Continuous-Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen

Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable‐temperature continuous‐flow LED‐photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α‐Aminonit...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2014-01, Vol.53 (2), p.557-561
Main Authors: Ushakov, Dmitry B., Gilmore, Kerry, Kopetzki, Daniel, McQuade, D. Tyler, Seeberger, Peter H.
Format: Article
Language:English
Subjects:
Amines
Amines - chemistry
Amino acids
Cyanides
Cyanides - chemistry
CH activation
flow chemistry
Imines
Imines - chemistry
Joining
Molecular Structure
Nitriles - chemical synthesis
Nitriles - chemistry
Oxidation-Reduction
Photochemistry
photooxidation
Porphyrins - chemistry
Precursors
Singlet oxygen
Singlet Oxygen - chemistry
Strecker reaction
Synthesis
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Summary:Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable‐temperature continuous‐flow LED‐photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α‐Aminonitriles were obtained in good to excellent yields when trimethylsilyl cyanide served as an in situ imine trap. At 25°C, primary amines were found to undergo oxidative coupling prior to cyanide addition and yielded secondary α‐aminonitriles. Primary α‐aminonitriles were synthesized from the corresponding primary amines for the first time, by an oxidative Strecker reaction at –50 °C. This atom‐economic and protecting‐group‐free pathway provides a route to racemic amino acids, which was exemplified by the synthesis of tert‐leucine hydrochloride from neopentylamine. The mild synthesis of imines paves the way to aminonitriles and amino acids. Aerobic oxidation of primary and secondary amines in a continuous photoreactor with singlet oxygen generated in situ led to the rapid formation of imines, which were quantitatively trapped as α‐aminonitriles (see scheme; TMS=trimethylsilyl). Benzylic and primary α‐aminonitriles, precursors for amino acids, could be efficiently produced in three minutes.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201307778