Toluene conjugate additions with

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 authors suggested a stepwise mechanism in which precomplexation of the sulfoxide to the lithium azaenolate would take place, thus allowing conjugate addition to follow. This notion was based on Posner s and Paquette s earlier work on conjugate additions of nucleophiles to 57. As before, thermal elimination of toluene sulfenic acid led to the conjugated products (not shown) in 92-93% yields for R2 = methyl.30 However, for R2 = H thermal elimination of arylsulfenic acid did not afford any dihydropyrrole product but rather led to the formation of pyrroles. Treating 58 or 59 with Raney nickel at low temperature led to the rapid formation of 60 and 61, respectively, in 82-86% yield. 

Building on the success of Woodward s use of an achiral NHC to catalyze the conjugate addition of dialkyl zincs, Alexakis and Roland simultaneously reported the use of chiral NHCs to achieve the asymmetric addition into enones. In Alexakis s system, the catalyst was generated in situ by addition of BuLi to a suspension of imidazolium salt 19, Cu(OTf)2, and enone in toluene followed by addition of Et2Zn (Eq. 28) [63]. While conversions and yields were found to be nearly quantitative, ee values were moderate with 51% being the highest reported. 

Catalytic Enantioselective Conjugate Addition of Dialkylzincs to Enones. A chiral nickel complex modified with DBNE and an achiral ligand such as 2,2 -bipyridyl in acetonitrile/toluene is an highly enantioselective catalyst for the addition of dialkylzincs to enones. p-Substituted ketones with up to 90% ee are obtained (eq 23). The method is the first highly enantioselective catalytic conjugate addition of an oiganometallic reagent to an enone. 

Carboxylic Acids and their Derivatives.—2,3-Seco-A -unsaturated dicarboxylic acids (443), obtained by ozonolysis of 2-hydroxymethylene-4-en-3-ones, have been considered rather resistant to cyclisation to form the A-nor-3-en-2-one system (444). Two convenient methods for achieving such a reaction are now described. Dieckmann condensation of the dimethyl ester (445) was successful with sodium hydride, in toluene containing a little methanol. The 5-methoxy-carbanion (446), resulting from conjugate addition of methoxide ion, is suggested as a possible activated intermediate. Alternatively, the diacid (in the B-nor-series)... 

Another conjugate addition, to the dehydroalanine derivative 38 on solid-phase, was reported by Yim et al. [19], Radical generation using t-butyl iodide and tribu-tyltin hydride afforded only 8% of the desired product, while better results were obtained with organomercurials (Scheme 8). The intermolecular addition of tosyl radicals to unactivated alkene and alkyne 39 has also been reported [20], and the reaction was found to be quite sensitive to solvent. Optimum results were obtained in toluene, although the scope is difficult to gauge with only two examples disclosed. 

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