Palladium-Catalyzed Cycloisomerization of Carbamimidothioates

Abstract

A palladium-catalyzed cycloisomerization of carbamimidothioates with the formation of a quaternary carbon and a sulfide is described. The use of (IPr)Pd(allyl)Cl (CX21), K₃PO₄, and Me-C(OTBS)=NTBS in refluxing xylenes was optimal, and the methoxycarbonyl group was the most suitable substituent for the nitrogen atom of the carbamimidothioate. Phenyl and alkyl groups can be used as tethers for carbamimidothioates, and alkyl and aryl carbamimidothioates can undergo Pd-catalyzed cycloisomerization in high yields.

Key words

carbamimidothioates - cycloisomerization - palladium catalysis - quaternary carbon - sulfides

• References and Notes


For selected papers, see:
• 1a Hosseyni S, Wojtas L, Li M, Shi X. J. Am. Chem. Soc. 2016; 138: 3994
• 1b Aubert C, Fensterbank L, Garcia P, Malacria M, Simonneau A. Chem. Rev. 2011; 111: 1954
• 1c Nolan SP. Acc. Chem. Res. 2011; 44: 91
• 1d Michelet V, Toullec PY, Genêt J.-P. Angew. Chem. Int. Ed. 2008; 47: 4268
• 1e Fürstner A, Davies PW. Angew. Chem. Int. Ed. 2007; 46: 3410

Selected papers on Pd-catalyzed reactions; for carbothiolation, see:
• 2a Delcaillau T, Schmitt HL, Boehm P, Falk E, Morandi B. ACS Catal. 2022; 12: 6081

Thioacylation:
• 2b Wu J, Xu W.-H, Lu H, Xu P.-F. Adv. Synth. Catal. 2021; 363: 3013

Oxycyanation:
• 2c Koester DC, Kobayashi M, Werz DB, Nakao Y. J. Am. Chem. Soc. 2012; 134: 6544

Selenocarbamoylation:
• 2d Toyofuku M, Murase E, Nagai H, Fujiwara S.-i, Shin-ike T, Kuniyasu H, Kambe N. Eur. J. Org. Chem. 2009; 3141

Carboiodination and Carbohalogenation:
• 2e Marchese AD, Durant AG, Reid CM, Jans C, Arora R, Lautens M. J. Am. Chem. Soc. 2022; 144: 20554
• 2f Chen X, Zhao J, Dong M, Yang N, Wang J, Zhang Y, Liu K, Tong X. J. Am. Chem. Soc. 2021; 143: 1924
• 2g Newman SG, Howell JK, Nicolaus N, Lautens M. J. Am. Chem. Soc. 2011; 133: 14916
• 2h Liu H, Li C, Qiu D, Tong X. J. Am. Chem. Soc. 2011; 133: 6187
• 2i Newman SG, Lautens M. J. Am. Chem. Soc. 2011; 133: 1778

Cyanoamidation:
• 2j Kamisaki H, Yasui Y, Takemoto Y. Tetrahedron Lett. 2009; 50: 2589
• 2k Yasui Y, Takeda H, Takemoto Y. Chem. Pharm. Bull. 2008; 56: 1567
• 2l Yasui Y, Takemoto Y. Chem. Rec. 2008; 8: 386
• 2m Kobayashi Y, Kamisaki H, Takeda H, Yasui Y, Yanada R, Takemoto Y. Tetrahedron 2007; 63: 2978
• 2n Kobayashi Y, Kamisaki H, Yanada R, Takemoto Y. Org. Lett. 2006; 8: 2771
• 3a Hosoya Y, Yasukochi H, Mizoguchi K, Nakada M. Heterocycles 2022; 104: 655
• 3b Hosoya Y, Kobayashi I, Mizoguchi K, Nakada M. Org. Lett. 2019; 21: 8280
• 4 Hosoya Y, Mizoguchi K, Yasukochi H, Nakada M. Synlett 2022; 33: 495
• 5 Ito R, Okura F, Nakada M. Synlett 2023; 34: 2319
• 6 Tomizawa T, Orimoto K, Niwa T, Nakada M. Org. Lett. 2012; 14: 6294
• 7 Viciu MS, Germaneau RF, Navarro-Fernandez O, Stevens ED, Nolan SP. Organometallics 2002; 21: 5470
• 8 Silylating reagents may accelerate the formation of Pd(0) species; for a related reference, see: Marion N, Navarro O, Mei J, Stevens ED, Scott NM, Nolan SP. J. Am. Chem. Soc. 2006; 128: 4101
• 9 For the preparation of 13b–e, see the Supporting Information.
• 10 For the preparation of 13f–q, see the Supporting Information.
• 11 For the preparation of 15a–f, see the Supporting Information.
• 12 Methyl {1,3-Dimethyl-3-[(phenylsulfanyl)methyl]-1,3-dihydro-2H-indol-2-ylidene}carbamate (14a); Typical Procedure A 10 mL test tube was charged with 13a (20.0 mg, 0.059mmol), K₃PO₄ (37.4 mg, 0.176 mmol, 3.0 equiv), BTBSA (0.0394 mL, 0.118 mmol, 2.0 equiv), CX20 (3.4 mg, 0.00594 mmol, 10 mol%), and xylenes (5.9 mL). The mixture was degassed and refluxed for 2 h, then cooled to r.t. H₂O (2 mL) was added, and the aqueous layer was extracted with EtOAc (3 × 2 mL). The combined organic layer was dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography [silica gel, CH₂Cl₂ (one drop) + hexane–EtOAc (20:1 to 10:1)] to give a colorless oil; yield: 19.2 mg (96%); R_f = 0.41 (hexane–EtOAc, 2:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (dd, J = 7.3 Hz, 1 H), 7.10–7.20 (m, 6 H), 6.96 (dd, J = 7.8, 7.3 Hz, 1 H), 6.85 (d, J = 7.8 Hz, 1 H), 3.98 (d, J = 12.8 Hz, 1 H), 3.73 (s, 3 H), 3.51 (d, J = 12.8 Hz, 1 H), 3.28 (s, 3 H), 1.61 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 170.4, 161.6, 143.6, 136.1, 134.2, 130.9, 128.7, 128.5, 126.5, 122.8, 122.5, 108.3, 53.0, 52.4, 43.4, 28.6, 23.1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₂₀N₂NaO₂S: 363.1138; found: 363.1138.