A simple and efficient L-prolinamide-catalyzed α-selenenylation reaction of aldehydes

Article abstract of DOI:10.1021/ol0488946

An efficient and simple L-prolinamide-catalyzed α-selenenylation reaction of aldehydes with N-(phenylseleno)phthalimide has been developed for the efficient preparation of a-phenylselenoaldehydes. Such compounds are versatile building blocks for the synth

Full text of DOI:10.1021/ol0488946

ORGANIC
LETTERS
2
004
Vol. 6, No. 16
817-2820
A Simple and Efficient
2
L-Prolinamide-Catalyzed
r-Selenenylation Reaction of Aldehydes
Wei Wang,* Jian Wang, and Hao Li
Department of Chemistry, UniVersity of New Mexico,
Albuquerque, New Mexico 87131-0001
wwang@unm.edu
Received June 11, 2004
ABSTRACT
An efficient and simple L-prolinamide-catalyzed r-selenenylation reaction of aldehydes with N-(phenylseleno)phthalimide has been developed
for the efficient preparation of r-phenylselenoaldehydes. Such compounds are versatile building blocks for the synthesis of r,â-unsaturated
aldehydes, allylic alcohols, and amines.
1
R-Selenoaldehydes are useful synthetic intermediates. The
selenoxide elimination reaction of R-selenoaldehydes is a
powerful, mild method for the preparation of R,â-unsaturated
aldehydes.1 Oxidation of these substances, followed by 2,3-
sigmatropic rearrangement, serves as a versatile route to
and in the latter case, the preformation of an enamine from
an aldehyde with piperidine is necessary. Herein, we wish
to report the first high-yielding (76-95%), catalytic R-se-
lenenylation reaction of aldehydes, catalyzed by the L-
prolinamide.
,2
3
4
allylic alcohols and amines. Several methods for preparing
In recent years, proline-represented small organic molecule
R-selenoaldehydes have been reported, including formylation
organocatalysts have emerged as a new frontier in organic
5
9-19
of R-lithioselenides, direct selenenylation of simple alde-
synthesis.
Proline and its derivatives have been used to
6
hydes, and R-selenenylation of aldehydes promoted by acid
promote a variety of organic reactions of enolizable carbonyl
7
8
(
p-TsOH) or base (piperidine). However, both methods
(9) For reviews of proline-catalyzed reactions, see: (a) List, B. Tetra-
require the use of stoichiometric amounts of acid and base,
hedron 2002, 58, 5573. (b) Gr o¨ ger, H.; Wilken, J. Angew. Chem., Int. Ed.
2
001, 40, 529. (c) Duthaler, R. O. Angew. Chem., Int. Ed. 2003, 42, 975.
(10) For a general review on organocatalysis, see: Dalko, P. I.; Moisan,
(1) (a) Back, T. G. Organoselenium Chemistry: A Practical Approach;
Oxford University Press: New York, 1999. (b) Paulmier, C. Selenium
Reagents and Intermediates in Organic Synthesis; Pergamon Press: Oxford,
L. Angew. Chem., Int. Ed. 2001, 40, 3726.
(11) For a review of amino acids and peptides as catalysts, see: Jarvo,
E. R.; Miller, S. J. Tetrahedron 2002, 58, 2481.
1
986.
(
2) Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975, 97,
(12) For a review on amine-catalyzed reactions, see: France, S.; Guerin,
D. J.; Miller, S. J.; Lectka, T. Chem. ReV. 2003, 103, 2985.
(13) For a review of asymmetric phase-transfer catalysis, see: Lygo,
B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, ASAP.
(14) We recently developed novel pyrrolidine sulfonamides (their
structures are shown in Table 1, entries 3 and 4) as organocatalysts for
catalyzing asymmetric R-aminoxylation and the Mannich-type reactions:
(a) Wang, W.; Wang, J.; Li, H. Angew. Chem., Int. Ed. 2004, submitted
for publication. (b) Wang, W.; Wang, J.; Li, H. Tetrahedron Lett. 2004,
submitted for publication.
5
434.
(3) (a) Lerouge, P.; Paulmier, C. Tetrahedron Lett. 1984, 25, 1983. (b)
Lerouge, P.; Paulmier, C. Tetrahedron Lett. 1984, 25, 1987. (c) Lerouge,
P.; Paulmier, C. Bull. Soc. Chim. Fr. 1985, 1225.
(4) (a) Fitzner, J. N.; Shea, R. G.; Fankhauser, J. E.; Hopkins, P. B. J.
Org. Chem. 1985, 50, 417. (b) Spaltenstein, A.; Carpino, P. A.; Hopkins,
P. B. Tetrahedron Lett. 1986, 27, 147. (c) Shea, R. G.; Fitzner, J. N.;
Fankhauser, J. E.; Spaltenstein, A.; Carpino, P. A.; Peevey, R. M.; Pratt,
D. V.; Tenge, B. J.; Hopkins, P. B. J. Org. Chem. 1986, 51, 5243.
(
(
5) Denis, J. N.; Dumont, W.; Krief, A. Tetrahedron Lett. 1976, 17, 453.
6) (a) Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am. Chem.
(15) For proline-catalyzed aldol reactions, see: (a) List, B.; Lerner, R.
A.; Barbas, C. F., III. J. Am. Chem. Soc. 2000, 122, 2395. (b) List, B.;
Pojarliev, P.; Castello, C. Org. Lett. 2001, 3, 573. (c) Northrup, A. B.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 6798. (d) Northrup, A.
B.; Mangion, I. K.; Hettche, F.; MacMillan, D. W. C. Angew. Chem., Int.
Ed. 2004, 43, 2152.
Soc. 1973, 95, 6137. (b) Houllemare, D.; Ponthieux, S.; Outurquin, F.;
Paulmier, C. Synthesis 1997, 101.
(
7) Cossy, J.; Furet, N. Tetrahedron Lett. 1993, 34, 7755.
(8) Williams, D. R.; Nishitani, K. Tetrahedron Lett. 1980, 21, 4417.
1
0.1021/ol0488946 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/13/2004

compounds.1
5-19
The general mechanism for these processes
but with a stoichiometric amount, gave only 56% yield with
8
involves initial formation of an electron-rich enamine, which
then adds to an electrophile to give an adduct. Intrigued by
the possibility that such a mechanistic scenario might be
expanded to encompass electrophilic forms of selenium
reagents, we have explored reactions of aldehydes with
N-(phenylseleno)phthalimide I catalyzed by proline deriva-
tive L-prolinamide. The results of this effort have demon-
strated that these R-selenenylation reactions proceed rapidly
using 2 mol % of L-prolinamide within 10-60 min to afford
R-phenylselenoaldehydes in high yields (76-95%).
30 mol % loading. The investigation promoted us to select
L-prolinamide as catalyst for the further examination of the
R-selenenylation reaction.
Next, we probed reactions of four commonly used
selenium reagents with isovaleraldehyde in the presence of
30 mol % L-prolinamide in CH Cl . The results showed that
2 2
facile selenenylation occurred with N-(phenylseleno)phthal-
imide I (Table 2, entry 1) to produce the seleno-aldehyde
In an initial study, eight organocatalysts (30 mol %) were
screened for the reaction of N-(phenylseleno)phthalimide I
Table 2. Effect of Selenium Reagents on R-Selenenylation
Reactions of Isovaleraldehydea
as selenium reagent with isovaleraldehyde in CH
2 2
Cl (Table
1). It was found that L-prolinamide exhibited the most highly
Table 1. Catalyst Screening for R-Selenenylation Reaction of
entry
selenium reagent
reaction time % yieldb
Isovaleraldehydea
1
2
3
4
N-(phenylseleno) phthalimide I
PhSeCl
PhSeBr
PhSeSePh
<5 min
15 h
1 d
96
75
24
1 d
<10
a
Reaction conditions (see footnote in Table 1). b Isolated yield.
product in less than 5 min and a 96% yield. Under the same
conditions, much longer times were required for reactions
of phenylselenyl chloride, bromide and diphenyl diselenide,
and lower yields were obtained (15 h, 75%; 1 d, 24%; and
1
d, <10% yield, respectively, Table 2). Consequently,
N-(phenylseleno)phthalimide I was selected as the selenium
reagent of choice for the R-selenenylation reactions of
aldehydes.
A survey of media for the L-prolinamide-catalyzed R-se-
lenenylation process revealed that solvents had a significant
effect on the reaction (Table 3). Reactions in less polar
solvents, such as CH
, entries 1, 2, and 4), took place in higher yields. In contrast,
the use of polar solvents CH CN, DMSO, CH NO , and
DMF (entries 5-8) resulted in low yields. Interestingly,
2 2
Cl , EtOAc, and 1,4-dioxane (Table
2
3
3
2
(16) For proline-catalyzed Mannich reactions, see: (a) List, B. J. Am.
Chem. Soc. 2000, 122, 9336. (b) List, B.; Pojarliev, P.; Biller, W. T.; Martin,
H. J. J. Am. Chem. Soc. 2002, 124, 827. (c) C o´ rdova, A.; Notz, W.; Zhong,
G.; Betancort, J. M.; Barbas, C. F., III. J. Am. Chem. Soc. 2002, 124, 1842.
(d) C o´ rdova, A.; Watanabe, S.; Tanaka, F.; Notz, W.; Barbas, C. F., III. J.
Am. Chem. Soc. 2002, 124, 1866. (e) C o´ rdova, A.; Barbas, C. F., III.
Tetrahedron Lett. 2003, 44, 1923. (f) Notz, W.; Tanaka, F.; Watanabe, S.-
I.; Chowdari, N. S.; Turner, J. M.; Thayumanavan, R.; Barbas, C. F., III. J.
Org. Chem. 2003, 68, 9624. (g) Hayashi, Y.; Tsuboi, W.; Ashimine, I.;
Urushima, T.; Shoji, M.; Sakai, K. Angew. Chem., Int. Ed. 2003, 42, 3677.
(h) Hayashi, Y.; Tsuboi, W.; Shoji, M.; Suzuki, N. J. Am. Chem. Soc. 2003,
125, 11208.
a
Reaction conditions: To a vial containing isovaleraldehyde (0.25 mmol),
0
.5 mL of anhydrous CH2Cl2, and catalyst (0.075 mmol) was added
N-(phenylseleno)phthalimide I (0.3 mmol) at room temperature. After a
certain period of time (see Table 1), the reaction mixture was treated with
water (5 mL), and then the solution was extracted with ethyl acetate (3 ×
5
mL). The combined extracts were dried over MgSO4, filtered, and
concentrated in vacuo. The crude product was purified by silica gel
chromatography. Isolated yields.
(17) For proline-catalyzed R-amination reactions, see: (a) List, B. J. Am.
Chem. Soc. 2002, 124, 5656. (b) Kumaragurubaran, N.; Juhl, K.; Zhuang,
W.; Bogevig, A.; Jorgensen, K. A. J. Am. Chem. Soc. 2002, 124, 6254.
b
(
18) For proline-catalyzed R-aminoxylation reactions, see: (a) Brown,
F. J.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc.
003, 125, 10808. (b) Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247.
c) Bogevig, A.; Sunden, H.; Cordova, A. Angew. Chem., Int. Ed. 2004,
3, 1109. (d) Hayashi, Y.; Yamaguchi, J.; Sumiya, T.; Shoji, M. Angew.
Chem., Int. Ed. 2004, 43, 1112.
19) Recently, Jørgensen and co-workers reported L-prolinamide-
2
(
4
catalytic activity (Table 1, entry 2). The reaction was
completed in less than 5 min in a nearly quantitative yield
(
96%). L-Proline also showed good activity (Table 1, entry
). However, it is worth noting that under the same reaction
conditions, piperidine, which has been used for the reaction
(
1
catalyzed R-chlorination of ketones: Halland, N.; Braunton, A.; Bachmann,
S.; Marigo, M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 4790.
2818
Org. Lett., Vol. 6, No. 16, 2004

Table 3. Effect of Solvents on R-Selenenylation Reaction of
Table 5. L-Prolinamide-Catalyzed R-Selenenylation Reactions
Isovaleraldehyde with Ia
of Aldehydesa
entry
solvent
CH2Cl2
reaction time
% yieldb
1
2
3
4
5
6
7
8
<5 min
10 min
2 h
15 min
30 min
1 h
96
88
38
93
74
83
66
46
EtOAc
toluene
1,4-dioxane
CH3CN
DMSO
CH3NO2
DMF
2 h
2 h
a
For reaction conditions, see footnote in Table 1. b Isolated yield.
nonpolar toluene gave a very poor yield (38%, Table 3, entry
3
), presumably as a result of the low solubility of N-
phenylseleno)phthalimide I in toluene. On the basis of these
results, we selected CH Cl as the solvent for reactions and
(
2
2
explored testing the effect of catalyst loadings on the process.
The studies of catalyst loadings on the R-selenenylation
reactions revealed that, remarkably, a catalyst loading as low
as 1 mol % still afforded significant reaction activity (Table
4, entry 6). From an operational perspective, use of 2 mol
Table 4. Effect of Catalyst Loadings on R-Selenenylation
Reactions of Isovaleraldehydea
entry
mol % catalyst
reaction time
% yieldb
1
2
3
4
5
6
7
30
20
10
5
2
1
<5 min
<5 min
<5 min
10 min
10 min
1 h
96
94
94
86
88
62
31
a
For reaction conditions, see footnote in Table 1. b Isolated yield.
0.5
2 d
Reaction proceeded rapidly (10 min, 88% yield) even with
the more hindered isovaleraldehyde (entry 4). However,
under these conditions, highly sterically crowded R,R-
disubstituted aldehydes (entries 11 and 12) only slowly
reacted with N-(phenylseleno)phthalimide I to give very low
yields of the selenation products. Importantly, addition of 4
Å molecular sieves resulted in significant enhancements of
the reaction rates. In these cases, reactions of R,R-disubsti-
tuted aldehydes were complete within 1 h and took place in
high yields (76-81%). The possible reason for the enhanced
reaction rate could be due to facilitated formation of the
enamine intermediate in the presence of molecular sieves.
In summary, an efficient L-prolinamide-catalyzed R-sele-
nenylation reaction of aldehydes with N-(phenylseleno)-
a
For reaction conditions, see footnote in Table 1. b Isolated yield.
%
of L-prolinamide is optimal to ensure high reaction
efficiency (88% yield) while maintaining a reasonable
reaction time (10 min, Table 4, entry 5).
Having established optimal reaction conditions for the
selenation process, we next probed reactions with a variety
of aldehydes (Table 5). The results show that considerable
variation in the steric demand of the aldehyde is possible
without loss in efficiency. Independent of the length of the
side chains (C1-C8) (entries 1-9, Table 5), aldehydes
reacted within a 10 min period in high yields (78-95%).
Org. Lett., Vol. 6, No. 16, 2004
2819

phthalimide I has been developed. The process is general
for a variety of aldehyde substrates, and high yields (76-
thank Professor Patrick S. Mariano for making critical
editorial comments about the manuscript.
9
5%) are observed. To our knowledge, this is the first study
Supporting Information Available: Experimental pro-
cedures and spectra data for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
in which an organocatalyst has been used to catalyze this
type of the reaction. The results of investigation of the
reaction mechanism and the asymmetric version of the
2
0
R-selenenylation process will be reported in due course.
OL0488946
(
20) L-Proline and L-prolinamide exhibited no enantioselectivity on the
Acknowledgment. This research was supported from the
Department of Chemistry, University of New Mexico. We
R-selenenylation of isovaleraldehyde. However, our pyrrolidine tosyl
sulfonamide (its structure is shown in Table 1, entry 4) provided 60% ee.
2820
Org. Lett., Vol. 6, No. 16, 2004