Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids

This review provides a comprehensive treatment of literature data dealing with asymmetric synthesis of α-amino-β-hydroxy and α,β-diamino acids via homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and Mannich-type reactions. These reactions proceed with synthetically useful chemical yields and thermodynamically controlled stereoselectivity and allow direct introduction of two stereogenic centers in a single operation with predictable stereochemical outcome. Furthermore, new application of Ni(II) complexes of α-amino acids Schiff bases for deracemization of racemic α-amino acids and (S) to (R) interconversion providing additional synthetic opportunities for preparation of enantiomerically pure α-amino acids, is also reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich-type and deracemization reactions, generality and limitations of these methodologies are critically discussed.     

Chromatographic approach to study the configurational stability of Ni(II) complexes of amino‐acid Schiff bases possessing stereogenic nitrogen

Herein, we disclose the design of a model Ni(II) complex of glycine Schiff base possessing single‐nitrogen stereogenic center, which was successfully used for high‐performance liquid chromatography (HPLC)‐assisted assessment of its configurational stability. The major finding is that the configurational stability of the Ni(II)‐coordinated nitrogen is profoundly dependent on the reaction conditions used, in particular the solvent, and can range from inconsequential (t_½ less than 5 min) to virtually completely stable (t_½ 90 y). The discovery reported in this study most likely to be of certain theoretical and synthetic value.     

The unusual action of (R,S)-2-hydroxy-2-trifluoromethyl-trans-n-octadec-4-enoic acid on 5-lipoxygenase from potato tubers

We found that (R,S)-2-hydroxy-2-trifluoromethyl-trans-n-octadec-4-enoic acid (HTFOA) is a powerful activator of 5-lipoxygenase from potato tubers. The degree of activation of the enzyme is proportional to the HTFOA concentration and is a maximum at about 0.1 mM independently of initial substrate concentration (25 microM or 0.1 mM). At greater concentrations of HTFOA, enzyme inhibition takes place. Enzyme activation is inversely proportional to the substrate (linoleic acid) concentration. The results may be explained by assuming that a regulatory center exists in the enzyme molecule, which shows affinity to both substances: activator and linoleic acid.     

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di‐(benzyl)glycine Schiff bases. We found that while the ortho‐fluoro derivatives are configurationally unstable, the pure enantiomers of corresponding axially chiral ortho‐chloro‐containing complexes can be isolated by preparative HPLC and show exceptional configurational stability (t_1/2 from 4 to 216 centuries) at ambient conditions. Synthetic implications of this discovery for the development of new generation of axially chiral auxiliaries, useful for general asymmetric synthesis of α‐amino acids, are discussed.     

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous transformations

The major goal of this review is a critical discussion of the literature data on asymmetric synthesis of α-amino acids via Michael addition reactions involving Ni(II)-complexes of amino acids. The material covered is divided into two conceptually different groups dealing with applications of: (a) Ni(II)-complexes of glycine as C-nucleophiles and (b) Ni(II)-complexes of dehydroalanine as Michael acceptors. The first group is significantly larger and consequently subdivided into four chapters based on the source of stereocontrolling element. Thus, a chiral auxiliary can be used as a part of nucleophilic glycine Ni(II) complex, Michael acceptor or both, leading to the conditions of matching vs. mismatching stereochemical preferences. The particular focus of the review is made on the practical aspects of the methodology under discussion and mechanistic considerations.     

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations

Alkylations of chiral or achiral Ni(II) complexes of glycine Schiff bases constitute a landmark in the development of practical methodology for asymmetric synthesis of α-amino acids. Straightforward, easy preparation as well as high reactivity of these Ni(II) complexes render them ready available and inexpensive glycine equivalents for preparing a wide variety of α-amino acids, in particular on a relatively large scale. In the case of Ni(II) complexes containing benzylproline moiety as a chiral auxiliary, their alkylation proceeds with high thermodynamically controlled diastereoselectivity. Similar type of Ni(II) complexes derived from alanine can also be used for alkylation providing convenient access to quaternary, α,α-disubstituted α-amino acids. Achiral type of Ni(II) complexes can be prepared from picolinic acid or via recently developed modular approach using simple secondary or primary amines. These Ni(II) complexes can be easily mono/bis-alkylated under homogeneous or phase-transfer catalysis conditions. Origin of diastereo-/enantioselectivity in the alkylations reactions, aspects of practicality, generality and limitations of this methodology is critically discussed.     

Effect of substituents on the configurational stability of the stereogenic nitrogen in metal(II) complexes of α‐amino acid Schiff bases

Herein, we report a general method for quantitative measurement of the configurational stability of the stereogenic nitrogen coordinated to M (II) in the corresponding square planar complexes. This stereochemical approach is quite sensitive to steric and electronic effects of the substituents and shown to work well for Ni(II), Pd(II), and Cu(II) complexes. Structural simplicity of the compounds used, coupled with high sensitivity and reliability of experimental procedures, bodes well for application of this approach in evaluation of chemical stability and stereochemical properties of newly designed chiral ligands for general asymmetric synthesis of tailor‐made amino acids.     

Note

This work demonstrates that self‐disproportionation of enantiomers via achiral chromatography can be recommended as inexpensive and general method for optical purifica‐ tion of enantiomerically enriched compounds. In particular, the advantage of this approach over conventional recrystallization is that it can be used for both crystalline as well as liquid com‐ pounds. Chirality, 25:365–368, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis of polysubstituted β-amino cyclohexane carboxylic acids via Diels–Alder reaction using Ni(II)-complex stabilized β-alanine derived dienes

This paper describes the design and synthesis of a new class of β-alanine derived dienes stabilized by Ni(II)-complex. Preliminary study of their Diels–Alder cycloaddition reactions with several types of dienophiles demonstrates their significant synthetic potential for the preparation of various polyfunctional β-aminocyclohexane carboxylic acids.