C(2) Enolate: Enolate or Enamine?

Pyrrolidin-3-ones enolise away from the ring nitrogen.1 Attempts to improve the C(2):C(4) enolate ratio only managed to equal the product ratios obtained previously.1

            
 Experimental Conditions		C(2)            	:     C(4)
           
				enolate(2)		enolate(3)     

LDA, TESCl, THF, -78 °C			1               :     1.3
            
LDA, TESCl, THF, -78 °C in situ		1               :     >8             
electrophile                                                                                
LDA, TESCl, THF, -78 °C reverse		1               :     >7             
addition                                                                                    
nBuLi, HN(C6H10)2, -78 °C		1               :     1.7
            
LTMP, TESCl, THF, -78 °C		1               :     3.5
            
Garst et al(ref1): LDA, TESCl
THF, -78 °C				1               :     1
Regioisomeric composition calculated from the 1H NMR of the silyl enol ethers.

LTMP=lithium tetramethyl-piperidide,

Preference for the C(4) enolate in the pyrrolidin-3-one can be attributed to steric interaction between hydrogens in the C(2) enolate conformation.

To study the C(2) enolate and its reactions in greater detail the 4,4'- dimethyl-pyrrolidinone(9) has been synthesised.

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Summary