Insertion of activated copper

Cut LiCl with lithium naphthalenide, it is possible to prepare allylic copper species that undergo smooth addition to enones leading to the 1,4-addition product such as 8 in 92% yield [11], Remote ester-functionalized aryl- and alkyl-copper compounds can be readily prepared by this method [12], Remarkably stable ortho-halophenylcopper reagents obtained by the direct insertion of activated copper undergo substitution reactions with alkyl iodides, benzylic bromides and various acid chlorides [13,14]. 

The intramolecular G-H insertion of aryldiazoacetates is a very powerful strategy for synthesizing heterocyclic rings such as dihydrobenzofurans and dihydrobenzopyrans. The first effective asymmetric copper-catalyzed C-H activation reaction was reported by the group of Sulikowski in the synthesis of the anti-tumor antibiotic FR-66979 93 (Scheme 7)123 219 The G-H insertion of the aryldiazoacetate 90 formed four diastereomeric products 91a, 91b, 92a,... 

Copper is the third most abundant trace element in humans, after iron and zinc (Underwood, 1977). It is critical to a variety of proteins with functions ranging from electron transfer to oxygen transport to active chemistry, such as insertion of oxygen in a substrate. Table I is a selected list of copper-containing proteins. 

Deviations from the Schulz-Flory distribution arc possible if secondary reactions such as cracking on acidic supports or insertion of product olefins into the growing chain occur [42]. It has been reported recently that the Schulz Flory constant a has a tendency to increase from C3 to C, [45]. This may be the reason why the values found are usually higher for methane and lower for Cj and C) j.)., as would be expected for an ideal Schulz-Flory distribution [40]. Investigations by Madon et at. on partly sulfur-poisoned iron/copper catalysts revealed a dual product distribution. This was explained by the assump tion of > 2 types of active sites for hydrocarbon chain formation, each with a slightly different value of the chain growth probability [46]. 

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