ORGANOZINC REAGENT

ROLE OF ORGANOZINC REAGENT IN C-C BOND FORMATION by VARINDER KHEPAR ( PhD Chemistry), Punjab Agricultural Chemistry, Ludhiana, Punjab, INDIA

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

2. Contents Introduction Synthesis From zinc metal Functional group exchange β - silyl diorganozinc compounds Transmetallation Reactions Reformatsky reaction Simmons–smith reaction Negishi coupling Fukuyama coupling 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 + R 3 Zn- with M = lithium or magnesium

4. Synthesis 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 ZnCl 2  with potassium, is another activated form of z inc.

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 Me 3 SiCH 2 - (TMSM), which is a non-transferable group .

7. Transmetallation Z inc can exchange with other metals such as  mercury ,  lithium and copper etc. E g : reaction of  diphenylmercury with zinc metal to form  diphenylzinc and metallic  mercury.

8. Reactions 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 .

10. Blaise reaction M odification of the Reformatsky reaction is the  Blaise reaction allows with zinc homo- enolates .

11. Simmons–Smith reaction U sed 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"

12. Zinc-copper couple is commonly used to activate zinc. Eg : e.  Zinc-copper couple  is commonly used to activate zinc. [21]

13. 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.

14. 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. 

15. Mechanism

16. 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.

17. Organozincates The reaction of elemental sodium with  diethylzinc . Two types of organozincates are recognized: tetraorganozincates ([R 4 Zn]M 2 ), which are dianionic , and triorganozincates ([R 3 Zn]M), which are monoanionic .

18. Triorganozincates ([R 3 Zn]M) involves the degradation of Triethylzincate degrades to sodium hydridoethylzincate (II)  Tetraorganozincates ([R 4 Zn]M 2 ) formed by mixing Me 2 Zn and MeLi in a 1:2 molar ratio

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

20. 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

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