Novel lactonization of ethenetricarboxylate derivatives: Intermolecular trapping of alkenes

Article abstract of DOI:10.1021/ol047693z

(Chemical Equation Presented) A novel cyclization of 1,1-diethyl 2-tert-butyl ethenetricarboxylate (1a) in the presence of a Lewis acid afforded a 5,5-dimethyl-γ-lactone derivative 2a. The reaction process has been shown to arise from formation by trappin

Full text of DOI:10.1021/ol047693z

ORGANIC
LETTERS
2005
Vol. 7, No. 5
759-762
Novel Lactonization of
Ethenetricarboxylate Derivatives:
Intermolecular Trapping of Alkenes
Shoko Yamazaki,* Kanae Ohmitsu, Kunihiro Ohi, Tetsuya Otsubo, and
Kayo Moriyama
Department of Chemistry, Nara UniVersity of Education, Takabatake-cho,
Nara 630-8528, Japan
yamazaks@nara-edu.ac.jp
Received November 10, 2004
ABSTRACT
A novel cyclization of 1,1-diethyl 2-tert-butyl ethenetricarboxylate (1a) in the presence of a Lewis acid afforded a 5,5-dimethyl-
γ-lactone derivative
2a. The reaction process has been shown to arise from formation by trapping of isobutylene generated in situ. Lewis acid-promoted intermolecular
reactions of 1,1-diethyl 2-hydrogen ethenetricarboxylate (5) and various alkenes to afford highly functionalized γ-lactones were also developed.
Ethenetricarboxylate derivatives have been employed as
highly electrophilic C2 components in Lewis acid-promoted
[2 + 2] and [2 + 1] cycloadditions.1,2 In addition, Lewis
acid-promoted intramolecular cyclizations of ethenetricar-
boxylate esters bearing nucleophilic CdC and CtC bonds
and aromatic rings have been studied.3 As part of our efforts
to demonstrate the utility of Lewis acid-promoted reaction
of highly electrophilic ethenetricarboxylates, a highly unusual
γ-lactone formation by trapping of isobutylene generated in
situ was discovered (eq 1). Furthermore, Lewis acid-
promoted intermolecular reactions of 1,1-diethyl 2-hydrogen
ethenetricarboxylate (5) and alkenes to highly functionalized
γ-lactones were also developed.
1,1-Diethyl 2-tert-butyl ethenetricarboxylate (1a) was used
as an electrophile in Lewis acid-promoted [2 + 1] cycload-
ditions with the nucleophilic olefin 1-(phenylseleno)-2-
(trimethylsilyl)ethene.2 The reactivity of 1a in the absence
of a nucleophile and in the presence of a Lewis acid is of
interest. The reaction of 1a in the presence of SnCl4 or TiCl4
(1.2 equiv) in CH2Cl2 at room temperature for 3 h gave the
γ-lactone 2a in 71-78% yield (eq 1). The reaction of 1a at
-40 °C for 3 h also gave 2a in 75% yield. The reaction at
-78 °C for 3 h did not proceed, and starting material 1a
was recovered. The structure of 2a was suggested by the
presence of two differentiated methyl groups (1H δ 1.39 and
1.48 ppm) and the disappearance of CdCH (1H δ 6.80) and
the tert-butyl group (1H δ 1.49) in 1a. 1H, 13C, 1H/1H-COSY,
1H/13C-HSQC, HMBC, and NOESY spectra and IR spectra
(1) Srisiri, W.; Padias, A. B.; Hall, H. K., Jr. J. Org. Chem. 1994, 59,
5424.
(2) Yamazaki, S.; Kumagai, H.; Takada, T.; Yamabe, S. J. Org. Chem.
1997, 62, 2968.
(3) (a) Snider, B. B.; Roush, D. M. J. Org. Chem. 1979, 44, 4229. (b)
Yamazaki, S.; Yamada, K.; Yamabe, S.; Yamamoto, K. J. Org. Chem. 2002,
67, 2889. (c) Yamazaki, S.; Yamada, K.; Yamamoto, K. Org. Biomol. Chem.
2004, 2, 257. (d) Yamazaki, S.; Morikawa, S.; Iwata, Y.; Yamamoto, M.;
Kuramoto, K. Org. Biomol. Chem. 2004, 2, 3134.
10.1021/ol047693z CCC: $30.25
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(CdO, 1770, 1750, 1735 cm-1) were in accord with the
lactone structure 2a. The reaction of 1a with other Lewis
acids (1.2 equiv) also gave 2a in somewhat lower yields
(FeCl3, 59%; AlCl3, 34%; GaCl3, 33%). The reaction also
proceeded with a catalytic amount of SnCl4 (0.2 equiv) at
room-temperature overnight to give 2a in 67% yield. The
reaction of 1,1-diethyl 2-isopropyl and 1,1,2-triethyl ethene-
tricarboxylates 3a,b in the presence of SnCl4 or FeCl3 (1.2
equiv) in CH2Cl2 at room temperature for 3 h was also
examined; however, only hydrated products 4a,b were
obtained in 12-56% yield, along with starting material 3a,b
(eq 2). The formation of 4 presumably arises from participa-
tion of adventitious water in situ.4
Scheme 1
In addition to the 1,1-diethyl 2-tert-butyl ester, 1,1-
isopropyl 2-tert-butyl ester 1b afforded γ-lactone 2b in 90%
yield; however, the reaction of 1,1-dibenzyl 2-tert-butyl ester
gave a complex, decomposed mixture using SnCl4, TiCl4,
or FeCl3. The reaction of tertiary esters (1,1-dimethylethyl)
1d,e also gave γ-lactones 2d,e in 61-78% yields regiose-
lectively in 3:1-4:1 diastereomer ratios.
Since it was discovered that the γ-lactone formation
reaction proceeds intermolecularly, reactions of carboxylic
acid 5 (prepared by treatment of 1a with CF3COOH)7 with
various alkenes were examined (eq 6, Table 1).8 Alkene
substrates giving cation intermediates stabilized by tertiary-
alkyl, phenyl, and â-silyl groups were investigated. At first,
It was suggested that the formation of γ-lactone 2a
probably proceeds by Lewis acid-catalyzed generation of
isobutylene driven by activation of the tert-butyl ester,
followed by elimination. Addition of isobutylene to the
double bond of ethenetricarboxylate 5 (activated by Lewis
acid chelation to two carboxyl ester groups), followed by
ring closure of carboxyl group to the stable tertiary carbo-
cation thus generated, delivers product 2a (Scheme 1).
To obtain information on the mechanism, the reaction of
1a with 2-methyl-2-butene (1.0 equiv for 1a) with SnCl4 (1.2
equiv for 1a) in CH2Cl2 was examined. The reaction gave a
mixture of 2d (3:1 diastereomer mixture, 71%) and 2a (29%)
(eq 4).5 Furthermore, the reaction of a 1:1 mixture of 1d
and 1b with SnCl4 gave 2a (17%), 2b (21%), 2d (30%),
and 2e (21%), respectively.6 These results demonstrate that
the reaction of carboxylic acids and alkenes generated in situ
proceeds not in an intramolecular but rather in an intermo-
lecular manner.
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Org. Lett., Vol. 7, No. 5, 2005

Table 1. Reaction of 5 with Various Alkenes
a Yields are based on compound 1a. b Structure shows a major diastereomer. c Compound 14b is somewhat volatile.
the reaction of 1a with 2-methyl-2-butene 6 with SnCl4 at
room temperature in CH2Cl2 gave a 3:1 (trans/cis) diastereo-
mer mixture of 2d (Table 1, entry 1), as expected by the
result obtained in eq 4. Compound 5 also reacted with
tetrasubstitued alkene 7 to give γ-lactone 8 in high yield
(entry 2). The reaction of 5 with methylenecycloalkenes 9
in the presence of SnCl4 at -78 °C for 3 h in CH2Cl2 gave
10 as major products (entries 3 and 4).9 The reaction of 5
with 1,1-diphenylethene (11a) and styrene (11b) in the
presence of SnCl4 at -78 °C for 3 h in CH2Cl2 gave 12
(entries 5 and 6). The reaction of 5 with allylsilanes 13 in
the presence of SnCl4 or TiCl4 at -78 °C gave 14 with high
diastereoselectivity (entries 7 and 8). On the other hand,
reaction of 5 with cyclohexene (15) gave γ-lactone 16 in
(8) Typical Procedure (Table 1, Entry 5). To 1a (272 mg, 1.0 mmol)
was added trifluoroacetic acid (4 mL) at 0 °C. The mixture was allowed to
warm to room temperature and stirred for 1.5 h. The mixture was evaporated
in vacuo to give 5 quantitatively. 5: colorless oil; 1H NMR (400 MHz,
CDCl3) δ (ppm) 1.33 (t, J ) 7.1 Hz, 3H), 1.34 (t, J ) 7.1 Hz, 3H), 4.32
(q, J ) 7.1 Hz, 2H), 4.37 (q, J ) 7.1 Hz, 2H), 6.89 (s, 1H), 11.31 (bs, 1H);
13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.72 (q), 13.88 (q), 62.34 (q),
62.79 (q), 128.97 (d), 140.59 (s), 161.97 (s), 164.07 (s), 168.37 (s); IR
(neat) 3200 (broad), 2987, 1737, 1652, 1374, 1338, 1253, 1067 cm-1; MS
(FAB) m/z 217 ((M + H)+); exact mass (M + H)+ 217.0715 (calcd for
C9H13O6 217.0712). To a solution of 5 (1.0 mmol) prepared above in
dichloromethane (1.8 mL) was added 1,1-diphenylethene (11a) (180 mg,
1.0 mmol), followed by SnCl4 (301 mg, 0.135 mL, 1.2 mmol) at -78 °C.
The mixture was stirred for 3 h. The reaction mixture was quenched by
water. The mixture was extracted with dichloromethane, and the organic
phase was washed with saturated aqueous NaHCO3, dried (Na2SO4), and
evaporated in vacuo. The residue was purified by column chromatography
over silica gel eluting with hexane-ether (1:1) to give 12a (417 mg, 92%).
(4) Reaction of 1a with FeCl3 at -40 °C for 3 h also gave hydrated
product 17 in 42% yield.
1
(5) Yields were determined by HNMR of the product mixture.
(6) Product mixture was separated into two fractions (Rf ) 0.4 and 0.5
(hexane-ether ) 1: 1)) by column chromatography, and the yields were
1
estimated by H NMR of the fractions. The diastereomer ratios of 2d and
2e were not precisely determined.
(7) Kelly, T. R. Tetrahedron Lett. 1973, 437.
Org. Lett., Vol. 7, No. 5, 2005
761

generated in situ in the presence of a Lewis acid such as
SnCl4 and TiCl4 gave γ-lactone products in high yields. The
reaction of predeprotected carboxylic acid 1,1-diethyl 2-hy-
drogen ethenetricarboxylate (5) and various alkenes in the
presence of Lewis acid gave cycloadduct γ-lactones. Because
the obtained highly functionalized γ-lactones can be synthetic
intermediates for biologically interesting compounds,12 fur-
ther transformation of the products is ongoing.
Scheme 2
Acknowledgment. This work was supported by the
Ministry of Education, Culture, Sports, Science, and Tech-
nology of the Japanese Government. We are grateful to Prof.
S. Umetani (Kyoto University) and Prof. K. Kakiuchi (Nara
Institute of Science and Technology) for measurement of
mass spectra and elemental analyses. We thank Ms. M.
Yamamoto for experimental help and Dr. S. Hamanaka for
helpful discussions.
low yield (16%) (entry 9). Alkenes such as 15, which give
a secondary alkyl carbocation, seem to be insufficient to
stabilize the intermediate in these reaction conditions.
Supporting Information Available: Experimental pro-
cedures, spectral data, and copies of 1H and 13C NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL047693Z
The stereochemistry of the γ-lactone products was deter-
mined by NOESY spectra. The observed 3,5-cis-selective
stereochemistry for reaction with allylsilanes can be ex-
plained by a synclinical transition state,10 possibly arising
from the secondary orbital interaction between ester carbonyl
and CH2SiR3 groups11 and subsequent γ-lactone ring closure
(Scheme 2).
(9) Reaction of 5 and 9b at room temperature or at -40 °C for 3 h gave
a complex mixture containing 10b and possibly compounds arising from
rearranged alkenes.
(10) (a) Seebach, D.; Golinski, J. HelV. Chim. Acta 1981, 64, 1413. (b)
Panek, J. S.; Jain, N. F. J. Org. Chem. 1993, 58, 2345.
(11) Pan, L.-R.; Tokoroyama, T. Tetrahedron Lett. 1992, 33, 1469.
(12) For examples, (a) Johnson, C. R.; Elliot, R. C.; Meanwell, N. A.
Tetrahedron Lett. 1982, 23, 5005. (b) Jackson, R. F. W.; Raphael, R. A.
Tetrahedron Lett. 1983, 24, 2117. (c) Sakurai, K.; Takahashi, K.; Yoshida,
T. Agric. Biol. Chem. 1983, 47, 1249. (d) Kaiser, R. HelV. Chim. Acta 1984,
67, 1198.
In summary, an unprecedented cyclization of a 1,1-diester
of 2-tert-butyl ethenetricarboxylate by trapping of alkenes
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Org. Lett., Vol. 7, No. 5, 2005