Glycine Schiff base catalysts

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... 

Maruoka and coworkers recently developed an efficient, highly diastereo- and enantioselective direct aldol reaction of glycine Schiff base 2 with a wide range of aliphatic aldehydes under mild phase-transfer conditions employing N-spiro chiral quaternary ammonium salt li as a key catalyst, as shown in Table 5.12 [41a]. 

Phase-transfer-catalyzed direct Mannich reaction of glycine Schiff base 2 with a-imino ester 79 was achieved with high enantioselectivity by the utilization of N-spiro chiral quaternary ammonium bromide le as catalyst (Table 5.14) [42],... 

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... 

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. 

Nagasawa and co-workers developed the C2-symmetric chiral pentacyclic guanidine 11 as a chiral phase-transfer catalyst for the enantioselective alkylation of tert-butyl glycinate Schiff base (Equation 10.25) [53]. 

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. 

O Donnell s pioneering studies were reported, the catalytic efficiency of newly developed phase-transfer catalysts has been evaluated by the alkylation of glycine Schiff base 5 and for these catalysts the particular allqrlation studied and enantiomeric excess will be given in parentheses during the discussion of the catalyst. 

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)." ... 

The reaction of a glycine Schiff base (159) with aldehydes can be catalyzed by cinchona-derived salts, though the stereoselectivity is rather low [171]. Maruoka reported that this reaction proceeded well with a C2-symmetric chiral quarternary ammonium salt (160) as a phase-transfer catalyst [172]. The reaction generated tz fi -(3-hydroxy-a-aminoacids with reasonable yields and stereoselectivities (Scheme 3.28). Further modifications of the catalyst structure led to a salt which provided predominantly jy -aldols [173]. 

SCHEME 3.28. syn- And a ti-selective quartemary ammonium salts as catalysts for the aldol reaction of a glycine Schiff base 159 with aldehydes. 

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

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. 

The application of 23 to the enantioselechve [3+2] cycloaddihon of dimethyl maleate with glycinate Schiff bases established a protocol for the preparation of pyrrolidine derivatives in a stereoselective fashion, where the acid-base dual function of the catalyst through the double hydrogen-bonding interaction was crucial for gaining substantial acceleration of the reachon (Scheme 7.42) [66]. 

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]. 

Chiral two-center phase-transfer catalyst 202 possessing 2,6-disubstituted cyclohexane spiroacetal catalyzes the syn-selective Mannich-type reaction of glycine Schiff base 186 with N-Boc-protected aromatic imines as weU as enoUzable aUcyl imines (201) in high yields with moderate to good enantioselectivities (Scheme 28.24) [103],... 

Later, a highly enantioselective Mannich reaction employing glycine Schiff base 145 as nucleophile was described by Zhang et al., in which a-amido sulfones 142a participated very well as precursors (Scheme 2.41). With dihydroquinine-derived thiourea 130c as catalyst, this Mannich reaction provided access to optically active a,p-diamino acid derivatives 146 with up to >99 1 dr and >99% ee [59]. 

Okada A, Shibuguchi T, Ohshima T, Masu H, Yamaguchi K, Shibasaki M. Enantio- and diastereoselective catalytic Man-nich-type reaction of a glycine Schiff base using a chiral two-center phase-transfer catalyst. Awgew. Chem. Int. Ed. 2005 44 (29) 4564 567. 

The addition of other deprotonated nucleophiles to vinyl ketone was further expanded recently to the synthesis of much more complex molecules. In 2006, the group led by Shibasaki reported on the concise synthesis of cylindricine C, a spirocychc molecule with numerous biological properties isolated from Clavelina cylindrical (Scheme 11.44). Glycine Schiff base 182 was found to react efficiently with enone 183. Catalyst 184 was the most effective for this transformation giving a good 82% ee at —40°C. Noteworthy, the process tolerated numerous functional groups such as the more substituted enone that was kept untouched. Remarkably, compound 185 could be transformed into the tricychc backbone 186 of cylindricine C by a tandem cych-zation in acidic conditions. 

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