Synthesis Of Chiral Ligands And Their Application In Enantioselective Sulfoxidation

Chiral sulfoxides and their derivatives are extensively used as important chiral intermediates, auxiliaries, chiral ligands, catalysts, and chiral drugs. Chiral sulfoxides may be obtained by biological and chemical methods. The chemical methods include chiral auxiliary's induction, chiral oxidant'soxidation, chiral resolution, and enantioselective catalysis. The most efficient way to prepare chiral sulfoxides is the asymmetric oxidation of prochiral sulfides catalyzed by chiral metal complexes. According to the reported procedures we prepared a chiral ligand (R)-1-(2-hydroxynaphthalen-1-yl)-3-(((R)-1-phenylethylimino)methyl)naphthalene-2- ol) from (R)-BINOL characterized by the rotation, IR, ¹HNMR, ¹³CNMR, MS, and the ligand was firstly applied in the asymmetric oxidation of prochiral sulfides.The hydroxyl groups of (R)-(+)-BINOL were protected by chloromethyl methyl ether to give the BINOL-MOM . The BINOL-MOM was otho-lithiumized with n-BuLi and reacted with DMF to form formyl group on the ortho position, The crude product was purified through column chromatograhy to give the (R)-3-hydroxy-4- (2-hydroxynaphthalen-1-yl)-2-naphthaldehyde. After the deprotection of hydroxyl group, (R)-3-hydroxy-4-(2-hydroxynaphthalen-1-yl)-2-naphthaldehyde was synthesiz- ed which reacted with (R)-(+)-phenylethylamine to give the object compound Schiff base 46. In the presence of chiral titanium catalyst formed in situ from Ti(O-i-Pr)₄ and the Schiff base ligand, sulfides were oxidized to sulfoxide by 30% H₂O₂ , 70% TBHP, CHP. The best results were obtained under the following reaction conditions: thioanisole /ligand/Ti(O-i-Pr)₄/oxidant=1.0/0.2/0.1/1.6(mmol ratio); CHP as oxidant. The factors on catalytical reaction were the amount of oxidant, temperature , water, time. The best results were obtained in 77% yield and 66% ee under the following reaction conditions: thioanisole/liagand/Ti(O-i-Pr)₄/CHP/H₂O=1.0/0.2/ 0.1/ 2.0/0.5(mmol), 0℃; CCl₄ as solvent ; CHP (2.0 equiv); 9 h.The catalyst V-complex prepared from the new chiral Schiff base ligand and VO(acac)₂ displays moderate yield (50.0-84.2%), but nearly list enantioselectivities(0.6-1.6%) for the asymmetric oxidation of thioanisole at 0℃using 10% catalyst (VO(acac)₂)/ligand=1.0/1.0, mmol/mmol) with 30% H₂O₂ as economic oxidant by the various amout from 0.8 eq. to 2.0 eq. The temperature on the reaction was also investigated , and the result displayed moderate yield(46-87.5%), but low enantioslec-tivities, nearly raceme.Amino acids and their derivatives were prepared vanadium complex catalyst. 0.5% mmol of the catalyst was used to catalyze the oxidantion of thioansole and the results were good. Phenylalanine and tert-butyl salicylaldehyde were prepared to formed vanadium complex. We investigated the oxidation of thioansole by 1%, 0.5%, 0.1%, 0.05%(mmol) of it. The yield of the sulfoxide were 85-94.7% and the ee were 30.6-70.8%.