Chapter 14: Organometallics, structure and nomenclature
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Transcript of Chapter 14: Organometallics, structure and nomenclature
Chapter 14: Organometallics, structure and nomenclatureChapter 14: Organometallics, structure and nomenclature
H CR3 Cl CR3
- +M CR3
-+
radical chemistry
carbonelectrophiles
carbonnucleophiles
Li
HCH2=CHNa (CH3CH2)2Mg
CH3MgI (CH3CH2)2AlCl
Cyclopropyl lithium
Vinyl sodium Diethyl magnesium
Methyl magnesium iodide Diethylaluminum chloride
14.1 – Organometallic nomenclature14.1 – Organometallic nomenclature
14.2 – Carbon-Metal Bonds in Organometallics14.2 – Carbon-Metal Bonds in Organometallics
Penny Miner, YSU MS (Ricerca Biosciences)
Organometallics at YSU
14.2 – Carbon-Metal Bonds in Organometallics14.2 – Carbon-Metal Bonds in Organometallics
Penny Miner, YSU MS (Ricerca Biosciences)
Organometallics at YSU
Dipolar interactions guide regioselectivity
14.2 – Carbon-Metal Bonds in Organometallics14.2 – Carbon-Metal Bonds in Organometallics
Miner, Wagner, Norris, Heterocycles 2005, 65, 1035-1049
Organometallics at YSU
N
NN (CH2)7CH3
H
OHOHO
OH
HO
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
100 200 400 800
Reciprocal of Antibody Dilution
Ab
sorb
ance
at
450
nm
50 µL EtOH
1 µL MV-II-065
0.1 µL MV-II-065
0.01 µL MV-II-065
50-75% decrease in capsule production
Preliminary Activity Against Preliminary Activity Against S. aureusS. aureus
Prof. Diana Fagan (YSU Biological Sciences)
14.3 – Preparation of Organolithium Compounds14.3 – Preparation of Organolithium Compounds
Organolithiums
XR + 2 M RM + M+X-
Cl2 Li
ether-30oC
Li + LiCl
Br2 Li
ether35oC
Li + LiBr
Organomagnesium compounds – Grignard reagents
XR + Mg RMgX
14.4 – Preparation of Organomagnesium Compounds14.4 – Preparation of Organomagnesium Compounds
Mg
etherRT
Br MgBr
BrMg
ether35oC
MgBr
CH3Li, (CH3)3CLi, n-BuLi are extremely powerful bases
Convenient preparation of LDA
14.5 – Organolithium Compounds as Bases14.5 – Organolithium Compounds as Bases
NH
Li+THF
- 78oC
NLi
H+
14.5 – Organolithium Compounds as Bases14.5 – 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!
CarbonylPolarization:
GrignardPolarization:
14.6 – Synthesis of Alcohols Using Grignard Reagents14.6 – Synthesis of Alcohols Using Grignard Reagents
O O
MgBr
-
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
New Mechanism: Nucleophilic Addition
O
MgBr
- OMgBr
Most often followed by a quench with acid:
OMgBr OHH3O+
Overall Sequence: Nucleophilic Addition then quench
OHBr
1. Mg, ether
2. (CH3)2C=O3. H3O
+
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Very versatile alcohol synthesis
Example: Br 1. Mg, ether
2. H2C=O3. H3O+
CH2OH
01234567PPM 01234567
PPM
Starting material product
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
Cl1. Mg, ether
2. CH3CHO3. H3O+
OH
010203040506070PPM 01020304050607080
PPM
Starting material product
Product IR: 3200 cm-1
Example:
Br 1. Mg, ether
2. Ph2C=O3. H3O+
OH
0123PPM 01234567
PPM
Starting material product
Product MS: M+ = 254
14.6-7 – Synthesis of Alcohols Using Organometallic Reagents14.6-7 – Synthesis of Alcohols Using Organometallic Reagents
14.8 – Synthesis of Acetylenic Alcohols14.8 – Synthesis of Acetylenic Alcohols
H3C H1. NaNH2
2. H2C=O3. H3O+
H3C CH2OH
OH3C Li1.
2. H3O+
OH
H3C
14.9 – Organic Synthesis – Molecular Engineering14.9 – Organic Synthesis – Molecular Engineering
DDT, 2003, 1128
14.9 – Molecular Engineering – Designing and Building14.9 – Molecular Engineering – Designing and Building
ACS Petroleum Research Fund Award 2006-2009
14.9 – Retrosynthetic Analysis – Planning the Synthesis14.9 – Retrosynthetic Analysis – Planning the Synthesis
Targetmolecule
Precursors
14.9 – Retrosynthetic Analysis – Planning the Synthesis14.9 – Retrosynthetic Analysis – Planning the Synthesis
Plan Synthesis
14.9 – Retrosynthetic Analysis14.9 – Retrosynthetic Analysis
Targetmolecule
Precursors
RMgX or RLi = R (synthetic equivalent)
OH O
+ CH3M
14.9 – Retrosynthetic Analysis14.9 – Retrosynthetic Analysis
(synthetic equivalent)
R C
H
H
OH OH
HR:
R C
CH3
H
OH OH3C
HR:
R C
CH3
CH3
OH OH3C
H3CR:
RMgX or RLi = R
14.9 – Retrosynthetic Analysis14.9 – Retrosynthetic Analysis
OHMgBr
+O
H
CH3MgBr +
OH
more accessible
Example:
14.9 – Retrosynthetic Analysis and Synthesis14.9 – Retrosynthetic Analysis and Synthesis
OH
Br
OH
OH
MgBr
OH
Br
+
1. Mg, THF
2.
3. H3O+
14.10 – Tertiary Alcohols from Esters and Grignard Reagents14.10 – Tertiary Alcohols from Esters and Grignard Reagents
R MgXH3C
O
OCH3
+2THF
then H3O+
OH
RR
CH3
3o alcohol
O
OCH3MgBr +2THF
then H3O+
OH
MgBr
2
O
OCH3THF
+then H3O+
OH
OH O
H3CO2 CH3MgBr +
CH3Br1. Mg, THF
2. PhCO2CH3 (0.5 eq)3. H3O+
OH
OHO
+MgBr
Retrosynthesis:
Synthesis:
Also possible:
14.10 – Tertiary Alcohols from Esters and Grignard Reagents14.10 – Tertiary Alcohols from Esters and Grignard Reagents
2 RLi + CuX R2CuLi + LiX
ether or THF
R Cu R LiProposed structure:
Br(CH3CH2CH2CH2)CuLi
ether or THF
14.11 – Alkane Synthesis Using Organocopper Reagents14.11 – 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
halides
• Mechanism not completely understood
CH3(CH2)8CH2CH3(CH3)2CuLi + CH3(CH2)8CH2Iether
0oC
14.11 – Alkane Synthesis Using Organocopper Reagents14.11 – Alkane Synthesis Using Organocopper Reagents
Iodomethyl zinc iodide
I-CH2-ZnI
CIZn I
HH C
HH
Simmons-Smith reaction
etherCH2I2 + Zn C
H
I ZnI
H
14.12 – An Organozinc Reagent for Cyclopropane Synthesis14.12 – An Organozinc Reagent for Cyclopropane Synthesis