The organocatalytic direct self-trimerization of acrolein: application to the total synthesis of montiporyne F

Article abstract of DOI:10.1016/j.tetlet.2006.12.055

The organocatalytic direct self-trimerization of acrolein, via cascade double-Michael and Mannich reactions, affording 5-methylenecyclohex-3-ene-1,3-dicarbaldehyde (1) is described. Synthetic application of the reaction was demonstrated by further transfo

Full text of DOI:10.1016/j.tetlet.2006.12.055

Tetrahedron Letters 48 (2007) 1121–1125
The organocatalytic direct self-trimerization of acrolein:
application to the total synthesis of montiporyne F
Bor-Cherng Hong,* Roshan Y. Nimje and Chun-Yao Yang
Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi, 621, Taiwan, ROC
Received 22 November 2006; revised 12 December 2006; accepted 13 December 2006
Available online 8 January 2007
Abstract—The organocatalytic direct self-trimerization of acrolein, via cascade double-Michael and Mannich reactions, affording 5-
methylenecyclohex-3-ene-1,3-dicarbaldehyde (1) is described. Synthetic application of the reaction was demonstrated by further
transformations of 1 to montiporyne F.
Ó 2006 Elsevier Ltd. All rights reserved.
Natural compounds occurring as dimers or trimers of
monomers are common in nature;1 applications of the
concepts of catalytic dimerization and trimerization
have led to remarkable advances in the total synthesis
of complex molecules.2 Recently, the discovery and
application of enzymes3 and enzyme-mimetic catalysts,4
(e.g., organocatalysts)5 in organic synthesis has received
a great deal of attention. For example, Wong and co-
workers reported that 2-deoxyribose-5-phosphate aldol-
ase (DERA) catalyzed the double-aldol sequence of
acetaldehyde, affording tetrahydro-6-methyl-2H-pyran-
2,4-diol, (Scheme 1, Type A).6 Recently, Barbas and
co-workers developed the direct asymmetric self-aldol-
ization of 3 equiv of acetaldehyde (i.e., a trimer of acet-
aldehyde) via cascade aldol and Mannich reactions,
affording (+)-(5S)-hydroxy-(2E)-hexenal in 2–13% yield
(Scheme 1, Type B).7 These two interesting one-pot mul-
ti-step transformations have illuminated a new route to
efficient synthesis catalyzed by enzyme and enzyme-like
compounds. However, the low yields of these reactions
remained a serious drawback. More recently, Barbas
and co-workers reported the L-proline- or pyrrolidine-
catalyzed self-cycloaddition of a,b-unsaturated ketones,
providing cyclohexanone derivatives in a higher yield
and with a subtle enantioselectivity (Scheme 2).8 In rela-
tion to the elegance of these reactions, the exploration of
novel organocatalytic cycloaddition remains a formida-
ble challenge. Herein, we report an unprecedented, novel
organocatalytic trimerization of acrolein and its applica-
tion to the synthesis of a marine natural product.
A. Aldolase-catalyzed self-aldolization of acetaldehyde
During the course of searching for new cycloadditions,9
we isolated an intriguing dialdehyde products 1 in a 27%
yield when freshly distilled acrolein10 was treated with
L-proline in DMF at an ambient temperature for 14 h
(Scheme 3). The novel adduct may be produced through
the stepwise cascade double-Michael/Mannich reaction
OH
OH OH
DERA
O
3 CH3CHO
CHO
OH
20% yield; α/β = 1:8
B. Proline-catalyzed self-Aldol reaction of acetaldehyde
OH
L
-proline
3 CH3CHO
CHO
o
THF, 0
C
(S)
O
O
O
L
-Proline
10% yield
+
R
R
R
R
Scheme 1. Trimerization of acetaldehyde.
R
O
O
*
Scheme 2. Proline-catalyzed self Diels–Alder reactions of a,b-unsatu-
rated ketones.
Corresponding author. Tel.: +886 5 2428174; fax: +886 5 2721040;
e-mail: chebch@ccu.edu.tw
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.055

1122
B.-C. Hong et al. / Tetrahedron Letters 48 (2007) 1121–1125
CO2H
O
1
N
H
CO2H
N
1
CO2H
N
1
2
+
CO2H
H
N
H
2
3
HO2C
H
H
2
3
N
3
7
CHO
CO2H
N
9
8
1
5
6
5
4
H
4
3
2
CHO
6
1
CO2H
N
H
4
8
CO2H
7
N
CO2H
H
N
1
6
HO2C
4
6
2
5
2
3
9
O
N
H
1
N
H
5
9
8
HO2C
3
7
Scheme 3. Proposed reaction mechanism for the proline-catalyzed trimerization of acrolein.
and equilibrium process shown in Scheme 3.11 It is likely
that the product of the proline-catalyzed double-
Michael reaction of acrolein subsequently adds to another
acrolein molecule via the Mannich reaction to yield the
cyclohexenedial product. To the best of our knowledge,
this process is the first example of a cascade double-
Michael/Mannich reaction of an a,b-unsaturated alde-
hyde.12 The structure of 1 was assigned unambiguously
by its COSY, HMBC, HMQC, and INADEQUATE
spectra and analysis.13 Unfortunately, dialdehyde 1
obtained was found to be a racemate, by chiral GC–MS
analysis.14 In order to increase the reaction yield, the
reaction was performed in the presence of various
organocatalysts and conditions. Selected results are
summarized in Table 1.
Generally, the reactions proceeded smoothly when mon-
itored by TLC. Except for the polymerization residue,
dialdehyde 1 is the major product shown above the base-
line residue on TLC and is the only isolable product.
Table 1. Catalyst screening and optimization for the direct catalytic trimerization of acrolein
TBSO
t
-BuO
HO
S
CO2H
O
CO2H
N
CO2H
CO2H
CO2H
CO2H
N
N
CO2H
N
N
N
H
N
H
H
H
H
H
H
VII
I
V
VI
III
IV
II
Me
O
OH
Ph
N
N
N
H
CONH2
NH
t-Bu
N
H
N
H
N
H
N
H
N
CO2H
Ph
H
Ph
+ TFA
+ HOAc
+ HOAc
XIII
XIV
XI
VIII
IX
XII
X
Entry
Catalyste
Additive
T (°C)
Solvent
Timeb (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
I
25
25
25
25
25
25
25
25
25
25
25
0
DMF
14
14
14
14
14
14
12
14
24
24
3
30
3
36
24
5
27
40
I
DMSO
CH2Cl2
THF
I
20
I
ꢀ0c
I
EtOH
8
55
I
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
If
I
40
15
8
8
58
26
61
Imidazole
Pyrrolidine
Piperidine
Spartein
Spartein
Et3N
I
I
I
I
I
25
0
I
Et3N
20
II
III
IV
V
VI
VII
VIII
25
25
25
25
25
25
25
ꢀ0c
52
10
24
24
24
24
48
ꢀ0c
ꢀ0c
ꢀ0c
ꢀ0c

B.-C. Hong et al. / Tetrahedron Letters 48 (2007) 1121–1125
1123
Table 1 (continued)
Entry
Catalyste
Additive
T (°C)
Solvent
Timeb (h)
Yielda (%)
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
IX
25
25
25
25
0
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
24
3
ꢀ0c
56
ꢀ0c
ꢀ0c
34
31
25
ꢀ0c
ꢀ0
5
30
25
5
5
23
25
X
XI
24
14
30
30
30
18
24
18
1d
24
24
36
6
XII
III
Spartein
Spartein
Spartein
IV
X
0
0
XIII
None
XIII
XIII
XIII
XIII
XIII
XIII
XIV
25
25
25
25
25
25
25
25
25
HOAc
HOAc
HOAc
TFA
TsOH
HFIP
Oxalic acid
HOAc
6
a Isolated yield.
b Reactions were allowed to proceed until acrolein was consumed.
c Polymerization.
d Reaction completed in 1 h with much of polymerization residue.
e Unless otherwise noted, 0.33 equiv of the catalyst was used.
f 1.0 equiv of the catalyst was used.
The polar polymerization residue can be easily separated
on TLC and removed by flash column chromatography.
idine and piperidine as achiral amine catalysts of this
reaction.17 The reaction gave dialdehyde 1 when an equal
amount of acetic acid and base was used as an additive
(Table 1, entries 29–37). These results imply that the
suitable bifunctional amine–acid catalysts,18 with the
Brønsted acid19 and Lewis base functionalities cooperat-
ing in the catalysis, is required to promote the reaction.
The reactions in different solvents were screened, and the
highest yield of 55% was observed in CH3CN (Table 1,
entries 1–6). The reaction with a large amount of proline
afforded no improvement, but reduced the yield (Table 1,
entry 7). Recently, co-catalyst effects on chemoselectivity
and stereoselectivity have been reported.15 Several such
additives were applied in the reactions for this study.
The addition of Et3N and spartein accelerated the reac-
tion and increased its yield (Table 1, entries 8–14).
Attempts to improve the yield and stereoselectivity by
perfoming the reaction at a low temperature (0 °C)
resulted in a reduced yield with no enantioselectivity,
(Table 1, entries 12 and 14). A series of organocatalysts
was screened for the cascade reaction, (Table 1, entries
15–25).16 Among them, catalysts III, IV, and X are the
most promising candidates for the transformation at
ambient temperature. Unfortunately, reaction with these
catalysts at 0 °C gave lower yields, even with the addition
of spartein (Table 1, entries 26–28). Since these chiral
amines provided racemate 1, we studied simple pyrrol-
The Michael-type reaction20 and Mannich reaction21 are
involved in many biosynthetic pathways.22 As far as we
are aware, our current organocatalyzed tandem double-
Michael/Mannich reaction has not been reported previ-
ously under conventional conditions. Since acrolein23
and the 1,3,5-trialkyl benzenes24 have been isolated from
many natural sources, it is interesting to speculate about
whether this type of cascade reaction is a biotransforma-
tion process and can be observed in nature. We envi-
sioned dialdehyde 1 would be a versatile synthon for
other synthetically valuable building blocks.25 To dem-
onstrate the synthetic potential of this reaction, dialde-
hyde 1 was transferred to montiporyne F (2), a natural
product isolated from the stony coral Montipora sp.
having some cytotoxic activities against human solid
CHO
CH2OH
CHO
NaIO4, OsO4
MnO2, CH2Cl2
96%
N2H4, KOH
LiAlH4, THF
0 oC; 86%
2,6-lutidine,
dioxane-H2O; 30%
diethyleneglycol; 60%
CH2OH
CHO
CH2OH
CH2OH
1
3
4
5
O
P
O
OMe
OMe
O
1-Bromonon-1-yne
N2
PCC, CH2Cl2
74%
CuBr, piperidine,
NH2OH-HCl; 89%
K2CO3, MeOH; 85%
CHO
O
O
O
CH2OH
H
6
7
8
montiporyne F (2)
Scheme 4. Total synthesis of montiporyne F.

1124
B.-C. Hong et al. / Tetrahedron Letters 48 (2007) 1121–1125
tumor cell lines (Scheme 4).26 The reduction of 1 to 3
(LiAlH4, THF, 0 °C; 86%) followed by the selective
oxidation of the allylic alcohol (MnO2, CH2Cl2; 96%)
afforded 4. Wolff–Kishner reduction of 4 (N2H4,
KOH, (HOCH2CH2)2O; 60%), followed by a modified
oxidative cleavage of the methylene group by Lemi-
eux–Johnson reagent with an improved procedure27
(NaIO4, OsO4, 2,6-lutidine, dioxane–H2O; 30%) pro-
vided hydroxyenone 6, which was oxidized (PCC,
CH2Cl2; 74%) to give ketoaldehyde 7. Modified Seyf-
erth–Gilbert homologation28 of ketoaldehyde 7 by the
Ohira–Bestmann procedure29 afforded ketoalkyne 8 in
an 85% yield. Cadiot-Chodkiewicz coupling of 8 with
1-bromonon-1-yne (CuBr, piperidine, NH2OHÆHCl;
MeOH) gave montiporyne F (2) in an 89% yield.30
Couladouros, E. A. J. Am. Chem. Soc. 2000, 122, 3071; (e)
Miyake, F. Y.; Yakushijin, K.; Horne, D. A. Org. Lett.
2000, 2, 3185; (f) Li, C.; Bardhan, S.; Pace, E. A.; Liang,
M.-C.; Gilmore, T. D.; Porco, J. A., Jr. Org. Lett. 2002, 4,
3267; (g) Mehta, G.; Pan, S. C. Org. Lett. 2004, 6, 3985;
(h) Li, W.-D.; Ma, B.-C. Org. Lett. 2005, 7, 271; (i) Smith,
A. B., III; Kozmin, S. A.; Adams, C. M.; Paone, D. V.
´
J. Am. Chem. Soc. 2000, 122, 4984; (j) Commeiras, L.;
Moses, J. E.; Adlington, R. M.; Baldwin, J. E.; Cowley, A.
R.; Baker, C. M.; Albrecht, B.; Grant, G. H. Tetrahedron
2006, 62, 9892; (k) Ogamino, T.; Obata, R.; Nishiyama, S.
Tetrahedron Lett. 2006, 47, 727; (l) Carlier, P. R.; Du,
D.-M.; Han, Y.-F.; Lin, J.; Perola, E.; Williams, I. D.;
Pang, Y.-P. Angew. Chem., Int. Ed. 2000, 39, 1775.
3. For recent review, see: (a) Enzyme Catalysis in Organic
Synthesis: A Comprehensive Handbook; 2nd ed.; Drauz,
K., Waldmann, H., Eds., Wiley: New York, 2002; (b)
Garcia-Urdiales, E.; Alfonso, I.; Gotor, V. Chem. Rev.
2005, 105, 313; (c) Bornscheuer, U. T.; Kazlauskas, R. J.
Angew. Chem., Int. Ed. 2004, 43, 6032; (d) Bordusa, F.
Chem. Rev. 2002, 102, 4817; (e) Reetz, M. T. Tetrahedron
2002, 58, 6595; (f) Koeller, K. M.; Wong, C.-H. Nature
2001, 409, 232; (g) Carrea, G.; Riva, S. Angew. Chem., Int.
Ed. 2000, 39, 2226; (h) Seoane, G. Curr. Org. Chem. 2000,
4, 283.
In summary, the organocatalytic direct asymmetric self-
trimerization of acrolein affording dialdehyde 1 on a
multigram scale has been developed.31 Our study further
demonstrates that the organocatalyst (e.g., proline and
bifunctional amine–acid catalysts) not only acts as the
catalyst for organic reactions but can also affect reac-
tions by giving rise to products that do not form with
conventional reagents. The facile reaction provides a
useful and unique building block for organic synthesis
that has been implemented in the total synthesis of mon-
tiporyne F. Further investigations of this reaction with
respect to its detailed mechanism, as well as more appli-
cations of 1 in other total synthesis are in progress.
4. Groger, H.; Wilken, J. Angew. Chem., Int. Ed. 2001, 40,
529.
5. For recent review, see: (a) Dalko, P. I.; Moisan, L. Angew.
Chem., Int. Ed. 2004, 43, 5138; (b) Notz, W.; Tanaka, F.;
Barbas, C. F., III. Acc. Chem. Res. 2004, 37, 580; (c)
Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719; (d)
Berkessel, A.; Gro¨ger, H. Asymmetric Organocatalysis:
From Biomimetic Concepts to Applications in Asymmetric
Synthesis; Wiley: New York, 2005.
6. (a) Gijsen, H. J. M.; Wong, C.-H. J. Am. Chem. Soc. 1994,
116, 8422; (b) Wong, C.-H.; Garcia-Junceda, E.; Chen, L.;
Blanco, O.; Gijsen, H. J. M.; Steensma, D. H. . J. Am.
Chem. Soc. 1995, 117, 3333; (c) Gijsen, H. J. M.; Wong,
C.-H. . J. Am. Chem. Soc. 1995, 117, 7585; (d) Liu, J.; Hsu,
C.-C.; Wong, C.-H. Tetrahedron Lett. 2004, 45, 2439.
Acknowledgments
We thank Professor Jee H. Jung, Pusan National
University, Korea, for generously providing the spectra
of natural montiporyne F. Financial support from the
National Science Council, Taiwan, ROC, for this study
is gratefully acknowledged.
´
7. Cordova, A.; Notz, W.; Barbas, C. F., III. J. Org. Chem.
2002, 67, 301.
8. Ramachary, D. B.; Chowdari, Naidu S.; Barbas, C. F., III.
Tetrahedron Lett. 2002, 43, 6743.
Supplementary data
9. For previous examples in this series, see: (a) Hong, B.-C.;
Wu, M.-F.; Tseng, H.-C.; Liao, J.-H. Org. Lett. 2006, 8,
2217; (b) Chen, S.-H.; Hong, B.-C.; Su, C.-F.; Sarshar, S. .
Tetrahedron Lett. 2005, 46, 8899.
10. Acrolein is well known to polymerize in prolonged storage
or upon exposure to acids or bases.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.12.055.
11. For a related domino reaction, see: Lee, M. J.; Park, D.
Y.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2006, 47,
1833.
References and notes
1. For recent examples, see: (a) Harinantenaina, L.; Tak-
aoka, S. J. Nat. Prod. 2006, 69, 1193; (b) Cruz, L. J.;
Insua, M. M.; Baz, J. P.; Trujillo, M.; Rodriguez-Mias, R.
A.; Oliveira, E.; Giralt, E.; Albericio, F.; Canedo, L. M. J.
Org. Chem. 2006, 71, 3335; (c) Isaka, M.; Palasarn, S.;
Rachtawee, P.; Vimuttipong, S.; Kongsaeree, P. Org. Lett.
2005, 7, 2257; (d) Isaka, M.; Prathumpai, W.; Wongsa, P.;
Tanticharoen, M. Org. Lett. 2006, 8, 2815; (e) Volk, C. A.;
Ko1ck, M. Org. Lett. 2003, 5, 3567.
2. For recent examples, see: (a) Barry, C. S.; Bushby, N.;
Charmant, J. P. H.; Elsworth, J. D.; Harding, J. R.; Willis,
C. L. Chem. Commun. 2005, 5097; (b) Mehta, G.; Islam,
K. Tetrahedron Lett. 2004, 45, 7683; (c) Nicolaou, K. C.;
Gray, D. Angew. Chem., Int. Ed. 2001, 40, 761; (d)
Nicolaou, K. C.; Vassilikogiannakis, G.; Simonsen, K. B.;
Baran, P. S.; Zhong, Y.-L.; Vidali, V. P.; Pitsinos, E. N.;
12. For a recent example of a triple cascade organocatalytic
reaction, see: Enders, D.; Huttl, M. R. M.; Grondal, C.;
¨
Raabe, G. Nature 2006, 441, 861.
13. See Supplementary data for detail.
14. Small enantioselectivity were observed in amine-catalyzed
self Diels–Alder reactions of a,b-unsaturated ketones, see:
Ref. 8.
15. (a) Peelen, T. J.; Chi, Y.; Gellman, S. H. J. Am. Chem.
Soc. 2005, 127, 11598; (b) Mase, N.; Nakai, Y.; Ohara, N.;
Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III. J.
Am. Chem. Soc. 2006, 128, 734.
16. For selected examples of such organocatalysis, see: (a)
Steiner, D. D.; Mase, N.; Barbas, C. F., III. Angew.
Chem., Int. Ed. 2005, 44, 3706; (b) Levina, A.; Muzart, J.
Tetrahedron: Asymmetry 1995, 6, 147; (c) Hayashi, Y.;
Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.;

B.-C. Hong et al. / Tetrahedron Letters 48 (2007) 1121–1125
1125
Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 958; (d) Enders,
D.; Grondal, C.; Vrettou, M.; Raabe, G. Angew. Chem.,
Int. Ed. 2005, 44, 4079–4083; (e) Kunz, R. K.; MacMillan,
D. W. C. J. Am. Chem. Soc. 2005, 127, 3240; (f) Steiner, D.
D.; Mase, N.; Barbas, C. F., III. Angew. Chem., Int. Ed.
2005, 44, 3706; (g) Ramachary, D. B.; Chowdari, N. S.;
Barbas, C. F., III. Angew. Chem., Int. Ed. 2003, 42, 4233;
(h) Cheong, P. H.-Y.; Zhang, H.; Thayumanavan, R.;
Tanaka, F.; Houk, K. N.; Barbas, Carlos F., III. Org.
Lett. 2006, 8, 811; (i) Robichaud, J.; Tremblay, F. Org.
Lett. 2006, 8, 597; (j) Aggarwal, V. K.; Lopin, C.;
Sandrinelli, F. J. Am. Chem. Soc. 2003, 125, 7596; (k)
Dambruoso, P.; Massi, A.; Dondoni, A. Org. Lett. 2005,
7, 4657; (l) Mitchell, C. E. T.; Brenner, S. E.; Ley, S. V.
Chem. Commun. 2005, 5346; (m) Kumarn, S.; Shaw, D.
M.; Ley, S. V. Chem. Commun. 2006, 3211; (n) Andreae,
M. R. M.; Davis, A. P. Tetrahedron: Asymmetry 2005, 16,
2487; (o) Sunden, H.; Dahlin, N.; Ibrahem, I.; Adolfsson,
H.; Cordova, A. Tetrahedron Lett. 2005, 46, 3385; (p)
Berkessel, A.; Koch, B.; Lex, J. Adv. Synth. Cat. 2004, 346,
1141; (q) Ramachary, D. B.; Chowdari, N. S.; Barbas, C.
F., III. Angew. Chem., Int. Ed. 2003, 42, 4233.
C. F. Acc. Chem. Res. 2004, 37, 580; (c) Christoffers, J.;
Baro, A. Angew. Chem., Int. Ed. 2003, 42, 1688; (d)
Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem.
2002, 1877; (e) Krause, N.; Hoffmann-Roder, A. Synthesis
2001, 171.
21. For recent reviews, see: (a) Marques, M. M. B. Angew.
Chem., Int. Ed. 2006, 45, 348; (b) Cordova, A. Acc. Chem.
Res. 2004, 37, 102; (c) Arend, M.; Westermann, B.; Risch,
N. . Angew. Chem., Int. Ed. 1998, 37, 1045; (d) Bur, S. K.;
Martin, S. F. Tetrahedron 2001, 57, 3221.
22. (a) Abe, N.; Arakawa, T.; Hirota, A. Chem. Commun.
2002, 204; (b) von Nussbaum, F. Angew. Chem., Int. Ed.
2003, 42, 3068; (c) Hale, K. J.; Dimopoulos, P.; Cheung,
M. L. F.; Frigerio, M.; Steed, J. W.; Levett, P. C. Org.
Lett. 2002, 4, 897; (d) Rohr, J. J. Chem. Soc., Chem.
Commun. 1989, 492.
23. Acrolein is released into the environment as a product of
fermentation and ripening processes. It is a byproduct of
lipid peroxidation and was isolated from the wood of oak
trees. For references and other examples, see: (a) Slooff,
W.; Bont, P. F. H.; Janus, J. A.; Pronk, M. E. J.; Ros, J. P.
M. National Institute of Public Health and Environmental
Protection, Bilthoven, Report No. 601014001, 1994,
Update of the exploratory report: acrolein; (b) Winter,
M.; Willhalm, B. Helv. Chim. Acta. 1964, 47, 1215; (c)
Reinder, S.; Spiritusind, Z. Chem. Zentralbl. 1941, 63,
3155; (d) Distillers Co.; German Patent, DE 831,838;
1950.
24. (a) Birch, S. F.; Norris, W. S. G. P. J. Chem. Soc. 1926,
2545; (b) Badger, G. M.; Donnelly, J. K.; Spotswood, T.
M. Aust. J. Chem. 1963, 392; (c) Pictet, A.; Bouvier, M.
Chem. Ber. 1915, 48, 926; (d) Salbut, P. D.; Wielopolski,
A. . Rocz. Chem. 1970, 44, 585; (e) Diallo, B.; Vanhaelen-
Fastre, R.; Vanhaelen, W. Phytochemistry 1991, 30, 4153;
(f) Addae-Mensah, I.; Waibel, R.; Achenbach, H. Liebigs
Ann. Chem. 1985, 1284; (g) Jong, T.-T.; Jean, M.-Y. J.
Chin. Chem. Soc. 1993, 40, 399; (h) Misra, T. N.; Singh, R.
S.; Pandey, H. S.; Kohli, Y. P.; Pandey, R. P. Indian J.
Chem. Sect. B 1997, 36, 203.
17. For promising examples of organocatalysis mediated by
pyrrolidine and acetic acid, see: (a) McNally, A.; Evans,
B.; Gaunt, M. J. Angew. Chem., Int. Ed. 2006, 45, 2116; (b)
Erkkilae, A.; Pihko, P. M. J. Org. Chem. 2006, 71, 2538;
(c) Li, D.-P.; Guo, Y.-C.; Ding, Y.; Xiao, W.-J. Chem.
Commun. 2006, 799; (d) Ramachary, D. B.; Ramakumar,
K.; Kishor, M. Tetrahedron Lett. 2005, 46, 7037; (e) Ji, C.;
Peng, Y.; Huang, C.; Wang, N.; Jiang, Y. Synlett 2005,
986; (f) Mase, N.; Tanaka, F.; Barbas, C. F. Org. Lett.
2003, 5, 4369.
18. For recent examples in bifunctional organocatalysis, see:
(a) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Eur. J.
Org. Chem. 2006, 2894; (b) Cao, C.-L.; Ye, M.-C.; Sun,
X.-L.; Tang, Y. Org. Lett. 2006, 8, 2901; (c) Liu, T.-Y.;
Long, J.; Li, B.-J.; Jiang, L.; Li, Rui; Wu, Y.; Ding, L.-S.;
Chen, Y.-C. Org. Biomol. Chem. 2006, 4, 2097; (d) Pratt,
R. C.; Lohmeijer, B. G. G.; Long, D. A.; Waymouth, R.
M.; Hedrick, J. L. J. Am. Chem. Soc. 2006, 128, 4556; (e)
Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Adv. Syn.
Cat. 2005, 347, 1643; (f) Hoashi, Y.; Okino, T.; Takemoto,
Y. Angew. Chem., Int. Ed. 2005, 44, 4032; (g) Lattanzi, A.
Org. Lett. 2005, 7, 2579; (h) Matsui, K.; Takizawa, S.;
Sasai, H. J. Am. Chem. Soc. 2005, 127, 3680; (i) Berkessel,
A.; Cleemann, F.; Mukherjee, S.; Mueller, T. N.; Lex, J.
Angew. Chem., Int. Ed. 2005, 44, 807; (j) Okino, T.;
Nakamura, S.; Furukawa, T.; Takemoto, Y. Org. Lett.
2004, 6, 625; (k) Mase, N.; Tanaka, F.; Barbas, C. F., III.
Org. Lett. 2003, 5, 4369.
19. For recent examples in Brønsted acid organocatalysis, see:
(a) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Cat.
2006, 348, 999; (b) Rueping, M.; Antonchick, A. P.;
Theissmann, T. Angew. Chem., Int. Ed. 2006, 45, 3683; (c)
Terada, M.; Machioka, K.; Sorimachi, K. Angew. Chem.,
Int. Ed. 2006, 45, 2254; (d) Hoffmann, S.; Seayad, A. M.;
List, B. Angew. Chem., Int. Ed. 2005, 44, 7424; (e)
Rueping, M.; Sugiono, E.; Azap, C.; Theissmann, T.;
Bolte, M. Org. Lett. 2005, 7, 3781; (f) Yamamoto, H.;
Futatsugi, K. Angew. Chem., Int. Ed. 2005, 44, 1924.
20. For recent reviews, see: (a) Xu, L.-W.; Xia, C.-G. Eur. J.
Org. Chem. 2005, 633; (b) Notz, W.; Tanaka, F.; Barbas,
25. Dialdehyde 1 is stable during prolonged storage at
ambient temperature, and is inert to some aromatization
agents tried, for example, DDQ.
26. Bae, B. H.; Im, K. S.; Choi, W. C.; Hong, J.; Lee, C.-O.;
Choi, J. S.; Son, B. W.; Song, J.-I.; Jung, J. H. J. Nat.
Prod. 2000, 63, 1511.
27. Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Org. Lett.
2004, 6, 3217.
28. (a) Kirmse, W. Angew. Chem., Int. Ed. 1997, 36, 1164–
1170; (b) Heydt, H. Sci. Synth. 2004, 27, 843; (c) Brown,
D. G.; Velthuisen, E. J.; Commerford, J. R.; Brisbois, R.
G.; Hoye, T. R. J. Org. Chem. 1996, 61, 2540.
29. (a) Ohira, S. Synth. Commun. 1989, 19, 561; (b) Muller, S.;
¨
Liepold, B.; Roth, G. J.; Bestmann, H. J. Synlett 1996,
512.
30. The 1H and 13C spectra of 2 were identical with the spectra
of natural montiporyne F, personal communication with
Professor Jee H. Jung, Pusan National University, Korea.
The optical rotation and absolute stereochemistry of
natural montiporyne F were unknown due to the limited
material isolated.
31. Reaction of crotonaldehyde and proline led to the
formation of [3+3] cycloaddition adducts, see Ref. 9a.