Recent Advances on Asymmetric Nitroso Aldol Reaction

Merino, Pedro; Tejero, Tomás; Delso, J. Ignacio; Matute, Rosa

doi:10.1055/s-0035-1561505

Cited by 27 publications

(15 citation statements)

References 76 publications

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“…[26][27][28] Recently, the aerobic oxidation of hydroxamic acids by metal catalysts under mild conditions has been developed as an efficient strategy for nitrosocarbonyl generation. [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] In general, however, the above methods are not suitable for HNO generation under physiological conditions. Herein, we report a novel class of nitrosocarbonyl donors that upon deprotonation and loss of the leaving group (Scheme 1, HX = pyrazolone) generate nitrosocarbonyl intermediates that can hydrolyze to release HNO under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

et al. 2016

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A new class of nitrosocarbonyl precursors, O-substituted hydroxamic acids with pyrazolone leaving groups (OHPY), is described.These compounds generate nitrosocarbonyl intermediates, which upon hydrolysis release nitroxyl (azanone, HNO) under physiologically relevant conditions. Pyrazolones have been used to confirm the generation of nitrosocarbonyls by competitive trapping to form isomeric N-substituted hydroxamic acids (NHPY) via an N-selective nitrosocarbonyl aldol reaction. The rate of nitrosocarbonyl release from OHPY donors is impacted by donor substituents, including the pyrazolone leaving group.

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Section: Introductionmentioning

confidence: 99%

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

et al. 2016

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“…Merino et al, suggests that ketone groups tend to react with nitroso groups by either α-oxyamination or α-aminoxyation mechanism (Fig. 2c) [27]. Hence, the nitrosobenzene reagent (1) could also react with the solvent 4M2P and form the side-products 6 and/or 7.…”

Section: Hetero-diels Alder Reactionmentioning

confidence: 98%

Ion mobility spectrometry-tandem mass spectrometry strategies for the on-line monitoring of a continuous microflow reaction

2021

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Continuous flow chemistry is an efficient, sustainable and green approach for chemical synthesis that surpasses some of the limitations of the traditional batch chemistry. Along with the multiple advantages of a flow reactor, it could be directly connected to the analytical techniques for on-line monitoring of a chemical reaction and ensure the quality by design. Here, we aim to use ion mobility, mass and tandem mass spectrometry (IMS-MS and MS/MS) for the on-line analysis of a pharmaceutically relevant chemical reaction. We carried out a model hetero-Diels Alder reaction in a microflow reactor directly connected to the IMS-MS and MS/MS using either electrospray or atmospheric pressure photo ionization methods. We were able to monitor the reaction mechanism of the Diels Alder reaction and structurally characterize the reaction product and synthesis side-products. The chosen approach enabled identification of two isomers of the main reaction product. A new strategy to annotate the ion mobility spectrum in the absence of standard molecules was introduced and tested for its validity. This was achieved by determining the survival yield of each isomer upon ion mobility separation and density functional theory calculations. This approach was verified by comparing the theoretically driven collision cross section values to the experimental data. In this paper, we demonstrated the potential of combined IMS-MS and MS/MS on-line analysis platform to investigate, monitor and characterize structural isomers in the millisecond time scale.

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“…The noteworthy and widely explored transformations of nitrosoarenes include nitroso ene reactions [9][10][11], Diels-Alder cycloadditions [12][13][14][15][16][17][18], and nitroso aldol reactions [19][20][21][22][23]. Among the various applications of nitrosoarenes, the asymmetric nitroso aldol reaction to achieve optically active α-aminoxy and α-hydroxyamino carbonyl compounds has received considerable attention in the past decades [24]. In 2003, the Yamamoto group demonstrated for the first time that nitrosobenzene could be used as a prac-Scheme 1: Catalytic asymmetric nitroso aldol reaction.…”

Section: Introductionmentioning

confidence: 99%