Conclusions
Inspired by Corey's suggestion of a hydrogen bond from formyl hydrogens,
we modified the transition state force field for the boron-mediated aldol
reaction. We conclude:
- The physical basis for the modification is a hydrogen bond between the formyl hydrogen of an aldehyde coordinated to a Lewis acid, and an electronegative group of the Lewis acid
- The modification has no effect on calculations for E and Z enol borinates, which have already been shown to be analysed effectively be this approach
- The modification improves the force field's ability to reproduce the transition structures for boat B, calculated by ab initio molecular orbital theory
- The modification slightly improves the force field's ability to reproduce experimental selectivities for the boron-mediated reactions of methyl ketones
- Replacement of a zero order bond with a single bond in the transition structure force field makes the calculation of stereoselectivity more straighforward
Acknowledgements
The Royal Society, the EPSRC and the Cambridge Centre for Molecular Recognition are thanked for financial support, and Ian Paterson (Cambridge), Cesare Gennari and Anna Bernardi (Milano) for helpful discussions.