Bifunctional organocatalyst

Takemoto and co-workers communicated that bifunctional organocatalyst 166 would promote aza-Henry reactions of phosphinoyl imines with nitroalkanes (Scheme 52) [104]. The catalytic additions provided high selectivities and yields... 

Pratt RC, Lohmeijer BGG, Long DA, Waymouth RM, Hedrick JL (2006) Triazabicyclodecene a simple bifunctional organocatalyst for acyl transfer and ring-opening polymerization of cyclic esters. J Am Chem Soc 128 4556-4557... 

Takemoto et al. were the first to report that bifunctional organocatalysts of the thiourea-tert-amine type efficiently promote certain Michael reactions, for example, the addition of 5-dicarbonyl compounds to nitro olefins [29-31]. 

In 2005, Nagasawa and co-workers developed a new catalyst design concept leading to novel hydrogen-bonding bifunctional organocatalysts, which incorpo-... 

Compared to the chemo-catalyzed kinetic resolution of alcohols, there are few reports of similar reactions for amines. Building on other work, one elegant example from Berkessel uses bifunctional organocatalysts to enantioselectively hydrolyze a racemic azlactone, and the dynamic kinetic resolution (DKR) is achieved by in-situ acid-catalyzed racemization of the azlactone under mild conditions to give product N-acylarnino esters in, for example, 72% ee and 96% conversion with phenylalanine [6]. 

Sterically and electronically tuneable and bifunctional organocatalysts based on diamides derived from proline are particularly selective in reactions of heterocyclic ketones with aldehydes.109... 

A diastereomeric guanidine-bisthiourea bifunctional organocatalyst gives high ees (g) and des in nitroaldols in a biphasic system toluene-water at 0°C.146... 

Chiral BINOL (60) is a bifunctional organocatalyst in addition to the phenolic Brpnsted acid groups, it has a Lewis base unit attached via a spacer moiety.167 This particular combination holds the groups in a conformational lock, where they can doubly activate a substrate while giving a high level of stereocontrol. For this example of an aza-Morita-Baylis-Hillman reaction of an enone and an imine, yields up to 100% and ees up to 96% have been achieved. 

S)-3-(A-Isopropyl-A-3-pyridinylaminomethyl)BINOL (4) has been established as an efficient asymmetric bifunctional organocatalyst for the aza-MBH reaction.23 The acid-base functionalities cooperate in substrate activation and fixing of the organocatalyst conformation to promote the reaction with high enantiocontrol. 

A series of diaryl-2-pyrrolidinemethanols have been tested as catalysts for the enan-tioselective Michael addition of malonate esters to nitroalkenes.30 Bis-(3,5-dimethyl-phenyl)[(S)-pyrrolidin-2-yl]methanol (6), easily prepared from L-proline, has been found the most efficient bifunctional organocatalyst, providing up to 56% ee. 

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... 

Scheme 1. Diastereo- and/or enantioselective aminoalkylation of ketones catalyzed by a chiral bifunctional organocatalyst [8a].

Scheme 4. Dynamic kinetic resolution of azlactones 6 by alcoholytic ringopening, effected by the bifunctional organocatalysts 8...

Hoashi Y, Okino T, Takemoto Y (2005) Enantioselective michael addition to alpha, beta-unsaturated imides catalyzed by a bifunctional organocatalyst. Angew Chem Int Ed Engl 44 4032... 

Okino T, Hoashi Y, Takemoto Y (2003) Enantioselective michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts. J Am Chem Soc 125 12672... 

Cao CL, Ye MC, Sun XL, Tang Y (2006) Pyrrohdine-thiourea as a bifunctional organocatalyst Highly enantioselective michael addition of cyclohexanone to nitroolefins. Org Lett 8 2901... 

In 2005, the groups of Connon [38] and Dixon [39] independently reported that epi-cinchona-based (thio)urea derivatives can serve as excellent bifunctional organocatalysts... 

Recently, more efforts have been devoted to the design of novel bifunctional organocatalysts derived from natural cinchona alkaloids, which have been successfully applied in a number of asymmetric reactions. Deng et al. promoted the extensive... 

Figure 4.4 Structure of guanidine-thiourea bifunctional organocatalyst 15...

Okino, T, Nakamura, S., Eurukawa, T. and Takemoto, Y. (2004) Enantioselective aza-Henry reaction catalysed by a bifunctional organocatalyst. Organic Letters, 6, 625-627. 

Bifunctional organocatalysts, particularly, (S)-3-(N-isopropyl-N-3-p5nidi-nylaminomethyl) BINOL for enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reactions 07Y1089. 

A number of BINOL-based bifunctional organocatalysts, for example (7.171-7.173), containing both Bronsted acidic and Lewis basic sites have been used to good effect in the asymmetric MBH reaction. The amine-thiourea (7.171) promotes the MBH reaction of aliphatic aldehydes with 2-cyclohexenone with ees ranging from 80 to 94% while both the (pyridinylaminomethyl)BINOL (7.172) and phosphine (7.173) catalyse the aza-Bayhs-Hilhnan reaction of simple a,p-carbonyls such as MVK and phenyl acrylate with N-tosyl arylaldmines with similar levels of enantioselectivity. 

Riguet developed guanidinyl derived pyrrolidine bifunctional organocatalysts 2g-i for the Miehael addition of malonate to 2-cyclohexenone in the presence of a protie aeid. The Michael adducts were generally obtained in high yields and with good enantioseleetivities, as described in Scheme 9.19. ... 

Chen et al, designed and synthesised a series of chiral pyrrolidinyl-sulfamide derivatives, identifying 3j as an efficient bifunctional organocatalyst for the direct Michael addition of cyclohexanone to a wide range of nitrostyrenes. The desired Michael adducts were obtained in high chemical... 

Oxazole-containing molecules found several applications in catalysis and materials chemistry. Pyrrolidinyl-oxazole-carboxamide catalysts 140 were reported as new chiral bifunctional organocatalysts effective in the asymmetric Michael addition of ketones to nitroolefins (140BC8008). Compound 141 exhibits different spectral properties (both in absorption and emission) in response to external stimuli, such as pressure and protonation, and it is therefore promising for the realization of piezofluorochromic materials (14CC2569). 

High yields of 2-substituted chromans are readily attained from the asymmetric intramolecular oxa-Michael addition reaction of phenols bearing an (f -a,P-unsaturated ketone or thioester moiety mediated by a cinchona-alkaloid-urea-based bifunctional organocatalyst (140BC119). Molecular iodine-catalyzed reaction of phenols with a,P-unsaturated alcohols affords a wide range of 2,2-disubstituted chromans (14T5221). Chiral derivatives result from the intramolecular allylic alkylation of phenols bearing an... 

Bifunctional organocatalysts in the asymmetric Michael additions of carbonylic compounds to nitroalkenes 12COC2440. 

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