Synthesis of highly functionalised spiro-indoles by a halogen atom transfer radical cyclization

Abstract

The halogen atom transfer radical cyclization (HATRC) has been evaluated on N-(indolylmethyl)trichloroacetamides under Cu(I)Cl catalysis using nitrogen containing ligands. The ring closure leads to the formation of 3,3-spiro-3H-indoles in moderate to good yields by a 5-exo-mechanism. Derivatives with an N-electron withdrawing substituent also lead to a 5-exo-trig and not to a 6-endo-trig cyclization.

Copper Catalyzed Atom Transfer Radical Cyclization Reactions

“…This approach was successfully employed in the total synthesis of the antibacterial agent (±)‐botryodiplodin 20c. A similar reactivity order was found for the cyclization of 44 to give 46 20d and 47 to give 48 (Scheme ) 36. Spiroindoles were also prepared by Cu(PMDETA)Cl catalyzed ATRC of 2‐substituted indole derivatives 20f…”

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

“…This α‐chloropyrrolidine 46 was expected to spontaneously eliminate a molecule of HCl to form the pyrroline intermediate 47 due to basic Cu(I/II)/PMDETA complex as reported by Stevens et al . However, when the reaction of 20 a under the optimized reaction condition was intercepted after 4 h, 2 h before the completion of the reaction, no pyrroline derivative (of type 47 or isopyrazole 48 ) except the pyrrole 21 a and the unreacted starting material 20 a were obtained by column chromatography of the crude product.…”

“…No pyrrole moiety of type 32 could be isolated by column chromatography of the crude product, formed expectedly through dehydrochlorinations of HATRC product 31 . A trace of pyrrole 37 was obtained on the purification of the crude product by column chromatography whereas enamines 20 a , n underwent the cyclization smoothly.…”

Synthesis of α‐Chlorolactams by Cyanoborohydride‐Mediated Radical Cyclization of Trichloroacetamides

“…The primary C‐centered radical is then reduced by cyanoborohydride to afford dichlorolactam III along with a borane radical anion, which can sustain the radical chain by abstracting a chlorine atom from trichloroacetamide 4 a , returning the dichloromethyl radical I and the chlorinated borane (NaBH 2 ClCN). Finally, a dehalogenation occurs through radical IV to afford a monochlorinated lactam (e.g., 5 ) …”