Organocatalysts catalysts

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

L-Proline catalyzes the aldol reaction. This approach has been applied to the synthesis of carbohydrate derivatives as illustrated by the glucose derivative 7 (Fig. 11) (237). The three-component Mannich reaction can be used to prepare p-amino and p-amino a-hydroxy carbonyl compounds in a single step (Fig. 12) (233). As with other types of catalysts, organocatalysts can be immobilized to aid recovery (253). 

In 2009, Kudo and coworkers investigated the asymmetric Michael-type addition of N-methylated and unsubstituted indoles to a,(3-unsaturated aldehydes by resin-supported polypeptides. In an initial survey of several amphiphilic polyethyleneglycol-grafted crosslinked polystyrene-supported catalysts, organocatalyst 22, which adopts a p-turn conformation aided by the polyleucine moiety under aqueous conditions, was revealed as the ideal catalyst for the preparation of a series of Michael adducts that were, in a final... 

In addition to metal-based catalysts, organocatalysts are also selective promoters of asymmetric Diels-Alder reactions. Several groups reported the use of cinchona alkaloid catalysts in standard Diels-Alder reactions. Deng combined 2-pyrones with a,P unsaturated ketones, while Bernard and Ricci focused on the reactions of vinylindoles with quinones and maleimides. Lectka reported enantioselective inverse electron demand hetero Diels-Alder reactions of ketene enolates and o-benzoquininone diimides catalyzed by a combination of benzoylquinidine and zinc triflate. For example, subjecting diimide 51 to the standard reaction conditions yields cycloadduct 52 as a single stereoisomer, which can be easily converted to... 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

This bifunctionnal amino-thiourea organocatalyst led to high selectivity because it was activating both the nitrone and the malonate, in its enol form, due to the acidic hydrogen atoms of the thiourea. Thus, the amino-thiourea catalyst promoted the Michael reaction of malonates to various nitroolefins... 

Recently, great advancement has been made in the use of air and oxygen as the oxidant for the oxidation of alcohols in aqueous media. Both transition-metal catalysts and organocatalysts have been developed. Complexes of various transition-metals such as cobalt,31 copper [Cu(I) and Cu(II)],32 Fe(III),33 Co/Mn/Br-system,34 Ru(III and IV),35 and V0P04 2H20,36 have been used to catalyze aerobic oxidations of alcohols. Cu(I) complex-based catalytic aerobic oxidations provide a model of copper(I)-containing oxidase in nature.37 Palladium complexes such as water-soluble Pd-bathophenanthroline are selective catalysts for aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic... 

In a recently published report by MacMillan s group [121] on the enantioselective synthesis of pyrroloindoline and furanoindoline natural products such as (-)-flustramine B 2-219 [122], enantiopure amines 2-215 were used as organocatalysts to promote a domino Michael addition/cyclization sequence (Scheme 2.51). As substrates, the substituted tryptamine 2-214 and a, 3-unsaturated aldehydes were used. Reaction of 2-214 and acrolein in the presence of 2-215 probably leads to the intermediate 2-216, which cyclizes to give the pyrroloindole moiety 2-217 with subsequent hydrolysis of the enamine moiety and reconstitution of the imidazolid-inone catalyst. After reduction of the aldehyde functionality in 2-217 with NaBH4 the flustramine precursor 2-218 was isolated in very good 90 % ee and 78 % yield. 

More recently, a series of sol-gel hydrophobized nanostructured silica matrices doped with the organocatalyst TEMPO (SiliaCat TEMPO) entered the market as suitable oxidation catalysts for the rapid and selective production of carbonyls and carboxylic acids. In the former case, SiliaCat TEMPO selectively mediates the oxidation of delicate primary and secondary alcohol substrates into valued carbonyl derivatives (Scheme 5.2), retaining its potent activity throughout several reaction cycles (Table 5.2).33 Using this catalyst, for example, enables the synthesis of extremely valuable a-hydroxy acids with relevant selectivity enhancement by coupling of SiliaCat TEMPO with rapid Ru04-mediated olefin dihydroxylation (Scheme 5.3).34... 

There are several reviews covering many aspects of nonlinear effects. The early examples of nonlinear effects almost exclusively dealt with organometallic catalysts. It is only very recently that some organocatalysts have been found to... 

Enantioselective organocatalysts were the first to be used as nonenzymatic catalysts in the early twentieth century. The literature on organocatalysts was reviewed in 2001. ... 

In the 1990s, short peptides,and other nucleophiles °° ° were used as organocatalysts for a number of enantioselective acyl transfer processes transformations that set the stage for the more recent research in the area of nucleophilic catalysis.One of the most appealing approaches to enantioselective acyl transfer was outlined by Fu using an azaferrocene catalyst (6) [Eq. (11.6)]. While these pyridyl systems are not organic catalysts in the strictest sense, these azaferrocene compounds function as chiral dimethylaminopyridine equivalents for a broad range of acyl transfer processes ... 

Michael additions using proline (2) as the organocatalyst have proven disappointing in terms of enantiocontrol, ° ° ° stimulating the search for a more selective enamine catalyst system. In this context, imidazolidinones (initially... 

Wang and co-workers reported a novel class of organocatalysts for the asymmetric Michael addition of 2,4-pentandiones to nitro-olefms [131]. A screen of catalyst types showed that the binaphthol-derived amine thiourea promoted the enantiose-lective addition in high yield and selectivity, unlike the cyclohexane-diamine catalysts and Cinchona alkaloids (Scheme 77, Table 5). 

Recently, Kunz et al. reported a new organocatalyst for the asymmetric Strecker reaction [132]. The paracyclophane-derived imine catalyst (280) promotes the hydrocyanation of various imines, both aromatic and aliphatic (Scheme 79). 

Fu s planar chiral ferrocenyl 4-DMAP derivative 16 is also the first organocatalyst that has been reported to efficiently perform the KR of certain propargylic ec-alcohols [83]. These KRs were achieved using 1 mol% of catalyst 16 and Acp as the acylating agent in tert-smyl alcohol at 0 °C in the absence of a stoichiometric auxiliary base... 

Groger has also reported a preliminary study on enantioselective acetyl migration in the Steglich rearrangement using one of Fu s commercially available catalysts and Birman s tetramisole-based organocatalyst [108]. 

In addition to the planar chiral ferrocenyl catalysts 15-18, 24 developed by Fu, a number of other chiral derivatives of 4-DMAP and 4-PPY [4, 47, 48] have been explored by other groups as organocatalysts for KR of ec-alcohols. Contributions have been made by the groups of Vedejs [104, 105, 110, 111], Fuji and Kawabata... 

The first catalyst of this type to be reported by Miller was tripeptide 48 in 1998 which adopts a ]3-tum type structure possessing one intramolecular hydrogen bond [159]. In addition, this organocatalyst judiciously incorporates a C-terminal R)-a-methylbenzylamide which prompts ji-ji stacking interactions (Scheme 17) [159]. 

Roles that are normally associated with metals as Lewis acids and as redox agents [4,5], can be emulated by organic compounds. This review will introduce the reader to the research field of Lewis acid organocatalysts. This field, compared to other types of organocatalysts, which are highlighted in the other chapters of this volume, is still limited. The number of asymmetric catalyzed examples is small, and the obtained enantiomeric excess is sometimes low. Therefore, this review will also cover a number of reactions promoted by achiral catalysts. Nevertheless, due to the broad variety of possible reactions, which are catalyzed by Lewis acids, this research field possesses a large potential. 

This review will concentrate on metal-free Lewis acids, which incorporate a Lewis acidic cation or a hypervalent center. Lewis acids are considered to be species with a vacant orbital [6,7]. Nevertheless, there are two successful classes of organocatalysts, which may be referred to as Lewis acids and are presented in other chapter. The first type is the proton of a Brpnsted acid catalyst, which is the simplest Lewis acid. The enantioselectivities obtained are due to the formation of a chiral ion pair. The other type are hydrogen bond activating organocatalysts, which can be considered to be Lewis acids or pseudo-Lewis acids. 

One section in this review will deal with silyl cations, another with hypervalent silicon compounds. The concept of hypervalent sihcon compounds belongs, strictly speaking, to the class of Lewis base catalysis. However, since a Lewis base forms in situ with a silicon containing reagent or SiCl an intermediate, which functions as a Lewis acid to activate substrates during the reaction, we would also present a few examples in this review. Since silicon is a semimetal we leave it up to the reader to decide whether silicon catalysts should be considered as organocatalysts. 

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