Sulfur-Mediated ipso-Cyclization of 4-(p-Methoxyaryl)alk-1-ynes Leading to 3-Thiospiro[4.5]deca-1,6,9-trien-8-ones

Abstract

A new method for the intramolecular electrophilic ipso-cyclization of alkynes with triflic anhydride-activated sulfoxides, followed by demethylation with triethylamine in one pot, is described for the synthesis of 3-thiospiro[4.5]-decatrienones in moderate to good yields. This method provides a facile strategy for assembling the sulfur-substituted spirocyclic compounds.

Key words

alkynes - sulfoxides - ipso-cyclization - spiro compounds - dearomatization

Publication History

Received: 30 October 2023

Accepted after revision: 22 November 2023

Accepted Manuscript online:
22 November 2023

Article published online:
11 January 2024

• References and Notes

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• 21 1-Phenyl-2-(phenylsulfanyl)spiro[4.5]deca-1,6,9-trien-8-one (3aa-1); Typical Procedure A flame-dried Schlenk tube was charged with alkyne 1a (0.15 mmol, 1.0 equiv) and PhS(=O)Me (2; 0.3 mmol, 2.0 equiv). The reactants were dissolved in CH₂Cl₂ (2 mL) under N₂, and the solution was cooled to –78 °C (liquid N₂–EtOAc bath), then 2-chloropyridine (28 μL, 0.3 mmol, 2.0 equiv) and Tf₂O (50 μL, 0.3 mmol, 2.0 equiv) were added dropwise. The mixture was stirred at –78 °C for 0.5 h and then Et₃N (0.199 mL, 1.5 mmol, 10.0 equiv) was added. When the reaction was complete, the mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic phase was dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel) to give a white solid; yield: 37.6 mg (74%); R_f = 0.2 (PE–EtOAc, 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.42 (m, 2 H), 7.37–7.30 (m, 3 H), 7.28–7.24 (m, 3 H), 7.23–7.19 (m, 2 H), 6.97 (d, J = 10.1 Hz, 2 H), 6.25 (d, J = 10.1 Hz, 2 H), 2.66 (t, J = 7.1 Hz, 2 H), 2.19 (t, J = 7.2 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 185.2, 152.5, 139.8, 137.2, 134.2, 132.2, 132.0, 128.7, 128.3, 127.6, 127.5, 57.7, 35.5, 34.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₉OS: 331.1152; found: 331.1157.