Organolithiums alcohols

The carbon-metal bonds of organolithium and organomagnesium compounds have appreciable carbamomc character Carbanions rank among the strongest bases that we 11 see m this text Their conjugate acids are hydrocarbons—very weak acids indeed The equilibrium constants for ionization of hydrocarbons are much smaller than the s for water and alcohols thus hydrocarbons have much larger pA s... 

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

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

Addition of Grignard reagents and organolithium compounds (Sections 14 6-14 7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols... 

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

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 and organomagnesium compounds find their- chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first exanine the reactions of these organometallic compounds with proton donors. 

Organolithium and organomagnesium compounds are stable species when prepaied in suitable solvents such as diethyl ether. They aie strongly basic, however, and react instantly with proton donors even as weakly acidic as water and alcohols. A proton is transfened from the hydroxyl group to the negatively polaiized caibon of the organometallic compound to fomn a hydrocaibon. 

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). 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

In some cases the yields were poor due to competing deprotonation of the substrate by the organolithium reagent. Deprotonation was the predominant reaction with methyllithium or when (Z)-2-(l-alkenyl)-4,5-dihydrooxazoles were employed. The stereochemical outcome has been rationalized as occurring from a chelated transition state. The starting chiral amino alcohol auxiliary can also be recovered without racemization for reuse. 

ADDITION OF ORGANOLITHIUM REAGENTS TO ALLYL ALCOHOL 2-METHYL-l-HEXANOL... 

Octynoic acid, methyl ester, 55, 76 ORGANOLITHIUM COMPOUNDS, addition to allyl alcohols, 55, 1... 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

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