Origin of High <i>E</i>‑Selectivity in 4‑Pyrrolidinopyridine-Catalyzed Tetrasubstituted α,α′-Alkenediol: A Computational and Experimental Study

We have developed 4-pyrrolidinopyridine catalysts for the geometry-selective (<i>E</i>-selective) acylation of tetrasubstituted α,α′-alkenediols. To elucidate the major factors of the high geometry selectivity, experimental and computational studies were carried out. The control experiments with respect to the substituent of the substrate indicated the fundamental hydrogen bonding of the acidic hydrogen of NHNs and the <i>Z</i>-OH in the substrate. Comparison between <i>C</i>₂- and <i>C</i>₁-symmetric catalysts exhibited the necessity of the <i>C</i>₂-symmetric catalyst structure. The computationally proposed transition state (TS) model well explained the experimental results. Whereas the fundamental NH/amide-CO and the two-point free-OH/acetate anion hydrogen bonds stabilize the transition state (TS), affording the <i>E</i>-product, the steric repulsion between the N-protecting group and the amide side chain destabilizes TS, affording the <i>Z</i>-product. The role of the two amide side chains of the catalyst in a <i>C</i>₂-symmetric fashion is the enhancement of the molecular recognition ability through the additional hydrogen bond in a cooperative manner