Organocatalysts chiral Bronsted acid

Some of the seminal studies of organocatalysts have been described, focusing on chiral Bronsted acid catalysts. Because this review is not comprehensive, there are a number of topics not covered in this chapter, such as carbene catalysts, bifunctional catalysts, and so on. 

A new approach to stereoselective transfer hydrogenation of imines was the application of chiral phosphoric acid esters as organocatalysts [50-52]. The mechanism is based on the assumption that the imine is protonated by a chiral Bronsted acid, which acts as the catalyst. The resulting diastereomeric iminium ion pairs, which may be stabilized by hydrogen bonding, react with the Hantzsch dihydropyridine at different rates to give an enantiomerically enriched amine and a pyridine derivative [50-52]. The exact mechanism is still under discussion however computational density functional theory (DFT) studies ]53, 54] suggest a three-point contact model. ... 

Other chiral Bronsted acid organocatalysts developed more recently include chiral binaphthyl-derived disulfonic acids [162] and sulfonimides [163] and SPINOL-derived phosphoric acids [164]. 

The use of chiral Bronsted acids (organocatalyst class) in asymmetric F-C reactions has been extensively reviewed. They can be used instead of oxophilic chiral Lewis acids for the asymmetric coupling of indoles to less reactive ketone substrates such as trihalopyruvates. The use by Mikami (2000) of a chiral phenol cocatalyst in boosting enantioselectivity ( 10%) perhaps provided the first clue to such a possibility. 

This chapter wiU concentrate on metal-free Lewis acids that possess a Lewis acidic cation or a hypervalent center. Lewis acids are compounds with a vacant orbital [7, 8]. It is also possible to consider two successful classes of organocatalysts as part of Lewis acids catalysts. Chiral Bronsted acid organocatalysts could be considered due to their proton, which is the simplest Lewis acid. The achieved... 

Considerable effort has been devoted to the development of enantiocatalytic MBH reactions, either with purely organic catalysts, or with metal complexes. Paradoxically, metal complex-mediated reactions were usually found to be more efficient in terms of enantioselectivity, reaction rates and scope of the substrates, than their organocatalytic counterparts [36, 56]. However, this picture is actually changing, and during the past few years the considerable advances made in organocatalytic MBH reactions have allowed the use of viable alternatives to the metal complex-mediated reactions. Today, most of the organocatalysts developed are bifunctional catalysts in which the chiral N- and P-based Lewis base is tethered with a Bronsted acid, such as (thio)urea and phenol derivatives. Alternatively, these acid co-catalysts can be used as additives with the nucleophile base. 

The most commonly used type of catalyst is a relatively small, bifunctional molecule that contains both a Lewis base and a Bronsted acid center, the catalytic properties being based on the activation of both the donor and the acceptor of the substrates. The majority of organocatalysts are chiral amines, e.g. amino acids or peptides. The acceleration of the reaction is either based on a charge-activated reaction (formation of an imminium ion 4), or involves the generalized enamine catalytic cycle (formation of an enamine 5). In an imminium ion, the electrophilicity compared to a keton or an oxo-Michael system is increased. If the imminium ion is deprotonated to form an enamine species, the nucleophilicity of the a-carbon is increased by the electron-donating properties of the nitrogen. ... 

Torok (2005) reported the use of chiral cinchona alkaloid Bronsted acid organocatalysts (5 mol %), cinchonidine (102) and cinchonine (103), in the... 

Catalytic chiral Mannich reactions in the next examples are promoted by organocatalysts [35]. Characteristic of the selected organocatalysts is their proton or Bronsted acidity and stabilization of the catalytic complex by hydrogen bonding to enamine. 

On the other hand, several groups have also recently developed asymmetric domino reactions through relay catalysis with combinations of organocatalysts with ruthenium catalysts. For example. You et al. demonstrated in 2009 that ruthenium catalyst could be compatible with Bronsted acid catalyst. They reported a practical and economical synthesis of chiral tetrahydropyrano[3,4-b]indols and tetrahydro-p-carbolines by the combination of ruthenium-catalysed olefin cross-metathesis and a chiral phosphoric acid-catalysed Friedel-Crafts alleviation reaction, as shown in Scheme 7.41. This domino reaction allowed the use of readily available materials to highly enantioselectively construct synthetically valuable polycyclic indole frameworks in enantioselectivity of up to 94% ee. 

Over the past decade, rapid growth has been achieved in organocatalytic asymmetric Diels-Alder and hetero-Diels-Alder reactions. Numerous organocatalysts such as chiral amines, guanidines, N-heterocyclic carbenes, Bronsted acids, and bifunctional catalysts have been successfully developed. The activation modes for these catalysts, such as imine-catalysis, enamine-catalysis, dienamine catalysis. 

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