Organozinc reagents play an important role in C-C bond formation through various reactions. They are synthesized through methods such as insertion of zinc metal into alkyl halides, functional group exchange, and transmetallation. Key reactions involving organozinc reagents include the Reformatsky reaction, Simmons-Smith reaction, Negishi coupling, Fukuyama coupling, and Barbier reaction. Organozincates, which involve sodium or lithium zincates, also participate in C-C bond forming reactions.

1. Role of Organozinc reagent in C-C bond
formation
VARINDER KHEPAR
( PhD Chemistry)
C-Zn

2. Contents
Introduction
Synthesis
o From zinc metal
o Functional group exchange
o β-silyl diorganozinc compounds
o Transmetallation
Reactions
o Reformatsky reaction
o Simmons–smith reaction
o Negishi coupling
o Fukuyama coupling
o Barbier reaction
Organozincates

3. Introduction
• In 1848 Edward Frankland prepared the first organozinc
compound diethylzinc.
• They are less reactive than Grignard and organolithium reagent.
• C–Zn bond is polarized due to the differences in
electronegativity : C (2.55) and Zn (1.65).
• Many organozinc compounds are pyrophoric and therefore
difficult to handle.
• Zinc(II) complexes adopts several coordination geometries,
commonly octahedral and tetrahedral.
• The three main classes of organozincs are: organozinc halides R-
Zn-X, diorganozincs R-Zn-R, and lithium zincates or magnesium
zincates M+R3Zn- with M = lithium or magnesium

4. Synthesis
o FROM ZINC METAL
• Alkylzinc iodides (RZnI) are best prepared by direct insertion of
zinc metal (activated zinc dust) into alkyl iodides or by treating
alkyl iodides with Rieke zinc.
• Rieke metals are highly reactive metal powders because they
have high surfaces areas.
• Rieke Zn produced by reduction of ZnCl2 with potassium, is
another activated form of zinc.

5. Functional group exchange
• The two most common zinc functional group
interconversion reactions are with halides and
boron, which are catalyzed by copper iodide (CuI) or
base, followed by treatment with diethyl zinc

6. β-Silyl diorganozinc compounds
• It involved Me3SiCH2- (TMSM), which is a non-
transferable group.

7. Transmetallation
• Zinc can exchange with other metals such
as mercury, lithium and copper etc.
• Eg: reaction of diphenylmercury with zinc metal to
form diphenylzinc and metallic mercury.

8. Reactions
o Reformatsky reaction
• convert α-haloester and ketone or aldehyde to a β-
hydroxyester.
• Acid is needed to protonate the resulting alkoxide.

9. Mechanism
• The initial step is an oxidative addition of zinc metal
into the carbon-halogen bond, thus forming a
carbon-zinc enolate.
• This C-Zn enolate can then rearrange to the Oxygen-
Zinc enolate via coordination.
• Once this is formed the other carbonyl containing
starting material will coordinate and give the
product after protonation.

11. Blaise reaction
• Modification of the Reformatsky reaction is
the Blaise reaction allows with zinc homo-enolates.

12. Simmons–Smith reaction
• Used to prepare cyclopropanes from olefin
using methylene iodide as the methylene source.
• The key zinc-intermediate formed is a carbenoid
(iodomethyl)zinc iodide which reacts with alkenes
to afford the cyclopropanated product.
• The intermediate is believed to be a three-centered
"butterfly-type"

13. Zinc-copper couple is commonly used to activate zinc. Eg:

14. Negishi coupling
• Reaction of an organohalide with an organozinc compound to give
the coupled product using a palladium or nickel catalyst.
• The palladium catalyzed mechanism begins with oxidative
addition of the organohalide to the Pd(0) to form a Pd(II) complex.
• Transmetalation with the organozinc then follows where the R
group of the organozinc reagent replaces the halide anion on the
palladium complex and makes a zinc(II) halide salt.
• Reductive elimination then gives the final coupled product,
regenerates the catalyst and the catalytic cycle begin again.

16. Fukuyama coupling
• Palladium-catalyzed reaction involving the coupling of an
aryl, alkyl, allyl, or α,β- unsaturated thioester compound.
• Thioester compound can be coupled to a wide range of
organozinc reagents in order to reveal the corresponding
ketone product.

17. Mechanism

18. Barbier reaction
• Involves nucleophilic addition of a carbanion equivalent
to a carbonyl.
• Similar to the Grignard reaction.
• Organozinc reagent is generated via an oxidative
addition into the alkyl halide.
• Reaction produces a primary, secondary, or tertiary
alcohol.

19. Organozincates
• The reaction of elemental sodium with diethylzinc.
• Two types of organozincates are recognized:
tetraorganozincates ([R4Zn]M2), which are
dianionic, and triorganozincates ([R3Zn]M), which
are monoanionic.

20. • Triorganozincates ([R3Zn]M) involves the degradation of
Triethylzincate degrades to sodium hydridoethylzincate(II)
• Tetraorganozincates ([R4Zn]M2)
• formed by mixing Me2Zn and MeLi in a 1:2 molar ratio

21. Reactions
• Aryl trimethylzincates participate in vanadium
mediated C-C forming reactions

22. References
• https://en.wikipedia.org/wiki/Organozinc_compound
• Rieke R D (1989). Preparation of Organometallic
Compounds from Highly Reactive Metal
Powders. Sci. 246 (4935): 1260–64.
• Shimizu, Toshiaki, Seki and Masahiko (2000). Facile
synthesis of (+)-biotin via Fukuyama coupling
reaction. Tetrahedron Letters 41 (26): 5099–01.
• Nicolaou K C, Bulger, Paul G, Sarlah and David (2005).
Palladium-Catalyzed Cross-Coupling Reactions in Total
Synthesis. Ang. Chem. Int. Edn. 44 (29): 4442–4489.
• https://en.chem-station.com/reactions
2/2014/10/fukuyama-reduction.html

23. THANK YOU