Lithio imines

Bromine-lithium exchange applied to the sulfide obtained from the reaction between 2-fluorobenzonitrile and 2-bromothiophenol promotes an intramolecular attack on the nitrile function. Hydrolysis of the resulting tricyclic lithio-imine produces thioxanthone (Scheme 209). Alternatively, the imine can be trapped with electrophiles... 

Treatment of tantalum-alkyne complexes, prepared in situ from TaCls, Zn and RC=CR (R = n-C5Hn), with the lithio-imine Li N=CR Me (R = n-CgHn), followed by aqueous NaOH, gives primary ( )-allylic amines E-RCH=CR-CR Me(NH2). Treatment of these complexes with the terminal alkyne R"C=CH (R" = n-CeHis), followed by aqueous NaOH, yields tetrasubstituted benzene derivatives (99a-d). ... 

Primary amines react with two equivalents of an alkyl-lithium to give lithio-imines, such as (190), which can be quenched to afford ketones or allowed to react with a further equivalent of alkyl-lithium to yield a more highly substituted primary amine (Scheme 113). ... 

The lithio derivative of Ar,Ar-dicthyl-2-toluamide 1 adds to each enantiomerically pure glycer-aldehyde acetonide 4-methoxybenzyl imine [(7 )-2 or (S)-2] to provide only one diastereomer exclusively or (3/ ,TA)-3, respectively]. The moderate yield (50%) is due. in part,... 

It turned out that the requirements of such a chiral d reagent are fulfilled by the l-bromo-l-lithio-l-aUcenes S- and /f-41, which are available from the corresponding enantiomer of lactate . When added to aldehydes or imines, significant diastereose-lectivity will be displayed only by the fi-diastereomer 41. Thus, the selective exchange of the bromine atom in the Z-position of the dibromoaUcene 40, outlined in Scheme 9, is prerequisite to the efficiency of this concept. 

Based on their fluorination protocol, Cahard and co-workers have elaborated a convenient synthesis of a-fluoro-a-phenylglycin derivatives [18]. For example, upon reaction with reagent 24 racemic nitrile 23 was converted into the fluorinated derivative 25 with 94% enantiomeric excess. The corresponding ester derivatives of 23 gave rise to somewhat lower ees. This difference was contributed to the fact that a-lithiated nitriles can be in equilibrium with axial-chiral lithio ketene imines of low racemization barriers thus leading to a potential dynamic kinetic resolution. 

Marcus treatment does not exclude a radical pathway in lithium dialkyl-amide reduction of benzophenone. It does, however, seem to be excluded (Newcomb and Burchill 1984a,b) by observations on the reductions of benzophenone by N-lithio-N-butyl-5-methyl-l-hex-4-enamine in THF containing HMPA. Benzophenone is reduced to diphenylmethanol in good yield, and the amine yields a mixture of the acyclic imines no cyclic amines, expected from radical cyclization of a putative aminyl radical, were detected. An alternative scheme (17) shown for the lithium diethylamide reduction, accounts for rapid formation of diphenylmethoxide, and for formation of benzophenone ketyl under these conditions. Its key features are retention of the fast hydride transfer, presumably via the six-centre cyclic array, for the formation of diphenylmethoxide (Kowaski et al., 1978) and the slow deprotonation of lithium benzhydrolate to a dianion which disproportion-ates rapidly with benzophenone yielding the ketyl. The mechanism demands that rates for ketyl formation are twice that for deprotonation of the lithium diphenylmethoxide, and, within experimental uncertainty, this is the case. 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

MacLean and co-workers (118,119) used the activated imine 136 as a carbon electrophile. Thus, condensation of 136 with the lithio derivative 137 produced the amidine 138 in 83% yield. Alkaline hydrolysis of 138 and subsequent debenzylation with hydrochloric acid afforded ( )-61 in good overall yield. Then, dehydrogenation of ( )-61 with iodine in EtOH, as in the case of (+)-61 (29,30), gave 56 in good yield. 

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