T. Harabe et al. / Tetrahedron 65 (2009) 4044–4052
4051
Each isomer was obtained as a colorless oil from the mixture by
silica gel column chromatography with hexane/EtOAc, 10/1.
4.21. Methyl 5-benzyl-2,5-dimethyl-1,3-dioxane-2-
carboxylate (1e)
A
mixture of 3e (10 g, 0.055 mol), MeCOCO2Me (5.7 g,
4.16. Methyl 2-methyl-c-5-benzyl-1,3-dioxane-r-2-
carboxylate (cis-1c)
0.055 mol), toluene (50 mL), and BF3$Et2O (7.9 g, 7.0 mL, 0.055 mol)
was stirred at 25 ꢀC for 65 h. After the reaction, 20% aq NaOH (24 g,
0.110 mol) was added below 20 ꢀC and the mixture was stirred at rt
for 1 h. The organic layer was washed with 10% aq NaOH, 10% aq
NaCl, and dried over MgSO4. After removal of the solvent in vacuo,
1e (10.8 g, 74%) was obtained as a colorless oil. GC analysis for de-
termination of the ratio of cis/trans of 1e: Shimadzu CBP1-S25-050,
FID, inj: 210 ꢀC, det: 250 ꢀC, column oven: 200 ꢀC (6 min), retention
time trans-1e: 4.1 min, cis-1e: 4.3 min.
IR (neat) nmax 2949, 2859, 1750, 1496, 1460, 1373, 1270, 1215,
1188, 1150, 1197, 1049, 975, 883, 804, 745, 702, 676, 617 cmꢁ1
(obtained as a mixture of cis/trans¼1); 1H NMR (CDCl3, 200 MHz)
d
1.50 (s, 3H), 2.33 (s, 2H), 2.29–2.40 (m, 1H), 3.49 (dd, J¼12.2,
12.2 Hz, 2H), 3.84 (s, 3H), 3.90 (dd, J¼12.2, 4.4 Hz, 2H), 7.10 (d,
J¼6.9 Hz, 2H), 7.20–7.33 (m, 3H); 13C NMR (CDCl3, 75 MHz)
d 25.9,
34.7, 35.0, 52.6, 68.1, 98.3,126.5,128.6,128.6,137.9,171.1. Anal. Calcd
for C14H18O4: C, 67.18; H, 7.25. Found: C, 66.86; H, 7.14; MS (FABþ):
251.
Each isomer was obtained as white crystals from the mixture by
silica gel column chromatography with hexane/EtOAc, 10/1.
4.17. Methyl 2-methyl-t-5-benzyl-1,3-dioxane-r-2-carboxylate
(trans-1c)
4.22. Methyl 2,5-dimethyl-t-5-benzyl-1,3-dioxane-r-2-
carboxylate (trans-1e)
Mp 83–85 ꢀC; IR (KBr) nmax 2967, 2869, 1746, 1456, 1373, 1277,
IR (neat) nmax 2949, 2859, 1750, 1496, 1460, 1373, 1270, 1215,
1188, 1150, 1197, 1049, 975, 883, 804, 745, 702, 676, 617 cmꢁ1
(obtained as a mixture of cis/trans¼1); 1H NMR (CDCl3, 200 MHz)
1261, 1196, 1144, 1118,1078, 1059, 1032, 998, 976, 886, 814, 763, 705,
673 cmꢁ1; 1H NMR (CDCl3, 200 MHz)
d 1.13 (s, 3H), 1.53 (s, 3H), 2.37
d
1.58 (s, 3H), 1.58–1.63 (m, 1H), 3.01 (d, J¼8.1 Hz, 2H), 3.77 (dd,
(s, 2H), 3.51 (d, J¼11.4 Hz, 2H), 3.68 (d, J¼11.4 Hz, 2H), 3.83 (s, 3H),
7.03–7.06 (m, 2H), 7.22–7.29 (m, 2H); 13C NMR (CDCl3, 75 MHz)
J¼10.5, 1.5 Hz, 2H), 3.83 (s, 3H), 3.94 (dd, J¼10.5, 2.7 Hz, 2H), 7.227–
7.231 (m, 2H), 7.27–7.32 (m, 3H); 13C NMR (CDCl3, 75 MHz)
d
25.8,
d
19.8, 25.5, 32.9, 42.6, 52.5, 72.6, 98.3, 126.5, 128.2, 130.1, 135.9,
35.3, 35.4, 52.5, 65.9, 98.6, 126.2, 128.5, 128.6, 140.1, 171.2. Anal.
Calcd for C14H18O4: C, 67.18; H, 7.25. Found: C, 66.67; H, 7.18; MS
(FABþ): 251.
171.1. Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C, 67.98; H,
7.70; MS (FABþ): 265.
4.23. Methyl 2,5-dimethyl-c-5-benzyl-1,3-dioxane-r-2-
carboxylate (cis-1e)
4.18. Methyl 5-(tert-butyl)-2-methyl-1,3-dioxane-2-
carboxylate (1d)
Mp 74–75 ꢀC; IR (KBr) nmax 2998, 2970, 2858, 1740, 1457, 1390,
A mixture of 3d (92 mg, 0.698 mol), MeCOCO2Me (71.2 mg,
63.11 mL, 0.698 mol), toluene (0.5 mL), and BF3$Et2O (99.1 g, 88.4 mL,
1368, 1274, 1258, 1219, 1186, 1138, 1122, 1079, 1057, 1032, 1014, 963,
920, 879, 800, 737, 711, 674 cmꢁ1; 1H NMR (CDCl3, 200 MHz)
d 0.60
0.060 mol) was stirred at 25 ꢀC for 15 h. After the reaction, 20% aq
NaOH was added below 20 ꢀC and the mixture was stirred at rt for
1 h. The organic layer was washed with 10% aq NaOH, 10% aq NaCl,
and dried over MgSO4. After removal of the solvent in vacuo, 1d
(119 mg, 79%) was obtained as a colorless oil. The ratio of cis/trans
of 1d was determined by 1H NMR analysis of tert-butyl protons,
(s, 3H), 1.64 (s, 3H), 2.94 (s, 2H), 3.45 (d, J¼11.4 Hz, 2H), 3.62 (d,
J¼11.4 Hz, 2H), 3.83 (s, 3H), 7.20–7.31 (m, 5H); 13C NMR (CDCl3,
75 MHz)
d 18.5, 26.0, 33.5, 40.0, 52.6, 71.3, 98.2, 126.2, 128.0, 130.8,
138.0, 171.3. Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C,
67.62; H, 7.59. HRMS (FAB) calcd for C15H20O4 (Mþ) 265.1395, found
265.1448.
trans-1d:
d 0.99, cis-1d: d 0.86.
Each isomer was obtained as a colorless oil from the mixture by
silica gel column chromatography with hexane/EtOAc, 10/1.
Acknowledgements
This work was financially supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
4.19. Methyl 2-methyl-c-5-(tert-butyl)-1,3-dioxane-r-2-
carboxylate (cis-1d)
IR (neat) nmax 2958, 2874, 1747, 1430, 1369, 1266, 1210, 1188,
Supplementary data
1155, 1119, 1060, 1011, 976, 883, 807, 755, 653 cmꢁ1 (obtained as
a mixture of cis/trans¼1); 1H NMR (CDCl3, 200 MHz)
d 0.86 (s, 9H),
Supplementary data associated with stabilities and charges/di-
pole moments can be found in the online version. Supplementary
data associated with this article can be found in the online version,
1.50 (s, 3H), 1.77–1.88 (m, 1H), 3.64 (dd, J¼11.0, 10.6 Hz, 2H), 3.84 (s,
3H), 4.02 (dd, J¼10.6, 4.4 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d 26.0,
27.3, 30.4, 42.5, 52.5, 65.2, 98.00, 171.3; HRMS (FAB) calcd for
C11H20O4 (Mþ) 217.1395, found 217.1446.
References and notes
4.20. Methyl 2-methyl-t-5-(tert-butyl)-1,3-dioxane-r-2-
carboxylate (trans-1d)
1. Garbi, A.; Mina, J. G.; Steel, P. G.; Longstaff, T.; Vile, S. Tetrahedron Lett. 2005, 46,
7175–7178.
2. Solomon, D. S.; Kitov, P. I.; Paszkiewicz, E.; Grant, G. A.; Sadowska, J. M.; Bundle,
D. R. Org. Lett. 2005, 7, 4369–4372.
3. Mishnev, A. F.; Bleidelis, Y. Y.; Liepin’sh, E. E.; Ramzaeva, N. P.; Goncharova, I. N.
Chem. Heterocycl. Compd. 1979, 15, 798–804.
4. (a) Kuwabara, K.; Murakami, K.; Todo, M.; Aoki, T.; Asaki, T.; Murai, M.; Yano, J.
J. Pharmacol. Exp. Ther. 2004, 309, 970–977; (b) Asaki, T.; Aoki, T.; Hamamoto, T.;
Sugiyama, Y.; Ohmachi, S.; Kuwabara, K.; Murakami, K.; Todo, M. Bioorg. Med.
Chem. 2008, 16, 981–994.
IR (neat) nmax 2958, 2874, 1747, 1430, 1369, 1266, 1210, 1188,
1155, 1119, 1060, 1011, 976, 883, 807, 755, 653 cmꢁ1 (obtained as
a mixture of cis/trans¼1); 1H NMR (CDCl3, 200 MHz)
d 0.99 (s, 9H),
1.38 (m, 1H), 1.51 (s, 3H), 3.81 (s, 3H), 3.92 (dd, J¼12.2, 4.8 Hz, 2H),
4.03 (dd, J¼12.2, 4.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d 23.0, 28.2,
31.7, 42.6, 52.5, 62.6, 97.7, 170.9; HRMS (FAB) calcd for C11H20O4
(Mþ) 217.1395, found 217.1442.
5. Harabe, T.; Matsumoto, T.; Shioiri, T. Tetrahedron Lett. 2007, 48, 1443–1446.