A. Heydari et al. / Tetrahedron Letters 48 (2007) 1135–1138
1137
On the basis of the encouraging results obtained on the
regioselective reductive amination of a,b-unsaturated
carbonyl compounds, it seemed logical to investigate
the possibility of extending this method to the prepara-
tion of allylic alcohols via selective 1,2-reduction of a,b-
unsaturated aldehydes and ketones. We first examined
the reduction of cinnamyl aldehyde using H3PW12O40
(0.5 mol %)/NaBH4 in methanol. We tested various
a,b-unsaturated carbonyls, the reactions were highly
regioselective and afforded only the corresponding
allyl alcohols (Scheme 2). Furthermore, treatment of
oxycodone 4f with H3PW12O40 (0.5 mol %)/NaBH4 led
to the corresponding 6b-alcohol 5f as the sole epimer.
The stereochemical assignment of the epimeric 6b-alco-
hol 5f has been previously deduced based on the relative
1H), 3.22 (d, J = 18.66 Hz, 1H), 3.88 (s, 3H), 4.67 (m,
1H), 4.93 (d, J = 6.61 Hz, 1H), 5.02 (br s, 1H), 5.54
(dd, J = 9.89, 3.04 Hz, 1H), 5.96 (d, J = 8.74 Hz, 1H),
6.62 (d, J = 8.2 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H); 13C
NMR (122 MHz, CDCl3): d 22.6 (CH2), 32.0 (CH2),
43.2 (NCH3), 45.6 (CH2), 47.1 (C), 56.7 (OCH3), 64.4
(CH), 65.6 (C), 69.1 (C), 90.3 (CH), 113.6 (CH), 119.7
(CH), 126.0 (C), 129.1 (C), 132.6 (C), 138.4 (CH),
143.0 (C), 145.9 (C).
References and notes
1. For reviews on reductive amination see: (a) Hutchins, R.
O.; Hutchins, M. K. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 8, p 25; (b) Baxter, E. W.; Reitz, A. B. In Organic
Reactions; Wiley: New York, 2002; Vol. 59, p 1; (c)
Hudlicky, M. In Reductions in Organic Chemistry, 2nd ed.;
ACS Monograph 188; American Chemical Society:
Washington, DC, 1996; p 187.
2. Tarasevich, V. A.; Kozlov, N. G. Russ. Chem. Rev. 1999,
68, 55.
3. Chen, B.-C.; Sundeen, J. E.; Guo, P.; Bednarz, M. S.;
Znao, R. Tetrahedron Lett. 2001, 42, 1245.
magnitude of the 1H NMR vicinal coupling constants of
17
J5,6
.
In summary, we have developed the H3PW12O40
(0.5 mol %)/NaBH4 promoted direct reductive N-alkyl-
ation methodology which is both selective and efficient.
This methodology also proved to be a general protocol
for the syntheses of allyl alcohols.
4. Micovic, I. V.; Ivanovic, M. D.; Piatak, D. M.; Bojic, V.
D. Synthesis 1991, 1043.
5. Suwa, T.; Sugiyama, E.; Shibata, I.; Baba, A. Synthesis
2000, 6, 789.
2. General procedure I: reductive amination of carbonyl
compounds
6. (a) Lane, C. F. Synthesis 1975, 135; (b) Abdel-Magid, A.
F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah,
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2000, 503; (h) Bhattacharyya, S. J. Org. Chem. 1995,
60, 4928; (i) Verardo, G.; Giumanin, A. G.; Strazzolini, P.;
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M.; Kim, E. G.; Son, H. S.; Choi, J. Synth. Commun. 1993,
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To a solution consisting of reagent grade methanol
(4 mL), carbonyl compound (2 mmol) and amine
(2.2 mmol) was added H3PW12O40 (30 mg, 0.5 mol %)
and the mixture vigorously stirred for 10 min at room
temperature. NaBH4 (20 mg, 2 mmol, 1 equiv) was
added and the mixture was stirred for an additional
30 min. The reaction mixture was washed with water fol-
lowed by brine then extracted with CH2Cl2. The com-
bined organics were dried over Na2SO4, concentrated
under vacuum and the crude mixture was purified by
column chromatography on silica gel (hexane/ethyl ace-
tate, 2:1) to afford pure products.
7. Kumpaty, H. J.; Bhattacharyya, S.; Rehr, E. W.; Gonz-
alez, A. M. Synthesis 2003, 14, 2206; Weis, A. L.; Bakos,
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Tetrahedron Lett. 1999, 40, 4863.
3. General procedure II: selective 1,2-reduction of
a,b-unsaturated aldehydes and ketones
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Kozhevnikov, I. V. In Catalysis by Polyoxometalates;
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An analogous procedure was used for 1,2-reduction to
that described above. Spectroscopic data for selected
examples follow. Compound 3f: 1H NMR (90 MHz,
CDCl3): d 3.61 (br s, 1H), 4.33 (s, 2H), 6.52–6.81 (m,
5H), 7.13 (d, J = 9 Hz, 2H), 8.54 (d, J = 9 Hz, 2H);
13C NMR (22.5 MHz, CDCl3): d 48.3 (CH2), 113.0
(CH), 117.9 (CH), 122.4 (CH), 128.9 (CH), 148.1
(CH), 149.5 (C), 159.3 (C). Compound 3i: 1H NMR
(500 MHz, CDCl3): d 1.64 (s, 3H), 1.72 (s, 3H), 1.75
(s, 3H), 2.04–2.13 (m, 4H), 3.63–3.74 (m, 2H), 5.12 (m,
1H), 5.33 (m, 1H), 6.61–6.64 (m, 2H), 6.74 (m, 1H),
7.13–7.25 (m, 2H); 1H NMR (122 MHz, CDCl3): d
16.3 (CH3), 17.6 (CH3), 25.7 (CH3), 26.4 (CH2), 39.4
(CH2), 41.9 (CH2), 112.8 (CH), 117.2 (CH), 121.5 (H),
122.2 (C), 123.9 (CH), 129.1 (CH), 138.9 (C), 148.9
(C). Compound 5f: 1H NMR (500 MHz, CDCl3): d
1.82 (m, 1H), 2.44 (t, J = 8.14 Hz, 2H), 2.47 (s, 3H),
2.55 (m, 2H), 2.97 (d, J = 10.16 Hz, 1H), 3.10 (br s,
Quartararo, J.; Kozhevnikov, I. V. Appl. Catal.
2003, 245, 69.
A
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