Three-Coordinate Iron(0) Complex-Catalyzed Regioselective C–H Alkylation of Indole Derivatives

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

The synthesis of alkylated indoles, which are key intermediates for various drugs and bioactive molecules, is great importance. However, most reports on the functionalized indoles use toxic expensive 4d or 5d metal catalysts, limiting further application these methods. Herein, we disclose a versatile regioselective C–H alkylation indole derivatives using well-defined three-coordinate iron(0) complex. Neither Grignard reagents nor additional additives required, making reaction sustainable, environmentally friendly, compatible with broad variety functional groups to afford C2-alkylated in high yields. In addition, by variation aryl substituent alkene substrate trisubstituted silyl group, regioselectivity can be altered from Markovnikov anti-Markovnikov. Detailed mechanistic studies revealed catalytic mode reaction.

Language: Английский

---

Advancement in the C–H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal–iron

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(8), P. 2397 - 2417

Published: Jan. 1, 2024

Advancement in the direct C–H bond alkylation of arenes and heteroarenes using catalysts based on most abundant transition metal, iron, is summarized.

Language: Английский

---

Divergent Synthesis of Di‐ and Mono‐Alkylated Indoles via Tunable Iron‐Catalyzed Hydroarylation of Styrenes

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(10), P. 2226 - 2233

Published: March 23, 2024

Abstract We report an iron‐catalyzed divergent synthesis of alkylated indoles based on precise control the activation sites through selection catalysts. Using and styrenes as starting materials, 3,5‐ di ‐alkylated could be prepared selectively directly for first time by treating with a catalytic amount Fe(OTf) 3 3‐alkylated were achieved exclusively adding γ ‐cyclodextrin cocatalyst . This simple method was demonstrated 52 examples high yields broad functional group compatibilities.

Language: Английский

---

Nickel‐Catalyzed Branch‐Selective C−H Alkylation of Indoles and Azoles with Alkenes: An Additive‐ and Solvent‐Free Approach

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(26)

Published: April 10, 2024

Abstract The development of sustainable protocols for the synthesis alkylated heteroarenes is crucial owing to their widespread existence in medicinally relevant and bioactive natural products. Herein, we describe an efficient, additive‐ solvent‐free approach regioselective C−H alkylation indoles azoles with alkenes using a nickel catalyst, which proceeds through chelation‐assistance strategy. reaction exclusively provided branched products compatibility alkyl, alkoxy, fluoro, trifluoromethyl, alkene, cyano, ester, carbonyl groups. This protocol applicable other heteroarenes, such as imidazoles benzimidazoles, providing desired exclusive Markovnikov selectivity. synthetic utility scale‐up are demonstrated, concord principles green chemistry. Alkylation facile reversible nickelation alkene insertion processes, presumably involving rate‐limiting reductive elimination.

Language: Английский

---

Iron-Catalyzed Functionalization of Heterocycles Through C─H Activation

Topics in heterocyclic chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 32

Published: Jan. 1, 2024

Language: Английский

---

Palladium‐Catalyzed Regioselective C(4)−H Fluoroalkoxylation of Indoles through Weak Chelation Assistance

ChemCatChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Abstract Installing fluoroalkyl motifs into biorelevant indoles is particularly interesting due to their ubiquitous presence in drug molecules. Herein, we demonstrate the regioselective C4 fluoroalkoxylation of using fluoroalcohols via palladium‐catalyzed chelation‐assisted C─H activation. The weak chelating benzoyl moiety at C3 position acts as a directing group for remote C(4)─H diversely substituted indoles. This methodology demonstrates high level regioselectivity and tolerates range crucial functional groups, yielding diverse trifluoroalkoxylated moderate good yields. Removal directing/protecting groups further functionalization established synthetic utility methodology. A preliminary mechanistic investigation conducted by isolating palladacycle intermediate performing deuterium scrambling study.

Language: Английский

---

Base‐Promoted Structural Rearrangement of Ynamide and Simultaneous N‐Desulfonylation

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(7), P. 1615 - 1626

Published: Feb. 7, 2024

Abstract Herein, we describe a base‐promoted regioselective and chemoselective cascade cyclization, ynamide N−C sp bond cleavage, selective intramolecular 1,3‐migration, simultaneous N ‐desulfonylation strategy for the synthesis of 2‐phenyl‐3‐(phenylethynyl)‐1H‐indole derivatives. We observed multiple breaking (−N−Ts, C 2 −Ts, −I/C −SePh) from ( E )‐3‐(1‐iodo‐2‐phenyl‐2‐tosylvinyl)‐2‐phenyl‐1‐tosyl‐indole/( )‐2‐phenyl‐3‐(2‐phenyl‐1‐(phenylselanyl)‐2‐tosylvinyl)‐1‐tosyl‐indole derivatives to prepare in 15–60 min using our standard reaction conditions. A gram‐scale experiment as well postsynthetic transformations synthesized were performed exhibit advantages this synthetic methodology.

Language: Английский

---

Iron-catalyzed Selective Construction of Indole Derivatives via Oxidative C(sp3)-H Functionalization of Indolin-2-ones

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(15), P. 3073 - 3079

Published: Jan. 1, 2024

We have developed a clean and efficient iron-catalyzed C(sp 3 )–H functionalization of indolin-2-ones for the chemodivergent synthesis value-added indole derivatives, including isatins, symmetrical non-symmetrical isoindigos.

Language: Английский

---