Atropisomers enantioselective

Characterization of enantiomer composition in the food web demonstrated enantioselective detoxification of POPs, including PCBs, in cetaceans. In the Bering-Chukchi-Beaufort Sea area, bowhead whales Balaena mysticetus) had nonracemic amounts of some chiral PCBs, while their Calanus zooplankton prey had racemic levels [189]. Given the simpUcity of the bowhead whale food chain, these observations indicate that these cetaceans had biotransformed PCB atropisomers enantioselectively. The EEs of PCB 91 were significantly correlated with body length in males only, while those of PCBs 95 and... 

The first use of non-biaryl atropisomers as chiral ligands in metal-catalyzed reactions was reported with ligand 21 [83] (Fig. 2). The allylic alkylation of 19 gave 20 in good enantioselectivity (90% ee) although in moderate yield (60%). Comparable results (89-99% yield, 90.2-94.7% ee) were obtained with 22 which possesses only axial chirality [84],... 

A number of new oxaziridinium epoxidation reagents have been reported. A new axially chiral epoxidation catalyst 4 has been reported <070BC501>. These catalysts, as are others, are converted to an oxaziridinium with Oxone, which then epoxidizes the olefin. This study examined several chiral groups on the nitrogen as well as both atropisomers. The (S,F)-isomer 4 provided the (1R,2R) epoxide with moderate enantioselectivity and 82% conversion. The (.V,A/)-isomcr of 4 provided the (lS,2S)-epoxide in slightly lower enantiomeric excess (76%) and lower conversion as well. 

Haglund, R, Enantioselective separation of polychlorinated biphenyl atropisomers using chiral high-performance liquid chromatography J. Chromatogr. A 1996, 724, 219-228. 

Kania-Korwel, L Hrycay, E.G. Bandiera, S.M. Lehntier, H.-J., 2,2, 3,3, 6,6 -Hexachlorobi-phenyl (PCB 136) atropisomers interact enantioselectively with hepatic nticrosomal cytochrome P450 enzymes Chem. Res. Toxicol 2008, 21, 1295-1303. 

Enantioselective Reduction of Imines. Oxazaborolidine (3) also enantioselectively reduces A-substituted ketimines to the corresponding A-substituted amine in low to moderate ee (eq 8, Table 3). In this case the enantioselectivity is the same as the reduction of ketones thus the (5)-oxazaborolidine catalyst gives (R)-amines. Oxazaborolidine (3) is reported to provide higher enantioselectivity than oxazaborolidine (6). An interesting application of this reaction is the preparation of a (a/ 5,5) diastereomerically enriched (63% de) sample of the more active atropisomers of the herbicide Metalochlor (eq 9)... 

The first enantioselective total synthesis of the 7,3 -linked naphthylisoquinoline alkaloid (-)-ancistrocladidine was accomplished by J.C. Morris and co-workers. The key steps of the synthesis were the Pinhey-Barton ortho-arylation and the Bischier-Napieralski cyclization. The natural product was isolated from the 1 1 mixture of atropisomers by recrystallization from toluene/petroleum ether. 

During the two decades after this important discovery, a tremendous amount of research has been directed toward the polymerization of sterically demanding achiral monomers with chiral initiators to create enantiomerically pure helical polymers (also known as helix-sense selective or screw-sense-selective polymerization ). These polymers, known as atropisomers, are stable conformational isomers that arise from restricted rotation about the single bonds of their main chains. Key aspects of these reactions are enantiopure initiators that begin the polymerization with a one-handed helical twist, and monomers with bulky side-chains that can maintain the helical conformation due to steric repulsion. Notable examples of this fascinating class of polymers that are configurationally achiral but conformationally chiral include [8, 38, 39] poly(trityl methacrylate), polychloral, polyisocyanates, and polyisocyanides. Important advances in anionic and metal-based enantioselective polymerization methods have been reported in recent years. 

One of the most studied polymerization systems employs alkyllithium initiators that are modified by chiral amine ligands for the polymerization of sterically bulky methacrylates [8,38,39,40,41], acrylates [42],crotonates [43], and acrylamides [44]. A primary example is the reaction of triphenylmethyl methacrylate with an initiator derived from 9-fluorenyllithium and (-)-sparteine (3) at -78 °C (Scheme 4). The resultant isotactic polymer is optically active, and is postulated to adopt a right-handed helix as it departs from the polymerization site. This polymer has been particularly successful as a chiral stationary phase for the chromatographic resolution of atropisomers [8]. Many modifications of the or-ganolithium initiator/chiral ligand system have been explored. Recently, Okamo-to has applied enantiopure radical initiators for the enantioselective polymerization of bulky methacrylate monomers [45]. 

Of the 209 PCB congeners, 78 display axial chirahty in their nonplanar conformations. Kaiser predicted that of these atropisomers (as these conformational isomers are known), the 19 congeners with three or four ortho chlorine atoms exist as pairs of stable enantiomers at ambient temperatures as a result of restricted rotation about the C-C biphenyl bond. The enantiomeric composition may give information about the enantioselective biodegradation of organochlorine compounds. ... 

Asymmetric induction (See also Enantioselective) chiral ketones, 62, 106-107 chiral sulfoxides, 8-9 steroid synthesis, 27, 278-281 Asymmetric syntheses. See Enantioselective. .. Asymmetry of vesicle membranes, 351 dATP. See 2 -Deoxynucleoside 5 -triphosphates Atropisomers binap chelands, 102-103 Kemp s acid arylimides, 347 porphyrin oligomers, 348—349 5,10,15,20-tetraarylporphyrins, 253 Axial/equatorial stereoselectivity ... 

Atropisomers of l,l -bis(diphenylphosphanyl)-3 -dimethyl-lH, l H-2,2 -biindole (BISCAP, 165) and l,P-bis(diphenylphosphoryl)-3,3 -dimethyl-lH,l H-2,2 -biindole (BISCAPO) were prepared and resolved to participate in a study of the electronic influence of the biheteroaryl groups on the hganding properties in metal assisted enantioselective catalysis (97JOM(529)445). 

Fuji et al. separated the atropisomers of 277 on Chiralcel OD-H at the preparative scale. CD spectra were recorded but the absolute configuration was not established. Reduction of each atropisomers afforded axially chiral NAD(P)H models that were engaged in the enantioselective reduction of methyl benzoylformate (95% ee) (92JCS(CC)905). 

Figure 3 (A) ID GC separation of PCBs on a DB-5 column and (B) enantioselective MDGC separation of CBs 153 and 105, and the atropisomers of CB 132 in a sediment extract [8]. The arrow in frame A indicates the position of the fraction transferred to the chiral column.

In contrast to the Rh-catalyzed asymmetric intramolecular direct C—H bond functionalization reactions described above, their asymmetric inter-molecular variants have been rarely explored. In 2000, Murai and co-workers reported a Rh-catalyzed intermolecular asymmetric C—H activation/olefin coupling reaction of achiral biaryl pyridine (132) or isoquinoline derivatives to deliver axially chiral biaryls (133) (Scheme 5.46a). Although both the efficiency (up to 37% yield) and the enantioselectivity (up to 49% ee) of the reaction were only moderate, this protocol provided an alternative method for the synthesis of optically active biaryl compounds. To some extent, this reaction was similar to a formal dynamic kinetic resolution. The two atropisomers of the biaryl starting materials could interconvert with each other freely due to a low inversion energy barrier. A properly chosen chiral catalyst could react preferentially with one atropisomer. The increased steric bulkiness of the final alkylated products can prevent the epimerization and the biaryl compounds possessing a stable axial chirality are established. However, due to the relatively low efficiency of the catalyst, the yields of the desired products are generally low and the starting materials can be recovered (Scheme 5.46b). 

Jorgensen et al. reported on enantioselective electrophilic additions to allylic C-H bonds activated by a chiral base, in a reaction of allylidene cyanoacetates or malononitriles with DBAD, catalysed by (DHQ)2PYR, giving y-aminated products in high yield (up to 90%) and excellent enantioselectivity (up to 99% ee). Ye et al. described y-amination of a,p-unsaturated acyl chlorides with azodicarbojylates, catalysed by O-trimethylsilylquinidine (O-TMS-QD) or O-trimethylsilylquinine (O-TMS-Q) to give dihydropyri-dazinones in up 92% yield, and up to 99% ee. Jorgensen s group also reported on asymmetric Friedel-Crafts amination of 2-naphthols with DBAD, to afford nonbiaryl atropisomers in up to 98% ee. ... 

In looking at vancomycin and teicoplanin, the hydroxyls are but one choice for functionalization reactions. Each natural product also possesses electron-rich arenes, which may be platforms for electrophilic aromatic substitution reactions. In parallel studies of enantioselective and atropisomer-selective bromination reactions [161-164], we were gaining experience with catalyst-controlled bromina-tions, and we wondered whether these might be extended to site-selective reactions. We speculated that an appropriately positioned Lewis base, such as a dimethyl amide unit, could assist in the delivery of electrophilic bromine... 

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