Phosphoramidite-based Catalysts

The first application of a copper-catalyzed conjugate addition of diethylzinc to 2-cyclohexenone, using chiral phosphorous ligand 12, was reported by AlexaHs (Fig. 7.1) [35]. An ee of 32% was obtained. 

It appears from these early studies that modest to rather high yields and enan-tioselectivities can be achieved with structurally very diverse chiral ligands. Furthermore, both relatively hard (amino alcohols) and soft (thiols, phosphines) ligands 

With these catalysts (3 mol%), prepared in situ from Cul or CuOTf and ligand 14, the following observations were made  

Use of ligand 15, with a sterically more demanding diisopropylamine moiety, further increased the enantioselectivity. 

Another significant improvement, resulting in better catalyst solubility and slightly enhanced ee values, was found when Cu(OTf)2 was used. The ease of handling of Cu(OTf)2, compared to that of CuOTf, is a major advantage for applications of this catalytic system in synthesis. The copper)11) complex is most probably reduced in situ to a copper(I) complex, which functions as the actual catalyst. 

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Platinum catalysts are also effective for the silaboration of 1,3-dienes.234 Although almost no stereoselectivitiy is observed in the silaboration of acyclic 1,3-dienes, 1,3-cyclohexadiene undergoes the stereoselective silaboration in fair yields (Equation (87)). Enantioselective silaboration of 1,3-cyclohexadiene has been achieved with 70% ee by using a platinum catalyst bearing a binol-based optically active phosphoramidite ligand.235... 

A number of structurally very different copper complexes were employed as catalysts. The copper complex of binaphthol-derived phosphoramidite 32 and the Schiff base complex 53 (derived from salicylaldehyde and phenylglycine) gave promising results in a screening reaction between 52 and MeMgBr, and 53 was chosen as the candidate for optimization. The effect of solvent (THF or Et20),... 

The synthesis of pure metalacycle la from [Ir(COD)Cl]2 and LI requires only amine base and heat, followed by precipitation and removal of amine hydrochloride. However, this complex was typically generated in situ during early studies by the treatment of a combination of [lr(COD)Cl]2 and LI with an amine base, such as uPrNH2, l,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), or l,8-diazabicyclo[5.4.0] undec-7-ene (DBU). If a 1 1 ratio of iridium to ligand is used, a mixture of la and [Ir(COD)Cl]2 is produced. Helmchen et al. have reported that catalyst activation in the presence of tetrahydrothiophene (THT) prevents coordination of the k -phosphoramidite [71]. 

Generally, alkoxides are problematic nucleophiles because of their basic character. In metal-catalyzed allylic substitutions, superior results were obtained with Zn-alkoxides (achiral Ir-catalysts) [66] and Cu-alkoxides (achiral Rh-catalyst with chiral substrates) [67]. Shu and Hartwig developed aUyUc substitutions with alkoxides using Ir/phosphoramidite catalysts [68] these authors used catalysts obtained from [Ir(COD)Cl]2 and LI or L3 without explicit base activation [procedure (a) in Section 9.2.4.2) (Scheme 9.34). 

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