Biphenyls, chirality

Copper-catalyzed systems have been developed that reduce ketones directly to silyl ethers. The reactions involve chiral biphenyl diphosphine type ligands and silane or siloxane hydride donors.187... 

In contrast to binaphthyls, chiral biphenyl derivatives are challenging systems because their twist ability shows a strong dependence on the molecular structure, which does not conform to the empirical correlation rule described above. In fact, homochiral biphenyls 33-40 are characterized by P helicity along the biphenyl axis. In spite of this common feature, the twisting power spans from a highly positive value for 33-45 to a relatively negative value... 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

Interestingly, the hydroformylation results obtained with ligands 2b and 2d, which have conformationally flexible axially chiral biphenyl moieties, are similar to those obtained with ligand 2m, which have conformationally rigid binaphthyl moieties. This indicates that diphosphite ligands that contain the conformationally flexible axially chiral biphenyl moieties predominantly exist as single atropoisomer in the [RhH(CO)2 (diphosphite)] complexes... 

A range of structural combinations has been reported. In the structures presented in Figure 8.23 the first R/S indicator refers to the binaphthyl (biphenyl) bridge and the second to the bisnaphthol (bisphenol) moiety. Thus for 48, which lacks the bisphenol chirality, we write in the table (R,--), and for 50, which contains a non-chiral biphenyl bridge, we write (—,R). 

Recently, Maruoka and coworkers have expressed interest in the development of C2-symmetric phase-transfer catalysts which consist of two chiral biphenyl units, as a new, easily modifiable subunit for further elaboration. To this end, chiral phase-... 

Very recently, Maruoka and co-workers described a new N-spiro quaternary ammonium bromide with two chiral biphenyl structures as easily modifiable subunits [37]. These phase-transfer catalysts with biphenyl subunits, containing methyl groups in the 6,6 -position for inducing chirality, and additionally bulky substituents in the 4-position, efficiently catalyzed the alkylation of protected glycinate with high enantioselectivity of up to 97% ee. The substrate range is broad, for example (substituted) benzyl bromide and allylic and propargylic bromides are tolerated [37]. 

A. di Matteo, S. M. Todd, G. GottareUi, G. Solladie, V. E. Williams and R. P. Lemieux, Correlation between molecular structure and helicity of induced chiral nematics in terms of short-range and electrostatic-induction interactions. The case of chiral biphenyls, J. Am. Chem. Soc., 123 (2001) 7842-7851. 

Chiral biphenyl-2,2 -sulfone-3,3 hisfenchol 436 is synthesized by cyclization of diphenylsulfone with BuLi and subsequent addition of (—)-fenchone 435 (Scheme 70) <2005T10449>. 

Recently, the preparation of the chiral biphenyl (6) and its use as a modifying agent with LAH has been reported." A complex of LAH-(6)-EtOH (1 1 1) at —78°C gives the best enantiose-lectivities in the reduction of prochiral ketones. Similar to Noyori s reagent, use of the LAH complex with (S)-(6) leads to the (S)-alcohol. Enantioselectivity is usually high for aromatic ketones (acetophenone 97% ee, 93% yield). This reagent reduces 2-octanone in higher enantioselectivity (76% ee) than 3-heptanone (36% ee). 

Welseloh, G. Wolf, C. Konig, W.A. New technique for the determination of interconversion processes based on capillary zone electrophoresis Studies with axially chiral biphenyls. Chirality 1996, 8, 441-445. 

Chiral biphenyl-bridged zirconocene dichlorides 1171 and the dimethyl derivative 1172 are obtained by salt metathesis routes according to Scheme 276.908 The reaction of the dimethyl complex with 0.5 equiv. of (i )-binaphthol gives the corresponding binaphtholate 1173. 

The last step is an adaptation of the original protocol (see Cahn3) and the method can also be conveniently applied to chiral biphenyls. 

Consider the case of the first chiral biphenyl to be resolved, one enantiomer of which is shown in 21. To determine the configuration of this enantiomer, one draws a projection formula similar to that previously shown for allenes, but with inclusion of relevant ortho groups this is shown in 22. If one tracks the substituents alphabetically, then the sense of turn between b and c is anti-clockwise, as in 16, and so 22 has S configuration. It is possible to construct molecules that additionally contain substituents at the unsubstituted aromatic carbons of 21 however, any additional substituents are not relevant to the question of atropisomerism. 

Molecules without chirality centers can be chiral. Biphenyls that are substituted can exhibit an axis of chirality. When A B, and X Y, the two conformations are nonsuperimposable mirror images of each other that is, they are enantiomers. The bond connecting the two rings lies along a chirality axis. 

Atropisomerism is significant because it introduces an element of chirality in the absence of stereogenic atoms. Axial chirality is observed with stereoisomers (or atropisomers) that result from hindered rotation about a single C—C or C—N bond. The barrier of rotation between atropisomers must be high enough to allow for their isolation. A minimum of three or/ho-substituents are generally required for an axially chiral biphenyl to have substantial stability toward racemization at room temperature. For general definitions and descriptions, see references [3-5]. 

A classic demonstration of this effect is in the racemization of the chiral biphenyl compound characterized by Mislow and shown in Eq. 8.6. Rotation about the central bond race-mizes the material and forces a severe steric clash between the two methyl groups in the transition state. Indeed, it is found that the deuterio compound racemizes faster than the protio, consistent with the notion that D is effectively smaller than H. The effect is certainly not a large one, as only a 15% difference is seen in a system with a really severe steric interaction and with multiple H/D substitutions. Nevertheless, steric isotope effects can be comparable to other secondary isotope effects, and so should be considered when evaluating experimental data. 

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