Chapter 14: Organometallics, structure and nomenclature
H CR3
- +
Cl CR3
radical
chemistry
carbon
electrophiles
+ M CR3
carbon
nucleophiles
14.1 – Organometallic nomenclature
Li
H
CH2=CHNa
Cyclopropyl
lithium
Vinyl sodium
CH3MgI
Methyl magnesium iodide
(CH3CH2)2Mg
Diethyl magnesium
(CH3CH2)2AlCl
Diethylaluminum chloride
14.2 – Carbon-Metal Bonds in Organometallics
14.2 – Carbon-Metal Bonds in Organometallics
Organometallics
at YSU
Penny Miner, YSU MS (Ricerca Biosciences)
14.2 – Carbon-Metal Bonds in Organometallics
Organometallics
at YSU
Dipolar interactions guide regioselectivity
Penny Miner, YSU MS (Ricerca Biosciences)
14.2 – Carbon-Metal Bonds in Organometallics
Organometallics
at YSU
Miner, Wagner, Norris, Heterocycles 2005, 65, 1035-1049
Preliminary Activity Against S. aureus
0.9
HO
HO
HO
O
OH
N N
N
(CH2)7CH3
0.8
0.7
H
Absorbance at 450 nm
0.6
0.5
50 µL EtOH
1 µL MV-II-065
0.1 µL MV-II-065
0.01 µL MV-II-065
0.4
0.3
50-75% decrease in
capsule production
Prof. Diana Fagan (YSU
Biological Sciences)
0.2
0.1
0
100
200
400
Reciprocal of Antibody Dilution
800
14.3 – Preparation of Organolithium Compounds
R X +2M
RM + M+X-
2 Li
Cl
ether
-30 oC
Li
+ LiCl
2 Li
Br
Li
+ LiBr
ether
35 oC
Organolithiums
14.4 – Preparation of Organomagnesium Compounds
R X + Mg
RMgX
Mg
Br
ether
RT
MgBr
Mg
MgBr
Br
ether
35o C
Organomagnesium compounds – Grignard reagents
14.5 – Organolithium Compounds as Bases
CH3Li, (CH3)3CLi, n-BuLi are extremely powerful bases
N
H
+
THF
Li
N
Li
+
o
- 78 C
Convenient preparation of LDA
H
14.5 – Organolithium Compounds as Bases
Lab Experiment
Grignard Reagent Preparation
• Glassware must be clean and dry
• Dry with the “heat gun”
• Cool then begin experiment
Be careful to use the right ether!
14.5 – Organolithium Compounds as Bases
14.6 – Synthesis of Alcohols Using Grignard Reagents
Carbonyl
Polarization:
O
Grignard
Polarization:
O
 - 
MgBr
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
New Mechanism:
Nucleophilic Addition
- 
MgBr
O
OMgBr
Most often followed by a quench with acid:
OMgBr
H3O+
OH
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Overall Sequence: Nucleophilic Addition then quench
1. Mg, ether
Br
2. (CH 3) 2C=O
3. H 3O+
Very versatile alcohol synthesis
OH
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Br
Example:
CH2OH
1. Mg, ether
2. H2C=O
3. H3O+
Starting material
7
6
5
4
PPM
3
product
2
1
0
7
6
5
4
PPM
3
2
1
0
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Cl
Example:
2. CH3CHO
3. H3O+
Starting material
70
60
50
40
OH
1. Mg, ether
PPM
30
20
10
0
80
product
70
60
50
40
PPM
30
Product IR: 3200 cm-1
20
10
0
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Br
OH
1. Mg, ether
Product MS: M+ = 254
2. Ph2C=O
3. H3O+
Starting material
3
product
2
PPM
1
0
7
6
5
4
PPM
3
2
1
0
14.8 – Synthesis of Acetylenic Alcohols
1. NaNH2
H3C
H
H3C
CH2OH
2. H2C=O
3. H3O+
H3C
O
1. H3C
2. H3O+
Li
OH
14.9 – Organic Synthesis – Molecular Engineering
DDT, 2003, 1128
14.9 – Organic Synthesis – Molecular Engineering
14.9 – Molecular Engineering – Designing and Building
ACS Petroleum Research Fund Award 2006-2009
14.9 – Retrosynthetic Analysis – Planning the Synthesis
Target
molecule
Precursors
14.9 – Retrosynthetic Analysis – Planning the Synthesis
Plan
Synthesis
14.9 – Retrosynthetic Analysis
Target
molecule
RMgX or RLi = R
OH
Precursors
(synthetic equivalent)
O
+ CH3M
14.9 – Retrosynthetic Analysis
H
R C OH
H
H
R:
O
H
RMgX or RLi = R
(synthetic equivalent)
CH3
R C OH
H
CH3
R C OH
CH3
H3C
R:
H
H3C
R:
O
H3C
O
14.9 – Retrosynthetic Analysis
Example:
OH
MgBr
O
+
more accessible
H
CH3MgBr
+
O
H
14.9 – Retrosynthetic Analysis
Example:
OH
MgBr
O
+
H
O
H
+
BrMg
14.9 – Retrosynthetic Analysis and Synthesis
H
OH
O
MgBr
+
1. Mg, THF
Br
2.
H
3. H3O+
O
OH
Br
14.10 – Tertiary Alcohols from Esters and Grignard Reagents
O
2
R MgX
THF
3o alcohol
H3C
OCH3
then H3O+
O
2
MgBr
OCH3
+
MgBr
+
R
R
CH3
OH
THF
then H3O+
OH
O
2
OH
+
OCH3
THF
then H3O+
14.10 – Tertiary Alcohols from Esters and Grignard Reagents
O
OH
2 CH3MgBr + H3CO
Retrosynthesis:
OH
1. Mg, THF
Synthesis:
Also possible:
CH3Br
OH
2. PhCO2CH3 (0.5 eq)
3. H3O+
MgBr
O
+
14.11 – Alkane Synthesis Using Organocopper Reagents
ether or THF
2 RLi + CuX
R2CuLi + LiX
Proposed structure:
R
Cu
Br
(CH3CH2CH2CH2)CuLi
ether or THF
R
Li
14.11 – Alkane Synthesis Using Organocopper Reagents
• Useful for coupling with primary alkyl halides
• Use of secondary and tertiary alkyl halides complicated by
competing E2 reactions
• Works for simple alkyl halides, vinyl halides and aryl
ether
halides
(CH3)2CuLi + CH3(CH2)8CH2I
o
CH3(CH2)8CH2CH3
0 C
• Mechanism not completely understood
14.12 – An Organozinc Reagent for Cyclopropane Synthesis
ether
CH2I2
+
Zn
H
I C ZnI
H
Iodomethyl zinc iodide
I-CH2-ZnI
H
C H
IZn I
Simmons-Smith reaction
C
H
H
Not covering 14.13 – 14.17