Carboxamides 3-lithiated

Lithiation by transmetallation of the diastereoisomeric organotin compounds according to equation 70 takes place with retention of configuration. Free rotation of the carboxamide... 

The reaction shown in Scheme 25 has been successfully used to deprotect Al-benzylic carboxamides using water as the quenching reagent, after the naphthalene-catalyzed lithiation . 

Lithiated alkyl carbamates [e.g. 44 from 32a (Cb for Cby)] decompose above —40°C with migration of the carbamoyl group to produce a-hydroxy carboxamides 45 (equation 8) . ... 

Regioselactive g-metallation of ir-excessive five ring heterocycles is not a novel reaction. Oxazoline and pyridine as well as carboxylate- and carboxamide -substituted heterocycles have been lithiated. From the point of synthetic utility thiophenes have been shown to be useful substrates after careful optimization of reaction conditions furans have been of less utility. 

Amination of a-Uthiated derivatives of f-butyl acetate and a-phenylacetamide with la were reported to be unsuccessful. However, a-amino derivatives of Af-mono- and Af,Af-disubstimted carboxamides could be prepared by reaction of their a-lithiated derivatives with la (Scheme 12) . ... 

In addition to the parent heterocycle, both AT,N-diethyl-l-methylpyr-role-3-carboxamide and l-methylpyrrole-3-carboxaldehyde have been selectively a-lithiated in the 2-position (85TL6213 87JOC104), the latter compound via the intermediacy of an a-(Af-methylpiperazino) alkoxide (Scheme 6). The a-amino alkoxide is formed in situ, via the addition of... 

Directed -lithiation of N-substituted indoles at the 3-position has been achieved with some 2-substituted indoles. Thus for example, N-t-Bu-1-methylindole-2-carboxamide can be lithiated at C-3 with 5-BuLi and TMEDA, but when a similar reaction was attempted with the 1-ben-zenesulfonyl analog, cleavage to an acetylene occurred readily, even at -78°C (Scheme 20)(86H2127). 

Scheme 41 Synthesis of spiro-P-lactams via cyclization of lithiated pyridine and quinoline carboxamides...

Clay den et al. [115] have reported the synthesis of spirocyclic p-lactams 176 (Scheme 41) by exo-cyclization of lithiated pyridine and quinoline carboxamides. The reaction of isonicotinamide or chlorinated isonicotinamide 175 with LDA at -40°C with addition of methyl chloroformate led to the formation of spirocyclic p-lactams 176 in good yields. Benzyl chloroformate, benzoyl chloride, methyl triflate can also be used as the effective acylating agents. In these type of reactions, lithiation of /V-benzyl pyridine and quinoline carboxamides to nitrogen provided... 

Hay, D. R. Song, Z. Smith, S. G. Beak, P. Complex-induced proximity effects and dipole-stabilized carbanions kinetic evidence for the role of complexes in the a -lithiations of carboxamides./. Am. Chem. Soc. 1988, 110, 8145-8153. 

The usually very powerfully orthodirecting groups such as secondary carboxamide surprisingly do not always lead to ortholithiation on pyrazine and pyridazine rings lithiation of 386 and 387, for example, takes place principally (at least kinetically) at the meta and para positions.339 340... 

Phthalic anhydrides can be prepared from 1-hydroxyphthalans by oxidation. The direct synthesis of phthalic anhydride can be achieved by lithiation of a carboxamide and introducing a carboxyl group at ortho position using carbon dioxide... 

The methyl ether of the aglycone of ( )-dihydrohomalicine 43, has also been synthesised by lithiation at an aromatic methyl group, which is ortho to the lithiation-directing N-methyl carboxamide function. The synthesis is shown below... 

Lithiation of diazines with directing groups (methoxy, methylthio, chloro, fluoro, even iodo, and various carboxamides) is straightforward and such derivatives are used widely. In contrast to the useful... 

Dianions (6) and (7) illustrate the concept of in situ protection of the carbonyl group, representing another class of synthetic protocol. 3-Lithiated -ketophosphonates, carboxamides and carboxylic acids have been generated and allowed to react with some electrophiles. 

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