Feringa’s phosphoramidite ligands

Najera et al. have shown that Feringa s phosphoramidite ligand 102 is superior to other ligands in the cycloaddition of aryl iminoesters 62 with tert-butyl acrylate (106), /V-methylphthalimide 114, and diisopropyl fumarate (118).57 As shown in Scheme 2.31 and Table 2.9, the products 116 and 117 were formed in excellent yields and exquisite endo selectivity. 

Scheme 5.9 Hydrovinylations of (a-alkylvinyl)arenes with an in situ generated nickel catalyst derived from Feringa s phosphoramidite ligand.

The above powerful methodology was applied to the synthesis of both steroid C20 (S ) and C20 (R) derivatives from the corresponding 1,3-dienes 8 and 9 derived from two prototypical steroids, estrone and 3-epiandrosterone. By the proper choice of ligands between Feringa s phosphoramidite ligand and another phosphoramidite ligand (S,S)-10, the authors showed that it was possible to install with complete stereoselectivity either the C20 (i ) or C20 (S) configuration. As shown in Scheme 5.12, the nickel-catalysed... 

Feringa and co-workers applied chiral phosphoramidite ligand (S,R,R)-67 in the conjugate addition of dimethylzinc to acyclic unsaturated malonates 68 and obtained up to 98% ee (Scheme 22).71... 

The enantioselective conjugate addition of dialkylzinc to nitroalkenes using other phosphoramidite,79,79a 83a sulfonamide,84 and binaphthol-based thioether ligands65 has also been studied in the past few years. Particularly noteworthy are the efficient chiral monodentate phosphoramidite ligands (S,R,R)-29 and (A,A)-55 developed by Feringa et al. and Alexakis et al., respectively, for this reaction. (S,R,R)-29 provided excellent enantioselectivities (up to 98% ee) for acyclic nitroalkenes (Scheme 25).80 It also worked well for other nitroolefin substrates such as 3-nitrocoumarin 7068 and methyl 3-nitropropenoate 7185. 

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

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