Intramolecular Diels-Alder Reactions of Ester-Tethered 1,7,9-Decatrienoates: Bis[chloro(methyl)aluminum]trifluoromethanesulfonamide as a Catalyst

Article abstract of DOI:10.1021/ol026963f

(Matrix Presented) The intramolecular Diels-Alder reaction of 1,7,9-decatrienoate derivative with an ester tether is efficiently catalyzed by the bidentate Lewis acid, bis-aluminated trifluoromethanesulfonamide.

Full text of DOI:10.1021/ol026963f

ORGANIC
LETTERS
2002
Vol. 4, No. 26
4619-4621
Intramolecular Diels−Alder Reactions of
Ester-Tethered 1,7,9-Decatrienoates:
Bis[chloro(methyl)aluminum]trifluoro-
methanesulfonamide as a Catalyst
Akio Saito, Hisanaka Ito,1 and Takeo Taguchi*
School of Pharmacy, Tokyo UniVersity of Pharmacy and Life Science,
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
taguchi@ps.toyaku.ac.jp
Received September 26, 2002
ABSTRACT
The intramolecular Diels−Alder reaction of 1,7,9-decatrienoate derivative with an ester tether is efficiently catalyzed by the bidentate Lewis
acid, bis-aluminated trifluoromethanesulfonamide.
The intramolecular Diels-Alder (IMDA) reaction is a
powerful method for the stereocontrolled construction of
functionalized cyclohexene frameworks.2,3 In IMDA reac-
tions, the nature of the tether linking the diene and dienophile
strongly influences the reactivity of the substrate and the
structure of the transition state, and thus the stereochemical
outcome. Incorporation of an ester linkage in the tether often
has a deleterious effect on the reaction. Even under the
conditions necessary to force a reaction, cyclized products
are obtained in low yields.2-4 Moreover, in some cases the
reaction fails to yield any cyclized products.4 Such reduced
reactivity of ester-tethered substrates, in particular 1,6,8-nona-
and 1,7,9-decatrienoate systems, has been attributed to a
preference for transoid ester geometry due primarily to dipole
repulsion between carbonyl and ethereal oxygen atoms and
the high energy rotational barrier to the cisoid form in which
the diene and dienophile are in close proximity and as such
are required for a reaction to proceed (Scheme 1).5-7
Scheme 1
(1) Current address: School of Life Science, Tokyo University of
Pharmacy and Life Science.
(2) For reviews on IMDA reactions, see: (a) Roush, W. R. In AdVances
in cycloaddition; Curran, D. P., Ed.; JAI Press: Greenwich, CT, 1990; Vol.
2, pp 91-146. (b) Roush, W. R. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 5, pp
513-550. (c) Ciganek, E. In Organic Reactions; Dauben, W. G., Ed.; John
Wiley & Sons: New York, 1984; Vol. 32, pp 1-374. (d) Weinreb, S. W.
Acc. Chem. Res. 1985, 18, 16.
(3) For references of natural product syntheses, see: (a) Fallis, A. G.
Acc. Chem. ReV. 1999, 32, 464-474. (b) Suzuki, Y.; Murata, T.; Takao,
K.; Tadano, K. J. Synth. Org. Chem. 2002, 60, 679-689.
(4) (a) Boeckman, R. K., Jr.; Demko, D. M. J. Org. Chem. 1982, 47,
1789-1792. (b) Martin, S. F.; Williamson, S. A.; Gist, R. P.; Smith, K. M.
J. Org. Chem. 1983, 48, 5170-5180.
Consequently, poor overlap of the nonbonding electrons of
the ethereal oxygen and carbonyl group in the transition state
is considered to be the major factor responsible for this low
reactivity.8 Lewis acid-mediated reaction, often effective for
intermolecular versions, does not always work well in the
10.1021/ol026963f CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/02/2002

IMDA reaction of the ester-tethered substrates.5d,9 In this
paper, we report that the bidentate Lewis acid 1 derived from
trifluoromethanesulfonamide (TfNH2, 1 mol) and dimethyl-
aluminum chloride (Me2AlCl, 2 mol) efficiently promotes
the IMDA reaction of the ester-tethered decatriene system
2.
generated in situ by mixing TfNH2 (1 mol) and Me2AlCl (2
mol) in 1,2-dichloroethane at 0 °C (Scheme 2), the IMDA
Scheme 2
We presumed that if both oxygen atoms of the ester group
could simultaneously coordinate to a bidentate Lewis acid
(possibly in equilibrium with other complexes such as a
doubly coordinated carbonyl oxygen atom), the cisoid
geometry of the ester would be encouraged and the dieno-
phile would be more strongly activated than with a mono-
dentate Lewis acid (Scheme 1).10 We screened Lewis acids
having a general formula Met-X-Met (Met ) Al, B, Ti, Zn;
X ) NSO2R, O) using 3,5-hexadienyl acrylate derivative
2a as a model substrate. The thermal IMDA reaction of 2a
was recently reported to give the cycloadduct 3a in 79%
yield (endo/exo ) 5), upon heating at 150 °C for 10 days8a
or in 43% yield after 20 h at 200 °C,11 respectively (entries
7 and 8; Table 1). With this substrate, monodentate Lewis
reaction of 2a proceeded at 80 °C within 3 h to give 3a in
83% yield with high endo-selectivity (endo/exo ) 11) (Table
1, entry 2). As shown in Table 1, with TfN(AlMe2)2, a longer
reaction time was required for complete conversion (10 h,
entry 1), while with TfN(AlCl2)2 the reaction proceeded
rapidly to provide 3a in much reduced yield (run 3). When
PhSO2N[Al(Me)Cl]2 was used, 4-methyl-3,5-hexadienol was
liberated (ca 15% based on 2a; entry 4). Finally, (Me2Al)2O
and (Me2AlO)2SO2 catalyzed the conversion of 2a to 3a at
slower rates (entries 5 and 6). Thus, of the Lewis acids
examined, we found TfN[Al(Me)Cl]2 (1) to be the most
effective catalyst for the conversion of 2a to 3a.
Table 1. Effect of Lewis Acid on the IMDA Reaction of 2a
The results of the IMDA reactions of substituted 3,5-
hexadienyl enoate derivatives 2b-f are shown in Table 2.
With 1 equiv of 1 the IMDA reaction of the acrylates 2b-e
Table 2. TfN[Al(Me)Cl]2-Catalyzed IMDA Reaction of
3,5-Hexadienyl Enoate Derivativesa
entry
Lewis acid
TfN(AlMe2)2
TfN[Al(Me)Cl]2
TfN(AlCl2)2
PhSO2N[Al(Me)Cl]2
(Me2Al)2O
(Me2AlO)2SO2
none
none
temp/°C time/h yield/%a endo/exo
1
2
3
4b
5c
6d
7e
8f
80
80
10
3
75
83
45
74
24
41
79
43
12
11
10
10
10
13
5
80
1
80
80
10
9
80
150
200
10
240
20
a Isolated yield. b 4-Methyl-3,5-hexadienol was isolated in 15% yield.
c Recovery of 2a, 50%. d Recovery of 2a, 48%. e Reference 8a. f Reference
11.
acids (TiCl4, MeAlCl2, etc.) were not effective.8a However,
in the presence of 1.1 equiv of TfN[Al(Me)Cl]2 (1)12
entry
2
solvent
CH2Cl2
toluene
ClCH2CH2Cl
CH2Cl2
toluene
ClCH2CH2Cl
CH2Cl2
temp/°C time/h
3
yield/%b
(5) (a) Nakanishi, H.; Fujita, H.; Yamamoto, O. Bull. Chem. Soc. Jpn.
1978, 51, 214. (b) Parker, K. A.; Adamchuk, M. R. Tetrahedron Lett. 1978,
1689-1692. (c) Perrin, C. L.; Young, D. B. Tetrahedron Lett. 1995, 36,
7185-7188. (d) Toyota, M.; Wada, Y.; Fukumoto, K. Heterocycles 1993,
35, 111-114.
(6) Polar solvent effect on the IMDA reaction of ester-tethered sub-
strates: (a) Jung, M. E.; Gervay, J. J. Am. Chem. Soc. 1989, 111, 5469-
5470. (b) Jung, M. E. Synlett 1990, 4, 186-190. See also intramolecular
radical addition of allyl R-iodoalkanoates in water: Yoshimitsu, H.;
Nakamura, T.; Shinokubo, H.; Oshima, K.; Omote, K.; Fujimoto, H. J. Am.
Chem. Soc. 2000, 122, 11041-11047.
1
2
3c
4
5
6c
7
8
2b
2b
2b
2c
2c
2c
2d
2d
2d
2e
2f
rt
0
1
2
7
1
2
6
1
2
1
2
5
3b
3b
3b
3c
3c
3c
3d
3d
3d
3e
3f
91
85
79
88
90
85
91
95
81
82
78
50
rt
0
50
rt
0
toluene
(7) Efficient IMDA reactions employing hydroxamate tethers have been
reported. Ichikawa, T.; Senzaki, M.; Kadoya, R.; Morimoto, T.; Miyake,
N.; Izawa, M.; Saito, S.; Kobayashi, H. J. Am. Chem. Soc. 2001, 123, 4607-
4608.
9c
10
11
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
50
rt
80
(8) (a) Jung, M. E.; Huang, A.; Johnson, T. W. Org. Lett. 2000, 2, 1835-
1837. For theoretical discussions of the transition states in the IMDA reaction
of 1,3,9-decatrienoates, see: (b) Tantillo, D. J.; Houk, K. N.; Jung, M. E.
J. Org. Chem. 2001, 66, 1938-1940. (c) See also ref 4a.
a 1.1 equiv of TfN[Al(Me)Cl]2 was used unless otherwise stated.
b Isolated yield. c 30 mol % of 1 was used.
4620
Org. Lett., Vol. 4, No. 26, 2002

proceeded within a short period (1-2 h) below room
temperature to give the cycloadducts 3b-e in good yields.
Even a catalytic amount of 1 (30 mol %) at 50 °C in 1,2-
dichloroethane affected the IMDA reaction in a synthetically
useful manner (entries 3, 6, and 9). In all cases shown in
Table 2, cis-fused IMDA adducts 3b-f were obtained as a
single isomer with the illustrated relative configuration.13 The
observed diastereoselectivity, in particular the relative con-
figuration between the Me group and the ring-junction in
3b, indicates that the reaction proceeds via endo-boatlike
transition state A. This conformational preference is in accord
with previous results in 1,3,9-decatrienone studies2a and fully
consistent with the favorable geometric influence of the
To gain a qualitative understanding of the activation of
ester-tethered substrates by Lewis acids such as 1, we have
carried out NMR studies using methyl crotonate. The 13C
NMR spectrum (100 MHz) of a mixture of methyl crotonate
and TfN(AlMe2)2 in CDCl3 at room temperature shows the
original signal of the â-carbon (δ 144.7) shifted to a lower
field (δ 155.8; ∆δ ) 11.1 ppm). The chemical shift
difference of the ester methyl group also shifted to a lower
field (∆δ ) 4.2 ppm). However, TfN[Al(Me)Cl]2 complex
exhibited greater corresponding shifts (∆δ ) 15.1 and ∆δ
) 6.2 ppm). These differences in chemical shift caused by
the complexation with 1 support a significant electronic
activation of the double bond of the enoate moiety.15
In conclusion, we have shown that the IMDA reaction of
1,7,9-decatrienoate derivatives with an ester tether is ef-
ficiently catalyzed by the bidentate Lewis acid, bis-alumi-
nated trifluoromethanesulfonamide 1. Further studies on the
structure of the bidentate complexes, scope in IMDA
reactions, and application to the synthesis of natural products
are under way.
8
bidentate Lewis acid on ester tether.
In the presence of 1 (1.1 equiv), the IMDA reaction of
methacrylate derivative 2g14 proceeded at 50 °C to give an
isomeric mixture of the cycloadducts 3g in 74% yield (endo/
exo ) 14) (Scheme 3). The cis-fused cycloadducts thus
Supporting Information Available: Experimental pro-
cedure for 2 and 3 and their characterization data, and
structure determination of 3b and 3g. This material is
available free of charge via the Internet at http://pubs.acs.org.
Scheme 3
OL026963F
(9) (a) Boeckman, R. K., Jr.; Flam, C. J. Tetrahedron Lett. 1983, 24,
5035-5038. (b) Alexakis, A.; Jachiet, D.; Toupet, L. Tetrahedron 1989,
45, 6203-6210.
(10) For examples of significant activation of the carbonyl group by a
bidentate Lewis acid, see: (a) Hanawa, H.; Maruoka, K. Tetrahedron Lett.
1999, 40, 5365-5368. (b) Hanawa, H.; Maekawa, N.; Maruoka, K.
Tetrahedron Lett. 1999, 40, 8379-8382.
(11) Kim, P.; Hantz, M. H.; Kurth, M. J.; Olmstead, M. M. Org. Lett.
2000, 2, 1831-1834.
(12) Reaction of sulfonamide (TfNH2, PhSO2NH2; 1 mol) and methyl-
aluminum reagent (2 mol) readily liberates 2 mol of gas suggesting the
formation of bis-aluminated sulfonamide. Although the exact structure of
each bis-aluminated sulfonamide is not clear from their NMR spectra, in
this text we have tentatively formulated it as N,N-bis-aluminated structure
RSO2N(AlLn2)2. It has been reported that bis(trimethylsilyl)trifluoro-
methanesulfonamide exists as a mixture of N,N- and N,O-bis-silylated forms
in solution, see: Jonas, S.; Westerhausen, M.; Simchen, G. J. Organomet.
Chem. 1997, 548, 131-137.
(13) Thermal IMDA reaction of 2c (210 °C, 5 h) was reported to give
the cycloadduct (42% yield) as a mixture of stereoisomers. See ref 4b.
(14) To the best of our knowledge, no successful example of the IMDA
reaction of 1,3,9-decatriene systems tethered by an R-substituted ester moiety
such as a methacrylate 2g has been reported.
obtained consist of two isomers in a ratio of 2.3:1. The major
isomer, 3g-endo-1, is derived via endo-boatlike transition
state B, in which R-methyl substituent has a psuedo-flagpole
interaction with the hydrogen attached on the ether carbon.
Endo-chairlike transition state C competitively participates
leading to the formation of the minor isomer 3g-endo-2.8b
(15) The 1H NMR (400 MHz) of TfN[Al(Me)Cl]2 complex at room
temperature showed broadened signals indicating the existence of plural
complex forms in relatively slow equilibrium, which, at -50 °C, turned to
sharp signals of a mixture of three sets of complexes in a ratio of 3:2:1.
Org. Lett., Vol. 4, No. 26, 2002
4621