Radical Addition-Initiated Domino Reactions of Conjugated Oxime Ethers

Abstract

The application of conjugated oxime ethers to the synthesis of complex chemical scaffolds using domino radical reactions has been described in detail. The triethylborane-mediated hydroxysulfenylation reaction allows for the regioselective construction of a carbon-sulfur bond and a carbon-oxygen bond in a single operation for the formation of β-hydroxy sulfides. This reaction proceeds via a radical pathway involving regioselective thiyl addition and the subsequent trapping of the resulting α-imino radical with O₂, where the imino group enhances the stability of the intermediate radical. Hydroxyalkylation reactions that occur via a carbon radical addition reaction followed by the hydroxylation of the resulting N-borylenamine with O₂ have also been developed. We investigated sequential radical addition aldol-type reactions in detail to explore the novel domino reactions that occur via the generation of N-borylenamine. The radical reaction of a conjugated oxime ether with triethylborane in the presence of an aldehyde affords γ-butyrolactone via sequential processes including ethyl radical addition, the generation of N-borylenamine, an aldol-type reaction with an aldehyde, and a lactonization reaction. A novel domino reaction has also been developed involving the [3,3]-sigmatropic rearrangement of N-boryl-N-phenoxyenamine. The triethylborane-mediated domino reactions of O-phenyl-conjugated oxime ethers afforded the corresponding benzofuro[2,3-b]pyrrol-2-ones via a radical addition/[3,3]-sigmatropic rearrangement/cyclization/lactamization cascade.

Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle

“…Most of these reactions are usually conducted under cheap transition metal catalyst and oxygen, allowing the construction of N-heterocycles with good functional group tolerance and more diverse transformation. It is worth noting that the radical strategy shows more powerful prospects than the conventional transition metal catalytic strategy [ 9 , 66 ], allowing the development dual catalysis systems, such as synergistic copper and photoredox catalysis and synergistic nickel and photoredox catalysis [ 67 , 68 , 69 , 70 ]. In particular, the iminyl radicals as unstable nitrogen radicals can be transformed more often to synthesize complex and diverse N-heterocycles [ 71 , 72 , 73 ].…”

Copper-Catalyzed Aerobic C(<i>sp</i>³)–H Oxidation of β-(Alkoxy)imino Carbonyl Compounds

“…30,34) Inspired by the oxidation of enamines and our previous re-search on the hydroxylation of α-imino radicals, 35,36) herein we report the direct synthesis of 1-imino-2,3-dicarbonyl compounds via the copper(II)-catalyzed C-H aerobic oxidation of β-(alkoxy) imino carbonyl compounds. Although the diverse reactivity of oximes has been investigated in depth, [37][38][39] the chemistry of α-carbon in the oxime, or N-alkoxyenamines as a tautomer of oxime ethers, remains underdeveloped.…”

A Base-Catalyzed, Domino Aldol/hetero-Diels–Alder Synthesis of Tricyclic Pyrano[3,4-c]chromenes in Glycerol

“…In the same way, imine generation coupled with hetero -Diels–Alder transformation happens to be an interesting example of a growing research area in synthetic organic chemistry. Hydroxylation-oxidation Diels–Alder, Sakurai Carbonyl-ene, Pictet–Spengler-ene, alkyl radical addition-aldol, Michael-aldol, and Claisen–Schmidt–Michael reactions are other domino routes that appear in the literature. To the best of our knowledge, aldol condensation coupled to the hetero -Diels–Alder reaction remains a very rarely employed synthetic sequence involving the use of a mono ketone unit relative to the domino Knoevenagel- hetero -Diels–Alder sequence, which utilizes diketone units .…”