Organolithium conjugate addition

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 conjugate addition substrate that we were considering bore an obvious resemblance to Stork s however, it would incorporate a free NH and OH, as well as a more sensitive aldehyde. In this light, an approach involving reactive organolithium species seemed unlikely to be successful, and a few experiments quickly validated this surmise. We therefore sought a precursor that could... 

However, diphenyl cyclopropenone undergoes conjugate addition via C1(2) with organolithium reagents227,228 as indicated by products of structure 337 and 338 ... 

Organolithium compounds are highly reactive and have been used in a variety of organic transformations. A major problem in the development of catalytic asymmetric conjugate additions of organolithium reagents to a,/3-unsaturated carbonyl compounds is that the high reactivity of RLi may cause both low chemoselectivity (1,2- vs. 1,4-addition) and low enantioselectivity. 

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. 

Whereas, the sulfur ylide 9 undergoes conjugate addition to enones thereby precluding 1,2-cyclopentyl annulation, the organolithium 37a undergoes clean carbonyl addition. Cyclopentenone participates smoothly in this sequence (Eq. 88)81>. 

Complexation of enones with MAD can be used to effect conjugate additions with organolithium reagents. This unusual 1,4-selectivity is observed mainly with cyclic systems and requires 2 equiv. of the aluminum reagent as well as of the nucleophile for full effect. 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

RCuCNLi (25-62%)]. Successful conjugate addition required the activating influence of TMSCl [11c], and rather modest yields (25-64%) were obtained with dialkyl-substituted 2-enones. Cuprate preparation directly from the organolithium... 

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