Atropisomerically chiral ligand, BINAP

Whereas the simple bidentate nitrogen ligands proved to be rather limited, the frequent occurrence of a set of four P-phenyl or alkyl substituents, e. g., in coordinated Binap, MeO-Biphep, Josiphos or Duphos (shown, from left to right in Scheme 1.4), offered many more reporters . In this way, one can develop a more detailed NOE picture of how the complexed substrate interacts with the chiral pocket offered by these auxiliaries. From these NOE studies [97, 98] it can be shown that the atropisomeric bidentate ligands Binap and MeO-Biphep tend to have fairly classical axial and equatorial P-phenyl substituents. 

Atropisomerism, the phenomenon of chirality due to restricted rotation about a single bond, has been an intellectually intriguing and practically widely applicable area of stereochemistry from the first resolution of a chiral atrop-isomeric biaryl by Kenner in 1921 through the discovery of numerous naturally occurring atropisomeric molecules and the development of atropisomeric chiral ligands. A high point in the history of atropisomerism must be the central role played by the atropisomeric ligand BINAP in Professor Noyori s share of the Nobel Prize for Chemistry in 2001. 

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

This reaction has lent itself to the development of its asymmetric version (Scheme 88). The trick here is to remove the choride ligands from the coordination sphere of the platinum-chiral ligand complex. This makes the metal center more electrophilic, thus reactive reactions can be run at lower temperature. Interestingly, the best ligand was found to be the atropisomeric monophosphine (fJ)-Ph-BINEPINE.312 Enantiomeric excess up to 85% was observed. Very recently, enantioselectivity up to 94% ee has been achieved using [(AuCl)2(Tol-BINAP)] as pre-catalyst for the reaction of another enyne.313... 

The reaction is quite sensitive to the chiral ligand used. Diphosphines with an axially disymmetric biaryl moiety in the backbone give the best results. The effectiveness of p-Tol-BINAP as ligand, for example, is similar to that of BINAP. The related atropisomeric ligand BIPHEMP can also be used [9]. Among chiral aliphatic diphosphines tested, CyDIOP, which only differs from DIOP in the type of P-substituents, also gives satisfactory results. 

When coordinated to the metal, the chiral ligand plays an important role in the control of enantioselectivity during the course of the catalysis reaction. These ligands can contain chirality in the backbone (e.g.. CHIRAPHOS, 1), at the phosphorus atom (e.g., DIP AMP, 2), or atropisomerically from C2 symmetric axial configurations (e.g., BINAP, 3). Typically, most chiral ligands possess di-phenylphosphine moieties (Figure 1). 

The discovery of the chiral atropisomeric ligand, BINAP, greatly expanded the number of asymmetric homogeneous hydrogenation catalyses. Rhodium and ruthenium complexes that contain BINAP and similar ligand systems have demonstrated an amazing versatility in the reduction of a wide variety of substrate classes in excellent stereoselectivities and reactivities. (-)-Menthol, a variety of... 

In 1980, Professor Noyori and the late H. Takaya consequently designed and synthesized a bidentate phosphine ligand BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthyl) 5, that contained an atropisomeric l,l -binaphthyl structure as a chiral element for use in transition metal catalyzed asymmetric hydrogenation reactions (Figure 1). 

In a third form, the cross-coupling process forms a biaryl compoimd that possesses axial chirality as a result of slow atropisomerism (Equations 19.22 and 19.23). " In most cases, this reaction has been studied for the formation of 1,1 -binaphthyls (Equation 19.22), which are found in BINAP, BINOL, and related ligands. In a fourth form, ttie Heck reaction has been conducted in a manner that forms a product containing a new stereocenter (Equations 19.24-19.26). This type of enantioselective coupling has been the most widely used of the four in the synthesis of natural products. ... 

Bidentate Phosphorus Ligands Supported on Atropisomeric Biaryl Backbones. Most ligands of this group contain binaphthyl or biphenyl moieties-providing an axial element of chirality. The flagship of this class of compounds is the atropisomeric diphosphane BINAP (36), whose complexes (primarily Ru(II) complexes (37)) play a pivotal role in asymmetric scale-up hydrogenations and isomerizations (Fig. 5). 

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