1. Gilman's reagent

Synthesis and application of Gilman's reagent is discussed in the lecture.

1. 1. Gilman’s reagent
Dr. Shivendra Singh
UGC-NET-JRF, PhD-IIT Indore

2. ...Gilman’s reagent (organocuprates)
AGilmanreagentisalithiumandcopper(diorganocopper)reagent
compound,R
2CuLi,whereRisanalkyloraryl.
Lithiumdimethylcopper(CH
3)
2CuLicanbepreparedbyadding
copper(I)iodidetomethyllithiuminether/tetrahydrofuranat−78°C.
The reagent were discovered by Henry Gilman and coworkers in 1952.

3. ..Gilman’s reagent
Thesereagentsareusefulbecause,theyreactwithorganichalidesto
replacethehalidegroupwithanRgroup(theCorey–Housereaction).
Gilman reagents are excellent nucleophiles for SN
2
reactions.
Most metals are less electronegative than carbon. Therefore, in general
a carbon bonded to a metal is nucleophilic and carbanion-like (C
–
).

4. ...Gilman’s reagent
1.1,4-Additiononconjugatedenones:Duetothesoftnessofthenucleophile.

5. ...Gilman’s reagent
Inthefirststep,thenucleophileformsabondwiththebetapositionoftheketone.
TheC-Cπbondbreaks,forminganegativechargeonthealphacarbon.Which
rearranges,togenerateenolateandthenegativechargeisontheoxygen,whichis
considerablymorestable(lessbasic)thanhavinganegativechargeoncarbon.
Addingacidwillprotonatetheenolate(whichisabase,afterall).

6. ...Gilman’s reagent

7. ...Gilman’s reagent
2. Alkyl cross-coupling with Gilman reagents: One of the alkyl group replaces
halide (except F
-
).
The alkyl cross-coupling reaction with Gilman reagents may also be carried
out with aryl, vinyl, allyl, and benzyl halides.

8. ...Gilman’s reagent
3. Addition of Gilman reagents to acid chlorides results in ketones:

9. ...Gilman’s reagent: Applications
4.TheGilmanreagentisamethylatingreagentreactingwithanalkyneina
conjugateaddition,andthenegativechargeistrappedinanucleophilic
acylsubstitutionwiththeestergroupformingacyclicenone.

10. ...Gilman’s reagent: Applications
5.Epoxideringopening:fromlesshinderedside.

11. ...Gilman’s reagent: Summary
1. 1,4 addition on conjugated enones.
2. Alkyl cross-couplings
3. Addition of Gilman reagents to acid chlorides results in ketones.
4. Formation of cyclic enone
5. Epoxide ring opening

12. Questions from NPTEL