Katalytische enantioselektive Difluoralkylierung von Aldehyden

Abstract

Die Kupfer‐katalysierte Bindungsspaltung von Pentafluorbutan‐1,3‐dionen erzeugt Difluorenolationen, die mit Aldehyden zu chiralen α,α‐Difluor‐β‐hydroxyketonen mit bis zu 99 % Ausbeute und 92 % ee reagieren. Der präparative Nutzen der Reaktion wird anhand der stereoselektiven Synthese eines chiralen anti‐1,3‐Diols mit einer zentralen Difluormethangruppe und der effizienten Umwandlung zu einer 2,2‐Difluor‐3‐hydroxycarbonsäure belegt.

Highly Efficient “On Water” Catalyst‐Free Nucleophilic Addition Reactions Using Difluoroenoxysilanes: Dramatic Fluorine Effects

“…It should be also noted that the organocatalytic asymmetric aldol reaction of 1 with aldehydes is unprecedented. [20] The crucial role of the C À F···H À O interactions in the C À C bond-formation step of this protocol was further supported by density functional theory (DFT) calculations using a fivewater model. The Gibbs free-energy profile and the optimized structures of the transition state (TS) are shown in Figure 1.…”

α,α‐Difluoro‐α‐(trimethylsilyl)acetamides as Versatile Reagents for the Preparation of Difluorinated Aldol and Mannich Adducts

“…During the study of a one‐pot three‐component tetra‐ n ‐butylammonium diphenyltrifluorosilicate (TBAT)‐catalyzed Mannich reaction starting from Ruppert–Prakash reagent, acylsilanes and various activated imines, we noticed that the ammonium difluoroenolate, which is supposedly generated during the one‐pot process, was unreactive towards N ‐( tert ‐butanesulfinyl)imines . A careful examination of the litterature indeed shows that the addition to sulfinylimines has been mostly accomplished either from difluoroenol ethers, under Lewis or Brønsted acid activation,,, or via imino‐Reformatsky reactions ,,. The addition of difluoroenoxysilanes to sulfinylimines promoted only by a Lewis base, without any activation of the electrophile, has never been reported.…”

The Asymmetric Difluoro‐Reformatsky Reaction

“…The reaction was mediated by bisoxazoline ligands. Optimum results in terms of high chemical yields of ketone 95 , enantioselectivity, and low catalyst‐loading, shown in Scheme 21, were reached with the ligand 98 [71] …”

“…Optimum results in terms of high chemical yields of ketone 95, enantioselectivity, and low catalyst-loading, shown in Scheme 21, were reached with the ligand 98. [71] Another protocol for in-situ generation of difluorinated ketone enolates is based on the decarboxylation of α,αdifluoro-β-keto carboxylate salts 99. For obtaining the latter enolate precursors, a multistep sequence is required that, again starts from a difluoro-Reformatsky reaction, as shown in Scheme 22.…”