Chemistry Letters 2001
713
(Entries 3–6). Interestingly, N-mesylbenzhydrylideneamine
which was formed after oxidation of N-mesylbenzhydrylamine
was difficult to be hydrolyzed with aqueous HCl solution and
98% of the imine was isolated after purification with silica gel-
column chromatography. On the other hand, one-pot hydroly-
sis of N-mesylbenzhydrylideneamine was smoothly carried out
by using 10% aqueous NaOH solution and benzophenone was
isolated in 98% yield. It was noted that N-mesyl ketimines
were readily formed by the present oxidation of N-mesyl
amines (Table 1, Entries 5–7), though it was previously report-
ed that oxidation of secondary amines giving N-alkyl ketimines
did not proceed smoothly by using 1 and DBU.1
Linear primary amines such as octylamine and 3-phenyl-
propylamine, however, were not effectively oxidized to the cor-
responding aldehydes by the above method probably due to the
instability of formed N-mesyl aldimines4 under the present oxi-
dation conditions (Table 1, Entries 8 and 9). Other nitrogen
substituents such as dimethylphosphinyl, 2-nitrobenzene-
sulfenyl, and 2-pyridyl groups were further examined, and alkyl
groups were found to be better than electron-withdrawing ones.
Then, cyclohexyl group5 was chosen as a promising alkyl sub-
stituent as it was directly introduced to primary amines under
reductive conditions.6 The desirable oxidation at primary alkyl
groups of N-cyclohexylated linear primary amines was also
thought to take place selectively even in the presence of cyclo-
hexyl group because of the steric reasons.
The oxidative deamination of 3-phenylpropylamine to
afford 3-phenylpropanal was improved up to 98% by changing
nitrogen substituents from mesyl (33%) to cyclohexyl group.
Various linear primary amines were also successfully employed
in the oxidative deamination which consisted of N-cyclohexyla-
tion, oxidation, and hydrolysis (Table 2). Most of N-cyclo-
hexylations of linear primary amines were carried out by using
cyclohexanone and NaBH(OAc)3,6a and all of N-cyclohexyl
secondary amines (5) were oxidized smoothly at –78 °C by the
combined use of 1 and DBU. Formed N-cyclohexyl aldimines
were hydrolyzed in a one-pot manner by using 10% aqueous
citric acid to give linear aldehydes in good yields. It was noted
that protecting groups such as acetonide, trityl, and ester groups
were kept safely during these reactions.
General experimental procedure is as follows: (Oxidation
of N-mesyl amines, Table 1): under argon atmosphere, a solu-
tion of 1 (1.08 mmol) in CH2Cl2 was added to a stirred mixture
of N-mesyl amines (0.54 mmol) and DBU (1.08 mmol) in
CH2Cl2 (3.0 mL) at –78 °C. The reaction mixture was stirred
for 1 h at –78 °C and quenched by adding 1 M HCl solution
(2.0 mL) and ether (20 mL). After stirring the mixture at room
temperature, yields of carbonyl products were determined by
GC-analysis. (Oxidation of N-cyclohexyl amines, Table 2): the
oxidation of N-cyclohexyl amines was carried out as described
above for 30 min at –78 °C and was quenched by adding 10%
aqueous citric acid solution (2 mL). After the resulting mixture
was stirred for 1 h at room temperature, linear aldehydes were
isolated by the usual work-up procedure.
The present work was partially supported by Grant-in-Aids
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and Notes
1
T. Mukaiyama, A. Kawana, Y. Fukuda, and J. Matsuo,
Chem. Lett., 2001, 390.
2
Review: R. J. Baumgarten, J. Chem. Educ., 43, 398 (1966).
Recent reports: R. V. Hoffman and A. Kumar, J. Org.
Chem., 49, 4011 (1984) and references are cited therein.
R. W. Layer, Chem. Rev., 63, 489 (1963).
a) F. Chemla, V. Hebbe, and J-F. Normant, Synthesis,
2000, 75. b) J. Sisko and S. M. Weinreb, J. Org. Chem.,
55, 393 (1990).
3
4
5
The N-cyclohexyl group was used as a nitrogen substituent
for thermal elimination of sulfinamides. However, only
benzylic amines were dehydrogenated by that method and
rather high temperatures were needed for the elimination
reaction. See: B. M. Trost and G. Liu, J. Org. Chem., 46,
4617 (1981).
6
a) A. F. Abdel-Magid, C. A. Maryanoff, and K. G. Carson,
Tetrahedron Lett., 39, 5595 (1990). b) R. F. Borch, M. D.
Bernstein, and H. D. Durst, J. Am. Chem. Soc., 93, 2897
(1971).