Natural bond orbital analysis of the intrinsic reaction barriers in nucleophilic displacements

Applications of natural bond orbital (NBO) analysis to the intrinsic reaction barriers involved in identity nucleophilic substitutions of halides (X = F, Cl or Br) at various carbon centres such as methyl, acyl, vinyl, imidoyl, cyclopropenyl and cyclopentadienyl halides are surveyed. The most important transition state stabilization in the pi attack (S(N)pi) path is the proximate sigma --> sigma* charge-transfer interactions, while that in the sigma attack (S(N)sigma) path is the non-charge-transfer term which includes bond energy, exclusion repulsion and electrostatic interactions. The tighter transition state with shorter C-X bond distance coupled with stronger bond energy for X = F often provides additional stabilization owing to stronger energy gain. In the open (loose) S(N)sigma transition state, the leaving group X- leaves behind an empty p (p(+)) orbital at C-alpha, which leads to strong pi(C=C) --> p(+) and/or n(X) --> p(+) charge-transfer stabilization. In the S(N)pi transition state the major stabilizing factors are n --> sigma(C-X)* and/or pi(C=C) --> sigma(C-C)* type charge-transfer interactions. The NBO analysis is shown to provide satisfactory explanations of the origins of intrinsic reaction barriers based on orbital interaction concepts.