Solvolyses of 17‐(tosyloxy)androstanes in hexafluoroisopropyl alcohol – an example for extreme reactivity differences without the occurrence of nonclassical intermediates

Schneider, Hans‐Jörg; Becker, Norman

doi:10.1002/cber.19861190108

Cited by 5 publications

(2 citation statements)

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“…The center of the debate was the solvolysis rate of 2‐exo norbornyl derivatives which was considered to be exceptionally fast, and the much smaller reactivity of the endo‐isomer . The steroids 1a , b and 2a , b show that such rate differences are by no means restricted to norbornyl esters . The rate difference, measured in hexafluoroisopropanol (HFIP), between the 17 α /17‐ ß ‐tosylates exceeds those of exo/endo‐2‐norbornyl compounds even by an order of magnitude, with an up to 30.000‐fold rate enhancement (Scheme and Table ).…”

Section: Systems With Large Reactivity Differences Close To or Exceedmentioning

confidence: 99%

The controversy about nonclassical ions: Finished too early?

Schneider

2018

J of Physical Organic Chem

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The debate on nonclassical ions centered almost exclusively on the behavior of 2norbornyl esters. The hallmark of a nonclassical charge distribution in solvolysis reactions was always seen in the seemingly exceptional fast reaction of the 2-exoderivatives, with slow rates of the endo-esters. While the nonclassical bridged structure of the free norbornyl ion has been unequivocally established, possible steric contributions to the rate differences in solution remained a matter of debate. Many formerly used solvents were less suited to exhibit uniform reaction mechanisms; the most appropriate solvent hexafluorisopropanol was introduced rather late. Solvolysis rates of many cyclic esters including medium rings can be predicted by force field calculated strain energy differences ΔSI sp3/sp2 between sp 3 and sp 2 states. Large deviations from the correlation are observed for 2-tosyloxy norbornane-and for 17-tosyloxy steroids; they indicate that both nonclassical charge delocalization and steric hindrance play a major role for the reactivity differences. These reach an unprecedented rate constant ratio of >30.000 between, eg, the 17-steroid epimers, much larger than the ratio of 1.550 in 2-norbornyl reactions. The presence of alkyl groups or hydrogen antiperiplanar to the leaving group can lead to extreme reactivities by 1,2-shifts or Wagner-Meerwein rearrangement if asymmetric bridged transition states can occur which approach the stability of tertiary cations.The long controversy about nonclassical ions illustrates how progress in science can deviate significantly from the ideal pathways lined out by Karl Popper.

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Section: Systems With Large Reactivity Differences Close To or Exceedmentioning

confidence: 99%

The controversy about nonclassical ions: Finished too early?

Schneider

2018

J of Physical Organic Chem

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“…The rearranged product itself rearranges when it is treated with collidine and methylsulphonyl chloride in dimethylformamide that is saturated with sulphur dioxide to give the 5a-methyl-6ketone (78), providing a convenient new method for introducing the 5a-methyl group into the steroid nucleus (Scheme 13).…”

Section: Molecular Rearrangementsmentioning

confidence: 99%