9
CO2CH3), 3.70 (3H, s, CO2CH3), 3.71 (3H, s, CO2CH3), 3.78
(3H, s, CO2CH3), 4.25 (1H, ddd, J = 10.8, 10.8, 2.3 Hz, H8); 13C
NMR (100 MHz, C6D6) δ 34.8, 39.0, 39.9, 44.1, 44.5, 46.9, 49.0,
49.4, 52.6, 52.7, 52.8, 52.9, 55.4, 58.4, 59.5, 112.2, 112.3, 170.0,
170.1, 171.6, 171.7; HRMS (ESI) calcd for C21H24Cl2N2O8Na
[M+Na]+ 525.0802, found 525.0787.
31G(d) level of theory (298 K, 1 atm, gas phase) to afford the
ACCEPTED MANUSCRIPT
most stable conformational isomer, which has no imaginary
frequencies.
Acknowledgments
(J1,2 = 10.1 Hz)
CN
NC
H 11
H
NOE
This research was financially supported by the Funding
Program for a Grant-in-Aid for Scientific Research (A) (JSPS
Grant Number 26253003) to M.I., a Grant-in-Aid for Scientific
Research (C) (JSPS Grant Number 16K08156) to M.N., and a
Grant-in-Aid for Young Scientists (A) (JSPS Grant Number
16H06213) to D.U.
H
CO2Me
3
1
CO2Me
4
2
9
7
MeO2C
MeO2C
6
8
NOE
H
H
H
Cl
2cb
(J7,8 = J8,9 = 11.0 Hz)
2cb: colorless oil; IR (film) 2956, 2360, 1732, 1436, 1250, 1205
cm-1; 1H NMR (400 MHz, CDCl3) δ 1.95-2.01 (2H, m, H3, H4A),
2.04 (1H, dd, J =14.0, 9.6 Hz, H6A), 2.11 (1H, dd, J = 14.6, 10.1
Hz, H1A), 2.19 (1H, dd, J =14.7, 11.0 Hz, H9A), 2.34-2.44 (2H,
m, H2, H4B), 2.64-2.70 (2H, m, H1B, H7), 2.85 (1H, ddd, J
=14.0, 7.8, 1.4 Hz, H6B), 3.05 (1H, ddd, J = 14.6, 1.8, 1.8 Hz,
H9B), 3.73 (3H, s, CO2CH3), 3.76 (3H, s, CO2CH3), 3.77 (3H, s,
CO2CH3), 3.81 (3H, s, CO2CH3), 3.96 (1H, d, J = 3.2 Hz, H11),
4.07 (1H, ddd, J = 11.0, 11.0, 1.4 Hz, H8); 13C NMR (100 MHz,
CDCl3) δ28.6, 36.3, 38.6, 39.5, 41.2, 43.4, 44.2, 48.6, 53.17,
53.19, 53.23, 53.5, 56.0, 58.1, 59.5, 110.2, 111.6, 170.18, 170.19,
170.9, 171.3; HRMS (ESI) calcd for C21H25ClN2O8Na [M+Na]+
491.1192, found 491.1180.
Supplementary Material
NMR spectra of all new compounds and Cartesian coordinates
for the optimized structures of 25c, 25d and 25e.
References and notes
1.
2.
For selected reviews on cascade reactions in natural product synthesis,
see: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115; (b) Nicolaou, K. C.;
Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006, 45, 7134;
(c) Pellissier, H. Chem. Rev. 2013, 113, 442; (d) Ardkhean, R.; Caputo,
D. F. J.; Morrow, S. M.; Shi, H.; Xiong, Y.; Anderson, E. A. Chem.
Soc. Rev. 2016, 45, 1557.
For reviews on radical cascade reactions, see: (a) McCarroll, A. J.;
Walton, J. C. Angew. Chem. Int. Ed. 2001, 40, 2224; (b) Baralle, A.;
Baroudi, A.; Daniel, M.; Fensterbank, L.; Goddard, J.-P.; Lacôte, E.;
Larraufie, M.-H.; Maestri, G.; Malacria, M.; Ollivier, C. Radical
Cascade Reactions, in Encyclopedia of Radicals in Chemistry, Biology
and Materials; Chatgilialoglu C.; Studer, A., Eds.; John Wiley & Sons
Ltd., Chichester, 2012, vol. 2, p. 729; (c) Wille, U. Chem. Rev. 2013,
113, 813; (d) Sebren, L. J.; Devery, J. J. III; Stephenson, C. R. J. ACS
Catal. 2014, 4, 703.
4.8. Synthesis of tricycle 2e
According to the general procedure, tricycle 2e (22.0 mg, 51.1
µmol) was synthesized in 44% yield from enyne 1e (42.2 mg,
0.115 mmol), CuCl (0.35 mg, 3.5 µmol), dppf (1.84 mg, 3.45
µmol) and Cl2C(CN)2 (59.0 µL, 0.575 mmol) in dioxane (12.0
mL). The residue was purified by flash chromatography on silica
gel (1 g, hexane/EtOAc 10:1 to 2:1).
2e: colorless oil; IR (film) 2956, 2349, 1733, 1435, 1258, 1206
cm-1; 1H NMR (400 MHz, CD3OD) δ 1.37 (1H, ddd, J = 7.7, 5.3,
5.3 Hz, H2), 1.63 (1H, dd, J = 14.3, 5.3 Hz, H1A), 1.96 (1H, dd, J
= 5.3, 5.3 Hz, H3), 2.62 (1H, d, J =14.2 Hz, H4A), 2.68 (1H, d, J
=14.2 Hz, H6A), 2.74 (1H, ddd, J =14.3, 7.7, 2.3 Hz, H1B), 2.77
(1H, dd, J =14.2, 5.2 Hz, H4B), 2.85 (1H, d, J = 17.2 Hz, H9A),
3.27 (1H, d, J = 14.2 Hz, H6B), 3.44 (1H, dd, J = 2.0, 17.2 Hz,
H9B), 3.70 (3H, s, CO2CH3), 3.73 (3H, s, CO2CH3), 3.74 (3H, s,
CO2CH3), 3.80 (3H, s, CO2CH3); 13C NMR (100 MHz, CDCl3) δ
26.4, 30.0, 34.5, 36.4, 37.6, 39.0, 41.5, 53.3, 53.38 (2C), 53.40,
54.6, 59.8, 87.1, 111.9, 112.1, 169.8, 170.0, 170.4, 172.5, 178.6;
HRMS (ESI) calcd for C21H22N2O8Na [M+Na]+ 453.1268, found
453.1247.
3.
4.
5.
(a) Kamijo, S.; Yokosaka, S.; Inoue, M. Tetrahedron 2012, 68, 5290;
(b) Kamijo, S.; Yokosaka, S. Inoue, M. Tetrahedron Lett. 2012, 53,
4324.
(a) Kharasch, M. S.; Jensen, E. V.; Urry, W. H. Science 1945, 102,
128; (b) Kharasch, M. S.; Urry, W. H.; Jensen, E. V. J. Am. Chem. Soc.
1945, 67, 1626.
For reviews on copper catalyzed atom transfer radical cyclization, see:
(a) Clark, A. J. Chem. Soc. Rev. 2002, 31, 1; (b) Eckenhoff, W. T.;
Pintauer, T. Catal. Rev. 2010, 52, 1; (c) Pintauer, T. Eur. J. Inorg.
Chem. 2010, 2449; (d) Muñoz-Molina, J. M.; Belderrain, T. R.; Pérez,
P. J. Eur. J. Inorg. Chem. 2011, 3155; (e) Clark, A. J. Eur. J. Org.
Chem. 2016, 2231.
For a review on transannulation reactions in the synthesis of natural
products, see: Clarke, P. A.; Reeder, A. T.; Winn, J. Synthesis 2009,
691.
For selected examples of syntheses of fused carbocyclic frameworks
by transannular radical reactions, see: (a) Winkler, J. D.; Sridar, V. J.
Am. Chem. Soc. 1986, 108, 1708; (b) Hitchcock, S. A.; Pattenden, G.
Tetrahedron Lett. 1992, 33, 4843; (c) Curran, D. P.; Shen, W.
Tetrahedron 1993, 49, 755; (d) Myers, A. G.; Condroski, K. R. J. Am.
Chem. Soc. 1995, 117, 3057; (e) Elliott, M. R.; Dhimane, A.-L.;
Malacria, M. J. Am. Chem. Soc. 1997, 119, 3427; (f) Tomida, S.; Doi,
T.; Takahashi, T. Tetrahedron Lett. 1999, 40, 2363; (g) Dhimane, A.-
L.; Aïssa, C.; Malacria, M. Angew. Chem. Int. Ed. 2002, 41, 3284; (h)
Morales, M. C. P.; Catalán, J. V.; Domingo, V.; Jaraíz, M.; Herrador,
M. M.; Quílez del Moral, J. F.; López-Pérez, J.-L.; Barrero, A. F.
Chem. Eur. J. 2013, 19, 6598.
(a) Deslongchamps, P.; Lamothe, S.; Lin, H.-S. Can. J. Chem. 1984,
62, 2395; (b) Deslongchamps, P.; Lamothe, S.; Lin, H.-S. Can. J.
Chem. 1987, 65, 1298.
The reaction of 1a at higher concentration (1 M) decreased the yield of
2a (37%) probably due to radical polymerization.
6.
7
4.9 Computational experiments
The conformational search of the 10-membered compounds
25c-e was first conducted by molecular mechanics simulation
using MacroModel.18 The calculation was performed using a
1000-step of Monte Carlo-based torsional sampling (MCMM)
and PRCG energy minimization with OPLS-2005 force field (gas
phase). The obtained structures within 12 kcal/mol were
transferred into Gaussian program 19 and optimized at PM6
semiempirical method (298 K, 1 atm, gas phase). The thus
obtained structures within 2 kcal/mol were subjected to the
geometry optimizations and frequency calculations at M06-2X/6-
8.
9
10. (a) Giese, B.; Lachhein, S. Angew. Chem. Int. Ed. Engl. 1982, 21, 768;
(b) Russell, G. A.; Li, C.; Chen, P. J. Am. Chem. Soc. 1996, 118, 9831;
(c) Tsuchii, K.; Ueta, Y.; Kamada, N.; Einaga, Y.; Nomoto, A.;
Ogawa, A. Tetrahedron Lett. 2005, 46, 7275.