Stereoelectronics of the Houk model

Question

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.

Answer 1

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]

^{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 A_1,2 strain and A_1,3 strain, as can be seen from the figure below:

^{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 A_1,2 strain and A_1,3 strain is minimal. In the left hand structure A_1,2 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 A_1,3 strain is present, this A_1,3 strain is far more significant than A_1,2, 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]

^{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, A_1,3 strain is already minimised by virtue of the olefin geometry, meaning that two possible 'low energy' conformers exist which have neither A_1,3 strain nor significant A_1,2 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.

^{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).

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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.}