Lithium in alkylation

While the initial surface species formed on lithium in alkyl carbonates consist of ROC02Li compounds, these species react with water to form Li,CO, C02, and ROH. This reaction gradually changes the composition of the surface films formed on... 

The lithiation of allene can also be carried out with ethyllithium or butyl-lithium in diethyl ether (prepared from the alkyl bromides), using THF as a cosolvent. The salt suspension which is initially present when the solution of alkyllithium is cooled to -50°C or lower has disappeared almost completely when the reaction between allene and alkyllithium is finished. 

Other large monocarbaboranes include /<7( -6-(NR3)-6-CB2H [f/oj o-l-CB H J [38192-43-7] and closo-C ]H. ][ [39102-46-0]. The closo monocarbaboranes can be functionalized at carbon via lithiation using reagents such as -butyl lithium in a manner similar to the dicarbaboranes. The small monocarbaboranes /oj o-l-CB H [25301-90-0], nido-2-C [12385-35-2], and a variety of their alkylated derivatives are also known (127,128). 

Deghenghi et al studied the reductive alkylation of 16-dehydropregneno-lone acetate in ammonia-tetrahydrofuran using excess lithium and alkyl iodides. Alkylation with methyl iodide followed by reacetylation of the 3-hydroxyl group affords 17a-methylpregnenolone acetate in 20% yield after purification by column chromatography. Ethyl iodide affords the 17a-ethyl analog in 40% yield, but n-propyl iodide affords the 17a-propyl compound in only a 12 % yield. 

The preparation of 17j -hydroxy-4a-methyl-5a-androstan-3-one (3) which cannot be obtained by direct alkylation or via formyl or oxalyl ketones was achieved by Schaub in 40% yield by the Stork " alkylation procedure. As discussed in the introduction this method proceeds by trapping the A -enolate (2), obtained from (1) and lithium in liquid ammonia, with methyl iodide. 

Most of the alkylations were carried out by adding a solution of 3,3-ethylenedioxypregna-5,16-dien-20-one in tetrahydrofuran to a solution of lithium in liquid ammonia to the point of color discharge. Treatment with the alkyl halide then furnishes the corresponding 17a-alkyl derivative (10). After hydrolysis of the 3-ketal group, 17a-methyl-, ethyl-, propyl-, butyl-, hexyl-, octyl-, allyl-, and benzylprogesterones are obtained. 

The mechanism of the asymmetric alkylation of chiral oxazolines is believed to occur through initial metalation of the oxazoline to afford a rapidly interconverting mixture of 12 and 13 with the methoxy group forming a chelate with the lithium cation." Alkylation of the lithiooxazoline occurs on the less hindered face of the oxazoline 13 (opposite the bulky phenyl substituent) to provide 14 the alkylation may proceed via complexation of the halide to the lithium cation. The fact that decreased enantioselectivity is observed with chiral oxazoline derivatives bearing substituents smaller than the phenyl group of 3 is consistent with this hypothesis. Intermediate 13 is believed to react faster than 12 because the approach of the electrophile is impeded by the alkyl group in 12. 

Kinetic stability of lithium and the lithiated carbons results from film formation which yields protective layers on lithium or on the surfaces of carbonaceous materials, able to conduct lithium ions and to prevent the electrolyte from continuously being reduced film formation at the Li/PC interphase by the reductive decomposition of PC or EC/DMC yielding alkyl-carbonates passivates lithium, in contrast to the situation with DEC where lithium is dissolved to form lithium ethylcarbonate [149]. EMC is superior to DMC as a single solvent, due to better surface film properties at the carbon electrode [151]. However, the quality of films can be increased further by using the mixed solvent EMC/EC, in contrast to the recently proposed solvent methyl propyl carbonate (MPC) which may be used as a single sol-... 

The chelated lithium anions 1 and 2, derived from enantiomerically pure tetrahydroisoquino-line-amidines or -oxazolines, exhibit high induced stereoselectivity in alkylation reactions (Section D.l.1.1.1.3.1.). 

Ester enolates which contain the chiral information in the acid moiety have been widely used in alkylations (see Section D.1.1.1,3.) as well as in additions to carbon-nitrogen double bonds (sec Section D.1.4.2.). Below are examples of the reaction of this type of enolate with aldehydes720. The (Z)-enolate generated from benzyl cinnamate (benzyl 3-phenylpropcnoate) and lithium (dimethylphenylsilyl)cuprate affords the /h/-carboxylic acid on addition to acetaldehyde and subsequent hydrogenolysis, The diastereoselectivity is 90 10. 

Ketosilanes react with alkyl lithiums in a diastereoselective manner (7), the preferred diastereoisomer being the one predicted on the basis of Cram s Rule acidic or basic treatment provides a stereoselective route to trisubstituted alkenes. 

Rajanikanth and Ravindranath44 have recently published a deoxygenation reaction for sulphoxides that uses metallic lithium in refluxing dimethoxyethane. Dialkyl and alkyl phenyl sulphoxides were reduced cleanly in yields around 70%, even if sterically hindered, but benzyl sulphoxides gave mixtures of products. For example, benzyl phenyl sulphoxide gave frans-stilbene (33%), benzyl phenyl sulphide (20%) and diphenyl disulphide (47%). These products can be rationalized by reaction pathways such as in equation (17) ... 

For use of other organocopper reagents in converting carboxylic acid chlorides to ketones, see G. H. Posner and C. E. Whitten, Tetrahedron Lett., 1815 (1973) G. H. Posner, C. E. Whitten, and P. E. McFarland, J. Amer. Chem. Soc., 94, 5106 (1972). For a recent report on direct and convenient preparation of lithium phenylthio (alkyl)-cuprate reagents, see G H Posner, D J Brunelle, and L. Sinoway, Synthesis, 662 (1974). 

Dialkyl-[alken-(l)-yl]-borane werden nach Uberfiihrung mit Alkyl-lithium in die Lithium-trialkyl-[alken-(l)-yI]-borate bereits mit 6 n Natronlauge bei 20° hydrolysiert5. 

The alkyl group R of certain carboxylic esters can be reduced to RH by treatment with lithium in ethylamine. The reaction is successful when R is a tertiary or a sterically hindered secondary alkyl group. A free-radical mechanism is likely. Similar reduction, also by a free-radical mechanism, has been reported with sodium in HMPA-r-BuOH. In the latter case, tertiary R groups give high yields of RH, but primary and secondary R are converted to a mixture of RH and ROH. Both of these methods provide an indirect method of accomplishing 10-81 for tertiary R. 

Begin not with the ketone itself, but with an a,P-unsaturated ketone in which the double bond is present on the side where alkylation is desired. Upon treatment with lithium in liquid NH3, such a ketone is reduced to an enolate... 

The 1,5-diene (19) was obtained from the salt (18) by alkylation of the ylide with allyl bromide and reduction of the resulting salt with lithium in ethylamine. 

In a variation of these reactions, Grieco and Masaki used p-toluenesulfonyl groups to direct alkylation reactions in the formation of carbon chains and then cleaved the sulphones with lithium in ethylamine. This type of synthetic construction involving the use of sulphur-containing molecules has become a typical sequence in organic syntheses. In this case, the reactions formed part of successful syntheses of squalene and sesquifenchene and were carried out without any migration or loss of stereochemical integrity of the double bonds. Similar sequences have been reported by Trost (prenylation reactions) and Marshall (synthesis of a cembranoid precursor). 

Alkyl lithium and alkyl Grignard reagents react with aromatic nitro compounds in a similar way to give alkylated products (Eq. 9.23).37... 

The most studied catalyst family of this type are lithium alkyls. With relatively non-bulky substituents, for example nBuLi, the polymerization of MMA is complicated by side reactions.4 0 These may be suppressed if bulkier initiators such as 1,1-diphenylhexyllithium are used,431 especially at low temperature (typically —78 °C), allowing the synthesis of block copolymers.432,433 The addition of bulky lithium alkoxides to alkyllithium initiators also retards the rate of intramolecular cyclization, thus allowing the polymerization temperature to be raised.427 LiCl has been used to similar effect, allowing monodisperse PMMA (Mw/Mn = 1.2) to be prepared at —20 °C.434 Sterically hindered lithium aluminum alkyls have been used at ambient (or higher) temperature to polymerize MMA in a controlled way.435 This process has been termed screened anionic polymerization since the bulky alkyl substituents screen the propagating terminus from side reactions. 

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