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In Clayden's Organic Chemistry it gives the Houk model as a way for predicting selectivity for alkene reactions where an existing stereocentre is present (diastereoselectivity).

Unlike the description of the Felkin-Ahn model, there is no real description of how the Houk model works, and I can't find this information in March Advanced organic chemistry either.

My feeling is that there must be some stabilising interaction between the pi system of alkene with a sigma orbital on the adjacent carbon, however this doesn't explain why one would be favoured over another.

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  • $\begingroup$ Regarding the question - which parts of the explanation in Clayden is insufficient? In pp 866-868 (2nd ed) there are already two examples given. $\endgroup$
    – orthocresol
    Jul 1 '17 at 10:55
  • $\begingroup$ I don't think there really is an 'orbital' explanation for this (in the same way as the Felkin-Ahn model), the Houk model really just concerns itself with the lowest energy conformation based on strain/steric (A1,2 vs A1,3) arguments, with this lowest energy conformation being the most reactive. As @orthocresol says, the explanation in Clayden is pretty much the whole of the Houk model $\endgroup$
    – NotEvans.
    Jul 1 '17 at 11:03
  • $\begingroup$ I don't see why this is the slowest energy conformation he gives conflicting examples where the reaction doesn't take place away from the bulky groip $\endgroup$ Jul 1 '17 at 12:30
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1. Origins of the Houk model

The initial idea behind the Houk model was infact provided by Kishi, who proposed that alkenes with a chiral centre on the adjacent carbon adopted a 'reactive conformation' in which the small group eclipsed the alkene in order to minimise unfavourable steric interactions.[1]

Kishi's reactive conformer model

Fig1: Kishi's "reactant conformer" model, taken from ref [1]

Houk took the 'reactive conformation' from the Kishi studies and modelled it computationally, showing that the lowest energy ground state conformation for alkenes with substituents at the allylic position was indeed the one in which the small group eclipsed the alkene, as proposed.[*]

2. Allylic strain

The Houk model works largely on steric grounds, balancing A1,2 strain and A1,3 strain, as can be seen from the figure below:

enter image description here

Fig2: The reactive conformation, taken from Organic Synthesis- Strategy & Control, Wyatt and Warren (Wiley)

The 'reactive conformation' is the middle structure (now days often known as the Houk conformation), in which A1,2 strain and A1,3 strain is minimal. In the left hand structure A1,2 strain is present, in the form of a H-H clash (doesn't look too significant, but raises the energy of the conformation significantly enough, similar to in the conformations of ethane). In the right hand structure A1,3 strain is present, this A1,3 strain is far more significant than A1,2, making this conformation sufficiently high in energy as to be barely populated at room temperature.

Based on the arguments above, it's worth pointing out that the Houk model works best for cis alkenes, with trans alkenes often giving poorer selectivity:[2]

enter image description here

Fig3: cis and trans alkenes reacting via the Houk model, taken from Organic Synthesis- Strategy & Control, Wyatt and Warren (Wiley)

This result is consistent with the fact that in a trans alkene, A1,3 strain is already minimised by virtue of the olefin geometry, meaning that two possible 'low energy' conformers exist which have neither A1,3 strain nor significant A1,2 strain.

3. Reactions not following the Houk model

Not all reactions for which the Houk model could be used give the expected 'Houk product'. The most common of these (and indeed the one in Clayden that you mention in the question as not following the Houk model) is when the starting material is an allylic alcohol.

enter image description here

Fig4: Reactions not following the Houk model due to directing effects, taken from Organic Chemistry, Clayden and Warren (Oxford University Press)

In the example above, the hydroxyl group is acting as a directing group, guiding epoxidation with the mCPBA to the same face (the steric argument, which would always predict epoxidation away from a bulky group, does not apply here).


Notes and references

[1]: Houk, K. N.; Rondan, N. G.; Wu, Y.-D.; Metz, J. T.; Paddon-Row, M. N. Theoretical studies of diasteroselective hydroborations. Tetrahedron 1984, 40 (12), 2257–2274. DOI: 10.1016/0040-4020(84)80009-5.

[2]: Vedejs, E.; McClure, C. K. Hyperconjugative effects of allylic substituents are not important in osmylations. J. Am. Chem. Soc. 1986, 108 (5), 1094–1096. DOI: 10.1021/ja00265a048.

[*]: The Houk group has been instrumental in providing a bridge between theoretical predictions and experimental results, providing weight to proposed models, and giving confidence in being able to look at a reaction and predict what product it may be.

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