Lithium alkyl derivatives

Essentially covalent compounds such as the lithium alkyls. Derivatives of any alkali metal where charge delocalization can occur over several carbon atoms (e. g. triphenylmethyl-sodium, lithium-benzyl) were also considered to be largely ionic in constitution. 

The same complex will induce anionic growth of ethene, and while one research school proposes that the propagating species is a lithium alkyl derivative intimately involving TMEDA, another suggests the action of the base is purely to release monomer Bu"Li from its hexameric form in hexane solution, and that this then acts as the initiator. More recent work has established that a Bu"Li/TMEDA complex in a 1 1 stoicheiometry is the active species, and that N,A, NW -tetraethylethylenediamine and pentamethyldi-ethylenetriamine are more effective than TMEDA. Furthermore the living polymer obtained has been terminally functionalized by reaction with CO2. 

Al—Ti Catalyst for cis-l,4-PoIyisoprene. Of the many catalysts that polymerize isoprene, four have attained commercial importance. One is a coordination catalyst based on an aluminum alkyl and a vanadium salt which produces /n j -l,4-polyisoprene. A second is a lithium alkyl which produces 90% i7j -l,4-polyisoprene. Very high (99%) i7j -l,4-polyisoprene is produced with coordination catalysts consisting of a combination of titanium tetrachloride, TiCl, plus a trialkyl aluminum, R Al, or a combination of TiCl with an alane (aluminum hydride derivative) (86—88). 

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). 

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. 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

The mechanism of anionic polymerization of styrene and its derivatives is well known and documented, and does not require reviewing. Polymerization initiated in hydrocarbon solvents by lithium alkyls yields dimeric dormant polymers, (P, Li)2, in equilibrium with the active monomeric chains, P, Li, i.e. 

Sn2 and SN2 Reactions with Halides and Sulfonates. Corey and Posner discovered that lithium dimethylcuprate can replace iodine or bromine by methyl in a wide variety of compounds, including aryl, alkenyl, and alkyl derivatives. This halogen displacement reaction is more general and gives higher yields than displacements with... 

The alkylation of 15 (path b, Scheme 15)40 has been performed according to conventional procedures using lithium or Grignard reagents. The preliminary isolation of 15 is not essential thus, the synthesis of the zirconium alkyl or aryl derivatives can be carried out in situ directly from 3 (path a, Scheme 15). The h NMR spectra of 71-74 all imply C2V symmetry, as revealed by the CH2 (one pair of doublets), Bu (two singlets), and MeO (one singlet) patterns. All the alkyl derivatives 71-73 are thermally stable up to 80°C in CgDg. The aryl derivative... 

Dialkylamino derivatives of elements located in the periodic table to the left or below those listed above cannot be prepared by the above method due to either the ionic character of some of the inorganic halides or the formation of stable metal halide-amine addition products. Therefore, other methods must be applied. Dialkylamino derivatives of tin7 and antimony8 are conveniently obtained by reaction of the corresponding halides with lithium dialkylamides. Others, such as the dialkylamino derivatives of aluminum,9 are made by the interaction of the hydride with dialkylamines. Dialkylamino derivatives of beryllium10 or lithium11 result from the reaction of the respective alkyl derivative with a dialkylamine. 

Similarly to the alkyl derivatives, the most common route for arylcopper compounds is the reaction of a copper halide and aryllithium compounds (Equation (4)). Organocuprates with aryl groups are obtained by using an appropriate excess of the lithium reagent. Magnesium aryls have also been employed in transmetallation reactions with Cu(l) salts to yield both arylcopper compounds and arylcuprates (Equations (5) and (6)). 

These compounds are thermally stable, but sensitive to oxidation. The boron atom is not very reactive, due to conjugation of its vacant orbital with the nitrogen lone electron pair, resulting in the absence of intermolec-ular coordination. However, these compounds undergo reactions with methanol, giving methoxy derivatives (172). The latter interact with lithium alkylides, and form, depending on their nature, borates (173) or 13-alkyl derivatives (174) [Eq. (131)]. 

These reactive compounds are useful for preparing numerous other derivatives of ferrocene. As would be expected, lithium alkyls react with any trace of moisture. 

Naphtho[l,8-de][l,2,3]triazine 114 can be alkylated with a variety of alkyl halides and lithium diisopropylamide (LDA) to give alkylated derivatives 115. Reduction of 115 with aluminium amalgam cleaves the naphthotriazine moiety to afford substituted a-aminoacids 116 in good overall yields <00TL6665>. 

Evans and Takacs23 demonstrated a diastereoselective alkylation based on metal ion chelation of a lithium enolate derived from a prolinol-type chiral auxiliary. This method can provide effective syntheses of a-substituted carbox-... 

TABLE 2-5. Diastereoselective Alkylation Reaction of the Lithium Enolates Derived from Imides 22 and 23... 

Table 2-5 summarizes the results of the asymmetric alkylation (Scheme 2-17) of the lithium enolates derived from 22 or 23.28 When chiral auxiliary 22 or 23 is involved in the alkylation reactions, the substituent at C-4 of the oxazolidine ring determines the stereoselectivity and therefore controls the stereogenic outcome of the alkylation reaction. 

As with the above pyrrolidine, proline-type chiral auxiliaries also show different behaviors toward zirconium or lithium enolate mediated aldol reactions. Evans found that lithium enolates derived from prolinol amides exhibit excellent diastereofacial selectivities in alkylation reactions (see Section 2.2.32), while the lithium enolates of proline amides are unsuccessful in aldol condensations. Effective chiral reagents were zirconium enolates, which can be obtained from the corresponding lithium enolates via metal exchange with Cp2ZrCl2. For example, excellent levels of asymmetric induction in the aldol process with synj anti selectivity of 96-98% and diastereofacial selectivity of 50-200 116a can be achieved in the Zr-enolate-mediated aldol reaction (see Scheme 3-10). 

Tetraalkyl- or tetrasilyltetragallium(I) compounds were also obtained by the reactions of the dioxane adducts of Ga2X4 (X = Cl, Br) with bulky alkyl- or silyllithium compounds [Eq. (5)], which were accompanied by disproportionation of Ga(+2) to Ga(+1) and Ga(+3) [44, 45], In particular the yield of the alkyl derivative 21 was very poor and several unknown byproducts were detected by NMR spectroscopy. Furthermore, the reaction requires the employment of a solvent-free lithium compound, which is not readily available. The reaction of tris(trimethylsilyl)silyl lithium yielded the expected product of the disproportionation [(Me3Si)3Si]2GaCl2Li-(THF)2 besides compound 11. 

In spite of the general ambiphilicity of phosphonio-substituted phosphoHde derivatives, the aromaticity of the phosphoHde ring [10, 11] tends to reduce their electrophilicity while the intramolecular compensation of the negative charge by the phosphonio-substituents lowers at the same time their nucle-ophilicity [15, 16]. Bis-phosphonio-benzophospholides and -1,2,4-diaza-phospholides are therefore less reactive towards electrophiles and nucleophiles than other types of phosphorus containing multiple-bond systems and lack the notorious hydrolytic instabihty of many of these species [15, 16, 24]. Reactions are observed, however, with sufficiently strong electrophiles such as triflic acid or methyl triflate, or nucleophiles such as OH" or lithium alkyls, respectively. 

As further proof of the course of the reaction between 85 and lithium alkyls, the primary product 86, resulting from the opening of the ring in compound 85 according to Eq. (13), was reacted anew with MeCl (44). At —40°C, formation of the symmetrical n-tetraphosphane 92 takes place, as shown in Eq. (17). This is an equally stable derivative, whose P H -NMR spectrum shows the characteristic resonances of an AA XX spin system. 

By contrast, lithium enolates derived from tertiary amides do react with oxiranes The diastereoselectivity in the reaction of simple amide enolates with terminal oxiranes has been addressed and found to be low (Scheme 45). The chiral bicyclic amide enolate 99 reacts with a good diastereoselectivity with ethylene oxide . The reaction of the chiral amide enolate 100 with the chiral oxiranes 101 and 102 occurs with a good diastereoselectivity (in the matched case ) interestingly, the stereochemical course is opposite to the one observed with alkyl iodides. The same reversal is found in the reaction of the amide enolate 103. By contrast, this reversal in diastereoselectivity compared to alkyl iodides was not found in the reaction of the hthium enolate 104 with the chiral oxiranes 105 and 106 °. It should be noted that a strong matched/mismatched effect occurs for enolates 100 and 103 with chiral oxiranes, and excellent diastereoselec-tivities can be achieved. 

In light of these significant challenges, Evans and Leahy reexamined the rhodium-catalyzed allylic alkylation using copper(I) enolates, which should be softer and less basic nucleophiles [23]. The copper(I) enolates were expected to circumvent the problems typically associated with enolate nucleophiles in metal-allyl chemistry, namely ehmina-tion of the metal-aUyl intermediate and polyalkylation as well as poor regio- and stereocontrol. Hence, the transmetallation of the lithium enolate derived from acetophenone with a copper(I) hahde salt affords the requisite copper] I) enolate, which permits the efficient regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of a variety of unsymmetrical acychc alcohol derivatives (Tab. 10.3). 

The occurrence of such equilibria may also account for the fact that deprotonation of l,3-Sg(NH)2 with ethyl-lithium and reaction of the resulting anion with methyl iodide produces S NMe but no alkylated derivatives of the diimide... 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

Let us now focus our attention on the interaction between lithium alkyls and Group III derivatives. These species are often considered to be metalates with discrete MR4 ions present, but a variety of studies show that substantial metal-anion interactions occur both in solution and in the solid state (45, 96, 131). More thorough examination of both of the structures and spectroscopic properties of these derivatives shows that they must be included in any treatment involving electron-deficient bonding. 

Acylmetallocenes undergo many reactions shown by acylbenzenes (35, 87, 91, 116, 124), but a detailed discussion is not presented here. Reductions with either lithium aluminum hydride or sodium borohydride give the corresponding carbinols, while Clemmensen reduction, reduction with lithium aluminum hydride plus aluminum chloride, catalytic hydrogenation, etc., yield corresponding alkyl derivatives. Acetylferrocenes undergo a variety of base condensation reactions and can be oxidized to ferrocenecarboxylic acids without apparent oxidation of the iron atom. 

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