Consecutive oxygen-based oxidations convert amines to α-cyanoepoxides

Abstract

Tri- or tetrasubstituted α-cyanoepoxides can be rapidly prepared from unactivated amines and malononitrile or methyl cyanoacetate when singlet oxygen, produced in a continuous-flow photoreactor, serves as an oxidant and in situ peroxide source. The hydrogen peroxide generated in amine oxidation epoxidizes an electron deficient olefin intermediate, formed by deaminative Mannich coupling. The corresponding α,α-dicyano- or α-cyano-α-esterepoxides were obtained in good yields (43-82%).

Aerobic Photooxidative Synthesis of Secondary Aldimines from Benzylamines by Using Methylene Blue

“…6,20 On the first path, the successive addition of amine and the elimination of NH 3 , which results in the coupled imine, are shown. 25 In the other, the formation of benzaldehyde and successive condensation, which results in the coupled imine, are shown.…”

Aerobic Oxidations in Continuous Flow

“…In this context Seeberger and coworkers developed a procedure for the oxidation of primary and secondary amines to the corresponding imines in continuous flow using singlet oxygen which was generated using low amounts of meso-tetraphenylporphyrin (TPP) [159][160][161][162]. The imines generated from secondary amines immediately resulted in the corresponding α-aminonitriles in good to excellent isolated yields at room temperature using CH 2 Cl 2 as solvent in the presence of trimethylsilyl cyanide as trapping agent (Scheme 22) [159].…”

“…The authors found that primary amines could be converted to α-aminonitriles in a selective manner by switching from CH 2 Cl 2 to THF as solvent at significantly lower temperatures (À50 C) adding sub-stoichiometric amounts of TBAF to activate the TMSCN. The concept was further expanded for the synthesis of α-cyanoepoxides and fluorinated α-amino acids [160,162].…”

A Novel Nebulizer‐Based Continuous Flow Reactor: Introducing the Use of Pneumatically Generated Aerosols for Highly Productive Photooxidations

“…The high productivity of this photoreactor was attributed to the increase in specific surface area (up to 25,300 m 2 m −3 versus 2,000 m 2 m −3 for equivalent batch reactors) when biphasic gas–liquid reactions were conducted at high flow rates . Similar set‐ups were applied to the synthesis of the antimalaria drug artemisinin, α‐aminonitriles, α‐cyanoepoxides and the photooxygenation of the bio‐derived 5‐hydroxymethylfurfural . Despite the excellent productivity of these CFRs, it is obvious that further increases in the reactor size would require added layers of complexity and additional problem solving to refine the equipment.…”

“…[21] Fluorinated ethylene propylene (FEP) tubing was wrapped around a4 50 Wm ercury lamp while the substrate and oxygen were mixed using ap olytetrafluoroethylene (PTFE) T-mixer.T he highp roductivity of this photoreactor was attrib-uted to the increase in specific surface area (up to 25,300 m 2 m À3 versus 2,000 m 2 m À3 for equivalent batch reactors) when biphasic gas-liquid reactions were conducted at high flow rates. [18,22,23] Similars et-upsw ere appliedt ot he synthesis of the antimalaria drug artemisinin, [24][25][26] a-aminonitriles, [27] a-cyanoepoxides [28] and the photooxygenation of the bio-derived 5-hydroxymethylfurfural. [29] Despite the excellent productivity of these CFRs, it is obvious that furtheri ncreases in the reactors ize would require added layers of complexity and additional problem solvingt or efine the equipment.F urthermore, maintaining the high productivity might become ever more challenging.…”