Organozinc compounds

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 (Et 2 Zn) 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 (N 2 / Ar ) Introduction

3. The three main classes of organozinc compounds Diorganozincs R-Zn-R ( Homoleptic ) Organozinc halides R-Zn-X ( Heteroleptic ) (3) Metal zincates (M + R 3 Zn - ) 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). Preparation

5. Organo zinc halides are also prepared by reaction of primary and secondary halides (Iodides) with Rieke Zinc.

6. Unfunctionalized dialkylzincs (R 2 Zn ) are obtained by transmetallation of zinc halides such as ZnCl 2 with RLi or RMgX . Practical way of preparing functionalized dialkylzincs are by iodide-zinc exchange reactions catalysed by CuI .

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

10. Zinc enolates are generated by addition of an α- haloester in THF , DME, Et 2 O , 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. C-Zn  enolate Oxygen-Zinc enolate

12. 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

13. 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. Mechanism

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

15. The Zinc carbenoid react chemoselectively with more nucleophilic double bond in dienes and polyenes .

16. The Zinc carbenoid react stereoselectively with hindered nucleophilic double bond.

17. 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.

18. 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

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

20. 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. Addition Reaction