Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines

Soloshonok, Vadim A.; Avilov, D.; Kukhar, V. P.; Tararov, Vitali I.; Savel’eva, T. F.; Churkina, T. D.; Ikonnikov, N. S.; Кочетков, К. А.; Orlova, S. A.; Pysarevsky, Alexander P.; Struchkov, Yuri T.; Raevsky, Nikolai I.; Belokoń, Yuri N.

doi:10.1016/0957-4166(95)00220-j

Cited by 94 publications

(29 citation statements)

References 39 publications

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“…As follows from Table , the stereochemical outcome of the reaction is dependent on the basicity of the solution, as it has been previously observed for aldol condensation of GlyNi with aldehydes . The C–H acidity of the α‐protons of the amino acid fragment is high enough for the complex to be deprotonated with even relatively weak bases (such as Et 3 N or DABCO) .…”

Section: Resultsmentioning

confidence: 64%

“…The C–H acidity of the α‐protons of the amino acid fragment is high enough for the complex to be deprotonated with even relatively weak bases (such as Et 3 N or DABCO) . Thus, the basicity of the reaction media influences mainly the equilibrium of the follow‐up epimerization of the reaction products (Scheme ). If the basicity of the solution is not sufficient for ionization of the hydroxy group in the product (in the presence of a weak base or at a low concentration of a strong base), the equilibrium is shifted toward more stable species with the ( S )‐configuration of the α‐amino acid carbon.…”

Section: Resultsmentioning

confidence: 99%

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Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes

2019

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A new electrochemical method for stereoselective hydroxyalkylation of glycine in the form of a chiral NiII complex of the Schiff base derived from (S)‐2‐[N‐(N′‐benzylprolyl)amino] benzophenone (GlyNi) is elaborated. The method is technologically simple: galvanostatic electrolysis of GlyNi is performed in a one‐compartment electrochemical cell in an alcohol solution (which serves as a reactant and a solvent simultaneously) in the presence of KOH. High chemical yields of α‐amino‐β‐hydroxy acids (in the form of NiII Schiff base complexes) were obtained for the C1–C3 primary alcohols; for the higher alcohols yields were low. The stereochemical outcome of the process is dependent on the pH of the solution and the reaction time between the end of the electrolysis and the work‐up procedure. Thermodynamically more stable (2R) product (for methanol) and (2R,28S)‐diastereomer (for the homologues) are formed at high pH with high diastereselectivity (de up to 94 %). In the media with low basicity, under kinetic control, the (2S) complex (for methanol) and (2S,28R)‐diastereomer (for higher alcohols) can be obtained (de = 100 %). The correlation between the chemical shift of the H8 proton in the 1H NMR spectra and the configuration of the amino acid α‐stereocenter in the NiII Schiff‐base complexes was established providing a new tool for determination of the absolute configuration of the α‐carbon stereocenter.

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Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes

2019

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“…Formation of the corresponding enolates 16 , in the presence of relatively strong bases (KO t -Bu), is an established step in general methods for homologation of the glycine moiety by alkyl halide alkylation [27,50–53], aldol [29,33,36–37] and Michael [28,31,34–35 38–39 43–47] addition reactions. The following oxidation step of the enolates 16 in the presence of atmospheric oxygen, is less studied [48]; however, plausible key transformations can be deduced based on the closely related results on the well-established general oxidation of enolates [55–64] and glycine-derived enolates [65–70], in particular, under similar conditions.…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

Soloshonok¹,

Aceña²,

Ueki³

et al. 2012

Beilstein J. Org. Chem.

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SummaryWe describe herein the design and synthesis of asymmetric, pentadentate ligands, which are able to coordinate to Ni(II) cations leading to quasi-diastereomeric complexes displaying two new elements of chirality: stereogenic axis and helix along with configurational stabilization of the stereogenic center on the nitrogen. Due to the stereocongested structural characteristics of the corresponding Ni(II) complexes, the formation of quasi-diastereomeric products is highly stereoselective providing formation of only two, (R a*,M h*,R c*) and (R a*,P h*,R c*), out of the four possible stereochemical combinations. The reversible quasi-diastereomeric transformation between the products (R a*,M h*,R c*) and (R a*,P h*,R c*) occurs by intramolecular trans-coordination of Ni–NH and Ni–O bonds providing a basis for a chiral switch model.

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“…Using the same approach, a series of fluorinated derivatives of b-phenylserine (2S,3R)-78, bearing from one to five fluorine atoms on the phenyl ring, were synthesized starting from the corresponding fluorinated benzaldehydes [120]. The mode of the asymmetric induction in this case was the same and the different (2S,3R) absolute configuration is simply a consequence of the Cahn-Ingold-Prelog priority rules.…”

Section: Addition Reactionsmentioning

confidence: 99%

“…It should be noted that the stereochemical outcome of these reactions was remarkably high favoring single (2S,3S,2´S)configured diastereomer 76, out of four theoretically possible stereoisomeric products. Importantly, the trifluoromethyl, or more generally, perfluoroalkyl, group was shown to be the stereo-controlling substituent, mechanistically similar in terms of its stereo-directing size to a tert-butyl [120]. The target a-amino-b-hydroxyb-perfluoroalkyl carboxylic acids (2S,3S)-77 were isolated from 76 in high chemical yield, using the standard procedure described previously in FiguRe 16.…”

Section: Addition Reactionsmentioning

confidence: 99%

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

2009

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Naturally occurring compounds containing a C-F bond are extremely rare; only a handful of fluorine-containing carboxylic acids have been described so far. By contrast, man-made fluorine-containing derivatives of all major classes of biologically important compounds are extremely promising medicinal targets used in the elucidation of biochemical, metabolic transformations and the development of new pharmaceuticals. Among the fluorine-containing derivatives of natural products, fluorinated analogs of amino acids are of particular interest and medicinal potential. This article presents a concise review of various synthetic methods, developed by the Kiev's school of bioorganic chemistry, for the preparation of fluorine-containing analogs of α- and β-amino acids, α-hydroxy acids, amines, as well as their phosphorus and sulfur-derived compounds, in enantiomerically pure form. One of the major methodological goals of the study was practicality, which is understood by us as stereochemical generality, operational convenience and synthetic affordance for each reaction step and isolation of the target products. The synthetic methods developed by our group can be roughly divided in two general categories: fluorine-adaptation of known synthetic approaches and discovery of new reactions. The former approach is most prominently represented by asymmetric homologation of nucleophilic glycine equivalents using fluorinated substrates via alkyl halide alkylations, aldol and Michael addition reactions. A plethora of discovered unexpected reaction outcomes, in particular stereochemical, are emphasized in this review and the particular role of fluorine, in altering the 'normal' reaction result, is explained. The latter direction is notably represented by the novel 1,3-proton shift reaction, a biomimetic reductive amination of fluorinated carbonyl compounds to the corresponding amines and amino acids, as well as the development of α-fluoroalkyl epoxides as true fluorinated synthons for generalized asymmetric synthesis of various biologically relevant compounds. Despite the highly anticipated potential of fluorine-containing amino compounds, their medicinal chemistry still remains underexplored. The major obstacle, in our opinion, is that these selectively fluorinated compounds are generally unavailable to the medicinal chemists for comprehensive, systematic study. We hope this review of synthetic methods will highlight and bring attention to particular types of fluorinated amino acids and related compounds readily available on a laboratory scale using methods developed by our group.

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Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines

Cited by 94 publications

References 39 publications

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

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Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines

Cited by 94 publications

References 39 publications

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of NiII‐Schiff‐Base Complexes

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of NiII‐Schiff‐Base Complexes

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

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Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes

Stereoselective Electrosynthesis of β‐Hydroxy‐α‐Amino Acids in the Form of Ni^II‐Schiff‐Base Complexes