15.1

OrganometallicOrganometallic CompoundsCompounds (R-M)(R-M)

Organomagnesium & Organolithium compds 15.1

Lithium Diorganocopper (Gilman) Reagents 15.2

Not covered: Organopalladium reagents, Heck reaction, carbenes, carbenoids, & alkene metathesis.

Synthesis, Concepts and the Final

HC

CC

C

H H

H H

H H

H

HM

E

HC

CC

C

H H

H H

H H

H

H

E

M+

Chapter 15

15.2

Organometallic CompoundsR-Mg-X or R-M

H3CC MgBr

HH

(-)(-)(+)

Recall pKa of alkanes

:B

H B

+

+

C

H

H

HH3C

C

H

H

H3CH3C

C Mg BrH

H

15.3

Prep of Organometallic Compounds

Grignard (organomagnesium compound)

H3CCH2

Br + Mgo ether H3CCH2

Mg-Br

H3CCH2

Br

:Mg

ether H3CC Mg Br

HH

(-) (-)(+)

free radical likeH3C

C Mg BrH

H

covalent

and

ionic view

15.4

Prep of Organometallic Compounds

Grignard

H3CCH2

Br + Mgo ether H3CCH2

Mg-Br

Alkyllithium

H3C CH2CH2-Br + 2Lio etherH3C CH2 CH2-Li + LiBr

H3C CH2 C

H

H

Li

OR

15.6Reactions - protic compounds (acids)

H3C- +

+ H3C HMgBr

H O

C

CH3

CH3

H

BrMg+ -O

CCH3

CH3

H+

++C

C

H

H

IMg CH2CH3

+ -C

C

H

CH2CH3H

MgI

H3C C

H3C

H3C

Li + H NH

HH3C C

H3C

H3C

H + NH

H

- +Li+

15.7

Prep of R-M (Nu:- +M)alkyl halide (sp3) + metal

e.g. Grignard or organomagnesium reagent

But also: vinyl halide (sp2) + metalaryl halide (sp2) + metal

MgXether Mgo

(metal)

X

+

15.8

Nucleophilic ReactionsMgX

1. etherO+

2. H+/H2O (neut.)

OH

MgX

1. etherO

+ +

O

2. H+/H2O (neut.)

OH

Attacks less hindered side of epoxide

15.9

LiO

H

HD

THF H+/ H2O

(neut.)+

- + OH

H

HD

Primary site inverted, secondary unchanged.

Reactions

15.10Lithium Diorganocopper Reagents

Prep and use in Synthesis

(CH3CH2)2CuLi'ether'

+2 CH3CH2Li + CuI LiI

R2CuLiRLi + CuI + LiI'ether'

(similar Grignard reagent can be made)'ether'

+2 CH3MgI + CuI (CH3)2CuMgI MgI2

15.11Use: Substitution rxn, replace halides

but cuprates are better

'ether'+I

H2C

R H3CH2CC

R(CH3CH2)2CuLi

- + H H

Grignards and alkyllithiums can be nucleophiles…..

H3C Li THFOS

O

O

R H3C+-+ H+/H2O

(neut.)

15.12Use: Substitution, replace leaving group

TMS = trimethylsilyl

Br OTMSLiCuOH

2 ether+ H+/H2O

(neut.)

I

R

R'R

R'

CuMgBr+

2

'ether' H+/H2O(neut.)

addeliminate*

ICuLiether

2+ H+/H2O

(neut.)

addeliminate*

*not really SN2, ignore mechanism, 2nd semester

15.13Organometallic Compounds

earlier = RMgX or RLi

Li O

HO1. ether

+2. H+/H2O

(neut)

Better

2. H+/H2O (neut)

O

CuMgX

HO1. ether

+

2

Nucleophile attacks less hindered side of epoxide

15.14

SYNTHESIS

SM target

O

CN?

Propose how to convert starting material (sm) to a target

rules: Use any number of stepsFor each step show:

- necessary reagents- necessary conditions - expected product or

products

15.15

SYNTHESIS

O

CN

starting material

target

Compare functional groups and carbon skeleton

Need: 1 carbon (CN) and ketone + nitrile from olefin

15.16

SYNTHESIS retroanalysis

OC:N

Br

+

OH

Br

Br2

H2OxsO

CN

SM

target

NC-/DMFPCC

15.17

SYNTHESIS retroanalysis

Br2

H2OxsPCC

NC-/DMF

OH

CNO

C:N+

RCO3H

1. DMSO2. H2O

PCC

O

CN

SM

target

O

Br

OH

Br

15.18

synthesissynthesis

O

O

OH

How?“thoughts”--- join---

OH

O

X

CH3

X+

15.19

synthesissynthesis

plan

O

O

OH

How?synthesissynthesis

O

O

OH

How?

OH

O

X

CH3

X+

NaH

O-

H

+Na

polaraprotic X

O

-NH2

or R:-

H3C-I

O

HgSO4H2O

O

Oexpectedbyproduct

+

O

H

reverse?

15.20

N

H

X

N

H H

+

SM target

NBS hv

BrDMF

N H

H

N

H

+

15.21

OH

OH

Br

O

OH

O

RCO3H PBr3 Mg/THF

H+/H2O

15.22Br

O

O

OR

compare carbon skeletonfunctional groups

convert 2-bromopropeneto 2-hexanone

15.23

O

O

OR

Br

compare carbon skeletonfunctional groups

O

X

X

15.24

NH2

1 eq. H

Br

O

NH2

1 eq.Br

HgSO4/H2O

O+

15.25

OH

Br

+

Br

O

NH2

1 eq.

NH2

1 eq.H

Br

O+

HgSO4/H2O

OH

OH

15.26Br

O

NH2

1 eq.

NH2

1 eq.H

Br

O+

HgSO4/H2O

Br

1 eq.Br

Br

+

BrH2Pd/C HO

H2O

+

PCC

Br

H

++

15.27

Br

Br NH2

(xs) H

Br

Br

How? dibromidesource?

15.28Br NH2

(xs) H

Br dibromidesource?

Br

Br

BrOH

1.BH3

2.H2O2

HO-PBr3

Br Br Br

Br

NBShv

H2Pd-C

Br H2Pd-C

BrO-tBu

Br2

others?

15.29

BrBr2

H2Pd-C

Br O-tBu

Br

Br

Br

Br

H2Pd-C

NBShv

BrOH

1.BH32.H2O2 HO-

Br

PBr3

Br

Br NH2

(xs) H

dibromidesource?

others?

15.30Br NH2

(xs) H

BrOH

1.BH3

2.H2O2

HO-

Br Base(NaHCO3)

O

Br

H3CO

HH

H3COH H

H3COH

:B

racemic

15.31Br

O

NH2

1 eq.

NH2

1 eq.H

Br

O+

HgSO4/H2O

Br

Br

+

O

OH

OH

H2Pd/C

PCC

15.32

I’ve enjoyed teaching the class! I appreciate your hard work.

chapters 1-11, 15-15.2 3 hour exam, models, pencilNO calculators or cell phones

Grades submitted (VIP), scores posted ASAP.Grade - determined by either: (1) accumulated total points (tests + final + recitation pts) or (2) final exam grade WHICHEVER IS HIGHER!

Final 200 pts: ~130 cumulative,~70 new material5:30 pm PSC 002, (possibly 006)