7598
Y.-C. Qiu et al. / Tetrahedron Letters 48 (2007) 7595–7598
12. Boerjesson, L.; Welch, C. J. Tetrahedron 1992, 48, 6325–
6334.
13. Berlage, U.; Schmidt, J.; Milkova, Z.; Welzel, P. Tetrahe-
dron Lett. 1987, 28, 3095–3098.
14. Terasaka, T.; Seki, N.; Tsuji, K.; Nakanishi, I.; Kinoshita,
T.; Nakamura, K. PCT Int. Appl. 200055155, 2000; Chem.
Abstr. 2000, 133, 252457.
15. Jacks, T. E.; Butler, D. E. PCT Int. Appl. 9804543, 1998;
Chem. Abstr. 1998, 128, 154074.
bond and nitro can be tolerated. Esters with b-hydroxy
were reduced more easily (entries 1–4). When the reduc-
tion products contained an amino group, an additional
treatment was necessary to hydrolyze the B–N adducts
or borate esters by 20% aqueous sodium hydroxide at
reflux for 2 h to afford the corresponding products
(entries 12–14). Addition of substrate in toluene to raise
the reaction temperature enhanced the reducing power
of KBH4–MgCl2 (entries 5 and 13–16).
16. Procedure for the reduction of ester 2 to alcohol 1: A dry,
250-mL three-neck flask with CaCl2 drying tube and
magnetic stirrer was charged with 100 mL of THF, 3.27 g
(purity: 95%, 57.47 mmol) of KBH4, and 5.46 g
(57.47 mmol) of MgCl2. The reaction mixture was heated
under reflux for 2 h, then 10.0 g (57.47 mmol) of 2 was
added dropwise over 5 min and maintained at reflux for an
additional 40 min. After cooling to 5–10 ꢁC, methanol
(15 mL) was carefully added dropwise to quench the
reaction and the white inorganic solid was filtrated and
washed with 80 mL of THF/MeOH (v/v = 10:1). The
combined filtrate was concentrated to dryness, MeOH
(40 mL) was added to the residue and concentrated to
dryness again. The resulting residue was dissolved in
300 mL of ethyl acetate and washed with brine, dried
over MgSO4 and concentrated to dryness to provide
7.58 g (yield 90.3%) of 1 as colorless oil: GC 97.8%; bp 75–
76 ꢁC/2 mmHg (lit.8a 55–61 ꢁC/0.05 mmHg); 1H NMR
(400 MHz, CDCl3): d 1.36 (s, 3H), 1.42 (s, 3H), 1.79–1.84
(m, 2H), 2.39 (br s, 1H), 3.58 (dd, 1H, J = 8.4, 6.0 Hz),
3.78 (t, 2H, J = 5.0 Hz), 4.08 (dd, 1H, J = 8.4, 6.0 Hz),
4.23–4.29 (m, 1H); ESI-MS m/z: [M+Na]+ 169. GC
condition: HP5890; column: INNOWAX (30 m ·
0.53 mm · 1 lm); oven: 150 ꢁC (hold 4.5 min) to 200 ꢁC
(hold 6 min) at 70 ꢁC/min; carrier gas: nitrogen; detector:
FID; 2.2 min: starting material (2); 3.3 min: 6-membered
acetonide (4); 3.9 min: product (1).
References and notes
1. (a) Brown, H. C.; Mead, E. J.; Subba Rao, B. C. J. Am.
Chem. Soc. 1955, 77, 6209–6213; (b) Brown, H. C.; Subba
Rao, B. C. J. Am. Chem. Soc. 1956, 78, 2582–2588; (c)
Brown, H. C.; Narasimhan, S.; Choi, T. M. J. Org. Chem.
1982, 47, 4702–4708.
2. (a) Yang, C.; Pittman, C. U. Synth. Commun. 1998, 28,
2027–2041; (b) Narasimhan, S.; Madhavan, S.; Prasad, K.
G. J. Org. Chem. 1995, 60, 5314–5315; (c) Narasimhan, S.;
Balakumar, R. Aldrichim. Acta 1998, 31, 19–26.
3. Suseela, Y.; Periasamy, M. Tetrahedron 1992, 48, 371–376.
4. Abiko, A.; Masamune, S. Tetrahedron Lett. 1992, 33,
5517–5518.
5. Kanth, J. V. B.; Periasamy, M. J. Org. Chem. 1991, 56,
5964–5965.
6. Lane, C. F.; Myatt, H. L.; Daniels, J.; Hopps, H. B. J.
Org. Chem. 1974, 39, 3052–3054.
7. (a) Wei, Y.; Geng, G.-W.; Wang, Q.-Z. Chin. J. Pharm.
1986, 17, 286; (b) Wei, Y.; Geng, G.-W.; Wang, Q.-Z.
Chin. J. Pharm. 1987, 18, 102–103; (c) Wei, Y.; Geng, G.-
W.; Wang, Q.-Z. Chin. J. Pharm. 1987, 18, 529–531; (d)
He, B.-M.; Qiu, Y.-C.; Chen, J.; Zhang, F.-L. Chin. J.
Pharm. 2005, 36, 657–659.
17. General method 1: MgCl2 and KBH4 were added in THF
and heated under reflux for 2 h, then the substrate or its
mixture with toluene was added. After the reaction was
completed, methanol was added dropwise at room tem-
perature to quench the reaction. After filtration, the
solvent was removed in vacuo and the residue was purified
via conventional techniques to afford the corresponding
product. General method 2 (product with amine group):
Same as method 1, but used brine to quench the reaction.
After filtration and extraction, the resulting organic layer
was isolated and concentrated to dryness, 20% aqueous
sodium hydroxide was added to the residue and refluxed
for 2 h. After cooling to room temperature, the result-
ing mixture was extracted with dichloromethane. The
combined organic layer was dried over Na2SO4 and
concentrated to dryness. The residue was purified via
conventional techniques to afford the corresponding
product.
8. (a) Meyers, A. I.; Lawson, J. P.; Walker, D. G.; Linder-
man, R. J. J. Org. Chem. 1986, 51, 5111–5123; (b) Gaunt,
M. J.; Jessiman, A. S.; Orsini, P.; Tanner, H. R.; Hook, D.
F.; Ley, S. V. Org. Lett. 2003, 5, 4819–4822; (c) Zemribo,
R.; Mead, K. T. Tetrahedron Lett. 1998, 39, 3895–3898;
(d) Nazare, M.; Waldmann, H. Angew. Chem., Int. Ed.
2000, 39, 1125–1128; (e) Li, S.; Xu, R.; Bai, D. Tetrahe-
dron Lett. 2000, 41, 3463–3466; (f) Steel, P. G.; Thomas, E.
J. J. Chem. Soc., Perkin Trans. 1 1997, 371–380; (g)
Sharma, G. V. M.; Reddy, C. G. Tetrahedron Lett. 2004,
45, 7483–7485; (h) Zheng, G.-R.; Lu, W.; Cai, J.-C. Chin.
Chem. Lett. 2000, 11, 663–664.
9. Meyers, A. I.; Lawson, J. P. Tetrahedron Lett. 1982, 23,
4883–4886.
10. Hanessian, S.; Ugolini, A.; Dube, D.; Glamyan, A. Can. J.
Chem. 1984, 62, 2146–2147.
11. Donaubauer, J. R.; Greaves, A. M.; McMorris, T. C. J.
Org. Chem. 1984, 49, 2834–2837.