Amine lithium amide

Amino derivatives are obtained by standard reactions with secondary amines, lithium amides or... 

In each of the following reactions an amine or a lithium amide derivative reacts with an aryl halide Give the structure of the expected product and specify the mechanism by which it is formed... 

Lithium acetyhde also can be prepared directly in hquid ammonia from lithium metal or lithium amide and acetylene (134). In this form, the compound has been used in the preparation of -carotene and vitamin A (135), ethchlorvynol (136), and (7j--3-hexen-l-ol (leaf alcohol) (137). More recent synthetic processes involve preparing the lithium acetyhde in situ. Thus lithium diisopropylamide, prepared from //-butyUithium and the amine in THF at 0°C, is added to an acetylene-saturated solution of a ketosteroid to directly produce an ethynylated steroid (138). 

Aromatic enamines were prepared by dehydroha logenation of /3-bromo-amines with strong base. While trans enamines were thus formed, one obtained mostly cis enamines from rearrangement of the corresponding allylic amines under similar reaction conditions (646). Vicinal endiamines were obtained from S-dichloroamines and lithium amides (647). 

Enantioselective deprotonation of prochiral 4-alkylcyclohexanones using certain lithium amide bases derived from chiral amines such as (1) has been shown (73) to generate chiral lithium enolates, which can be trapped and used further as the corresponding trimethylsilyl enol ethers trapping was achieved using Corey s internal quench described above. 

Diboratacarbazole heterocycles 137 are obtained in 60% isolated yield by heating the phosphine-stabilized 2,2 -diborabiphenyl derivative 138 with primary amines in toluene for 20h (Scheme 55). Further double deprotonation of the heterocycle 137 (Ar = Ph) with a lithium amide leads to the dianionic 9,11-diboratacarbazole derivative 139 (98%, S nB 31.71 ppm). Structures 137 (Ar = Ph) and 139 were characterized by X-ray crystallography <20040M3085>. 

Lithium r-butyl(trialkylsilyl)amides, LiN(SiR,)C(CH,)v The t-butyl(trialkylsilyl)amines are prepared by deprotonation of r-butylamine and reaction with a trialkylsilyl chloride yields are 50-70%. They are converted to the corresponding lithium amides by BuLi in THF. 

Kinetic enolates. Alkyllithium reagents have the advantage over lithium amides for deprotonation of ketones in that the co-product is a neutral alkane rather than an amine. This bulky lithium reagent is useful for selective abstraction of the less-hindered a-proton of ketones with generation of the less-stable enolate, as shown previously for a hindered lithium dialkylamide (LOBA,12,285). Thus reaction of benzyl methyl ketone (2) with 1 and ClSifCH,), at - 50° results mainly in the less-stable enolate (3), even though the benzylic protons are much more acidic than those of the methyl group, the less hindered ones. Mesityllithium shows... 

In a related procedure, tellurium tetrachloride is treated with lithium amides giving tellurium(II) amides via the successive reduction and amination of TeCl4. 

Free acids require still an additional hydride equivalent because their acidic hydrogens combine with one hydride ion of lithium aluminum hydride forming acyloxy trihydroaluminate ion. Complete reduction of free carboxylic acids to alcohols requires 0.75 mol of lithium aluminum hydride. The same amount is needed for reduction of monosubstituted amides to secondary amines. Unsubstituted amides require one full mole of lithium aluminum hydride since one half reacts with two acidic hydrogens while the second half achieves the reduction. 

A regioselective deprotonation with amide base by preferential abstraction of the a-methylene hydrogen syn to the phenylaziridyl moiety in 116 and subsequent decomposition of the resulting monoanion furnishes, with extrusion of styrene and nitrogen, the alkyllithium 118. After abstraction of the amine proton, the c -alkene 117 is formed with regeneration of the lithium amide base for further use in the catalytic cycle. 

Methylbenzoic acid 513 can be laterally lithiated with two equivalents of lithium amide base (LDA" or L1TMP °) or alkyllithium provided the temperature is kept low to avoid addition to the carbonyl group (Scheme 201). It is usually preferable to carry out the lithiation using aUcyllithiums", since with lithium amides the subsequent reaction of 514 with electrophiles is disrupted by the presence of the amine by-product (diisopropylamine, for example) . The dilithio species 514 is stable in THF even at room temperature, and (as with the amide 483) since LDA will also dilithiate 515 stabilization presumably comes principally from conjugation with the carboxylate. 

Formation of the most stable organolithium is much faster when a lithium amide is used as the base, since re-deprotonation of the amine by-product provides a mechanism for anion translocation from one site to another. Several examples were discussed in Sections I, II and IV the lithiations of 642 and of 643 with BuLi and with EDA illustrate the point well (Scheme 249). 

The authors proposed a chelating transition state model to explain these results (Fig. 8.14). The thermodynamically more stable intermediate resulting from initial lithium amide addition should have the amino group on the face opposite to the bulky tert-butyl group. Due to the same steric effect, the HMPA ligand should also occupy a position on the p face. The electrophile approaches the enolate from the ot face and gives the trans product. For bulky amines, either the aza enolate does not form due to severe steric hindrance or the aza enolate is inactive for the same reason. 

This important synthetic problem has been satisfactorily solved with the introduction of lithium dialkylamide bases. Lithium diisopropylamide (LDA, Creger s base ) has already been mentioned for the a-alkylation of acids by means of their dianions1. This method has been further improved through the use of hexamethylphosphoric triamide (HMPA)2 and then extended to the a-alkylation of esters3. Generally, LDA became the most widely used base for the preparation of lactone enolates. In some cases lithium amides of other secondary amines like cyclo-hexylisopropylamine, diethylamine or hexamethyldisilazane have been used. The sodium or potassium salts of the latter have also been used but only as exceptions (vide infra). Other methods for the preparation of y-Iactone enolates. e.g., in a tetrahydrofuran solution of potassium, containing K anions and K+ cations complexed by 18-crown-6, and their alkylation have been successfully demonstrated (yields 80 95 %)4 but they probably cannot compete with the simplicity and proven reliability of the lithium amide method. 

Bei der Umsetzung von Hexafluorbenzol mit ein oder zwei Aquivalenten Lithium-amid in Tetrahydrofuran entsteht Pentafluor-anilin nur in sehr geringer Menge das Hauptpro-dukt ist Bis- pentafluor-phenyl]-amin (67%)7. 

Anstclle der Amine + Katalysator konnen anch die gesondert hergestellten Lithium-amide eingesetzt werden, so z.B. bei der Oberfiihrung von Ethenyl- und Allyl-phosphanen in (2-Amino-alkyl)-phos-phane in siedendem Toluol (maBige bis gute Ausbeuten)7. 

The magnesium amides may be prepared either by reaction of lithium amide and magnesium bromide, by reaction of DIBAL-H with RiMg, or by reaction of the corresponding amine with a Grignard reagent " . ... 

Secondary amines 268 are prepared using TBS-protected lithium amides 269 (Scheme 21), while the preparation of polyfunctional trlarylamines applies lithium amides which are derived from secondary amines. 

Lithium diethylamide has been shown to be an effective initiator for the homopolymerization of dienes and styrene llr2). It is also known that such a polymerization process is markedly affected by the presence of polar compounds, such as ethers and amines (2,3). However, there has been no report of the use of a lithium amide containing a built-in polar modifier as a diene polymerization initiator. This paper describes the preparation and use of such an initiator, lithium morpholinide. A comparison between polymerization with this initiator and lithium diethyl amide, with and without polar modifiers, is included. Furthermore, we have examined the effects of lithium-nitrogen initiators on the copolymerization of butadiene and styrene. 

A. Preparation of Initiators. The lithium amides were prepared by the reaction of n-butyllithium with the corresponding amines in hexane with the amounts shown in Table I. In general, the n-butyllithium in hexane (15%) was added to the amine-hexane solution slowly because a strong exotherm is associated with the reaction. The lithium amides precipitated from the solution in the form of crystalline compounds. The lithium amides were isolated by means of filtration and were then washed four times with a total of two liters of hexane. 

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