Enantioselective Syntheses oftrans-3,4-Difluoropyrrolidines and Investigation of Their Applications in Catalytic Asymmetric Synthesis

Abstract

[reaction: see text] Asymmetric syntheses of enantiopure trans-3,4-difluoropyrrolidines have been prepared by the introduction of fluorine at both centers in a single operation; asymmetric epoxidations and additions to benzaldehyde were conducted using catalysts whose chirality depends on organofluorine asymmetry.

Fluorine Conformational Effects in Organocatalysis: An Emerging Strategy for Molecular Design

“…An important contribution, especially in the context of this Minireview, is the use of C 2 -symmetric, enantiopure vicinal difluorides employed in combination with [Ti(OiPr) 4 ] by Marson and Melling (Scheme 5). [42] Whilst the nitrogen substituent clearly influences the enantioselectivity of epoxidation (n-C 8 H 17 66 % ee versus cyclohexyl 10 % ee), the only stereochemical information is relayed from the configurationally defined vicinal difluoro motif (b-fluoroamine) by virtue of its influence on the conformation of the pyrrolidine ring. Despite the energetic preference for a gauche relationship in acyclic vicinal polyfluorinated systems such as 1,2-difluoroethane, [43] this conformation is arduous in 3,4-pyrrolidines.…”

Konformative Fluoreffekte in der Organokatalyse: eine neuartige Strategie zum molekularen Design

“…Ein wichtiger Beitrag, insbesondere im Hinblick auf diesen Kurzaufsatz, ist die Verwendung enantiomerenreiner C 2 -symmetrischer vicinaler Difluoride in Kombination mit [Ti(OiPr) 4 ] durch Marson und Melling (Schema 5). [42] Während der Stickstoffsubstituent eindeutig die Enantioselektivität der Epoxidierung beeinflusst (66 % ee für n-C 8 H 17 und 10 % ee für Cyclohexyl), wird die einzige stereochemische Information von dem konfigurativ festgelegten vicinalen Difluormotiv (b-Fluoramin) durch dessen Einfluss auf die Konformation des Pyrrolidinrings weitergegeben. In acyclischen, vicinal mehrfach fluorierten Systemen wie 1,2-Difluorethan [43] wird eine gaucheAnordnung bevorzugt, doch diese Konformation ist in 3,4-Pyrrolidinen schwer zu erreichen.…”

Tartaric acid and its O-acyl derivatives. Part 8. Direct synthesis of novel N-substituted mono- and diacyltartrimides: unusual reaction course

“…In the total synthesis of UCS1025A, which is an active agent against cancer human cells by the inhibition of telomerase, the starting materials were diacyl tartrimides ( Figure 1 Diacyl tartrimides are easily converted to enantiomeric vicinal difluoro-, 9 diamino-, 10 or dihydroxypyrrolidines. [9][10][11] These valuable compounds were used as chiral ligands, for example, in the asymmetric epoxidation of allyl alcohols, 9,12 or the enantioselective addition of diethylzinc to aromatic aldehydes. 9,11 We have found only two references regarding monoacyl tartrimides.…”

“…[9][10][11] These valuable compounds were used as chiral ligands, for example, in the asymmetric epoxidation of allyl alcohols, 9,12 or the enantioselective addition of diethylzinc to aromatic aldehydes. 9,11 We have found only two references regarding monoacyl tartrimides. A preparation of O-benzoyl-N-methyltartrimide raises doubts.…”