Enantioselective electron-withdrawing ligands

Scheme 6.27. Zr-catalyzed enantioselective Mannich reactions when more electron-withdrawing chiral ligands are used, enantioselectivity and reactivity levels are enhanced. Deprotection is carried out in two steps.

The enantioselectivity increases dramatically when the ligands contain electron-withdrawing P-aryl substituents. Electron-donating substituents on the substrate give the highest ee (91% for 6-methoxy-2-vinylnaphthalene in apolar solvents). Mechanistic studies at room temperature have shown that at low concentration of HCN nickel zero species are the resting states, but at higher concentrations of HCN q3-benzyl nickel cyanide species were also observed. 

The first enantioselective, iridium-catalyzed allylic substitution was reported by Helmchen and coworkers soon after the initial report by Takeuchi. Helmchen studied catalysts generated from phosphinooxazoline (PHOX) ligands and [Ir(COD)Cl]2 for the reactions of sodium dimethylmalonate with cinnamyl acetates (Scheme 2) [50]. The alkylation products were isolated in nearly quantitative yield and were formed with ratios of branched-to-Unear products up to 99 1 and with enantioselectivities up to 95% ee. In this and subsequent studies with PHOX ligands [51,52], Helmchen et al. demonstrated that the highest yields and selectivities were obtained with a PHOX ligand containing electron-withdrawing substituents and... 

An exciting development has come from work with an iridium catalyst. The use of the complex derived from phosphinoaryloxazoline ligand 149 leads to an efficient alkylation of E-cinnamyl acetate (Eq. 8E.32) [217], It is of note that electron-withdrawing substituents on the phosphorus atom, which are known to be required to give a good regioselectivity in general [218], also increased the enantioselectivity dramatically. 

There is only one example of a catalytic enantioselective cyclopropanation of allylic alcohols using an electron withdrawing chiral disulfonamide 19 as a chiral ligand (Protocol 6).33 Stoichiometric highly enantioselective cyclo-propanations of allylic alcohols are reported using a chiral diethyl tartrate34 and a chiral tartamide.35... 

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