A Combined Theoretical and Experimental Investigation on the Enantioselective Oxidation of Aryl Benzyl Sulfides in the Presence of a Chiral Titanium Catalyst

Abstract

An experimental investigation of the enantioselective oxidation of aryl benzyl sulfides by tert-butyl hydroperoxide in the presence of a titanium/hydrobenzoin catalyst has shown that these sulfides are ideal substrates for this catalytic system, with negligible interference by the substituents on the aryl groups. A reaction mechanism based on DFT computations has been proposed. The DFT MPWB1K functional was used in the theoretical investigation to account for weak hydrogen-bonding and pi interactions. The computed reaction profile explains the experimentally observed enantioselectivity, which is determined by the thermodynamics of the first phase of the reaction. A detailed discussion of the hydrogen-bonding and pi interactions that drive the reaction along the observed stereochemical path is given.

Aromatische Ringe in chemischer und biologischer Erkennung: Energien und Strukturen

“…[101] Frühere Arbeiten zeigten, dass aromatische T-förmige Edge-to-Face-Wechselwirkungen in enantioselektiven Reduktionen eine bedeutende Rolle spielen können. [102] Ein Effekt dieser Wechselwirkungen auf die Ausbeute und/oder Selektivität wurde für unterschiedliche Transformationen vorgeschlagen: intra-und intermolekulare photochemische Reaktionen, [103] allylische Oxidationen, [104] Ruthenium-katalysierte Transferhydrierungen, [105] Titan-katalysierte Oxidationen von Sulfiden [106] und andere. [107] Zwei Beispiele illustrieren diese Fortschritte (Abbildung 8).…”

A Study of Factors Affecting Enantioselectivity in the Oxidation of Aryl Benzyl Sulfides in the Presence of Chiral Titanium Catalysts

“…[7,8] For many years, titanium catalyst chemistry in the oxidation of sulfides has focused mainly on the synthetic aspects, whereas mechanistic investigations have seldom been reported. [11][12][13] However, in 2009, three similar studies [6,14,15] on titanium-catalyzed enantioselective oxidation of sulfides were published, two of them [6,15] also considered theoretical aspects.…”

“…[16] Enantiopure (S)-omeprazole was obtained when (1R,2R)-1,2-bis(2-bromophenyl)ethane-1,2-diol was used as a ligand of the titanium. [14] Our contribution to the same topic was represented by a combined theoretical and experimental investigation [15] of the highly enantioselective TBHP oxidation of aryl benzyl sulfides in the presence of a complex between titanium and hydrobenzoin. [16] In the contribution, we described our most recent research on the application of this oxidation protocol.…”

Synthesis of enantioenriched sulfoxides

“…-is a water soluble species, and it was confirmed by 51 V NMR that its concentration increased when the oxidant was added rapidly. 94 Ellman et al investigated whether the effects seen due to different addition rates were influenced by the nature of the solvent.…”

“…Bolm speculated that the oxidising species formed in this oxidation were vanadium(V) species having oxoperoxy groups 90. 97 Bryliakov conducted a more extensive investigation of the vanadium species formed using 51 V NMR analysis and found that the monoperoxy species formed can exist in more than one form. 98 Two principal species were proposed to be present in equilibrium with each other -an unchelated form 91 and a chelated form 92, in which the primary alcohol coordinates to the vanadium (Scheme 34).…”