Reversibility enantioselectivity

For imines, a-imino esters with an N-p-methoxyphenyl substituent (21b) also reacted with Danishefsky s diene in the presence of 10 mol% of CUCIO4-T0I-BINAP to give the corresponding adduct in high yield with good enantiomeric excess (Scheme 5.10). Remarkably, reverse enantioselectivity was observed when the a-imino esters 21a and 21b were used. This notable selectivity was explained by as-... 

The Bacillus subtilis lipase A (BSLA) was the subject of two short directed evolution studies [19,47]. In one case systematic saturation mutagenesis at all of the ISlpositions of BSLA was performed [19]. Using meso-l,4-diacetoxy-2-cyclopentene as the substrate, reversed enantioselectivity of up to 83% ee was observed. In another study synthetic shuffling (Assembly of Designed Oligonucleotides) was tested using BSLA [47]. 

In contrast, both the ammonium and the carboxylic acid group of L-valine interacts preferentially with the narrow rim of permethylated jS-CD, whereas only the ammonium of d-valine interacts in the same way and its carboxylic acid group interacts preferentially with the wider rim of the host. Such a difference in the binding of the two enantiomers accounts for the observed high (and reverse) enantioselectivity (kolkL = 0.32). 

Naturally occurring Upases are (R)-selective for alcohols according to Kazlauskas rule [58, 59]. Thus, DKR of alcohols employing lipases can only be used to transform the racemic alcohol into the (R)-acetate. Serine proteases, a sub-class of hydrolases, are known to catalyze transesterifications similar to those catalyzed by lipases, but, interestingly, often with reversed enantioselectivity. Proteases are less thermostable enzymes, and for this reason only metal complexes that racemize secondary alcohols at ambient temperature can be employed for efficient (S)-selective DKR of sec-alcohols. Ruthenium complexes 2 and 3 have been combined with subtilisin Carlsberg, affording a method for the synthesis of... 

Scheme 10. Reverse enantioselectivity for the neutral and cationic pathways.

Asymmetric dihydroxylation of alkenes (14, 235-239). Further study1 of this reaction reveals that the optical yields of products can be markedly improved by slow addition (5-26 hours) of the alkene to the catalyst in acetone-water at 0° with stirring. The enantioselectivity can also be increased by addition of tetraethylam-monium acetate, which facilitates hydrolysis of osmate esters. The report suggests that the first product (1) of osmylation can undergo a second osmylation to provide 2, with reverse enantioselectivity of the first osmylation. 

Enzymes catalyze the reversible enantioselective addition of ammonia to a./ -unsaturated carboxylic acids to give L-a-amino acids. Immobilized enzymes and whole-cell bioreactor technology competes well with chemical methods31,32. For practical purposes, immobilized whole cells are preferred over immobilized enzyme because of the added cost of enzyme isolation. 

Catalytic asymmetric 1,3-dipolar cycloaddition of a nitrone with a dipolarophile has been performed using a chiral scandium catalyst [31]. The chiral catalyst, which was effective in asymmetric Diels-Alder reactions, was readily prepared from Sc(OTf)3, (7 )-(-i-)-BINOL, and d5 -l,2,6-trimethylpiperidine. The reaction of benzylbenzylide-neamine A-oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one was performed in the presence of the chiral catalyst to yield the desired isoxazolidine in 69 % ee with perfect diastereoselectivity (endolexo = > 99 1) (Sch. 8) [31,46], It was found that reverse enantioselectivity was observed when a chiral Yb catalyst, prepared from Yb(OTf)3, the same (i )-(-i-)-BINOL, and cd-l,2,6-trimethylpiperidine, was used instead of the Sc catalyst under the same reaction conditions. 

Similar to the chiral Yb catalyst, aging was observed in the chiral Sc catalyst. It was also found that 30 or 3-benzoyl-l,3-oxazolidin-2-one was a good additive for stabilization of the catalyst, but that reverse enantioselectivities by additives were not observed. This can be explained by the coordination numbers of Yb(III) and Sc(III) while Sc(III) has up to seven ligands, specific coordination numbers of Yb(III) allow up to twelve ligands [69,78]. 

A/-Benzoyldiazenes underwent [4 + 2] cycloaddition with ketenes under NHC catalysis (Scheme 163) (2009AGE192). Notably, this reaction is the subject of a computational investigation (2012JOC10729). Reverse enantioselectivities were observed for the NHC-catalyzed reaction of precursors 46a and 46b. The bulky mesityl substituent and the free hydroxy... 

In 2010, Janssen and co-workers reported that the kinetic resolution of p-phenylalanine catalysed by a tandem biocatalytic system composed of phenylalanine aminomutase (PAM) and phenylalanine ammonia lyase (PAL) yielded the corresponding enantiopure (5)-p-phenylalanine in good yield (48%) and excellent enantiomeric excess of >99% ee (Scheme 4.13). The process was based upon the PAM-catalysed, reversible, enantioselective transformation of (I )-p-phenylalanine to (S)-a-phenylalanine. The latter one was transformed in a PAL-catalysed regioselective process into ( )-cinnamic acid, with liberation of ammonia. This constituted an example of a tandem biocatalytic, kinetic resolution in which one enzyme catalysed the equilibration between the substrate and reaction intermediate, while the other shifted this equilibrium between the substrate towards the final product... 

The ester salts derived from L-proline (type I compounds Figure 8) afforded the BigineUi adducts in good yields (>80%) and enantioselectivity. The enantioselectivity was correlated with increasing steric hindrance of the group present on these catalysts [31]. Additionally, type II compounds (Figure 8), which would not lead to the formation of enamine intermediates, provided BigineUi adducts in lower yields and enantioselectivities. This result confirms the hypothesis that the enantioselectivity observed in tire former reaction involves an enamine intermediate. Notably, the use of o-proline provided the same products but witii a reverse enantioselectivity [31],... 

Conformational rigidity and flexibility are two key features for the development of an efficient chiral catalyst. Ma and coworkers developed a new generation of chiral dinuclear phase-transfer catalysts 47 by connecting two structurally rigid BINOL-derived chiral N-spiro quaternary ammonium salts with a flexible linker [80]. These catalysts were proven to act via dual activation of both nucleophiles and electrophiles and to be very efficient catalysts for the conjugate addition of hindered nitroalkanes to enones. Notably, a completely reversed enantioselectivity could be easily switched with catalysts (S,S)-47a and (S,S)-47b, which differ in the length of the methylene chain of the linker but not in the chiral element of backbone. 

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