Total Syntheses of Spirooliganones A and B

Abstract

This paper describes the total syntheses of spirooliganones A and B, which provides control over the stereochemistry of the spiro center via a cascade reaction involving the in situ formation of an o-quinone methide and a hetero-Diels–Alder reaction.

Key words

total synthesis - spirooliganones A and B - spiro center - hetero-Diels–Alder reaction - {¹⁹F}-¹H HOESY

Publication History

Received: 10 December 2021

Accepted after revision: 07 February 2022

Article published online:
08 March 2022

• References and Notes

• 1 Ma S.-G, Gao R.-M, Li Y.-H, Jiang J.-D, Gong N.-B, Li L, Lü Y, Tang W.-Z, Liu Y.-B, Qu J, Lü H.-N, Li Y, Yu S.-S. Org. Lett. 2013; 15: 4450
• 2 Wei L, Xiao M, Xie Z. Org. Lett. 2014; 16: 2784
• 3 Song L, Yao H, Tong R. Org. Lett. 2014; 16: 3740
• 4 Nan Z, Ren X, Ren J, Lü H, Ma S, Gao R, Li Y, Xu S, Li L, Yu S. Org. Lett. 2015; 17: 3118
• 5a Koser S, Hoffman HM. R, Williams DJ. J. Org. Chem. 1993; 58: 6163
• 5b Krause M, Hoffman HM. R. Tetrahedron Lett. 1990; 31: 6629
• 5c Koser S, Hoffman HM. R. Heterocycles 1994; 37: 661
• 5d Kim I, Kim SG, Choi J, Lee GH. Tetrahedron 2008; 64: 664
• 5e Lee YR, Hung TV. Tetrahedron 2008; 59: 7338
• 5f Tietze LF. Chem. Rev. 1996; 96: 115
• 6a Kosugi M, Kazuo S, Shimizu Y, Migita T. Chem. Lett. 1977; 301
• 6b Milstein D, Stille JK. J. Am. Chem. Soc. 1978; 100: 3636
• 6c Stille JK. Angew. Chem., Int. Ed. Engl. 1986; 25: 508
• 7 Tamura Y, Yakura T, Haruta J, Kita Y. J. Org. Chem. 1987; 52: 3927
• 8a Xu D, Crispino GA, Sharpless KB. J. Am. Chem. Soc. 1992; 114: 7570
• 8b Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
• 8c Becker H, Soler MA, Sharpless KB. Tetrahedron 1995; 51: 1345
• 8d Li Y, Hu Y, Xie Z, Chen X. Tetrahedron: Asymmetry 2003; 14: 2355
• 8e Duan Z.-Y, Zhang J.-Z, Xu X.-X. Acta Chim. Sin. 2004; 62: 811
• 9a Morita M, Ohmori K, Suzuki K. Org. Lett. 2015; 17: 5634
• 9b Ohmori K, Suzuki K. Synlett 2021; in press
• 9c Morita M, Kurouchi H, Nemoto N. Synlett 2022; DOI:
• 10 Potassium triethylborohydride (0.194 mL, 1.0 M THF solution, 0.194 mmol) was added to a solution of 9 (50.0 mg, 0.129 mmol) in THF/HMPA (5:1, 2 mL) at –78 °C. After 15 min of stirring at –78 °C, saturated aqueous NH₄Cl was added to the reaction mixture, and the mixture was extracted with EtOAc (3×). The combined organic extracts were dried (MgSO₄) and concentrated in vacuo. The residue was purified by PTLC (hexane/EtOAc = 7:1) to afford 8 (22.5 mg, 47%) as a white solid and 16 (5.3 mg, 11%) as a white solid.Compound 8: R_f = 0.63 (hexane/EtOAc = 7:1); [α]_D ²³ –29 (c 1.2, CHCl₃). IR (neat): 2944, 1685, 1123, 881 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.07–1.14 (m, 21 H), 1.35 (s, 3 H), 1.37 (s, 3 H), 2.15 (dd, J = 13.5, 4.3 Hz, 1 H), 2.72 (dd, J = 13.5, 5.5 Hz, 1 H), 4.40 (t, J = 4.8 Hz, 1 H), 5.85 (dd, J = 13.3, 1.6 Hz, 1 H), 6.03 (d, J = 9.8 Hz, 1 H), 6.97 (t, J = 10.3 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 10.2, 15.96, 15.99, 21.7, 25.4, 41.0, 74.2 (d, J _CF = 23.1 Hz), 77.0, 85.2, 106.8 (d, J _CF = 11.6 Hz), 123.3, 146.0 (d, J _CF = 4.8 Hz), 172.6 (d, J _CF = 290.9 Hz), 185.2 (d, J _CF = 16.4 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –98.4. HRMS (ESI): m/z calcd for C₂₀H₃₄O₃FSi [M + H]⁺: 369.2256; found: 369.2242.Compound 16: R_f = 0.57 (hexane/EtOAc = 7:1). [α]_D ²³ –9.3 (c 0.57, CHCl₃). IR (neat): 2944, 1683, 1139, 883 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.07–1.12 (m, 21 H), 1.30 (d, J = 0.9 Hz, 3 H), 1.40 (s, 3 H), 2.26 (dd, J = 12.9, 7.0 Hz, 1 H), 2.58 (dd, J = 12.6, 9.6 Hz, 1 H), 4.38 (dd, J = 9.5, 6.7 Hz, 1 H), 5.87 (dd, J = 13.0, 1.6 Hz, 1 H), 6.03 (dt, J = 9.8, 1.3 Hz, 1 H), 6.62 (t, J = 10.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.2, 17.9, 18.0, 22.4 (d, J _CF = 2.9 Hz), 28.4, 41.2, 74.3 (d, J _CF = 24.1 Hz), 78.2, 85.2, 109.3 (d, J _CF = 11.6 Hz), 125.5, 146.7 (d, J _CF = 4.8 Hz), 174.0 (d, J _CF = 291.9 Hz), 187.1 (d, J _CF = 15.4 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –96.6. HRMS (ESI): m/z calcd for C₂₀H₃₄O₃FSi [M + H]⁺: 369.2256; found: 369.2247.
• 11a Yu C, Levy GC. J. Am. Chem. Soc. 1983; 105: 6994
• 11b Yu C, Levy GC. J. Am. Chem. Soc. 1984; 106: 6533
• 11c Dewis L, Crouch R, Russell D, Butts C. Magn. Reson. Chem. 2019; 57: 1143
• 11d Claridge TD. W. High-Resolution NMR Techniques in Organic Chemistry, 3rd ed. Elsevier Science; Amsterdam: 2016
• 12 For the in situ generation of o-quinone methide 6 in a sealed tube, see ref. 2.
• 13 The diastereomeric mixture of adduct 17 and 18 was separated by recycling HPLC (LC-Forte/R equipped with YMC-Pack SIL-60, hexane/EtOAc = 9:1, 25 mL/min).
• 14 Johnson CR, Adams JP, Braun MP, Senanayake CB. W, Wovkulich PM, Uskoković MR. Tetrahedron Lett. 1992; 33: 917
• 15a Han X, Stoltz BM, Corey EJ. J. Am. Chem. Soc. 1999; 121: 7600
• 15b Fuwa H, Kainuma N, Tachibana K, Sasaki M. J. Am. Chem. Soc. 2002; 124: 14983