Rapid Route-Finding for Bifurcating Organic Reactions

A large
number of organic reactions feature post-transition-state
bifurcations. Selectivities in such reactions are difficult to analyze
because they cannot be determined by comparing the energies of competing
transition states. Molecular dynamics approaches can provide answers
but are computationally very expensive. We present an algorithm that
predicts the major products in bifurcating organic reactions with
negligible computational cost. The method requires two transition
states, two product geometries, and no additional information. The
algorithm correctly predicts the major product for about 90% of the
organic reactions investigated. For the remaining 10% of the reactions,
the algorithm returns a warning indication that the conclusion may
be uncertain. The method also reproduces the experimental and the
molecular dynamics product ratios within 15% for more than 80% of
the reactions. We have successfully applied the method to a trifurcating
organic reaction, a carbocation rearrangement, and solvent-dependent
Pummerer-like reactions, demonstrating the power of the algorithm
to simplify and to help understand highly complex reactions.