Evaluation of a Bidentate ‘Clamp-Like’ Halogen-Bond Donor Motif Based on Iodonium(III) Moieties

Abstract

A new motif for iodine(III)-based halogen-bond donors consisting of a 1,3-phenylene core and two cyclic five-membered diaryliodonium(III) wings was designed and its potential as a catalyst was evaluated. Its properties were analyzed in the solid state by X-ray crystallography and in solution by benchmark catalytic activation of a nitro-Michael addition between 5-methoxyindole and trans-β-nitrostyrene.

Key words

halogen bonding - hypervalent iodine - structure–activity relationship - organocatalysis - diaryliodonium

• References and Notes

• 1 Schreiner PR. Chem. Soc. Rev. 2003; 32: 289
• 2 Seayad J, List B. Org. Biomol. Chem. 2005; 3: 719
• 3 Busschaert N, Caltagirone C, Van Rossom W, Gale PA. Chem. Rev. 2015; 115: 8038
• 4 Sutar RL, Huber SM. ACS Catal. 2019; 9: 9622
• 5 Bamberger J, Ostler F, Mancheño OG. ChemCatChem 2019; 11: 5198
• 6 Breugst M, Koenig JJ. Eur. J. Org. Chem. 2020; 5473
• 7 Bruckmann A, Pena M, Bolm C. Synlett 2008; 900
• 8 Ochiai M. Top. Curr. Chem. 2003; 224: 5
• 9 Wirth T. Angew. Chem. Int. Ed. 2005; 44: 3656
• 10 Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
• 11 Robidas R, Reinhard DL, Legault CY, Huber SM. Chem. Rec. 2021; 21: 1912
• 12 Wang W. J. Phys. Chem. A 2011; 115: 9294
• 13 Kirshenboim O, Kozuch S. J. Phys. Chem. A 2016; 120: 9431
• 14 Pinto De Magalhães H, Togni A, Lüthi HP. J. Org. Chem. 2017; 82: 11799
• 15 Labattut A, Tremblay P.-L, Moutounet O, Legault CY. J. Org. Chem. 2017; 82: 11891
• 16 Zhang Y, Han J, Liu Z.-J. RSC Adv. 2015; 5: 25485
• 17 Merritt E, Olofsson B. Angew. Chem. Int. Ed. 2009; 48: 9052
• 18 Ackermann L, Dell’Acqua M, Fenner S, Vicente R, Sandmann R. Org. Lett. 2011; 13: 2358
• 19 Peng X, Rahim A, Peng W, Jiang F, Gu Z, Wen S. Chem. Rev. 2023; 123: 1364
• 20 Pacheco-Benichou A, Besson T, Fruit C. Catalysts 2020; 10: 483
• 21 Wang M, Chen S, Jiang X. Chem. Asian J. 2018; 13: 2195
• 22 Heinen F, Engelage E, Dreger A, Weiss R, Huber SM. Angew. Chem. Int. Ed. 2018; 57: 3830
• 23 Mayer RJ, Ofial AR, Mayr H, Legault CY. J. Am. Chem. Soc. 2020; 142: 5221
• 24 Reinhard DL, Heinen F, Stoesser J, Engelage E, Huber SM. Helv. Chim. Acta 2021; 104: e2000221
• 25 Robidas R, Huber SM, Legault CY. ARKIVOC 2021; 128
• 26 Robidas R, Reinhard DL, Huber SM, Legault CY. ChemPhysChem 2023; 24: e202200634
• 27 Karandikar SS, Bhattacharjee A, Metze BE, Javaly N, Valente EJ, McCormick TM, Stuart DR. Chem. Sci. 2022; 13: 6532
• 28 Grushin VV. Chem. Soc. Rev. 2000; 29: 315
• 29 Heinen F, Reinhard DL, Engelage E, Huber SM. Angew. Chem. Int. Ed. 2021; 60: 5069
• 30 Boelke A, Kuczmera TJ, Lork E, Nachtsheim BJ. Chem. Eur. J. 2021; 27: 13128
• 31 Jungbauer SH, Huber SM. J. Am. Chem. Soc. 2015; 137: 12110
• 32 Voelkel MH. H, Wonner P, Huber SM. ChemistryOpen 2020; 9: 214
• 33 Gliese J.-P, Jungbauer SH, Huber SM. Chem. Commun. 2017; 53: 12052
• 34 Walker SD, Barder TE, Martinelli JR, Buchwald SL. Angew. Chem. Int. Ed. 2004; 43: 1871
• 35 Krasnokutskaya E, Semenischeva N, Filimonov V, Knochel P. Synthesis 2007; 81
• 36 Bielawski M, Olofsson B. Chem. Commun. 2007; 2521
• 37 Bielawski M, Zhu M, Olofsson B. Adv. Synth. Catal. 2007; 349: 2610
• 38 Bis(iodolium) Triflate 3^OTf Step 1: Under air, syn-9 (1.12 g, 1.90 mmol, 1.0 equiv) was partly dissolved in MeCN (20 mL, 0.1 M). On addition of PTSA (2.27 g, 11.9 mmol, 6.3 equiv), a yellow solution formed. The reaction flask was placed in a water bath, and a solution of KI (1.63 g, 9.82 mmol, 5.2 equiv) and NaNO₂ (551 mg, 7.99 mmol, 4.2 equiv) in double-distilled H₂O (16 mL) was added dropwise. The water bath was removed 10 min after complete addition. The mixture was then stirred for 1 h at r.t. and for 17 h at 60 °C, then cooled to r.t. The reaction was then quenched with sat. aq NaHCO₃ (20 mL) and sat. aq Na₂SO₃ (20 mL). The mixture was extracted with Et₂O (3 × 50 mL), and the combined organic extracts were washed with brine (50 mL), dried (MgSO₄), and concentrated in vacuo to give the crude product as a slightly yellowish solid (yield: 1.44 g), which was used in the next step without further purification. Step 2: Under air, the crude product from Step 1 was dissolved in DCM (40 mL, 48 mM) and mCPBA (1.26 g, ≤77%, ≤5.62 mmol, ≤3.0 equiv) was added. The mixture was cooled to 0 °C and stirred for 30 min. Subsequently, TfOH (1.0 mL, 1.69 g, 11.3 mmol, 5.9 equiv) was added dropwise from a glass pipette. The cooling bath was removed and the mixture was stirred for 15 h at r.t. The solvent was then removed in high vacuum (hv) at r.t. using an external cold trap. The crude residue was mixed with Et₂O (40 mL) and the mixture was stirred for 30 min to give a homogeneous suspension. The precipitate was collected by vacuum filtration (Buchner funnel and paper filter), washed with Et₂O (×3), and dried in hv. The resultant product was shown to be clean by ¹H NMR, but ¹⁹F NMR showed an excess of triflate, so the product was dissolved in EtOAc (150 mL) and washed with double-distilled H₂O (3 × 50 mL each). The organic phase was dried (Na₂SO₄), filtered, and concentrated in vacuo to give a brownish solid; yield: 819 mg (739 μmol, 39% over two steps) ATR-IR: 513 (m), 517 (m), 573 (w), 633 (s), 708 (m), 768 (s), 889 (m), 989 (m), 1016 (s), 1022 (s), 1057 (m), 1095 (m), 1098 (m), 1121 (s), 1212 (s), 1234 (s), 1277 (s), 1315 (w), 1356 (w), 1360 (w) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.99 (s, 2 H), 8.83 (dd, J = 8.0, 1.2 Hz, 2 H), 8.36 (d, J = 8.3 Hz, 2 H), 7.96 (t, J = 7.5 Hz, 2 H), 7.86 (d, J = 1.1 Hz, 2 H), 7.80 (ddd, J = 8.7, 7.2, 1.5 Hz, 2 H), 7.53 (s, 1 H), 2.20 (s, 6 H), 1.76 (s, 3 H). ¹³C{¹H} NMR (101 MHz, DMSO-d ₆): δ = 144.2, 142.4, 141.7, 138.0, 137.8, 133.6, 132.7 (q, J = 32.7 Hz), 132.1, 132.0, 131.3, 131.2, 131.0, 128.8, 127.3–126.9 (m), 124.1, 123.5 (q, J = 273.2 Hz), 123.2–122.8 (m), 120.7 (q, J = 322.4 Hz), 20.0, 17.6. ¹⁹F NMR (376 MHz, DMSO-d ₆): δ = –60.65 (s, 6 F), –77.74 (s, 6 F). ESI-MS: m/z [M–2OTf]²⁺ calcd: 404.98; found: 404.7, [M – 2OTf + OMe]⁺ calcd: 840.99; found: 840.2, [OTf]^– calcd: 148.95; found: 148.7. Anal. Calcd: C, 40.09; H, 2.00; S, 5.79. Found: C, 40.41; H, 2.08; S, 6.24.
• 39 Wu B, Yoshikai N. Angew. Chem. Int. Ed. 2015; 54: 8736
• 40 Bis(iodolium) Barfate 3^BArF
  Under air, bis(iodolium) triflate 3^OTf (387 mg, 349 μmol, 1.0 equiv) and NaBArF₂₄ (619 mg, 668 μmol, 2.0 equiv) were mixed with dry MeOH (7.5 mL, 47 mM), and the mixture was heated to 50 °C, stirred for 63 h and then cooled to r.t. The solvent was removed in vacuo, and the residue was suspended in DCM (7.5 mL) and stirred for 30 min. It was then stored in a refrigerator for 15 min and subsequently filtered through a syringe filter that was washed with DCM (2 x 2.5 mL). A stirring bar was added to the filtrate, which was stirred while pentane (40 mL) was added, and then stirred for a further 5 min. The mixture was placed in a refrigerator for 15 min before the solvent layer was decanted, and the residue was dried on a rotary evaporator for 5 min. The residue was dissolved in DCM (10 mL) and pentane (40 mL) was added with stirring. After a further 5 min of stirring, 15 min standing in a refrigerator, and decantation of the solvent layer, the residue was dried on a rotary evaporator for 5 min. This process was repeated four times (once again with DCM, and three times with Et₂O as the solvent). After drying in high vacuum, product 3BArF containing ~0.65 equiv of Et₂O and ~0.15 equiv of THF (mass purity: 98%) was obtained as a slightly brownish foam; yield: 623 mg (98% mass purity, 241 μmol, 69%). ATR-IR: 669 (m), 682 (m), 712 (m), 746 (w), 761 (w), 839 (m), 886 (m), 979 (w), 1059 (m), 1114 (s), 1273 (s), 1354 (m), 1611 (w) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.99 (d, J = 0.6 Hz, 2 H), 8.84 (dd, J = 8.0, 1.2 Hz, 2 H), 8.36 (d, J = 8.3 Hz, 2 H), 7.98 (t, J = 7.3 Hz, 2 H), 7.88–7.79 (m, 4 H), 7.72 (s, 8 H), 7.62 (s, 16 H), 7.51 (s, 1 H), 2.18 (s, 6 H), 1.74 (s, 3 H). ¹³C{¹H} NMR (101 MHz, DMSO-d ₆): δ = 161.0 (dd, J = 99.6, 49.7 Hz), 144.3, 142.4, 141.8, 137.9, 137.7, 134.1, 133.8, 132.9 (q, J = 32.7 Hz), 132.2, 131.9, 131.3, 131.2, 130.9, 128.8, 129.2–127.6 (m), 127.3–126.9 (m), 124.3, 124.0 (q, J = 272.4 Hz), 123.5 (q, J = 273.4 Hz), 123.3–122.9 (m), 117.6–117.2 (m), 19.9, 17.4. ¹⁹F NMR (376 MHz, DMSO-d ₆): δ = –60.67 (s, 6 F), –61.61 (s, 48 F). ESI-MS: m/z [M–2BArF₂₄]²⁺ calcd: 404.98; found: 404.7 [M – 2BArF₂₄]²⁺, [M – 2BArF₂₄ + OMe]⁺ calcd: 840.99; found: 840.3; [BArF₂₄]^– calcd: 863.07; found: 826.6, Anal. Calcd: C, 46.87; H 1.83. Found: C, 46.93; H, 1.59.
• 41 CCDC 2298229 contains the supplementary crystallographic data for compound 3^OTf . The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 42 Ochiai M, Sueda T, Miyamoto K, Kiprof P, Zhdankin VV. Angew. Chem. Int. Ed. 2006; 45: 8203
• 43 Bondi A. J. Phys. Chem. 1964; 68: 441
• 44 Rowland RS, Taylor R. J. Phys. Chem. 1996; 100: 7384
• 45 Dessole G, Herrera RP, Ricci A. Synlett 2004; 2374
• 46 Zhuang W, Hazell RG, Jørgensen KA. Org. Biomol. Chem. 2005; 3: 2566
• 47 Herrera RP, Sgarzani V, Bernardi L, Ricci A. Angew. Chem. Int. Ed. 2005; 44: 6576
• 48 Wonner P, Dreger A, Vogel L, Engelage E, Huber SM. Angew. Chem. Int. Ed. 2019; 58: 16923
• 49 Tarannam N, Voelkel MH. H, Huber SM, Kozuch S. J. Org. Chem. 2022; 87: 1661