Archive for October 21st, 2025

The mechanism of borohydride reductions. Part 2: 4-t-butyl-cyclohexanone – Dispersion induced stereochemistry.

Tuesday, October 21st, 2025

Part one of this topic was posted more than ten years ago.[1] I clearly forgot about it, so belatedly, here is part 2 – dealing with the stereochemistry of the reduction of tert-butyl-cyclohexanone by borohydride in water. The known stereochemistry is nicely summarised in this article, along with an extensive  history of possible explanations of the reasons for the stereochemical preference.[2] Put simply, the hydride nucleophile attacks the carbonyl from an axial rather than equation direction with a ratio of 10:1 (ΔΔG 1.37 kcal/mol). So does the model I previously proposed[1] support this and give any indication of why the stereochemistry is axial?

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References

  1. H. Rzepa, "Part 1: ethanal.", 2015. https://doi.org/10.59350/aqrgh-jw887
  2. R. Kobetić, V. Petrović-Peroković, V. Ključarić, B. Juršić, and D.E. Sunko, "Selective Reduction of Cyclohexanones with NaBH<sub>4</sub> in β-Cyclodextrin, PEG-400, and Micelles", Supramolecular Chemistry, vol. 20, pp. 379-385, 2008. https://doi.org/10.1080/10610270701268815