2-Methyl-3- atropisomerism

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. 

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... 

K. Therefore, the chloro group in compound 124 (M = Si) raises the barrier more than did the methoxycarbonyl group in 125, when the skeleton is 9,10-dihydro-9,10-ethenoanthracene. As expected, when the skeleton was changed from dihydroethenoanthracene to triptycene, the barrier was raised. Thus 9-trimethylsilyl-l,4-dimethoxytriptycene (126) did not show coalescence of the methyl signals, although the solution was heated to 180°C. The barrier to rotation was thus estimated to be in excess of 25 kcal/mol. In order to confirm the indication from NMR spectroscopy that atropisomerism of this type should be... 

Desymmetrisation of the enantiotopic methyl groups of 432 with a chiral lithium amide base leads to atropisomeric amides in good enantiomeric excess.186... 

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. 

Due to the still functionalized methyl groups, the stable atropisomeric alcohols 109 could be separated from each other unusually well, before their transformation to the methyl compounds 23a and 23b. 

Furusho et al. reported on a series of atropisomeric 4-methyl-3-(2 -methoxy-l -naphthyl)pyrrole-2-carboxylates. The enantiomers were obtained by crystallization of the diastereoisomers of the (R)-phenethyl ester and further hydrogenolyse. An X-ray of the isolated diastereomer allowed the determination of the absolute configuration. The (S) antipode of the free acid presented a positive CD curve at 231 nm. The acid was applied in the predetermined synthesis of a chiral atropisomeric porphyrin 213 (Figure 12) (94JCS(CC)653). 

Atropisomeric thioureas were assayed in organocatalyzed enantiose-lective cyanosilylation of aldehydes (06TA999). 3-(2-Aminophenyl)-4-methyl-thiazoline-2-thione (397e) was the starting material to prepare a series of bis-(N-aryl) atropisomeric triads such as l,2-bis-[4-methyl-2-(thi) oxo-2,3-dihydrothiazol-3-yl] -benzene (09CFH160). 2-Arylimino-3-arylthia-zoline derivatives showed atropisomerism (02ARK(x)72, 08JOC403). 

The quinazolinone structure is found in many biologically active compounds methaqualone, mecloqualone, piriqualone, afloqualone, and so on. Methaqualone (MQ, 470), 2-methyl-3-(2-methylphenyl)quinazolin (3H)-one, an hypnotic and anticonvulsive drug, is one of the leading examples of atropisomeric six-membered N-aryl heterocycles. Methaqualone gives stable atropisomers at room temperature due to the three substituents in ortho positions of the N-aryl rotating bond. 

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