Benzamides lithiation

By carrying out a subsequent ortholithiation at low temperature, it was possible to show that tertiary benzamides also react atroposelectively in laterally lithiation-electrophilic quench sequences . Either atropisomer 575 or 578 could be made starting from 573 or 576 (Scheme 231). 

Another preparative route for synthesis of benzisoselenazol-3(27/)-ones is based on the lithiation of the benzamides, followed by the conversion of dilithium derivatives by direct treatment with selenium, or via 2-[(carbamoyl)phenyl]methyl selenides or 2,2 -bis[(carbamoyl)phenyl] diselenides [167-172], These diselenides are oxidatively cyclized and, depending on the oxidant used, benzisoselenazol-3 (2H)-ones or their 1-oxides are produced in high yields [92, 173],... 

Non-enolizable amides, for example N,N-dialkyl pivalamides [212], benzamides, thiobenzamides [213], or phosphinamides (Ph2P(0)NR2[214]), can be lithiated a to the amino group by treatment with sBuLi[54, 213, 215] or tBuLi[216], without further additives, in THF at -78 °C. N,N-Dimethylbenzamides can be attacked at the carbonyl group by these organolithium reagents to yield ketones [217] or alcohols, but with sterically more demanding amides metalation is usually faster than addition. 

Derdau, V. Snieckus, V. Condensation of laterally lithiated o-methyl and o-ethyl benzamides with imines mediated by (-)-sparteine. Enantioselective synthesis of tetrahydroisoquinolin- 236 1-ones./. Org. Chem. 2001, 66, 1992-1998. 

Reed, J. N. Snieckus, V. ortho-Amination of lithiated tertiary benzamides. Short route to polysubstituted anthranilamides. Tetrahedron Lett. 1983, 24, 3795-3798. 

Anthraquinone synthesis.1 The original anthraquinone synthesis (10, 75) from benzamides and benzaldehydes involving a tandem orf/io-lithiation can be improved by use of an ort/to-bromobenzaldehyde as the second component. In this version, the second lithiation involves halogen-metal exchange, which results in higher yields. In the example cited here, the yield was only 15% in the absence of the bromine substituent on the aldehyde. 

For the synthesis of 1,4-naphthoquinones from benzamides, a tandem lithiation has been performed using intermediates 678 and 679982. Intermediates 679 reacted with... 

Secondary amides may direct ortho lithiation, but they must first be deprotonated. This makes them somewhat weaker ortho directors than tertiary amides, but they may still serve the purpose quite well. For example, the lithiation and addition of benzamide (12) to aldehyde (13) was us in a synthesis of 11-deoxycaiminomycinone (Scheme 8). More recently, it has been shown that the amide monoanion may be obtained by addition of a phenylsodium to an isocyanate. ... 

Two groups report the addition of metalated benzamides to aldehyde carbonyls. The methods differ in the metal. Lithiated diethylamides must be transmetalated with MgBr2 before addition to the aldehyde, but p-aminoamides react similarly as the lithium derivative. Following addition, the hydroxyamide is hydrolyzed to afford phthalides in moderate overall yield (Scheme 11). 

A one-pot procedure for the activation and metalation of tetrahydroisoquinoline involves the carbona-tion of tie li ium amide anion and then further metalation. As is illustrated in Scheme 45, the dipole-stabilized anion species may be added to carbonyl compounds in good yield.For the activation of tetrahydroisoquinoline Grignards, Seebach examined benzamides, pivalamides and phosphoramides, and found that the benzamides would not metalate, and that although the phosphoramides were most easily removed, the pivalamides were the most nucleoj ilic species. As is shown in Scheme 46, the lithiated pi-valoylisoquinoline adds to cyclohexanone in good yield. 

Snieckus, V. Heterocycles via ortho-lithiated benzamides. Heterocycles 980, 14,1649-1676. 

A simple synthesis of 4-methoxy phthalide is only via an organolithium intermediate derived by the lithiation of mefa-methoxy N-methyl benzamide. This is because the... 

Another synthesis of isoochracinic acid (27), utilises an interesting application of Wittig reaction. 3-Methoxyphthalic anhydride on reaction with carbobenzyl-oxymethylenetriphenyl phosphorane, followed by hydrogenation and demethylation furnishes 21. It may be noted that 3-methoxyphthallc anhydride can be readily obtained by aromatic lithiation of N,N-diethyl w-methoxy benzamide followed by treatment with COj (vide supra). 

Directed lithiation. 2-Arenesulfonyl benzamides are deprotonated in a re-gioselective fashion, furnishing thioxanthen-9-one 10,10-dioxides in good yields (57-96%). 3-Halopyridines, including the iodo compounds, manifest directed o-lithiation and regioselective reaction (at C-4) with electrophiles. It should be noted that 3-chloro-4-iodopyridine generates 3,4-pyridyne on treatment with either BuLi or f-BuLi. Halogen dance is also observed. ... 

Electrophilic quench of aryllithium species with carbonyl electrophiles is particularly efficient. However, alkyl halides (other than iodomethane) are poor electrophiles, probably owing to competing elimination reactions (see Section 2.1). The formation of alkyl-substituted aromatic compounds can be achieved, however, by using epoxide electrophiles or by lithiation and reaction of 2-methylbenzamides, themselves generated by orr/ o-lithiation. For example, the benzamide 128 can be deprotonated at the benzylic position and treated with a variety of electrophiles. Addition of aromatic aldehydes gives, after lactonization, 3-aryl-3,4-dihydroisocoumarins (1.119). 

Principal among these are amides either benzamides, exemplified by 197, or anilides, exemplified by 200 (Scheme 50). Given the known lithiation directing ability of amide groups [ 1,114], these compounds are clearly prime candidates for asymmetric synthesis using enantioselective lithiation. 

Aryl-lithiums. Details of the ort/io-lithiation of tertiary benzamides have appeared.In a popular year for syntheses of rosefuran, one such synthesis has involved the sequence shown in Scheme 5, and proceeds in 71% overall yield." ... 

---