Gold-Catalyzed Cyclization/Intermolecular Methylene Transfer ­Sequence of O-Propargylic Oximes Derived from Glyoxylates

Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

We successfully extended our gold-catalyzed skeletal rearrangement reaction of O-propargylic oximes through C=N bond cleavage to include substrates having an ester group on the oxime moiety, affording the corresponding 2-isoxazolines having an alkoxycarbonylmethylene group at the 4-position in good to high yields. Our mechanistic studies indicated that the transfer of the alkoxycarbonylmethylene group proceeded in an intermolecular manner, confirming that the reaction proceeds through cyclization followed by intermolecular transfer of the alkoxycarbonylmethylene group.

Key words

gold catalysis - rearrangement - heterocycles - cyclization - progargylic oximes - isoxazolines

• References and Notes


For selected reviews on gold catalysis, see:
• 1a Li Y, Li W, Zhang J. Chem. Eur. J. 2017; 23: 467
• 1b Harris RJ, Widenhoefer RA. Chem. Soc. Rev. 2016; 45: 4533
• 1c Yang W, Hashmi AS. K. Chem. Soc. Rev. 2014; 43: 2941
• 1d Obradors C, Echavarren AM. Chem. Commun. 2014; 50: 16
• 1e Hashmi AS. K. Angew. Chem. Int. Ed. 2010; 49: 5232
• 1f Adcock HV, Davies PW. Synthesis 2012; 44: 3401
• 1g Bhunia S, Liu R.-S. Pure Appl. Chem. 2012; 84: 1749
• 1h Lu B.-L, Dai L, Shi M. Chem. Soc. Rev. 2012; 41: 3318
• 1i Kirsch SF. Synthesis 2008; 3183
• 1j Skouta R, Li C.-J. Tetrahedron 2008; 64: 4917
• 1k Hashmi AS. K. Chem. Rev. 2007; 107: 3180

For pioneering works, see:
• 2a Trost BM, Tanoury GJ. J. Am. Chem. Soc. 1988; 110: 1636
• 2b Chatani N, Morimoto T, Muto T, Murai S. J. Am. Chem. Soc. 1994; 116: 6049

For reviews, see:
• 2c Wang Q, Shi M. Synlett 2017; 28: 2230
• 2d Dorel R, Echavarren AM. J. Org. Chem. 2015; 80: 7321
• 2e Michelet V. Top. Curr. Chem. 2015; 357: 95

For pioneering works, see:
• 3a Rautenstrauch V. J. Org. Chem. 1984; 49: 950
• 3b Mainetti E, Mouriès V, Fensterbank L, Malacria M, Marco-Contelles J. Angew. Chem. Int. Ed. 2002; 41: 2132

For reviews, see:
• 3c Boyle JW, Zhao Y, Chan PW. H. Synthesis 2018; 50: 1402
• 3d Fensterbank L, Malacria M. Acc. Chem. Res. 2014; 47: 953
• 3e Mauleon P, Toste FD. In Modern Gold Catalyzed Synthesis . Chap. 4, Hashmi SK, Toste FD. Wiley-VCH; Weinheim: 2012: 75
• 4a Nakamura I, Gima S, Kudo Y, Terada M. Angew. Chem. Int. Ed. 2015; 54: 7154
• 4b Gima S, Nakamura I, Terada M. Eur. J. Org. Chem. 2017; 4375
• 5 Identifiable byproducts were not obtained from the reaction of (Z)-1a. It is therefore unclear at the present stage why the reaction of (Z)-1a resulted in a low chemical yield.
• 6 Ethyl (2Z)-(3,5-Diphenylisoxazol-4(5H)-ylidene)acetate [(Z)-2a]; Typical ProcedureOxime (E)-1a (61.5 mg, 0.2 mmol) in CH₂Cl₂ (0.4 mL) was added to (4-F₃CC₆H₄)₃PAuNTf₂ (18.9 mg, 0.02 mmol) in a V-vial under argon, and the mixture was stirred at 30 °C for 2 h. The mixture was then passed through a short pad of silica gel, eluting with CH₂Cl₂ (50 mL). The solvents were evaporated in vacuo, and the crude product was purified by flash column chromatography [silica gel, hexane–EtOAc (8:1)] to give a colorless liquid; yield: 50 mg (81%, Z/E = 90:10). IR (neat): 3063, 3033, 2981, 2939, 2903, 1709, 1641, 1494, 1455, 1444, 1367, 1331, 1310, 1299, 1269, 1199, 1130, 1096, 1077, 1035, 1007, 912, 899, 873 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.67–7.62 (m, 2 H), 7.55–7.50 (m, 3 H), 7.39–7.31 (m, 5 H), 6.76 (d, J = 3.2 Hz, 1 H), 6.32 (d, J = 3.2 Hz, 1 H), 4.06 (q, J = 7.3 Hz, 2 H), 1.14 (t, J = 7.3 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.22, 157.47, 155.10, 137.69, 130.36, 129.07, 128.70, 128.63, 128.33, 127.58, 127.39, 115.57, 88.03, 60.83, 14.01. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₇NNaO₃: 330.1101; found: 330.1100.
• 7 A substrate having a trichloromethyl group was not converted into the desired product under the optimal reaction conditions; 60% of the starting material was recovered. Preparations from substrates having a cyano or keto group instead of an ester group failed.
• 8 The reaction of 1i at 50 °C afforded the desired product 2i in 12% yield.
• 9a Dunn PJ, Graham AB, Grigg R, Higginson P, Sridharan V, Thornton-Pett M. Chem. Commun. 2001; 1968
• 9b Broggini G, Bruché L, Zecchi G, Pilati T. J. Chem. Soc., Perkin Trans. 1 1990; 533