ACCEPTED MANUSCRIPT
Tetrahedron
(4s)
6.29 (s, 1H), 6.16 – 6.07 (m, 1H), 5.83 (d, J = 3.2 Hz, 1H), 3.93
(dd, J = 14.4, 4.0 Hz, 1H), 3.61 (dd, J = 16.8, 14.6 Hz, 1H), 2.68
(dd, J = 16.9, 4.0 Hz, 1H), 1.66 (s, 3H). 13CNMR (CDCl3, 75
MHz) δ 196.4, 173.3, 154.7, 153.5, 150.9, 142.2, 130.60, 129.9,
128.3, 124.8, 123.8, 110.9, 110.1, 107.6, 57.1, 43.3, 37.2, 21.5.
HRMS (EI) Calc. for C18H14O4 [M]+: 294.0892; Found:
294.0884;
White solid, [α]D20 = -101.5 (c 0.47, CHCl3), 47% yield; >20:1
dr, 91% ee, determined by HPLC (Chiralcel AD-H column,
hexane/i-PrOH = 95/5, 1.0 mL/min, 220 nm), t major =12.74 min, t
= 13.19 min. 1HNMR (300MHz, CDCl3) δ 7.28-7.22 (m,
minor
3H), 7.10-7.07 (m, 3H), 6.87-6.79 (m, 3H), 6.33 (s, 1H), 3.80-
3.67 (m, 2H), 2.68-2.59 (m, 1H), 2.06-1.99 (m, 1H), 1.82-1.74
(m, 1H), 0.99 (s, 3H); 13CNMR (CDCl3, 75 MHz) δ 197.7, 174.0,
160.0, 153.4, 136.2, 129.8, 129.4, 128.4, 128.2, 128.1, 127.9,
124.6, 123.9, 110.8, 58.7, 49.7, 38.2, 27.6, 11.3; HRMS (EI)
Calc. for C21H18O3 [M]+: 318.1256 ; Found: 318.1276;
4.3.14. (1'S,6'S)-2'-methyl-6'-(thiophen-2-yl)-2H-
spiro[benzofuran-3,1'-cyclohex[2] ene]-2,4'-dione
(4o)
White solid, [α]D20 = -122.9 (c 0.41, CHCl3), 81% yield; >20:1
dr, 88% ee, determined by HPLC (Chiralcel AD-H column,
hexane/EtOH = 92/8, 1.0 mL/min, 220 nm), t major =15.03 min, t
4.3.19. (1'S,6'R)-2',6'-diphenyl-2H-
spiro[benzofuran-3,1'-cyclohex[2]ene] -2,4'-dione
(4t)
= 19.32 min. 1H NMR (300 MHz, CDCl3) δ 7.36-7.26 (m,
minor
20
3H), 7.04-6.94 (m, 2H), 6.79 (dd, J = 5.1, 3.7 Hz, 1H), 6.63 (d, J
= 3.5 Hz, 1H), 6.31 (s, 1H), 4.04 (dd, J = 14.5, 3.8 Hz, 1H), 3.67
(dd, J = 16.5, 14.5 Hz, 1H), 2.77 (dd, J = 16.5, 3.9 Hz, 1H), 1.68
(s, 3H). 13CNMR (CDCl3, 75 MHz) δ 196.4, 173.1, 154.6, 153.9,
138.9, 130.9, 130.6, 130.2, 128.5, 126.6, 125.8, 125.0, 123.7,
111.1, 58.9, 44.2, 39.3, 21.7; HRMS (EI) Calc. for C18H14O3S
[M]+: 310.0664 ; Found: 310.0662;
White solid, [α]D = +136.1 (c 0.65, CHCl3), 46% yield; >20:
dr, 95% ee, determined by HPLC (Chiralcel AD-H column,
hexane/EtOH = 92/8, 1.0 mL/min, 220 nm), t major =14.90 min, t
= 22.03 min. 1HNMR (300MHz, CDCl3) δ 7.34 (d, 1H),
minor
7.28-6.95 (m, 10H), 6.85 (dd, J = 25.2 Hz, 3H), 6.49 (s, 1H),
4.32 (dd, J = 3.8 Hz, J = 14.5 Hz, 1H), 3.67 (dd, J = 16.8 Hz,
14.7 Hz, 1H), 2.57 (dd, J = 16.9 Hz, J = 3.8 Hz, 1H); 13CNMR
(DMSO, 75 MHz) δ 196.7, 174.2, 156.1, 152.1, 137.4, 136.6,
131.0, 129.5, 129.1, 128.6, 128.5, 128.1, 127.9, 127.8, 126.1,
125.3, 124.5, 109.9, 57.3, 48.8, 37.6;HRMS (EI) Calc. for
C25H18O3 [M]+: 366.1256 ; Found: 366.1254;
4.3.15. (1'S,6'S)-2'-methyl-6'-propyl-2H-
spiro[benzofuran-3,1'-cyclohex[2] ene]-2,4'-dione
(4p)
20
Colorless oil, [α]D = -111.6 (c 0.49, CHCl3), 98% yield;
4.3.20. (1'S,6'R)-6'-(4-bromophenyl)-4'-
(hydroxyimino)-2'-methyl-2H-spiro[benzofuran-
3,1'-cyclohex[2]en]-2-one(5)
>20:1 dr, 80% ee, determined by HPLC (Chiralcel AD-H
column, hexane/EtOH = 92/8, 1.0 mL/min, 220 nm), t major =6.31
min, t minor = 8.01 min. HNMR (300MHz, CDCl3) δ 7.44-7.38
1
White solid, Z/E (or E/Z) = 3.8:1 (Two isomers can be easily
separated by column chromat ography ); 84% total yield; >20: dr,
93% ee, determined by HPLC (Chiralcel AD-H column, hexane/
(m, 1H), 7.28-7.11 (m, 3H), 6.19 (s, 1H), 2.87 (dd, J = 16.6, 13.7
Hz, 1H), 2.61-2.50 (m, 2H), 1.58 (s, 3H), 1.32-1.21 (m, 2H),
0.95-0.89 (m, 2H), 0.71 (s, 3H), 13CNMR (CDCl3, 75 MHz) δ
197.6, 173.9, 155.2, 153.9, 130.5, 129.9, 129.0, 125.2, 123.2,
110.9, 57.2, 42.7, 37.3, 32.3, 21.3, 19.6, 13.6; HRMS (EI) Calc.
for C17H18O3 [M]+: 270.1256 ; Found: 270.1255;
i-PrOH = 85/15, 1.0 mL/min, 220 nm), t major =23.37 min, t minor
=
15.07 min. 1HNMR (300MHz, CDCl3) δ 9.20 (brs, 1H), 7.26-
7.14 (m, 5H), 6.86-6.77 (m, 3H), 6.43 (s, 1H), 3.43-3.25 (m, 3H),
1.56 (s, 3H); 13CNMR (DMSO, 75 MHz) δ 174.9, 153.1, 143.1,
139.6, 136.5, 131.4, 129.8, 129.7, 129.6, 128.7, 125.4, 124.4,
123.7, 121.7, 58.2, 47.3, 23.5, 21.1; HRMS (ESI) Calc. for
C20H16BrNO3 [M+Na]+: 420.0211 ; Found: 420.0206;
4.3.16. (1'S,6'S)-6'-butyl-2'-methyl-2H-
spiro[benzofuran-3,1'-cyclohex[2] ene]-2,4'-dione
(4q)
20
Colorless oil, [α]D = -112.6 (c 0.74, CHCl3), 98% yield;
>20:1 dr, 75% ee, determined by HPLC (Chiralcel AD-H
Acknowledgments
column, hexane/i-PrOH = 95/5, 1.0 mL/min, 220 nm), t
=7.97 min, t minor =12.40 min. HNMR (300MHz, CDCl3) δ 7.40-
major
1
We are grateful for the financial support from National
Natural Science Foundation of China (No. 21272230) and the
Chinese Academy of Sciences.
7.38 (m, 1H), 7.37-7.10 (m, 3H), 6.19 (s, 1H), 2.86 (dd, J = 16.6
Hz, 13.8 Hz, 1H), 2.62-2.55 (m, 2H), 1.58 (s, 3H), 1.24-0.99 (m,
6H), 0.71 (s, 3H); 13CNMR (CDCl3, 75 MHz) δ 197.53, 173.90,
155.13, 153.97, 130.54, 129.87, 129.0, 125.1, 123.2, 110.9, 57.3,
42.9, 37.3, 29.7, 28.5, 22.0, 21.3, 13.6. HRMS (EI) Calc. for
C18H20O3 [M]+: 284.1412 ; Found: 284.1416;
References and notes
1.
(a) Garduño-Ramírez, M. L.; Trejo, A.; Navarro, V.; Bye, R.;
Linares, E.; Delgado, G. J. Nat. Prod. 2001, 64, 432-435; (b) Su,
B.-N.; Takaishi, Y.; Tori, M.; Takaoka, S.; Honda, G.; Itoh, M.;
Takeda, Y.; Kodzhimatov, O. K.; Ashurmetov, O. Org. Lett. 2000,
2, 493-496; (c) Li, W.; Asada, Y.; Yoshikawa, T. Phytochemistry
2000, 55, 447-456; (d)Takai, S.; Sakaguchi, M.; Jin, D.; Baba, K.;
Miyazaki, M. Life Sci. 1999, 64, 1889-1896; (e) Inman, W. D.;
Luo, J.; Jolad, S. D.; King, S. R.; Cooper, R. J. Nat. Prod. 1999,
62, 1088-1092; (f) Sakuma, S.; Fujimoto, Y.; Tsunomori, M.;
Tagano, S.; Nishida, H.; Baba, K.; Fujita, T. Prostaglandins,
Leukotrienes and Essential Fatty Acids 1998, 58, 143-146; (g)
Wandji, J.; Awanchiri, S. S.; Fomum, Z. T.; Tillequin, F.; Michel-
Daniwicz, S. Phytochemistry 1995, 38, 1309-1313; (h) Baba, K.;
Takeuchi, K.; Doi, M.; Kozawa, M. Tennen Yuki Kagobutsu
Toronkai Koen Yoshishu 1987, 29, 668-675; (i) Baba, K.;
Takeuchi, K.; Doi, M.; Inoue, M.; Kozawa, M. Chem. Pharm.
Bull. 1986, 34, 1540-1545.
4.3.17. (1'S,6'S)-6'-hexyl-2'-methyl-2H-
spiro[benzofuran-3,1'-cyclohex[2] ene]-2,4'-dione
(4r)
Colorless oil, 98% yield; 3.7:1 dr, 74% ee, determined by
HPLC (Chiralcel AD-H column, hexane/EtOH = 97/3, 1.0
1
mL/min, 220 nm), t major =7.65 min, t minor =11.90 min. HNMR
(300MHz, CDCl3) δ 7.41-7.38 (m, 1H), 7.28-7.10 (m, 3H), 6.19
(s, 1H), 2.87 (dd, J = 16.6 Hz, 13.8 Hz, 1H), 2.62-2.55 (m, 2H),
1.58 (s, 3H), 1.28-1.05 (m, 10H), 0.79 (s, 3H); 13CNMR (CDCl3,
75 MHz) δ 197.5, 173.9, 155.1, 154.0, 130.6, 129.9, 129.1,
125.2, 123.3, 110.9, 57.3, 42.9, 37.3, 31.3, 30.1, 28.6, 26.4, 22.4,
21.3, 13.9; HRMS (EI) Calc. for C20H24O3 [M]+: 312.1725 ;
Found: 312.1727;
2.
(a) Guerrero, I. C.; Andrés, L. S.; León, L. G.; Machín, R. P.;
Padrón, J. M.; Luis, J. G.; Delgadillo, J. J. Nat. Prod. 2006, 69,
1803-1805; (b) Fraga, B. M.; González, A. G.; Herrera, J. R.;
Luis, J. G.; Perales, A.; Ravelo, A. G. Phytochemistry 1985, 24,
4.3.18. (1'S,6'R)-2'-ethyl-6'-phenyl-2H-
spiro[benzofuran-3,1'-cyclohex[2] ene]-2,4'-dione