Of organolithium reagents

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. 

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

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 ... 

Reaction of organolithium reagents with aldehydes and ketones (Section 14.7) Organolithium reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to form alcohols. 

The asymmetric addition of organolithium reagents to arylox azolines has been used to construct highly complex polycyclic terpene structures found in natural products. For example, the asymmetric addition of vinyllithium to chiral naphthyloxazoline 3 followed by treatment of the resulting anionic intermediate with iodoethyl dioxolane 61... 

Table 1. Enantioselectivc Addition of Organolithium Reagents to Imines 1 Mediated by the Enantiomerically Pure Amino Ether 241...

Table 2. Stereoselective Addition of Organolithium Reagents to Racemic Hydrazones l2 OR1...

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

Table 5. Addition of Organolithium Reagents R2Li to Oxime Ethers 4 and Reduction of the Resulting Alkoxyamines 5 to Amines 6"...

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

The reaction of organolithium reagents is rapid and complete in less than 1 min even at low temperature, while Grignard reagents require 12-24h at room temperature to react completely. Treatment of ( )- or (Z)-l-methylsulfonyl-2-phenylethylene with trialkylbo-ranes yields exclusively ( )-olefins via a vinyl radical intermediate14. 

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

Mechanisms for the addition of organolithium reagents have been investigated... 

In 1997, the intermolecular addition of organolithium reagents to fluoro-alkynylsilanes was used to synthesize three novel, stable 1-silaallenes. In this... 

Scheme 7.2. Preparation of Organolithium Reagents by Halogen-Metal Exchange... 

Cerium reagents have also been found to give improved yields in the reaction of organolithium reagents with carboxylate salts to give ketones. 

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