Br0nsted base activation

The group of Enders recently disclosed an original use of probnol TMS ether as organocatalyst to promote the Michael addition of oxindoles to nitrooiefins (Scheme 34.25) [65]. The reaction proceed through Br0nsted base activation despite the fact that such a catalyst stracture, chiral pyrrolidine, was usually employed in... 

Abstract The organocatalytic asymmetric Mannich reaction and the related aza-Morita-Baylis-Hillman have been reviewed. The activities in this field have been snbdivided based on the types of catalysts that have been ntilized, which includes catalysis by enamine-forming chiral amines, chiral Br0nsted bases, chiral Brpnsted acids, and phase-transfer catalysts. 

Instead of using Br0nsted bases, chiral Br0nsted acids can also be utilized to enanti-oselectively acquire Mannich products. The acidic catalyst assists in the Mannich reaction by protonating the imine, thereby forming an iminium ion to which the deprotonated Brpnsted acid catalyst coordinates. This chiral counterion directs the incoming nucleophile and leads to an optically active Mannich product. 

Most reports on organocatalytic sulfa-Michael reactions are based on Br0nsted base catalysis, in order to activate pro-nucleophiles containing a S H or a Se—H bond. The early works, appeared in the lates 1970s, featured natural cinchona alkaloids 1-4 as basic catalysts (Figure 14.1). In their seminal works, Wynberg and co-workers employed less than 1 mol% of quinine 1 as chiral catalyst for the conjugated addition of arenethiols to 2-cyclohexen-l-ones. The enantiocontrol was unsatisfactory with benzyhnercaptan [6]. The quasi-enantiomeric catalyst quinidine 2 furnished the... 

Bifunctional Br0nsted Acid-Base Active (Thio)-Ureas... 

The bifunctional thioureas represent a group of bifunctional catalysts based on an interplay of Br0nsted acid-base activation that have obtained a prominent position over the last few years. Using these, the second functionality of choice is most often a basic nitrogen, such as a tertiary amine, and a simultaneous activation of nucleophile and electrophile can be achieved (409). 

The catalytic potential of base functionalities has been referred to in the previous chapter (see Sect. 7.4), wherein the interplay between an acidic (thio-)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such brfunctional thiourea-containing acid-base catalysts, chiral catalysts containing Lewis or Br0nsted-) base functionality as the sole catalyticaUy active group as weU as those having another H-bond donor like a hydroxy group e.g. Cinchona alkaloids) have found widespread applications in asymmetric catalysis (443-449). 

Activity series, 130 Anhenius acid, 123 Arrhenius base, 123 Base, 112 Bronsted acid. 123 Br0nsted base, 123 Combustion, 134... 

Fig. 8 Carbon-based Br0nsted acid activated oxazaborolidine catalyst for asymmetric Diels-Alder reaction of alkynyl ketones...

In general, most chiral Br0nsted base catalysts are equipped with an additional hydrogen bond donor (Brpnsted acid), which activates the electrophile. Moreover, coordination of both the nucleophile and electrophile to the rigid chiral backbone of the bifunctional catalyst via hydrogen bonding and a basic tertiary amine anchors the electrophile and nucleophile in an optimal transition state, which seems essential for the highly stereoselective and predictable formation of a... 

On the other hand, non-covalent interactions [4] have been proposed to justify the stereochemical control of the process when Br0nsted bases or acids and phase-transfer catalysts [5] are used to promote these types of reactions, especially when 1,3-dicarbonyl compounds [6] were used as substrates. While the formation of chiral ion-pairs governs the heteroatom approach for basic catalysts, the formation of hydrogen bonds is responsible in the case of chiral Br0nsted acids. In both cases, the effective shielding of one face of the nucleophile by the chiral catalyst determines the formation of the optically active product. 

It is seen that metal and metal oxide catalysts have significant roles in the catalyHc process for the production of fuels and chemicals. There are several catalysts that are used commercially in the biorefinery system to produce fuels and chemicals. Metal oxides are composed of cations possessing Lewis acid sites and anions wifh Br0nsted base sites. They are classified into single metal oxides and mixed metal oxides. Transition metal oxides have catalytic activity for cellulose hydrolysis, and when used as solid acid catalysts, they are reusable and thus may be easily separated from the reaction mixture. 

As an essential component to asymmetric organocatalysis, chiral, metal-free Bron-sted bases have mediated several types of C-C and C-X bond-forming reactions mediated by enamine and enolates. Br0nsted bases (Figure 13.1) have the functional capacity to accept a hydrogen (or proton) from an acidic source or equivalent activated species. This proton transfer forms the basis of the key activation component to new-bond formation reactions. 

The mechanistic role played by Br0nsted bases involves either a pro-nucleophile or a stabilized, charged nudeophUe-electrophile adduct both species lose a proton to the amine moiety of the Br0nsted base, resulting in newly activated intermediates with basic character (Figure 13.1). The activated intermediate species during the course of the reaction are involved in a second proton transfer event from the protonated Bronsted base, which frees up the Bronsted base for subsequent cycles of activity. 

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 Br0nsted base catalyst has been demonstrated in asymmetric Mannich 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. 

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