Chiral amine catalysts

Shi and Xu reported that the chiral amine catalyst 142 also performs quite efficiently in the related addition of N-tosyl aryl imines to methyl vinyl ketone (MVK), to methyl acrylate, and to acrylonitrile (Scheme 6.61) [155]. As shown in Scheme 6.61, enantiomeric excesses > 95% were achieved for several />-N-tosylamino enones 147 obtained by addition of aryl imines (146) to MVK, > 80% for addition to methyl acrylate, and 55% ee (max.) for addition to acrylonitrile (not shown in Scheme 6.61). Reaction times were typically 1-3 days. N-Sulfonylimines derived from aliphatic aldehydes gave rise to complex product mixtures. Under the reaction conditions shown in Scheme 6.61 addition of p-nitrobenzaldehyde to MVK proceeded with only 20% ee. 

Other centrally chiral amine catalysts reported for kinetic resolution of alcohols include the (S)-prolinol-derived dihydroisoindolines 12a,b (Scheme 12.4), devel-... 

Angew. Chem. 1978, 90, 602-615 Angew. Chem., Int. Ed. Engl. 1978, 37, 569-583 (c) for a recent review on nucleophilic chiral amine catalysts see ... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used stoichiometrically. For achiral reactions, NEt3 can serve both functions. The subsequent reaction follows the pathway known from the reverse mode reactions, with the catalyst recovered unchanged ... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used... 

C-Oxo Acid or Ester Chiral Amine Catalyst Yield (%) Amino Acid ee(%) Configuration Ref. 

The condensation of an aldehyde with a chiral amine leads to the formation of an iminium intermediate 510. The product 511 can be hydrolyzed to yield the enantioenriched product 512 and regenerates the chiral amine catalyst (Scheme 105) <2004ASC1175>. 

A ry -selective, organocatalytic, enantioselective vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to a,/ -unsaturated aldehydes to produce 7-butenolides was achieved by using a chiral amine catalyst... 

The phenylalanine-derived chiral amine catalyst 10 was used to promote the asymmetric [4-1-3] cycloaddition between 2,5-dialkylfurans and trialkylsilyloxypentadienals to generate seven-membered carbocycles with OTrfo-selec-tivity and 81-90% ee, as represented in Equation (46) <2003JA2058>. However, the absolute configurations of the cycloadducts have not been determined. 

The chiral amine catalyst shown below was used to promote the asymmetric [4+3] cycloaddition between 2,5-disubstituted furans and trialkylsilyloxypentadienals to generate 7-membered carbocycles with enJo-selectivity and in a promising 89% ee <03JA2058>. Computational studies of the AICI3-catalyzed [4+3] cycloaddition between 2-(trimethylsilyloxy)acrolein and furan at the B3LYP/6-31G level showed that the reaction was a three-step process <03OL4117>. 

Recently, kinetic studies have shown that the catalytic osmylation of alkenes in the presence of cinchona derivatives as chiral amine catalysts (vide infra) is first order with respect to 0s04 and alkene, but shows saturation behavior with respect to the amine ligand42. The influence of the reaction temperature on the enantioselectivity of these reactions has also been studied. Eyring plots according to the equation ... 

Compared with aldehydes, the asymmetric CDC reactions of THIQs with ketones are much more challenging due to the diminished reactivity of the carbonyl group of ketones. Since 2000, the chiral amine catalysts including secondary amines and primary amines have witnessed rapid development as a significant category of organocatalysts, providing versatile reactivities... 

The reaction of A -Fmoc-L-leudnal (139) with l,l,l>3,3>3-hexafluoroisopropyl acrylate (140) proceeded smoothly in the presence of a stoichiometric amount of cinchona alkaloid 141, even at very low temperature, to give a 6 1 mixture of j yw-ester 142 and dioxane derivative 143 (Scheme 1.62). However, the same reaction with N-Fmoc-o-leucinal (ent-139) turned out to be sluggish and only a mixture of dioxanones 143 was obtained in low yield. Thus, it can be concluded that the (/ )-selectivity of the chiral amine catalyst matches well with L-config-uration of the substrate, leading to high yn-selectivity. ... 

To realize an efficient catalytic asymmetric MBH reaction, wherein a high level of asymmetric induction as well as desired rate acceleration is obtained, the appropriate combination of chiral amine catalyst and suitably activated alkene is required. Besides cinchona derivative catalysts, more chiral catalysts have been developed from achiral molecules such as DABCO, quinuclidine, indoli-zine or pyrrolizine-derived catalysts by introducing asymmetric functions. Hirama and co-workers have examined chiral C2-symmetric 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octanes such as 2,3-(dibenzoxymethyl)-DABCO (162) as a catalyst for the asymmetric MBH reaction between 4-nitrobenzaldehyde and MVK (Scheme 2.79). Compared with achiral DABCO, chiral catalyst 162 showed diminished reactivity and the reaction required high pressure to ensure a reasonable reaction rate. The corresponding adduct was obtained in up to 47% ee. 

The amine-catalysed asymmetric conjugate addition of aldehydes to nitroalkenes is a powerful tool for stereoselective carbon-carbon bond formation, and hence, a large number of chiral amine catalysts have been developed to date. ° In most amine-catalysed reactions, q n-conjugate adducts were obtained as major diastereomers. For instance, the reaction catalysed by a chiral pyrrolidine (5 )-6 gave a sy -conjugate adduct with excellent enantioselectivity (Scheme 17.13). In contrast, the reaction using a biphenyl-based amine catalyst (S)-7 is complementary to most amine-catalysed... 

OxidatiV0 Enamine Catalysis. The oxidative transformation of enam-ines derived from saturated aldehydes into a,(3-unsaturated iminium ions by dehydrogenation has been independently disclosed in 2011 by Li, Wang, and co-workers [108] and by Hayashi and co-workers [109]. This chemistry provides an alternative procedure to the standard iminium catalysis, which relies on the use of a,(3-unsaturated aldehydes. Both research groups used diphenylprolynol trimethylsilyl ether as the chiral amine catalyst but while Wang employs o-iodoxybenzoic acid (IBX) as the stoichiometric oxidant [108], Hayashi s procedure relies on the use of 2,3-dichloro-5,6-dicyanoquinone (DDQ) as the oxidant [109]. This oxidation can be performed in the presence of a suitable nucleophile... 

Chiral amines have been extensively applied as catalysts in enantioselective BH reactions. Selected examples with chiral amine catalysts except for cinchona derivatives were listed in Scheme 9.24. It is logical to explore chiral DABCO... 

In 2007, the Jorgensen group reported a highly enantioselective procedure for the conjugate addition of oximes to a,p-unsaturated aldehydes in the presence of a chiral amine catalyst (296). This protocol was later expanded to the one-pot synthesis of optically active p-diols by carrying out a vinylogous addition of oxime 317 to different a,p-unsaturated aldehydes in the presence of catalyst 276 followed by a direct reduction of the primary addition product with LiAlHj (297). 

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