Atrop isomers

The axial chirality of the atropisomeric oxalic acid derivatives 57a, Z) according to Brewster also can be classified as helicity. (/ )-()-N,N,N, N -Tetramethyl-dithiooxamide 31a then constitutes one of the smallest molecular helices, the enantiomers of which have been separated semipreparatively using liquid chromatography 

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Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

Dih symmetrical porphyrins such as porphin itself,7 H2TPP and H2OEP9 are conveniently prepared from pyrrole and aldehyde by cyclocondensations (Scheme 1). Addition of Zn11 ion often improves the yield.10 The product is often contaminated with chlorin by-product, which can be converted to porphyrin by oxidants such as DDQ,10 or separated by chromatography.11 Bulky substituents tend to lower the yield, and meso o-substituted phenyl groups give rise to atrope isomers. 

The steric requirements of the tetramesityl porphyrin ligand are likewise determining the optimal geometry of the transition states in these reactions. Therefore, it was consequent to look for a chiral porphyrin ligand which could add enantioselectivity to the processes already described. Simonneaux et al. [370] have synthesized a set of chiral porphyrins derived from the four atrop-isomers of tetrakis(o-aminophenyl) porphyrin, H2(ToAPP), by acylation with (R)-( + )-a-methoxy-a-trifluormethylphenylacetyl chloride. This mixture of chiral porphyrins H2(P ) was metallated with Ru3(CO)i2 in o-dichlorobenzene and the resulting chiral isomers of RuCO(P )THF separated by thin layer... 

The chiral center most frequently encountered is the asymmetric carbon atom, a tetrahedral C atom, bonded to four different substituents. Chiral centers of this type are known for many other elements (4). However, chiral centers are also found in other polyhedra, e.g., the metal atoms in octahedral compounds containing three bidendate chelate ligands. Chirality axes, present in the atrop isomers of ortho-substituted biaryls, occur in coordination chemistry in appropriately substituted aryl, pyridyl, and carbene metal complexes. Well known examples of planar chirality in organometallic chemistry are ferrocenes, cymantrenes, and benchrotrenes containing two different substituents in 1,2- or 1,3-positions relative to each other (5-5). 

Chiral molecules with an axis of dissymmetry (atrop isomers) can also be stereochemically resolved on the CTA-ICSE The resolution and pharmacological testing of the enantiomers of methaqualone illustrate this type of application (44). Methaqualone (Fig. 3) is a quinazolinone derivative that possesses hypnotic and anticonvulsive activities. The molecule exists in two enantiomeric forms, M(+) and M(—), due to the hindered rotation around the N-phenyl bond. Mannschreck et al. (44) were able to partially resolve this compound using the CTA-I CSP to optical purities of 0.75 for the (+) isomer and 0.68 for the (—) isomer. The anticonvulsive activity of the two enantiomers was evaluated by the mouse electroshock test, and the (—) isomer was found to be significantly more potent than the (+) isomer. 

Solutes containing asymmetric sulfur atomes or asymmetric phosphorous atoms can be resolved v/ith or without an aromatic moiety in the molecule. For example, the anticancer drug ifosfamide, an oxazaphos-phorane not containing an aromatic moiety, has been resolved on this type of CSP (73). In addition, these are excellent CSPs for the resolution of enantiomeric molecules with an axis of dissymmetry (atrop isomers) (9-11). 

Ancistrocladus hamatus (Vahl) Gilg is a related climber, found in Sri Lanka. Chemical investigation by Govindachari s group showed that this plant also contains ancistrocladine (1) as the major alkaloid, accompanied by its atrop-isomer, called hamatine (10). Compound 10, on dehydrogenation of its methyl ether, gives an aromatic isoquinoline, enantiomeric to 4, whereas ozonolysis yields the same p-amino acid 3, as ancistrocladine (1) (20,21). 

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