| Catalytic asymmetric carbon-carbon bond formation is one of the most active research areas in organic synthesis. In this field, the application of chiral ligands in enantioselective addition of diethylzinc to aldehydes has attracted much attention, lots of ligands such as chiral amino alcohols, amino thiols, piperazines, quaternary ammonium salts, 1,2-diols, oxazaborolidines and transition metal complex with chiral ligands have been empolyed in the asymmetric addition of diethylzinc to aldehydes. In this dissertation, we report some new chiral ligands and their application in enantioselective addition of diethylzinc to aldehydes.1 Synthesis and application of chiral ligands containing sulfur atomSeveral a-hydroxy acids were prepared using the literature method with modifications from the corresponding amino acids valine, leucine, and phenylalanine. Improved yields were obtained by slowly simultaneous addition of three fold excess of sodium nitrite and 1 tnol/L H2SO4. In the preparation of a-hydroxy acid methyl esters from a-hydroxy acids following the procedure described by Vigneron, a low yield (45%) was obtained It was found that much better results (yield 82%) could be obtained by esterifying a-hydroxy acids with methanol-thionyl chloride.The first attempt to convert (S)-2-hydroxy-3-methylbutanoic acid methyl ester to the corresponding (R)-1,1-diphenyl-2-mercapto-3-methyl-l-butanol is as the following: (S)-2-Hydroxy-3-methylbutanoic acid methyl ester was treated with excess of phenylmagnesium bromide to give (S)-1,1-diphenyl-3-methyl-1,2-butanediol, which was then mesylated to obtain (S)-1,1-diphenyl-3-methyl-2-(methanesulfonyloxy)-l-butanol. Unfortunately, conversion of (S)-1,1-diphenyl-3-methyl-2-(methanesulfonyloxy)-l-butanol to the corresponding thioester by reacting with potassium thioacetate under Sn2 reaction conditions can be achieved neither in DMF at 20-60 nor in refluxing toluene in the presence of 18-crown-6 as catalyst. When (S)-1l,l-diphenyl-3-methyl-2-(methane sulfonyloxy)-l-butanol was refluxed with thioacetic acid in pyridine, an optical active epoxide (R)-2,2-diphenyl -3-isopropyloxirane was obtained. Then we tried to convert (S)-1,1-diphenyl-3-methyl-l,2-butanediol to the thioester by reacting with PPh3, DEAD and thioacetic acid (the Mitsunobu reaction), but we failed either, probably due to the steric hindrance around the reaction center.The actually successful synthesis is as described below: a-hydroxy acid methyl esters was mesylated and treated with KSCOCH3 in DMF to give thioester, this was than treated with phenyl magnesium bromide to gave the target compound B-mercaptoalcohols. The enantiomeric excesses of p-mercaptoalcohols can be determined by 1H NMR as their (S)-mandeloyl derivatives.(S)-2-amino-3-phenylpropane-l-thiol hydrochloride was synthesized from L-Phenylalanine. L-Phenylalanine was reduced to the amino alcohol (S)-2-amino-3-phenylpropanol. Protection of the amino group using tert-butyl pyrocarbonate gave (S)-2-tert -butoxycarbonylamino-3-phenylpropane-l-ol, which was then O-mesylated to give (S)-2-tert-butoxycarbonylamino-3-phenylpropyl methanesulfonate. The mesylate was treated with potassium thioacetate in DMF to give l-acetylthio-2-tert-butoxycarbonylamino-3-phenylpropane. The acetyl group was then removed by treating with ammonia in alcohol to gave (S)-2-tert-butoxycarbonylamino-3-phenyl-propane-l-thiol, which was then deprotected with hydrochloric acid to give the desired (S)-2-amino-3-phenylpropane-1-thiol hydrochloride.The enantioselective addition of diethylzinc to aldehydes promoted by these sulfur containing chiral ligands produce secondary alcohols in 65-79% yield with the ee rangedfrom 0 to 49%.2 Synthesis and application of chiral aminophenolsThree substituted prolinols were prepared from the naturally-occurring L-proline using reported method with modifications. And the chiral aminophenols were obtained by heating these prolinols with excess of salicylaldehyde in benzene at reflux.The results of enantioselective ad...
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