Selectivity in Sodium Borohydride Reductions of α-Substituted Esters
FULL PAPER
–1
3
004, 1046, 748, 699 cm . HRMS (APPIA, M-1): calcd. for
tion was analyzed by HPLC and the percent of the unreacted start-
C
8
H
9
O 121.0653; found 121.0631.
ing material was obtained by HPLC using PhCO
ternal standard.
2
Me as the in-
4
H
7
2 2
NaBH Reductions of 1-C10 CH CO Me (15): The reduction was
carried out using the general procedure mentioned above. The on-
set reaction temperature was 114 °C. Yield: 95%. H NMR
NaBH4 Reductions with α-Halogenated Methyl Acetates: NaBH4
(300 mg, 8.0 mmol) in 10 mL of diglyme was added to a solution
of methyl α-halogenated ester (4.0 mmol) in 10 mL of diglyme at
1
3
(400 MHz, CHCl ): δ = 8.05 (d, J = 7.9 Hz, 1 H), 7.86 (d, J =
7
.6 Hz, 1 H), 7.75 (d, J = 8.1 Hz, 1 H), 7.52 (m, 2 H), 7.41 (m, 2 the on-set reaction temperature. After 3 h, the mixture was filtered
1
3
H), 3.92 (t, J = 6.7 Hz, 2 H), 3.31 (t, J = 6.6 Hz, 2 H) ppm.
NMR (100 MHz, CHCl
C
and the solid was washed with dry diethyl ether. A drop of concen-
trated aqueous HCl solution was added to the combined organic
solution. This solution was then dried with anhydrous Na SO for
3
): δ = 134.3, 133.9, 132.0, 128.8, 127.2,
1
3
27.1, 125.9, 125.6, 125.4, 123.6, 62.9, 36.1 ppm. IR (KBr): ν˜ =
363, 3289, 3048, 1042, 1015, 800, 776 cm . HRMS (FAB ): calcd.
2
4
–1
+
30 min. The dried solution was analyzed by HPLC and the percent
for C12
H12ONa 195.0785; found 195.0779.
of the unreacted starting material was obtained using PhCO Me
2
as the internal standard.
NaBH
4
Reductions of 2-Benzoylamino-2-(methoxycarbonyl)ethyl
Benzoate (16): The reduction was carried out using the general pro-
The obtained NMR spectroscopic data for products from the two
cedure mentioned above at 40 °C.
α-haloester reductions are listed below (FCH CH OH is so soluble
): δ = 8.02 (d, in water that it is difficult to purify because of its low boiling point
2
2
1
17: Liquid. Yield: 41%. H NMR (400 MHz, CHCl
3
J = 1.4 Hz, 2 H), 7.76 (d, J = 1.6 Hz, 2 H), 7.44 (m, 6 H), 6.90 (d,
and so we were unable to obtain it pure enough to record the NMR
spectra, even though the reaction was repeated several times):
J = 7.3 Hz, 1 H), 4.55 (m, 3 H), 3.83 (m, 2 H) ppm. 1 C NMR
3
(
1
3
100 MHz, CHCl
29.3, 128.6, 128.5, 127.0, 63.1, 61.8, 51.2 ppm. IR (KBr): ν˜ = 3407,
318, 3064, 1725, 1637, 711, 694 cm . HRMS (FAB ): calcd. for
300.1235; found 300.1245.
8: Liquid. Yield: 95%. H NMR (400 MHz, CH
3
): δ = 167.8, 167.5, 133.8, 133.5, 131.8, 129.8,
ClCH
2
CH
2
OH: 1H NMR (400 MHz, CHCl
3
): δ = 3.65 (t, J =
1
3
5.0 Hz, 2 H), 3.84 (t, J = 5.4 Hz 2 H) ppm. C NMR (100 MHz,
–1
+
CHCl
3
): δ = 62.8, 46.7 ppm.
17 4
C H18NO
1
1
1
OH): δ = 7.83 BrCH
2
CH
2
OH: H NMR (400 MHz, CHCl
3
): δ = 3.51 (m, 2 H)
3
3.88 (t, J = 5.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CHCl
): δ =
(d, J = 7.7 Hz, 2 H), 7.52 (m, 1 H), 7.43 (m, 2 H), 4.17 (m, 1 H),
3
3
1
3
.73 (t, J = 5.8 Hz, 4 H) ppm. 13C NMR (100 MHz, CH
70.5, 135.7, 132.6, 129.5, 128.4, 62.2, 55.2 ppm. IR (KBr): ν˜ =
OH): δ = 62.6, 35.6 ppm.
3
–
1
379, 3290, 3085, 1637, 1552, 1341, 1075, 1036, 694, 672 cm .
Acknowledgments
+
HRMS (FAB ): calcd. for C10
NaBH Competitive Reductions: An equimolar mixture of 1 and 3
180 and 178 mg, respectively; 1:1 mol/mol, 2.0 mmol of each) was
dissolved in diglyme (15 mL). NaBH (2 equiv., 2.0 mmol) was then
3
H14NO 196.0973; found 196.0981.
4
Financial support was provided by the Chinese Academy of Sci-
ences “Hundred Talents Program” Fund, the Science and Technol-
ogy Committee of Yunnan Province, and the Key State Lab of
Phytochemistry and Plant Resources in West China to H. J. Z. The
Ferro Corporation is thanked for partial support of this work at
Mississippi State University (C. U. P. Jr).
(
4
added (in 15 mL diglyme) at 0–4 °C (ice bath cooled). The reaction
temperature was then raised to 33–35 °C. After 3 h, the reaction
mixture was filtered to remove diglyme. The residue was then
washed three times with dry diethyl ether, followed by the addition
of drops of concentrated aqueous HCl solution to decompose unre-
acted borohydride. The resulting mixture was then extracted a
minimum of five times with methanol/diethyl ether (50:50, v/v,
[
[
1] a) J. V. B. Kanth, M. Periasamy, J. Org. Chem. 1991, 56, 5964;
b) M. J. McKennon, A. I. Meyers, J. Org. Chem. 1993, 58,
3568.
1
5 mL). The combined organic layers were dried with anhydrous
Na SO . The solvents were then removed in vacuo. This residue
was purified by column chromatography to give ethylene glycol
105 mg, 84% yield). Unreacted 3 (169 mg) was recovered in 93%
2] For a recent review, see: M. Periasamy, M. Thirumalaikumar,
2
4
J. Organomet. Chem. 2000, 609, 137.
[3] a) H. J. Zhu, K. T. Lu, G. R. Sun, J. B. He, H. Q. Li, C. U.
Pittman Jr, New J. Chem. 2003, 27, 409; b) H. J. Zhu, C. U.
Pittman Jr, Synth. Commun. 2003, 33, 1733; c) H. C. Brown,
R. B. C. Subba, J. Am. Chem. Soc. 1955, 77, 3164; d) H. C.
Brown, R. B. C. Subba, J. Am. Chem. Soc. 1956, 78, 2582; e)
H. Seki, K. Koga, H. Matsuo, S. Ohki, I. Matsuo, S. Yamada,
Chem. Pharm. Bull. 1965, 13, 995; f) S. W. Chaikin, W. G.
Brown, J. Am. Chem. Soc. 1949, 71, 122; g) H. I. Schlesinger,
H. C. Brown, H. R. Hoekstra, L. R. Rapp, J. Am. Chem. Soc.
1953, 75, 199.
(
yield.
Competitive reductions of 3 with 11 (178 and 300 mg, respectively)
and 11 with 10 (86 and 78 mg, respectively) were carried out in the
same manner as described above for the competitive reduction of
equimolar amounts of 1 with 3, except different temperatures were
employed and the diglyme was removed at about 40 °C under 1–
3
8
Torr. The competitive reductions of 3/11 were performed at 82–
5 °C for 3 h. 2-Aminoethanol was produced (90 mg, 74% yield)
[
4] A. F. Abdel-Magid, Reductions in Organic Synthesis, ACS Sym-
posium series 641, Washington DC, USA, 1996, pp. 167.
and 11 (278 mg) was recovered in 93% yield. The competitive re-
ductions of 10 and 11 were performed at 110–5 °C. Benzyl alcohol
(
[5] S. C. Gatling, J. E. Jackson, J. Am. Chem. Soc. 1999, 121, 8655–
+
8656. Na was not involved in these TS calculations. The semi-
65 mg) was obtained in 93% yield and 89% of 10 (70 mg) was
empirical AM1 method was used in the computations.
6] a) H. C. Brown, N. Narasimhan, Y. M. Choi, J. Org. Chem.
recovered.
[
[
1
982, 47, 4702; b) K. Soai, A. Ookawa, J. Org. Chem. 1986,
4
General Procedure for NaBH Reductions of Methyl α-Haloacetates
1
5
1, 4000.
4
2–14: NaBH (300 mg, 8.0 mmol) in 10 mL of diglyme was added
7] For some recent experimental studies on the reductions of
ketonesters with sodium borohydride, see: a) P. V. Ramachand-
ran, S. Pitre, H. C. Brown, J. Org. Chem. 2002, 67, 5315; b) E.
Marcantoni, S. Alessandrini, M. Malavolta, J. Org. Chem.
to a solution of methyl α-haloacetate (34.0 mmol) in 10 mL of di-
glyme at the previously determined on-set reaction temperature for
each. After 3 h, the mixture was filtered and the solid was washed
with dry diethyl ether. A drop of concentrated aqueous HCl solu-
tion was added to the combined organic solution. This solution
1
999, 64, 1986; c) C. A. M. Fraga, L. H. P. Teixeira, C. M.
de S. Menezes, C. M. R. Sant’Anna, M. da C. K. V. Ramos,
F. R. A. Neto, E. J. Barreiro, Tetrahedron 2004, 60, 2745.
2 4
was then dried for 30 min over anhydrous Na SO . The dried solu-
Eur. J. Org. Chem. 2006, 1981–1990
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www.eurjoc.org
1989