Intramolecular and intermolecular Mn(III)-induced carbon monoxide trapping reactions of alkynes with malonate and cyano ester units

Article abstract of DOI:10.1021/jo9607673

Intra- and intermolecular carbon monoxide trapping reactions of alkynes with malonates and cyano esters were developed using a Mn(III)-induced oxidative system. Phenylacetylene was treated with diethyl ethylmalonate in the presence of Mn(OAc)₃·H₂O, in AcOH-CH₃CN (1:1) under carbon monoxide, affording (Z)-4,4-dicarbethoxy-2-phenyl-2-hexenoic acid. Similarly, intramolecular reactions of 4-alkynylmalonates and cyanoacetates proceeded regio- and stereoselectively under the same conditions to afford the corresponding methylenecycloalkanecarboxylic acids in moderate yields. The reaction involves carbon monoxide trapping of vinyl radicals which are formed by the addition of malonate or cyanoacetate radicals induced by Mn(III) to alkynes.

Full text of DOI:10.1021/jo9607673

5312
J . Org. Chem. 1996, 61, 5312-5315
In tr a m olecu la r a n d In ter m olecu la r Mn (III)-In d u ced Ca r bon
Mon oxid e Tr a p p in g Rea ction s of Alk yn es w ith Ma lon a te a n d
Cya n o Ester Un its
Kazumi Okuro and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received April 26, 1996X
Intra- and intermolecular carbon monoxide trapping reactions of alkynes with malonates and cyano
esters were developed using a Mn(III)-induced oxidative system. Phenylacetylene was treated with
diethyl ethylmalonate in the presence of Mn(OAc)3‚2H2O, in AcOH-CH3CN (1:1) under carbon
monoxide, affording (Z)-4,4-dicarbethoxy-2-phenyl-2-hexenoic acid. Similarly, intramolecular
reactions of 4-alkynylmalonates and cyanoacetates proceeded regio- and stereoselectively under
the same conditions to afford the corresponding methylenecycloalkanecarboxylic acids in moderate
yields. The reaction involves carbon monoxide trapping of vinyl radicals which are formed by the
addition of malonate or cyanoacetate radicals induced by Mn(III) to alkynes.
Manganese(III) acetate is well-known as a strong
olefins to form new alkyl radicals which can trap carbon
monoxide. It seemed reasonable to anticipate the car-
bonylation of alkynes in a manganese(III)-induced oxida-
tive system, where carbon monoxide trapping by a vinyl
radical is the key step in the process. Indeed, radical
carbonylation via a vinyl radical has been described.6
Herein we report the manganese(III)-induced intra-
molecular and intermolecular carbonylation of alkynes
with malonate esters and cyanoesters.
oxidizing agent for enolizable carbonyl compounds to
produce R-oxoalkyl radicals. Reactions involving such
species with olefins or alkynes have attracted consider-
able attention during the last decade because of the
prospects of new carbon-carbon bond-forming processes.1
In particular, Mn(III)-induced intramolecular cyclization
reactions have been successfully utilized for the synthesis
of a variety of compounds,2 including biologically active
ones.3
Resu lts a n d Discu ssion
Although metal-catalyzed carbonylation reactions have
been extensively investigated,4 comparatively few reports
have appeared on radical-mediated carbonylation reac-
tions. Examples include the tin hydride-mediated free
radical carbonylation of halides5 and AIBN-initiated
reaction of alkynes with thiols.6 Recently, one of us
demonstrated the first examples of a manganese(III)-
induced carbon monoxide trapping reaction of dimethyl
malonate and ethyl acetoacetate derivatives with olefins.7
This process is believed to proceed via a radical pathway
where manganese(III) initiates the oxidation of enolizable
compounds to give radicals which undergo addition to
Treatment of phenylacetylene (1) (1.5 mmol) with
diethyl ethylmalonate (2) (3.0 mmol) in the presence of
Mn(OAc)3‚2H2O (4.0 mmol) in acetic acid (10 mL) at 60
°C for 18 h under 600 psi of carbon monoxide gave the
desired carbon monoxide trapping compound 3 in 21%
yield (eq 1). The structure of the product was established
X Abstract published in Advance ACS Abstracts, J uly 15, 1996.
(1) (a) de Klein, W. J . In Organic Synthesis by Oxidation with Metal
Compounds; Mijs, W. J ., de J onge, C. R. H., Eds.; Plenum Press: New
York, 1986; pp 261-314. (b) Iqbal, J .; Bhatia, B.; Nayyar, N. K. Chem.
Rev. 1994, 94, 519. (c) Badanyan, Sh. O.; Melikyan, G. G.; Mkrtchyan,
D. A. Russ. Chem. Rev. 1989, 58, 286. (d) Badanyan, Sh. O.; Melikyan,
G. G.; Mkrtchyan, D. A. Uspekhi Khimii 1989, 58, 475. Recent
publications: (e) Melikyan, G. G.; Vostrowsky, O.; Bauer, W.; Best-
mann, H. J .; Khan, M.; Nicholas, K. M. J . Org. Chem. 1994, 59, 222.
(f) Snider, B. B.; Cole, B. M. J . Org. Chem. 1995, 60, 5376. (g) Hwu, J .
R.; Chen, C. N.; Shiao, S.-S. J . Org. Chem. 1995, 60, 856. (h) Dalko, P.
I. Tetrahedron 1995, 7579.
by spectroscopic methods including NOE measurements
(selective irradiation of the vinylic proton enhanced the
integration of the aromatic and ethyl protons at C-2)
which were of value in assigning stereochemistry. When
the reaction was repeated under 1200 psi of carbon
(2) Melikyan, G. G. Synthesis 1993, 9, 833 and references cited
therein.
(3) (a) Cossy. J .; Leblanc, C. Tetrahedron Lett. 1989, 30, 4531. (b)
Corey, E. J .; Kang, M.-C. J . Am. Chem. Soc. 1984, 106, 5384. (c) Snider,
B. B.; Mohan, R.; Kates, S. A. J . Org. Chem. 1985, 50, 3659. (d) Snider,
B. B.; Mohan, R.; Kates, S. A. Tetrahedron Lett. 1987, 28, 841. (e)
Snider, B. B.; Merritt, J . E.; Dombroski, M. A.; Buckman, B. O. J . Org.
Chem. 1991, 56, 5544. (f) Oumar-Mohamat, H.; Moustrou, C.; Surzur,
J .-M; Bertrand, M. P. J . Org. Chem. 1989, 54, 5684. (g) Paquette, L.
A.; Schaefer, A. G.; Springer, J . P. Tetrahedron 1987, 43, 5567. (h)
Rama Rao, A. V.; Rao, B. V.; Reddy, D. R.; Singh, A. K. J . Chem. Soc.,
Chem. Commun. 1989, 400. (i) White, J . D.; Somers, T. C.; Yager, K.
M. Tetrahedron Lett. 1990, 31, 59. (j) Colombo, M. I.; Singnorella, S.;
Mischne, M. P.; Gonzalez-Sierra, M.; Ruveda, E. A. Tetrahedron 1990,
46, 4149. (k) Yang, F. Z.; Trost, M. K.; Fristad, W. E. Tetrahedron Lett.
1987, 28, 1493.
(5) (a) Ryu, I.; Nagahara, K.; Yamazaki, H.; Tsunoi, S.; Sonoda, N.
Synlett 1994, 8, 643. (b) Ryu, I.; Yamazaki, H.; Ogawa, A.; Kambe, N.;
Sonoda, N. J . Am. Chem. Soc. 1993, 115, 1187. (c) Ryu, I.; Yamazaki,
H.; Kusano, K.; Ogawa, A.; Sonoda, N. J . Am. Chem. Soc. 1991, 113,
8558. (d) Ryu, I.; Kusano, K.; Yamazaki, H.; Sonoda, N. J . Org. Chem.
1991, 56, 5003. (e) Ryu, I.; Kusano. K.; Hasegawa, M.; Kambe, N.;
Sonoda, N. J . Chem. Soc., Chem. Commun. 1991, 1018. (f) Ryu, I.;
Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. J . Am. Chem. Soc. 1990,
112, 1295. (g) Ryu, I.; Kusano, K.; Masumi, N.; Yamazaki, H.; Ogawa,
A.; Sonoda, N. Tetrahedron Lett. 1990, 31, 6887.
(6) Nakatani, S.; Yoshida, J .-I; Isoe, S. J . Chem. Soc., Chem.
Commun. 1992, 880.
(7) Ryu, I.; Alper, H. J . Am. Chem. Soc. 1993, 115, 7543.
(4) Colquhoun, H. M.; Thompson, D. J .; Twigg, M. V. Carbonylation;
Plenum: New York, 1991.
S0022-3263(96)00767-0 CCC: $12.00 © 1996 American Chemical Society

Mn(III)-Induced Carbon Monoxide Trapping Reactions
J . Org. Chem., Vol. 61, No. 16, 1996 5313
Ta ble 1. Ca r bon Mon oxid e Tr a p p in g of Alk yn yl
Ma lon a te a n d Cya n oa ceta te Der iva tives by Mn (III)a
monoxide, the yield was improved somewhat to 30%,
while an increase in temperature to 100 °C afford 21%
of 3. While the reaction proceeded in acetonitrile alone
as a solvent (10%), the mixed-solvent system of acetic
acid-acetonitrile (1:1) gave the best results, the yield of
pure 3 being 40%. No simple oxidative addition products
such as ethyl 2-carbethoxy-2-ethyl-5-phenyl-3-butene-
carboxylic acid were observed in these reactions. No
reaction occurred when 1-decyne was used instead of
phenylacetylene. Para-substituted phenylacetylenes
(-CN, -OMe, and -Pri) and 2-naphthylacetylene reacted
with ethyl diethylmalonate (2) and carbon monoxide to
some extent, but the yields of the desired products were
too low (4-12%) to be of synthetic use. Therefore, we
turned our attention to the intramolecular reaction which
we expected to be more efficient than the intermolecular
process.
Methyl 2-carbomethoxy-6-heptynoate (4a ) was sub-
jected to the optimum conditions used for the Mn(OAc)3-
induced reaction of 1 with 2, and (E)-dimethyl 2-[(hy-
droxycarbonyl)methylene]-1,1-cyclopentanedicarbox-
ylate (5a ) was formed as the only product in 27% yield
(Table 1).8 In contrast to the intermolecular reaction, the
yield of 5a increased substantially (to 44%) when the
reaction was carried out at 90 °C.10 While other enoliz-
able analogs such as ethyl 2-acetyl-6-heptynoate, 6,6-
dicyano-1-hexynoate, and 2-(4-toluenesulfonyl)-6-hep-
tynoate did not undergo reaction, ethyl cyanoacetate
derivatives were successfully employed in the Mn(OAc)3-
induced carbonylation reaction. For instance, when ethyl
2-cyano-6-heptynoate (4b) was treated with carbon mon-
oxide and Mn(OAc)3‚2H2O under the standard conditions,
the corresponding conjugated acid 5b was formed in 43%
isolated yield. The results of other cyclization reactions
are listed in Table 1. Methyl 2-carbomethoxy-7-oc-
tynoate, (4c), which has four methylene units between
the reactive centers, also underwent carbonylation to
selectively afford the six-membered ring compound 5c.
Also, the presence of a gem-dimethyl group in the
reactant (4d and 4e) has no effect (4e), or can be
beneficial (4d ), in terms of the yield. Similarly, a 58:42
mixture of diastereomers 4f, underwent carbonylation to
give a 64:36 mixture of the stereoisomers 5f. It should
be noted that these reactions are both regio- and stereo-
selective in nature. The 1H-NMR spectrum of crude
material obtained in each reaction indicated the exclusive
formation of the exo-type product. The stereochemistry
of this reaction is apparently kinetically controlled since
the vinyl radical is known to rapidly undergo stereoiso-
meric equilibration.11 It seems likely that carbon mon-
oxide is trapped by the stereoisomer with the less
sterically hindered site (i.e. A in Scheme 1). If electron
transfer from the acyl radical to the Mn(III) species
leading to an acyl cation (B f C and B′ f C′) takes place
by complexation, the conversion of B f C may be more
a
Reaction conditions: [substrate]/[Mn(OAc)3‚2H2O] (1:2.7), CO
b
1200 psi, 90 °C, CH3COOH/CH3CN (1:1) (10 mL), 15 h. Reaction
at 60 °C. c The ratio of two diastereoisomers was determined on
the basis of the 1H-NMR spectra of methyl protons at C-3. (R*,S*)/
(R*,R*) (58:42).
Sch em e 1
facile than that of B′ f C′ since steric repulsion may
occur between the substituents E, E′ and Mn(III) in the
case of intermediate B′. The intramolecular reaction is
also applicable to the allenic diester 4g, affording 5g and
5g′ as the byproduct, the latter being derived from 5g
by isomerization.
Several internal alkynes were used as reactants for the
Mn(III)-induced process. Methyl 2-carbomethoxy-4-un-
decynoate (4h ) reacted with carbon monoxide in the same
manner as terminal alkynes affording the acid 5h in 40%
yield (eq 2). However, methyl 2-carbomethoxy-7-phenyl-
6-heptynoate (4i) reacted to give three compounds 6
(17%), 7 (26%), and 8 (yield was not determined) in which
no CO incorporation took place (eq 3). The same products
(8) To confirm the five-membered ring structure, the compound
obtained from the carbonylation of 4a was subjected to oxidation with
RuCl3-NaIO4 in CH3CN-CCl4-H2O at room temperature for 30 min
under N2,9 affording 2,2-bis(methoxycarbonyl)cyclopentanone in 20%
isolated yield as the sole product. The low yield is probably due to the
strong oxidation conditions used: 1H-NMR (200 MHz, CDCl3) δ 1.99
(tt, 2 H, J ) 7.0, 7.5 Hz), 2.43 (t, 2 H, J ) 7.5 Hz), 2.63 (t, 2 H, J ) 7.0
Hz), 3.79 (s, 3 H), 3.80 (s, 3 H); 13C-NMR (50 MHz, CDCl3) δ 20.27,
33.51, 38.04, 53.92, 68.55, 167.97, 207.41; MS m/z 200 (M+).
(9) Carlsen, P. H. J .; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J .
Org. Chem. 1981, 46, 3936.
(10) The yield was 47% when the reaction temperature was in-
creased to 120 °C.
(11) (a) Kampmeier, J . A.; Fantazier, R. M. J . Am. Chem. Soc. 1966,
88, 1959. (b) Singer, L. A.; Kong, N. P. J . Am. Chem. Soc. 1966, 88,
5213. (c) Bentrude, W. G. Annu. Rev. Phys. Chem. 1967, 18, 283.

5314 J . Org. Chem., Vol. 61, No. 16, 1996
Okuro and Alper
and concentrated. The resulting crude product was treated
with dimethyl malonate according to the procedure previously
1
reported:13 yield 49%; oil; H-NMR (200 MHz, CDCl3) δ 0.67
(s, 6 H), 2.01-2.11 (m, 5 H), 3.45 (t, 1 H, J ) 6.4 Hz), 3.74 (s,
6 H); 13C-NMR (50 MHz, CDCl3) δ 26.09, 31.72, 33.19, 39.35,
47.99, 52.59, 70.55, 81.38, 170.29; MS (CI) m/z 227 (M + 1);
HRMS (EI) calcd for C11H15O3(M - OCH3) 195.1021, found
195.1013.
Syn th esis of Eth yl 2-Cya n o-4,4-d im eth yl-6-h ep tyn oa te
(4e). The trifluoromethanesulfonyl ester of 2,2-dimethyl-4-
pentyn-1-ol15 (20 mmol, 2.24 g) was reacted with ethyl cy-
anoacetate (20 mmol, 2.26 g) in the same manner as 4a :13 yield
37%; oil; 1H-NMR (200 MHz, CDCl3) δ 1.09 (s, 6 H), 1.33 (t, 3
H, J ) 7.1 Hz), 2.02-2.22 (m, 5 H), 3.51 (dd, 1 H, J ) 5.0, 8.5
Hz), 4.27 (q, 2 H, J ) 7.1 Hz); 13C-NMR (50 MHz, CDCl3) δ
13.84, 26.18, 26.37, 26.54, 31.73, 33.36, 40.32, 62.91, 71.21,
80.74, 117.42, 166.50; MS (CI) m/z 208 (M + 1); Anal. Calcd
for C12H17NO2: C, 69.52; H, 8.28; N, 5.47. Found: C, 69.67;
H, 8.18; N, 5.37.
Syn th esis of Meth yl 4-Ca r beth oxy-2-ca r bom eth oxy-3-
m eth yl-6-h ep tyn oa te (4f). To a suspension of NaH (80% in
mineral oil, 80 mmol, 2.4 g) in THF (50 mL) was added ethyl
cyanoacetate (80 mmol, 10.4 g) under N2. Propargyl bromide
(80% toluene solution, 80 mmol, 12 g) was then added to this
solution and the mixture was refluxed for 20 h under N2. After
the usual workup, 4-carbethoxy-5-oxo-1-heptyne (45 mmol,
7.47 g) was obtained by distillation under reduced pressure.
To a solution of 4-carbethoxy-5-oxo-1-heptyne in MeOH (20
mL) was added NaBH4 (60 mmol, 2.28 g) at 0 °C. The mixture
was stirred for 30 min at room temperature. Water was added,
and the solution was extracted with ether. After the organic
layer was dried over Na2SO4 and evaporated, the correspond-
ing alcohol (6.0 g, 36 mmol) was obtained by distillation under
reduced pressure. Its trifluoromethanesulfonyl ester was
reacted with dimethyl malonate in the same manner as 4a :13
yield 55% ; oil; 1H-NMR (200 MHz, CDCl3) δ 0.95 (d, 3 H, J )
6.8 Hz), 1.04 (d, 3 H, J ) 6.6 Hz), 1.29 (t, 3 H, J ) 7.1 Hz),
2.02-2.07 (m, 1 H), 2.43-2.80 (m, 4 H), 3.55-3.61 (m, 1 H),
3.75 (s, 6 H), 4.14-4.21 (m, 2 H); 13C-NMR (50 Mz, CDCl3)
(R*, S*) δ 12.70, 13.94, 19.25, 34.02, 45.92, 52.26, 55.07, 60.48,
70.08, 80.55, 168.29, 171.89; (R*, R*) 13.14, 13.94, 17.47, 33.94,
46.69, 52.05, 54.14, 60.61, 70.08, 80.71, 168.41, 172.73; MS
(CI) m/z 285 (M + 1); HRMS (EI) calcd for C13H17O5(M -
OCH3) 253.1076, found 253.1091.
were also observed under N2 (6, 30%; 7, 44%; 8, 9%). The
carbonyl oxygen of the benzoyl group in 6 and 7 may
originate from water contained in manganese(III) acetate.
The formation of these products could be rationalized as
follows. The cyclopentylidene vinyl radical formed from
4i may be oxidized by Mn(III) to the corresponding vinyl
cation much faster than the trapping of carbon monoxide,
and reaction of the cation with water or acetic acid gives
6 or 8, respectively. It is conceivable that further
oxidation of 6 to 7 by Mn(III) can occur since 6 still has
an enolizable hydrogen. However, 6 was recovered
unchanged when treated with manganese(III) acetate
under the same conditions. Similarly, 7 was not detected
on exposure of 8 to manganese(III) acetate. Therefore,
7 is not formed from 6 or 8.
In conclusion, the regio- and stereoselective manga-
nese(III)-induced carbon monoxide trapping reaction of
alkynyl malonate and cyano ester derivatives has been
established, affording functionalized methylenecyclo-
alkanes in moderate yields. [(Hydroxycarbonyl)methyl-
ene]cycloalkanes obtained in this work are of consider-
able utility in the organic synthesis. For example, they
serve as reactants with dihydroxybenzenes in the syn-
thesis of 2-spirobenzopyrans, some of which are biologi-
cally active.12
Syn th esis of Meth yl 2-Ca r bom eth oxy-6-u n d ecyn oa te
(4h ). 1-Chloro-4-nonyne (15.12 mmol, 2.4 g) was reacted with
dimethyl malonate (18.16 mmol, 2.4 g) using NaH (80% in
mineral oil, 16.64 mmol, 500 mg) and KI (7.52 mmol, 1.26 g)
in DMF/THF (15 mL/15 mL) in the same manner as 4a ,13 yield
Exp er im en ta l Section
1
64%, oil; H-NMR (200 MHz, CDCl3) δ 0.90 (t, 3 H, J ) 7.1
Gen er a l. Proton and carbon magnetic resonance spectra
were recorded on a 500 MHz spectrometer. Preparative high-
performance liquid chromatography was carried out using a
J AI LC-908 instrument containing a J AIGEL 2H column.
Elemental analyses were performed by the elemental analysis
service of the department of chemistry at the University of
Ottawa.
Glacial acetic acid and acetonitrile were used as received.
Manganese(III) acetate dihydrate was purchased from Aldrich
and was used as received. Phenylacetylene (1) and diethyl
ethylmalonate (2) were purchased from Aldrich and were
distilled prior to use. The reactants 4a ,13 4b,13 4c,14 and 4g14
were prepared according to the previously reported methods.
Syn th esis of Meth yl 2-Ca r bom eth oxy-4,4-d im eth yl-6-
h ep tyn oa te (4d ). To a solution of 2,2-dimethyl-4-pentyn-1-
ol15 (20 mmol, 2.24 g) in anhydrous dichloromethane (15 mL)
were added pyridine (25 mmol, 2.0 g) and trifluoromethane-
sulfonic anhydride (22.3 mmol, 6.3 g) at 0 °C. The mixture
was stirred for 2 h at room temperature under N2 and diluted
with dichloromethane; it was then washed with diluted
hydrochloric acid. The organic layer was dried over Na2SO4
Hz), 1.38-1.55 (m, 6 H), 1.95-2.22 (m, 6 H), 3.41 (t, 1 H, J )
7.6 Hz), 3.74 (s, 3 H); 13C-NMR (50 MHz, CDCl3) δ 13.49, 18.30,
21.80, 26.62, 27.87, 31.02, 51.13, 52.34, 78.75, 80.88, 169.61;
MS (CI) m/z 255 (M + 1); HRMS (EI) calcd for C13H19O3(M -
OCH3): 223.1334; Found: 223.1318.
Syn th esis of Meth yl 2-Ca r bom eth oxy-7-p h en yl-6-h ep -
tyn oa te (4i). 1-Chloro-5-phenyl-4-pentyne (15.2 mmol, 2.7 g),
obtained from the reaction of iodobenzene with 4-chloro-1-
16
pentyne using PdCl2(PPh)3 as a catalyst, was reacted with
dimethyl malonate (18.3 mmol, 2.42 g) using NaH (80%
mineral oil, 16.8 mmol, 502 mg) and KI (7.2 mmol, 1.2 g) in
THF / DMF (1:1) (30 mL) in a similar manner to that of 4a :13
1
yield 88%; oil; H-NMR (200 MHz, CDCl3) δ 1.60-1.71 (m, 2
H), 2.02-2.14 (t, 2 H, J ) 7.0 Hz), 2.44 (t, 2 H, J ) 7.0 Hz),
3.73 (s, 6H), 7.25-7.41 (m, 5 H); 13C-NMR (50 MHz, CDCl3) δ
18.96, 26.26, 27.92, 51.11, 52.37, 81.13, 88.89, 123.63, 127.51,
127.77, 128.06, 131.41, 169.53; MS (EI) m/z 274 (M+); HRMS
C16H18O4 calcd 274.1205, found 274.1227.
Ca r bon yla tion of P h en yla cetylen e (1) w ith Dieth yl
E t h ylm a lon a t e (2). Deaerated acetic acid-acetonitrile
(1:1) (10 mL), Mn(OAc)3‚2H2O (4.0 mmol, 1074 mg), phenyl-
acetylene 1 (1.5 mmol, 152 mg), and diethyl ethylmalonate (3.0
mmol, 565 mg) were placed in a 50 mL stainless steel autoclave
containing a glass liner. The autoclave was pressurized to
(12) Dike, S. Y.; Merchant, J . R.; Sapre, N. Y. Tetrahedron 1991,47,
4775.
(13) Fournet, G.; Balme, G.; Gore, J . Tetrahedron 1991, 47, 6293.
(14) Bates, R. W.; Devi, T. R. Tetrahedron Lett. 1995, 36, 509.
(15) Magnus, P.; Slater, M. J .; Principe, L. M. J . Org. Chem. 1989,
54, 5148.
(16) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 50, 4467.

Mn(III)-Induced Carbon Monoxide Trapping Reactions
J . Org. Chem., Vol. 61, No. 16, 1996 5315
1200 psi with carbon monoxide and then heated with stirring
at 60 °C for 15 h. After the reaction, the mixture was diluted
with ether and washed twice with water, and the aqueous
layer was extracted with ether. The combined organic extracts
were washed with aqueous potassium carbonate. The organic
layer was dried over Na2SO4 and concentrated by rotary
evaporation to give recovered starting material. The aqueous
layer was acidified with dilute HCl and then extracted with
ether. The organic layer was washed twice with water and
dried over Na2SO4. The acid 3 (205 mg, 40%) was obtained
by flash chromatography on silica gel with hexane/EtOAc/
MeOH (8:2:1) as an eluant. This procedure was used for the
intramolecular reactions.
(Z)-4,4-Dica r beth oxy-2-p h en yl-2-h exen oic a cid (3): oil;
1H-NMR (200 MHz, CDCl3) δ 0.92 (t, 3 H, J ) 7.5 Hz), 1.25 (t,
3 H, J ) 7.1 Hz), 2.34 (q, 2 H, J ) 7.5 Hz), 4.22 (q, 2 H, J )
7.1 Hz), 6.86 (s, 1 H), 7.33-7.46 (m, 5H), 9.83 (brs, 1 H); 13C-
NMR (50 MHz, CDCl3) δ 9.28, 13.88, 29.32, 60.09, 61.84,
127.75, 128.21, 128.28, 135.20, 137.12, 137.53, 169.73, 171.87;
MS (CI) m/z 335 (M + 1); HRMS Calcd for C18H22O6 334.1416,
found 334.1410.
NMR (50 Mz, CDCl3) δ 13.84, 27.85, 28.05, 39.76, 46.00, 48.63,
51.58, 52.19, 63.71, 118.94, 119.48, 160.17, 165.84, 166.42; MS
m/z 250 (M - CH3); HRMS calcd for C14H19NO4 265.1314;
found 265.1305.
(E)-1,1-Dim eth yl-3-eth yl 5-[(h yd r oxyca r bon yl)m eth yl-
en e]-2-m eth yl-1,1,3-cyclop en ta n etr ica r boxyla te (5f): 1H-
NMR (500 MHz, CDCl3) δ trans, 1.01 (d, 3 H, J ) 6.6 Hz),
1.27 (t, 3 H, J ) 7.1 Hz), 2.70-2.76 (m, 1 H), 2.92-3.03 (m, 2
H), 3.46-3.52 (m, 1 H), 3.72 (s, 3 H), 3.73 (s, 3 H), 4.17 (q, 2
H, J ) 7.1 Hz), 6.21 (t, 1 H, J ) 2.5 Hz), 10.02 (brs, 1 H); cis
0.76 (d, 3 H, J ) 7.2 Hz), 3.16-3.25 (m, 3 H), 3.33-3.38 (m, 1
H), 3.73 (s, 3 H), 3.81 (s, 3 H), 6.21 (t, 1 H, J ) 2.5 Hz), 10.02
(brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ trans 14.10, 14.21,
36.67, 44.47, 48.17, 52.69, 53.18, 60.94, 68.90, 117.14, 120.98,
160.91, 168.34, 171.39, 173.52; cis 11.72, 14.21, 32.42, 41.42,
45.97, 52.69, 53.49, 60.71, 70.09, 120.90, 128.28, 168.47,
168.61, 171.39, 172.07; MS (CI) m/z 329 (M + 1); Anal. Calcd
for C15H20O8: C, 54.87; H, 6.15; found: C, 55.01; H, 6.13.
Dim et h yl 2-[1-(h yd r oxyca r b on yl)et h en yl]-1,1-cyclo-
p en ten ed ica r boxyla te (5g): mp 94-95 °C; 1H-NMR (200
MMz, CDCl3) δ 1.67-1.97 (m, 5 H), 2.01-2.18 (m, 1 H), 3.60
(s, 3 H), 2.72 (s, 3 H), 3.93 (t, 1 H, J ) 7.6 Hz), 5.72 (s, 1 H),
6.38 (s, 1 H), 9.10 (brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ
23.45, 31.65, 35.10, 45.83, 52.03, 52.65, 64.09, 127.59, 140.36,
170.76, 172.21, 172.56; MS (CI) m/z 257 (M + 1); Anal. Calcd
for C12H16O6: C, 56.24; H, 6.31. Found: C, 56.67; H, 6.23.
(E)-Dim eth yl 2-(Hyd r oxyca r bon ylm eth ylen e)-1,1-cy-
clop en ta n ed ica r boxyla te (5a ): mp 76-77 °C; 1H-NMR (200
MHz, CDCl3) δ 1.82 (tt, 2 H, J ) 7.0, 7.0 Hz), 2.38 (t, 2 H, J
) 7.0 Hz), 2.93 (dt, 2 H, J ) 2.0, 7.0 Hz), 3.77 (s, 6 H), 6.15 (s,
1 H), 9.55 (brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ 23.73, 32.97,
35.18, 53.02, 66.06, 117.44, 128.11, 163.18, 169.62; MS (CI)
m/z 243 (M + 1). Anal. Calcd for C11H14O6: C, 54.53; H, 5.84.
Found: C, 54.61; H, 5.85.
(E)-Dim eth yl 2-[(Hyd r oxyca r bon yl)bu tylm eth ylen e]-
1,1-cyclop en ta n ed ica r boxyla te (5h ): mp 94-96 °C; 1H-
NMR (200 MHz, CDCl3) δ 0.89 (t, 3 H, J ) 6.8 Hz), 1.29-1.32
(m, 4 H), 1.74 (tt, 2 H, J ) 7.0, 7.0 Hz), 2.26-2.32 (m, 2 H),
2.41 (t, 2 H, J ) 7.0 Hz), 2.86 (t, 2 H, J ) 7.0 Hz), 3.76 (s, 6
H), 10.12 (brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ 13.89, 23.11,
24.76, 29.67, 31.76, 34.89, 38.96, 52.91, 65.38, 131.05, 151.81,
170.79, 174.26; MS (CI) m/z 299 (M + 1). Anal. Calcd for
(E)-Eth yl 2-[(h yd r oxyca r bon yl)m eth ylen e]-1-cya n o-1-
cyclop en ta n eca r boxyla te (5b): mp 238-241 °C decomposi-
1
tion; H-NMR (200 MHz, acetone-d6) δ 1.32 (t, 3 H, J ) 7.1
Hz), 1.91-2.01 (m, 2 H), 2.18-2.29 (m, 1 H), 2.47-2.53 (m, 1
H), 2.89-2.97 (m, 2 H), 4.28 (q, 2 H, J ) 7.1 Hz), 6.19 (s, 1 H),
9.81 (brs, 1 H). 13C-NMR (50 MHz, acetone-d6) δ 13.96, 24.89,
31.80 37.26, 53.48, 63.50, 119.44, 122.64, 157.01, 167.65,
172.02. This acid was converted to the corresponding methyl
ester17 using MeI and KHCO3, which was characterized as
follows. 1H-NMR (200 MHz, CDCl3) δ 1.34 (t, 3 H, J ) 7.1
Hz), 1.98-2.09 (m, 2 H), 2.23-2.33 (m, 1 H), 2.50-2.60 (m, 1
H), 2.97-3.04 (m, 2 H), 3.75 (s, 3 H), 4.30 (q, 2 H, J ) 7.1 Hz),
6.25 (t, 1 H, J ) 2.6 Hz); 13C-NMR (50 MHz, CDCl3) δ 13.85,
24.35, 31.72, 36.34, 51.52, 52.96, 63.48, 117.74, 118.33, 160.10,
165.77, 166.45; MS (CI) m/z 238 (M + 1); HRMS calcd for
C12H15NO4 237.1001, found 237.0982.
C
15H22O6: C, 60.38; H, 7.45. Found: C, 60.45; H, 7.51.
Dim et h yl 2-Ben zoyl-1,1-cyclop en t a n ed ica r b oxyla t e
(6): oil; 1H-NMR (200 MHz, CDCl3) δ 1.69-1.74 (m, 1 H),
1.84-1.97 (m, 2 H), 2.18-2.31 (m, 2 H), 2.68-2.74 (m, 1 H),
3.56 (s, 3 H), 3.76 (s, 3 H), 4.70 (dd, 1 H, J ) 4.4 , 8.9 Hz),
7.42-7.60 (m, 3 H), 7.97-8.01 (m, 2 H); 13C-NMR (50 Mz,
CDCl3) δ 23.51, 30.81, 34.06, 51.87, 52.29, 53.01, 63.86, 128.54,
128.60, 133.10, 133.31, 136.07, 170.71, 172.28, 200.47. MS (EI)
m/z 290 (M+); HRMS calcd for C16H18O5 290.1154, found
290.1153.
(E)-Dim eth yl 2-[(h yd r oxyca r bon yl)m eth ylen e]-1,1-cy-
cloh exa n ed ica r boxyla te (5c): mp 141-142 °C; 1H-NMR
(200 MHz, CDCl3) δ 1.56-1.64 (m, 2 H), 1.76-1.89 (m, 2 H),
2.05-2.25 (m, 2 H), 2.48-2.53 (m, 2 H), 3.78 (s, 6 H), 7.24 (s,
1 H), 9.85 (brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ 25.17, 25.37,
25.81, 31.76, 53.13, 60.05, 137.07, 140.62, 170.27, 173.04; MS
(CI) m/z 257 (M + 1). Anal. Calcd for C12H16O6: C, 56.24; H,
6.31. Found: C, 56.40; H, 6.24.
Dim eth yl 2-Ben zoyl-2-cyclop en ten e-1,1-d ica r boxyla te
(7): oil; 1H-NMR (200 MHz, CDCl3) δ 2.70-2.76 (m, 4 H), 3.78
(s, 6 H), 6.57 (dd, 1 H, J ) 1.4, 2.1 Hz), 7.40-7.56 (m, 3 H),
7.76-7.82 (m, 2 H); 13C-NMR (50 MHz, CDCl3) δ 32.35, 34.15,
52.82, 66.53, 127.56, 128.19, 128.51, 129.15, 132.37, 137.73,
142.27, 146.82, 171.63, 191.91; MS m/z 288 (M+); HRMS calcd
for C16H16O5 288.0998, found 288.0979.
Dim eth yl 2-(1-Acetoxyben zylid en e)cyclop en ta n e-1,1-
d ica r boxyla te (8): oil; 1H-NMR (200 MHz, CDCl3) δ 1.71 (tt,
2 H, J ) 7.0, 7.0 Hz), 2.10 (s, 1 H), 2.45 (t, 2 H, J ) 7.0 Hz),
2.57 (t, 2 H, J ) 7.0 Hz), 3.42 (s, 6 H), 7.27-7.32 (m, 3 H),
7.45-7.50 (m, 2 H); 13C-NMR (50 MHz, CDCl3) δ 20.76, 22.66,
29.58, 39.81, 52.50, 64.18, 127.63, 128.26, 128.38, 128.58,
129.23, 134.59, 168.31, 170.45; MS m/z 322 (M+); HRMS (EI)
calcd for C16H17O5 (M - COCH3) 289.1076, found 289.1074.
(E)-Dim et h yl 2-[(H yd r oxyca r b on yl)m et h ylen e]-4,4-
d im eth yl-1,1-cyclop en ta n ed ica r boxyla te (5d ): mp 132-
1
134 °C; H-NMR (500 MHz, CDCl3) δ 1.00 (s, 6 H), 2.36 (s, 2
H), 2.79 (d, 2 H, J )2.5 Hz), 3.75 (s, 6 H), 6.15 (t, 1 H, J ) 2.5
Hz), 10.31 (brs, 1 H); 13C-NMR (50 MHz, CDCl3) δ 28.21, 38.29,
47.60, 47.66, 53.34, 66.05, 118.81, 163.40, 170.22, 171.75; MS
(CI) m/z 271 (M + 1); Anal. Calcd for C13H18O6: C, 57.76; H,
6.73. Found: C, 58.10; H, 6.45.
(E)-E t h yl 2-[(h yd r oxyca r b on yl)m et h ylen e]-1-cya n o-
4,4-d im eth yl-1-cyclop en ta n eca r boxyla te (5e): 1H-NMR
(200 MHz, CDCl3) δ 1.14 (s. 3H), 1.21 (s, 3 H), 1.35 (t, 3 H, J
) 7.1 Hz) 2.23 (dd, 1 H, J ) 11.7, 1.8 Hz), 2.43-2.54 (m, 2 H),
3.25 (dd, 1 H, J ) 16.2, 1.8 Hz), 4.33 (q, 2 H, J ) 7.2 Hz),
6.27-6.30 (m, 1 H), 10.15 (brs, 1 H); 13C-NMR (50 Mz, CDCl3)
δ 13.88, 27.95, 28.10, 39.88, 46.39, 48.64, 52.45, 63.90, 118.69,
119.29, 162.84, 166.86, 170.24. This acid was converted to the
methyl ester17 using MeI and KHCO3,which was characterized
as follows: 1H-NMR (200 MHz, CDCl3) δ 1.13 (s, 3 H), 1.21 (s,
3 H), 1.34 (t, 3 H, J ) 7.1 Hz), 2.20 (dd, 1 H, J ) 11.6, 2.0 Hz),
2.44-2.53 (m, 2 H), 3.24 (dd, 1 H, J ) 16.0 Hz, 2.0 Hz), 3.75
(s, 3 H), 4.28 (q, 2 H, J ) 7.1 Hz), 6.25-6.28 (m, 1 H); 13C-
Ack n ow led gm en ts. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for support of this research. We thank Dr. Ilhyong Ryu
and Dr. Yasushi Imada for helpful suggestions and
discussions.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
3, 4d -f, h -i, 5b, methyl ester of 5b, 5e, methyl ester of 5e,
and 6-8 (13 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(17) Hamada, Y.; Shibata, M.; Sugiura, T.; Kato, S.; Shioiri, T. J .
Org. Chem. 1987, 52, 1252.
J O9607673