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

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

2. ...Gilman’sreagent(organocuprates)
 A Gilman reagent is a lithium and copper (diorganocopper) reagent
compound, R2CuLi, where R is an alkyl or aryl.
 Lithium dimethylcopper (CH3)2CuLi can be prepared by adding
copper(I) iodide to methyllithium in ether/tetrahydrofuran at −78 °C.
The reagent were discovered by Henry Gilman and coworkers in 1952.

3. ..Gilman’sreagent
These reagents are useful because, they react with organic halides to
replace the halide group with an R group (the Corey–House reaction).
Gilman reagents are excellent nucleophiles for SN2 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’sreagent
1. 1,4-Addition on conjugated enones: Due to the softness of the nucleophile.

5. ...Gilman’sreagent
 In the first step, the nucleophile forms a bond with the beta position of the ketone.
The C-C π bond breaks, forming a negative charge on the alpha carbon. Which
rearranges, to generate enolate and the negative charge is on the oxygen, which is
considerably more stable (less basic) than having a negative charge on carbon.
 Adding acid will protonate the enolate (which is a base, after all).

6. ...Gilman’sreagent

7. ...Gilman’sreagent
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’sreagent
3. Addition of Gilman reagents to acid chlorides results in ketones:

9. ...Gilman’sreagent:Applications
4. The Gilman reagent is a methylating reagent reacting with an alkyne in a
conjugate addition, and the negative charge is trapped in a nucleophilic
acyl substitution with the ester group forming a cyclic enone.

10. ...Gilman’sreagent:Applications
5. Epoxide ring opening: from less hindered side.

11. ...Gilman’sreagent: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