Organocatalysts activations

In the research on new potential antitubercular agents, Botta et al. applied a Knoevenagel-HDA MCR, which was catalyzed by a,a-diphenylprolinol 84 under microwave irradiation at 110 °C (Scheme 13.24) [41], The organocatalyst activates the carbonyl group in a double hydrogen bond donation motif. 

Both the ureas and thioureas are highly suitable organocatalysts for the asymmetric Strecker synthesis. For example, the thiourea function was replaced by an urea function (note the opposite configurations). The organocatalysts thus obtained showed similar activity and slightly higher enantioselec-tivities with N-allyl benzaldimine (Scheme 39,74% yield with 95% ee for Ri = Bn and R2 = H). Once again, better enantioselectivity (up to 99% ee) was at-... 

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... 

Aromatic thioureas were more active than alkyl (octyl, cyclohexyl) derivatives. Thioureas with trilluoromethyl substituents were even more effective. The same group also showed that these organocatalysts can act as weak Lewis acids and are thus able to alter the stereochemistry of the Diels-Alder reaction between cyclopentadiene and chiral acrylamide derivatives (Scheme 49) [167]. 

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... 

Abstract A-Heterocyclic carbenes (NHCs) have developed into an important class of ligands in transition metal coordination chemistry. They have been employed successfully as spectator ligands in various catalytically active metal complexes and as organocatalysts. In this chapter we present some important synthetic methods for the preparation of various NHCs and their metal complexes. 

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... 

Miscellaneous Reactions Berkessel " has identified peptide-like urea-based bifiinctional organocatalysts for the highly efficient dynamic kinetic resolution of azalactones (Scheme 11.14a). Another selective hydrogen-bonding activation mechanism that enables the addition of pyrroles to ketenes using catalytic quantities of azaferrocene 36 has been introduced by Fu and coworkers (Scheme 11.14b). ° ... 

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. 

After having proven that BINOL phosphates serve as organocatalysts for asymmetric Mannich reactions, Akiyama and Terada et al. reasoned that the concept of electrophilic activation of imines by means of chiral phosphoric acids might be applicable to further asymmetric transformations. Other groups recognized the potential of these organocatalysts as well. They showed that various nucleophiles can be used. Subsequently, chiral phosphates were found to activate not only imines, but also other substrates. 

Finally, a highly efficient organocatalytic asymmetric approach was described by Gong et al. in 2006, using chiral phosphoric acids as catalysts. These results opened a window for the development of new optically active DHPMs synthesis (Scheme 19) [96, 97]. More recently, chiral organocatalysts such as Cinchona... 

Figure 6.1 Chronological order of milestone achievements toward catalytically active (thio)urea organocatalysts utilizing explicit double hydrogen-bonding interactions for substrate activation.

As demonstrated in a series of kinetic experiments by Wittkopp and Schreiner, nitrone N-benzylideneanihne N-oxide can be activated for 1,3-dipolar cycloadditions through double hydrogen-bonding 9 [Ij. Takemoto and co-workers, in 2003, published the nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes proceeding in the presence of thiourea organocatalyst 9 (Figure 6.4) [147]. 

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