Amino enantioselective reaction

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

Ligands for catalytic Mukaiyama aldol addition have primarily included bidentate chelates derived from optically active diols,26 diamines,27 amino acid derivatives,28 and tartrates.29 Enantioselective reactions induced by chiral Ti(IY) complex have proved to be one of the most powerful stereoselective transformations for synthetic chemists. The catalytic asymmetric aldol reaction introduced by Mukaiyama is discussed in Section 3.4.1. 

Enantioselective conjugate addition of cuprates. This enantioselective reaction has been demonstrated using the amino alcohol 1, prepared by reaction of (2-chloroethyl)dimethylamine with(lR,2S)-(-)ephedrine, as a ligand.1 The cuprates obtained from 1 by deprotonation (RLi), reaction with CuI-S(CH,)2, and... 

Amino Alcohol Catalyzed Alkylation. (—)-3-exo-(Dimethylamino)-isobomeol [( —)-DAIB] is a sterically restrained jS-dialkylamino alcohol that has proven to be an extremely efficient catalyst 13). For instance, in the presence of 2 mol % of (—)-DAIB, the reaction of benzaldehyde and diethylzinc proceeds smoothly to give, after aqueous workup, (5)-1 -phenyl-1 -propanol in 98% ee and in 97% yield along with a small amount of benzyl alcohol (Scheme 9). Nonpolar solvents such as toluene, hexane, ether, or their mixtures produce satisfactory results. The optical yield in toluene is affected by temperature and decreases from 98% at —20°C to less than 95% at 50°C. The catalytic enantioselective reaction has been extended to a range of alkylating agents and aldehyde substrates, which are summarized in Scheme 10 (75). p-Substituted ben-... 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

Protected glycine derivatives have been used as the nucleophilic partner in enantioselective syntheses of amino acid derivatives by chiral PTC (Scheme 10.9). Loupy and co-workers have reported the addition of diethyl acetylaminomalonate to chalcone without solvent with enan-tioselectivity up to 82% ee [44]. The recent report from the Corey group, with catalyst 8a used in conjunction with the benzophenone imine of glycine t-butyl ester 35, discussed earlier, results in highly enantioselective reactions (91-99% ee) with various Michael acceptors (2-cyclo-hexenone, methyl acrylate, and ethyl vinyl ketone) to yield products 71-73 [21], Other Michael reactions resulting in amino acid products are noted [45]. 

Ferrocenylphosphines, chiral. Hayashi et al.1 have prepared a large number of chiral ferrocenylophosphines, which have planar chirality owing to 1,2-unsymmetrical substitution on the ferrocene group. In addition, one of the substituents contains a chiral carbon atom. The most interesting phosphines have amino or hydroxyl groups in the side chain. These phosphines, in combination with transition metals, can promote highly efficient enantioselective reactions. 

Mannich reactions varied from excellent to low depending on the reactants Table 2.16 includes the results of highly enantioselective reactions. Reactions using 2,2-dimethyl-l,3-dioxane-5-one (5) provide for concise syntheses of enantiomerically enriched protected amino sugars (entries 8-10) [91]. In reactions using 5, the addition of 1 to 10 equiv. of H20 increased the rate and stereoselectivity of the reaction. 

The multitude of hetero Diels-Alder reactions found in the literature clearly demonstrates the importance of this transformation. Thus, this type of cycloaddition is today one of the most important methods for the synthesis of heterocycles. Striking features of this method are the tremendous diversity, excellent efficiency especially in those cases where the reactive dienes and dienophiles are formed in situ, and high stereoselectivity in many cases. There is a broad scope and only little limitation. In recent years the use of Lewis acid, the development of diastereoselective and enantioselective reactions as well as the application of high pressure gave an enormous push. In addition, many of the obtained heterocycles can be transformed into acyclic compounds allowing the stereoselective preparation of e.g. amino and hydroxyl functionalized open chain compounds or even carbocycles to be of interest. Also, for the synthesis of natural products, the hetero Diels-Alder reaction is of great value. Since heterocycles,... 

Chiral amino alcohols catalyze the enantioselective reaction of diethyl zinc with benzaldehyde to give 1-phenyl propanol. A mixture of the two enantiomers of the amino alcohol, not in equal proportion, is used as the catalyst, and the relative amounts varied. More than 90% e.e. is obtained with a ratio of 1.2, but zero e.e. is obtained when it is 1.0 (exactly racemic). Explain. 

A new diastereoselective and enantioselective synthesis of a-amino-y-oxo acid esters has been reported involving the alkylation of enamines with acyliminoacetates (78). The stereocontrol is attributed to formation of a Diels-Alder like transition state (79). Ring opening of the adduct leads to a zwitterion or alkylated enamine, hydrolysis of which gives the single diastereoisomer (80 de > 96%)174 (Scheme 71). The use of a chiral ester [R = ( + )- or ( —)-menthyl or (—)-8-phenylmenthyl] converted this process into an enantioselective reaction (de and ee 24-67%). Since the reaction proceeds with complete anti-diastereoselectivity the two stereoisomers, enantiomeric at the two new stereogenic centres, could readily be separated by fractional crystallization. The main isomer of 80 (X = CH2), obtained in 80% yield, was shown to have the (l S, 2R)-configuration174. 

The CHF and CF2 groups are superior to CH2 as isosteres of oxygen and this has led to extensive interest in their chemistry. The a-difluorophosphonate analogues of the phosphates of L-serine (219), L-threonine (220), and L-allothreonine (221) have been prepared by highly enantioselective reactions of difluoromethylpho-sphonate carbanion with chiral esters. Lipase PS catalysed acetylation of prochiral 1,3-propandiol alkylphosphonates 222 is reported to be highly enantioselective and the resulting monoacetate enantiomers 223 have been used to synthesise a series of (o-phosphono-a-amino acids, 224 and 225.Other routes to 225, one of... 

Analogously, starting from A-methyl-A-phenyl-3-amino-2-cyclohexen-l-one derivatives, an enantioselective reaction took place forming A-methylhexahy-dro-4-carbazolones.5 ... 

Kobayashi and coworkers pioneered the use of enamides or enecarbamates as nucleophiles in enantioselective reactions with either glyoxylates or glyoxylate derived imines catalyzed by chiral copper complexes [65]. The reaction using enamides or enecarbamates as nucleophilic components, namely, the aza ene reaction, with imines provides P amino imines that can be readily transformed into... 

Muzart and coworkers have succeeded in a catalytic asymmetric protonation of enol compounds generated by palladium-induced cleavage of 3-ketoesters or enol carbonates under nearly neutral conditions [47,48]. Among the various optically active amino alcohols tested, (-i-)-e do-2-hydroxy-endo-3-aminoborn-ane (25) was effective as a chiral catalyst for the enantioselective reaction. Treatment of the P-ketoester of 2-methyl-1-indanone 58 with a catalytic amount of the amino alcohol 25 (0.3 equiv) and 5% Pd on charcoal (0.025 equiv) under bubbling of hydrogen at 21 °C gave the (P)-enriched product 59 with 60% ee... 

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great taiget for researchers. Many excellent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantioselective reaction, asymmetric hydrogenation of OC-acetamidoacrjdic acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

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