Schiff Bases Derived from Glycine

Monoalkylation of Schiff Bases Derived from Glycine 

In 1989, O Donnell and coworkers successfully utilized cinchona alkaloid-derived chiral quaternary ammonium salts for the asymmetric synthesis of a-amino acids using tert-butyl glycinate benzophenone Schiff base 1 as a key substrate [5]. The asymmetric alkylation of 1 proceeded smoothly under mild phase-transfer 

Asymmetric Phase Transfer Catalysis. Edited by Keiji Maruoka Copyright 2008 WILEY-VCH GmbH Co. KGaA, Weinheim ISBN 978-3-527-31842-1 

These reports have accelerated research investigations into improving the asymmetric alkylation of 1 in terms of catalytic activity and stereoselectivity, the result being the emergence of a series of appropriately modified cinchona alkaloid-based catalysts. The performance of the representative monomeric catalysts in the asymmetric benzylation and allylation of 1 are summarized in Table 2.1, in order to provide an overview of the relationship between the structure, activity and enantioselectivity. 

Armstrong and Scutt reported a synthesis of 3-(trans-2-aminocyclopropyl)alanine, a component of Balactosin A, through the highly diastereoselective alkylation of 1 with optically pure alkyl iodide 8. Under thoroughly optimized conditions, the 

---

Conversely, ester condensation reactions join acyl groups from CoA derivatives to Schiff bases derived from glycine or serine. Succinyl-CoA is the acyl donor... 

The pioneering contribution from Maruoka and coworkers [37] on the enantioselec-tive phase-transfer alkylation of Schiff bases derived from glycine has opened the way to other related, more recent MBTs. 

Fluoral has been condensed with an equivalent of chiral glycinate anion. The chirality stems from a chiral nickel complex with a chiral Schiff base derived from proline as hgand (Figure 5.17). (25, 35)-Difluorothreonine has thus been obtained with an excellent selectivity (de > 95%). This method also allows preparation of numerous fluoroalkyl and fluoroaryl analogues of threonine. Enantiopure difluorothreonine could also be prepared from ascorbic acid. ... 

Magnetic exchange interactions have also been identified in the oxovanadium-(iv) complexes with the Schiff bases derived from 2-hydroxy-l-naphthaldehyde and ethanolamine or propanolamine. Such complexes can accommodate two further donor atoms per metal and [VO(A)(L)] (A = bipy or phen HjL = Schiff base from salicylaldehyde or 2-hydroxy-l-naphthaldehyde with glycine, alanine, anthranilic acid, or o-aminophenol) complexes have been shown to involve six-co-ordinate vanadium. Similarly, VOL,B [HjL = 2-hydroxy-naphthylideneamino-acid, B = HjO, phen, or (py)2 HjL = 2-hydroxy-naphthylidene-o-aminophenol, B = phen] have normal magnetic moments ifi = 1.70—1.74 BM) at room temperature. The complex VOL (HjL = 6,ll-dimethyl-7,10-diazahexadeca-6,10-diene-2,4,13,15-tetrone) has been prepared from V0(0H)2, heptane-2,4,6-trione, and en in MeOH. The structure... 

Long-range C-C, C-N and N-N couplings in selectively labelled Ni(II) complexes of the Schiff base derived from (S)-iV-benzylproline(2-benzoylphenyl)am-ide and glycine have been measured by Popkov et al in CDCb solution. Their analysis provided evidence that the donation of electron density from the jt-system of the benzyl ring to the nickel orbitals takes place. 

Table 8 Box-calcium complex-catalyzed [3-1-2] cycloaddition reactions of glycine Schiff bases derived from benzophenone with a,p-unsaturated carbonyl compounds...

Using the Schiff base (17) derived from glycine,... 

The Schiff s base derived from ethyl glycinate and benzophenone has been alkylated under both anhydrous and phase transfer conditions yielding, after hydrolysis, a-amino acids. Under phase transfer conditions, alanine, a-aminobutyric acid, valine, leucine and phenylalanine were prepared in 91%, 86%, 61%, and 55% yields, based on starting imine. 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from o -amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the o-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The Q-allyl-o-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+ )-A, jV-dicyclohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ec[72]. 

Alternatively, various 4-substituted derivatives have been prepared via synthesis of amino acid (68) by reaction of the anion formed from protected glycine and an appropriately substituted Schiff base. 

Diastereoselective preparation of a-alkyl-a-amino acids is also possible using chiral Schiff base nickel(II) complexes of a-amino acids as Michael donors. The synthetic route to glutamic acid derivatives consists of the addition of the nickel(II) complex of the imine derived from (.S )-,V-[2-(phenylcarbonyl)phenyl]-l-benzyl-2-pyrrolidinecarboxamide and glycine to various activated olefins, i.e., 2-propenal, 3-phenyl-2-propenal and a,(f-unsaturated esters93- A... 

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 enolate derived from the Schiff base 3 has been added to a,/ -unsaturated esters and ketones with a high level of enantioselectivity. For example, in the presence of 10 mol% lb, the enolate of the glycine derivative 3 was added to cyclohexenone with excellent diastereo-selectivity to give the ketoester 20 with >99% ee (Scheme 7) [15]. Promising results have also been obtained in the Michael additions of malonates to chalcone deriviatives [16], The novel cinchonidinium bromide lg was found to be the most effective catalyst for this transformation, yielding the Michael adduct 21 with 70% ee (Scheme 8). 

---