Highly Efficient Catalytic Synthesis of -Amino Acids under Phase-Transfer Conditions with a Novel Catalyst/Substrate Pair

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

“…C-H bond activation of glycine in the context of a nickel Schiff-base complex has been used to produce a variety of amino acid derivatives including α,β-diamino acids 1 and UAA's bearing fluorinated 2 or heterocyclic side-chains. 3 After addition of unnatural side-chains, functionalized UAA's are typically removed from the Schiff-base complex by reflux in hydrochloric acid 4 and are subsequently isolated using ion-exchange chromatography. While generally efficient, this protocol generates amino acids that may be unsuitable for use in solid-phase peptide synthesis (SPPS).…”

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

“…In particular, homologation of Ni(II) complex 1 via alkyl halide alkylation [48–50], aldol [51–53], Mannich [54–55] and Michael [56–58] addition reactions can be conducted at room temperature and without specially controlled conditions. Achiral derivatives of 1 , compounds 2 [59–60] and 3 [61–63], show even greater features of practicality and found application in the convenient synthesis of symmetrically α,α-disubstituted α-AAs [64–65], homologation under asymmetric PTC [66–67] and Michael addition reactions [68–72]. Nevertheless, the commercial application of chiral complex 1 is rather limited.…”

Gram Scale Conversion of R-BINAM to R-NOBIN

“…Atropisomers (axially chiral biaryls) are stereoisomers that arise from hindered rotation of two aromatic groups connected by a single C–C bond. This barrier to rotation allows for the isolation of many atropisomers in their single enantiomer forms. , The biaryl scaffold is considered a privileged structural motif (capable of binding to multiple receptors with high affinity) in pharmaceutical research with demonstrated activity as antitumor, antiamebic, antifungal, antihypertensive, anti-inflammatory, and antirheumatic agents among other therapeutic classes. , Biaryl backbones, embedded in 4.3% of all known drugs, are of a great significance due to their utility in biomolecular targeting and recognition. − Substituted biaryls have found a myriad of uses in organic synthesis, natural products chemistry, and material science devices such as light-emitting diodes, solar cells, and photoconductors. − Atropisomers such as ( R )-(+)-2′-amino-1,1′-binaphthalen-2-ol ( R -NOBIN, 3 ) have demonstrated usefulness as ligands and chiral auxiliaries in asymmetric catalysis leading to a wide array of catalytic enantioselective conversions. ,,,− Kagan et al have shown NOBIN’s usefulness as a phase transfer catalyst. − Chiral ligands made from optically pure NOBIN by Carreira have been utilized in numerous Ti-catalyzed aldol reactions. − NOBIN-derivatized ligands and catalysts have been reportedly used for Michael addition, diethyl zinc addition to aldehydes, allylation of aldehydes, allylic substitutions, 1,4-addition to α,β-unsaturated ketones, intermolecular cyclopropanation, asymmetric metathesis, aldol-type reactions, Diels–Alder and hetero-Diels–Alder reactions, transfer hydrogenation of ketones, α-vinylation of ketones, and Suzuki coupling reactions . Substituting the binaphthyl backbone with a variety of functional groups can alter the electronic and steric properties of the molecule that influence its catalytic behavior .…”