Catalyst Comparison for Additive-Free Acceptorless Dehydro­genation of Indoline Derivatives

Abstract

A group of thirteen catalysts of type [Ru(Cp/Cp*)(P–P)(MeCN)]PF₆, bearing cooperative or noncooperative bidentate phosphine ligands, were evaluated for the catalytic acceptorless dehydrogenation of indoline. The systematic comparison revealed that the optimal cooperative catalyst structure included a Cp ancillary ligand, and an N,N-disubstituted P,P-disubstituted 1,5-diaza-3,7-diphosphacyclooctane ligand, denoted as (P^R ₂N^R′ ₂). A cooperative complex bearing a P^Ph ₂N^Ph ₂ ligand exhibited about a twofold longer lifetime than a noncooperative analogue with (diphenylphosphino)ethane (dppe) as the supporting bisphosphine ligand. The cooperative catalyst effectively dehydrogenated a range of indoline substrates to give substituted indoles.

Key words

cooperative catalysis - dehydrogenation - indoles - ruthenium catalysis - ligands

Publication History

Received: 02 December 2022

Accepted after revision: 18 January 2023

Article published online:
15 February 2023

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• 17 [Ru(Cp/Cp*)(P–P)(MeCN)]PF₆ (4c and 5a); General Procedure A 100 mL Schlenk flask equipped with a stirrer bar was charged with [Ru(Cp/Cp*)(MeCN)₃]PF₆ (0.106 mmol, 1 equiv), ligand P–P (0.111 mmol, 1.05 equiv), and MeCN (20 mL). The flask was then heated to 65 °C for 4 h with stirring. The solvent was removed under vacuum, and the remaining solid was triturated with pentane (3 × 2 mL). MeCN (2 mL) was added, and the resulting suspension was filtered. The solid was washed with MeCN until the washings were colorless. The filtrate was concentrated under vacuum to ~0.5 mL, and Et₂O (5 mL) was added to precipitate the product. The solvent was decanted and the solid product was dried under a vacuum. [Ru(Cp)(dpbz)(MeCN)]PF₆ (4c) solid; yield: 62%. ¹H NMR (400 MHz, CD₂Cl₂): δ = 7.63–7.58 (m, C_Ar-H, 4 H), 7.51–7.40 (m, C_Ar-H, 16 H), 7.33–7.25 (m, C_Ar-H, 4 H), 4.63 (s, C₅ H ₅, 5 H). 0.96 (t, ⁵ J _H–P = 1.2 Hz, NCCH ₃, 3 H). ¹³C{¹H} NMR (101 MHz, CD₂Cl₂): δ = 144.5 (C_Ar), 137.6 (C_Ar), 137.1 (C_Ar), 134.4 (C_Ar), 133.5 (C_Ar), 132.0 (C_Ar), 131.9 (C_Ar), 131.1 (C_Ar), 130.8 (C_Ar), 129.5 (C_Ar), 129.4 (C_Ar), 124.9 (NCCH₃), 82.9 (t, ² J _C–P = 1.9 Hz, C ₅H₅), 2.2 (NCCH₃). ³¹P{¹H} NMR (162 MHz, CD₂Cl₂): δ = 83.8 (s, RuPPh₂Ar), –144.5 (sept, ¹ J _P–F = 710.4 Hz, PF₆). MALDI MS (pyrene matrix): m/z calcd for [Ru(Cp)(dpbz)]⁺: 613.1; found: 613.1. [Ru(Cp*)(dppp)(NCCH₃)]PF₆ (5a) solid; yield: 89%. ¹H NMR (400 MHz, CDCl₃): δ = 7.51–7.39 (m, C_Ar-H, 8 H), 7.38–7.24 (m, C_Ar-H, 8 H), 7.24–7.17 (m, C_Ar-H, 4 H), 2.69 (t, ⁴ J _H–P = 1.2 Hz, NCCH₃ , 3 H), 2.65–2.50 (m, P-CCH₂ C, 2 H), 2.30 (t, ³J_H–P = 12.8 Hz, P-CHH′, 2 H), 1.68–1.50 (m, P-CCH₂ C, 2 H), 1.30 (t, ⁴J_H–P = 1.6 Hz, Cp-CH₃ , 15 H). ¹³C{¹H} NMR (101 MHz, CDCl₃): δ = 133.9 (t, J = 6.06 Hz, C_Ar ), 131.9 (t, J = 5.05 Hz, C_Ar ), 130.5 (s, C_Ar ), 130.3 (s, C_Ar ), 128.7 (t, J = 6.06 Hz, C_Ar ), 128.6 (s, Ru-NC), 128.2 (t, J = 5.05 Hz, C_Ar ), 92.4 (s, Cp), 60.1 (P-CH₂-P), 48.1 (P-CH₂-P), 9.6 (s, Cp-CH₃), 4.2 (s, Ru-NC-CH₃). ³¹P{¹H} (162 MHz, CDCl₃): δ = 19.0 (s, PPh₂), –144.3 (sept, ¹ J _P–F = 711.18 Hz, PF₆). MALDI MS (pyrene matrix): m/z calcd for [Ru(Cp*)(dppp)]⁺: 649.2; found: 649.2. High-Throughput Catalytic Procedure; Typical Procedure for Indoline A stock solution of indoline (634 mg, 5.32 mmol, 0.500 M) and the internal standard tetralin (246 mg, 1.86 mmol, 0.175 M) in anisole (10.64 mL) and stock solutions of the various catalysts in anisole (15 mM and 2.5 mM) were prepared in a glovebox. The reaction components were added to a cooled (0 °C) 8 × 12 reaction plate in the following order: catalyst, solvent, substrate. Stock solutions of catalysts were robotically dispensed to their appropriate concentrations (0.25, 1.25, 2.50, or 7.50 mM; 0.1, 0.5, 1.0, 3.0 mol%). The solvent and substrate were added from an Eppendorf pipette to the well plate and to a T0 sample. The final conditions were as follows: substrate (250 mM), catalyst (0.1, 0.5, 1.0. or 3.0 mol%), reaction volume 100 μL in anisole. To minimize evaporation, the 96-well plate was sealed with a Teflon sheet, a rubber sheet, and an aluminum cover. The plate was then heated to 110 °C for 24 h. When the plate had cooled, the solutions were daughtered into a second plate and diluted to 2.5 mM (based on the starting concentration of indoline) in MeCN for GC-FID analysis. A 10 μL aliquot of the T0 sample was diluted with MeCN (990 μL) and analyzed by GC-FID. General Procedure for the Catalytic AD of Substrates A representative procedure is given for four substrates. In a glovebox, the following stock solutions were prepared: internal standard (IS) tetrahydronaphthalene (132 mg, 1.00 mmol, 0.4 M) in anisole (2.5 mL); 4-chloroindoline (77 mg, 0.50 mmol, 1.00 M) in IS stock solution (0.50 mL); 5-chloroindoline (77 mg, 0.50 mmol, 1.00 M) in IS stock solution (0.50 mL); 6-chloroindoline (77 mg, 0.50 mmol, 1.00 M) in IS stock solution (0.50 mL); 5-fluoroindoline (69 mg, 0.50 mmol, 1.00 M) in IS stock solution (0.50 mL); 1c (10 mg, 0.011 mmol, 5 mM) in anisole (2.20 mL). To avoid insolubility issues, the 1h stock solution was prepared using acetone instead of anisole. The correct portion of 1h stock solution was transferred to the 4 mL screw cap reaction vials, and the acetone was removed prior to addition of other reaction components. Four 4 mL vials (A–D) containing stir bars were charged with the substrate/IS stock solution (125 μL, A = 4-chloroindoline, B = 5-chloroindoline, C = 6-chloroindoline, D = 5-fluoroindoline) and additional anisole (125 μL). To each vial was added 1c stock solution (250 μL,) giving a final volume of 500 μL. The final concentrations for all vials were 0.250 M in substrate and 2.5 mM in catalyst. A final vial was charged with substrate/IS stock solution (100 μL) for use as the time = 0 sample, required for accurate quantification of substrate and product. The vials (A–D) were capped and removed from the glove box and heated to 110 °C with stirring. After 24 hours all vials were removed from heat, cooled, and exposed to air to quench. A 40 μL aliquot was diluted to 10 mM (960 μL) in acetonitrile and analyzed by GC-FID. A 10 μL aliquot of the T0 sample was diluted with acetonitrile (990 μL) and analyzed by GC-FID. Representative Procedure for the Catalytic AD of Indoline Monitored by In Situ IR Spectroscopy In the glovebox the following two stock solutions were prepared in anisole: 1) indoline (500 mM) and internal standard tetrahydronaphthalene (200 mM); and 2) 1a (5 mM). To a 250 mL three-neck round-bottom flask with a stir bar, was added 1.5 mL of the indoline/IS stock solution. To a 25 mL round-bottom flask, 2 mL of the 1a stock solution was added. Both flasks were sealed with rubber septa. To a separate 4 mL screw-cap vial was added 0.5 mL of the indoline/IS stock solution and 0.5 mL of anisole, to act as the time = 0 sample. The 250 mL three-neck flask was removed from the glovebox and affixed above an oil bath, which was heated to 110 °C. To the three-neck round-bottom, a reflux condenser was equipped to the middle neck, the ReactIR SiComp probe was inserted into a side-neck of the reaction flask, and the final neck was sealed with a septum. A portion of the catalyst stock solution (1.5 mL) was added to the now stirring reaction solution by syringe through the septum on the third neck, to give a total reaction volume of 3 mL. The final reaction concentrations were: 250 mM substrate, 100 mM IS and 2.5 mM 1a (1 mol%). The reaction flask was placed into the oil bath, and the ReactIR experiment was initiated. Data acquisition involved 1 scan every 30 seconds, for 20 h. Peak height increase of a diagnostic peak for the product at 1354 cm^–1 was monitored over this time period. After the full reaction time had elapsed an aliquot (20 μL) was removed. Two separate GC-FID samples (5 mM) were prepared in acetonitrile, one using the reaction aliquot and the other the time = 0 sample. The solutions were analyzed by calibrated GC-FID, which gave a quantitative final conversion value. Using this in situ yield of indole, the time-trace data obtained by IR spectroscopy was corrected.