Dearomatization of Indoles via a Phenol‐Directed Vanadium‐ Catalyzed Asymmetric Epoxidation and Ring‐Opening Cascade

Abstract

An enantioselective dearomatization of indole derivatives was realized by the complexes derived from the vanadium complexV O(acac) 2 and C 2 -symmetric bis-hydroxamic acid (BHA) ligands. Ther eactionp roceeded via asymmetric epoxidation and ring-opening by the linked phenolc ascade, affording 5a,6,10b,11-tetrahydrochromeno[2,3-b]-indol-10b-ol derivatives in up to 83% yield and 98% ee under mild reactionc onditions.Keywords: asymmetric catalysis; dearomatization; epoxidation;i ndoles;vanadium Epoxides exist as key moieties in numerous natural productsa nd biologicallya ctive molecules,a nd also serve as important synthetic intermediates associated with versatile sequential ring opening processes.[1]Since more than one stereogenic center couldb e launched in as ingle step,a symmetric epoxidation reactions have received broad research interest andw itnessed dramaticg rowthd uring the past decades. [2] Enantiomerically enriched epoxides derivedf rom unfunctionalized olefins, [3] electron-deficient olefins [4] and (homo)allylic alcohols [5] have been achieved by well-developed chiral catalytic systems including either transitionm etal catalysts or organocatalysts. Meanwhile,c atalytic asymmetric dearomatization Scheme 1. Enantioselective epoxidative dearomatization reaction.

From Benzofurans to Indoles: Palladium‐Catalyzed Reductive Ring‐Opening and Closure via β‐Phenoxide Elimination

“…HRMS (EI) m/z: [M] + Calcd for C 16 H 15 NO 237.1154; Found 237.1151. Spectral data are in agreement with the literature …”

Electrochemical Dearomative Dihydroxylation and Hydroxycyclization of Indoles

“…In the case of oxygenated nucleophiles, the C2position of the oxidized indole is intramolecularly intercepted by this nucleophile, while the C3-position is attacked by water. [20] Hydroxy-tetrahydropyranoin-dolines 12 a-d were thus obtained from indoles containing a primary or a tertiary alcohol. Replacing the alcohol by a carboxylic acid led to the corresponding δ-valerolactones 12 e,f.…”

Recent Developments in Enantioselective Metal‐Catalyzed Domino Reactions

“…In 2015, the same authors applied the same precatalyst combined to another chiral ligand 168 to the asymmetric vanadium‐catalyzed domino epoxidation/intramolecular ring‐opening reaction of indole derivatives 169 performed in dichloromethane at 0 °C 84. The process evolved through enantioselective vanadium‐catalyzed epoxidation of indoles 169 with tert‐ butyl hydroperoxide as oxidant, which was followed by ring‐opening with the linked phenol to afford important chiral tetracyclic products 170 in moderate to good yields (45–83%) and very good enantioselectivities of 90–98% ee , as shown in Scheme .…”