Privileged Ligands

A subsequent Pd-catalyzed coupling reaction with diphenylphosphine oxide produces mainly the monophosphorylated product. Reduction of the phosphine oxide with silane followed by hydrolysis of the ester group produces a hydroxy phosphine. The final condensation with (S)-binaphthophosphorchloridite affords (R,S)-BINAPHOS. In the same way, enantiomeric (S,R)-BINAPHOS was prepared. Both were the first in a series of chiral ligands used in target-oriented 

(R)-BIPNITE, a mixed phosphine-phosphinite, was developed for target-oriented hydroformylation within the framework of fi-lactams [21]. It 

In general, such diphosphites are prepared in moderate to good yields by condensation of 2 equiv of the corresponding phosphorchloridite with chiral diols in the presence of a base such as NEtj (see also Section 2.2.3). Alternatively, atropiso-meric bromidites (e.g., ((/ )-BlPHEN) bromidite) have been utilized for the phosphorylation reaction [46]. 

Several aliphatic or aromatic diols were employed for the construction of the backbone, such as l-benzyl-3,4-dihydroxypyrrolidine-2,5-dione, enan-tiopure binaphthols or achiral biphenols, brenzcatechol, aliphatic diols, or spiro[4.4]nonane-1.6-diol (see also Section 2.2.2) [44-47]. Three-carbon bridged diols proved to be more effective compared to two-carbon or four-carbon bridged analogs, which has been explained by a counterproductive fluxional behavior in the corresponding rhodium complexes [48]. Diphosphites based on 1,3-diphenylpropane also produced iirferior enantioselectivities in comparison to the 2,4-pentanediol backbone of Chiraphite. For the design of both side arms, it was concluded that a diphosphite based on the unsubstituted biphenol is less suited 

The requisite enantiopure biphenol (5 )-BIPHEN-H2 can be purchased or it can be prepared in-house from 3,4-dimethylphenol by alkylation with isobutylene, followed by I 2Cr207-mediated oxidative coupling. The final resolution of diastere-omeric (-)-menthyl phosphates has been elaborated in 50 scale by Schrock and coworkers [51]. After reaction with PCI3, the produced phosphorchloridite was condensed with 2,2 -biphenol to produce (S.Si-Kelliphite. 

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FIGURE 15.1 Design elements for chiral metal complexes and some privileged ligand classes (with selected examples). 

Structures of Ligands Generating Highly Selective Catalysts ( Privileged Ligands )... 

CHART 5.1 Chiral privileged ligand and metal sources commonly employed in the catalytic enantioselective alkylation of electron-rich arenes. 

Table 2.3 Comparison of typical regio- and enantioselectivities of model substrates with privileged ligands.

Phenylpropanoids The regio- and stereoselective hydroformylation of P-aryl-propenes (aryl propanoids) gives access to several flavoring compounds (see Section 6.1) [46]. Cobley and Clarke [47] screened privileged ligands for this... 

Wang and Buchwald [2, 58] generated chiral P-formyl esters from a-alkyl acrylates by taking benefit from Keulemans rule. Remarkably, all privileged ligands developed for AHF induced poor results. The optimal catalyst identified was based on the P-chiral diphosphine (R,R)-BenzP (Scheme 4.83). In order to achieve full conversion, a fivefold excess of H2 in comparison to CO was necessary. These structures can be found in inhibitory agents owned by Pfizer and Roche, respectively. 

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