Ortfto lithiation

Lithium antiidocyanocuprates, LiCu(CN)N-C6H4R2 (1). ortfto-Lithiated benza-... 

One last word of warning with regard to a-lithiations. The benzofuran 158 has a methoxy group on the benzene ring and we might expect this to direct an ortfto-lithiation. It would be easy to overlook the a-lithiation of the furan ring this, in fact, happens instead. 

Direct lithiation, i.e. C-deprotonation of quinolines requires an adjacent substituent, such as chlorine, fluorine or alkoxy. Historically, what is probably the first ever strong base C-lithiation of a six-membered heterocycle was the 3-lithiation of 2-ethoxyquinoline. Both 4- and 2-dimethylaminocarbonyloxyquinolines lithiate at C-3 4-pivaloylaminoquinoline lithiates at the peri position, C-5. Quinolines with an ortfto-directing... 

Direct 3-lithiation can be accomplished with ortfto-assistance from a 2-(2-pyridyl)- or a 2-carboxyl group. Direct 3-lithiation even without a snbstitnent at C-2 can be achieved with an iV-di(f-butyl) flnorosilyl-, iV-tri-i-propylsilyl- or iV-(2,2-diethylbntanoyl)-snbstitnent in place, the latter nsing sec-bntyllithium in the presence of iV,iV,iV, iV iV -pentamethyldiethylenetriamine. Other directed metallation processes in the hetero-ring include 2-lithiation of 1-substituted indole-3-carboxylic acids and amides, and of 3-hydroxymethyl-l-phenylsulfonylindole. ... 

Lithiation of benzoxazole leads to a mixture of the 2-lithiated species and a ring-opened ortfto-isocyano-phenolate. This difficulty can be avoided by magnesation and good yields of 2-substituted products obtained thereby. ... 

Larger alkyl substituents on the nitrogen favor meta lithiation [55]. The extreme case of a t-BuMe2Si or TIPS group further disfavor ortfto-metallation, and the process becomes very selective for meta [55,117]. 

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