Conjugate addition reactions organolithium reagents

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. 

In addition to the reactions discussed above, a,//-unsaturated oxazolines can also act as chiral electrophiles to undergo conjugated addition of organolithium reagent to give optically active / ,/ -disubstituted carboxylic acids.52 The vinyl oxazolines 48 are prepared using the two methods outlined in Scheme 2-27. 

The chromium complex 46 of benzaldehyde imine is also a good substrate for asymmetric conjugate addition of organolithium reagents, where the reaction was mediated by a stoichiometric amount of chiral diether 18 in toluene to give, following propargylic electrophile incorporation, the cyclohexadienal 48 in up to 93% ee (Scheme 13) [38]. SAMP [(S)-l-amino-2-(methoxymethyl)pyrrolid-ine] hydrazones were used effectively in diastereoselective nucleophilic additions to (arene)Cr(CO)3 complexes [39]. 

An auxiliary approach was developed by Meyers, who found that unsaturated oxazolines such as 58 participate in asymmetric conjugate addition reactions with organolithium reagents (Equation 11) [74, 75]. With these substrates, a wide variety of chiral /1-substituted acids, including 59, were obtained with excellent enantioselectivity [75]. The yields were highest for substrates lacking allylic protons, as y-deprotonation was observed as a competing unwanted side reaction. 

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