Biaryls, chiral BINAP

The hydrogenation of allylic alcohols and a,/>-unsaluraled acids leads to products with a very high synthetic potential, and both transformations were used quite early for industrial applications. In both cases Ru complexes with axially chiral biaryl ligands (binap analogues) are the catalysts of choice. Here, we will dis-... 

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. 

The highly efficient stereoselective transformations catalyzed by transition metals that contain BINAP have resulted in extensive efforts in the development of both new Ru-BINAP catalysts and chiral atropisomeric bisphosphines based on biaryl backbones and biheteroaryl backbones.49 Coupled with the various classes of Ru(BINAP) catalysts and chiral bisphosphines, the number of efficient industrial asymmetric hydrogenations are sure to increase because optimization for fine precision and easy optimization in catalyst activity and enantioselectivity made easier.57 66... 

These mirror images (enantiomers) are not superimposable and so the allene is chiral. Similarly, some biaryl compounds such as this important bisphosphine known as BINAP (we come back to BTNAP in Chapter 45) exist as two separate enantiomers because rotation about the green bond is restricted. 

Asymmetric synthesis of chiral biaryls is a very attractive notion, since some such compounds, e.g., BINAP, have served as useful chiral ligands. In this sense, the synthesis of (/ )-2,2 -dimethyl-l,r-binaphthyl in 63% yield and in 83% ce using Br2Ni(PPFOMe) as a catalyst is noteworthy L175] (Scheme 1-48). 

The chiral biaryl bisphosphine ligand SEGPHOS 34, developed by Takasago, possesses a smaller dihedral angle than BINAP. The ligand has provided greater enantioselectivity over BINAP in Ru-catalyzed hydrogenation of a wide variety of carbonyl compounds.31... 

Arylboranes with aryl bromides and iodides Coupling of arylboranes with aryl bromides and iodides offers an extremely useful synthetic method for biaryl compounds, and numerous examples are known. Asymmetric S-M aryl-aryl coupling of 33 with 34 in the presence of chiral 2-aminobinaphthyl-based phosphine (S)-VI-8 afforded the highly enantiomerically enriched biaryl 35 (92 % ee), which was converted to the axially chiral l-aryl-2-naphthylphosphine 36. BINAP is not an effective ligand for this asymmetric reaction [51]. 

Axially chiral biaryls are an important class of molecules primarily because of their biological activity, as well as their use as chiral ligands. Although enantioselective cyclotrimerization of 1,6-diynes with alkynes or nitriles catalyzed by transition metals has been developed, it was difficult to realize the intermolecular cross-cyclotrimerization process with three alkynes. However, a cationic Rh-complex with (5)-H8-BINAP was found to catalyze effectively the regioselective and enantioselective intermolecular cross-cyclotrimerization of two alkynes 392 and 394 to give chiral biaryls 395 with 89-96% ee in good yields (Scheme 2-35). ... 

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. ... 

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. 

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