Initiators lithium alkyl amide

The unique feature of the alkyllithium compounds that makes them useful as diene initiators is their character as exceedingly powerful bases yet they are soluble in organic solvents and quite thermally stable. Alkyllithium compounds are sufficiently basic to add to hydrocarbon monomers. However, lithium salts of stabilized anions, such as acetylide and fluorenyl anions, are too weakly basic to add to such double bonds. Similarly, alkoxides and mercaptides fail to react with hydrocarbon monomers, but lithium alkyl amides react analogously to alkyllithium compounds. 

Lithium Alkyl Amide as Initiator for Polymerizations of Isoprene and 1,4-Divinylbenzene... 

Lithium dialkylamides eject lithiumalkyl if the latter is sufficiently resonance-stabilized. When A -l-phenyl-A -2,2,2-(triphenylethyl)amine is treated with an alkyl- or aryllithium, the resulting lithium amide undergoes cleavage to triphenylmethyllithium and 7V-methylene-l-phenylethylamine, which immediately combines with the initially used alkyl- or aryllithium. Analogously, cyanide departs as soon as (benzylamino)acetonitrile is A-lithiated and again the organolithium, as far as not yet consumed in amide-generation, adds onto the transient A-methylenebenzylamine. ... 

As continuation and extension of the parallel synthesis and libraries from libraries concept, there is the simultaneous synthesis of various libraries (i.e., a resin-bound library is converted in parallel into several new libraries employing different reagents). Figure 12 illustrates the strategy. The initial step is the preparation of the dipeptide library 45. Introduction of the benzyl group was achieved by selective N-alkylation of N-terminally trityl-protected resin-bound amino acids in the presence of lithium f-butox-ide and benzyl bromide. As expected, the alkylation of the amide nitrogen... 

Selective lithium-bromine exchange in 1-alkyl-5,7-dibromoindoles 149 offers a route to the corresponding indoles 150 or 151 in one pot. The initial, highly selective metalation at C-7 is the key feature of this approach <03TL689>. Moreover, indole-5-carboxylates attached to a resin via an amide linkage, which also acts as a directing group, have been shown to... 

A useful technique to accomplish overall vicinal dialkylation of enones is to trap the enolate initially formed in the conjugate addition with TMS-Cl, and then regenerate the enolate under suitable conditions for its alkylation. Lithium 1-enolates of 3,5-dialkylcyclohexanones generated from the reaction of the corresponding TMS enol ethers with lithium amide in liquid ammonia-THF can be alkylated efficiently in liquid ammonia-THF, even with an unreactive alkylating agent such as n-butyl iodide (Scheme 10). ... 

Patterson and Fried found that the clean lithium enolate (14), generated by conjugate addition of the lithium divinylcuprate (15) to cyclopentenone with subsequent trapping of the initial enolate with TMS-Cl and cleavage of the TMS enol ether with lithium amide in liquid ammonia-THF, could be alkylated in a reasonable yield with the (Z)-allylic iodide (16) to give the 11-deoxyprostaglandin derivative (17 ... 

Alkoxides, Amides, and other Bases. The use of alkoxides as initiators has recently received some attention because of their ease of handling relative to metal alkyls. In principle such species might be expected to be active only with monomers capable of yielding a more stable anion. Potassium methoxide in dimethylsulphoxide/methanol solution will oligomerize 4-vinylpyridine and here initiation seems to proceed via an acid/base equilibrium rather than by addition to the vinyl double bond (Scheme 15). With methyl methacrylate lithium t-butoxide is an initiator although an inefficient one. Furthermore, unused... 

Sterically Hindered Base for Enolate Formation. Like other metal dialkylamide bases, sodium bis(trimethylsilyl)amide is sufficiently basic to deprotonate carbonyl-activated carbon acids and is sterically hindered, allowing good initial kinetic vs. thermodynamic deprotonation ratios. The presence of the sodium counterion also allows for subsequent equilibration to the thermodynamically more stable enolate. More recently, this base has been used in the stereoselective generation of enolates for subsequent alkylation or oxidation in asymmetric syntheses. As shown in eq 1, NaHMDS was used to selectively generate a (Z)-enolate alkylation with lodomethane proceeded with excellent diastereoselectivity. In this case, use of the sodium enolate was preferred as it was more reactive than the corresponding lithium enolate at lower temperatures. 

Initial attempts using vigorous stirring of glycine derivatives and allyl iodide in aqueous lithium hydroxide-TBAB in dichloromethane required one to two days to reach completion and suffered from competitive hydrolysis of the amide bond. Sonication dramatically increased the alkylation rate, and a 79% yield of piirified product was obtained after only 5 min sonication at -10°C. The a-alkylated amino acid is liberated by a classical treatment by aqueous hydrogen chloride. 

Alternatively, when the counterion of the initial adduct 18 is exchanged with tetramethyl anunonium, the mixed anhydride can be prepared by reaction with pivaloyl chloride. Further reaction with alcohols or amines then yields chromate esters and amides, respectively. Functional groups can be introduced into the heteroatom-linked chains that are not compatible with alkyl and aryl lithium species. The pimary alkyl iodide 19 was prepared by this method. ... 

Proton removal adjacent to a heteroatom is further facilitated if the lithium can be internally coordinated to proximate electron donors, such as the carbonyl oxygen, permitting the formation of dipole-stabilized carbanions. Thus lithiations of various amides, thioamides, imides, esters, Boc derivatives of cyclic amines (pyrrolidines, piperidines, and hexahydroaze-pines), thioesters, )V,iV-dialkylthiocarbamates, and various formamidine derivatives are achieved conveniently using s-BuLi (eqs i3 i7) 32,43b.44.47a,48a Subsequent addition of electrophiles followed by hydrolytic removal of the activating carbonyl, carbamoyl, or formamidine moiety provides a valuable synthetic route to a variety of a-substituted amines, alcohols, and thiols. Successful alkylation of the dipole-stabilized car-banions may require the conversion of the initial lithio carban-ions into their organocuprate derivatives, e.g. by the addition of n-PrC=CCu. ... 

Alkah metal derivatives, including hydrides, alkyls and aryls, hydroxides, alkoxides, and amides, have been used as initiators for the anionic polymerization of epoxides. Sodium, potas-sirrm, and to a lesser extent cesium are the most often used alkali metals. Lithium derivatives are generally avoided since after the insertion of the first epoxide unit, they yield alkoxide species that are unable to properly propagate the polymerization, due to sUong association. Anionic polymerization of... 

Usually, carbanions with good leaving groups in the beta position do not couple efficiently, but just eliminate. Scott D. Rychnovsky of the University of California, Irvine has found Organic Lett. 2007, 9, 4757) that initial protection of 6 as the alkoxide allowed smooth reduction of the sulfide and addition of the derived alkyl lithium to the amide 7 to give 8. Doubly-activated Michael acceptors such as 11 are often too unstable to isolate. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has shown Tetrahedron Lett. 2007, 48, 7546) that Baylis-Hillman adducts such as 9 can be oxidized in situ, with concomitant Sakurai addition to give 12. Rather than use the usual Li or Na or... 

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