Cyclopropanes stereomutations

The latest theoretical treatment of cyclopropane stereomutations predicts270 that k, and ki2 are about equal for cyclopropane and for 1,2,3-d3-cyclopropanes, in fair agreement with an experimental value k,.kn - 1.0 0.2 determined with C,d3-labeled cyclopropanes166. 

While there remain open questions on a few experimental aspects of early work on the stereomutations of 1 -phenyl-2-d-cyclopropanes and 1,2-d2-cyclopropanes, the preponderance of data and theory now provides a consistent understanding of the thermal stereomutations of cyclopropanes multiple paths and three types of diradical transition structures are involved. Evolving theory relevant to cyclopropane stereomutations and to vinylcyclopropane to cyclopentene isomerizations, and to other 1,3-carbon shifts283 288, may well provide more detailed insights, rationales and predictions. 

I thank the National Science Foundation for support of our work on cyclopropane stereomutations, now through CHE-9100246, and the coworkers and colleagues who have contributed so invaluably to our studies in this area. 

Ab initio MRCI calculations showed that the barrier from trimethylene to propene is 7.9kcalmol 1 higher than that from trimethylene to cyclopropane.11 Thus, cyclopropane stereomutation may occur through trimethylene as an intermediate (Chart 3). Trimethylene biradical may cyclize by double rotation of the two C C bonds in conrotatory or disrotatory fashion or successive single rotation. The calculations showed that the PES at the... 

The classical trimethylene diradical model for cyclopropane stereomutations featured a deep potential energy well for the intermediate and internal rotations about 10 times faster than ring closure Improved experimental estimates for the heat of formation for the singlet trimethylene diradical, and for the energy required for the isomerizations of l,2-d2-cyclopropanes, place the diradical in an extremely shallow energy well, one on the order of only 1 kcal moP deep The classical model can never accommodate k + k. k i ratios less than 2, and several substituted cyclopropanes exhibit such ratios. Thus the model, at least in its original form, seems thermochemically flawed and unable to accommodate experimental data for some systems. 

Hrovat, D. A. Fang, S. Borden, W. T. Carpenter, B. K. Investigation of cyclopropane stereomutation by quasiclassical trajectories on an analytical potential energy surface, ... 

The ultimate test of the theoretical predictions for the mechanism of cyclopropane stereomutation would be to use an optically active disubstituted cyclopropane in which the substituents were just isotopes of hydrogen. This is a challenging problem both from a synthetic standpoint and from an analytical one. The analytical difficulty is particularly acute because one has to analyze a small, volatile molecule for both optical purity and cis-trans isomer ratio, and both measurements have to rely solely on the difference between isotopes. There are no functional groups to be used as handles for an optically active NMR shift reagent and so determination of optical purity must come from direct measurement of rotations—with a probable maximum specific rotation of < 1 ° ... 

As usual, the singly subscripted rate constants refer to one-center epimerizations and the doubly subscripted rate constants refer to two-center epimerizations at the carbons indicated by the numbers. There should, in principle, be a secondary deuterium isotope effect included in the mechanistic rate constants comprising but this would have its largest effect on k 2 and 23 and the previous experience in cyclopropane stereomutations suggests that these are likely to be minor contributors at best. 

It is interesting to note that if a similar phenomenon were to apply to cyclopropane stereomutation, one would expect inversion of configuration at both ends of the breaking C-C bond giving a stereochemistry in accord with the observations for cyclopropane-1,2-d2 (Section III. A. 3). Stabilization of the trimethylene biradical might place it in a potential... 

Thermal deazetization of pyrazolines results in the formation of cyclopropanes and alkenes, illustrated in Figure 44 for the parent compound (18). This reaction is of interest in that one could imagine that it would involve the same trimethylene biradical (19) proposed to be an intermediate in cyclopropane stereomutation (Section III.A). Supporting this notion is the observation that the parent pyrazoline gives 89% cyclopropane and 11 % propylene at 250° C. If one took this product ratio as a reflection of the branching ratio from a common trimethylene intermediate, it should then be possible to compare these figures with the relative rates of stereomutation and propylene formation from cyclopropane-d2 . Interestingly, they are identical. 

Additional work needs to be done to develop a theoretical model to represent the trimethylene kinetics. The dynamics in the trimethylene region of the potential energy surface is neither statistical nor direct, and instead contains both these elements. Future work on the kinetics of cyclopropane stereomutation will include developing a theoretical model for trimethylene s dynamics, assessing the accuracy of assuming RRKM dynamics for cyclopropane, and determining a more accurate PES for trimethylene. 

Investigation of Cyclopropane Stereomutation by Quasiclassical Trajectories on an Analytical Potential Energy Surface. 

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