Asymmetric glycine imine derivatives

In addition, in 2(X)4 Mamoka and co-workers [72] synthesized a recyclable fluorous chiral phase-transfer catalyst which was successfully applied for the catalytic asymmetric alkylation of a glycine-imine derivative followed by extractive recovery of the chiral phase-transfer catalyst using fluorous solvent. Later, in 2010 Itsuno and co-workers [73] published a new type of polymer-supported quarternary ammonium catalysts based on either cinchona alkaloids or Maruoka s-type catalyst bound via ionic bonds to the polymeric sulfonates. 

Asymmetric Phase-Transfer Reactions of Glycine Imine Derivatives... 

Some phase-transfer catalytic asymmetric alkylation reactions of glycine imine derivatives have been explored to access natural products and biologically active compounds. For example, by employing an enantioselective phase-transfer catalytic alkylation, Kim et al. accomplished the first asymmetric total synthesis of the naturally occurring phenanthroindolizidine alkaloid (—)-antofine (Scheme 12.2) [102]. The key feature of this synthesis is the creation of the stereogenic center by reacting 65a with electrophile 66 in the presence of the dimeric catalyst 28 under the phase-transfer conditions. 

More recently, catalytic asymmetric allylations of imines and imine derivatives in aqueous media have been studied. An /V-spiro C2-symmetrical chiral quaternary ammonium salt (5,5)-I-Br (,S, .S )-()-Np-NAS-Br] has been evaluated in the allylation of glycine tert-Bu ester benzophenone Schiff base [Ph2C=NCH2COOCMe3] for synthesis of both natural and unnatural a-amino acids (Eq. 11,45).76... 

Addition of nucleophiles to electrophilic glycine templates has served as an excellent means of synthesis of a-amino acid derivatives [2c, 4—6]. In particular, imines derived from a-ethyl glyoxylate are excellent electrophiles for stereoselective construction of optically active molecules [32], This research and retrosyn-thetic analysis led us to believe that amine-catalyzed asymmetric Mannich-type additions of unmodified ketones to glyoxylate derived imines would be an attractive route for synthesis of y-keto-ce-amino acid derivatives [33], Initially, L-proline-catalyzed direct asymmetric Mannich reaction with acetone and N-PMP-protected a-ethyl glyoxylate was examined in different solvents. The Mannich-type reaction was effective in all solvents tested and the corresponding amino acid derivative was isolated in excellent yield and enantioselectivity (ee >95 %). Direct asymmetric Mannich-type additions with other ketones afford Mannich adducts in good yield and excellent regio-, diastereo- and enantioselectivity (Eq. 8). 

Alkylations of acyclic enolates containing a collection of chiral auxiliary groups have been used successfully for the asymmetric synthesis of carboxylic acids. The chiral, nonracemic substrates that have been used include amides, imides, esters, imine derivatives of glycinates and acyl derivatives of chiral transition metals. In these systems either extraannular or chelate-enforced intraannular chirality transfer may control the sense of the alkylation step. 

ASYMMETRIC PHASE-TRANSFER CATALYSED ALKYLATION OF GLYCINE IMINES USING CINCHONA ALKALOID DERIVED QUATERNARY AMMONIUM SALTS... 

Numerous guanidine-catalysed asymmetric Michael reactions and its related variants such as aza-Michael, oxa-Michael, phospha-Michael, sulfa-Michael have been reported in the literature. A nonexhaustive selection of conjugate addition reactions that is relevant to green chemistry will be presented. Glycine imines are commonly employed in Michael additions. They are protected a-amino acids and must he deprotected if an amino acid derivative is desired (Scheme 23.5). The large molecular mass of the imine group then makes waste generation a problem. 

Some chiral phase-transfer catalysts can also promote enantioselective aldol and Mannich condensations of glycine imine donors with aldehyde and imine acceptors. These reactions provide important tools for the asymmetric constmction of P-hydroxy-a-amino acid and a,p-diamino acid derivatives, which are extremely interesting chiral units in the synthesis of pharmaceutical and natural products. For... 

By using tartrate-derived bisammonium salts as chiral phase-transfer catalysts, Shibasaki and coworkers developed the asymmetric Mannich condensation of glycine imine ester 65a with N-Boc-protected aldimines [82,115]. The condensation products were obtained with high diastereoselectivities and moderate to good enantioselectivities. This method could be applied to access the enantiomerically enriched 3-amino pyrrolidine intermediate 88 for the further synthesis of (-1-)-nemonapride (Scheme 12.13). 

The imines of ( )-(l/ ,2/ ,5/ )-2-hydroxy-3-pinanone and glycine, alanine and norvaline methyl esters were highly successful as Michael donors in the asymmetric synthesis of 2,3-di-substituted glutamates. The chiral azaallyl anions derived from these imines by deprotonation with lithium diisopropylamide in THF at — 80 "C undergo addition to various ,/ -unsaturated esters with modest to high diastereoselectivities210,394. 

Grigg and co-workers (383) found that chiral cobalt and manganese complexes are capable of inducing enantioselectivity in 1,3-dipolar cycloadditions of azomethine ylides derived from arylidene imines of glycine (Scheme 12.91). This work was published in 1991 and is the first example of a metal-catalyzed asymmetric 1,3-dipolar cycloaddition. The reaction of the azomethine yhde 284a with methyl acrylate 285 required a stoichiometric amount of cobalt and 2 equiv of the chiral ephedrine ligand. Up to 96% ee was obtained for the 1,3-dipolar cycloaddition product 286a. 

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

An important issue is the right choice of substrate 1 which functions as an anion precursor. Successful organocatalytic conversions have been reported with indanones and benzophenone imines of glycine derivatives. The latter compounds are, in particular, useful for the synthesis of optically active a-amino acids. Excellent enantioselectivity has been reported for these conversions. In the following text the main achievements in this field of asymmetric organocatalytic nucleophilic substitutions are summarized [1, 2], The related addition of the anions 2 to Michael-acceptors is covered by chapter 4. 

Asymmetric synthesis of ot-amino acids.1 This optically active phase-transfer catalyst (1) can effect enantioselective alkylation of the imine (2) derived from glycine. The highest enantioselectivity obtains with the t-butyl ester the lowest with benzylic type esters. Alkylation of 2 results in a mixture of enantiomers, but crystallization of the mixture removes the racemic product and leaves the highly pure optically active amino ester in solution. 

Bagley MC, Brace C, Dale JW, Ohnesorge M, Phillips NG, Xiong X, Bower J (2002) J Chem Soc [Perkin 1] 1663 Belattar A, Saxton JE (1992) J Chem Soc [Perkin 1] 679 Bernardi L, Gothelf AS, Hazell RG, Jprgensen KA (2003) Catalytic asymmetric Mannich reactions of glycine derivatives with imines. A new approach to optically active alpha,beta-diamino acid derivatives. J Org Chem 68 2583-2591... 

A few years ago Cahard reported a series of studies on the use of immobilized cinchona alkaloid derivatives in asymmetric reactions with phase-transfer catalysts [17[. Two types of polymer-supported ammonium salts of cinchona alkaloids (types A and B in Scheme 8.4) were prepared from PS, and their activity was evaluated. The enantioselectivity was found to depend heavily on the alkaloid immobilized, with the type B catalysts usually giving better results than the type A catalysts. By performing the reaction in toluene at -50 °C in the presence of an excess of solid cesium hydroxide and 0.1 mol equiv of catalyst 10, benzylation of the tert-butyl glycinate-derived benzophenone imine afforded the expected (S)-product in 67% yield with 94% ee, a value very close to that observed with the nonsupported catalyst. (Scheme 8.4, Equation b) Unfortunately-and again, inexplicably-the pseudoenantiomer of 10 proved to be much less stereoselective, affording the R)-product in only 23% ee. No mention of catalyst recycling was reported [18]. 

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