D
S. Tuokko, P. M. Pihko
Letter
Synlett
Acknowledgment
alumina column. The column was eluted with EtOAc (10 mL).
The filtrate was left to oxidize overnight to allow the reaction to
proceed to completion. Isolation of the product was unsuccess-
ful. Product 4a decomposes/polymerizes when concentrated.
Characterization was carried out from the crude filtrate con-
taining EtOAc and Et3SiOH (7). IR (film): 3379, 2955, 2877, 1734,
Support from the Graduate School of the Faculty of Science, Universi-
ty of Jyväskylä (to S.T) and grant from Tekes (2671/31/2013) are
gratefully acknowledged. We thank Dr. Elina Kalenius and Ms. Johan-
na Lind (University of Jyväskylä) for HRMS analyses and Mr. Esa
Haapaniemi (University of Jyväskylä) for assistance with NMR spec-
troscopy.
1455, 823, 728, 701, 681 cm–1 1H NMR (300 MHz, CDCl3): δ =
.
9.71 (s, 1 H), 8.40 (br s, 1 H), 7.44–7.08 (m, 5 H), 3.19 (d, 1 H,
J = 14.3 Hz), 2.88 (d, 1 H, J = 14.3 Hz), 1.22 (s, 3 H). 13C NMR (75
MHz, CDCl3): δ = 203.0, 134.5, 130.7, 128.5, 127.2, 89.0, 38.5,
17.1. HRMS (ESI+): m/z [M + MeOH + Na] calcd for C11H16O4Na:
235.0941; found: 235.0945, Δ = –0.4 mDa.
Supporting Information
Supporting information for this article is available online at
(7) General Procedure for the Preparation of 2-Methyl-1,2-diols
Et3SiH (1.65 mmol, 1.1 equiv) was added to the suspension of α-
substituted acrolein (1.50 mmol, 1.0 equiv), water (100 μL) and
Pd/C (5 wt%, 5 mg) in EtOAc (5 mL). After 10 min of stirring, the
reaction mixture was filtered through a small pad of neutral
alumina column. The column was eluted with EtOAc (15 mL).
The filtrate was stirred overnight to allow the autoxidation to
proceed to completion.To the filtrate was added MeOH (20 mL)
and NaBH4 (9.00 mmol, 6.0 equiv). After 3 h of stirring, 40 mL
NH4Cl (aq) was added to quench the reaction. The reaction
mixture was extracted with EtOAc (3 × 20 mL). The organic
phases were combined, dried with NaSO4 and concentrated in
vacuum. The residue was purified by flash chromatography
(silica gel, n-hexane–EtOAc gradient from 80:20 to 50:50) to
afford the products. For more details and characterization of the
products, see Supporting Information.
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References and Notes
(1) For review of α-hydroxylation of carbonyl compounds, see:
(a) Jones, A. B. In Comprehensive Organic Synthesis; Vol. 7; Trost,
B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991, 151–191.
(b) Chen, B.-C.; Zhou, P.; Davis, F. A.; Ciganek, E. In Organic Reac-
tions; Vol. 62; Overman, L. E., Ed.; John Wiley and Sons: New
York, 2003, 1–356; and references cited therein. For selected
examples of α-hydroxylation of carbonyl compounds with
molecular oxygen, see: (c) Enslin, P. R. Tetrahedron 1971, 27,
1909. (d) Kohler, E. P.; Tishler, M.; Potter, H. J. Am. Chem. Soc.
1935, 57, 2517. (e) Crombie, L.; Godin, P. J. J. Chem. Soc. 1961,
2861. (f) Irie, H.; Katakawa, J.; Tomita, M.; Mizuno, Y. Chem. Lett.
1981, 637. (g) Ohnuma, T.; Seki, K.; Oishi, T.; Ban, Y. J. Chem.
Soc., Chem. Commun. 1974, 296. (h) Corey, E. J.; Ensley, H. E.
J. Am. Chem. Soc. 1975, 97, 6908. (i) Wassermann, H. H.;
Lipshutz, B. H. Tetrahedron Lett. 1975, 1731. (j) Kim, M. Y.;
Starrett, J. E.; Weinreb, S. M. J. Org. Chem. 1981, 46, 5383.
(2) For silyl enol ethers, see: (a) Hassner, A.; Reuss, R. H.; Pinnick, H.
W. J. Org. Chem. 1975, 40, 3427. (b) Rubottom, G. M.; Marrero,
R.; Gruber, J. M. Tetrahedron 1983, 39, 861. For organocatalysts
methods, see: (c) Melchiorre, P. Angew. Chem. Int. Ed. 2012, 51,
9748. (d) Vilaivan, T.; Bhanthumnavin, B. Molecules 2010, 15,
917.
(8) The characterization of enol 6 was carried out from a solution
which was partly exposed to the air during the concentration
and contains compounds 3a and 4a. If air was completely
excluded during the preparation of 1H NMR sample, only traces
of 3a and 4a were observed. The full characterization of 6 was
not possible due to significant solvent content of the sample.
Characteristic 1H NMR Resonances of the Enol Intermediate
6.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.15 (m, 5 H), 6.34 (br dd, 1
H, J = 1.4, 5.9 Hz), 3.42 (s, 1 H), 1.51 (d, 3 H, J = 1.5 Hz). For more
details, see Supporting Information.
(9) Kamachi, T.; Shimizu, K.; Yoshihiro, D.; Igawa, K.; Tomooka, K.;
Yoshizawa, K. J. Phys. Chem. C 2013, 117, 22967.
(10) The exothermic background reaction warms the reaction mix-
ture. The amount of the excess Et3SiH increases from 0.03 mmol
to 0.15 mmol in the scaled reaction.
(3) (a) Inoki, S.; Kato, K.; Isayama, S.; Mukaiyama, T. Chem. Lett.
1990, 1869. (b) Magnus, P.; Payne, A. H.; Waring, M. J.; Scott, D.
A.; Lynch, V. Tetrahedron Lett. 2000, 41, 9725.
(4) (a) Tuokko, S.; Pihko, P. M. Org. Process Res. Dev. 2014, 18, 1740.
(b) Benohoud, M.; Tuokko, S.; Pihko, P. M. Chem. Eur. J. 2011, 17,
8404.
(11) No products were lost during the autoxidation, confirmed by
internal standard in 1H NMR analysis.
(5) See the Supporting Information for details.
(6) Preparation of α-Hydroperoxide 4a
(12) Collins, K. D.; Glorius, F. Nat. Chem. 2013, 5, 597.
(13) Transfer hydrogenation with Et3SiD gives the β-deuterated
product 3a in 12:88 H/D ratio in the presence of H2SO4. See ref
4a.
Et3SiH (38 mg, 53 μL, 0.33 mmol, 1.1 equiv) was added to a sus-
pension of α-substituted acrolein (1a, 44 mg, 0.30 mmol, 1.0
equiv), water (20 μL) and Pd/C (5 wt%, 1 mg) in EtOAc (1 mL).
After 4 min of stirring, gas formation was observed, and the
reaction mixture was filtered through a small pad of neutral
(14) For a proposed mechanism, see Supporting Information.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D