The Nobel Prize in Chemistry 2001 sI for his work on sPfor their work on chirall chirally catalysed oxidation reactions reactions" hydrogenation catalysed hy K. Barry Sharpless William S. Knowles Ryoji Noyori
The Nobel Prize in Chemistry 2001 "for their work on chirally catalysed hydrogenation reactions" "for his work on chirally catalysed oxidation reactions" K. Barry Sharpless William S. Knowles Ryoji Noyori
Thalidomide(反应停) 手性分子的性质差异 o HN (R)型,有效,不致畸 (S)型,致畸形 COOH COOH NH (S)-天冬酰胺 (R)-天冬酰胺 苦味 甜味
手性分子的性质差异 Thalidomide(反应停 ) NOO N H O N O OO H N O O (R) 型 ,有效,不致畸 (S) 型 ,致畸形 H2N C O O H O N H2 H2N C O O H O N H2 (S) -天冬酰胺 苦味 (R) -天冬酰胺 甜味
Sharp1ess环氧化反应 "o"(s,s)D-)- tartrate(天然) R Me3 COOH,Ti(oPr)4 OH cH2Cl2,70%-90% OH R o"(RR)-L(+)- - tartrate(非天然) >90%ee COOH COOH HO--H H OH OH HO H COOH COOH (S, S)-D-()-tartrate (R, R)-L-(+)-tartrate
Sharpless环氧化反应 R2 R1 R3 OH "O" "O" (S,S)-D-(-)-tartrate (R,R)-L-(+)-tartrate Me3COOH,Ti(OPr i )4 CH2Cl2 ,70%-90% R2 R1 R3 OH O >90% e.e R2 R1 R3 OH or O (非天然) (天然) COOH HO H COOH H OH COOH H OH COOH HO H (S,S)-D-(-)-tartrate (R,R)-L-(+)-tartrate
催化剂 ●●●●● ROOC OR OR RO i OR OR ● RO COOR 双核T酒石酸络合物
催化剂…… 双核Ti-酒石酸络合物 Ti OR O RO O O O RO COOR Ti O OR ROOC OR O OR
催化剂前体的形成 OPrl COOH OOH Pro--Ti-OPr Ho-H HO H-OH OP COOH
催化剂前体的形成 Ti OPr i Pr iO OPr i OPr i Ti O O O O O OOH * HO COOH H OH COOH HO H + + +
反应机理 ●●●0●● OH Ti OOH o HO
反应机理…… Ti O O O O * O Ti O O O O O * Ti O O O O O * * OH OOH Ti O O O O * HO O * HO Ti O O O O O * *