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

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!

14.5 – Organolithium Compounds as Bases14.5 – Organolithium Compounds as Bases

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 – Organic Synthesis – Molecular Engineering14.9 – Organic Synthesis – Molecular Engineering

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 Analysis14.9 – Retrosynthetic Analysis

Example: OH MgBr

H

O+

O

H BrMg+

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

Not covering 14.13 – 14.17