Biaryl axis

Figure 7.15 Chirality transfer from dopant to solvent. Chiral inducer with an (M)-helidty aligned with its biaryl axis parallel to biphenyl axis of solvent can have close contact only with molecules of solvent having same helicity Chirality is therefore transferred from dopant to near solvent molecule and from this to next near one and so on, via chiral conformations.

Contrary to most allocolchicinoids which lack a C-ll substituent, compounds 78 and 80 show stable axial chirality. The above study constitutes the first example in the allocolchicinoid series where both configurations at the biaryl axis can be obtained from a given stereochemistry at C-7. In the natural alio series, free rotation around the biaryl axis is often possible at room temperature, and the configuration of the biaryl axis is controlled by the stereochemistry at C-7 due to conformational constraints in the C-ring [14]. While several total enantioselective syntheses of colchicine address the control of the stereochemistry at C-7 [106], no direct enantioselective synthesis of natural allocolchicines has been reported to date. ... 

Further studies described the interconversion of stegane diastereoisomers via thermal (for the biaryl axis) or acid/base-induced (for the a-lactone position) processes, Fig. (18) [110,111,112], These isomerization possibilities were largely exploited in the different total syntheses discussed in the following pages. 

This synthetic plan, which initially involved an efficient asymmetric biaryl synthesis, suffered from two weaknesses, namely in the manipulation of configurationally fragile intermediates and in the epimerization at the biaryl axis during the decarboxylation step. These... 

This synthesis resolved one of the issues encountered in the Meyers synthesis, i. e. the epimerization of configurationally labile intermediates, since in this case the rotation around the biaryl axis is precluded by the presence of the bulky chromium tricarbonyl group. 

These extensive SAR studies have shown that the rigid biaryl/nine-membered lactam structure of rhazinilam adopting a boat-chair conformation is an essential feature for its antimitotic properties. Moreover, the absolute aR configuration of the biaryl axis is, as in the allocolchicine and stegane series, absolutely required for biological... 

Recently, the anti-HIV alkaloids michellamines A (4) and B (5) have attracted much attention. The tetraaryl skeleton of the michellamines is constructed by first forming the inner (nonstereogenic) biaryl axis and then adding the two other (stereogenic) axes by means of a double Suzulci-type cross-coupling reaction between binaphthalene ditriflate (2) and iso-quinolineboronic acid (3) (Eq. (13)) [31]. 

Restricted rotation about the biaryl axis as a result of bulky substituents leads to the existence of atropisomers. Depending upon the degree of steric hindrance due to the ortho substituents, three or four substituents are needed to produce a sufficient barrier to rotation at room temperature. This particular form of axial chirality is not generally resistant to heat. To produce acceptable yields of hindered biaryls under Suzuki conditions, high temperatures (60-110 °C) [78, 85] and reaction times of several hours are required. In atropisomer-selective reactions, these conditions would be deleterious to the discrimination between dia-stereomeric transition states and could racemize the biaryls formed. As a consequence, it is necessary to carry out such Suzuki reactions at ambient temperature. Recently, conditions employing Pd(OAc)2 and 95 % ethanol were used to generate mono-ortho-substituted biaryls at 20 °C (Eq. (54)) [86],... 

The benzannulation reaction further allows the concomitant generation of an axial and chiral plane in a single reaction step (Scheme 28) [68f]. The diastereomeric ratio of the benzannulation products depends on the protocol used for phenol protection. Thus, in situ protection gives the kinetic ratio of 74a 74b — 11 89, whereas a two-step benzannulation/ protection sequence results in thermodynamic control to give a ratio of 74a 74b >99 1. These results can be explained in terms of a possible or arrested rotation around the biaryl axis in the benzannulation product before protection to give either 74a or 74b. 

High-performance liquid chromatography (HPLC) techniques have been used lately for enantiomeric separations of benzazocine having a chiral biaryl axis <1998TA3497> and in analytical methods for purity determination <1996JME669, 1997JME1578, 2000JME2362>. 

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