FeCl₃-Catalyzed Coupling of Propargylic Acetates with Alcohols

Abstract

A new method for the synthesis of propargylic ethers by FeCl₃-catalyzed alcoholysis of propargylic acetates was developed. The reaction was carried out at room temperature in acetonitrile without exclusion of moisture or air. High product yields were obtained with excellent reaction regioselectivity.

Key words

propargylic ethers - propargylic esters - alcohols - etherification

References and Notes

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• The ruthenium-catalyzed propargylic substitution was reported to run via allenylidene complex intermediates which can be produced only from the propargylic alcohols bearing terminal alkyne group see ref. 4. On the other hand ruthenium-catalyzed substitution of propargylic alcohols bearing an internal alkyne group were also investigated, see:
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• 12a Preparation of propargylic acetates: Bartels A. Mahrwald R. Müller K. Adv. Synth. Catal.  2004,  346:  483 
• 12b

  Propargylic Ethers; Typical Procedure
  1,3-Diphenylprop-2-ynyl acetate (1a) (0.250 g, 1 mmol), n-BuOH (0.222 g, 3.0 mmol), MeCN (2 mL), and anhyd FeCl₃ (0.008 g, 0.05 mmol) were successively added to a 5-mL flask, and then the mixture was stirred magnetically at r.t. for 2.5 h. The solution was concentrated under reduced pressure by an aspirator and then the residue was purified by silica gel column chromatography to afford 3-butoxy-1,3-diphenylprop-1-yne (2a) as a clear colorless oil (0.243 g, 92%).
  The ¹H NMR and ¹³C NMR spectra of known compounds 2b, 2d, 2g, 2h, 2i, 2k, [6b] 2c, 2e, 2f, [8a] 2j, [14] 2l, [4a] 2m, 2o, 2p, [6c] and 2q [5a] are in accordance with those previously reported.
  Compound 2a: Pale yellow oil. IR (film): 3063, 3032, 2229, 1597, 1493, 1452 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.94 (t, 3 H, J = 7.2 Hz), 1.39-1.50 (m, 2 H), 1.62-1.71 (m, 2 H), 3.55-3.62 (m, 1 H), 3.72-3.80 (m, 1 H), 5.39 (s, 1 H), 7.24-7.63 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.3, 19.8, 32.0, 68.3, 72.0, 87.1, 87.2, 122.3, 127.0, 127.8, 128.0, 128.1, 131.3, 138.5. Anal. Calcd for C₁₉H₂₀O (264.36): C, 86.32; H, 7.63. Found: C, 86.03; H, 7.42.
  Compound 2n: Yellow oil. IR (film): 3387, 1598, 1510, 1452cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.92 (t, 3 H, J = 7.2 Hz), 1.38-1.59 (m, 4 H), 2.27 (td, 2 H, J = 7.2, 2.0 Hz), 4.66-4.76 (br s, 1 H), 4.91 (s, 1 H), 6.72-6.77 (m, 2 H), 7.16-7.25 (m, 3 H), 7.29 (t, 2 H, J = 7.6 Hz), 7.32-7.37 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.7, 18.7, 22.1, 31.1, 42.5, 80.8, 85.0, 115.3, 126.6, 127.8, 128.5, 129.1, 135.0, 142.8, 154.2. Anal. Calcd for C₁₉H₂₀O (264.36): C, 86.32; H, 7.63. Found: C, 86.51; H, 7.35.

• In TiCl₄-catalyzed nucleophilic substitution of 1-phenyl-hept-2-ynyl acetate(1b) with phenol the ether was obtained in moderate yield, see:
• 13a Mahrwald R. Quint S. Tetrahedron  2000,  56:  7463 
• 13b Bartels A. Mahrwald R. Quint S. Tetrahedron Lett.  1999,  40:  5989 
• 14 Henseling K.-O. Chem. Ber.  1977,  110:  1027 

11

We suppose that HCl (from the reaction of water with FeCl₃) might be the actual catalyst, therefore a control experiment was done but no reaction occurred in a model reaction between 1a and 1-butanol in the presence of 10% HCl.