Atropisomerization substituted

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 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... 

An important application of an isomerisation is found in the Takasago process for the commercial production of (-)menthol from myreene. The catalyst used is a rhodium complex of BINAP, an asymmetric ligand based on the atropisomerism of substituted dinaphthyl (Figure 5.5). It was introduced by Noyori [1],... 

Mechanistic Studies of Thermal and Photoinduced Atropisomerization of Substituted Tetraphenyl Porphyrins in Solution and Organized Assemblies... 

The present paper reviews our study of the thermal and photochemical atropisomerization of a number of "picket fence (substituted TPP) porphyrins. The study of the thermal atropisomerization with a number of different free-base and diacid "picket fence porphyrins indicates that the thermal process likely involves a simple rotation around the porphyrin-phenyl bond in which ruffling of the porphyrin ring can assist but is not prerequisite ... 

An intriguing feature is that the previously unknown bisindoles 154 display atropisomerism as a result of the rotation barrier about the bonds to the quaternary carbon center. With the use of A-triflyl phosphoramide (1 )-41 (5 mol%, R = 9-phenanthryl), bisindole 154a could be obtained in 62% ee. Based on their experimental results, the authors invoke a Brpnsted acid-catalyzed enantioselective, nucleophilic substitution following the 1,2-addition to rationalize the formation of the bisindoles 154 (Scheme 65). 

Modification of the electronic and steric properties of BINAP, BIPHEMP, and MeO-BI-PHEP led to the development of new efficient atropisomeric ligands. Although most of them are efficient for ruthenium-catalyzed asymmetric hydrogenation [3], Zhang et al. have recently reported an ortho-substituted BIPHEP ligand, o-Ph-HexaMeO-BIPHEP, for the rhodium-catalyzed asymmetric hydrogenation of cyclic enamides (Scheme 1.2) [31]. 

The possibility of optical isomerism arising from restricted rotation (atropisomerism) about the 2,2 -bond in 3-substituted 2-(2-naphthyl)-benzo[6]thiophenes has been recognized by Lamberton and McGrail.54 Schuetz and Ciporin164 have interpreted the UV spectra of six 3-aryl-benzo[6]thiophenes according to a theory of steric hindrance to free rotation about the pivot bond of the two aromatic rings, but the results are now invalid, since some of the 3-arylbenzo[6]thiophenes used in this study have been shown to be the corresponding 2-isomers (see Section IV, C). No attempt appears to have been made to resolve compounds of this type. 

Diastereo- and enantio-selectivity in nucleophilic aromatic substitution is limited to atropisomerism in binaphthyl- and biaryl-forming reactions.21-42... 

Attempts to induce asymmetry in the cyclisation of 57 using the chiral lithium amides, which had worked well with simple benzamides, were frustrated by the inherent chirality, at low temperature, of the naphthamide itself. This feature is common to all 2-substituted tertiary aromatic amides, which may become atropisomeric at low temperature due to slow rotation about the Ar-CO bond.48 We therefore sought to... 

Atropisomerism has also been observed for the dipyridyl substituted naphthalene 50, which can exist in syn- and anti-forms, using FI NMR spectroscopy <1996T8703, 1996JOC7018>. While the ratio of the two forms varies with the temperature and the solvent used, each form is present in approximately equal quantities. Computational studies at the AMI and PM3 levels were required to determine that the predominant isomer was the anti-form, with the... 

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... 

Direct synthesis of atropisomeric benzamides and anilides from prochiral precursors has been reported using chiral-amide-mediated deprotonation of 2,6-dimethyl-substituted ben-zamide and anilide chromium complexes. A screening of amides revealed that (R,R) 3 was the most selective in the deprotonation of the benzylic methyl groups (Scheme 51)92 94. 

The introduction of chirality into the NHC framework follows diffoent principles than that of traditional phosphane ligands. Whaeas phosphanes are conically shaped [1] ligands with a tet-rahedrally coordinated central phosphorus atom, NHC are planar disc-like ligands based on the aromatic imidazole system (see Chapter 1). It follows that phosphanes are asymmetric owing to a stericaUy active and stable lone pair, whereas the chirality in the traditionaT NHC defines itself through a peripheral chiral element This element can be an asymmetric atom (central chirality), an axial chiral element (an atropisomeric binaphthyl substiment) or planar chirality (double substitution on an aromatic ring system, planar chiral substituent). Combinations of these three types of chirality are possible and can be realised in a more or less facile protocol. 

As an extension of this chemistry, the [3+2] cycloaddition reaction of new atropisomeric 4-dialkylamino-5-chloro-l,2-dithiole-3-thiones 130 and DMAD or its diethyl analogue has been utilized to give thioacid chlorides 131 (Scheme 13) <20030L929>. These have been converted into thioamides 132 with 2 equiv of pyrrolidine (or morpholine) by substitution of the 5-chloro substituent and phthalimide ring opening. Similar reactivity toward 1 or 2 equiv of pyrrolidine was noted for 130, which was obtained according to the general method described. 

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