Ethers reaction with organolithium reagents

The equatorial selectivity observed with organolithium reagents is enhanced in diethyl ether as the reaction solvent by the addition of lithium perchlorate (Table l)12. I3C-NMR studies47 indicate that the formation of a complex between lithium perchlorate and the carbonyl group, which also leads to a dramatic enhancement of the rate of the addition reaction, accounts for the increased diastereoselectivity. 

A similar procedure was used with organolithium reagents [152], and when the reaction was run in ether HMPA was added before the alkylation step. 

Reaction with (172) and other aldoximes may require oxime activation, which can be achieved with the addition of 1 equiv. of BF3-OEt2." " Yields in the addition of organometallic reagents to substituted aldoximes are modest and are a function of the isomeric composition of the oxime ethers, as the (Z)-oxime isomers are reported to preferentially react with organolithium reagents (entries 1 and 2, Table 13). ° The reaction has been employed for the preparation of 6-aminoalkyl-substituted pencillins (entry 3, Table 13)."° Cyclic oxime ether additions have also been evaluated (entries 4 and 5, Table 13). ° With the lability of the nitrogen-oxygen bond, addition to S-substituted isoxazolines provides a potential avenue for stereospecific synthesis of substituted 3-aminoalcohols (entry 5, Table 13). 

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. 

Both 19 and 20 react readily with a variety of organometallic compounds to afford the corresponding ti -vinylcyclopentadienyl monomers. The reaction between organolithium reagent 2 and (ri -cyclo-pentadienyl)trichlorotitanium on ethyl ether produces (n -vinylcyclo-pentadienyl)(n cyclopentadienyl)dichlorotitanium, (mp 154-157°C, 16%) (Equation 5). Pol3nners of after reduction could function... 

Cyclic imines, generated from cyclic N-chloramine precursors by reaction with potassium superoxide in ether solution, react with organolithium reagents to give the corresponding regioselectively alkylated products (Scheme 44). ... 

SCHEME 26.29. Reaction of CFs-containing enol ether with organolithium reagent. 

The mechanism of organolithium addition to naphthyl oxazolines is believed to occur via initial complexation of the alkyllithium reagent to the oxazoline nitrogen atom and the methyl ether to form chelated intermediate 17. Addition of the alkyl group to the arena 7t-system affords azaenolate 18, which undergoes reaction with an electrophile on the opposite face of the alkyl group to provide the observed product 4. The chelating methyl... 

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. 

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