Download Chapter 1 Structure and Bonding

I.
Organometallic Reagents = carbon-metal bonds
A.
Nucleophilic Carbon
1) OH- contains a nucleophilic oxygen that can give a new C—O bond
HO-
2)
B.
+
HO CH3
H3C Br
+
Br
Formation of new C—C bonds is the key requirement in organic synthesis
OH
R'
C O
R' C CH2R''
R''CH2
R
R
Alkylmetal Reagents
1) Haloalkanes can be transformed into organometallic compounds
a) Alkyllithium Synthesis (I > Br > Cl reactivity)
CH3CH2OCH2CH3
diethyl ether
O
RBr + 2 Li
b)
ether or THF
0 oC
RLi + LiBr
Tetrahydrofuran
Alkylmagnesium Synthesis (Grignard Reagent)
RI + Mg
ether or THF
o
0 C
RMgI
2)
Alkylmetals are very basic, very strong Nucleophiles
a) pKa of CH3—H bond is about 50
b) Alkylmetal reagent is the conjugate base of a very weak acid H3C:c) Use them as soon as you make them (…made in situ…)
d) Air and water sensitive, must do reaction under N2 or Ar
-
+
R MgX
3)
O
R
Mg
O
I
4)
+ H OH
Hydrolysis
RH + XMOH
True structure involves coordinated solvent—require ether or THF
+
Very polar bond, metal is electropositive
H3C Br
a) Opposite of usual situation for carbon, as in Haloalkanes
b) Treat the molecule like R- = Carbanion
c) Resonance forms
R

M
+
C
M
C:
+ M
C.
Alkylmetal reagents in Alcohol Synthesis
1) Goal: Formation of new C—C bonds by using C Nucleophile
2) Nucleophilic attack of Haloalkane by alkylmetal reagent is unsuccessul
R- +MgBr
3)
Cl
+
R
Elimination Reactions give side products because of extreme basicity
H
R- +MgBr
4)
Cl
We will need a more successful carbon electrophile
+
RH
5)
Carbonyl electrophiles (C+==O-) react more cleanly with alkylmetals
a) Ketones give tertiary alcohol products
-
O
RLi +
ether or THF
C
R'
O
R'
R'
OH
+
H , H2O
R'
C
R'
R
R
b)
Aldehydes give secondary alcohol products
O
RLi +
R'
H , H2O
ether or THF
C
OH
+
H
R'
C
R
c)
Formaldehyde (CH2O) gives primary alcohol product
O
RLi +
C
ether or THF
C
H
H
+
H , H2O
OH
H C
R
H
H
R'
II. Oxidation of Alcohols to Carbonyls
1)
2)
Reduction reactions can be reversed to give the aldehydes or ketones
Oxidizing Reagent is Cr(VI)
a) (Na2Cr2O7 or K2Cr2O7 or CrO3) and H2SO4 and H2O
R'
CH OH
R
b)
Na2Cr2O7
H2SO4, H2O
R'
C
O
R
Primary alcohols can be overoxidized to carboxylic acids
RCH2 OH
Na2Cr2O7
H2SO4, H2O
O
R
C
OH
3)
Do Primary alcohol oxidation without water
NH+ CrO3Cl a) PCC = pyridinium chlorochromate =
b) Anhydrous conditions and PCC don’t overoxidize primary alcohol
R CH2 OH
4)
O
PCC
CH2Cl2
R
C
H
Mechanism involves Chromic Ester
O
O
RCH2
OH +
VI
RCH2O Cr
OH + H2O
VI
HO Cr
OH
O
Chromic Ester
O
O
RCHO Cr OH
H2O
H
O
Like E2
O
RCH
+
H3O+
+
CrVIO3H
III. Synthesis of Complex Alcohols Using Alkylmetal Reagents
A. Useful Reaction Sequence
CH4
Br2
B.
CH3Br
CH3OH
CH2Cl2
H2C O
+
RMgBr
H
THF
RCH2OH
OH2
Retrosynthetic Analysis = Work Backwards from Target
1) Complex molecules are made from simple parts
2) Look for C—C bonds to break (form)
OH
CH3CH2CH2
-OH
PCC
CH2CH3
strategic
disconnection
CH3CH2CH2MgBr
+
CH3
CrO3, H2SO4, H2O
O
H+, H2O
THF
H3C
H3C
CH2CH3
OH
CH2CH3
H
H+, H2O
THF
O
CH3Li
+
H
CH2CH3