Chiral ammonium betaines

The new chiral ammonium betaine 112 was developed and utilized by Ooi et al. as a bifunctional organic base catalyst for Mannich-type reaction of a-nitrocarbox-ylates [63]. This quaternary ammonium compound is an internal salt, unlike the aforementioned intermolecular ion-pairing ammonium salts. Consequently, the anion could act as a Brpnsted base and deprotonate a pronucleophile. The resulting... 

FIGURE 2.47. Structure of Ooi s chiral ammonium betaines and their mechanism of catalysis. 

An ammonium betaine of type (R)-16 could be considered as an intramolecular version of ammonium phenoxide. The potential of chiral ammonium betaine (R)-16 as Brpnsted base catalyst has been demonstrated in asymmetric Mamiich reactions (Scheme 14.9) [6b, 32]. The basic phenoxide anion is responsible for abstraction of the active methine proton of a nucleophile 18 and thus gives the corresponding chiral ammonium enolate. Subsequent stereoselective bond formation with imine 17 afforded ammonium amide that can be rapidly protonated by the in situ formed phenolic hydrogen to regenerate the ammonium betaine (R)-16. 

Chiral Ammonium Betaine-Cataiyzed Mannich Reactions... 

Quaternary ammonium betaines possessing an anion moiety have emerged as Bronsted base catalysts. The C2-symmetric axially chiral ammonium betaine 177 deprotonates the a-substituted a-nitrocarboxylates (176) to form a structured ion pair that reacts with imines (173) to furnish the corresponding anti-Mannich... 

Scheme 28.19 Chiral ammonium betaine catalyzed Mannich reactions.

Chiral ammonium betaines are a particular class of bifunctional BB-based catalysts that have been successfully applied in the aza-Henry reaction of N-Boc imines and a-substituted a-nitroesters [42]. The catalyst structure displays an intramolecular ion-pairing quaternary ammonium aryl-oxide and the mode of action may involve deprotonation of the pronucleophile by the basic anion to furnish and onium ion as its conjugate acid form. Catalyst loadings as low as lmol% produced the corresponding quaternary-tertiary aza-Henry adducts in excellent yields and enantioselectivities, albeit with low to moderate diastereoselectivities (Scheme 29.18). The lowest de s (up to 33%) were obtained with aliphatic N-Boc imines (R = CH2CH2Ph, -octyl). 

Scheme 29.18 Chiral ammonium betaine 35 catalyzed aza-Henry reaction.

In 2010, Ooi and coworkers proposed the use of chiral ammonium betaines as asymmetric ionic nucleophilic catalysts [29], They reasoned that an intramolecular alkoxonium salt could be an efficient catalyst for the Steglich rearrangement- since the alkoxide anion would displace the carbonyl substituent in the intermediate ion pair the ammonium cation would be engaged in an ionic interaction with the azlactone anion, enhancing both the rate and the stereoselectivity of the acyl transfer step (Scheme 40.22). 

In accordance with this working hypothesis, the chiral ammonium betaine 16 proved to be a highly efficient catalyst for the O- to C-rearrangement of azlactone carbonates (Scheme 40.23). 

Scheme 40.23 Asymmetric Steglich rearrangement catalyzed by a chiral ammonium betaine.

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