Ketones with organolithium reagents

Carbonyl- 4 C KIE in the reactions of ketones with organolithium reagents... 

Reaction with Organolithium Reagents (Section 16.5B) Reactions of aldehydes and ketones with organolithium reagents are similar to those with Grignard reagents. 

Synthesis of ketones using organolithium reagents with carboxylic acids (Section 18-8)... 

With organolithium reagents, stable intermediates are produced by addition to a carboxylic acid. On workup, these intermediates produce ketones. As with Grignard reagents, the reaction of organolithium reagents with esters produces tertiary alcohols because the intermediates decompose to ketones under the reaction conditions. The mechanisms for these processes are illustrated in the examples that follow. 

As further illustrated in Scheme 2, the 1-methyl- and 1,3,3-trimethylcyclopropene are rapidly metallated with organolithium reagents in ether to afford stable solutions of the 1-lithiocyclopropenes (18) In comparison, solutions of the metallocyclopropenes (16) are significantly less stable and even at — 40°C are observed to degrade slowly to a mixture of dimeric and trimeric products apparently formed by nucleophilic addition of 16 to the highly reactive cyclopropene n system L Alkylation of 18 (R=H or Me) with methyl iodide produced 1,2-dimethyl- and 1,2,3,3-tetramethylcyclopropene . The trimethyl derivative 18 (R = Me) has also been carbonated and acylated to afford the corresponding 2,3,3-trimethylcyclopropene carboxylic acid, methyl ketone and carboxaldehyde. 

Chiral boronic esters react with organolithium reagents to form diorganylalkoxyboranes (borinic esters). Subsequent reaction with the anion of dichloromethyl methyl ether then yields chiral ketones by rearrangement of both of the groups on boron (Scheme 42). No racemization is observed in this sequence and alkyl-, aryl- or alkynyl-lithium reagents can be used. 

Acyl addition to aldehydes and ketones with Grignard reagents organolithium reagents enolate anions alkyne anions... 

The type of alcohol produced depends on the carbonyl compound. Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.1, formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. Analogous reactions take place with organolithium reagents. 

A regioselective synthesis of 1,4-dienes (69) from a,/3,7,5-unsaturated ketones, e.g. (68), proceeds in excellent yield on alkylation with organolithium reagents followed by reduction with lithium in liquid ammonia. The reaction is not successful with the corresponding aldehydes and the lithamide reduction product must be quenched with ethanol or t-butyl alcohol rather than with conventional protic sources such as ammonium chloride. Where applicable, the 1,4-diene is formed as a mixture of the E- and Z-stereoisomers at the newly developed double bond. 

The alkyl halide must be one (primary or secondary) which is reactive toward Sn2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic. Deprotonation can be carried out with organolithium reagents n-butyllithium in tetrahydrofuran is frequently used. Deprotonation using the sodium salt of dimethyl sulfoxide in dimethyl sulfoxide as the solvent is probably the most popular means of converting phosphonium salts to ylides." The ylide once formed is not normally isolated, but is treated directly with the carbonyl compound. Ylides of this type, where R is hydrogen, alkyl, or aryl, are quite reactive toward aldehydes and ketones. 

Metallated tosylhydrazones react with aldehydes and ketones to afford /8-hydroxytosylhydrazones in good to excellent yield. Further reaction with organolithium reagent gives the corresponding homoallylic alcohol (Scheme... 

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