Radical Beckmann Rearrangement and Its Application in the Formal Total Synthesis of Antimalarial Natural Product Isocryptolepine via C–H Activation

Abstract

The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and (18)O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples. The developed protocol and Pd-catalyzed intramolecular double C-H activation were used as key steps in the formal total synthesis of antimalarial natural product isocryptolepine.

β‐Cyclodextrin: A Green and Efficient Supramolecular Catalyst for Organic Transformations

“…Conventional Beckmann rearrangement usually requires relatively high temperature, large amount of strongly acidic and dehydrating media such as concentrated H 2 SO 4 (forms ammonium sulfate as byproduct), polyphosphoric acid, P 2 O 5 ‐methanesulfonic acid, that leads to the large waste products (formation of inorganic salts caused by neutralization) and not applicative to sensitive substrate. Some other reported methods for Beckmann rearrangement includes use of cyanouric chloride along with ZnCl 2 , mercury(II) chloride, silica‐supported phosphorus chloride, Bromodimethylsulfonium bromide along with imidazolium‐based ionic liquid [bmim]PF 6 , triflic anhydride, CBr 4 /PPh 3 , ammonium persulfate‐DMSO, Mukiyama reagent, etc. However, some of these processes require hazardous high cost solvents like DCM, DMF, acetonitrile, toluene, etc.…”

Visible Light‐Promoted Beckmann Rearrangements: Separating Sequential Photochemical and Thermal Phenomena in a Continuous Flow Reactor

“…Apart from the well‐established methods mentioned above, many endeavors have been devoted to achieving Beckmann rearrangements under more benign and controllable conditions. These procedures include the use of boronic acid catalysts or radical pathways induced by (NH 4 ) 2 S 2 O 8 /DMSO . Several examples of photochemical Beckmann rearrangements were reported in the 1960s and 1970s using UV‐C irradiation .…”

SO2F2‐Activated Efficient Beckmann Rearrangement of Ketoximes for Accessing Amides and Lactams

“…Intriguingly, a boronic acid were identified as an efficient catalyst for the activation of oximes . Other amusing variants, such as a facile radical (Scheme c) and visible‐light‐driven (Scheme d) Beckmann rearrangements,, also provides alternative strategies. Although those above related organic compounds could be employing as promoters or catalysts to achieve effective activation of oxime N–OH bonds in the Beckmann rearrangement, pre‐synthesis of those structurally specific organic compounds is oftentimes required and mild catalytic manifolds are rare.…”