Luck and Logic - Problem Solving in Synthesis

Abstract A series of early choices led to the accidental discovery of an exceptionally facile allene ether Nazarov cyclization. This led to the elucidation of an unexpected mechanism for asymmetry transfer from a pyran-derived chiral auxiliary to a ring carbon atom. We subsequently developed four distinct approaches to the catalytic asymmetric Nazarov, including two that lead to adjacent, all-carbon atom quaternary centers. The rational choices made at critical points were also very lucky. Had we chosen differently we would have missed opportunities for discovery. Although research is planned rationally, chance often plays a decisive role.