Cuprate mediated coupling reactions

Cuprate-mediated coupling reactions using a C-labeled alkyl iodide or a "C-labeled methyl cuprate, (e.g., methyl C-labeled fatty acids, C-labeled steroids, see Kihlberg and Langstrom 1994a, b Lidstrfim et al. 1997 Neu et al. 1998). 

Coupling Reactions to Dienes and Enynes. The silyl bromide (1) participates readily in copper or transition metal-mediated coupling reactions to produce 1,3-butadienes, which are very useful s)mthetic intermediates. For example, 2,3-bis[(trimethylsilyl)methyl]-1,3-butadiene (8), derived from the oxidative dimerization of cuprate (2) (M = Cu) is useful for rapid construction of multicyclic systems via tandem Diels-Alder reactions, as depicted in eq 15 The diene 2-dimethylaminomethyl-3-... 

Copper(I) mediated reactions of alkenyliodonium salts with nucleophiles proceed with complete retention of configuration, which is probably explained by the mechanism involving oxidative addition of cuprates, ligand coupling at the iodine center of 67, and then ligand coupling at the copper(III) of 68 (Scheme 31) [42,54]. 

The Apple codhng moth (Laspeyresia pomonella) is a pest of worldwide distribution (Fig. 8.79). Its pheromone can be produced in a few stages starting from sorbic acid, via a cuprate-mediated Grignard coupling (a Schlosser-Fouquet reaction) as the essential step. [162]... 

Herein, three syntheses of morphine or related alkaloids are discussed in detail, which utilize completely different protocols for the coupling of the ring motifs of the alkaloid. Rice published a biomimetic approach with an acid-mediated electrophilic cyclization strategy as key step [144]. Mulzer employed a Friedel-Crafts acylation and a Robinson annulation to construct the phenanthrenone ring system [145]. The D ring of the alkaloid was elaborated with a 1,4-cuprate addition as key step. In his most recent contribution to morphine research, Hudlicky employed a Diels-Alder cycloaddition reaction to construct the ABCE ring system of the natural product. The requisite diene was obtained after oxidative dearomatization of the A ring precursor [146]. 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

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