We present a new sustainable and efficient approach that consists of a telescoped CDC/Mannich reaction in continuous flow to access enantiopure carbonyl derivatives of masked non-proteinogenic mmino acids (NPAAs). The protocol consists of two reactions: the C−H activation of glycine analogues enabled by mesoporous graphitic carbon nitride (mpg-CN), followed by a Mannich reaction between α-enolizable ketones or aldehyde, activated by a supported proline-like organocatalyst (Si-Ley), and the imine formed in the first step. The protocol was designed embracing the principles of green chemistry (metal-free catalysis, the reuse of medium and catalysts to reduce the E-factor, and the use of air for oxidation). Furthermore, good results were obtained in terms of yield and enantioselectivity (Y = up to 91% and ee = up to 99%). Long-term stability experiments and reactivation studies were performed providing excellent results in terms of the durability of the system; furthermore; we were able to obtain 1.8 g of the desired product of the benchmark reaction (gram scale) after cumulative runs. Furthermore, NMR measurements were employed to shine light on the deactivation of the catalysts during the operative conditions.

A Telescoped Photo-/Organo-Catalyzed Cross Dehydrogenative Coupling (CDC) between Glycine Derivatives and Ketones to Afford Non proteinogenic Amino Acids (NPAAs) Enabled by Heterogeneous Continuous Flow Catalysis

Lorenzo Poletti;Daniele Ragno;Carmela De Risi;Sofia Toldo;Olga Bortolini;Paolo Dambruoso;Alessandro Massi;Graziano Di Carmine
2024

Abstract

We present a new sustainable and efficient approach that consists of a telescoped CDC/Mannich reaction in continuous flow to access enantiopure carbonyl derivatives of masked non-proteinogenic mmino acids (NPAAs). The protocol consists of two reactions: the C−H activation of glycine analogues enabled by mesoporous graphitic carbon nitride (mpg-CN), followed by a Mannich reaction between α-enolizable ketones or aldehyde, activated by a supported proline-like organocatalyst (Si-Ley), and the imine formed in the first step. The protocol was designed embracing the principles of green chemistry (metal-free catalysis, the reuse of medium and catalysts to reduce the E-factor, and the use of air for oxidation). Furthermore, good results were obtained in terms of yield and enantioselectivity (Y = up to 91% and ee = up to 99%). Long-term stability experiments and reactivation studies were performed providing excellent results in terms of the durability of the system; furthermore; we were able to obtain 1.8 g of the desired product of the benchmark reaction (gram scale) after cumulative runs. Furthermore, NMR measurements were employed to shine light on the deactivation of the catalysts during the operative conditions.
2024
Poletti, Lorenzo; Codecà, Nicola; Ragno, Daniele; DE RISI, Carmela; Toldo, Sofia; Bortolini, Olga; Shao, Jiaye; An, Lan; Lee, Daniel; D’Agostino, Car...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2568510
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