Construction of Successive Stereogenic Centers of ent-Kauranoid through an Oxidative Dearomatization/1,2-Shift Cascade

Abstract

The construction of the successive stereogenic centers, including an all-carbon quaternary stereogenic center, of ent-kauranoid through an oxidative dearomatization/1,2-shift cascade is described. The developed cascade reaction of a substrate bearing a trans-2-(p-methoxyphenyl)vinyl group as the migrating group afforded the desired product in 83% yield. The 1,2-shift in the cascade is strongly affected by a stereoelectronic effect. The X-ray crystal structure of a compound bearing four successive stereogenic centers in the fused-ring moiety of ent-kauranoid diterpene, which was prepared by the oxidative dearomatization/1,2-shift cascade and subsequent stereoselective transformations, is also reported.

Key words

kauranoid - diterpenes - dearomatization - 1,2-shift reaction - quaternary carbon

• References and Notes

• 1a Sun H.-D, Huang S.-X, Han Q.-B. Nat. Prod. Rep. 2006; 23: 673
• 1b Liu M, Wang W.-G, Sun H.-D, Pu J.-X. Nat. Prod. Rep. 2017; 34: 1090
• 2a Hill RA, Connolly JD. Nat. Prod. Rep. 2015; 32: 273
• 2b Spino C. Synlett 2006;  23
• 3 Wang Z, Xun Y. Yunnan Zhiwu Yanjiu 1982; 4: 407
• 4a Kupchan SM, Britton RW, Ziegler MF, Sigel CW. J. Org. Chem. 1973; 38: 178
• 4b Kupchan SM, Britton RW, Lacadie JA, Ziegler MF, Sigel CW. J. Org. Chem. 1975; 40: 648
• 5a Guérard KC, Guérinot A, Bouchard-Aubin C, Ménard M.-A, Lepage M, Beaulieu MA, Canesi S. J. Org. Chem. 2012; 77: 2121
• 5b Guérard KC, Sabot C, Beaulieu MA, Giroux MA, Canesi S. Tetrahedron 2010; 66: 5893
• 5c Guérard KC, Chapelle C, Giroux MA, Sabot C, Beaulieu MA, Achache N, Canesi S. Org. Lett. 2009; 11: 4756

For our recent efforts towards constructing all-carbon quaternary stereogenic centers, see:
• 6a Hosoya Y, Yasukochi H, Mizoguchi K, Nakada M. Heterocycles 2022; 104: 655
• 6b Hosoya Y, Mizoguchi K, Yasukochi H, Nakada M. Synlett 2022; 33: 495
• 6c Hosoya Y, Kobayashi I, Mizoguchi K, Nakada M. Org. Lett. 2019; 21: 8280
• 6d Sato Y, Hosoya Y, Kobayashi I, Adachi K, Nakada M. Asian J. Org. Chem. 2019; 8:  1033
• 6e Fujii T, Oki Y, Nakada M. Tetrahedron Lett. 2018; 59: 882

For our recent efforts towards constructing trans-ring junctions of polycyclic ring systems:
• 7a Sekita H, Adachi K, Kobayashi I, Sato Y, Nakada M. Org. Lett. 2017; 19: 2390
• 7b Usui K, Suzuki T, Nakada MA. Tetrahedron Lett. 2015; 56: 1247
• 7c Fujii T, Nakada M. Tetrahedron Lett. 2014; 55: 1597
• 7d Fujii T, Orimoto K, Nakada M. Tetrahedron Lett. 2014; 55: 1100
• 8 Liu W, Li H, Cai P.-J, Wang Z, Yu Z.-X, Lei X. Angew. Chem. Int. Ed. 2016; 55: 3112
• 9 Cai G, Zhou Z, Wu W, Yao B, Zhang S, Li X. Org. Biomol. Chem. 2016; 14: 8702
• 10 Dohi T, Yamaoka N, Kita Y. Tetrahedron 2010; 66: 5775
• 11 Plourde GL. Tetrahedron Lett. 2002; 43: 3597
• 12 He L.-Y, Schulz-Senft M, Thiedemann B, Linshoeft J, Gates JP, Staubitz A. Eur. J. Org. Chem. 2015; 2498
• 13 Compound 2c Pb(OAc)₄ (661 mg, 2.0 equiv) was added to a solution of 1c (293 mg, 1.0 equiv, 0.745 mmol) in dry DCM (4 mL) and dry HFIP (4 mL) at 0 °C. The mixture was stirred for 5 min and then the reaction was quenched with sat. aq NaHCO₃ (10 mL) and sat. aq Na₂S₂O₃ (10 mL). The aqueous layer was extracted with EtOAc (3 × 10 mL), and the combined organic layer was washed with brine (1 × 20 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (10:1)] to give a pale-yellow amorphous solid; yield: 240 mg (0.615 mmol, 83%), R_f = 0.34 (hexane–EtOAc, 4:1). ¹H NMR (500 MHz, CDCl₃): δ = 7.26 (d, J = 9.7 Hz, 1 H), 7.21 (d, J = 8.6 Hz, 2 H), 6.85 (d, J = 8.6 Hz, 2 H), 6.38 (d, J = 1.7 Hz, 1 H), 6.30 (d, J = 16.0 Hz, 1 H), 6.15 (dd, J = 1.7, 9.7 Hz, 1 H), 5.70 (d, J = 16.0 Hz, 1 H), 3.80 (s, 3 H), 2.74 (dt, J = 13.2, 14.3 Hz, 1 H), 2.47–2.39 (m, 2 H), 2.14 (br d, J = 13.2 Hz, 1 H), 1.75–1.66 (m, 1 H), 1.65–1.60 (m, 1 H), 1.53 (dt, J = 3.4, 13.2 Hz, 1 H), 1.48 (br d, J = 13.5 Hz, 1 H), 1.18 (dt, J = 3.4, 13.8 Hz, 1 H), 1.15 (s, 3 H), 0.92 (s, 3 H), 0.81 (s, 3 H). ¹³C-NMR (125 MHz, CDCl₃): δ = 206.0, 186.7, 170.9, 160.0, 148.1, 131.9, 128.3, 127.7, 126.4, 125.6, 124.2, 114.2, 60.4, 55.3, 43.3, 41.0, 40.7, 39.4, 35.5, 33.0, 32.8, 24.2, 21.8, 19.0. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₃₁O₃: 391.2268; found: 391.2269.
• 14 CCDC 1978621 contains the supplementary crystallographic data for compound 1a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures