Asymmetric Organocatalytic Protonation of Silyl Enolates Catalyzed by Simple and Original Betaines Derived from Cinchona Alkaloids

Abstract

The asymmetric protonation of silyl enolates derived from tetralone, benzosuberone, and cyclohexanone has been successfully achieved by using simple and original betaine catalysts derived from Cinchona alkaloids (quinine and quinidine series) to afford the desired α-substituted ketones in high yields and moderate enantioselectivities. The ease of imple-[a] Normandie University, COBRA, UMR 6014 & FR3038,

Redox Non‐Innocence of Coordinated 2‐(Arylazo) Pyridines in Iridium Complexes: Characterization of Redox Series and an Insight into Voltage‐Induced Current Characteristics

“…Recently, Levacher et al have proposed another strategy for the EP of silyl enolates derived from tetralones 10 , indanones 11 , benzosuberones 19 and cyclohexanones 3 by making use of betaine‐type catalyst 21 , derived from a Cinchona alkaloid and a phenol as achiral stoichiometric proton source 20. Unlike in the previous approach, which consisted of generating a catalytic amount of chiral proton source in situ, the postulated chiral intermediate would be an enolate/quaternary ammonium ion pair of type 22 .…”

Chiral Ammonium Aryloxides as Brønsted Base Catalysts for the Henry Reaction of Nitroalkanes to Aromatic and Aliphatic Aldehydes

“…Accordingly, there is still a need for the development of efficient and general diastereo‐ and enantioselective organocatalyzed Henry reaction. Recently, we have demonstrated the potential of chiral quaternary ammonium aryloxides, and betaines as efficient and general Lewis base organocatalysts in useful organic transformations such as vinylogous Mukaiyama aldol reaction of ( 5H )‐furan‐2‐ones, protonation of silyl enolates, desymmetrization of 4‐substituted cyclohexanones by silylation or Brook/elimination/aldol reaction sequence for the direct one‐pot preparation of difluorinated products . Following these successes, we were interested in probing the performances of chiral quaternary ammonium aryloxides as Brønsted base organocatalysts.…”

“…With the aim of improving the conversion, we then examined the influence of BSA ( N,O ‐bistrimethylsilylacetamide), an additive which is expected to limit the retro‐Henry reaction by silylation of the aldol product. Moreover, this additive would promote the formation of a more basic chiral quaternary ammonium amide intermediate resulting from the reaction between the phenoxide and BSA . Pleasingly, BSA exhibits a positive impact not only on the conversion but also on the diastereo‐ and enantioselectivity in the case of benzaldehyde 1 a (Table , entry 3 vs entry 1).…”

“…Moreover, this additive would promote the formation of a more basic chiral quaternary ammonium amide intermediate resulting from the reaction between the phenoxide and BSA. [15][16][17][18] Pleasingly, BSA exhibits a positive impact not only on the conversion but also on the diastereo-and enantioselectivity in the case of benzaldehyde 1 a ( Table 1, entry 3 vs entry 1). By contrast, the use of BSA with 3-phenylpropanal 1 b resulted in a decrease of the diastereo-and enantioselectivity, albeit a higher conversion could also be observed ( Table 1, entry 4 vs entry 2).…”

New Developments in Chiral Cooperative Ion Pairing Organocatalysis by Means of Ammonium Oxyanions and Fluorides: From Protonation to Deprotonation Reactions.

“…Such a type of catalyst, even if already described in the literature mainly by the group of Mukaiyama in 2000′s, were then sparingly exploited in the literature. [21],[22] We thus decided to undertake the synthesis of such catalysts and to assess their performances in enantioselective protonation of silyl enol ethers 2 derived from cyclic aromatic ketones (Scheme ) …”