1375014-96-2Relevant academic research and scientific papers
Studies of the Mechanism and Origins of Enantioselectivity for the Chiral Phosphoric Acid-Catalyzed Stereoselective Spiroketalization Reactions
Khomutnyk, Yaroslav Ya.,Argüelles, Alonso J.,Winschel, Grace A.,Sun, Zhankui,Zimmerman, Paul M.,Nagorny, Pavel
, p. 444 - 456 (2016)
Mechanistic and computational studies were conducted to elucidate the mechanism and the origins of enantiocontrol for asymmetric chiral phosphoric acid-catalyzed spiroketalization reactions. These studies were designed to differentiate between the SN1-like, SN2-like, and covalent phosphate intermediate-based mechanisms. The chiral phosphoric acid-catalyzed spiroketalization of deuterium-labeled cyclic enol ethers revealed a highly diastereoselective syn-selective protonation/nucleophile addition, thus ruling out long-lived oxocarbenium intermediates. Hammett analysis of the reaction kinetics revealed positive charge accumulation in the transition state (ρ = -2.9). A new computational reaction exploration method along with dynamics simulations supported an asynchronous concerted mechanism with a relatively short-lived polar transition state (average lifetime = 519 ± 240 fs), which is consistent with the observed inverse secondary kinetic isotope effect of 0.85. On the basis of these studies, a transition state model explaining the observed stereochemical outcome has been proposed. This model predicts the enantioselective formation of the observed enantiomer of the product with 92% ee, which matches the experimentally observed value.
Chiral phosphoric acid-catalyzed enantioselective and diastereoselective spiroketalizations
Sun, Zhankui,Winschel, Grace A.,Borovika, Alina,Nagorny, Pavel
, p. 8074 - 8077 (2012/07/14)
Catalytic enantioselective and diastereoselective spiroketalizations with BINOL-derived chiral phosphoric acids are reported. The chiral catalyst can override the inherent preference for the formation of thermodynamic spiroketals, and highly selective formation of nonthermodynamic spiroketals could be achieved under the reaction conditions.
