3370
P.-Q. Huang, Z.-Y. Li / Tetrahedron: Asymmetry 16 (2005) 3367–3370
1H, CH2CH2COOH), 2.48 (ddd, J = 6.7, 8.1, 15.6 Hz,
1H, CH2CH2COOH), 2.81 (d, J = 16.0 Hz, 1H,
CH2COOH), 2.84 (d, J = 16.0 Hz, 1H, CH2COOH),
5.24 (s, 1H, CH(C(CH3)3)); 13C NMR (125 MHz,
CD3OD): d 24.1, 28.9 (2C), 35.1, 39.8, 81.0, 109.1,
171.7, 175.7, 176.0; MS (ESI) m/z 273 ([Mꢀ1]ꢀ, 24%),
187 ([Mꢀ1ꢀ86]ꢀ, 100%). Anal. Calcd for C12H18O7:
C, 52.55; H, 6.62. Found: C, 52.81; H, 6.74.
References
1. Zabriskie, T. M.; Jackson, M. D. Nat. Prod. Rep. 2000, 17,
85–97.
2. (a) Kim, J.; Rees, D. C. Science 1992, 257, 1677–1682; (b)
Kim, J.; Wood, D.; Rees, D. C. Biochemistry 1993, 32,
7104–7115.
3. For racemic synthesis of homocitric acid, see: (a) Mara-
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Li, Z.-C.; Xu, J.-Q. Molecules 1998, 3, 31–34.
4. For a racemic synthesis followed by resolution, see:
Ancliff, R. A.; Russell, A. T.; Sanderson, A. J. Tetrahe-
dron: Asymmetry 1997, 8, 3379–3382.
5. For chiral synthesis, see: (a) Thomas, U.; Kalyanpur, M.
G.; Stevens, C. M. Biochemistry 1966, 5, 2513–2516; (b)
Tavassoli, A.; Duffy, J. E. S.; Young, D. W. Tetrahedron
Lett. 2005, 46, 2093–2096.
6. Only racemic homocitric lactone is commercially available
at price of >US$1000/g.
7. (a) Rodriguez, R.; G, H.; Biellmann, J. F. J. Org. Chem.
1996, 61, 1822–1824; (b) Ma, G.; Palmer, D. R. J.
Tetrahedron Lett. 2000, 41, 9209–9212; (c) Xu, P. F.;
Matsumoto, T.; Ohki, Y.; Tatsumi, K. Tetrahedron Lett.
2005, 46, 3815–3818.
4.6. Homocitric acid lactone 2
A solution of (2S,5S)-9 (60 mg) in 3 mL of TFA (50%
solution) was heated to reflux for 6 h. The solvents were
removed under reduced pressure. The residue was dried
in freeze dryer over 12 h to afford 40 mg of homocitric
20
acid lactone 2 (yield: 98%). ½a ¼ þ20:2 (c 1.18,
D
20
D
CH3OH) {lit.7c ½a ¼ þ21:3 (c 1.12, CH3OH)}; IR
(film): 3428, 2930, 1777, 1730 cmꢀ1
;
1H NMR
(500 MHz, D2O): d 2.36–2.43 (m, 1H, Ha-4), 2.50–2.56
(m, 1H, Hb-4), 2.65–2.72 (m, 2H, H-3), 3.01 (d,
J = 17.5 Hz, 1H, CH2COOH), 3.35 (d, J = 17.5 Hz,
1H, CH2COOH); 13C NMR (125 MHz, D2O): d 27.6,
31.1, 41.4, 84.6, 173.1, 174.6, 178.0; MS (ESI) m/z 211
([M+Na]+, 100%), 189 ([M+H]+, 11%). HRMS calcd
for [C7H8O6ꢀ1]ꢀ: 187.0240, found: 187.0237.
8. Paju, A.; Kanger, T.; Pehk, T.; Eek, M.; Lopp, M.
Tetrahedron 2004, 60, 9081–9084.
4.7. (2S,5S)-5-Benzyl-2-tert-butyl-5-(3-phenylpropyl)-
1,3-dioxolan-4-one 10
9. For reviews on the SRS methodology, see: (a) Seebach, D.;
Sting, A. R.; Hoffmann, M. Angew. Chem., Int. Ed. 1996,
35, 2708–2748; (b) Seebach, D.; Imwinkelried, R.; Weber,
T. EPC syntheses with C–C bond formation with acetals
and enamines. In Modern Synthetic Methods; Scheffold,
R., Ed.; Springer: Berlin, 1986; Vol. 4, pp 125–259.
10. For recent applications of SRS methodology to the
asymmetric synthesis of other natural products, see: (a)
Papke, M.; Schulz, S.; Tichy, H.; Gingl, E.; Ehn, R.
Angew. Chem., Int. Ed. 2000, 39, 4339–4341; (b) El Bialy,
S. A. A.; Braun, H.; Tietze, L. F. Eur. J. Org. Chem. 2005,
2965–2972.
11. (a) Seebach, D.; Naef, R.; Calderari, G. Tetrahedron 1984,
40, 1313–1324; (b) Grover, P. T.; Bhongle, N. N.; Wald, S.
A.; Senanayake, C. H. J. Org. Chem. 2000, 65, 6283–6287;
(c) Su, X.; Bhongle, N. N.; Pflum, D.; Butler, H.; Wald, S.
A.; Bakale, R. P.; Senanayake, C. H. Tetrahedron:
Asymmetry 2003, 14, 3593–3600.
12. (a) Shinkai, H.; Nishikawa, M.; Sate, Y.; Toi, K.;
Kumashiro, I.; Seto, Y.; Fukuma, M.; Dan, K.; Toyo-
shima, S. J. Med. Chem. 1989, 32, 1436–1441; (b)
Chandrasekhar, B.; Sawanth, M. S.; Naik, S. J.; Gaikwad,
N. B.; Kulkarni, P. V.; Bhirud, S. B. Org. Prep. Proced.
Int. 2004, 36, 459–467.
13. (a) Wasserman, H. H.; Xia, M. D.; Petersen, A. K.;
Jorgensen, M. R.; Curtis, E. A. Tetrahedron Lett. 1999, 40,
6163–6166; (b) Nemoto, H.; Ma, R. J.; Suzuki, I.;
Shibuya, M. Org. Lett. 2000, 2, 4245–4247; (c) Wasser-
man, H. H.; Petersen, A. K.; Xia, M. D. Tetrahedron 2003,
59, 6771–6784.
To a solution of LHMDS (0.50 mmol) in 3.6 mL of a
mixed solvent (THF–hexane = 9:1), was added a solu-
tion of cis-5 (100 mg, 0.43 mmol) and HMPA
(0.37 mL, 2.14 mmol) in 7 mL of THF at ꢀ78 ꢁC. After
30 min, 3-phenylpropyl iodide (437 mg, 1.71 mmol) was
added. After 4 h, the reaction mixture was quenched
with 30 mL of an aqueous solution of ammonium chlo-
ride (15.7% w/w), and the aqueous layer extracted with
Et2O (3 · 2 mL). The combined organic phases were
washed with brine (2 mL), and dried over anhydrous
Na2SO4. After being concentrated in vacuum, the resi-
due was purified by flash chromatography (eluent:
diethyl ether–petroleumether = 1:40) to afford
10
20
(48 mg, yield: 32%) as a colorless oil. ½a ¼ þ15:6 (c
D
0.59, CHCl3). IR (film): 2921, 1792, 1598 cmꢀ1
;
1H
NMR (500 MHz, CDCl3): d 0.67 (s, 9H, C(CH3)3),
1.68–1.77 (m, 4H, CH2CH2CH2Ph), 2.50–2.56 (m, 2H,
CH2CH2CH2Ph), 2.92 (d, J = 14.25 Hz, 1H, CH2Ph),
3.05 (d, J = 14.25 Hz, 1H, CH2Ph), 5.02 (s, 1H,
CH(C(CH3)3)), 7.06–7.22 (m, 10H, Ar); 13C NMR
(125 MHz, CDCl3): d 23.2 (3C), 25.5, 34.3, 34.4, 35.8,
41.4, 82.8, 108.6, 126.0, 127.0, 128.2, 128.4, 130.7,
135.0, 141.4, 174.8; MS (ESI) m/z 375 ([M+Na]+,
100%), 370 (½MþNH4þþ, 90%). HRMS calcd for
[C23H28O3+Na]+: 375.1924, found: 375.1931.
14. (a) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless,
K. B. J. Org. Chem. 1981, 46, 3936–3938; For a review on
the use of phenyl group as a synthetic equivalent of
carboxyl group, see: (b) Mander, L. N.; Williams, C. M.
Tetrahedron 2003, 59, 1105–1136.
Acknowledgements
The authors are grateful to the NSF of China
(20272048; 203900505) and the Ministry of Education
(Key Project 104201), for financial support.
15. Wunsch, B.; Zott, M. Liebigs Ann. Chem. 1992, 39–
¨
45.