Zinc enolates conjugate addition-alkylation

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Where possible, it may be most economical to effect a chiral transformation on a pre-formed, pro-chiral ring. Ben Feringa of the University of Groningen prepared (Chem Commun. 2005, 1711) the enone 2 from 4-methoxypyridine 1. Cu -catalyzed conjugate addition of dialkyl zincs to 2 proceeded in up 96% . Pd-mediated allylation of the intermediate zinc enolate led to 3, with the two alkyl subsituents exclusively trans to each other. 

The zinc enolate formed as an intermediate in these conjugate addition reactions can be trapped by an electrophile in situ to provide further functionalization of the substrate. This is demonstrated by the synthesis of the anticancer agent clavularin B (eq 103). Sequential conjugate addition to cycloheptenone of Me2Zn in the presence of catalytic CuOTf-chiral peptide ligand complex, and enolate alkylation with 4-iodo-1-butene provide the key compound with 97% ee. 

Scheme 5.109 Copper-catalyzed enantioselective conjugate addition of dimethyl zinc and enolate trapping by palladium-catalyzed allylic alkylation to ketone 427. Application to a synthesis of pumiliotoxin C.

The allylic or benzylic alkylation of chiral zinc enolates, resulting from an asynunetric copper-catalysed conjugate addition reaction of dialkylzinc, has been performed with allylic or benzylic halides in reasonable yields and high diastereoselectivities (up to 20 1 dr). ... 

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