Degradation of aldehydes to one carbon lower homologs

Article abstract of DOI:10.1016/S0040-4039(03)00695-6

Degradation of aldehydes to one carbon lower homologs has been achieved by using a mixture of N-methylmorpholine, N-methylmorpholine N-oxide, a catalytic amount of OsO₄ and NaIO₄ in a mixture of acetone/H₂O.

Full text of DOI:10.1016/S0040-4039(03)00695-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3613–3615
Degradation of aldehydes to one carbon lower homologs
Damien Belotti, Ga e¨ lle Andreatta, Fabienne Pradaux, Samir BouzBouz and Janine Cossy*
Laboratoire de Chimie Organique associ e´ au CNRS, ESPCI, 10 rue Vauquelin, 75231-Paris Cedex 05, France
Received 6 March 2003; revised 12 March 2003; accepted 14 March 2003
Abstract—Degradation of aldehydes to one carbon lower homologs has been achieved by using a mixture of N-methylmorpholine,
N-methylmorpholine N-oxide, a catalytic amount of OsO and NaIO in a mixture of acetone/H O. © 2003 Elsevier Science Ltd.
4
4
2
All rights reserved.
In the aim of synthesizing the C –C fragment of
9
17
1
leucascandrolide, we needed to transform compound 1
to aldehyde 2 (Scheme 1). The oxidative cleavage of the
double bond by using OsO (0.05 equiv.) in the pres-
4
ence of N-methylmorpholine N-oxide (NMO) (1.7
equiv.) in a mixture of acetone/H O (3/1) followed by
2
the addition of NaIO (2 equiv.) was quite surprising
4
as, after 14 hours, a mixture of two aldehydes was
obtained: the expected aldehyde 2 in low yield (18%)
and the one carbon lower homolog, aldehyde 3, which
was isolated in 20% yield. Under similar conditions, the
protected homoallylic alcohol 4 led to two aldehydes 5
and 6. Aldehyde 5 was isolated in 36% yield and its
corresponding lower homolog, aldehyde 6, was also
isolated in 36% yield (Scheme 1).
The a-substituted aldehydes 3 and 6 are probably
formed respectively from aldehydes 2 and 5. Under
these oxidative conditions, aldehydes of type A are
probably in equilibrium with enol intermediates of type
B in the presence of N-methylmorpholine (NMM) lib-
erated in the reaction media. These enol intermediates
are then dihydroxylated by NMO/OsO4 to produce
intermediates of type C which are probably cleaved by
NaIO to produce aldehyde D (Scheme 2).
4
To verify this hypothesis, aldehyde 5 was treated with
NMM (1 equiv.), NMO (2 equiv.), a catalytic amount
of OsO (0.05 equiv.) and NaIO (4 equiv.) in acetone/
4
4
H O (10/1) at room temperature. Under these condi-
2
tions, aldehyde 5 was transformed to 6 in good yield
2
(
58%) (Scheme 3).
*
0
Corresponding author. Tel.: +33-1-4079-4429; fax: +33-1-4079-4660;
e-mail: janine.cossy@espci.fr
Scheme 1.
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00695-6

3
614
D. Belotti et al. / Tetrahedron Letters 44 (2003) 3613–3615
Scheme 3.
previously3 observed by using copper-catalyzed
oxidation but, to our knowledge, only one method
which corresponds to the degradation of aldehydes to
one carbon lower homologs has been reported in the
4
litterature. This process consists in the treatment of an
Scheme 2.
aldehyde with iodine bromide followed by the treat-
ment of the resulting a-bromoaldehyde with potassium
hydroxide, and the obtained hydrate of a-hydroxyalde-
hyde was cleaved by sodium periodate. This procedure
was applied to the degradation of the side chain of
This oxidative one-pot process transformation of alde-
hydes to one carbon lower homologs is not a common
process. A complete degradation of unbranched alde-
hydes to acetaldehyde and formate units has been
4
cholanic aldehyde.
Table 1. Degradation of aldehydes to one carbon lower homologs

D. Belotti et al. / Tetrahedron Letters 44 (2003) 3613–3615
3615
a-Substituted aldehydes and particularly chiral
a-hydroxyaldehydes can be prepared very easily by
degradation of protected b-hydroxyaldehydes. These
latter compounds are very useful synthons and their use
in the elaboration of biological active compounds will
be reported in due course.
Due to the importance of a-substituted aldehydes in
synthesis, the easy NMM/NMO/OsO and NaIO one-
pot procedure for the oxidative cleavage of aldehydes
has been applied to aldehydes 7–13. The results are
reported in Table 1.
4
4
When aldehydes 7–13 were treated by NMM/NMO/
OsO4 and NaIO , the respective one carbon lower
homologs 14–20 were isolated in yields higher than
4
References
5
0%. It is worth noting that the presence of a quater-
1
. (a) D’Ambrosio, M.; Guerriero, A.; Debitus, C.; Pietra, F.
Helv. Chim. Acta 1996, 79, 51–59; (b) Guella, G.; Mancini,
I.; Chiasera, G.; Pietra, F. Helv. Chim. Acta 1989, 72,
nary center (compounds 14–16) as well as the presence
of a protected hydroxy group (compounds 17–20)
avoids further enolisation in aldehydes 14–20. It has
been also verified that an a-alkyl substituted aldehyde
such as 21 was not transformed to ketone 22 under
these oxidative conditions (Scheme 4).
237–245.
2
. General procedure: To a stirred solution of b-substituted
aldehyde (2 mmol), N-methylmorpholine (0.22 mL, 2
mmol) and N-methylmorpholine N-oxide (0.47 g, 4 mmol)
in acetone/water (30 mL/3 mL) were added a 4% osmium
tetroxide solution in water (0.64 mL, 0.1 mmol of OsO4)
and, after 10 min, sodium periodate (1.71 g, 8 mmol). The
resulting suspension was stirred for 24 h (TLC or GC/MS
monitoring) and then filtered through Celite, which was
washed with acetone. The solvent was evaporated in vacuo
and the residue was taken up with ethyl acetate (50 mL)
and washed with water (10 mL). The organic layer was
Scheme 4.
dried over MgSO and concentrated in vacuo. The residue
4
was purified by flash chromatography on silica gel to give
These oxidative conditions are very mild as a t-
butyldimethylsilyl protecting group was tolerated. Fur-
thermore, no epimerization of the stereogenic center
was observed when a-substituted aldehydes were
formed from b-substituted aldehydes (Table 1, entries 6
and 7).
the a-substituted aldehyde.
3. Brackman, W.; Gaasbeek, C. J.; Smit, P. J. Rec. Trav.
Chim. Pays-Bas 1966, 85, 437–445.
4. (a) Yanuka, Y.; Katz, R.; Sarel, S. J. Chem. Soc., Chem.
Commun. 1968, 851–852; (b) Yanuka, Y.; Katz, R.; Sarel,
S. Tetrahedron Lett. 1970, 11, 5229–5232.