Asymmetric glycine Schiff base

The fate of the onium carbanion Q+R incorporated into the organic phase depends on the electrophilic reaction partner. The most studied area in the asymmetric phase-transfer catalysis is that of asymmetric alkylation of active methylene or methine compounds with alkyl halides, in an irreversible manner. The reaction mechanism illustrated above is exemplified by the asymmetric alkylation of glycine Schiff base (Scheme 1.5) [8]. 

Direct Asymmetric Aldol Reaction of Glycine Schiff Base... 

In addition to the glycinate Schiff base 1, glycine amide derivatives can be used as prochiral substrates for asymmetric alkylation under phase-transfer conditions. Kumar and Ramachandran examined the benzylation of various Schiff bases of... 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-a-amino acids. Corey utilized 4d as catalyst for asymmetric Michael addition of glycinate Schiff base 1 to a,(3-unsaturated carbonyl substrates with high enantioselectivity (Scheme 2.15) [35,36]. With methyl acrylate as an acceptor, the a-tert-butyl-y-methyl ester of (S)-glutamic acid can be produced, a functionalized glutamic acid... 

The vast synthetic utility of the asymmetric phase-transfer alkylation of glycine Schiff base 2 has been realized by its successful application to the synthesis of various useful amino acid derivatives and natural products. 

Arai et al. also reported another BINOL-derived two-center phase-transfer catalyst 31 for an asymmetric Michael reaction (Scheme 6.11) [8b]. Based on the fact that BINOL and its derivatives are versatile chiral catalysts, and that bis-ammonium salts are expected to accelerate the reaction due to the two reaction sites - thus preventing an undesired reaction pathway - catalyst 31 was designed and synthesized from the di-MOM ether of (S)-BINOL in six steps. After optimization of the reaction conditions, the use of 1 mol% of catalyst 31a promoted the asymmetric Michael reaction of glycine Schiff base 8 to various Michael acceptors, with up to 75% ee. When catalyst 31b or 31c was used as a catalyst, a lower chemical yield and selectivity were obtained, indicating the importance of the interaction between tt-electrons of the aromatic rings in the catalyst and substrate. In addition, the amine moiety in catalyst 31 had an important role in enantioselectivity (34d and 34e lower yield and selectivity), while catalyst 31a gave the best results. 

The glycinate Schiff base of benzophenone 17 was also shown to be a suitable Michael donor for the asymmetric 1,6-addition to the activated dienes 44 having ketones, esters, and sulfones as substituents. Using Corey s phase-transfer catalyst, 16, the corresponding allylated products 47 were obtained as a single E-isomer with high enantioselectivity (from 92 to 98% ee). The synthetic utility of this reaction... 

Using a IM KOH aq solution, it is possible to perform the asymmetric alkylation of the benzophenone glycine Schiff base with benzyl bromide using 10 mol% of 15 at room temperature, as shown in Figure 14. 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

A phase-transfer-catalyzed direct Mannich reaction of glycinate Schiff base 5 with a-itnino ester 78 was achieved with high enantioselectivity by the use of N-spiro chiral quaternary ammonium bromide 9e as catalyst (Scheme 11.21) [62]. This method enabled the catalyhc asymmetric synthesis of differentiatly protected 3-aminoaspartate, a nitrogen analogue of dialkyl tartrate, the utility of which was demonstrated by the conversion of product (sy -79) into a precursor (80) of strep-tohdine lactam. 

Minowa, N., Huayama, M., and Fukatsu, S., Asymmetric synthesis of (-i-)-phosphinothricin and related compounds by the Michael addition of glycine Schiff bases to vinyl compounds. Bull. Chem. Soc. Jpn., 60, 1761, 1987. 

Ma et al. examined guanidine catalysed Michael reaction of ferf-butyl glycinate Schiff base with ethyl acrylate in THF and observed 30% ee as the asymmetric induction when an acyclic guanidine (2) was used as a catalyst [10b]. Ishikawa et al. succeeded in greatly improving the asymmetric induction by the use of guanidine 17a, originally prepared based... 

Phase transfer reactions have featured in several sections of this book, including epoxidation (Section 4.5), Darzens condensation (Section 7.5) and Wadsworth-Emmons reactions (Section 12.5). Another important aspect of phase-transfer catalysed reactions has been with alkylation reactions. The asymmetric alkylation of glycinate Schiff base (12.45) using N-benzylcinchoninium halides as catalysts is particularly noteworthy, since the products are readily converted into amino acids. Corey and coworkers have developed the original work. 

In 2004, the gronp of Maruoka reported the direct asymmetric Mannich reaction of glycinate Schiff base 104 with a-imino ester 10a catalyzed by A-spiro-C -symmetric chiral quaternary ammoninm bromide 103 to provide the protected 3-aminoaspartate 105 in 88% yield (81 18 dr, 91% ee) [60]. The latter was afterwards converted into a precnrsor of the streptothricin antibiotics core structure (Scheme 5.43). 

Najera and coworkers also prepared the dimeric catalysts lie, Ilf, and llg, which incorporate a dimethylanthracenyl bridge as a spacer. These catalysts were utilised for the PTC adulation of 5 with various allqrl halides. They investigated the influence of the counterions on the asymmetric allqr-lation of 5 and found that tetrafluoroborate (Ilf) and hexafluorophosphate (llg) counteranions showed higher enantioselectivity than bromide anion in the allgflation with terf-butyl bromoacetate. In addition, Siva and coworkers in India reported various dimeric and trimeric catalysts (llh. Hi, 12a) and successfully applied them to the PTC benzylation of glycinate Schiff base 5 (Scheme 16.7)." ... 

SCHEME 8.1. Asymmetric alkylation of glycine Schiff base 1 using CB catalysts I-VIII. 

In 2006, Shibasaki and co-workers [91] developed phase-transfer-catalyzed asymmetric Michael addition of glycine Schiff base 237 and dienone 238 to afford dienone 240 in 84% isolated yield and 82% ee for the total synthesis of (+)-cylin-dricine C (242) and a formal synthesis of (—)-lepadiformine (244), using a chiral two center organocatalyst 239 (TaDiAS Tartrate-derived Di-Ammonium Salt) (Scheme 17.41). (+)-cylindricine C (242) was achieved three steps from 240 using... 

The combinational use of inorganic base and chiral phase-transfer catalyst provides an efficient process for the synthesis of -hydroxyl-a-amino acids via the aldol reaction (260-262). A representative and successful example was reported by Maruoka and co-workers (319) that a highly efficient direct asymmetric aldol reaction of a glycinate Schiff base with aliphatic aldehydes has been achieved under mild organic/aqueous biphasic conditions with excellent stereochemical control activity (Scheme 67) (96 99% ee). 

The asymmetric 1,4-addition of nucleophiles to a,p-unsaturated carbonyl and related compounds is also an important and valuable method for preparation of highly functionalized aUcyl chains. While chiral Brpnsted base-catalyzed asymmetric transformation has been intensively explored (for reviews of asymmetric 1,4-addition reactions of 1,3-dicarbonyl compounds, see [26-33] for reviews of asymmetric 1,4-addition reactions of glycine Schiff bases, see [34—37] for reviews of asymmetric [3-1-2] cycloaddition reactions, see [38-41]), chiral alkaline-earth metal catalysts have been also successfully employed in this reaction. 

Recently, the synthesis of enantioenriched 1,2-diamino acid derivatives [109, 110] was reported by Kobayashi and colleagues combining a glycine Schiff base and an imine in an asymmetric Maimich-type reaction [111]. To achieve simultaneous activation and deprotonation of the glycine Schiff base, which was hypothesized to be a crucial feature... 

Figure 14.2 (a) Chiral phase-transfer catalysts (Q X ) for the asymmetric alkylation of glycine Schiff base 1 (b) substrates for asymmetric alkylations. 

The spiro-type phase-transfer catalyst (188, Ar = H) possessing a C2-symmetry axis provides a single type of asymmetric environment in contrast, a newly designed spiro-type phase-transfer catalyst (188, Ar H) has two different asymmetric environments. The substituents of the binaphthyl subunits affect enantioselectiv-ity, and the 3,5-bis[3,5-bis(trifluoromethyl)phenyl]phenyl group is the best substituent of those evaluated in the anti-selective aldol reactions of glycine SchifF base 186 with aldehydes (35) (Scheme 28.21) [94]. Similarly, simpMed chiral phase-transfer catalyst 189 bearing the 3,5-bis[3,5bis(trifluoromethyl)phenyl] phenyl substituent, which is prepared in a combinatorial approach from the readily available (S)-l,l -binaphthyl-2,2 -dicarboxylic acid, effectively catalyzes syn-selective aldol reactions [95]. 

SCHEME 2.41 Asymmetric Mannich reaction between a-amido sulfones and glycine Schiff base. 

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