Advanced organic reactions 2000 - Warren.pdf

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selectivity.pdf
SELECTIVITY 1
SELECTIVITY
Science 1983 , 219 , 245
Chemoselectivity
preferential reactivity of one functional group (FG) over another
- Chemoselective reduction of C=C over C=O:
O
H 2 ,
Pd/C
O
- Chemoselective reduction of C=O over C=C:
O
NaBH 4
OH
O
+
O
NaBH 4 , CeCl 3
OH
only
- Epoxidation:
MCPBA
+
OH
OH
OH
O
O
(2 : 1)
VO(acac) 2 ,
tBuOOH
OH
OH
exclusively
O
Regioselectivity
- Hydration of C=C:
1) B 2 H 6
2) H 2 O 2 , NaOH
R
OH
R
OH
R
1) Hg(OAc) 2 , H 2 O
2) NaBH 4
- Friedel-Crafts Reaction:
O
RCOCl,
AlCl 3
R
+
R
O
O
SiMe 3
RCOCl,
AlCl 3
R
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SELECTIVITY 2
- Diels-Alder Reaction:
R
O
R
O
R
+
+
major
minor
O
O
R
O
R
+
+
R
O
major
minor
O
O
+
O
H
O
OAc
O
H
O
OAc
O
OAc
O
OAc
O
OAc
Raney Ni, H 2
+
O
O
SPh
O
O
SPh
O
H
O
H
H
Change in mechanism:
PhSH, H +
SPh
R
R
R
SPh
PhSH, (PhCO 2 ) 2
Stereochemistry:
Relative stereochemistry: Stereochemical relationship between two or more stereogenic centers
within a molecule
H
H
H
H
HO
enantiomers
same relative stereochemistry
OH
cholesterol
syn: on the same side ( cis)
anti: on the opposite side (trans)
- differences in relative stereochemistry lead to diastereomers.
Diastereomers= stereoisomers which are not mirror images; usually have different physical
properties
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SELECTIVITY 3
Absolute Stereochemistry: Absolute stereochemical assignment of each stereocenter (R vs S)
Cahn-Ingold-Prelog Convention (sequence rules)
- differences in absolute stereochemistry (of all stereocenters within the molecule) leads to
enantiomers.
- Reactions can "create" stereocenters
O
MeMgBr
HO CH 3
Ph
H
Ph
H
MeMgBr
H 3 C OH
Ph
H
O
enantiomers
(racemic product)
Ph
H
HO CH 3
Ph
H
MeMgBr
Diastereome r ic transition states- not necess ar ily e q ual in energy
Me Me
Me Me
N
O
Ph
N
O
H
Zn
O
O
Zn
CH 3
CH 3
CH 3
CH 3
H
Ph
Zn
Zn
H 3 C
H 3 C
HO CH 3
HO CH 3
Ph
H
H
Ph
Diastereoselectivity
CH 3 MgBr
CH 3
CH 3
+
Ph
Ph
Ph
CHO
HO H
H OH
syn
anti
Diastereomers
Cram Model (Cram's Rule): empirical
O
O
O
M
S
M
H 3 C
H
S
R
Nu
CH 3 MgBr
CH 3 MgBr
favored
L
R
H
L
Ph
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SELECTIVITY 4
Felkin-Ahn Model
O M
S
O
L
Nu
Nu
L
R
S
M
R
favored
disfavored
Chelation Control Mode
M
OR
O
O
HO
M
OR
S
R
CH 3 MgBr
CH 3 MgBr
Nu
S
M
S
M
R
OR
favored
R
HO
TBSO
MgBr
TBSO
O
relative stereochemical control
H
O
H
O
OBn
OBn
Stereospecific
Stereochemictry of the product is related to the reactant in a mechanistically defined manner; no
other stereochemical outcome is mechanistically possible.
i.e.; SN2 reaction- inversion of configuration is required
Br 2
H 3 C
H
Br
meso
H
Br
CH 3
Br 2
CH 3
Br
Br
CH 3
H
H
+
H
H
Br
CH 3
CH 3
Br
enantiomers (racemic)
Stereoselective
When more than one stereochemical outcome is possible, but one is formed in excess (even if that
excess is 100:0).
H 2 , Pd/C
CH 3
H
H
H
H
+
CH 3
H
H
a
-pinene
only isomer
not observed
O
O
O
O
O
O
LDA, CH 3 I
Diastereoselective
Enantiospecific
N
O
N
O
+
N
O
S
S
S
(96 : 4)
Diasteromers
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OXIDATIONS 5
Oxidations
Carey & Sundberg: Chapter 12 problems: 1a,c,e,g,n,o,q; 2a,b,c,f,g,j,k; 5; 9 a,c,d,e,f,l,m,n; 13
Smith: Chapter 3
March: Chapter 19
I. Metal Based Reagents
1. Chromium Reagents
2. Manganese Rgts.
3. Silver
4. Ruthenium
5. other metals
II Non-Metal Based Reagents
1. Activated DMSO
2. Peroxides and Peracids
3. Oxygen/ ozone
4. others
III. Epoxidations
Metal Based Reagents
Chromium Reagents
- Cr(VI) based
- exact stucture depends on solvent and pH
- Mechanism: formation of chromate ester intermediate
Westheimer et al. Chem Rev. 1949 , 45 , 419
JACS 1951 , 73 , 65.
HO
O -
HCrO 4 -
R
R
Cr
R
R
R 2 CH-OH
O
+ HCrO 3 - + H +
C
O
O -
H +
H
+ H 2 O
Jones Reagent (H 2 CrO 4 , H 2 Cr 2 O 7 , K 2 Cr 2 O 7 )
J. Chem. Soc. 1946 39
Org. Syn. Col. Vol. V , 1973 , 310.
- CrO 3 + H 2 O
®
Cr(III)
(black) (green)
- 2°- alcohols are oxidized to ketones
Jones
reagent
R
R
R 2 CH-OH
acetone
O
- saturated 1° alcohols are oxidized to carboxyli c acid s .
Jones
reagent
O
hydration
HO OH
Jones
reagent
O
RCH 2 -OH
R
H
R
H
acetone
acetone
R
OH
- Acidic media!! Not a good method for H + sensitive groups and compounds
H 2 CrO 4 (aqueous solution)
K 2 Cr 2 O 7 + K 2 SO 4
- Cr(VI)
®
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