Lithiated amines, with

The reaction of the lithiated amine with an electrophile (disulfides to obtain sulfides26 21, chlorodiphenylphosphine for phosphines25,28 29) produces the chiral ligands 10 and 11 used in transition metal catalysis. 

These phosphinous amide anions are presumably responsible for the formation of the by-products AT-phosphino phosphinous amides 11 and mono-phosphazenes derived from diphosphanes 12 in the sequential treatment of primary amines with n-BuLi and chlorophosphanes for preparing NH phosphinous amides [75,88] (Scheme 14). Compounds 11 and 12 are presumably derived from anions 9 and 10, respectively, generated by deprotonation of the newly formed phosphinous amide with the lithiated amine R NHLi. In solution, 9 can establish a metallotropic equilibrium with 10. 

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (—78 °C). N,N-Dimethyl, diethyl (495) and diisopropyl amides have all been laterally lithiated with aUcyllithiums or LDA, but, as discussed in Section I.B.l.a, these functional groups are resistant to manipulation other than by intramolecular attack" . Clark has used the addition of a laterally lithiated tertiary amide 496 to an imine to generate an amino-amide 497 product whose cyclization to lactams such as 498 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures (Scheme 194) ". The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures. ... 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

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) . ... 

For conversion of functionalized diorganozincs into tertiary amines, aromatic compounds which contain a directed metallation group, such as Af,Af-dialkylbenzamides, methoxymethyl phenyl ether, phenyl oxazolines and phenyl Af,Af-dialkylcarbamates, were ortho-lithiated, transmetallated and then aminated with 2a in good yields, but with a slower reaction rate (Scheme 19). 

Beak and coworkers offered an SAr2-type mechanism for the amination of a-lithiated nitriles with A, A -disubstituted 0-phosphinylhydroxylamines". ... 

A lithiated chiral ferrocene was also converted to the bis(ferrocenyl)cyano cuprate and aminated with 5h to yield an aminoferrocene (Scheme 50) °. 

Aminofluorosilanes 679 are formed in the reaction of difluorosilanes with lithiated amines. 679 can then be metalated by RLi (R = Me, Bu) to give the corresponding lithium salts (e.g. 680a). The structure of salts 680 depends on the basicity of the nitrogen atom and on the solvent. Representative structure types (680a-c) will be discussed in the subsection dedicated to structural features. The thermal elimination of LiF leads to silanimine dimers (e.g. 682 from 680c), if sterically possible (equation 223), or to rearrangements. 

Fraser, R. R. Mansour, T. S. Aridity measurements with lithiated amines steric reduction and electronic enhancement of acidity. /. Org. Chem. 1984, 49, 3442-3443. 

In some cases the Hoffmann test fails to be useful. For example, the lithiated amine 9 gives a 50 50 mixture of diastereoisomers 10 and 11 on reaction with ( )-6. No useful information can be drawn in such an instance.6... 

Cyclic five-membered silylhydrazine systems are obtained via different methods of preparation. One possibility is the reaction of bis(fluorosilyl)-hydrazines with lithiated amines as shown in Eq. (31)38 ... 

Similarly, (S)-fi-tyrosine hydrochloride is prepared by addition of the lithium amide of N-[(R)-l-phenylethyl]benzylamine to methyl ( )-3-[(4-benzyloxy)phenyl]-2-propenoate and subsequent hydrogenolysis and saponification24. Recently, a number of publications concerning related work has appeared139-146. The reaction of lithiated, mono-silylated 1-phenylethyl-amines with a-enones has also been studied130131. 

The rapid development of chiral phosphine derivatives of ferrocene was undoubtedly due to their application in catalysis. In contrast, chiral sulfur compounds from lithiated iV,iV-dimethyl-l-ferrocenylethylamine were only prepared about 15 years later [140], For the synthesis of such derivatives, the lithiated amine is treated with disulfides as shown in Fig. 4-24, top (and analogously, diselenides [141]). The sulfides obtained are easily oxidized by peracids or NaI04 to the corresponding sulfoxides. As sulfur becomes a new center of chirality by the oxidation, diastereoisomeric sulfoxides are formed in ratios depending on the oxidant [140]. If chiral oxaziridines [106, 142] are used as oxidizing agents, the diastereoisomeric ratio is appreciably... 

Among the carbon electrophiles, carbonyl compounds [113,114] were first applied in the reaction with lithiated ferrocenylalkyl amines (Sect. 4.S.3.3 and Fig. 4-18). Analogously, carboxylic acids are obtained from CO2 [153]. The reactivity pattern of palladated ferrocenylalkyl amines with carbon electrophiles is somewhat different. Carbon monoxide in alcohols leads to the formation of esters of substituted ferrocenecarboxylic acids [124]. With prochiral alcohols, a moderate asymmetric induction is observed [154]. a, -Unsaturated ketones react with palladated ferrocenylalkyl amines not with addition to the carbonyl group, but with substitution of a hydrogen at the carbon—carbon double bond, allowing the introduction of longer side chains at the ferrocene ring (Fig. 4-27c) [124, 152]. 

An interesting method for die synthesis of amines and the homologation of carbonyl compounds has been reported that utilizes the condensation of a lithiated formamidine with a carbonyl compound. 41 Typical examples are shown in Scheme 39. 

With the nitrogen already at the oxidation level of amine, but carrying a t-butoxycarbonyl group to assist the ortho-methy (alkyl) lithiation, reaction with oxalate as in the classical sequence and final removal of the A-substituent with acid, again leads to an indole-2-ester. The synthesis of 2-unsubstituted indoles is achieved by reaction of the A,C-dilithiated species with dimethylformamide. °... 

C-Lithiations can be easily effected on A -1-protected 1,2,4-triazoles, the resulting 5-lithio derivatives being much more stable than C-hthiated 1,2,3-triazoles 5-Silylation can even be achieved using triethyl-amine with trimethylsilyl bromide - deprotonation of an iV -trimethylsilyl triazolium cation is presumably involved Exactly comparable silylations can be achieved with 2-aryl-l,3,4-oxa- and -thia-diazoles application of this regime to 1-phenyltetrazole produced phenyl trimethylsilyl carbodiimide in 90% yield ... 

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