Ryosuke Takeda

Chemical Dynamic Kinetic Resolution and S/R Interconversion of Unprotected α-Amino Acids†

Reported herein is the first purely chemical method for the dynamic kinetic resolution (DKR) of unprotected racemic α-amino acids (α-AAs), a method which can rival the economic efficiency of the enzymatic reactions. The DKR reaction principle can be readily applied for S/R interconversions of α-AAs, the methodological versatility of which is unmatched by biocatalytic approaches. The presented process features a virtually complete stereochemical outcome, fully recyclable source of chirality, and operationally simple and convenient reaction conditions, thus allowing its ready scalability. A quite unique and novel mode of the thermodynamic control over the stereochemical outcome, including an exciting interplay between axial, helical, and central elements of chirality is proposed.

Recognition of Aromatic Compounds by π Pocket within a Cage‐Shaped Borate Catalyst

Taking shape: the ability of a Lewis acid catalyst to distinguish between aromatic and aliphatic hydrocarbon moieties was accomplished by using cage-shaped borate catalysts B(OC(6)H(3)Aryl)(3)CH having a π pocket derived from aryl substituents surrounding the boron center. The catalyst predominantly activated aromatic aldehydes over aliphatic ones for reaction.

Cage‐Shaped Borate Esters with Tris(2‐oxyphenyl)methane or ‐silane System Frameworks Bearing Multiple Tuning Factors: Geometric and Substituent Effects on Their Lewis Acid Properties

Boron complexes that contain new tridentate ligands, tris(o-oxyaryl)methanes and -silanes, were prepared. These complexes had a cage-shaped structure around a boron center and showed higher Lewis acidity and catalytic activity than open-shaped boron compounds. The cage-shaped ligands determined the properties of the borates by altering the geometry and were consistently bound to the metal center by chelation. The synthesized compounds were L⋅B(OC(6)H(4))(3)CH, L⋅B(OC(6)H(4))(3)SiMe, and its derivatives (L=THF or pyridine as an external ligand). Theoretical calculations suggested that the cage-shaped borates had a large dihedral angle (C(ipso)-O-B-O) compared with open-shaped borates. The geometric effect due to the dihedral angle means that compared with open-shaped, the cage-shaped borates have a greater Lewis acidity. The introduction of electron-withdrawing groups on the aryl moieties in the cage-shaped framework increased the Lewis acidity. Substitution of a bridgehead Si for a bridgehead C decreased the Lewis acidity of the boron complexes because the large silicon atom reduces the dihedral angle of C(ipso)-O-B-O. The ligand-exchange rates of the para-fluoro-substituted compound B(OC(6)H(3)F)(3)CH and the ortho-phenyl-substituted compound B(OC(6)H(3)Ph)(3)CH were less than that of the unsubstituted borate B(OC(6)H(4))(3)CH. The ligand-exchange rate of B(OC(6)H(4))(3)SiMe was much faster than that of B(OC(6)H(4))(3)CH. A hetero Diels-Alder reaction and Mukaiyama-type aldol reactions were more effectively catalyzed by cage-shaped borates than by the open-shaped borate B(OPh)(3) or by the strong Lewis acid BF(3) ⋅OEt(2). The cage-shaped borates with the bulky substituents at the ortho-positions selectively catalyzed the reaction with less sterically hindered substrates, while the unsubstituted borate showed no selectivity.

Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base

Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2′ alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.

Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by sequential SN2–SN2′ dialkylation of (R)-N-(benzyl)proline-derived glycine Schiff base Ni(II) complex

This work describes a new process for the asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid of high pharmaceutical importance. The sequence of the reactions includes PTC alkylation (SN2), homogeneous SN2′ cyclization followed by disassembly of the resultant Ni(II) complex. All reactions are conducted under operationally convenient conditions and suitably scaled up to 6 g of the starting Ni(II) complex.

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

Summary A family of chiral ligands derived from α-phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II) salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements.