Atropisomeric biphenyl

The most classical examples of atropisomerism, biphenyls, fall into this category. They form enantiomers because the two benzene rings are not coplanar and both rings are substituted unsymmetrically so that the plane passing through the pivot bond and one of the benzene rings cannot be a a plane. If we consider the conformations of biphenyls in more detail, we recognize that there are two diastereomeric conformations possible, as depicted in Scheme 3 for a compound... 

F. Leroux, Atropisomerism, biphenyls, and fluorine A comparison of rotational barriers and twist angles, ChemBioChem 5(5) (2004) 644-649. 

Next, other unsaturated carbocyclic systems are discussed, such as dibenzo-cyclo-heptadienes ( atropisomeric biphenyls), dihydropleiadenes, cycloheptatrienes and their benzo-derivatives. Most of these compounds exist in a half-boat or boat conformation. Tropones are considered in the light of recently published work. 

Lloyd-Williams, P., Giralt, E. Atropisomerism, biphenyls and the Suzuki coupling peptide antibiotics. Chem. Soc. Rev. 2001, 30,145-157. Dupont, J., de Souza, R. F., Suarez, P. A. Z. Ionic Liquid (Molten Salt) Phase Organometallic Catalysis. Chem. Rev. 2002, 102, 3667-3691. Hassan, J., Sevignon, M., Gozzi, C., Schulz, E., Lemaire, M. Aryl-Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction. Chem. Rev. 2002, 102, 1359-1469. 

Wolf, C., Konig, W. A. and Roussel, C. (1995) Influence of substituents on the rotational energy barrier of atropisomeric biphenyls - Studies by polarimetry and dynamic gas chlomatography. Liebigs Ann., 781-786. 

There is a difference between biphenyl- and 1,3-butadiene systems with respect to symmetry Atropisomeric biphenyl compounds, because of their dihedral symmetry, need a specific substitution pattern to be chiral. In contrast, nonplanar, helical butadienes belong to the point groups C2 or Cj and are chiral without bearing specific substituents. 

Lloyd-Williams P, Giralt E (2001) Atropisomerism, biphenyls and the Suzuki coupling peptide antibiotics. Chem Soc Rev 30 145-157... 

Diphosphine diversity was also exploited by atropisomeric biphenyl ligands. An interesting approach toward water solubilization was disclosed for one of these BINAP-type diphosphines (Scheme 1, MeOBIPHEP-S) [12] (cf. Section 3.2.1). The indolylsulfonyl group withstands the Grignard reaction and phosphine oxide re-... 

A heavily functionalized atropisomeric biphenyl derivative (designed for use as liquid crystal dopant) has been recently synthesized, although in low yield, with Suzuki coupling as the key step [40], The coupling reaction is complicated by rapid hydrolytic deboronation of the sterically crowded electron-deficient boronate ester 55. Rigorously anhydrous conditions are required to avoid the deboronation step (Scheme 3.24). 

With the purposes of structure simplification and reactivity enhancement, further optimization led to a series of catalysts of the type 36-38 by replacing the rigid and highly lipophilic binaphthyl moiety with flexible and more polar straight-chain alkyl groups (Figure 12.9) [68-70]. In addition, the modification of the electronic and steric properties of atropisomeric biphenyl backbone could lead to the development of new, efficient C2-symmetric chiral phase-transfer catalysts 39 [71], 40 [72], and 41 [73] with conformationally fixed biaryl unit core, which were found to be quite effective for the asymmetric alkylation reactions. 

On page 132, atropisomerism was possible when ortho substituents on biphenyl derivatives and certain other aromatic compounds prevented rotation about the bond. The presence of ortho-substituents can also influence the conformation of certain groups. In 88, R= alkyl, the carbonyl unit is planar with the trans C=0 - F conformer more stable when X=F. When X=CF3, the cis and trans are planar and the trans predominates. When R = alkyl there is one orthogonal conformation but there are two interconverting nonplanar conformations when R=0-alkyl. In 1,2-diacylbenzenes, the carbonyl units tend to adopt a twisted conformation to minimize steric interactions. " ... 

Glausch, A., Nicholson, G.J., Eluck, M., Schurig, V. (1994). Separation of the enantiomers of stable atropisomeric polychlorinated biphenyls (PCBs) by multidimensional gas chromatography on Chiraldex. J. High Res. Chromatogr. 17, 347-349. 

MeOBIPHEP is the atropisomeric diphosphine 2,2,-bis(diphenylphosphino)-6,6 -dimethoxy-l,-l -biphenyl (100), has been synthesized. In the presence of SnCl2, this species is an efficient catalyst for the asymmetric hydroformylation of styrene. Asymmetric inductions are higher than those attainable using the system [PtCl2 (i )-(+)-BINAP ]/SnCl2, where BINAP is 2,2 -bis(di-phenylphosphino)-l,l,-binaphthyl. The influence of CO and H2 partial pressures on the catalytic activity of the (99)/SnCl2 system has also been studied.328 Complexes [PtMeCl(P-P)][(101), P-P = (5)-6,6,-(dimethoxybiphenyl)-2,2,-diylbis(diphenylphosphine) ((5)-MOBIPH) (102),... 

Considerable attention has to be directed to the subsequent removal of the chiral 4,5-dihy-drooxazole auxiliary. Due to the presence of only three orffto-substituents, mild reaction conditions are essential in order to prevent atropisomerization in the biphenyl products, i.e., careful hydrolysis12 (TFA H20/Na2S04) or reductive cleavage10. 

Schurig, V., and A. Glausch, Enantiomer Separation of Atropisomeric Polychlorinated Biphenyls (PCBs) by Gas Chromatography on Chirasil-Dex. Naturwissenschaften, 1993 80, 468-469. 

It is remarkable that a biphenyl unit in combination with a chiral amine 11 plays a role of an alternate binaphthol, inducing atropisomerism and giving ethylcyclohexanone in 96% ee [13]. Alexakis also succeeded in his search for efficient copper salts and solvents and reported the combination of CuTC (copper thiophene-2-carboxylate) and ether as a suitable choice. It is also noteworthy that trapping of the resulting zinc enolate with TMSOTf gave a TMS enolate 26, which is a useful intermediate for further synthetic manipulation [26]. Tandem... 

O-Alkylation leads to derivatives in which rotation around Ar—Ar bonds is impossible, since the O-alkyl groups cannot pass each other. Hence, the single diphenol units become chiral and the macrocycle may be considered as resulting from R or S configured atropisomeric subunits. These compounds may also be regarded as inherently chiral since in a linear analogue the biphenyl unit can racemize not only via a cisoid transition state, where the O-Y groups have to pass each other (the only possibility in the macrocycle) but also via a transoid transition state. 

Other brominated compounds of environmental concern are also chiral. Polybrominated biphenyls, like PCBs, were used as capacitor fluids in mixtures of congeners (e.g. Fire-master), and are also atropisomeric [4]. While HBCDD is the most common chiral brominated flame retardant, others exist, such as 2,3-dibromopropyl-2,4,6-tribromophenyl ether (Figure 4.7). As of this writing, little is known about environmental occurrence, fate, and effects of these other chiral flame retardants, and with one exception [5] nothing has yet been published on their enantiomers. 

Schurig, V Reich, S., Determination of the rotational barriers of atropisomeric polychlorinated biphenyls (PCBs) by a novel stopped-flow multidimentional gas chromatographic technique Chirality 1998, 10, 316-320. 

Harju, M.T. Haglund, R, Determination of the rotational energy barriers of atropisomeric polychlorinated biphenyls Fresenius J. Anal. Chem. 1999, 364, 219-223. 

Bucheli, T.D. Brandli, R.C., Two-dimensional gas chromatography coupled to triple quadm-pole mass spectrometry for the unambiguous determination of atropisomeric polychlorinated biphenyls in environmental samples J. Chromatogr. A 2006,1110, 156-164. 

Harju, M. Bergman, A. Olsson, M. Roos, A. Haglund, P, Determination of atropisomeric and planar polychlorinated biphenyls, their enantiomeric fractions and tissue distribution in grey seals using comprehensive 2D gas chromatography J. Chromatogr. A 2003,1019, 127-142. 

Singer, A.C. Wong, C.S. Crowley, D.E., Differential enantioselective transformation of atropisomeric polychlorinated biphenyls by multiple bacterial strains with differing inducing compounds Appl Environ. Microbiol 2002, 68, 5756-5759. 

---