Addition of Organozinc Reagents to Ketones

RSC Catalysis Series No. 2 Chiral Sulfur Ligands Asymmetric Catalysis By Helene Pellissier Helene Pellissier 2009 

In 1998, two other examples of chiral ligands that enabled the asymmetric addition of organozinc reagents to ketones were reported by two groups independently. Thus, Dosa and Fu employed the nonsulfur-containing Noyori s DAIB ligand in the asymmetric addition of ZnPh2 to ketones with 

Alkynylations of ketones with bis(hydroxycamphorsulfonamides) ligand bearing xylenediamine as linker. 

Another idea developed by Yus et al. was to use other linkers with a low conformational freedom, such as 1,2-cyclohexanediamine derivatives.  

4-bromophenyl methyl ketone produced the expected corresponding alcohol with similar results to those using ZnPh2 as the initial substrate. The results were very good for the reactions with alkyl aryl ketones, decreasing as the alkyl group 

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Mixed bis-sulfonatnide ligands of the type 46 were also prepared and shown to be highly effective for the addition of organozinc reagents to ketones (eqs 19 and 20). ... 

Addition of Organozinc Reagents to Aldehydes, Ketones, and a-Ketoesters 383... 

Addition of Organozinc Reagents to Aldehydes, Ketones, and a-Ketoesters 2.06.16.2.1 Chiral ligands used in addition reactions of diorganozincs with aldehydes... 

COPPER-CATALYZED CONJUGATE ADDITION OF ORGANOZINC REAGENTS TO a.p-UNSATURATED KETONES, 76, 252... 

On the basis of this concept the same group has developed a similar strategy using a copper-catalyzed addition of organozinc reagents to enones, followed by trapping of the resulting zinc-enolate by ketones, esters or nitriles as terminal electrophiles (Scheme 35) [83]. 

The new binaphthyl ligands 49 [22] and 50 [23] have led to a breakthrough in the copper catalyzed 1,4-addition of organozinc reagents to a,jff-unsatu-rated ketones, a reaction which has proved to be difficult if carried out enantioselectively. Selectivities up to 96 % ee have been reached with cyclic substrates, while acyclic substrates still leave room for further improvement. 50 has also been successfully employed in palladium-catalyzed alkylations of allyl acetates [24]. 

A detailed experimental procedure for the copper-mediated conjugate addition of organozinc reagents to a,p-unsaturated ketones is given later in the text. 

A conjugated addition of organozinc reagents to a,jd-unsaturated carbonyl compound has been well studied in the presence of various catalysts. If this reaction is possible with bis(iodozincio)methane, the transformation gives y-zinc substituted enolate. As shown in Scheme 8.34, i)is(iodozincio)methane reacts with s-cis a,/3-unsaturated ketone in the presence of chlorotrimethylsilane to afford a sUyl... 

The first catalytic asymmetric addition of functionalized organozinc reagents to ketones has been reported.107 These investigations indicated that catalyst (40) is tol- erant to a variety of functionalized zinc reagents and enantioselectivities generally exceed 90%. 

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