Organic Synthesis - Introductory Organic Synthesis - Lecture Notes | CHEM 144, Study notes of Chemistry

Download Organic Synthesis - Introductory Organic Synthesis - Lecture Notes | CHEM 144 and more Study notes Chemistry in PDF only on Docsity! Chemistry 144 M. E. Jung Organic Synthesis Acyclic Enantiocontrol Sharpless Asymmetric Epoxidation and Kinetic Resolution Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974; Rossiter, B. E.; Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 464. tBuOOH -20 °C L - (+) - DET L - (+) - DET R2 R 1 R3 O H O R2 R 1 R3 O H COOEt EtOOC H O O H H H O R2 R 1 R3 O H D - (-) - DET Ti(OiPr)4 ditto C H2Cl2 Sharpless Kinetic Resolution Sharpless, K. B.; et al. J. Am. Chem. Soc. 1981, 103, 6237. O O H R H R O O H R H R R O H R H O O H R R H O O H R R H COOiPr iPrOOC H O O H H H R O H H R L - (+) - DIPT + fast erythro threo L - (+) - DIPT (S) 98 : 2 (R) L - (+) - DIPT slow + threo38 : 62erythro O H RH H C H2 O H HR H C H2 H C H2 O H H R (S) but worse than (R) Therefore, when you epoxidize a racemic mixture of the secondary allylic alcohol at -20 °C using only 0.5 equivalent of tBuOOH, all of the (S) enantiomer is epoxidized to give the erythro epoxy alcohol while the (R) enantiomer remains unreacted. These two compounds can be easily separated by simple chromatography. Therefore in this process you have kinetically resolved the racemic allylic alcohol (resolved by a difference in the rates of reaction of the enantiomers)! R O H R H O O H R R H erythro Ti(OiPr)4 tBuOOH C H2Cl2 -20 °C O H R H R 0.5 eq (RS) + (R) L - (+) - DET 50% 50% but cis-substituted has steric problems and gives low ee's in kinetic resolution R' OH H R OH RH H (S) R' H vs. H (R) R' HH OH R