Ethyllithium, alkylation

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. 

Note 1. Butyl- or ethyllithium in diethyl ether, prepared from the alkyl bromide, contains LiBr, which may react with chlorine to form bromine, so that RCeC-Br will also be formed. 

Anionic polymerization of vinyl monomers can be effected with a variety of organometaUic compounds alkyllithium compounds are the most useful class (1,33—35). A variety of simple alkyllithium compounds are available commercially. Most simple alkyllithium compounds are soluble in hydrocarbon solvents such as hexane and cyclohexane and they can be prepared by reaction of the corresponding alkyl chlorides with lithium metal. Methyllithium [917-54-4] and phenyllithium [591-51-5] are available in diethyl ether and cyclohexane—ether solutions, respectively, because they are not soluble in hydrocarbon solvents vinyllithium [917-57-7] and allyllithium [3052-45-7] are also insoluble in hydrocarbon solutions and can only be prepared in ether solutions (38,39). Hydrocarbon-soluble alkyllithium initiators are used directiy to initiate polymerization of styrene and diene monomers quantitatively one unique aspect of hthium-based initiators in hydrocarbon solution is that elastomeric polydienes with high 1,4-microstmcture are obtained (1,24,33—37). Certain alkyllithium compounds can be purified by recrystallization (ethyllithium), sublimation (ethyllithium, /-butyUithium [594-19-4] isopropyllithium [2417-93-8] or distillation (j -butyUithium) (40,41). Unfortunately, / -butyUithium is noncrystaUine and too high boiling to be purified by distiUation (38). Since methyllithium and phenyllithium are crystalline soUds which are insoluble in hydrocarbon solution, they can be precipitated into these solutions and then redissolved in appropriate polar solvents (42,43). OrganometaUic compounds of other alkaU metals are insoluble in hydrocarbon solution and possess negligible vapor pressures as expected for salt-like compounds. 

Substitutcd 2-AIkanones and 4-Substituted 3-Alkanones 6 by Reaction of Methyl- and Ethyllithium, Respectively, with Alkylated A-Acylephedrines General Procedure2 ... 

Organometallics are generally strong nucleophiles and bases. They react with weak acids, e.g. water, alcohol, carboxylic acid and amine, to become protonated and yield hydrocarbons. Thus, small amounts of water or moisture can destroy organometallic compounds. For example, ethylmag-nesium bromide or ethyllithium reacts with water to form ethane. This is a convenient way to reduce an alkyl halide to an alkane via Grignard and organolithium synthesis. 

The properties of lithium metal are well known, but the properties of its alkyls have until recently received much less attention. The lowest member of the series, methyllithium, is a non-volatile microcrystalline powder insoluble in hydrocarbons. Ethyllithium is a colourless crystalline compound melting at 95°. n-Propyl and n-butyllithium are almost colourless fairly viscous non-volatile oils soluble in hydrocarbons and ethers. These properties are to be compared with those of the corresponding sodium alkyls which are all colourless, non-volatile crystalline solids, insoluble in hydrocarbons. The difference in properties is usually attributed to differences in the type of bond between lithium and sodium alkyls, the former being considered covalent and the latter ionic compounds. Thus Coates (17) distinguishes between two types of compounds ... 

In solution lithium alkyls are extensively associated especially in non-polar solvents. Ethyllithium in benzene solution exists largely as a hexamer (9, 43) in the concentration range down to 0.1 molar and there is no evidence for a trend with concentration so presumably the hexamers persist to even lower concentrations. Indeed even in the gas phase at high dilution it exists as hexamer and tetramer in almost equal amounts (3). In a similar way n-butyllithium in benzene or cyclohexane is predominantly hexameric (62, 122). t-Butyl-lithium however is mostly tetrameric in benzene or hexane (115). In ether solution both lithium phenyl and lithium benzyl exist as dimers (122) and it has been suggested that butyllithium behaves similarly in ether (15) although this does not agree with earlier cryoscopic measurements (122). It is however certain that more strongly basic ethers cause extensive breakdown of the structure. 

Thus the isotactic control of polystyrene requires a significantly anionic initiator system such as alfin, alkyl sodium and sodium ketyl catalysts. Ethyllithium is at the border line in ionicity to produce isotactic polystyrene. Only when a somewhat more basic component such as lithium hydroxide is present, can steric control be realized. Even in these cases the amount of steric control is not large. The less anionic... 

Richardson and Sacher (41) showed that the anionic polymerization of butadiene with ethyllithium in THF produces mainly 1.2 structure in the polybutadiene. Roha (2) reviewed the typical anionic polymerization of butadiene to polymers containing 1.2 structure by catalysts such as alkyl sodium and alkyl potassium. Sodium naphthalene with THF produces 88% 1,2 polybutadiene (42). 

There were two reasons why Colonius and I were favored to be the first to hit on this very simple reaction in 1930. First, it was just then that lithium was first used for certain technical applications (e.g., as an alloy component for bearing metals), and therefore became easily accessible at a tolerable price. Second, the experiments described under II above had induced us to study the kinetics of certain lithium alkyl reactions. From these we had found that ethyllithium and alkyl halides, especially chlorides, essentially do not react with each other. Therefore the course of our decisive experiments had been predictable (38). This impetus had been necessary to overcome the prejudice about the Wurtz synthesis originating from the textbooks. 

During my time in Heidelberg, that is, earlier than 1936, we found, in the course of experiments to distill butyllithium under high vacuum, that the lithium alkyl smoothly decomposed into lithium hydride and 1-butene. In carrying out similar experiments with ethyllithium immediately after the war, Gellert and I (41) found firstly that the lower lithium alkyls were distillable under suitable conditions, and secondly that 1-butene was formed from ethylene in contact with ethyllithium. From this observation it was a very short step to discover the stepwise organometallic synthesis (42)... 

In the spectrum of ethyllithium vapor, the major ions observed were Li6R and Li4Rj", and fragments derived from these (30,46,47). One alkyl... 

The alkylation of pyrazine at a nuclear carbon atom has been discussed in detail in Section 1C (612-615, 617, 634). For example, 2-butylpyrazine was prepared from pyrazine and butyllithium in ether at —20 (612), 2-s-butylpyrazine was prepared from pyrazine, ethyl methyl ketone, and alkali or alkaline earth metals in liquid ammonia (614) the effect of temperature on the products, specificity, and yields from the alkylation of pyrazine by ethyllithium (and other alkyllithiums) in ether or hexane solutions between — 25° and 34° has been examined (615). 

Methyl ketones are often directly prepared from carboxylic acids by reaction with methyllithium. Other simple alkyl ketones may also be prepared in the same fashion, making this a method that should be considered whenever these substrates are required. An important demonstration of this protocol was reported by Masamune and coworkers in their synthesis of chiral propionate surrogates (Scheme 13). The ethyl and cyclopropyl ketones are important starting materials for macrolide total synthesis and have been prepared on a large scale. The overall yield for the ethyl ketone is 65% using 3.5 equiv. of ethyllithium without protection of the hydroxy group. 

In a synthetic effort directed toward a segment of erythronolide A, the addition of (2) to aldehyde (22) gave, after treatment with MeMgBr/CuI, an approximately 80 20 mixture of ring-opened products (23) and (24 equation ll). Interestingly, direct alkylation of this aldehyde (as a mixture of double bond isomers) with ethyllithium gave an 18 82 mixture of adducts. The factors responsible for the complementary face selectivity shown by (2) versus ethyllithium are unclear. Comparisons are particularly difficult due to the fact that most organolithium additions to carbonyl compounds are irreversible, kinetically controlled processes, whereas reactions of (2) can be reversible. 

Treatment of cyclopropyl phenyl ketone and cyclopropyl methyl ketone with ethyllithium and phenyllithium, respectively, afforded the corresponding (alkyl)(cyclopropyl)(phenyl)methox-ides which underwent deoxygenation on exposure to lithium in ammonia before hydrolysis to give the corresponding hydrocarbons in excellent yields.For example, formation of 1-phenylethylcyclopropane (1). ... 

The high thermal stability of the metal-carbon bond in the actinide methyl derivatives suggests that a series of alkyl derivatives can be made. This does not prove to be the case. Reaction of C1M[N(SiMe3)2]3/ where M is thorium or uranium, with either ethyllithium or trimethylsilylmethyllithium at room temperature in diethyl ether yields the metallocycle (VI) and ethane or tetramethylsilane. A mechanism for this transformation, which involves a y-proton abstraction, is shown below. 

The addition of metal and metalloid hydrides to carbon-carbon double bonds is not a new reaction, having been observed from time to time with silanes of the type R3SiH under free-radical conditions (4%, 85) and with boron hydrides (68). The versatility of such hydride-olefin interactions, nevertheless, first became evident with the recent researches of Ziegler with lithium and aluminum alkyls (139). The observation that attempted distillation of ethyllithium led to decomposition into lithium hydride, ethylene, and higher olefins prompted the following formulation of the reaction course (see 18) ... 

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