Reagents organolithium

An organolithium reagent behaving as a base towards a proton (deuteron) donor. 

The preparation of a primary alcohol from an organo-lithium compound and formaldehyde. 

Grignard reagents react with halides of less electropositive metals to give other organometallic compounds. The less electropositive (more electronegative) metals include Hg, Zn, Cd, Si, and the nonmetal P. An example of this type of reaction is 

Less electronegative metals, such as sodium, tend to form ionic organometallic compounds. These compounds have limited use in synthesis. One example of using a different organometallic in a synthesis is 

The cyclopentadienyl rings react like aromatic systems because, well, they re aromatic. The bond is between the iron ion and the tr-electron cloud of the aromatic system. Another metal ion may replace the iron in ferrocene. 

The earliest reports of the addition of organolithium reagents to oxabicydic compounds were in the context of dihydronaphthalene oxide 257. Caple and Berchtold found that the additions occur in an SN2 fashion, leading to alcohols 279a-c,Eq. 176 [211,212], 

279a R= n-Bu, 85% yield 279b R= t-Bu, 100% yield 279c R= Me, 61% yield 

However, when the hydroxyl group was protected as a benzyl ether, the regio-selectivity decreased dramatically, Eq. 178 [105], as it did for the homologous alcohol, Eq. 179. 

The directing effect of a hydroxyl group alpha to the bridgehead carbon was also observed with an oxabicyclo[3.2.1] substrate, although only f-BuLi is sufficiently reactive to induce ring opening, Eq. 180 [213]. 

The increased strain in oxabicyclo[2.2.1]heptenes such as 256b makes them more reactive toward organolithium reagents. The ring opening reactions occurred at lower temperatures and with higher regioselectivities, Eq. 187. 

Lithium reacts with haloalkanes to give organolithium reagents. For example, bromomethane reacts with lithium to give methylhthium. The organic portion of the organolithium reagent behaves as a carbanion. 

Methyllithium reacts with carbonyl compounds to place the equivalent of a methyl carbamon (CHj ) at the carbon atom of a carbonyl group, as in benzaldehyde. 

OrganoUthium compounds are used as bases to remove protons from very weak acids. The pA of methane is about 50, and the methyl carbanion is one of the strongest bases encountered in organic chemistry. OrganoUthium compounds, such as methyllithium, are used to prepare conjugate bases of a variety of organic compounds. For example, amines react with methyUithium in an acid—base reaction to form amide salts. The equiUbrium constant for the reaction of methyUithium with diisopropylamine is approximately 10 .  

The percent ionicity (ionic character) is related to the difference between the EN values of the atoms of the C-Met bond (ENc-EN gJ. These are estimated values, which are affected by the nature of the substituents on carbon. Nevertheless, they indicate that the C-Li, C-Mg, C-Ti, and C-Al bonds are more ionic than C—Zn, C-Cu, C-Sn, and C-B, which form mainly covalent bonds with carbon. Manipulation of certain organometallic reagents requires special techniques.  

Organoiithiums from Alkyl Halides and Lithium Metal 

AP ER 7 Formation of Carbon-Carbon Bonds via Organometallic Reagents 

Important points to consider when preparing and using organolithiums are 

MeLi in Et20 — tetrameric n-BuLi in hexane — hexameric 

Ph2C=NCH2Li can be used for simple aminomethylation and, by subsequent reaction with SOCI2 or by introduction of a triphenylsilyl group into the reagent, for the synthesis of A-alkenylimines. Lithiated A-benzylidenebenzylamine 

Taguchi, H. Yamamoto, and H. Nozaki, Bull. Chem. Soc. Japan, 1977, SO, 1592. 

Additions to the repertoire of anions stabilized by an adjacent sulphur atom include lithiated polymer-bound methylthiophenyl units which can be used for chain-extension of iodoalkanes, cyclopropylthiobenzene, and doubly lithiated allylthiol, benzylthiol, and ethyl 2-thioacetate, which all react as C-nucleophiles. 

The methyl group of methyl 2,4,6-tri-isopropylbenzoate can be lithiated to give a species which may be used as a nucleophilic hydroxymethylating agent.Anions stabilized by an a-phenylseleno-substituent may be obtained by direct lithiation of 

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Carbocyclic substitution can also be achieved by first introdueing a reactive organomelallic substituent. Preparation of organolithium reagents can be done by one of the conventional melhods. especially halogen-metal exchange or directed lithiation. Table 14.2 gives examples. 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Often the precursor is not defined completely but rather its chemical nature is empha sized by writing it as a species to which it is equivalent for synthetic purposes Thus a Grignard reagent or an organolithium reagent might be considered synthetically equiva lent to a carbanion... 

Organolithium reagents (Section 14 3) Lithi um metal reacts with organic halides to pro duce organolithium compounds The organic halide may be alkyl alkenyl or aryl Iodides react most and fluorides least readily bro mides are used most often Suitable solvents include hexane diethyl ether and tetrahy drofuran... 

These reagents contain a negatively charged copper atom and are formed by the reaction of a copper(l) salt with two equivalents of an organolithium reagent... 

Reaction of organolithium reagents with aldehydes and ketones (Section... 

Organolithium reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to form alcohols... 

Organolithium reagents react with epoxides in a similar manner... 

Section 15 4 Grignard and organolithium reagents react with ethylene oxide to give primary alcohols... 

Organolithium reagents react in the same way and are often used instead of Grignard reagents... 

Products are contaminated with more highly alkylated compounds, but less so than without the active metal. The phosphide can be generated from a Grignard or organolithium reagent. 

R Tl compounds, eg, methyl [3003-15-4], ethyl [687-82-1], isobutyl [3016-08-8], and phenyl [3003-04-1] thaHium(III), are usuaHy prepared by the reaction between a dialkyl or diarylthaHium haHde and an organolithium reagent in ether (16) ... 

In ether or tetrahydrofuran organolithium reagents cleave the silicon-oxygen bond in hexamethylphosphoramide, they react at the carbon atom. ... 

This complex should be used when the organolithium is in solution in a hydrocarbon solvent. For organolithium reagents prepared in ether (see Note 4), the same complex may be used or, more conveniently, copper iodide (Cull can be used. The Cul purchased from Prolabo or Merck 4 Company, Inc. may be used directly. Other commercial sources of Cul (Fluka, Aldrich Chemical Company, Inc., Alfa Products, Morton/Thiokol, Inc.) furnish a salt which affords better results when purified. 1 mol of Cul is stirred for 12 hr with 500 ml of anhydrous tetrahydrofuran, then filtered on a sintered glass funnel ( 3), washed twice with 50 ml of anhydrous tetrahydrofuran, once with 50 ml of anhydrous ether and finally dried under reduced pressure (0.1 imO for 4 hr. 

These mechanisms ascribe in jortance to the Lewis acid-Lewis base interaction between the allyl halide and the organolithium reagent. When substitution is complete, the halide ion is incorporated into the lifliium cluster in place of one of the carbon ligands. 

OrganometalUc reagents, prepared from fluorohalocarbons, including Grig-nard reagents [52] or organolithium reagents prepared by transmetaUation [50], are silylated with readily a variable alkylchlorosilanes (equations 70 and 71). 

Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but nonnally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthennore, organolithium reagents are strong bases and react rapidly with even weak proton sources to fonn hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. 

The fonnation of a Giignaid reagent is analogous to that of organolithium reagents except that each magnesium atom can participate in two separate one-electron transfer steps ... 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

Table 17.2 summarizes the reactions of aldehydes and ketones that you ve seen in earlier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12.8), to alcohols by reduction (Section 15.2) or by reaction with Grignard or organolithium reagents (Sections 14.6 and 14.7). 

Suitable strong bases include the sodium salt of dimethyl sulfoxide (in dimethyl sulfoxide as the solvent) and organolithium reagents (in diethyl ether or tetrahydrofuran). 

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