Copper phosphoramidite catalysis

The copper-catalyzed enantioselective Michael addition of organometallic reagents to enones was the first successful application of phosphoramidite chiral ligands in catalysis [4, 43]. Since this early report, substantial enhancement of the enantioselectivity and/or of the substrate scope has been achieved through an untiring effort to optimize the ligand structure [5a, 44]. 

Phosphoramidite ligands are also suitable for the challenging enantioselective addition of alkenyl aluminium reagents to p-substituted cychc enones [36]. Although the introduction of alkenyl groups to enones has been largely the domain of Rh catalysis [40, 41], the remarkable advances in copper-catalysed ECA have now made this transformation possible. 

The copper-NHC-catalysed addition of organoaluminium reagents to cyclo-hexenones and cycloheptenones reported by Hoveyda [58] is, in some cases, slightly less selective than those performed in the presence of phosphoramidites or phosphinamine catalysts (<90% ee for the imidazolium ligands versus <99% ee that the phosphoramidites and phosphinamine can provide). However, NHC-Cu catalysis provides better results (up to 97% ee and 97% conv) when challenging cyclopentenones and bulky p-substituted cycUc enones (bearing n-butyl, alkynyl, aryl or an ester group as the p substituent) are used as substrates (Scheme 25). 

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