SmI(2)-promoted oxidation of aldehydes in the presence of electron-rich heteroatoms.

Article abstract of DOI:10.1021/ol027095p

[reaction: see text] The Evans-Tishchenko reaction provides an efficient and practical solution for the oxidation of aldehydes possessing sensitive electron-rich heteroatoms to the corresponding esters. Careful selection of the sacrificial beta-hydroxy ke

Full text of DOI:10.1021/ol027095p

ORGANIC
LETTERS
2
002
Vol. 4, No. 25
539-4541
SmI -Promoted Oxidation of Aldehydes
in the Presence of Electron-Rich
Heteroatoms
2
4
Amos B. Smith, III,* Dongjoo Lee, Christopher M. Adams, and
Marisa C. Kozlowski*
Department of Chemistry, Laboratory for Research on the Structure of Matter,
Monell Chemical Senses Center, and Roy and Diana Vagelos Laboratories,
UniVersity of PennsylVania, Philadelphia, PennsylVania 19104
smithab@sas.upenn.edu
Received October 12, 2002
ABSTRACT
The Evans−Tishchenko reaction provides an efficient and practical solution for the oxidation of aldehydes possessing sensitive electron-rich
heteroatoms to the corresponding esters. Careful selection of the sacrificial â-hydroxy ketone provides considerable subsequent flexibility to
access the desired carboxylic acid.
The oxidation of aldehydes to carboxylic acids or related
congeners is one of the most common reactions in synthetic
organic chemistry. Although a large variety of reagents have
Scheme 1
1
been developed, oxidations in the presence of electron-rich
heteroatoms (i.e. S, Se, N, P) can prove to be challenging.
Our long-term interest in the use of 1,3-dithianes as an
effective linchpin for constructing architecturally complex
2
natural and unnatural products has revealed the critical need
for a reliable method for oxidizing aldehydes in the presence
3
of sulfur.
2
In 1990, Evans and co-workers introduced the SmI -
catalyzed Tishchenko reaction, a process involving reduction
of â-hydroxy ketones via hydride transfer from a sacrificial
aldehyde for the stereoselective elaboration of anti 1,3-diols
4
reaction conditions might prove to be useful for the oxidation
of aldehydes in the presence of electron-rich heteroatoms.
(Scheme 1). Alternatively, this reaction can be viewed as
an oxidation of an aldehyde via hydride transfer to a
sacrificial hydroxy ketone. We reasoned that these mild
4
Pleasingly, treatment of â-hydroxy ketone 1a with 1 equiv
5
of dithiane aldehyde 2 and 20 mol % SmI
°
2
in THF at -10
*
To whom correspondence should be addressed.
1) ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 7.
6
C results in the formation of ester 3a in high yield (Scheme
(
2).
1
0.1021/ol027095p CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/12/2002

Scheme 2
Table 2. Formation of Acid 4 from Esters 3a-f
entry ester
conditions
yield (%)
1
2
3
4
5
6
7
8
9
0
1
3a LiOH, aqueous MeOH, rt, 5 h
3a SO3‚Pyr, Et3N, DMSO, then DBU
3b LiOH, aqueous MeOH, rt, 4 h
95
86
96
94
90
70
89
92
95
75
92
To make this tactic synthetically useful, we explored the
use of a series of â-hydroxy ketones, each offering a different
method for liberation of the required carboxylic acid. A
number of racemic â-hydroxy ketones (1a-f) were prepared
from inexpensive commercially available ketones and alde-
3c LiOH, aqueous MeOH, rt, 2.5 h
3d Pd(PPh3)4, morpholine, THF, rt, 1 h
3d Rh(PPh ) Cl, aqueous EtOH, 80 °C, 3-5 h
3
3
7
hydes via the aldol reaction. In each case, 1 equiv of
3d LiOH, aqueous MeOH, rt, 2 h
3e BF3‚Et2O, 1,3-propanedithiol, rt
3e LiOH, aqueous MeOH, rt, 2 h
3f DDQ, aqueous DMSO, 80 °C, 1 h
3f LiOH, aqueous MeOH, 2.5 h
â-hydroxy ketones (1a-f) reacted smoothly, and in good
yield, with 1 equiv of dithiane aldehyde 2 to furnish the
desired esters (Table 1).
1
1
Table 1. Oxidation of Aldehyde 2 with Various â-Hydroxy
Ketones
2
). Treatment of 3a-f with LiOH/aqueous MeOH afforded
acid 4 in high yield (entries 1, 3, 4, 7, 9, 11, Table 2).
8
Alternatively, Parikh-Doering oxidation of the secondary
hydroxyl in 3a, followed by â-elimination using DBU,
afforded the desired carboxylic acid 4 in one pot (entry 2,
Table 2). Carboxylic acid 4 could also be liberated from allyl
ester 3d either via Rh-catalyzed isomerization of the allyl
9
group, followed by heating at reflux in aqueous ethanol
(
9
entry 6, Table 2) or by a Pd-catalyzed allyl transfer to
entry
R
product
time (min)
yield (%)
morpholine in THF at room temperature (entry 5, Table 2);
both reactions are quite mild and proceed in good to excellent
yield. Benzyl ester 3e could also be converted to 4 in 92%
1
2
3
4
5
6
i-Pr
Et
Me
3a
3b
3c
3d
3e
3f
60
45
60
45
60
15
89
78
67
75
85
80
yield via treatment with 1,3-propanedithiol in the presence
CHdCH2
Ph
p-MeOPh
10,11
of boron trifluoride etherate
(entry 8, Table 2). Finally,
1
2
oxidative-cleavage employing DDQ in DMSO furnished
carboxylic acid 4 from PMB ester 3f in good yield (entry
1
0, Table 2).
With the desired esters in hand, various means for
liberation of the carboxylic acid were investigated (Table
We next turned our attention to aldehydes containing other
electron-rich heteroatoms. Aldehydes (5a-d) were prepared7
and reacted in a similar fashion with 1 equiv of 1a in the
presence of 20 mol % SmI (Table 3). In all cases, the
2
reaction reliably furnished the desired ester in good yield.
For phenylselenyl aldehyde 5a the reaction temperature was
reduced to -15 °C to prevent decomposition. Aldehyde 5c,
(
2) (a) Smith, A. B., III; Guaciaro, M. A.; Schow, S. R.; Wovkulich, P.
M.; Toder, B. H.; Hall, T. W. J. Am. Chem. Soc. 1981, 103, 219. (b) Smith,
A. B., III; Dorsey, B. D.; Visnick, M.; Maeda, T.; Malamas, M. S. J. Am.
Chem. Soc. 1986, 108, 3110. (c) Smith, A. B., III; Chen, K.; Robinson, D.
J.; Laasko, L. M.; Hale, K. J. Tetrahedron Lett. 1994, 35, 4271. (d) Smith,
A. B., III; Qiu, Y.; Jones, D. R.; Kobayashi, K. J. Am. Chem. Soc. 1995,
17, 12011. (e) Smith, A. B., III; Condon, S. M.; McCauley, J. A.; Leazer,
J. L., Jr.; Leahy, J. W.; Maleczka, R. J., Jr. J. Am. Chem. Soc. 1997, 119,
62. (f) Smith, A. B., III; Boldi, A. M. J. Am. Chem. Soc. 1997, 119, 6925.
g) Smith, A. B., III; Condon, S. M.; McCauley, J. A. Acc. Chem. Res.
998, 37, 35-46. (h) Smith, A. B., III; Friestad, G. K.; Barbosa, J.;
1
9
(
1
(6) Stereochemical assignments of ester 3a have been identified by
comparison of the spectral data of its diol obtained by methanolysis
(K2CO3/MeOH) with those of both known anti-1,3 diol and syn-1,3 diol.
(7) Experimental procedures for the synthesis of all new compounds can
be found in Supporting Information.
(8) Parikh, J. R.; von Doering, W. E. J. Am. Chem. Soc. 1967, 89, 5505.
(9) (a) Kunz, H.; Waldmann, H. HelV. Chim. Acta 1985, 68, 618. (b)
Kunz, H.; Waldmann, H. Angew. Chem., Int. Ed. Engl. 1984, 23, 71. (c)
Jeffrey, P. D.; McCombie, S. W. J. Org. Chem. 1982, 47, 587-590.
(10) (a) Nakamura, H.; Arata, K.; Wakamatsu, T.; Ban, Y.; Shibasaki,
M. Chem. Pharm. Bull. 1990, 38, 2435. (b) Node, M.; Hori, H.; Fujita, E.
J. Chem. Soc., Perkin Trans. 1 1976, 2237.
Bertounesque, E.; Hull, K. G.; Iwashima, M.; Qiu, Y.; Salvatore, B. A.;
Spoors, P. G.; Duan, J. J.-W. J. Am. Chem. Soc. 1999, 121, 10468. (i) Smith,
A. B., III; Lin, Q. Y.; Doughty, V. A.; Zhuang, L.; McBriar, M. D.; Kerns,
J. K.; Brook, C. S.; Murase, N.; Nakayama, K. Angew. Chem., Int. Ed.
2
001, 40, 196. (j) Smith, A. B.; Doughty, V. A.; Sfouggatakis, C.; Bennett,
C. S.; Koyanagi, J.; Takeuchi, M. Org. Lett. 2002, 4, 783. (k) Smith, A.
B., III; Pitram, S. M. Org. Lett. 1999, 1, 2001. (l) Smith, A. B., III; Pitram,
S. M.; Gaunt, M. J.; Kozmin, S. A. J. Am. Chem. Soc. In press.
(3) Smith, A. B., III; Adams, C. A.; Barbosa, S. A. L.; Degnan, A. P. J.
Am. Chem. Soc. Submitted for publication.
(11) Attempts at Pd-mediated hydrogenolysis proved to be unsuccessful,
presumably due to sulfur poisoning of the catalyst.
(12) Yoo, S.-E.; Kim, H. R.; Yi, K. Y. Tetrahedron Lett. 1990, 31, 5913.
(4) Evans, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990, 112, 6447.
5) Konosu, T.; Oida, S. Chem. Pharm. Bull. 1993, 41, 1012.
(
4540
Org. Lett., Vol. 4, No. 25, 2002

on the other hand, required longer reaction times and slightly
higher temperature, presumably due to the steric bulk of the
gem-dimethyl substitution R to the aldehyde group. Finally,
aldehyde (+)-5e (Table 3), a model system used in our (+)-
Table 3. Oxidations in the Presence of S, Se, N, P, and Sn
1
3,14
15
tedanolide
and (+)-13-deoxytedenolide synthetic ven-
3
ture, was also successfully oxidized in 70% yield.
In summary, the Evans-Tishchenko reaction provides an
efficient and practical solution for the oxidation of aldehydes
possessing sensitive electron-rich heteroatoms to esters.
Importantly, careful selection of the sacrificial â-hydroxy
ketone provides considerable flexibility to liberate the desired
carboxylic acid.
Acknowledgment. Support was provided by the National
Institutes of Health (Institute of General Medical Sciences)
through Grant GM-29028 and 3-Dimensional Pharmaceuti-
cals, Inc., for a Graduate Fellowship (C.M.A.)
Supporting Information Available: Spectroscopic and
analytical data, as well as experimental details for compounds
1
b, 1d, 1f, 3a-f, 4, 5b, 5d, 5e, and 6a-f. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL027095P
(13) Schmitz, F. J.; Gunasekera, S. P.; Yalamanchili, G.; Hossain, M.
B.; van der Helm, D. J. Am. Chem. Soc. 1984, 106, 7251.
(
14) Smith, A. B., III; Lodise, S. A. Org. Lett. 1999, 1, 1249.
(15) Fusetani, N.; Sugawara, T.; Matsunaga, S.; Hirota, H. J. Org. Chem.
1991, 56, 4971.
Org. Lett., Vol. 4, No. 25, 2002
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