Westphalen rearrangement

In the early days of steroid chemistry, dehydrations were usually carried out under rather drastic conditions, frequently in the presence of strong acids (see, for example, ref. 176, 181, 182). Such conditions have been replaced by milder and more selective methods, except in those instances when either the product is stable e.g. ref. 183, 184) or rearrangement is desired. The importance of stereochemical factors in rearrangements is widely recognized for instance, the Westphalen rearrangement of 5a-alcohols (92) cf. ref. 185,... 

Scheme 30 Bi(0Tf)3-vH20-catalyzed Westphalen rearrangement of 5(3,6(3-epoxysteroids...

Despite the uncertainty surrounding the mechanism of the Westphalen rearrangement for which both the involvement of a carbocation intermediate [121] and a concerted mechanism [122] have been thought, it is evident from the available data that electronic (electron-withdrawing capability of a substituent... 

The well-known Westphalen rearrangement [8 ] of cholestane-3 S,5c(,6 S-diol, 3,6-diacetate (i) to give the 5j f-methyl-A -oiefin (2) [86] has received considerable study. 

Despite the foregoing account of the specific need for an electronegative 6ji -substituent in the Westphalen rearrangement, comparable reactions involving migration of the C(i9)-methyl group to an electron-deficient C(5> have been reported in other special situations. 

A normal Westphalen rearrangement occurred in the 19-methylene derivative (387), giving the 5j8-ethenyl (vinyl) product (388). Migration of the ethenyl... 

A retro-Westphalen rearrangement occurred when the 10) -fluoro-5) -methyl-7j -ol (396) was treated with boron trifluoride, to abstract fluoride ion. The product was the 4-en-7)3-ol (397). Contrasting behaviour when a 10)8-hydroxy-group was eliminated by acid treatment, reported last year to give a backbone-rearranged A -olefinic compound, requires an explanation. The most obvious difference in the reactants, apart from the different 10)8-leaving... 

The 10 -ethyl derivative (552) undergoes Westphalen rearrangement 5.3 times more rapidly than the 10/5-methyl compound, probably indicating 10 8-alkyl participation in ionisation at C-5. The need for such alkyl participation explains the failure of 5j8-hydroxy-steroids to undergo Westphalen rearrangement. 

Sterols and Related Products - The Westphalen rearrangement of some JP-substituted-bp-acetoxy-5Q -hydroxycholestanes has been studied and the products and kinetics shown to be dependent on the nature of the 5-substituent. The conformations of the products were studied and in the case of the Westphalen-Lettre derivatives it was shown that ring B is in the boat conformation. The boron trifluoride catalyzed cleavage of 30 -acetoxy-4a,5-epoxy-5Ci -cholestane afforded the expected backbone rearrangement products containing a 15(17) doable bond." A similar experiment with 5Q -acetoxy-5,ba-epoxy-5o -cholestane yielded some of the rearranged derivative XW after a reaction time of 25 seconds, along with the e q)ected isomer " ... 

Angular methyl migrations of this type have been observed in the heterolyses of 5a-substituted steroids, a process known as the Westphalen rearrangement 234), As an example, the nitrous acid deamination of diacetoxy amine 148 is shown below 235), The presence of an electronegative substituent in the 6P-position is apparently usually a prerequisite for the Westphalen rearrangement. 

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