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![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Total Synthesis of the Spirocyclic Bis-Indole Alkaloid (-)-Owerreine via a [4+2] Annulation
Elisa Coll1, Vincent Gandon1, Cyrille Kouklovsky1
1Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Saclay and CNRS, Orsay, France.
Abstract:
We report the total synthesis of (-)-owerreine, a bis-indole alkaloid biosynthetically assembled from two deoxoapodine units. This aspidosperma monomeric template was synthesized via a domino Michael/Mannich/N-allylation sequence from a chiral indolyl-N-sulfinylimine and a DIAD-oxidation-promoted cycloetherification. It was further divergently transformed into an enamine precursor and an α,β-unsaturated indolenine, which were diastereoselectively assembled in the presence of the Eschenmoser salt through a [4+2] annulation. DFT calculations were deployed to gain insight into the mechanism and diastereoselectivity of this key step.
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Preparation of Epoxides
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...