Phenylcyclopropanes stereomutations

The thermal stereomutations of deuterium-labeled phenylcyclopropanes (Scheme 3) were studied in a progressive manner. First, the racemic and both achiral isomers were synthesized to provide material for kinetic work and to verify analytical methods 62. The isomerizations among these three isomers at 309.3 °C were followed using either 2H decoupled H NMR spectroscopy or Raman spectroscopy the two kinetic parameters (k, + k22) = 0.36 x 10 5 s 1 and (k2 + k]2) - 1.07 x 10"5 s 1 at 309.3 °C were measured. Published spectra of both sorts for authentic samples of syn, anti and trans isomers, and of thermal reaction mixtures, provided... 

A complete solution to the kinetic problem was attained through further studies of (2R, 3R)-1,2,3-d3-phenylcyclopropane and (1/ , 2S, 3 R) 1,2,3-d, -phenylcyclopropane-2-13C l6 Reaction mixtures from the first were analyzed by NMR and by Raman spectroscopy, and with the aid of the chiral lanthanide shift reagent Eu(hfc)3 on each derived mixture of deuterium-labeled benzoylcyclopropanes. Concentration versus reaction time data for all four isomers led to k22 = 0 and kx - 0.36 x 10 5 s. From kinetic work based on the l3C, d3-labelled substrate (equation 4) the final distinction between ka and k2 reactions was secured kl2 = 0.20 x 10 5s 1 andk2 0.87 x 10 5 s. Thanks to the 13C,d3 labeling, stereomutations allowed for equilibrations among eight rather than four isomers, and the distinction between k2 and kn products could be made163. 

Other experimental work on the stereomutations of labeled phenylcyclopropanes and of 1,2-d2-cyclopropanes is discussed below. 

One of the nice features of the synthesis used by Berson and Pedersen to prepare optically active trans-cyclopropane-l,2-d2 is that it involved synthesis of optically active trflns-phenylcyclopropane-2-d as an intermediate. It was thus possible from one synthetic sequence to determine not only the mechanism of stereomutation of the dideuterated cyclopropane but also to find out what effect, if any, a phenyl substituent had on the mechanism. 

Person and coworkers followed this study with a related analysis of the stereomutation of phenylcyclopropane-2,3-d2. In this system one can separate 2 from 23 cannot separate ki from ki2- However the two studies together would, in principle, allow complete determination of all of the mechanistic rate constants. In the event, experimental difficulties did not allow this complete dissection of the rate constants. The study did, however, provide an independent measure of /cj, which was found here to be 0.15 x 10" s" again showing correlated double rotation to be by far the dominant process for stereomutation at C(l). 

In fact the results are not quite as dramatically different as they appear when presented this way. The mechanistic rate constants are derived from phenomenological rate constants that can be described as linear combinations of the mechanistic ones. The discrepancy between the two results can be traced to a difference in just one of the phenomenological rate constants—the one corresponding to the first order loss of optical activity for a 1 1 mixture of (1R,25)- and (lR,2R)-phenylcyclopropane-2-d. The peculiar feature of this problem is that the Berson group obtained an internally consistent set of results from two independent experiments with one value for this rate constant and the Baldwin group also obtained an internally consistent set from two independent experiments but with a value that differed by a factor of 2.7 from that found by the Berson group. It is hard to know how to reconcile such results and so, to be objective, one must probably say that despite the immense amount of effort put into the problem the mechanism of stereomutation of phenylcyclopropane remains something of a mystery. 

A careful study of the stereomutation of 2-phenylcyclopropane-l,3-d2-l-carbonitrile by Baldwin and Carter revealed that the reaction could be identified with exclusive cleavage of the bond between the two substituents. Thus the absolute configuration of the CHD carbon (C(3)) did not change, as indicated in Figure 16. 

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