2-Quinolone, 3-lithiation

On deprotonation, pyridones and quinolones carry an oxyanion substituent which turns out to be a good director of lithiation. Two equivalents of LDA lead to the compounds... 

Quinolones behave similarly, and unlike quinolines are not attacked by BuLi at the ring. A-Substituted pyridones and quinolones are lithiated, sometimes on the N-substituent, sometimes ortho to N and sometimes ortho to O . By way of example, the 4-pyridone 226 lithiates a to N in the ring, while in the 2-pyridone 227 the combined lateral directing effect of the O and the a-directing effect of N lead to lithiation on the side chain (Scheme 110). ... 

Attempted lithiation of (V-methyl-4-quinolone with alkyllithiums was unsuccessful, due to nucleophilic addition at the 2-position, but efficient... 

Lithiation of 1-substituted 4-quinolones and 3-lithiation of 2-quinolone provides derivatives with the usual nucleophilic propensity, as illustrated below. 

Another high-yield synthesis of furoquinoline alkaloids, devised by Narasimhan and Mali (197), also involves the preparation of aldehydes 247 and their cyclization with polyphosphoric acid, and is illustrated in Scheme 21 for dictamnine. In this route, treatment of lithiated 2,4-dimethoxyquinolines with W-methylformanilide gave 3-formylquinolines 260. Wittig reactions with methoxymethylene triphenylphosphonium chloride and /ert-butoxide led to a mixture of cis- and frans-enol ethers, which were hydrolyzed to the 2-quinolone aldehydes. Dictamnine, evoli-trine, pteleine, and y-fagarine were synthesized by this method. 

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