Computational Approach to Diarylprolinol-Silyl Ethers in Aminocatalysis

• DOI: 10.1021/acs.accounts.6b00008
• Publication Date: 2016-04-29T18:03:16Z
• Authors: Kim Søholm Halskov; Bjarke S. Donslund; Bruno Matos Paz; Karl Anker Jørgensen
• Keywords: Iminium; Reactivity; Enamine

ConspectusAsymmetric organocatalysis has witnessed a remarkable development since its "re-birth" in the beginning of millenium. In this rapidly growing field, computational investigations have proven to be an important contribution for elucidation mechanisms and rationalizations stereochemical outcomes many reaction concepts developed. The improved understanding mechanistic details facilitated further advancement field. diarylprolinol-silyl ethers their introduction been one most applied catalysts asymmetric aminocatalysis due robustness generality. Although aminocatalytic methods at first glance appear follow relatively simple principles, more comprehensive studies shown that notion some cases is deceiving complex pathways might operating.In Account, application density functional theory (DFT) other on systems catalyzed by described. It will illustrated how shed light structure reactivity intermediates aminocatalysis, such as enamines iminium ions formed from aldehydes α,β-unsaturated aldehydes, respectively. Enamine ion catalysis can classified HOMO-raising LUMO-lowering activation modes. these systems, exclusive through possible often requisite achieving high stereoselectivity; therefore, appreciation subtle energy differences vital efficient new stereoselective reactions.The also allowed novel modes unsaturated which opened up avenues remote functionalization reactions poly-unsaturated carbonyl compounds via di-, tri-, tetraenamine vinylogous ions. Computational played pivotal role regioselectivities observed because pose challenge presence multiple reactive sites intermediates. Charge distribution π-orbital coefficient calculations explain regioselectivity given reactions. calculation elaborate energetic silico identification high-energy intermediates, zwitterions, transition-state structures, provided information driving force controlling course outcome.