Atropisomerization

It has been shown that aromatic rings of B-ttiaryl-A/-ttiaryl substituted rings are orientated perpendicular to the plane of the bota2iae ring (114,115). If the aryl rings are substituted it is possible to obtain mixtures of cis and trans isomers (atropisomerism) ia which the aryl substituents ate on the same or opposite sides of the plane of the bora2iae ring, respectively (115). 

The axially chiral natural product mastigophorene A (70) was synthesized via a copper-catalyzed asymmetric homocoupling of bromooxazoline 68. Treatment of 68 with activated copper in DMF afforded 69 in 85% yield as a 3 1 mixture of atropisomers. The major atropisomer was converted into mastigophorene A (70) the minor regioisomer was transformed into the atropisomeric natural product mastigophorene... 

Optical activity owing to restricted rotation (atropisomerism) has been demonstrated in two phenylthiophenes 2-(6-methyl-2-nitro-phenyI)-3-thiophenecarboxylic acid (41), which rapidly racemized in solution, and 2,5-dimethyl-4- (6 -methyl-2 -nitrophenyl) 3-thio-phenecarboxylic acid (42), which was optically stable (at room temperature). Recently the first bithienyl, 2,2 -dicarboxy-4,4 -dibromo-5,5 -dimethyl-3,3 -bithienyl (43), has been resolved into optical anti-podes which were optically stable. 

The first examples of macrocyclization by enyne RCM were used in Shair s impressive biomimetic total synthesis of the cytotoxic marine natural product longithorone A (429) [180]. This unique compound features an unusual hep-tacyclic structure which, in addition to the stereogenic centers in rings A-E, is also chiral by atropisomerism arising from hindered rotation of quinone ring G through macrocycle F (Scheme 85). It was assumed that biosynthesis of 429 could occur via an intermolecular Diels-Alder reaction between [12]paracy-... 

Atropisomerism occurs in other systems as well. A sulfoxide (16), for example, forms atropisomers with an interconversion barrier with its atropisomer of 18-19kcal mol . The atropisomers of hindered naphthyl... 

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),... 

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... 

The atropisomerization of the helical configuration entails movement of the C2, C2 - and C7,C7 -groups past one another (Fig. 7.1), and the barrier to this isomerization varies substantially for the different perylenequinones. While the calphostins (4) and phleichrome (5) are atropisomerically stable at room temperature and require temperatures over 110 °C to isomerize, the additional seven-membered ring bridge at the C2,C2 -positions in cercosporin (3) lowers the barrier allowing it to atropisomerize at 37 °C [34]. 

The barrier to atropisomerization is also lower for the hypocrellins due to introduction of the seven-membered ring bridging the Cl,Cl -positions. In fact, hypocrellin A (7) and hypocrellin (ent-1) both exist as rapidly atropisomerizing mixtures of diastereomers at room temperature, as revealed by NMR studies by Mondelli. Here, two sets of sharp peaks of the resultant diastereomers are observed in the NMR spectra of each natural product [35]. Figure 7.2 presents the structures of hypocrellin A (7) and its atropisomer, atrop-1, which exist as an equilibrium... 

See reference [45] for a study of atropisomerization thresholds for model biaryls and perylenequinones. 

While the discovery of this novel D-ring atropisomerism reveals the unique and intricate architecture of these tricycles, it alerted to us the actual alignment of the C3 allyl methyl group in the desired ABD-tricycle 2 and, more importantly, the... 

A new class of phosphines (30) containing only an axial element of chirality (atropisomerism) has been made (253, 254). An in situ 1 1 rhodium/2,2-bis(diphenylphosphinomethyl)-1,1 -binaphthyl system (30a) hydrogenated a-acetamidocinnamic acid to a 54% ee (S) using 50 atm H2, the solvent not being recorded (253). The corresponding diphenyl-phosphinite system (30b) in toluene-acetone was particularly effective (76% ee) for hydrogenation (95 atm) of a-acetamidocinnamic and a-acet-amidoacrylic esters (254). 

Huhnerfuss, H., B. Pfaffenberger, B. Gehrcke, L. Karbe, W.A. Konig, and O. Landgraf. 1995. Stereochemical effects of PCBs in the marine environment seasonal variation of coplanar and atropisomeric PCBs in blue mussels (Mytilus edulis L.) of the German Bight. Mar. Pollut. Bull. 30 332-340. 

Modification of the electronic and steric properties of BINAP, BIPHEMP, and MeO-BIPHEP can lead to the development of new efficient atropisomeric ligands (Figure 1). In fact, Takaya has found that a modified BINAP... 

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