Switching Chemoselectivity Based on the Ring Size: How to Make Ring-Fused Indoles Using Transition-Metal-Mediated Cross-Coupling

Cited 2 time in webofscience Cited 0 time in scopus
  • Hit : 67
  • Download : 18
Pyrroloazocine indole alkaloids consisting of eight-membered azacycle fused to pyrrole and indole units exhibit intriguing pharmacological functions but still pose a synthetic challenge. Here, we report an alternative syn thetic strategy for the pyrroloazocine indole core from two key steps: (i) regioselective Fischer indolization and (ii) transition-metal-mediated C-N cross-coupling reaction of N-Boc aryl hydrazine with azacyclic vinyl triflate. In our investigation, Pd(0)- and Cu(I)-catalysts are found to display distinct and complementary selectivities for the ring size of cyclic vinyl triflates. For rings that are five- and six-membered, a Pd(0)-catalyst afforded the corresponding ene-hydrazines while completely ineffective for seven-membered or larger rings. A Cu(I)-catalyst exhibited the opposite selectivities. Computational studies reveal that their ring size dependency is due to the two bottlenecks of reductive elimination for Pd and oxidative addition for Cu along with bond strengths in products and reactants and degree of stage at transition states. These findings led us to establish a straightforward protocol for accessing a variety of ring-fused indoles highlighted with the formal synthesis of (-)-lundurine A.
Publisher
AMER CHEMICAL SOC
Issue Date
2021-10
Language
English
Article Type
Article
Citation

ACS CATALYSIS, v.11, no.20, pp.12821 - 12832

ISSN
2155-5435
DOI
10.1021/acscatal.1c03797
URI
http://hdl.handle.net/10203/289384
Appears in Collection
CH-Journal Papers(저널논문)
Files in This Item
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 2 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0