Chiral Quaternary Ammonium Aryloxide/N,O‐Bis(trimethyl‐ silyl)acetamide Combination as Efficient Organocatalytic System for the Direct Vinylogous Aldol Reaction of (5H)‐Furan‐2‐one Derivatives

Abstract

A chiral quaternary ammonium amide was generated in situ from N,O-bis(trimethylsilyl)-A C H T U N G T R E N N U N G acetamide (BSA) as non-nucleophilic Brønsted base precursor and the combination of chiral quaternary ammonium halide/sodium aryloxide as chiral Lewis base. This system was applied to an anti-selective organocatalytic direct vinylogous aldol (ODVA) reaction of (5H)-furan-2-one derivatives with aldehydes. Several 5-(1'-hydroxy)-g-butenolides were obtained in good diastereomeric ratios (up to 95/5) and excellent enantioselectivities (up to 94%) with both aliphatic or (hetero)aromatic aldehydes, so providing a rare example of general and efficient conditions for the ODVA reaction.

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

“…[15] After quaternization of the quinuclidine moiety, the betaine was obtained by treatment with ion-exchanged resin (Amberlyst A26 OH form; Scheme 1). Several other chiral quaternary ammonium aryloxide salts were tested at this temperature (Table 1, entries [5][6][7][8][9][10][11][12][13][14]. First, we ensured that in the absence of catalyst no conversion could be detected (Table 1, entry 1).…”

“…Then the reaction was performed at several temperatures by using QN + 1 as the catalyst (Table 1, entries 2-4). Chiral betaines QN + 5-8 were also tested (Table 1, entries [11][12][13][14]. General strategy for the synthesis of betaines.…”

“…The betaine QN + 5 bearing two benzyl substituents on both the nitrogen and oxygen of the quinine led to a slightly improved enantiomeric excess (Table 1, entry 11). The benzosuberone series and, above all, indanone furnished significantly lower ees (Table 2, entries [10][11][12]. Having defined the best catalyst, the effect of solvent was investigated.…”

“…The main contributions have mainly emanated from the groups of Mukaiyama [9] and Ooi [10] and involved chiral quaternary ammonium phenoxides derived from Cinchona alkaloids and chiral ammonium betaines derived from BINOL, respectively. [11] To further study the catalytic potential of quaternary ammonium aryloxides, we report herein an enantioselective protonation of silyl enolates catalyzed by simple and readily accessible quaternary ammonium aryloxides derived from Cinchona alkaloids including original betaine catalysts acting as cooperative ion pairs. [11] To further study the catalytic potential of quaternary ammonium aryloxides, we report herein an enantioselective protonation of silyl enolates catalyzed by simple and readily accessible quaternary ammonium aryloxides derived from Cinchona alkaloids including original betaine catalysts acting as cooperative ion pairs.…”

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

“…Surprisingly, even if racemic approaches were already reported in the literature for the in situ generation of Brønsted base from various C ‐ or N ‐ silylated pro‐bases, asymmetric version was totally unexplored. In order to test our hypothesis, we elected the direct vinylogous aldol reaction of ( 5H )‐furan‐2‐one derivatives 13 as model reaction . With regard to different aspects, our approach discloses several advantages regarding this model reaction.…”