| Autor: |
Halskov KS; Department of Chemistry, Aarhus University , DK-8000 Aarhus C, Denmark., Donslund BS; Department of Chemistry, Aarhus University , DK-8000 Aarhus C, Denmark., Paz BM; Department of Chemistry, Aarhus University , DK-8000 Aarhus C, Denmark., Jørgensen KA; Department of Chemistry, Aarhus University , DK-8000 Aarhus C, Denmark. |
| Jazyk: |
angličtina |
| Zdroj: |
Accounts of chemical research [Acc Chem Res] 2016 May 17; Vol. 49 (5), pp. 974-86. Date of Electronic Publication: 2016 Apr 29. |
| DOI: |
10.1021/acs.accounts.6b00008 |
| Abstrakt: |
Asymmetric organocatalysis has witnessed a remarkable development since its "re-birth" in the beginning of the millenium. In this rapidly growing field, computational investigations have proven to be an important contribution for the elucidation of mechanisms and rationalizations of the stereochemical outcomes of many of the reaction concepts developed. The improved understanding of mechanistic details has facilitated the further advancement of the field. The diarylprolinol-silyl ethers have since their introduction been one of the most applied catalysts in asymmetric aminocatalysis due to their robustness and generality. Although aminocatalytic methods at first glance appear to follow relatively simple mechanistic principles, more comprehensive computational studies have shown that this notion in some cases is deceiving and that more complex pathways might be operating. In this Account, the application of density functional theory (DFT) and other computational methods on systems catalyzed by the diarylprolinol-silyl ethers is described. It will be illustrated how computational investigations have shed light on the structure and reactivity of important intermediates in aminocatalysis, such as enamines and iminium ions formed from aldehydes and α,β-unsaturated aldehydes, respectively. Enamine and iminium ion catalysis can be classified as HOMO-raising and LUMO-lowering activation modes. In these systems, the exclusive reactivity through one of the possible intermediates is often a requisite for achieving high stereoselectivity; therefore, the appreciation of subtle energy differences has been vital for the efficient development of new stereoselective reactions. The diarylprolinol-silyl ethers have also allowed for novel activation modes for unsaturated aldehydes, which have opened up avenues for the development of new remote functionalization reactions of poly-unsaturated carbonyl compounds via di-, tri-, and tetraenamine intermediates and vinylogous iminium ions. Computational studies have played a pivotal role in the elucidation of the regioselectivities observed for such systems because these pose a challenge due to the presence of multiple reactive sites in these intermediates. Charge distribution and π-orbital coefficient calculations have been applied to explain the observed regioselectivity of the given reactions. The calculation of more elaborate energetic pathways has allowed for in silico identification of high-energy intermediates, such as zwitterions, and transition-state structures, which have also provided information on the driving force controlling the reaction course and outcome. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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