Nucleophilic reaction with organocopper

Nucleophilic substitutions reactions with organocopper compounds or the more widely applied organocyanocuprates in the presence of Lewis acids have been reported on a./S-ethylenic acetals and allylic mesylates or acetates. Mangeney and co-workers have reported regio- and diastereoselective Sn2 or Sn2 reactions on chiral acetals of cyclic aldehydes promoted by PhCu and Furthermore, organocoppers react efficiently... 

With respect to the nucleophilic addition of organocopper reagents, a sharp contrast between the rigid isopropylidene glyceraldehyde and its open-chained analog, 2,3-bis(benzyloxy)propanal. was observed (compare Tables 15 and 16). With the isopropylidene-protected aldehyde a high syn diastereoselectivity could only be obtained when tetrahydrofuran was used as reaction solvent, and the diastereoselectivity dropped considerably in diethyl ether. In contrast, the latter solvent allows excellent syn selectivities in additions to the dibenzyl-protected glyceraldehyde81. On the other hand, tetrahydrofuran yields better results than diethyl ether in the... 

Sn2 substitution reactions of alkyl halides with hard nucleophiles such as alkyl anions can be achieved most readily with the aid of organocopper chemistry [95]. Sn2 reactions with epoxides and aziridines are also synthetically useful [96]. The... 

Similar to the addition reactions of acceptor-substituted dienes (Scheme 16), the outcome of the transformation depends on the regioselectivity of the nucleophilic attack of the organocopper reagent (1,4- vs. 1,6-addition) and of the electrophilic capture of the enolate formed. The allenyl enolate obtained by 1,6-addition can afford either a conjugated diene or an allene upon reaction with a soft electrophile, and thus opens up the possibility to create axial chirality. The first copper-mediated addition reactions to Michael acceptors of this type, for example, 3-alkynyl-2-cyclopentenone 75,... 

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... 

The majority of reported reactions of aryl and heteroaryl substrates with organocopper reagents are examples of Stephens-Castro coupling or the more recent catalytic version of that reaction. The reaction has found recent application in syntheses of C-(6)-substituted pterins and pteridines, substituted pyridines, and the antitumor antibiotic fredericamycin A," to name a few. Aryl iodide can be che-mospecifically displaced in the presence of bromide," and 2,5-dibromopyridine is regioselectively substituted at the 2-position. Substitution of halobenzenes by propargyl alcohol, followed by oxidative cleavage, provides a convenient route to terminal arylalkynes. " Fused heterocycles are formed in reactions of aryl halides bearing nucleophilic ortho substituents. - "... 

Nucleophilic addition using organometallics showed that the C-4 position of (la) is a hard reaction site, whereas the C-5 position has soft reactivity (Equation (15)) <85CC1370>. These results are in accord with those from MO calculations. Softer nucleophiles such as organocopper reagents underwent a redox reaction with triazine to give 2,5-dihydro derivatives without ring substitution. 

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