Tanaka et al.
SCHEME 7a
a Reagents and conditions: (a) NaBH4, Na2CO3 aq; (b) aniline, Bu2SnHCl, HMPA.
Experimental Section
Culture, Sports, Science and Technology of the Japanese
Government. We also acknowledge financial support from the
Tokuyama Science Foundation. S.T. expresses his special thanks
for Research Fellowships of the Japan Society for JSPS Research
Fellowships for Young Scientists.
Representative Procedure: Synthesis of 4gb. 2-Bromo-3-
phenylpropanal 2b (0.74 mmol) was added to a stirred suspension
of 3-benzyloxypropanal 1g (0.60 mmol), PPh3 (0.028 mmol), and
GeCl2-dioxane (0.72 mmol) in dioxane (2 mL) at room temper-
ature. After the mixture was stirred for 1 h at room temperature,
methanol (8 mL) was added. The resulting solution was stirred for
an additional 1 h at room temperature, and then aqueous NaHCO3
(saturated; 10 mL) was added. The mixture was extracted with Et2O/
hexane (4/1, three times), dried (MgSO4), and evaporated to give
the crude product 4gb (66%, syn/anti ) 91:9). The crude product
was purified by silica gel chromatography (hexane/EtOAc ) 95/5
to 0/100) to afford the pure product 4gb as a pale yellow liquid
(0.31 mmol, 51%, syn/anti ) 91:9). Data for syn-4gb: IR, (neat)
Supporting Information Available: Experimental proce-
dures, spectroscopic details of new compounds, listing of
absolute energies and geometries for calculated species, and
X-ray data for 8, 4ee, and disilylated compound 27 from 23
(CIF). This material is available free of charge via the Internet
1
3525 (OH) cm-1. H NMR: (400 MHz, CDCl3) 7.37-7.14 (m,
JO800904U
10H), 4.51 (s, 2H), 4.23 (d, J ) 4.7 Hz, 1H), 4.12-4.06 (m, 1H),
3.69-3.58 (m, 2H), 3.42 (s, 3H), 3.28 (s, 3H), 3.21-3.17 (brs,
1H), 2.79 (dd, J ) 14.3, 7.9 Hz, 1H), 2.72 (dd, J ) 14.3, 7.1 Hz,
1H), 2.09 (dddd, J ) 7.9, 7.1, 4.7, 2.0 Hz, 1H), 1.89-1.72 (m,
2H). 13C NMR: (100 MHz, CDCl3) 140.6, 138.2, 128.9, 128.3,
128.2, 127.6, 127.4, 125.8, 107.1, 73.1, 68.4, 68.0, 56.1, 54.2, 47.4,
33.9, 30.9; MS: (CI, 200 eV) 313 (M+ + 1 - MeOH, 6), 295 (M+
+ 1 - H2O - MeOH, 84), 264 (20), 263 (100), 235 (40), 191
(51), 189 (51), 173 (32), 165 (94), 161 (21), 149 (50), 148 (25), 91
(73), 75 (21). HRMS: (CI, 200 eV) calcd (C20H25O3), 313.1804
(M+ + 1 - MeOH); found, 313.1803; calcd (C20H23O2), 295.1698
(M+ + 1 - H2O - MeOH); found, 295.1704; calcd (C19H21O2),
281.1542 (M+ - 2MeOH); found, 281.1534. Anal. Calcd for
C21H28O4 (344.4446): C, 73.23; H, 8.19. Found: C, 73.19; H, 8.18.
Data for anti-4gb (selected signals are shown): 1H NMR, (400 MHz,
CDCl3) 4.33 (d, J ) 3.9 Hz, 1H), 3.86 (dddd, J ) 8.9, 4.5, 4.5, 4.5
Hz, 1H), 3.40 (s, 3H), 3.35 (s, 3H). 13C NMR: (100 MHz, CDCl3)
138.2, 129.1, 125.8, 69.4, 68.7, 55.4, 47.6, 35.2, 32.0. Some signals
are obscured by those of the major isomer.
(21) All calculations were performed with Gaussian 03. The method we
employed was the B3PW91 HF/DFT hybrid method. A basis set used was
DGDZVP for all the atoms. Total energies for evaluation corrected with zero
point energies. Solvent effects were included via a PCM model. The dielectric
constant chosen was of diethyl ether, 4.335, and atomic radii with UFF referred
as UA0.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala,
P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski,
V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul,
A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.;
Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision C.02;
Gaussian, Inc.: Wallingford, CT, 2004.
Acknowledgment. This work was supported by a Grant-in-
Aid for Scientific Research from the Ministry of Education,
(23) (a) Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K. J. Am. Chem.
Soc. 1980, 102, 7107–7109. (b) Nakamura, E.; Yamago, S.; Machii, D.;
Kuwajima, I. Tetrahedron Lett. 1988, 29, 2207–2210. (c) Denmark, S. E.; Henke,
B. R. J. Am. Chem. Soc. 1989, 111, 8032–8034.
(18) We previously reported a remarkable effect of a bromide anion on the
activation of tin enolate. Yasuda, M.; Chiba, K.; Ohigashi, N.; Katoh, Y.; Baba,
A. J. Am. Chem. Soc. 2003, 125, 7291–7300. (b) Yasuda, M.; Hayashi, K.; Katoh,
Y.; Shibata, I.; Baba, A. J. Am. Chem. Soc. 1998, 120, 715–721. (c) Yasuda,
M.; Chiba, K.; Baba, A. J. Am. Chem. Soc. 2000, 122, 7549–7555.
(19) Denmark and co-workers observed the formation of chlorohydrin in the
aldol addition of trimethylsilyl enol ether to aldehyde in the presence of SiCl4
(see ref 5b).
(20) (a) Power, M. B.; Bott, S. G.; Atwood, J. L.; Barron, A. R. J. Am. Chem.
Soc. 1990, 112, 3446–3451. (b) Power, M. B.; Bott, S. G.; Clark, D. L.; Atwood,
J. L.; Barron, A. R. Organometallics 1990, 9, 3086–3097.
(24) The same transition state model was suggested by Nakamura et al. in
the TBAF catalyzed cross-aldol reaction of silyl enol ethers (see ref 23b).
(25) For examples of successive transformation of cross-aldol products, see:
(a) Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 2762–2763. (b)
Boxer, M. B.; Yamamoto, H. Org. Lett. 2008, 10, 453–455. (see also ref 5b).
(26) Suwa, T.; Sugiyama, E.; Shibata, I.; Baba, A. Synthesis 2000, 789–
800.
(27) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17, 1295–1298.
(28) Evans, D. A.; Allison, B. D.; Yang, M. G.; Masse, C. E. J. Am. Chem.
Soc. 2001, 123, 10840–10852.
6320 J. Org. Chem. Vol. 73, No. 16, 2008