Concerning Tishchenko-like side products in oxidation of hydroxymethyl to formyl groups

Article abstract of DOI:10.1055/s-2003-39307

Oxidation of a hydroxymethyl group to an aldehyde sometimes gives a dimeric ester reminiscent of a Tishchenko aldehyde-ester disproportionation. This process has been observed only with Cr(VI)/pyridine based reagents, and can be avoided most notably by us

Full text of DOI:10.1055/s-2003-39307

LETTER
1067
Concerning Tishchenko-Like Side Products in Oxidation of Hydroxymethyl to
Formyl Groups
T
ishchenko-like
h
S
ide Produ
i
cts in O
w
xidation of Hydro
e
xymethyl to
i
Formyl
GroG
Bert Fraser-Reid*b
a
Synthon Chiragenics, 7 Deer Park Drive, Monmouth Junction, NJ 08852, Department of Chemistry, Michigan State University,
East Lansing, MI-48824, USA
E-mail: kumar@synthoncorp.com
b
Natural Products and Glycotechnology Research Institute, Inc., (NPG), 4118 Swarthmore Road, Durham, North Carolina, 27706, USA
E-mail: Dglucose@aol.com
Received 16 April 2003
HO
O
Abstract: Oxidation of a hydroxymethyl group to an aldehyde
sometimes gives a dimeric ester reminiscent of a Tishchenko alde-
hyde-ester disproportionation. This process has been observed only
with Cr(VI)/pyridine based reagents, and can be avoided most nota-
bly by using Dess–Martin and Swern (DMSO/COCl2) reagents.
+1
CH2OH
CHO
O
O
R
2
R
R
R
R
R
4
3
1
Key words: Tishchenko, Cr(VI)/pyridine based reagents, oxidation
O
O
O
O
(c)
(a)
R=
(b)
R=
R=
A recent Letter by Ermolenko, Sasaki and Potier1 to Syn-
lett concerning the oxidative coupling 1→4, depicted in
Scheme 1 prompts us to report related observations in our
laboratories. In 1975, one of us2 reported the anomalous
oxidative dimerization of glycosides 1a and 1b upon treat-
ment with CrO3·2C5H5N, prepared before hand or in situ,
during attempts to obtain the corresponding aldehydes 2a
and 2b. The major products obtained by us2 were esters 4a
and 4b, and we suggested hemiacetals, such as 3 as inter-
mediates. The recent letter by Sasaki and co-workers,1
reporting similar observations for oxidation of the iso-
propylidene glycerol 1c with PCC or PDC, indicates that
such oxidative dimerizations may not be as ‘anomalous’
as was thought in 1975.2 Indeed, this conclusion is ap-
parent from the cases cited below for the butane triol de-
rivatives (Scheme 2).
OAc
Scheme 1
OEt
OAc
OEt
A common structural feature of the substrates in
Scheme 1 is the presence of an oxygen a- to the hy-
droxymethyl function. In 1975 we had rationalized that
the electron withdrawing effect of the a-oxygen upon the
initially formed aldehyde 2 would facilitate ready forma-
tion of a hemiacetal, 3, as a precursor to 4.2 Sasaki and co-
workers1 also proposed an hemiacetal as an intermediate.
That rationalization was seemingly upheld by the present-
ly-reported observations that PCC oxidations of the ben-
zylidene and ethylidene derivatives 5a3 and 5b, led to
R
R
O
R
H
PCC, NaOAc
R
OH
+
CH2Cl2
Molecular sieves
O
O
6
5
7
Ph
O
O
O
O
(a)
(b) R=
R=
Ph
(e) R=
(c)
R=
O
R=
(d)
O
O
O
O
O
Scheme 2
Synlett 2003, No. 7, Print: 02 06 2003.
Art Id.1437-2096,E;2003,0,07,1067,1069,ftx,en;S02103ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1068
Z. Guo et al.
LETTER
aldehyde 6a and ester 7a respectively in 1:19 and 0:1 by Sasaki and us with oxidations of 1 and 5 by several
ratios [Table 1, entries (i) and (ii)].
other reagents, dimerization was observed only with
Cr(VI)/pyridine based reagents.10,11 Indeed Sasaki and co-
workers found that a 5:2 ratio of the desired aldehyde 2c
and ester 4c was optimum for various Cr(VI) reagents that
were tried.1
However, that the a-oxygen is not necessary for dimeriza-
tion to occur is apparent from entries (iii)–(vi). Thus sub-
strates 5c, 5d, and 5e, which contain hydroxyethyl
residues, also gave appreciable amounts of dimeric esters
(e.g. 7). The nucleofugal character of aldehyde 6d was In light of the transition metal connection, it is noteworthy
also evident in the attempted DIBALH reduction of ester that use of the Swern DMSO–oxalyl chloride12 reagent af-
8, which afforded the Claisen condensation product 9 forded a 75% yield of 6a (Table, entry vii). Similarly,
(Scheme 3).
Dess–Martin Periodinane13 oxidation of 5a14 gave a 72%
yield of 6a (Table 1, entry viii).
Table 1 Oxidation of some Hydroxymethyl-containing Substrates:
Avoidance of Tishchenko-Like Dimerization Products
It therefore appears that the Tishchenko-like ester forma-
tion in oxidation of primary alcohols can be avoided by
refraining from using Cr(VI)-based reagents.
Entry
(i)
Substrate Oxidant
Ratio 6:7 Overall
yield
5a
5b
5c
5d
5d
5e
5b
5b
PCC, NaOAc
CH2Cl2
–:1
1:19
3:1
7:3
3:7
3:7
1:–
1:–
20%
33%
15%
12%
23%
33%
75%
75%
References
(1) Ermolenko, L.; Sasaki, N. A.; Potier, P. Synlett 2001, 1565.
(2) Yunker, M. B.; Fraser-Reid, B. J. Chem. Soc., Chem.
Commun. 1975, 61.
(ii)
PCC, NaOAc
CH2Cl2
(3) Synthesis of Ester 7b from 5b with PCC: To a stirred
mixture of PCC (129.4 g), sodium acetate (49.2 g),
molecular sieves (120 g) in CH2Cl2 (600 mL) at ambient
temperature was added a solution of alcohol 5b (38.8 g) in
100 mL of CH2Cl2. After 5 h, the mixture was filtered
through a pad of Celite and washed with CH2Cl2. The
combined filtrate and washings was passed through a pad of
celite and a pad of silica gel. Removal of the solvent by
rotatory evaporation gave 50 g crude product mixture with a
6b:7b ratio of 1:19 estimated by 1H NMR. Pure 7b (5.2 g)
was obtained from 10 g of the crude product mixture by flash
chromatography eluted with hexane–EtOAc (7:3). 1H NMR
(CDCl3): d = 7.2–7.3 (m, 10 H), 5.3–5.5 (2 s, 2 H), 3.6–4.6
(m, 10 H), 1.2–2.2 (m, 6 H) ppm. 13C NMR (CDCl3): d =
170.5, 139.0, 138.5, 129.5 (2 C), 129.38 (2 C), 128.74 (2 C),
126.85 (2 C), 126.68 (2 C), 101.78, 101.69, 75.95, 75.16,
67.49, 67.13, 67.03, 28.75, 28.00 ppm. GC-MS: 384 (M).
(4) Tishchenko, J. Russ. Phys. Chem. Soc. 1906, 38, 355.
(5) (a) Saegusa, T.; Ueshima, T. J. Org. Chem. 1968, 33, 3310.
(b) Buehler, C. A.; Pearson, D. E. Survey of Organic
Synthesis, Vol. 2; John Wiley and Sons: New York, 1977,
754. (c) March, J. Advanced Organic Chemistry, 4th ed;
John Wiley and Sons: New York, 1992, 235.
(6) Ito, J.; Horino, H.; Koshiro, Y.; Yamamoto, A. Bull. Chem.
Soc. Jpn. 1982, 55, 504.
(7) For a review see: Geissman, T. A. Org. React. 1944, 2, 94.
(8) Stapp, P. R. J. Org. Chem. 1973, 38, 1433.
(9) Yamashita, M.; Watanbe, Y.; Mitsudo, T.; Takegami, Y.
Bull. Chem. Soc. Jpn. 1976, 49, 3597.
(10) Corey, E. J.; Schmidt, G. Tetrahedron Lett. 1979, 5, 399.
(11) Piancatelli, G.; Scettri, A.; D’Aure, M. Synthesis 1982, 245.
(12) Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem.
1978, 47, 2480.
(iii)
(iv)
(v)
PCC, NaOAc
CH2Cl2
PCC, NaOAc
CH2Cl2
PCC, NaOAc
CH2Cl2
(vi)
(vii)
(viii)
PCC, NaOAc
CH2Cl2
DMSO
COCl2
Dess–Martin
In the 1975 publication, we suggested that the ester-for-
mation was reminiscent of a Tischenko aldehyde-ester
disproportionation.4,5 Although the mechanism proposed
for the reaction6 involves an intramolecular hydride trans-
fer, the Tishchenko reaction occurs readily in aldehydes
with an a-hydrogen-unlike in Canizzarro reactions.7 In-
deed we now report relevant examples in Table 1, entries
(iii)–(iv).
Furthermore, it is notable that the Tishchenko-coupling7
can be induced by a variety of ‘complexation’ catalysts in-
cluding boric acid,8 iron carbonyls,9 and hydroruthenium
complexes.6 In view of this fact, it is noteworthy that al-
though ‘difficulties’ and/or poor yields were experienced
OH
O
O
O
+8
O
O
DIBAL-H
6d
O
CO2Me
CO2Me
9
8
Scheme 3
Synlett 2003, No. 7, 1067–1069 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
Tishchenko-Like Side Products in Oxidation of Hydroxymethyl to Formyl Groups
1069
(13) Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem.
1999, 64, 4537.
and washed with EtOAc. The combined filtrate and
washings was washed with 100 mL of sat. NaHCO3 and 100
mL of brine, dried over Na2SO4 (200 g) overnight, filtered,
concentrated to dryness under reduced pressure. The residue
was purified on 350 g of silica gel eluted with hexane–
EtOAc 1/0 to 7/3 to give 24.8 g of aldehyde 6b in 72% yield.
1H NMR (CDCl3): d = 9.62 (s, 1 H), 7.2–7.6 (m, 5 H), 5.50
(s, 1 H), 4.1–4.3 (m, 2 H), 3.75–3.85 (m, 1 H), 1.6–2.0 (m, 2
H) ppm. 13C NMR (CDCl3): d = 200.68, 138.52, 129.69,
128.86 (2 C), 126.77 (2 C), 101.63, 80.88, 66.94, 26.40. GC-
MS: 192 (M).
(14) Synthesis of Aldehyde 6b from 6b with Dess–Martin
Periodinane: To a stirred mixture of alcohol 5b (35 g),
pyridine (87 mL) and anhyd DCM (500 mL) was added a
cooled solution of DMP (15 wt% in CH2Cl2, 1000 mL) in 20
min. The mixture was stirred at ambient temperature for 22
h. The reaction mixture was concentrated to 500 mL under
reduced pressure, then diluted with 2 L of EtOAc followed
by 100 mL of aq 2 M NaOH. After stirred for 1 h, the white
precipitate was removed by filtration through a pad of Celite
Synlett 2003, No. 7, 1067–1069 ISSN 1234-567-89 © Thieme Stuttgart · New York