a new synthetic method and the organic applications of α-hydroxy ketones:Under carbon dioxide atmosphere, Ag OAc/DBU was an efficient binary catalytic system to catalyze the hydration of propargylic alcohols for the regioselective α-hydroxy ketones synthesis. Compared to the previous reports, this method is more eco-friendly without using toxic mercury salts as catalysts; both internal tertiary propargylic alcohols with a aryl or alkyl substituent at the acetylenic terminus and terminal tertiary propargylic alcohols could smoothly undergo this reaction, which features wider substrate scopes, higher functional group tolerance and higher regioselectivity.Utilizing the synthetic α-hydroxy ketones as raw materials, we systematically explored its further organic applications. First, a copper-catalyzed and base-promoted [4+1] cascade annulation between α-hydroxy ketones and nitriles for the construction of highly substituted 3(2H)-furanones has been developed. The important features of this method included the use of readily available substrates and cheap catalysts, wide substrate scope, high functional group tolerance and an easy work-up procedure. With this method, we successfully synthesize 4-(3-acetylphenyl)-2,2-dimethyl-5-(4-(methylsulfonyl)phenyl)furan-3(2H)-one, a potent selective COX-2 inhibitor, in one-pot, which further highlights the advantages of our protocol in terms of step-economy, practicability and potential application value.Additionally, we have developed a straightforward access to pyrano[4,3-a]quinolizine- 1,4,6(2H)-triones and 2H-pyran-2,5(6H)- diones via base-promoted annulation of α-hydroxy ketones and dimethyl but-2-ynedioate. There are few synthetic methods for quinolizinones and pyrandiones compounds even they are relatively important heterocyclic molecules. This synthetic method was characterized by very mild reaction conditions, simple operation and high functional group tolerance.Last, we have disclosed a base-promoted reaction of α-hydroxy ketones(or phenyl acetones) with phenylacetylenes for the novel assembly of 1,3-diarylpropenes and bullatenones, which undergoes a new-type Haller-Bauer carbon-carbon bond cleavage process.