Synthesis Of Novel Chiral Diphosphine Ligands And Their Applications In Asymmetric Catalytic Hydrogenation Of Functionalized Ketones

In this dissertation, a class of C2 axial chiral bidentate phosphine ligands, SunPhos, was synthesized. When the ligands were applied to the asymmetric hydrogenation of functionalized ketones, excellent catalytic efficiency and stereoselectivities were obtained.The main contents include:1. Ligand L1 was synthesized successfully in hundred gram-scale under the optimized reaction conditions. SunPhos series ligands were synthesized following the following procedure: Arbuzov reaction catalyzed by NiCl2, lithiation of the ethyl phosphate with LDA, oxidative coupling with FeCl3, reaction of the diphosphate with SOCl2, Grignard reaction, optical resolution with (-)-DBTA or (-)-DTTA as resolving agent, and finally reduction with HSiCl3. The absolute configuration of the lidands was determined by the means of single crystal X-ray diffraction of the salts of the diphosphine oxides with (-)-DBTA or (-)-DTTA.2. Asymmetric hydrogenation of aromaticα-ketoesters with Ruthenium and Sunphos ligands. In the presence of catalytic amounts of CeCl3·7H2O, [RuCl(benzene) L1]Cl is found to be the highly effective catalyst for the asymmetric hydrogenation of aromaticα-ketoesters. A variety of ethylα-hydroxy-α-arylacetates have been prepared with ee up to 98.3%. It is of great significance that challenging aromaticα-ketoesters with ortho substituents were also hydrogenated with high enantioselectivities. The reaction intermediate was proposed to be the coordination complexes of the CeCl3·7H2O/substrate/catalyst. Chiral ethyl mandelate can be prepared at 40-gram scale with a TON of 10,000 and 93.6 % ee. Mandelate acid was gotten with 85% yield at 99% ee after single recrystallization from 1, 2-dichloroethylene.3. In the presence of iodine, the ruthenium complexes [RuCl(benzene)L3]Cl was the highly effective catalyst for the asymmetric hydrogenation of sulfonyl ketones. A variety of optically activeβ-hydroxy sulfones have been prepared with up to 99.4% ee. Further investigation revealed that the in situ generated anhydrous HI was the operating additive.4. Starting from a cheap and readily available substrate, an efficient procedure making the key intermediate of Prils was developed. The hydrogenation of (E)-ethyl 2-oxo-4-arylbut-3-enoate with [NH2Me2]+ [{RuCl[(S)-SunPhos]}2(μ-Cl3)] in the presence of the 1 N HCl gave ethyl 2-hydroxy-4-arylbutyrate with 93.7~95.7% ee. Further investigation has proved that the hydrogenation proceeds via a sequential hydrogenation of C=O and C=C bonds which is sensitive to the reaction temperature. Hydrolysis of ethyl 2-hydroxy-4-phenylbutyrate (ee: 93%) provides the 2-hydroxy-4-phenylbutyric acid with 81% yield at 99% ee after a single recrystallization from 1, 2-dichloroethylene.