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Although the synthesis of α-tertiary amino acids (ATAAs) has been extensively studied, the development of an inexpensive and facile methodology to incorporate multifunctionality on ATAAs remains challenging. In this article, we present a single-step radical approach for the modular synthesis of functionally diverse ATAAs. This synthesis takes place under mild conditions with an absence of metals, photocatalysts, and all other additives. We demonstrate the broad applications of this approach on a variety of aliphatic and aromatic carboxylic acids, alkenes, 1,3-enynes, and oxazolones. The results prove that our method provides excellent functional group tolerance and late-stage applicability, as well as gram-scale synthesis via flow chemistry. Additionally, we include mechanistic studies which reveal that the excited state of oxazolone enolate upon light excitation is a key intermediate that acts as a radical precursor and an efficient reductant., (© 2022 Wiley-VCH GmbH.)

A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids., (© 2022 Wiley Periodicals LLC.)

The hydroxyphenyl chiral ketone, (S)-3, reacts with D-amino acids bearing hydrophobic side chains exclusively over the L-amino acids in a two-phase liquid-liquid extraction, and thus acts as a highly stereoselective extractant. Calculations for the energy-minimized structures for the imine diastereomers and the comparison of the selectivities with other phenyl ketones, (S)-4 and (S)-5, demonstrate that the hydrogen bond between the carboxylate group and the phenolic hydroxyl group contributes to the remarkable enantioselectivities. The multiple hydrogen bonds present in the imine of (S)-3 reinforce the rigidity, and results in the difference between the stabilities of the imine diastereomers. The imine could be hydrolyzed in methanolic HCl solution, and the extraction of the evaporated residues revived the organic layer of (S)-3, which could enter into a new extractive cycle and leaves the D-amino acid with enantiomeric excess (ee) values of over 97 % in the aqueous layer., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The chiral ketone (S)-3 shows high kinetic enantioselectivities toward the L form for general underivatized amino acids with hydrophobic side chains and a high thermodynamic enantioselectivity toward the D form for cysteine with its -SH polar side chain when used as an extractant in enantioselective liquid-liquid extractions in the presence of Aliquat 336. Consecutive extractions by imine formation and hydrolysis increase the enantiopurity of the amino acid, as both of these reactions are L-form-selective.

Although the synthesis of α‐tertiary amino acids (ATAAs) has been extensively studied, the development of an inexpensive and facile methodology to incorporate multifunctionality on ATAAs remains challenging. In this article, we present a single‐step radical approach for the modular synthesis of functionally diverse ATAAs. This synthesis takes place under mild conditions with an absence of metals, photocatalysts, and all other additives. We demonstrate the broad applications of this approach on a variety of aliphatic and aromatic carboxylic acids, alkenes, 1,3‐enynes, and oxazolones. The results prove that our method provides excellent functional group tolerance and late‐stage applicability, as well as gram‐scale synthesis via flow chemistry. Additionally, we include mechanistic studies which reveal that the excited state of oxazolone enolate upon light excitation is a key intermediate that acts as a radical precursor and an efficient reductant. [ABSTRACT FROM AUTHOR]

The derivative of aminophenyl‐aldehyde with an asymmetric carbon and an uryl group, (S)‐2, was synthesized. The combination of (S)‐2 and aliquat‐336 in CDCl3 extracted underivatized amino acids in water layer by imine formation with enantioselectivities of 12/1 for Phe, 13/1 for Val, and 12/1 for Leu, which are comparable with those of previously reported binaphthol‐based extractor (S)‐1. The enantioselectivities of (S)‐2 is remarkable considering the low molecular weight compared to (S)‐1. Density functional theory computations and experimental data demonstrate that imine bond is strengthened by resonance‐assisted hydrogen bond with the nearby NH group. [ABSTRACT FROM AUTHOR]

The hydroxyphenyl chiral ketone, ( S)- 3, reacts with D-amino acids bearing hydrophobic side chains exclusively over the L-amino acids in a two-phase liquid-liquid extraction, and thus acts as a highly stereoselective extractant. Calculations for the energy-minimized structures for the imine diastereomers and the comparison of the selectivities with other phenyl ketones, ( S)- 4 and ( S)- 5, demonstrate that the hydrogen bond between the carboxylate group and the phenolic hydroxyl group contributes to the remarkable enantioselectivities. The multiple hydrogen bonds present in the imine of ( S)- 3 reinforce the rigidity, and results in the difference between the stabilities of the imine diastereomers. The imine could be hydrolyzed in methanolic HCl solution, and the extraction of the evaporated residues revived the organic layer of ( S)- 3, which could enter into a new extractive cycle and leaves the D-amino acid with enantiomeric excess ( ee) values of over 97 % in the aqueous layer. [ABSTRACT FROM AUTHOR]