[81380-82-7]  · C11H14LiNO  · 2-Lithio-N,N-diethylbenzamide  · (MW 183.179)

(reagent used for production of highly substituted benzene derivatives)

Preparative Method: solutions of the title compound can be obtained by deprotonation of N,N-diethylbenzamide using s-Butyllithium in THF/TMEDA at -78 °C.

General Considerations.

A variety of benzamides have been deprotonated at the ortho position to give the corresponding lithiated species which then undergo reaction with electrophiles (eq 1).

A large amount of data in this area has been compiled by Snieckus1 and represents the state of the art in the use of (2) and related reagents. Two derivatives of (1) which undergo clean deprotonation and reaction with electrophiles are the N,N-diethyl and N,N-diisopropyl amides. Both can be converted near quantitatively to the corresponding o-lithio reagents with s-BuLi in THF/TMEDA at -78 °C. Both react with a variety of electrophiles in high yield.

Manipulation of Alkylated Products.

Although N,N-dialkylbenzamides are quite stable to acidic or basic hydrolysis, some adducts undergo replacement of the N,N-dialkyl group quite easily as a consequence of proximal functionality. Thus, adducts of the o-lithio species with aldehydes and ketones can be cyclized to phthalides (6) with acid (eq 2).2 The phthalides in turn have been converted to anthraquinones (7 -> 8) (eq 3).3 Anthraquinones may also be prepared without going through phthalide intermediates. After addition of the aryllithium to a benzaldehyde (9), the alkoxide (10) can be further metalated to (11), which closes to (12). Oxidation gives the anthraquinone (eq 4).4

Cross Coupling via Boronic Acids.

Ortho-lithiated benzamides can be converted to o-substituted boronic acids (14). These can be coupled with aryl halides in a palladium-catalyzed process leading to a general synthesis of biaryls.5 This is only the beginning of a versatile synthetic method. The presence of the amide in (15) enables further metalation and elaboration to a diverse array of aromatic compounds.

Related Reagents.

o-Lithioanisole; 3-Lithiofuran; 2-Lithiopyridine; Phenyllithium.

1. Snieckus, V. CR 1990, 90, 879.
2. (a) Beak, P.; Brown, R. A. JOC 1982, 47, 34. (b) de Silva, S. O.; Watanabe, M.; Snieckus, V. JOC 1979, 44, 4802.
3. Mills, R. J.; Snieckus, V. JOC 1989, 54, 4386.
4. Watanabe, M.; Snieckus, V. JACS 1980, 102, 1457.
5. (a) Sharp, M. J.; Snieckus, V. TL 1985, 26, 5997. (b) Sharp, M. J.; Cheng, W.; Snieckus, V. TL 1987, 28, 5093.

Kim F. Albizati

University of California, San Diego, CA, USA

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