Stereomutation mixture

In the 7,7 -diacetylenic series it has recently been shown that no all-trans isomer can be detected in the iodine catalyzed stereomutation mixtures examined by HPLC of alloxanthin (31) and 7,8,7, 8 -tetra-dehydroastaxanthin (34) diacetate, in which the 9,9 -di-cis isomers are dominant (76). However, in the absence of iodine aW-trans (31) and all-trans (34) diacetate are rather stable. In the monoacetylenic series exemplified by diatoxanthin (41) and the diacetate of 7,8-didehydroasta-xanthin (80), appreciable amounts of the aW-trans isomers are present in the iodine catalyzed stereomutation mixture 76,89). Again the preference for cw-configuration is probably caused by both steric and electronic factors. 

Reduction of the diazaphospholines (151) by trichlorosilane yields a mixture of cis- (Ra = H, R3 = Ph) and trans- (R2 = Ph, R3 = H) phosphines, the lack of stereospecificity being attributed to changes in a pentaco-ordinate intermediate. Stereomutation of the starting oxide is brought about by hexachlorodisilane or silicon tetrachloride.118... 

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. 

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. 

Ethyl(methyl)carboxymethylsulfonium bromide (4) was resolved into optical enantiomers by Pope and Peachey (1900), and since that time a large number of optically pure sulfonium salts have been obtained by resolution of racemic mixtures or by stereospecific syntheses. Chiral sulfonium salts can suffer stereomutation at sulfur by three major mechanisms (Scheme 2) (i) pyramidal inversion, (ii) reversible dissociation into the sulfide... 

When there is a second stereogenic center in the molecule, stereomutation of the sulfoxide center yields a diastereomer, rather than an enantiomer. Kagan extended this concept to the supramolecular case and found that use of a chiral naphthalene derivative as sensitizer induces a modest enantiomeric excess in racemic sulfoxide substrates [78]. A unimolecular case was Kropp s phenyl norbornyl sulfoxide. Though other photochemistry accompanied the stereomutation vide supra), a ratio of 2 3 for 110 to 155 was obtained on photolysis in THF. Another product in that mixture that is important to this discussion is the isomer 156, found in small yield. 

There are at least two fundamentally different mechanisms which may come into play for photochemical stereomutation on direct irradiation. First, there is a-cleavage followed by recombination. The presence of 156 in the above reaction mixture is very strong evidence for just such a process. The work of Guo et al. made that mechanistic assumption in determining the quantum yield of a-cleavage ( 0.4) for aryl benzyl sulfoxides, as the quantum yield for loss of optica] rotation was taken for the quantum yield of cleavage [60]. This is supported by the fact that homolytic cleavage is also the mechanism for thermal racemization of the same compound [71]. 

Direct irradiation of 280 (X, = 277 nm) produced a mixture of 90% 280 and 10%. of its diastereomer 281 [139]. The ratio did not change with further irradiation, but the mixture gradually decomposed due to an additional photochemical reaction. This was apparently not a true photostationary state, since irradiation of 281 produced a 77 23 mixture which also gradually decomposed. It is ambiguous whether this stereomutation is due to a-cleavage and recombination or another process not involving actual bond scission. 

Conversion of an acetylenic compound to a trans alkene is achieved with sodium or lithium and liquid ammonia though this reduction is not usually as simple as that using Lindlar s catalyst. Alternatively the cw-alkenes can be converted to raw5-alkenes by stereomutation (Section 10.9) and the trans isomer isolated from the equilibrium mixture by crystallization and/or silver ion chromatography. 

It is more usual, however, to treat the readily available cis isomer with a reagent which establishes the cis trans equilibrium and to isolate the trans isomer from this mixture by silver ion chromatography (Section 4.6) or by crystallization (Section 4.1). The higher melting trans acid is less soluble than its cis isomer. The reagent should promote stereomutation without double-bond migration or hydrogen transfer. 

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