Ligand-controlled regiodivergent direct arylation of indoles via oxidative boron Heck reaction

Yang, Yo‐Sep; Lee, Sang‐Min; Son, Seung Hwan; Yoo, Hyung-Seok; Jang, Yoon Hu; Shin, Jeong-Won; Won, Hyuck-Jae; Sim, Jaehoon; Kim, Nam‐Jung

doi:10.1039/d2qo01326f

Cited by 11 publications

(2 citation statements)

References 39 publications

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“…Nevertheless, direct arylation for the synthesis of 2-aryl indoles still faces the regioselectivity challenge as the most reactive position of indoles is the C3 site ( 41 ). Strategies in achieving high site selectivity of indole C2 arylation include preinstallation of directing groups or protecting groups on the nitrogen atom, the use of acidic/basic additives, the switch of ligand, and the limited substrate scope ( 42 ).…”

Section: Introductionmentioning

confidence: 99%

Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs

Feng,

Zhen,

et al. 2024

Sci. Adv.

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Achieving regioselective synthesis in complex molecules with multiple reactive sites remains a tremendous challenge in synthetic chemistry. Regiodivergent palladium-catalyzed C─H arylation of complex antitumor drug osimertinib with various aryl bromides via the late-stage functionalization strategy was demonstrated here. This reaction displayed a switch in regioselectivity under complete base control. Potassium carbonate (K 2 CO 3 ) promoted the arylation of acrylamide terminal C(sp 2 )-H, affording 34 derivatives. Conversely, sodium tert -butoxide ( t -BuONa) mediated the aryl C(sp 2 )-H arylation of the indole C2 position, providing 27 derivatives. The derivative 3r containing a 3-fluorophenyl group at the indole C2 position demonstrated similar inhibition of EGFR T790M/L858R and superior antiproliferative activity in H1975 cells compared to osimertinib, as well as similar antiproliferative activity in A549 cells and antitumor efficacy in xenograft mouse model bearing H1975 cells. This approach provides a “one substrate–multi reactions–multiple products” strategy for the structural modification of complex drug molecules, creating more opportunities for the fast screening of pharmaceutical molecules.

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Section: Introductionmentioning

confidence: 99%

Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs

Feng,

Zhen,

et al. 2024

Sci. Adv.

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“…Direct C–H arylation reaction has been proved to be a particularly efficient methodology for the formation of carbon–carbon bonds without the use of organometallic nucleophiles. 11–22 Direct arylation reactions have been reported by many researchers including our group, 15–22 and proven to be useful for synthesizing a variety of π-conjugated polymers with high molecular weights. In the past decade, comprehensive efforts have been made on transition metal ( e.g.…”

Section: Introductionmentioning

confidence: 99%

Polymers based on thieno[3,4-c]pyrrole-4,6-dione and pyromellitic diimide by CH–CH arylation reaction for high-performance thin-film transistors

et al. 2022

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Catalyst‐Controlled Divergent C3/C5 Site‐Selective C−H Arylation of 2‐Pyridylthiophenes

Huang,

Zhou,

Yang

et al. 2023

Adv Synth Catal

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The development of a rational protocol to realize the complete regioselectivity and the capability to switch regioselectivity is an appealing yet challenging task. Herein, a regiodivergent C−H arylation of 2‐pyridylthiophenes has been demonstrated via the choice of RuII and PdII catalysts. The reactions proceeded smoothly in a good regioselective manner to afford the corresponding C3‐ and C5‐arylated thiophenes. Late‐stage diversification of biologically relevant scaffold derived from estrone and successful transformation of the products further highlighted the potential utility and importance of this synthetic strategy.

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Ligand-controlled regiodivergent direct arylation of indoles via oxidative boron Heck reaction

Abstract: Ligand-controlled direct arylation of indoles via Pd(II) catalyzed oxidative boron Heck reaction in an aerobic condition is reported. This methodology provides a regiodivergent route for C2 or C3 aryl indole...

Cited by 11 publications

References 39 publications

Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs

Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs

Polymers based on thieno[3,4-c]pyrrole-4,6-dione and pyromellitic diimide by CH–CH arylation reaction for high-performance thin-film transistors

Catalyst‐Controlled Divergent C3/C5 Site‐Selective C−H Arylation of 2‐Pyridylthiophenes

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