Organocopper compounds alkylation

During the last decade, a substantial number of novel (sometimes even stereoselective) strategies for the preparation of allenic prostaglandins have been devised. The approach used by Patterson involves a three-component coupling via a 1,4-addi-tion of the organocopper compound 121 to the enone 120, followed by alkylation of the enolate formed with the bromide 122 (Scheme 18.40) [121]. However, due to the notoriously low reactivity in the alkylation of the mixed copper-lithium enolate formed during the Michael addition [122], the desired product 123 was obtained with only 28% chemical yield (the alkylation was not even stereoselective, giving 123 as a 1 1 mixture of diastereomers). 

Reactions with hthium or Grignard reagent yield alkyl or aryl copper(I) derivatives, respectively. Such organocopper compounds containing Cu-Cu bonds are formed only by Cu+ and not Cu2+ ions. 

Table 5.1. Alkylations with organolithium, organosodium, and organocopper compounds.

Few comparisons have been made among the relative stabilities of other classes of organocopper compounds. Generally, for simple derivatives, the order of decreasing stability is RC=CCu > Aryl-Cu > Alkyl-Cu. For vinylcopper compounds, 2-butenylcopper is more stable than propenylcopper 294). The higher homologs of methylcopper and lithium dimethylcuprate are less stable (69, 276, 297). 

The consensus favors a transitory copper(III) intermediate in the reaction of a copper corapound with an alkyl or vinyl halide 37, 57, 65, 185, 297), although Tamura and Kochi consider such an intermediate unlikely for alkyl halides (276). Collman (57) has suggested that organocopper compounds are representative of a number of transition... 

There is presumably more than a subtle difference between the reactions of alkyl and aryl halides with organocopper compounds, as a straightforward nucleophilic displacement of aryl halide by the d electrons of a copper species is hardly likely. Simple aryl halides are nearly all inert to the usual nucleophiles, such as alkoxides, unless strongly activated by electron-attracting groups in the ortho and para positions. However, coordination of the halogen to copper may be sufficient to... 

Organocopper compounds of stoichiometric ratio RCu do not always react with alkyl bromides (29, 44, 66, 147, 181). Where possible, a reaction may be effected at higher temperatures (128), in a more strongly coordinating solvent (31, 297), or by means of the cuprate species (297). An unsubstantiated coupling reaction between phenylcopper and butyl bromide in an aromatic solvent was mentioned (24), although it is doubtful that an organocopper species was employed (285). 

In this chapter, the substitution reactions of organometallic reagents with organic halides and related electrophiles are reviewed. - The major portion of the chapter is devoted to a discussion of organocopper compounds, which first transformed the alkylation of nonstabilized carbanions into a reaction of general synthetic utility. More recently, transition metals other than copper have also found widespread application in such coupling reactions, and developments in this area are outlined in Section 1.5.3. 

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