Organolithium imine reaction

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

Preliminary experiments prove that the substitution pattern of the /V-aryl moiety of imine 1 is crucial for the stereoselectivity of this reaction. The 2-substituent on the aryl group is of special importance. Namely, introduction of a methoxy group leads to a considerable decrease of enantioselectivity compared to the corresponding 2-H derivative, probably due to disfavor-able coordination with the organolithium complex. In contrast, alkyl groups show the reverse effect along with increased bulkiness (e.g., Tabic 1, entries l-3a) but 2,6-dimethyl substitution provides lower ee values. Furthermore, the 4-substituent of the TV-aryl moiety is of minor importance for the stereoselectivity of the reaction [the Ar-phcnyl and the /V-(4-methoxyphenyl) derivatives give similar results], whereas a substituent in the 3-position results in lower stereoselectivities (e.g., Et, Cl, OCHj)41. 

An efficient primary amine synthesis via iV-diisobutylaluminium imines has been described. A cyanide R CN (R1 = Bu, CsHn, Ph, 2-furyl or 2-thienyl) is treated with diisobutylaluminium hydride and the product is converted into the amine by reaction with an organomagnesium or organolithium compound R2M (R2 = Bu, t-Bu, allyl or benzyl)... 

The directing effect of the amide group can then be used a second time in the lateral lithiation of 503 to give an organolithium 507 which adds to the imine 508 in a stereoselective manner, probably under thermodynamic control (imine additions of laterally lithiated amides appear to be reversible). Warming the reaction mixture to room temperature leads to a mixture of 509 and some of the (ultimately required) cyclized product... 

SCHEME 18. Enantioselective reaction of organolithiums with imines. 

Hashimoto, Y. Takaoki, K. Sudo, A. Ogasa-wara, T. Saigo, K. Stereoselective addition reaction of organolithium reagents to chiral imines derived from erythro-2-amino-l,2-diphenylethanol. Chem. Lett. 1995, 235-236. 

Some imidoyllithiums 52 derived from triphenylmethyl isocyanide (51) dissociate to produce nitriles, which react with an organolithium reagent to give the corresponding imines and, after their hydrolysis, ketones. The intermediate nitrile can be isolated working at —78°C, whereas for the isolation of imines or ketones, after addition of the organolithium, the reaction was allowed to warm to room temperature (Scheme 14)74. The structure of the imidoyllithium intermediate has been assigned by IR spectroscopy... 

Monoalkylation of primary amines.1 A two-step sequence for this reaction involves conversion of the amine to the N-(cyanomethyl)amine (2) by reaction with chloroaceto-nitrile or with formaldehyde and KCN. Reaction of 2 with an organolithium or a Grignard reagent generates an unstable formaldehyde imine (a) that reacts with a second equivalent of the organometallic reagent to form a secondary amine (3). 

Organolithium species may form coloured and EPR-active intermediates not only with conventional acceptors such as carbonyl or imine compounds [14-16] but also with unsaturated inorganic ions such as ambidentate thiocyanate-SCN the reaction between n-BuLi and NH4SCN in the presence of strongly ion-stabilizing hexamethylphosphoric triamide 0 = P(NMe2)3 (HMPA) eventually produced LiNCS 2 HMPA via some unusually colored intermediates and thiocyanate-based radical species [62]. 

The reaction of cerium reagents with imines and nitriles which possess a-hydrogens has been studied by Wada et al ° Available data indicate that the reagents do not effectively d to these substrates, although the results are better than with alkyllithiums themselves. A modification of the procedure improves the yields of addition products. Thus, addition of the organocerium or organolithium reagent to an... 

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