【文章內(nèi)容簡介】 3 CO HC NC 6 H 5 C HO S i M e3C NC H 3 CO HC NH 3 OM e 3 S i C l 1 ) L D A2 ) B rC H3CO S i M e3C NO HC H3CO8 5 %Example 3 1, 3 –二噻烷法 S HS H+ R C H OH C l / C H 3 C lSSRHB u L iSSRL iR 39。 XSSRR 39。 H3 O+ / H g 2 +ORR 39。不易發(fā)生 Michael 加成反應。 Example 4 乙基乙硫甲基亞砜法 SSC2H5OC2H51 ) L D A2 ) R XSSC 2 H 5OC2H5R1 ) R 39。 X2 ) H3O+R 39。RO1 )O2 ) H3O +ROOM i c h e a l a d i t i o n1, 4 – 二酮 四、縮合反應 (Condensation) 1. Aldol Reaction 2. Michael Addition 3. Mannich Reaction 4. Claisen Condensation 5. Dieckmann Condrnsation 6. Darzen’s Reaction 7. Reformatsly reaction 1. Aldol Reaction (condensation) 1) 經(jīng)典 Aldol 反應的兩大缺點 ? 不同醛、酮之間的反應常得到混合產(chǎn)物； ? 立體選擇性差 2) 定向醇醛縮合反應 （ Directed Aldol condensation) Metood 1 Preformed Lithium Enolates ? Zenolates give predominantly syn (or threo) aldol products (thermodynamic enolates). ? Eenolates give predominantly anti (or erythro) aldol products (kiic enolates). Example 1 Steric size of R1 affects diastereoselectivity ? Origin of Diastereoselectivity a. Zenolates ? Diastereoselectivity for Zenolate (giving syn aldol product) is maximized when R1 and R3 are sterically demanding (R1/R3 interaction is maximized). ? Diastereoselectivity also increases as metal is changed to boron. This is attritubted to a tighter . (B–O bond shorter, so R1/R3 steric interactions are magnified in . for anti product). ? When R2 is very large the R3/R2 gauche interaction R1/R3 1,3diaxial interaction (Why?). b. Eenolates ? Diastereoselectivity increases as R1 and R3 bee sterically large, and a switch to the boron enolate will increase selectivity. ? Diastereoselectivity may switch when R2 is very large (Why?). ? Effect of R1 ? Effect of R3 ? Effect of R2 Metood 2 Preformed Boron Enolates a. Zenolate Preparation and Reactions b. Eenolate Preparation and Reactions Originally difficult to control but: c. Examples of more recent methods to control boron enolate geometry Aldol Condensation with Chiral Enolates ? Ti enolate promoted Evans aldol (nonEvans syn aldol) ? Chelated and nonchelated Ti enolates Metood 3 AcidCatalysed Directed Aldol Reactions R1R2O S i M e3R3T i C l4C H2C l2R1R2R3OS i M e3OR4R5T i C l3C lC l M e3S i C lR1R2R3OT i C l3OR4R5H2OR1R2R3O HOR4R5 該方法是 在酸性條件 下反應；但 立體選擇性 較差。 3) 有機小分子催化醇醛縮合反應 （ Small Organic Molecules Catalysted Aldol Reactions) OOOOOOA l d o l a s e A n t i b o d y 3 8 C 2B a r b a s , C . F . , I I I e t a l . J . A m . C h e m . S o c . 1 9 9 7 , 1 1 9 , 8 1 3 1L P r o l i n eH a j o s E d e r S a u e r W i e c h e r t r e a c t i o nH a j o s , Z . G . e t a l . J . O r g . C h e m . 1 9 7 4 , 3 9 , 1 6 1 5E d e r , U . 。 S a u e r 。 G . , W i e c h e r t , R . A n g e w . C h e m . I n t . E d . E n g l . 1 9 7 1 , 1 0 , 4 9 6H o w e v e r , t h e p r o l i n e c a t a l y z e d d i r e c t i n t e r m o l e c u l a r a s y m m e t r i c a l d o l r e a c t i o n h a s n o t b e e n d e s c r i b e d . F u r t h e r , t h e r e a r e n o a s y m m e t r i c s m a l l m o l e c u l e a l d o l c a t a l y s t s t h a t u s e a n e n a m i n e m e c h a n i s m . B a s e d o n o u r o w n r e s u l t s a n d S h i b a s a k i 39。 s w o r k o n l a n t h a n u m b a s e d s m a l l m o l e c u l e a l d o l c a t a l y s t s , w e r e a l i z e d t h e g r e a t p o t e n t i a l o f c a t a l y s t s f o r t h e d i r e c t a s y m m e t r i c a l d o l r e a c t i o n .OHN O2OD M S ON O2O O HOHN O2OD M S ON O2O O HOHOD M S OO O HRR+L p r o l i n e3 0 m o l %6 8 % ( 7 6 % e e )+ d i f f e r e n t a m i n o a c i d3 0 m o l %+L p r o l i n e3 0 m o l %L p r o l i n e i s b e s ty i e l d : 5 4 9 7 % 。 % e e : 6 0 9 6 %OH NH OOHNH OOHO HNOOHNH OOHNOOHOHRHR C H O NOOHO HRH2ONOOHO HO HRHOO HRH NH OOH+ H2O+a b cd+++ge f P r o p o s e d E n a m i n e M e c h a n i s m o f t h e P r o l i n e c a t a l y z e d A s y m m e t r i c A l d o l R e a c t i o nC a r l o s F . B a r b a s I I I e t . a l . J . A m . C h e m . S o c . 2 0 0 0 , 1 2 2 ( 1 0 ) , 2 3 9 5 6C a t a l y t i c A s y m m e t r i c S y n t h e s i s o f a n t i 1 , 2 D i o l sO HH ROOD M S OO O HO H+L P r o l i n e2 0 3 0 m o l %r . t .2 4 7 2 hs y n : a n t i : 1 5 : 1 2 0 : 1 。 y i e l d : 3 8 9 5 % 。 % e e : 6 7 9 9 %C a r l o s F . B a r b a s I I I e t . a l . J . A m . C h e m . S o c . 2 0 0 0 , 1 2 2 ( 3 0 ) , 7 3 8 6 7P r o l i n e C a t a l y z e d A s y m m e t r i c A l d o l R e a c t i o n s b e t w e e nHOOO O H+L P r o l i n e1 0 2 0 m o l %3 7 dy i e l d : A 2 2 3 5 % , B 3 5 5 0 % 。 % e e : 3 6 7 3 %R ROR+2 0 v o l %A BO O HRORABHOROL P r o l i n eL P r o l i n eNC O2HR+ONC O2HRO P r o l i n eC o m p o u n d B w a s f o r m e d v i a M a n n i c h C o n d e n s a t i o nK e t o n e s a n d a U n s u b s t i t u t e d A l d e h y d e sB e n j a m i n l i s t e t a l . O r g . L e t t . 2 0 0 1 , 3 ( 4 ) , 5 7 3 5 7 5C H C l3ROR 39。 A r C H OROR 39。A rO H+a m i n o a c i dB a r b