Binap backbones

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

Fig. 3.3 The structures of diphosphines with four atoms in the backbone (a) dppb (b) (-)-(R,R)-diop (c) (R)-binap.

In addition to oxygen, the phosphorus can be tied to the backbone through nitrogen. Indeed, this was one of the earliest variations of the DIOP family (see Section 23.3) with PNNP (45) [22, 280, 287]. Care must be taken to avoid hydrolysis of the labile P-N bonds [22, 288]. Other examples of nitrogen-linked compounds are BDPAB (46 and 47) and its derivatives (Fig. 23.4). These ligands are clearly variations of the BINAP series [289-291]. 

The most common chiral auxiliaries are diphosphines (biphep, binap and analogues, DuPhos, ferrocenyl-based ligands, etc.) and cinchona and tartaric acid-derived compounds. It is clear that the optimal chiral auxiliary is determined not only by the chiral backbone (type or family) but also by the substituents of the coordinating groups. Therefore, modular ligands with substituents that can easily be varied and tuned to the needs of a specific transformation have an inherent advantage (principle of modularity). 

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

Fig. 24 Minimized structure of 47 showing the kink in the mPE backbone brought about by the binap moiety...

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... 

The binaphthyl backbone of BINAP has inspired many variations of atropisomeric biaryl bisphosphines. One approach by Roche was to substitute the binaphthyl backbone with a 6,6 -dimethox-ybiphenyl backbone. MeO-Biphep (96a) was synthesized in approximately 26% yield in 6 steps from 3-bromoanisole (97a) (Scheme 12.30). MeO-Biphep can also be synthesized in 5 steps from 2-iodo-3-nitroanisole in approximately 18% yield. Several phosphine analogues can be prepared by the addition of R2PC1 to the lithio intermediate.117... 

The decrease in the dihedral angle of the biaryl backbone had a profound effect on both reactivity and enantioselectivity. It was determined that the catalyst [NH2Me2]+ (RuCl(/ -ScgPIIOS) 2(Li-Cl)3] can hydrogenate 2-oxo-l-propanol to (2R)- 1,2-propanediol in 98.5% ee and with an S/C ratio of 10,000. (2R)- 1,2-propanediol is used in the production of Levofloxacin (see Section 12.2.2.5). The current catalyst used in production is a R-Tol-BINAP-Ru(II) complex.130... 

Several examples of heterocyclic BINAP analogues have been reported which sometimes offer an improved performance in a variety of transition-metal-catalyzed transformations when compared to standard BINAP ligands. In this review, we survey the efforts of developing atropisomeric biheteroaryl backbone-containing bisphosphines, their designing concept, synthetic approaches and some of their important applications. 

A chiral bisphosphine that is analogous to BINAP but that contains a biferrocenyl backbone has been obtained by optical resolution of the corresponding phosphine oxide [22]. 

Application of this cyclization reaction to a large variety of 4-pentenals with the aid of the rhodium complex has been reported. The first example of an asymmetric cyclization of 4-pentenals via hydro acylation using a chiral rhodium diphosphine catalyst was published by Sakaki et al. in 1989 [ 104]. The diphosphine ligand ((lS,2S)-rraws-l,2-bis(diphenylphosphinomethyl)cyclohexane) having a cyclohexane backbone in the chiral center shows the better asymmetric induction than DIOP ligand. Various types of enals are applicable to this asymmetric intramolecular hydro acylation reaction [105,106]. The use of BINAP ligand as the chiral auxiliary improves the optical yield to >99% ee when 4-substituted 4-pentenals are used as the substrate (Eq. 49) [106]. Steric repulsion between the substituent at the 4-position and the substituent on the phosphine atom controls the enantiofacial selection. 

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