Atropisomeric interconversions

Liquid-Crystalline Solvents as Mechanistic Probes The Properties of Ordered Chiral Media That Influence Thermal and Photochemical Atropisomeric Interconversions of l,l -Binaphthyl... 

Atropisomerism occurs in other systems as well. A sulfoxide (16), for example, forms atropisomers with an interconversion barrier with its atropisomer of 18-19kcal mol . The atropisomers of hindered naphthyl... 

In the first of four chapters in this volume of Topics in Stereochemistry, Michinori Oki presents a comprehensive review of atropisomerism with special reference to the literature of the past two decades. The review summarizes restricted rotation about sp2-sp2, sp2-sp, and sp3-sp3 bonds and it concludes with an analysis of reactions of isolated rotational isomers. It places particular emphasis on the magnitude of rotation barriers as a function of structure (incidentally identifying some of the largest barriers yet measured to conformer interconversion) and on the isolation of stable single-bond rotational diastereomers. 

The broad and nearly universal applicability of the cinchonan carbamate CSPs for chiral acid separations is further corroborated by successful enantiomer separations of acidic solutes having axial and planar chirality, respectively. For example, Tobler et al. [124] could separate the enantiomers of atropisomeric axially chiral 2 -dodecyloxy-6-nitrobiphenyl-2-carboxylic acid on an C-9-(tert-butylcarbamoyl)quinine-based CSP in the PO mode with a-value of 1.8 and Rs of 9.1. This compound is stereolabile and hence at elevated temperatures the two enantiomers were interconverted during the separation process on-column revealing characteristic plateau regions between the separated enantiomer peaks. A stopped-flow method was utilized to determine the kinetic rate constants and apparent rotational energy barriers for the interconversion process in the presence of the CSP. Apparent activation energies (i.e., energy barriers for interconversion) were found to be 93.0 and 94.6 kJ mol for the (-)- and (-l-)-enantiomers, respectively. 

We have investigated various factors which contribute to solvent-induced partial resolution or race-mization of 1,1 -binaphthyl (BN). Only photochemical interconversions of BN conducted in cholesteric mesophases influenced the steady state concentration of atropisomers. Thermal equilibriun in cholesteric media or photochemical interconver-sions in chiral isotropic solvents did not alter appreciably the atropisomeric ratio of initially racemic BN. Solvent order accelerates the rate of BN thermal racemization. A discussion of the physical properties of the solvents and BN responsible for the observations is presented. 

In each mesophase mixture, the dominant atropisomer after photo or thermal resolution experiments was S(+). The sole exception occurred during irradation of a 3% BN solution in mixture C. Since the sample solidified partially during the experiment, the mechanism by which the R(-) atropisomer arose is unclear. The thermal lability of the atropisomers toward interconversion and the possible contribution of cholesteric contaminants in recovered BN samples make an accurate assessment of atropisomeric excess a formidable task. Extreme care was taken to handle all solutions containing BN during work-up at temperatures which preclude significant thermal racemization at 25°C, the half-life for racemization is ca. 10 h in normal isotropic solvents all manipulations were conducted at 4°C or below. 

Photochemical experiments with BN in cholesteric and optically active isotropic phases. Photoinduced interconversions of BN atropisomers are in competition with thermally induced racemization at the temperatures of our experiments. Thus, the observed rotations reflect lower limits to the actual atropisomeric pho-... 

Atropisomerism occurs in other systems as well, including monopyrroles. Sulfoxide 16, for example, forms atropisomers with an interconversion barrier with its atropisomer of 18-19 kcalmoP. The atropisomers of hindered naphthyl alcohols, such as 17 exist as the ip-atropisomer (17a) and the ap-atropisomer (17b).Atropisomers can also be formed in organometalhc compounds, such as the bis(phosphinoplatinum) complex (see 18), generated by reaction with R-BINAP (see p. 1801). ... 

It is possible to isolate isomers in some cases, often due to restricted rotation. In 9,10-bis(trifluorovinyl)phenanthrene (19) torsional diastereomers (see p. 163) are formed. The value of K for interconversion of 19a and 19b is 0.48, with AG° = 15.1 kcalmol. The ability to isolate atropisomers can depend on interactions with solvent, as in the isolation of atropisomeric colchicinoid alkaloids, which have been isolated, characterized, and their dichroic behavior described. ... 

As it can be seen, lUPAC definition covers more situations than the present review that is restricted to biphenyl heterocyclic analogues. Natta and Farina (72M11) offer an interesting discussion on this subject (they used the term atropisomerism, also found in the old references). In the authoritative book by Eliel et al. (94MI1), Chapter 14-5 is devoted to biphenyls atropisomerism. They report that this type of enantiomerism was discovered by Christie and Kenner in 1922 (22JCS614) in the case of 6,6 -dinitro-2,2 -diphenic acid (1) that they were able to resolve. It was later called (33MI1) atropisomerism. An important aspect of all the concepts related to a barrier is (we quote) It is immediately obvious that the term suffers from all the problems discussed previously How slow must be the interconversion of the enantiomers (i.e., how long is their half-life) before one speaks of atropisomerism At what temperature is the measurement to be made Does atropisomerism still exists when isolation of stereoisomers becomes difficult or impossible but their existence can be revealed by NMR (or other spectral) study and so on. ... 

The occurrence of these two forms is an indication of the high barrier around the Aryl-N bond. The B-trichloro analogue did not display diaste-reoisomerism in the condition of the study (90 MHz NMR and 0 °C). The isomeric B-tri-o-tolyl-N-triethylborazin showed atropisomerism and the interconversion barrier was determined at 50 C AG ds trans = 107 kj... 

The stereochemical implications of hindered rotation in non-planar molecules, termed atropisomerism, have intrigued chemists since 1921, constituting a challenge in drug discovery. In particular, atropisomerism opens new ways for DKR processes by exploiting the interconversion of atropisomeric unstable... 

Atropisomerism of the telenzepine molecule results from highly hindered rotation about the C—N-bond, forming a stereogenic axis. In neutral aqueous solution, the atropisomer interconversion half-life is of the order of 1000 years. The resolution of both enantiomers of... 

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