Conformation interconversion

Fischer S, P D J Groothenuis, L C Groenen, W P van Hoorn, F C J M van Geggel, D N Reinhoudt and M Karplus 1995. Pathways for Conformational Interconversion of CaUx[4]arenes. Journal of the American Chemical Society 117 1611-1620. 

In addition to constitution and configuration, there is a third important level of structure, that of conformation. Conformations are discrete molecular arrangements that differ in spatial arrangement as a result of facile rotations about single bonds. Usually, conformers are in thermal equilibrium and cannot be separated. The subject of conformational interconversion will be discussed in detail in Chapter 3. A special case of stereoisomerism arises when rotation about single bonds is sufficiently restricted by steric or other factors that- the different conformations can be separated. The term atropisomer is applied to stereoisomers that result fk m restricted bond rotation. ... 

Molecules that are chiral as a result of barriers to conformational interconversion can be racemized if the enantiomeric conformers are interconverted. The rate of racemization will depend upon the conformational barrier. For example, -cyclooctene is chiral. E-Cycloalkenes can be racemized by a conformational process involving reorienting of the... 

Fig. 1. 13C-NMR fast exchange-slow exchange transition for the conformational interconversion of cyclododecane in solution of propane-d, (left side) and in the solid by CP-MAS techniques (right side) at 75.47 MHz. The temperature decreases from top to bottom as indicated at the spectra. Chemical shifts are given at the signals and refer to TMS = 0 ppm. (Ref.7))...

Fig. 3a and b. Fast exchange-slow exchange NMR transition for the conformational interconversion of octamethyltetrasiloxane. a, MAS 13C-NMR solid state spectra on the left side in comparison to solution spectra in propane-di on the right side (at 75.47 MHz), b. MAS 29Si-NMR spectra at 59.63 MHz. Temperatures are indicated in K, shift positions refer to TMS = 0 ppm and correspond to the scale at the bottom. (Ref. I0))... 

X-ray crystallography and variable temperature H NMR studies show that the conformation of the coordinated imidazolidin-2-ylidene, in both the neutral and cationic complexes 70, is anti, anti with respect to the Ph of the backbone of the NHC, exclusively in the solid state and predominantly in solution at lower temperatures (-75°C). At room temperature in solution, possible conformer interconversion by the rotation around the phenyl-N bond of the NHC substituent is apparent from the broadness of the peaks in the NMR spectra. Hydrosilylation of acetophenone by Ph SiH catalysed by 70 at room temperature or at -20°C results in maximum ee of 58%. However, at lower temperatures the reaction rates are much slower [55]. 

It is worth noting that whilst we have restricted discussion in this section to conformational interconversion based on the slow rotation of bonds, the concept of the NMR timescale is equally applicable to other types of interconversion, such as can sometimes be seen in cyclic systems which may exist in two different conformational forms. 

Fig. 7 Correlations between the two OC-O torsional angles x and 2 for acyclic C-O-C-O-C systems [6]. The ellipsoidal curve marks the suggested pathway for conformational interconversions. Reprinted from Cosse-Barbi and Dubois (1986), copyright 1986, with kind permission from Pergamon Press Ltd, Headington Hill Hall, Oxford 0X3 OBW, UK.

The annulation evidently proceeds much more rapidly than conformational interconversion of the intermediate cations. For example, the annulation of ( )-3-methyl-3-penten-2-one 88 with allene 89 leads to acetylcyclopentene 90 as the sole reaction product in 71% yield (Eq. 13.28) [32]. The stereochemical relationship of the two methyls is preserved in the product. When the reaction is repeated with (Z)-3-meth-yl-3-penten-2-one 91 (Eq. 13.29), acetylcyclopentene 92 is isolated as the major product, along with a small amount of 90 [32]. 

Intriguingly, the conical intersection model also suggests that E,Z-isomerization of acyclic dienes might be accompanied by conformational interconversion about the central bond, reminiscent of the so-called Hula-Twist mechanism for the efficient ,Z-photo-isomerization of the visual pigment rhodopsin in its rigid, natural protein environment101. A study of the photochemistry of deuterium-labelled 2,3-dimethyl-l,3-butadiene (23-d2) in low temperature matrices (vide infra) found no evidence for such a mechanism in aliphatic diene E,Z -photoisomerizations102. On the other hand, Fuss and coworkers have recently reported results consistent with the operation of this mechanism in the E,Z-photoisomerization of previtamin D3 (vide infra)103. 

Photochemical d.s jraw.v-confonnational interconversion is also known to occur in larger polyenes. Brouwer and Jacobs have reported the results of irradiation of E- and Z-2,5-dimethyl-l,3,5-hexatriene (14) in argon matrices at 10 K108. Irradiation of the -isomer gives rise to various retainers, while irradiation of the Z-isomer results only in ,Z-isomerization. Photochemical translcis conformer interconversion has also been observed for , -1,3,5,7-octatricnc in matrices at temperatures below 10 K32. 

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. 

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