Organocopper reagents acylation

Scheme 2.13. Acylation of organocopper reagents derived from organoboranes.

Zirconium(IV) propoxide, 352 with organocopper reagents Dilithium acyl(alkyl)(cyano)cuprates, 209... 

Step a Cul and /-BuMgCl generate an in situ organocopper reagent which adds only once to the acyl chloride functionalities. 

Step lb Alternatively, Cul can be used to generate an organocopper reagent which would work equally well for a controlled 1,2-addition to an acyl chloride. 

Often, better results are obtained by transmetal I ating (see Chapter 9) the Grignard reagent, or the organolithium, with copper salts. Organocopper reagents are too unreactive to add to the product ketones, but they react well with the acyl chloride. Consider this reaction, for example the product was needed for a synthesis of the antibiotic septamycin. 

Methyl ketonesfrom carboxylic acid chlorides (3,112). Posner e/n/. report that the synthesis of ketones from acid chlorides and organocopper reagents is applicable to acid chlorides containing iodo, cyano, acyl, and carboalkoxy groups. The reaction, however,... 

A recent example by McGarvey demonstrates the formation of chiral derivatives (73)-(76) which are useful for elaboration into the ubiquitous propionate unit through stereoselective enolate-based alkylation (equation 56)." The thiol ester substrates were derived from aspartic acid in seven steps. The acylation of either dimethylcuprate or the Grignard-derived organocopper reagent was extremely clean when these organometallics were used in excess. No epimerization of the adjacent center was observed during the addition. 

The organocopper reagents are more selective and can be acylated with acid chlorides without concomitant attack on ketones, alkyl halides, and esters. 

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