Synthesis of α-Amino Acids via Asymmetric Phase Transfer-Catalyzed Alkylation of Achiral Nickel(II) Complexes of Glycine-Derived Schiff Bases
TL;DR: An unusually large positive nonlinear effect was observed in these reactions, and implications of the association and self-association of NOBIN for the observed sense of asymmetric induction and nonlinear effects are discussed.
Abstract: Achiral, diamagnetic Ni(II) complexes 1 and 3 have been synthesized from Ni(II) salts and the Schiff bases, generated from glycine and PBP (7) and PBA (11), respectively, in MeONa/MeOH solutions. The requisite carbonyl-derivatizing agents pyridine-2-carboxylic acid(2-benzoyl-phenyl)-amide 7 (PBP) and pyridine-2-carboxylic acid(2-formyl-phenyl)-amide 11 (PBA) were readily prepared from picolinic acid and o-aminobenzophenone or picolinic acid and methyl o-anthranilate, respectively. The structure of 1 was established by X-ray crystallography. Complexes 1 and 3 were found to undergo C-alkylation with alkyl halides under PTC conditions in the presence of beta-naphthol or benzyltriethylammonium bromide as catalysts to give mono- and bis-alkylated products, respectively. Decomposition of the complexes with aqueous HCl under mild conditions gave the required amino acids, and PBP and PBA were recovered. Alkylation of 1 with highly reactive alkyl halides, carried out under the PTC conditions in the presence of 10% mol of (S)- or (R)-2-hydroxy-2'-amino-1,1'-binaphthyl 31a (NOBIN) and/or its N-acyl derivatives and by (S)- or (R)-2-hydroxy-8'-amino-1,1'-binaphthyl 32a (iso-NOBIN) and its N-acyl derivatives, respectively, gave rise to alpha-amino acids with high enantioselectivities (90-98.5% ee) in good-to-excellent chemical yields at room temperature within several minutes. An unusually large positive nonlinear effect was observed in these reactions. The Michael addition of acrylic derivatives 37 to 1 was conducted under similar conditions with up to 96% ee. The (1)H NMR and IR spectra of a mixture of the sodium salt of NOBIN and 1 indicated formation of a complex between the two components. Implications of the association and self-association of NOBIN for the observed sense of asymmetric induction and nonlinear effects are discussed.
Summary (1 min read)
- The synthesis of nonproteinogenicR-amino acids remains a subject of considerable interest because of their great importance in biology, medicine, and synthetic chemistry.
- More recently, the authors employed NOBIN (2-amino-2′-hydroxy-1,1′-binaphthyl) as a novel type of PTC catalyst in the alkylation reaction ofN-alanine esters producingR-methyl-R-amino acids with modest enantioselectivity (68% ee).
- Complexes1 and3 were prepared from glycine, Ni(NO3)2, and the respective ligand precursors7 (PBP) and11 (PBA) in the presence of KOH or MeONa in methanol (Schemes 1 and 2).
- The slight variation of the bond lengths in the ligand in1 and ( )-2 cannot be rationalized as the consequence of the presence of the methyl group at C(20) or the influence of crystal packing and seems to originate from a systematic bias introduced by the disorder in (-2.
- In addition, the sense of chirality of the product was reversed, as compared with the alkyl halide alkylations catalyzed by31a (Table 5, entries 1-3; compare with Tables 3 and 4).
- Evidently, the glycine-derived complex1 is a very convenient substrate for the synthesis of racemicR-amino acids, retaining oneR-proton of the original glycine moiety.
- Clearly, in addition to the probable decrease in theR-CH acidity of the amino acid moiety in the mono-alkylated complexes derived from1, further steric hindrance to the approach of the second alkylating agent also contributes to the predominant mono-alkylation of1.
- As the NH2 group of free NOBIN (31a) was shown by IR not to be involved in any coordination prior to the reaction, it seems that the phenolate oxygen atom replaced the carboxyl group in the coordination sphere of Ni(II), and thus, the group became partially or fully liberated, forming a strong ionic bond with Na+.
- In fact,31f and 31h failed to catalyze the reaction entirely.
- The authors have developed a new series of efficient nucleophilic substrates for the synthesis ofR-amino acids, both chiral and achiral, employing very simple and easily reproducible modes of operation.
- Combined with the use of the chiral catalysts, (S)- and (R)-NOBIN,19 (S)and (R)-iso-NOBIN,7b and their derivatives (31 and 32), this method opens a convenient synthetic route to the enantiomerically pureR-amino acids of both configurations.
- Further experiments will be needed to shed more light on this complex problem; work toward this direction is underway in these laboratories.
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Q1. What are the contributions in "University of groningen synthesis of α-amino acids via asymmetric phase transfer-catalyzed alkylation of achiral nickel(ii) complexes of glycine-derived schiff bases belokon," ?
Implications of the association and self-association of NOBIN for the observed sense of asymmetric induction and nonlinear effects are discussed.
Q2. What future works have the authors mentioned in the paper "University of groningen synthesis of α-amino acids via asymmetric phase transfer-catalyzed alkylation of achiral nickel(ii) complexes of glycine-derived schiff bases belokon," ?
However, further experiments will be needed to shed more light on this complex problem ; work toward this direction is underway in these laboratories.