Normant reagents, addition

Acetylene itself (R = H) undergoes the reaction with R2CuLi instead of the Normant reagent.1106 The use of R containing functional groups has been reported.1107 If the alkyl iodide is omitted, the vinylic copper intermediate 123 can be converted to a carboxylic acid by the addition of C02 (see 6-34) or to an amide by the addition of an isocyanate... 

Scheme 6.74. The use of addition of an organocuprate-magnesimn bromide (Normant) reagent to produce an intermediate that can be converted to a variety of alkenes.

Normant and Poisson prepared allenylzinc bromide reagents from TMS acetylenes along the lines of Epsztein and coworkers5, by sequential lithiation with s-BuLi to yield a lithiated species, and subsequent transmetallation with ZnBr2 (equation 35)27,28. Additions to racemic /J-silyloxy aldehydes proceed with low diastereoselectivity to afford mixtures of the anti,anti and anti,syn adducts (Table 17). The latter adducts are formed via an anti Felkin-Anh transition state. Additions to the racemic IV-benzylimine analogs, on the other hand, proceed with nearly complete Felkin-Anh diastereoselectivity to yield the anti,anti amino alcohol adducts (Table 18). 

When they subjected the allenylzinc reagent to the Hoffmann test for configurational stability,29 Poisson, Chemla and Normant found that at — 50 °C, racemization does not occur at a significant rate (equation 36)30,31. Accordingly, when the racemic allenylzinc reagent was added slowly to the /V-benzy limine of (R)-mandehc aldehyde at — 50 °C, a 1 1 mixture of the anti,syn and anti,anti adducts was isolated in 65% yield. However, when the addition process was reversed, a 3 1 mixture favoring the matched anti,anti adduct was formed in 53% yield, suggestive of a partial kinetic resolution. 

Chemla, Normant and coworkers also reported a one-pot 1,4-addition/carbocyclization domino sequence as a new access to 3-carbomethoxypyrrolidines. Conjugate addition of the mixed organocopper-zinc reagent n-BuCu(CN)ZnBr LiBr to the Michael acceptor 427 in ether at room temperature directly led after hydrolysis to the 3-carbomethoxypyr-rolidine 428 as a 84/16 diastereomeric mixture, the trans disubstituted isomer being predominant (equation 185). A similar explanation as described above was proposed for the stereochemical outcome264. 

Chuit Foulon Normant Tetrahedron 1980, 36. 2305. 1981,37, 1385. For a review, sec Alexakis. Chuit Com-mer on-Bourgain Foulon Jabri Mangency Normant Pure Appi. Chem. 1984,56, 91-98. A better reagent for the addition of a methyl group to an a, 3-unsaturatcd aldehyde is McsCu3Li2 Clive Farina, Beaulieu. J. Org. Chem. 1982, 47, 2572. 

The fruitfulness of the idea of a stepwise addition with an independent variation of the addends was brilliantly illustrated by Normant s studies, which resulted in the elaboration of a general method of alkene synthesis based on the reaction of alkyne carbometallation. Basically this reaction represents a case of the well-known nucleophilic addition to a carbon-carbon triple bond. In the Normant reaction, however, the initial addition of a nucleophile (an organome-tallic reagent) across the triple bond results in the formation of a stabilized carbanion-like intermediate equivalent to a vinyl carbanion. This intermediate can similarly be further reacted with an external electrophile. Most typically, copper-modified Mg or Li reagents, which are unable to react with acidic acetylenic hydrogens, are used in this sequence. 

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