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

Publication History

Received: 11 November 2023

Accepted after revision: 29 November 2023

Article published online:
30 January 2024

• References and Notes


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• 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.