Why do cations violate Baldwin's rules?

For example, the following acetalization mechanism is plausible even though it contains a 5-endo-trig step: enter image description here

Image taken from: Clayden, J. Organic Chemistry; Oxford University Press: Oxford, 2013


The acetal formation in question is actually an example of a 5-endo-trig cyclisation, which, according to Baldwin's rules should be unfavourable.

The first thing to realise about Baldwin's rules is that they are largely empirical, that is, based on observation of data rather than theoretical proof (though they can be rationalised based upon orbital overlap arguments).

The second thing to realise is that, as with any rule, there are many exceptions.

From Wikipedia: Baldwin's rules discuss the relative rates of ring closures of these various types. These terms are not meant to describe the absolute probability that a reaction will or will not take place, rather they are used in a relative sense. A reaction that is disfavoured (slow) does not have a rate that is able to compete effectively with an alternative reaction that is favoured (fast). However, the disfavoured product may be observed, if no alternate reactions are more favoured.

The 5-endo-trig acetal formation is actually one of the most well known exceptions to Baldwin's rules (Baldwin himself acknowledged this).

In an 1981 JOC paper (J. Org. Chem. 1981, 46, 2196), Mike Perkins and Jack Barrett attempted to understand why it was that these acetalizations were so 'favourable'.

Using very basic computational methods (MNDO methods), they studied the energy needed in order to get the molecule into the correct conformation for the hydroxyl to attack the oxonium (this is the ring closing step, and the one which you might expect to he the disfavoured step).

The conclusions of the paper are that the barrier is actually much smaller than expected, making formation of the acetal acceptable, in spite of baldwin suggesting otherwise.

  • $\begingroup$ Is there any suggestion why the activation energy is much smaller than expected? Cations violate the rules frequently, some intrinsic property has to account for that. $\endgroup$
    – EJC
    Sep 3 '16 at 20:27
  • $\begingroup$ Read the paper and see what you think. And well, oxoniums are activated species. They're intrinsically more reactive which will overcome some of the geometric issues $\endgroup$
    – NotEvans.
    Sep 3 '16 at 20:39
  • $\begingroup$ Okay, I see they made a correlation between torsion barrier of the double bond and the feasibility of the 5-endo-trig process. Could you add in your last sentence "torsion" before "barrier"? $\endgroup$
    – EJC
    Sep 3 '16 at 21:12

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