Basic organocatalysts

A new, metal-free protocol involving (heteroaryl)oxazoline catalysts for the enantioselective reduction of aromatic ketones (up to 94% ee) and ketimines (up to 87% ee) with trichlorosilane has been developed. The reaction is characterized by an unusual, long-ranging chiral induction.The enantiodifferentiation is presumed to be aided by aromatic interactions between the catalyst and the substrate.360 Asymmetric reduction of A-arylketimines with trichlorosilane is catalysed by A-methyl-L-amino acid-derived Lewis-basic organocatalysts with high enantioselectivity (up to 92% ee) 61... 

Formamides as Lewis-Basic Organocatalysts in Hydrosilylation of Imines... 

Chiral N heterocyclic carbenes (NHCs), as Lewis basic organocatalysts, have been synthesized and applied to enantioselective organocatalytic reactions in recent years. Encouraged by Sheehan and Hunneman s first report of chiral thiazolium salts as NHC precursors for organocatalytic reactions [37], Leeper, Enders, Rovis, Glorius, Herrmann, and others have synthesized series of novel chiral NHCs with mono cyclic, bicyclic, or tricyclic backbones [38]. Recently, a series of bifunctional NHCs were synthesized and applied to aza BMH reaction of cyclopent 2 enone with... 

The allylation of aldehydes provides a useful route to homoallylic alcohols. The most popular methods for achieving this in an asymmetric fashion are by the use of metal-based Lewis acid catalysts or using Lewis basic organocatalysts. ... 

Sun and co-workers developed a novel Lewis basic organocatalyst 86 (Scheme 31), easily synthesized from commercially available L-pipecolinic acid. The catalyst 86 promoted the reduction of IV-aryl ketimines 85 with HSiCl3 2 in high yield and... 

On the basis of the experimental results, the methoxy group on C2 has proven to be critical for the high efficiency of catalyst 87 in the reduction of the imines. A hexacoordinate silicon transition structure was proposed to justify the experimental observations. In a more extended mechanistic study iV-funtionalized pipecoli-namides 88 were proposed as an example of efficient catalyst after several variations in the C2 and the A-protected group ([185], for more recent L-pipecolinic basic organocatalysts for hydrosilylation of imines, see [186, 187]). 

Wang Z, Ye X, Wei S, Wu P, Zhang A, Sun J. A highly enantioselective Lewis basic organocatalyst for reduction of iV-aryl imines with unprecedented substrate spectrum. Org. Lett. 2006 8 999-1001. 

The Michael additions of 3-benzyl-substituted oxindoles to M-substituted maleimides has been reported to proceed with <99% ee in the presence of the C2-symmetric bicyclic guanidine (302) as a basic organocatalyst in toluene at -50 C over 48 h. A plausible transition state has been proposed4 ... 

Scheme 6.55 Design principle of amine-functionalized bifunctional thiourea organocatalysts derived from privileged monofunctional thiourea 9 cooperating with an amine base additive (A) and basic bifunctional mode of action of chiral amine...

Optimized reaction conditions call for the use of Wilkinson s catalyst in conjunction with the organocatalyst 2-amino-3-picoline (60) and a Br0nsted add. Jun and coworkers have demonstrated the effectiveness of this catalyst mixture for a number of reactions induding hydroacylation and C—H bond fundionalization [25]. Whereas, in most cases, the Lewis basic pyridyl nitrogen of the cocatalyst ads to dired the insertion of rhodium into a bond of interest, in this case the opposite is true - the pyridyl nitrogen direds the attack of cocatalyst onto an organorhodium spedes (Scheme 9.11). Hydroamination of the vinylidene complex 61 by 3-amino-2-picoline gives the chelated amino-carbene complex 62, which is in equilibrium with a-bound hydrido-rhodium tautomers 63 and 64. 

Another class of bifunctional organocatalysts for the enantioselective aza-Morita-Baylis-Hillman reaction of imines (112) with enones (113) (Scheme 6) is based on BINOL (115). The efficiency of the catalysts proved to be mainly influenced by the position of the Lewis basic moiety attached to the BINOL scaffold. The activation of the substrate by acid-base functionalities and the fixing of conformation of the catalyst (115) are apparently harmonized to maximize the enantiocontrol (<95% ee) 52... 

For similar reactions, Takemoto et al. developed a novel organocatalyst 40, which was designed to place both acidic and basic moieties appropriately on the same catalyst scaffold (Scheme 20) [23]. It was proposed the thiourea activated nitroolefins by hydrogen bonding. 

Although the turnover frequency (TOF) and turnover number (TON) of the various above-described organocatalysts remain modest when compared to metal catalysis, the chiral organocatalysts are of relatively simple structure, and this permits easy tuning of the reaction. Clearly, one can predict many improvements in this area in the future, and undoubtedly new organocatalytic reactions relating to reduction will be introduced, using some of the basic processes described in Section 11.1. 

S.C. PanandB. List s paper spans the whole field of current organocat-alysts discussing Lewis and Brpnsted basic and acidic catalysts. Starting from the development of proline-mediated enamine catalysis— the Hajos-Parrish-Eder-Sauer-Wiechert reaction is an intramolecular transformation involving enamine catalysis—into an intermolecular process with various electrophilic reaction partners as a means to access cY-functionalized aldehydes, they discuss a straightforward classification of organocatalysts and expands on Brpnsted acid-mediated transformations, and describe the development of asymmetric counteranion-directed catalysis (ACDC). 

The recent development of polymers containing imidazolium, thiazolium and related structures as supported equivalents of ionic liquids (i.e. 148 and 149, Scheme 10.23) is an interesting development of this field [356-361], The corresponding salts containing basic counter-anions can act as basic catalysts but can also be transformed, depending on the exact structure, into N-heterocydic car-benes that can act as nucleophilic organocatalysts [362]. As an example, resins 148... 

In summary, development of functional polymers that can act as efficient organocatalysts is at the origin of the application of modified polymers as reagents and catalysts in chemistry. To date, the most successful accomplishments have been carried out in the area of basic and acid catalysts. Not surprisingly, this area includes some of the most important industrial applications for supported reagents and catalysts. In general, the development of non-chiral polymer-supported organocatalysts is a field of research that involves both industrial and academic research. In many cases, it has been possible to demonstrate how the use of the... 

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