Quantum mechanical study on the facial selectivity of dioxa and trioxa cage molecules

High facial selectivity (> 99%) of nucleophilic addition to the carbonyl gr oups of the title compounds (1 and 2) has been achieved for the novel triox a cage 2, but not for the dioxa 1. Similar experimental observations were m ade for the carbene addition to the double bonds of cage compounds, 3 and 4 . Calculations were carried out for the cage compounds and their reaction t ransition structures, with LiH as a nucleophile and :CCl2 as an attacking c arbene. The calculated facial preference for nucleophilic and carbene addit ion agreed well with experimental results. The origins of facial selectivit y are examined from the viewpoints of structure, frontier orbitals, and mol ecular electrostatic potential of the reactants, as well as strain, electro static, and hyperconjugation effects in the transition state;For dioxa cage s; the structural facial difference around the reaction center is minor, bu t the electronic difference of syn and anti faces generated by the two remo te oxygen atoms is clearly demonstrated via frontier orbital and MEP analys es. For trioxa cages, the close proximity of the third ether oxygen (O-s) t o the reaction center brings large structural and electronic changes around the reaction center. The calculated electrostatic and strain energy differ ences of syn and anti transition structures are significantly larger for tr ioxa cages than for the dioxa cages. Therefore, they both contribute to the enhanced facial selectivity of trioxa compounds. Finally, analysis of hype rconjugative stabilization in transition structures reveals the danger of r elying solely on Cieplak or Anh models in rationalization of facial selecti vity, especially when nonequivalent steric and electrostatic effects as tho se present in the trioxa systems are involved.