Small Organic Molecules Asymmetric Catalytic Reactions In Supercritical Fluids

In recent years, supercritical fluid (SCF), as an environmentally friendly reaction mediem, plays an important role in chemistry and has drawn wide attention. Supercritical fluid extraction (SFE) is a very important part in the chemical industry. It also has advantages for chemical reactions, such as adjusting the solvent properties of SCF, separating products from SCF by controlling the pressure and temperature.With the developments of synthesis and analysis, more and more chiral compounds can be synthesized by a chemical process. Asymmetric reaction is paid more and more attention.Domino or cascade reactions have become the frontier and hot topics in organic chemistry. Domino reactions enable rapid construction of complex molecular scaffolds in an efficient way, and are even more appealing due to their high atom economy, operational simplicity and environmental friendliness. Domino reactions have been widely used for the construction of heterocycles and in enantioselective synthesis and total synthesis.A number of physical parameters of supercritical fluid can be effective regulated and controlled by changing pressure and temperature. Domino reactions have many advantages, such as easy operation and high atom economy. Based on these reasons, L-proline-catalyzed asymmetric aldol reactions and organocatalytic asymmetric domino reactions are studied in this thesis. The following two aspects are carried out:(1) On the basis of precedent researches on L-proline-catalyzed asymmetric aldol reactions between acetone and aromatic aldehydes in supercritical carbon dioxide, the effects of cosolvents, mixed fluids (CO2+HFC-134a), catalysts and substrates on the performance of the direct asymmetric aldol reaction were investigated in supercritical carbon dioxide at 40℃and under 25 MPa.①Depending on boiling point, volatility and polarity, we chose dimethyl sulfoxide (DMSO), ethyl acetate (CH3COOC2H5), trichloromethane (CHCl3), ethanol alcohol (C2H5OH), and 2,2,2-trifluoroethanol (CF3CH2OH) as cosolvents. L-proline-catalyzed asymmetric aldol reactions between acetone and aromatic aldehydes in supercritical carbon dioxide were investigated under the conditions of 25 MPa,40℃,24 h, and 1 mL cosolvent. The consequences demonstrate that an appropriate cosolvent could promote the aldol reactions, but the enantioselectivity was not decreased.②The investigation of cosolvent has been involved in a mixed fluid, and the properties of mixed fluid changed with a change in component. L-proline-catalyzed asymmetric aldol reactions between acetone and aromatic aldehydes in mixed fluid were studied under the condition of 25 MPa, 40℃,24 h, and HFC-134a 0～100%(wt%). Results indicated that, with increasing the HFC-134a content, the yield of aldol reactions increased, but the enantioselectivity decreased.③Organocatalytic asymmetric aldol reactions between ketones and aldehydes in supercritical carbon dioxide were investigated under the condition of 25 MPa,40℃, and 24 h. Results showed that the best catalyst is L-proline, and this catalytic system showed moderate chiral induction for withdrawing substituents aromatic aldehydes and moderate yield.(2) Based on L-proline as a raw material, we synthesized a containing fluorine catalyst that was applied for the Michael-Aldol reactions between 2-mercaptobenzaldehyde and 3-phenylpropenal. The effects of reaction time, pressure, temperature and other conditions on Michael-Aldol reaction were studied. The experimental results showed that the configuration may inverse under the high pressure. The enantioselectivity of 92% ee to the targeted product was achieved under 16 h,20 MPa, and 40℃. It gave a basis for choosing appropriate chemical reaction models in supercritical carbon dioxide.