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DOI: 10.1055/s-0042-1751372
Chiral-at-Ru Catalyst with Cyclometalated Imidazo[1,5-a]pyridinylidene for Enantioselective Intramolecular Cyclopropanations
The authors thank the Deutsche Forschungsgemeinschaft (ME1805/15-1) and Philipps-Universität Marburg for funding of this project.
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Dedicated to Prof. Masahiro Murakami’s impressive career accomplishments
Abstract
A chiral ruthenium catalyst is introduced which contains a cyclometalated N-(3-nitrophenyl)-imidazo[1,5-a]pyridinylidene ligand in addition to a bidentate 4-mesityl-2-(pyridin-2-yl)thiazole and two acetonitriles to complement the octahedral coordination sphere of the monocationic complex. Tetrafluoroborate serves as the counterion. Since all coordinated ligands are achiral, the overall chirality is formally due to a stereogenic metal center generating either a left-handed (Λ) or right-handed (Δ) helical topology of this chiral-at-metal complex. Nonracemic Λ and Δ complexes were synthesized using (R)- and (S)-N-benzoyl-tert-butanesulfinamide as chiral auxiliary ligands, respectively. The position of the nitro group in the metalated phenyl moiety is of crucial importance for the generation of enantiomerically pure complexes. The catalytic activity of the cycloruthenated chiral-at-metal catalyst was demonstrated for the enantioselective intramolecular cyclopropanation of trans-cinnamyl diazoacetate and an alkenyl diazoketone to generate bicyclic cyclopropanes in high yields (96–97%) and with satisfactory enantioselectivity (93% ee).
Key words
cyclometalation - imidazo[1,5-a]pyridinylidene - chiral-at-metal - stereogenic metal - ruthenium - asymmetric catalysis - cyclopropanationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751372.
- Supporting Information
Publication History
Received: 07 August 2022
Accepted: 06 September 2022
Article published online:
19 October 2022
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References and Notes
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- 18 Λ-(S)-Ru3bTo a 10 mL Schlenk tube was added rac-Ru2b (see the Supporting Information for the synthesis) (169 mg, 0.2 mmol, 1 equiv), (R)-N-(phenylsulfinyl)benzamide (90 mg, 0.4 mmol, 4 equiv), and K2CO3 (82 mg, 0.6 mmol, 3 equiv). EtOH (2 mL, 0.1 M) was added, and the resulting solution was stirred at 100 °C in a sealed Schlenk tube for 4 h. Afterwards, the liquid phase was removed by filtration. The residue was dried under reduced pressure and was purified by column chromatography (CH2Cl2–EtOAc, 10:1 → 1:1) to afford Λ-(S)-Ru3b as a purple solid (39 mg, 0.046 mmol, 46%). TLC (CH2Cl2–EtOAc, 1:1): Rf = 0.5. 1H NMR (300 MHz, CDCl3): δ = 10.8 (d, J = 5.7 Hz, 1 H), 8.24–8.20 (m, 2 H), 8.02 (d, J = 7.4 Hz, 1 H), 7.91 (td, J = 7.4, 1.4 Hz, 1 H), 7.90 (d, J = 2.2 Hz, 1 H), 7.65 (dd, J = 7.3, 0.8 Hz, 1 H), 7.62 (s, 1 H), 7.55 (ddd, J = 7.4, 5.8, 1.4 Hz, 1 H), 7.50–7.49 (m, 1 H), 7.48 (dd, J = 8.3, 2.2 Hz, 1 H), 7.43–7.38 (m, 1 H), 7.36–7.32 (m, 1 H), 6.91 (s, 1 H), 6.88 (dt, J = 9.3, 1.0 Hz, 1 H), 6.86 (d, J = 8.5 Hz, 1 H), 6.52 (dd, J = 9.3, 6.2 Hz, 1 H), 6.48 (s, 1 H), 6.40 (s, 1 H), 6.03 (ddd, J = 6.7, 6.3, 1.0 Hz, 1 H), 2.23 (s, 3 H), 2.10 (s, 3 H), 1.36 (s, 3 H), 0.39 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 196.1, 183.8, 178.4, 165.8, 158.8, 156.5, 152.5, 149.5, 142.0, 138.5, 137.1, 137.0, 136.1, 135.3, 133.2, 133.0, 130.5, 129.9, 129.4, 129.1, 128.9, 128.5, 128.0, 127.9, 127.7, 125.9, 122.1, 122.0, 118.3, 118.2, 117.6, 111.9, 104.6, 104.2, 66.8, 23.2, 22.2, 21.7, 20.9, 20.8 ppm. IR (neat): ν = 3063, 2965, 2921, 1735, 1600, 1406, 1240, 1054, 1022, 707, 600 cm–1. HRMS (APCI): m/z calcd for [C41H39N6O4RuS2]+ [(M + H)+]: 845.1522; found: 845.1522. CD (CH2Cl2): λ, nm (Δε, M–1 cm–1): 255 (–9), 309 (+19), 340 (–4), 390 (+1), 450 (–5), 515 (+10).
- 19 Δ-(R)-Ru3b Following the same procedure as for Λ-(S)-Ru3b, the reaction of rac-Ru2b with (S)-N-(phenylsulfinyl) benzamide afforded Δ-(R)-Ru3b as a purple solid (38 mg, 0.045 mmol, 45% yield). Δ-(R)-Ru3b and Λ-(S)-Ru3b are enantiomers. CD (CH2Cl2): λ, nm (Δε, M–1 cm–1) 255 (+9), 309 (–19), 340 (+4), 390 (–1), 450 (+5), 515 (–10). All other spectroscopic data are in agreement with the enantiomer Λ-(S)-Ru3b.
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- 22 Λ-Ru2bTo a 10 mL Schlenk tube was added Λ-(S)-Ru3b (83 mg, 0.1 mmol, 1 equiv) and NH4BF4 (163 mg, 1 mmol, 10 equiv). MeCN (1 mL, 0.1 M) and H2O (0.2 mL) were added, and the resulting solution was stirred at 60 °C for 16 h. Afterwards, the liquid phase was removed by filtration. The residue was dried under reduced pressure and purified by silica gel column chromatography. The chiral auxiliary (R)-N-(tert-butylsulfinyl)benzamide could be recovered as a colorless oil (21 mg, 0.093 mmol, 93%) using the eluent CH2Cl2–MeCN (200:1). Increasing the polarity to CH2Cl2–MeCN (20:1) then provided Λ-Ru2b as a red solid (82 mg, 0.095 mmol, 95%). 19F NMR (282 MHz, CD3CN): δ = –151.0, –151.1 ppm. Enantiomeric excess was established by HPLC analysis using a Daicel Chiralpak IB-N5 column, ee = 99.1% (HPLC: 254 nm, H2O + 0.1% TFA–MeCN = 50:50, flow rate 1 mL/min, 25 °C, t R (Λ-Ru2b) = 16.9 min, t R (Δ-Ru2b) = 19.3 min). CD (CH3CN): λ, nm (Δε, M–1 cm–1) 265 (+30), 309 (+8), 318 (–16), 375 (+2), 450 (+12), 505 (–1). All other spectroscopic data are in agreement with rac-Ru2b.
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- 26 (1R,5S,6S)-6-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one (6) A pre-dried 10 mL Schlenk tube was charged with Λ-Ru2b (4.2 mg, 0.05 mmol, 1 mol%). The tube was evacuated and backfilled with nitrogen for three times. A solution of the diazo substrate 5 (101 mg, 0.5 mmol, 1 equiv.) dissolved in distilled CH2Cl2 (2.5 mL, 0.2 M) was added via syringe. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 5 min. Afterwards, the mixture was directly transferred to a silica gel column and purified by flash chromatography (EtOAc–n-hexane, 1:50 → 1:10) to afford analytical pure product 6 as a white solid (84.4 mg, 0.485 mmol, 97% isolated yield) with 93% ee as determined by GC analysis (Macherey-Nagel HYDRODEX β-TBDAc column, Agilent GC 7820A, oven temperature = 190 °C, H2, FID; t R (major) = 8.0 min, t R (minor) = 9.8 min). [α]D 25 +127 (CH2Cl2, c 1.0). Spectroscopic data are in agreement with ref. 28.
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- 29 (1S,5S,6S)-6-Phenylbicyclo[3.1.0]hexan-2-one (8) A pre-dried 10 mL Schlenk tube was charged with Λ-Ru2b (4.2 mg, 0.05 mmol, 1 mol%). The tube was evacuated and backfilled with nitrogen for three times. A solution of the diazo substrate 7 (100 mg, 0.5 mmol, 1 equiv) dissolved in distilled CH2Cl2 (2.5 mL, 0.2 M) was added via syringe. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 5 min. Afterwards, the mixture was directly transferred to a column and purified by flash chromatography on silica gel (EtOAc–n-hexane, 1:50 → 1:10) to afford analytical pure product 8 that was obtained as a white solid (82.5 mg, 0.48 mmol, 96% yield) with 93% ee as determined by GC analysis (Macherey-Nagel HYDRODEX β-TBDAc column, Agilent GC 7820A, oven temperature = 140 °C, H2, FID; t R (major) = 16.9 min, t R (minor) = 17.4 min). [α]D 25 +116 (CH2Cl2, c 1.0). Spectroscopic data are in agreement with ref. 28.
See also:
For reviews on different aspects of metal-centered chirality, see: