Organic Letters
Letter
Notes
a terminal oxidant. The reactions were complete in under 1 h at
rt. However, with phenylacetaldehyde 1g these conditions
proved to be inefficient resulting in a poor conversion.
Oxidative cleavage in 1g could be achieved by replacing NaH
by a combination of KH with 18-crown-6, under the conditions
developed for aliphatic aldehyde 1b (Table 1, entry 16), to
furnish benzaldehyde 2g in 80% yield (Table 2, entry 6).
Moving to the aliphatic series and employing conditions
from Table 1 entry 16, analogues of 1b with different ring sizes,
such as aldehydes 1h and 1i, were successfully converted to the
respective ketones 2h and 2i (entries 8, 9). It is worth noting
that isolation of aliphatic ketones proved to be cumbersome
due to their volatility. Therefore, the ketones of the aliphatic
series were isolated and characterized as their 2,4-dinitrophe-
nylhydrazones. Acyclic aldehydes 1j and 1k exhibited similar
reactivity (entries 10, 11), as did terpene derivatives 1l and 1m
(entries 12, 13).
Aldehyde 1n is the product of a Diels−Alder cycloaddition
between cyclopentadiene and acrolein. The reaction can be
carried out enantioselectively where the aldehyde serves as a
convenient handle for a chiral catalyst.8 In the past, conversion
of the adducts of type 1n to ketones like 2n would require
several synthetic steps.9 Therefore, it was of interest to examine
the oxidative dehomologation of 1n. The reaction proceeded
smoothly yielding ketone 2n in 85% (entry 14), which
represents a considerable shortcut to this valuable synthetic
building block.
Not all the tested substrates reacted well in the oxidative
cleavage reaction. Thus, hydrocinnamyl aldehyde 1o gave a
complex product mixture, where, according to the GC-MS
analysis, conversion to the desired ketone 2o was about 32%
(entry 15). The reason for this anomalous behavior of 1o is not
clear at the moment.
The reaction mechanism has not been investigated, but it is
likely to involve formation of the enolate first, followed by
autoxidation10 and intermediate formation of oxetane, analo-
gously to the route proposed for the cleavage of enamines,4,11
to furnish ketone 2 and a formate salt of Na or K.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank Russian Science Foundation for Grant 15-
13-00092. We also acknowledge RUDN University and the
Ministry of Education and Science of the Russian Federation
(Agreement 02.A03.21.0008) for access to the analytical
facilities (HRMS).
REFERENCES
■
(1) For selected examples on the use of dehomologated products in
total synthesis, see: (a) Baars, H.; Classen, M. J.; Aggarwal, V. K. Org.
Lett. 2017, 19, 6008−6011. (b) Nicolaou, K. C.; Pulukuri, K. K.; Yu,
R.; Rigol, S.; Heretsch, P.; Grove, C. I.; Hale, C. R.; ElMarrouni, A.
Chem. - Eur. J. 2016, 22, 8559−70.
(2) (a) Vetelino, M. G.; Coe, J. W. Tetrahedron Lett. 1994, 35, 219−
222. (b) Wooten, J.; Savitsky, G. B.; Jacobus, J. J. Am. Chem. Soc. 1975,
97, 5027−5028. (c) Huber, J. E. Tetrahedron Lett. 1968, 9, 3271−
3272. (d) Foote, C. S.; Lin, J. W. P. Tetrahedron Lett. 1968, 9, 3267−
3270. (e) Witkop, B. J. Am. Chem. Soc. 1956, 78, 2873−2882.
(f) Slomp, G., Jr.; Shealy, Y. F.; Johnson, J. L.; Donia, R. A.; Johnson,
B. A.; Holysz, R. P.; Pederson, R. L.; Jensen, A. O.; Ott, A. C. J. Am.
Chem. Soc. 1955, 77, 1216−1221.
(3) Havare, N.; Plattner, D. A. Org. Lett. 2012, 14, 5078−5081.
(4) Tiwari, B.; Zhang, J.; Chi, Y. R. Angew. Chem., Int. Ed. 2012, 51,
1911−4.
(5) Sun, H.; Yang, C.; Gao, F.; Li, Z.; Xia, W. Org. Lett. 2013, 15,
624−627.
(6) (a) Althaus, M.; Togni, A.; Mezzetti, A. J. Fluorine Chem. 2009,
130, 702−707. (b) Diaz-Rodriguez, A.; Rios-Lombardia, N.; Sattler, J.
H.; Lavandera, I.; Gotor-Fernandez, V.; Kroutil, W.; Gotor, V. Catal.
Sci. Technol. 2015, 5, 1443−1446. (c) Fraile, J. M.; Garcia, N.;
Mayoral, J. A.; Santomauro, F. G.; Guidotti, M. ACS Catal. 2015, 5,
3552−3561. (d) Fuchs, C. S.; Hollauf, M.; Meissner, M.; Simon, R. C.;
Besset, T.; Reek, J. N. H.; Riethorst, W.; Zepeck, F.; Kroutil, W. Adv.
Synth. Catal. 2014, 356, 2257−2265. (e) Miles, K. C.; Abrams, M. L.;
Landis, C. R.; Stahl, S. S. Org. Lett. 2016, 18, 3590−3593. (f) Babudri,
F.; Cicciomessere, A. R.; Farinola, G. M.; Fiandanese, V.; Marchese,
G.; Musio, R.; Naso, F.; Sciacovelli, O. J. Org. Chem. 1997, 62, 3291−
3298. (g) Qin, Y.; Cheng, Y.; Luo, X.; Li, M.; Xie, Y.; Gao, Y. Synlett
2015, 26, 1900−1904. (h) Shokri, A.; Que, L. J. Am. Chem. Soc. 2015,
137, 7686−7691. (i) Tcho, W.-Y.; Wang, B.; Lee, Y.-M.; Cho, K.-B.;
Shearer, J.; Nam, W. Dalton Trans. 2016, 45, 14511−14515.
(j) Tokunaga, M.; Aoyama, H.; Shirogane, Y.; Obora, Y.; Tsuji, Y.
Catal. Today 2006, 117, 138−140. (k) Tokunaga, M.; Shirogane, Y.;
Aoyama, H.; Obora, Y.; Tsuji, Y. J. Organomet. Chem. 2005, 690,
5378−5382. (l) Van Rheenen, V. Tetrahedron Lett. 1969, 10, 985−988.
(7) (a) Incerti-Pradillos, C. A.; Kabeshov, M. A.; O’Hora, P. S.;
Shipilovskikh, S. A.; Rubtsov, A. E.; Drobkova, V. A.; Balandina, S. Y.;
Malkov, A. V. Chem. - Eur. J. 2016, 22, 14390−6. (b) O’Hora, P. S.;
Incerti-Pradillos, C. A.; Kabeshov, M. A.; Shipilovskikh, S. A.; Rubtsov,
A. E.; Elsegood, M. R.; Malkov, A. V. Chem. - Eur. J. 2015, 21, 4551−5.
(8) (a) Hatano, M.; Mizuno, T.; Izumiseki, A.; Usami, R.; Asai, T.;
Akakura, M.; Ishihara, K. Angew. Chem., Int. Ed. 2011, 50, 12189−92.
(b) Maruoka, K.; Murase, N.; Yamamoto, H. J. Org. Chem. 1993, 58,
2938−2939.
In conclusion, we have developed a mild, facile protocol for
an aerobic oxidative cleavage of C−C bonds in aldehydes
producing the respective ketones. The reaction works well with
a wide range of aldehydes. It avoids the use of transition metals
catalysts, and the only byproduct generated during the reaction
is a water-soluble alkali formate.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
1
Experimental procedures; H and 13C NMR spectra for
(9) (a) Corey, E. J.; Loh, T. P. J. Am. Chem. Soc. 1991, 113, 8966−
8967. (b) Corey, E. J.; Ravindranathan, T.; Terashima, S. J. Am. Chem.
Soc. 1971, 93, 4326−4327.
AUTHOR INFORMATION
■
(10) Hammond, C. J.; Lindsay Smith, J. R.; Nagatomi, E.; Stark, M.
S.; Waddington, D. J. New J. Chem. 2006, 30, 741.
Corresponding Authors
(11) Zhang, C.; Xu, Z.; Shen, T.; Wu, G.; Zhang, L.; Jiao, N. Org.
Lett. 2012, 14, 2362−5.
ORCID
C
Org. Lett. XXXX, XXX, XXX−XXX