Synthesis of 2-Alkyl-2-(2-furanyl)-1,3-cyclopentanediones

Abstract

2,2-Disubstituted 1,3-cyclopentanediones are versatile building blocks for synthesizing complex natural products with bicyclic structures including cyclopentane rings. The reported method for the synthesis of these compounds involves the semi-pinacol rearrangement of a Mukaiyama aldol adduct prepared from a ketone/ketal and 1,2-bis(trimethylsilyloxy)cyclobutene. However, the adoption of α-oxy-functionalized ketones/ketals is quite difficult, as demonstrated by our experiments. To overcome this limitation of the method, 2-acylfuran derivatives were used as the reactants to synthesize 2,2-disubstituted 1,3-cyclopentanediones. Furthermore, two reaction conditions, that is, the use of 1.4 equivalents of a boron trifluoride-diethyl ether complex or 0.4 and 0.2 equivalent of trimethylsilyl triflate and methoxytrimethylsilane, respectively, were established for the conversion of 2-acylfurans into the corresponding 1,3-cyclopentanediones in acceptable yields. The transformations of the furan rings in the obtained products were also investigated.

Key words

1,3-cyclopentanedione - 1,2-bis(trimethylsilyloxy)cyclobutene - 2-acylfuran - semi-pinacol rearrangement - trimethylsilyl triflate

Publication History

Received: 28 October 2022

Accepted after revision: 27 December 2022

Accepted Manuscript online:
27 December 2022

Article published online:
31 January 2023

• References

• 1 Present address: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603 Japan.
• 2 Hajos ZG, Parrish DR. J. Org. Chem. 1974; 39: 1615
• 3a Bradshaw B, Bonjoch J. Synlett 2022; 23: 337
• 3b Yadav GD, Deepa, Singh S. ChemistrySelect 2019; 4: 5591
• 4a Ikeuchi K, Haraguchi S, Yamada H, Tanino K. Chem. Pharm. Bull. 2022; 70: 435
• 4b Komine K, Ninomiya R, Fukuda H, Ishihara J. Chem. Pharm. Bull. 2022; 70: 89
• 4c Kawamoto Y, Noguchi N, Ozone D, Kobayashi T, Ito H. Tetrahedron Lett. 2021; 85: 153495
• 4d Zhang Y, Tong X. Org. Lett. 2017; 19: 5462
• 4e Cichowicz NR, Kaplan W, Khomutnyk Y, Bhattarai B, Sun Z, Nagorny P. J. Am. Chem. Soc. 2015; 137: 14341
• 5a Siekmeyer B, Lübken D, Bajerke K, Bernhardt B, Schreiner PR, Kalesse M. Org. Lett. 2022; 24: 5812
• 5b Kawamoto Y, Ozone D, Kobayashi T, Ito H. Eur. J. Org. Chem. 2020; 4050
• 5c Schmiedel VM, Hong YJ, Lentz D, Tantillo DJ, Christmann M. Angew. Chem. Int. Ed. 2018; 57: 2419
• 5d Koshino S, Kwon E, Hayashi Y. Eur. J. Org. Chem. 2018; 5629
• 5e Mukai K, Kasuya S, Nakagawa Y, Urabe D, Inoue M. Chem. Sci. 2015; 6: 3383
• 6 Ikeuchi K, Sasage T, Yamada G, Suzuki T, Tanino K. Org. Lett. 2021; 23: 9123
• 7a Carr JM, Snowden TS. Tetrahedron 2008; 64: 2897
• 7b Lavallée J.-F, Deslongchamps P. Tetrahedron Lett. 1988; 29: 6033
• 7c Dauben WG, Bunce RA. J. Org. Chem. 1983; 48: 4642
• 8a Wu G.-J, Zhang Y.-H, Tan D.-X, He L, Cao B.-C, He Y.-P, Han F.-S. J. Org. Chem. 2019; 84: 3223
• 8b Bedekar AV, Watanabe T, Tanaka K, Fuji K. Synthesis 1995; 1069
• 8c Schick H, Schwarz H, Finger A. Tetrahedron 1982; 38: 1279
• 9a Jacques R, Pullin RD. C, Fletcher SP. Nat. Commun. 2019; 10: 21
• 9b Aikawa K, Okamoto T, Mikami K. J. Am. Chem. Soc. 2012; 134: 10329
• 9c Pottie IR, Crane SN, Gosse AL, Miller DO, Burnell DJ. Can. J. Chem. 2010; 88: 1118
• 9d Trost BM, Simas AB. C, Plietker B, Jäkel C, Xie J. Chem. Eur. J. 2005; 11: 7075
• 9e Vicart N, Goré J, Cazes B. Tetrahedron 1998; 54: 11063
• 9f RajanBabu TV. J. Org. Chem. 1985; 50: 3642
• 10 Nakamura E, Kuwajima I. J. Am. Chem. Soc. 1977; 99: 961
• 11a Crane SN, Burnell DJ. J. Org. Chem. 1998; 63: 1352
• 11b Jenkins TJ, Burnell DJ. J. Org. Chem. 1994; 59: 1485
• 12 Clark JS, Delion L, Farrugia LJ. Chem. Eur. J. 2015; 21: 4772
• 13 Noyori R, Murata S, Suzuki M. Tetrahedron 1981; 37: 3899
• 14 We also examined the use of TMSOCH₂CH₂OTMS instead of TMSOMe; however, the yield of 24a was poor (40% NMR yield).
• 15 We isolated by-product 30 (Figure 1) in this reaction in a considerable yield (ca. 47%). IR (ATR): 3133, 2987, 2938, 1709, 1504, 1126, 934, 785 cm^–1. ¹H NMR (CDCl₃, 500 MHz): δ = 6.27 (d, J = 3.5 Hz, 1 H), 6.17 (d, J = 3.5 Hz, 1 H), 3.82 (q, J = 7.0 Hz, 1 H), 2.76–2.73 (m, 2 H), 2.69–2.56 (m, 2 H), 1.44 (d, J = 7.0 Hz, 3 H). ¹³C NMR (CDCl₃, 126 MHz): δ = 206.3, 178.0, 155.3, 121.0, 112.2, 109.6, 46.3, 34.8, 27.7, 14.5. HRMS (FD): m/z [M]⁺ calcd for C₁₀H₁₁ ⁷⁹BrO₄: 273.9841; found: 273.9839. The m/z for the isotope C₁₀H₁₁ ⁸¹BrO₄ was detected at 275.9826.
• 16 Kuwajima I, Urabe H. Tetrahedron Lett. 1981; 5191
• 17 We also attempted at the conversion of 26 into 28 via the formation of boronic ester, followed by the oxidation; however, no desired products were obtained.
• 18 Reddy MD, Kobori H, Mori T, Wu J, Kawagishi H, Watkins EB. J. Nat. Prod. 2017; 80: 2561
• 19 Pelly SC, Parkinson CJ, van Otterlo WA. L, de Koning CB. J. Org. Chem. 2005; 70: 10474
• 20 Sumiya T, Ishigami K, Watanabe H. Tetrahedron 2016; 72: 6982
• 21 Crawford JJ, Henderson KW, Kerr WJ. Org. Lett. 2006; 8: 5073
• 22 Qiu Z, Pham HD. M, Li J, Li C.-C, Castillo-Pazos DJ, Khaliullin RZ, Li C.-J. Chem. Sci. 2019; 10: 10937