Visible‐Light Catalytic Photooxygenation of Monoterpene Indole Alkaloids: Access to Spirooxindole‐1,3‐oxazines

Abstract

Few natural oxindole alkaloids possess an exceptional spiro-[(1,3)oxazinan-3,6'-oxindole] core structure, which results from an unusual oxidative indole rearrangement. The Rauvolfia alkaloid reserpine can be converted into the spirooxindole-1,3-oxazines dioxyreserpine and trioxyreserpine through efficient visible-light catalytic photooxygenation with anthraquinone photocatalysts. A mechanistic investigation sheds new light on the photooxidative rearrangement of reserpine and related monoterpene indole alkaloids, and the spirooxindole-1,3-oxazine products can be valorized by reductive ring opening, to obtain cis-decahydroisoquinolines as new enantiopure synthetic building blocks, as demonstrated for dioxyreserpine.

Anthraquinones: Versatile Organic Photocatalysts

“…[64] The Brasholz group found that reserpine (66) could be photooxidized to spirocycle 67 with light, O 2 , and an AQ catalyst (Scheme 17). [65] The structure of hemiaminal 67 was determinated by X-ray crystallography and could be further oxidized to tryoxyreserpine (68). These findings may shed light on the biosynthesis of spirooxindole-1,3-oxazine natural products.…”

“…In the last decade, some researchers have begun to employ AQs in visible‐light induced, catalytic photooxidations obtaining products such as carboxylic acids, gem ‐diols, aromatic methyl esters, phenols, diacylamines, epoxides, and hydroxyalkyl esters. This activation involves either hydrogen‐atom or electron transfer …”

“…Indole alkaloids and spirocyclic 2‐oxindoles are significant classes of bioactive natural products . The Brasholz group found that reserpine ( 66 ) could be photooxidized to spirocycle 67 with light, O 2 , and an AQ catalyst (Scheme ) . The structure of hemiaminal 67 was determinated by X‐ray crystallography and could be further oxidized to tryoxyreserpine ( 68 ).…”

Visible Light Mediated Synthesis of Oxindoles

“…In the same year, the synthesis of dioxyreserpine 97 from reserpine 96 via visible light mediated photooxygenation with 1,5‐diaminoanthraquinone (as a photocatalyst) was achieved by Brasholz and co‐workers (Scheme 35). [57] Despite narrow substrate scope, the protocol opened a potential route to synthesize the potent dioxyreserpine in good yields.…”

Recent Developments in Photo‐Catalyzed/Promoted Synthesis of Indoles and Their Functionalization: Reactions and Mechanisms

“…[165] Brasholz et al developed an effective visible light induced photooxygenation strategy to give the valuable spirooxindole-1,3-oxazines from monoterpene indole alkaloids involving in an unusual oxidative indole rearrangement (Scheme 107). [166] This transformation is initiated through hydrogen abstraction from indole by excited catalyst AQ*, followed by stereoselective radical oxygenation with O 2 . Then, the generated peroxyradical 309 undergoes intramolecular 1,5-HAT to deliver a stabilized and strain-relieved allylic radical 310.…”