Organolithium reagents protonation

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. 

Organolithium reagents cause deprotonation of the a-C atom of SENA (306). If these protons are absent, deprotonation occurs at the (>-carbon (Scheme 3.93). These transformations produce oximes (109) or (110), respectively. 

As emphasized above, the practical utility of organocerium compounds is to circumvent the problems which are faced with the corresponding Grignard and organolithium reagents because of their inability to react effectively with sterically demanding carbonyl compounds and carbon-heteroatom unsaturated bonds which have acidic a-protons. Some of the latest examples are shown below. 

This method does not allow the formylation of aliphatic Grignard or organolithium reagents since in these cases the enhancement in base strength in the presence of hexamethylphosphoramide produces side reactions due to proton abstraction. 

Carbamate substituents have also been found to permit the direct removal of allylic, propargylic and allenic protons by organolithium reagents [32, 33]. In the latter case, the resulting lithioallenes can be converted to the allenyltitanium reagents with ClTi(OiPr)3 (Eq. 9.28) [8]. As illustrated, subsequent addition to acetaldehyde proceeds with only modest diastereoselectivity. 

Organolithium reagents, like Grigncird reagents, are bases that react with proton (or deuteron) donors. Figure 14-13 illustrates this reaction. In this reaction D2O (heavy water) is the deuterated form of water in which the hydrogen atoms (H) are replaced with deuterium atoms (D). 

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

Fluorinated dicarbonyl triphenylphosphoranes, easy to prepare (by trifluoro-acetylation of the stabilised ylides), have been transformed stereoselectively into / -substituted jS-trifluoromethyl alkenoates by treatment with organolithium reagents (Eq. 115) [306]. The stereoselectivity could be reversed by O-methyla-tion of the initial adduct followed by protonation [307]. 

Grignard and organolithium reagents provide some of the best methods for assembling a carbon skeleton. These strong nucleophiles add to ketones and aldehydes to give alkoxide ions, which are protonated to give alcohols. 

Like other strong nucleophiles, Grignard and organolithium reagents attack epoxides to give (after protonation) ring-opened alcohols. 

Organolithium reagents can be used to synthesize ketones from carboxylic acids. Organolithiums are so reactive toward carbonyls that they attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone (see Section 18-13). 

If the organolithium reagent is inexpensive, we can simply add two equivalents to the carboxylic acid. The first equivalent generates the carboxylate salt, and the second attacks the carbonyl group. Subsequent protonation gives the ketone. 

Esters and Acid Chlorides Grignard and organolithium reagents add twice to acid chlorides and esters to give alkoxides (Section 10-9D). Protonation of the alkoxides gives alcohols. 

The synthesis of equation (14) illustrates another useful reaction of Fischer carbenes, the abstraction of a proton to the metal by a base such as an organolithium reagent. The resulting negative charge can be delocalized onto the metal, and is therefore stabilized. The anion can be alkylated by carbon electrophiles as shown. 

This reaction follows the general mechanism for nucleophilic addition (Section 20.2A)—that is, nucleophilic attack by a carbanion followed by protonation. Mechanism 20.6 is shown using R"MgX, but the same steps occur with organolithium reagents and acetylide anions. 

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