Preparation and uses of organozinc compounds in organic synthesis

1. CPT-4.1
UNIT-II
Prepared By
Dr. Krishnaswamy. G
Faculty
DOS & R in Organic Chemistry
Tumkur University
Tumakuru
Use of Organozinc reagents

2. The organozinc compounds are less reactive compared to
Organo lithium and Organo magnesium compounds since the
C–Zn bond is highly covalent and hence allowing the
preparation of functionalized derivatives.
The first organozinc compound diethylzinc (Et2Zn) was
prepared by Edward Frankland in 1849 and this was also the
first compound with metal to carbon sigma bond.
Organo zinc compounds are sensitive to oxidation hence they
are prepared in situ and reactions require inert atmosphere (N2
/ Ar)
I
Zn Zn

DiethylzincEthyliodide
Introduction

3. The three main classes of organozinc compounds
(1) Diorganozincs R-Zn-R (Homoleptic)
(2) Organozinc halides R-Zn-X (Heteroleptic)
(3) Metal zincates (M+R3Zn-) M = Li / Mg
or Ionic organozinc

4. Organo zinc compounds are generally prepared by reaction of
primary and secondary halides (Iodides) with zinc metal
(Oxidative addition reaction-direct insertion of zinc into
carbon-halogen bond).
I
Zn
Zn

I
(or)
Zn
(or)
With Zinc dust activated by 1,2-dibromoethane
Preparation

5. With Rieke Zinc
ZnCl2 Zn
Li-naphthalenide
LiLi-naphthalenide
FG-RX
[FG-RZnX]
Rieke Zinc
R= Alkyl, Aryl, Benzyl
X = Br, I
FG = CO2R, CN, halide
Organo zinc halides are also prepared by reaction of primary
and secondary halides (Iodides) with Rieke Zinc.

6. Unfunctionalized dialkylzincs (R2Zn) are obtained by
transmetallation of zinc halides such as ZnCl2 with RLi or
RMgX.
Practical way of preparing functionalized dialkylzincs are by
iodide-zinc exchange reactions catalysed by CuI.
MgBr
ZnCl2
Zn
2MgClBr
FG-RCH2I
Et2Zn, CuI
(FG-RCH2)2Zn

7. Triorganozincates are generally prepared by the reaction of zinc
halide with three equivalents of alkyllithium or Grignard reagent
or from stoichiometric reaction of organolithium or Grignard
reagent with diorganozinc.

8. Utilization of organozinc reagents in organic syntheses
Reformatsky reaction
Cyclopropanation (Simmons-Smith reaction)
Transmetallations with transition metals.

9. Condensation of ester-derived zinc enolates (Reformatsky
reagent) with aldehydes or ketones to give corresponding β-
hydroxyesters
Reformatsky reaction
OR2
OZnX
R H/R'
O
R H/R'
HO OR2
O
-hydroxyesters
Aldehydes /
Ketones
Reformatsky
reagent
XZn
OEt
O
X
OEt
O
Zn
a-halo ester

10. Zinc enolates are generated by addition of an α-haloester in THF,
DME, Et2O, benzene, or toluene to an activated zinc, such as a
Zn-Cu couple or zinc obtained by reduction of zinc halides with
potassium (Rieke zinc).

11. BrZn
OEt
O
OEt
OZnBr
C-Zn enolate Oxygen-Zinc enolate

13. In 1958, Simmons and Smith reported that treatment of a zinc-
copper couple with diiodomethane in ether produces a reagent
that adds to alkenes to form cyclopropanes through Zn-carbenoid
intermediate (Iodomethyl)zinc iodide).
It is also known as cyclopropanation reaction
(Iodomethyl)zinc iodide
Simmons and Smith Reaction

14. The cyclopropanation reaction of simple alkenes appears to
proceed via concerted stereospecific syn-addition of a Zn-
carbenoid (carbene-like species) to the double bond without the
involvement of a free carbene.
C IH
I
H
Zn-Cu
Oxidative addition
Mechanism

15. The reaction is stereospecific with respect to to the alkene

16. The Zinc carbenoid react chemoselectively with more
nucleophilic double bond in dienes and polyenes.
Zn-Cu
CH2I2

17. The Zinc carbenoid react stereoselectively with hindered
nucleophilic double bond.
Zn-Cu
CH2I2
Major Minor

18. Stereoselectivity will be reversed if any chelating groups (OR,
OH, C=O) are present near to double bond. Cyclopropanation
occurs from the same face of the double bond as that of the oxy
substituents.
Zn-Cu
CH2I2
OR OR OR
Major

19. Carbon-carbon bond forming cross coupling reaction of an
organic halide and an organozinc halide reagent in the presence
of a nickel or palladium catalyst is known as Negishi coupling.
Transmetallation Reaction

20. The palladium-catalyzed coupling of organozinc compounds
with thioesters to form ketones is known as Fukuyama
coupling.
Transmetallation Reaction

21. The Barbier reaction involves nucleophilic addition of a
carbanion equivalent to a carbonyl.
The reaction produces a primary, secondary, or tertiary alcohol
via 1, 2-addition.
R3
-X Zn
Addition Reaction