Proline-catalyzed aldol reactions of cyclic diketones: fluorine modifies pathways as well as transition states

• Published in: Tetrahedron Vol. 66; no. 40; pp. 8021 - 8028
• Main Authors: Díaz, Jesús, Goodman, Jonathan M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 02.10.2010; Elsevier
• Subjects: Aldol reactions; Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Asymmetric catalysis; Catalysis; Catalysts: preparations and properties; Chemistry; DFT; Epimerization; Exact sciences and technology; General and physical chemistry; Organic chemistry; Preparations and properties; Proline; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Epimerization; MKRRAXGMWSCRCO-VSEIDBEKSA-N; PLKSVHDXFUWGOG-JAXQBETCSA-N; Proline; ARIRUJWBRZBUBF-SCZZXKLOSA-N; Asymmetric catalysis; QRTCLBASRMVLFT-IONNQARKSA-N; MKRRAXGMWSCRCO-BDWDCIJZSA-N; DFT; Aldol reactions; QRTCLBASRMVLFT-VXNVDRBHSA-N; KPIMDGSAHAETIV-YPPLFUCFSA-N; QRTCLBASRMVLFT-APPZFPTMSA-N; NYOJDLLSQQFPPH-WZRBSPASSA-N; KPIMDGSAHAETIV-WPAALNNJSA-N; KPIMDGSAHAETIV-USIBJPKCSA-N; ZIWHMENIDGOELV-DMTCNVIQSA-N; ARIRUJWBRZBUBF-PSASIEDQSA-N; KBSGQTAYVRWUEO-UHFFFAOYSA-N; ARIRUJWBRZBUBF-WPRPVWTQSA-N; QRTCLBASRMVLFT-CBAPKCEASA-N; PQOZOIXDFLJALL-UHFFFAOYSA-N; MKRRAXGMWSCRCO-XBNNWQEZSA-N; NYOJDLLSQQFPPH-NTZNESFSSA-N; KPIMDGSAHAETIV-GFJNPJNJSA-N; ARIRUJWBRZBUBF-WCBMZHEXSA-N; MKRRAXGMWSCRCO-VGYDOTAVSA-N; Water; Intramolecular reaction; Catalytic reaction; Molecular structure; Fluorine; Nitrogen heterocycle; Theoretical study; Selectivity; Diketone; Experimental study; Aldol condensation; α-Aminoacid; Cyclic compound; Aminoacid; Transition state; Density functional method; Aromatic compound; Indene derivatives; Catalyst
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.08.003

Proline-catalysed aldol reactions are central to the development of organocatalysis, and have been the subjects of many studies. List’s results on the effect of fluorine substitution on proline catalysts for an intramolecular aldol condensation provide a perfect test set for computational analysis, as subtle changes in the catalyst structure lead to clear changes in the product ratios. The results show that the carbon–carbon bond forming transition states for the Hajos–Parrish–Wiechart reaction do not account for the observed selectivity in all cases. However, if an analysis of post transition-state epimerization pathways is also included, together with the effect of water, it is possible to account for all of the experimental data. [Display omitted]