One-Pot Conversion of α,β-Unsaturated Alcohols into the Corresponding Carbon-Elongated Dienes with a Stable Phosphorus Ylide-BaMnO4 System. Synthesis of 6′-Methylene Derivatives of Neplanocin A as Potential Antiviral Nucleosides. New Neplanocin Analogues. 11

Full text of DOI:10.1021/jo971374m

J . Org. Chem. 1998, 63, 4489-4493
4489
Sch em e 1
On e-P ot Con ver sion of r,â-Un sa tu r a ted
Alcoh ols in to th e Cor r esp on d in g
Ca r bon -Elon ga ted Dien es w ith a Sta ble
P h osp h or u s Ylid e-Ba Mn O4 System .
Syn th esis of 6′-Meth ylen e Der iva tives
of Nep la n ocin A a s P oten tia l
Sch em e 2
An tivir a l Nu cleosid es. New Nep la n ocin
An a logu es. 111
Satoshi Shuto, Satoshi Niizuma, and Akira Matsuda*
Graduate School of Pharmaceutical Sciences, Hokkaido
University, Kita-12, Nishi-6, Kita-ku,
Sapporo 060-0812, J apan
Received J uly 24, 1997
Wittig reaction is a highly versatile method for forming
alkenes from carbonyl derivatives.2 An example of utiliz-
ing Wittig reaction is shown in Scheme 1: oxidation of
R,â-unsaturated alcohols (I),3 in which the C-H bonds
at the R-position of the hydroxyl group are “activated”
by an adjacent π-bond, and subsequent Wittig reaction
of the resulting R,â-unsaturated aldehydes (II) gives the
corresponding diene derivatives (III). This type of pro-
cedure is often useful for constructing carbon-elongated
diene structures in synthetic organic chemistry. In this
paper, we describe an efficient one-pot method for
converting R,â-unsaturated alcohols (I) into the corre-
sponding carbon-elongated diene products (III) with a
stabilized phosphorus ylide-BaMnO4 system.
NPA, 2) and 6′-homoneplanocin A (HNPA, 3), showed
significant antiviral activities. During the course of the
study, we further needed 6′-methylene derivatives of
NPA, such as 4 and 5. A straightforward method for
preparing these compounds would be that as indicated
in Scheme 1. Thus, we examined the oxidation of 6 by
various methods,7 and the 6′-formyl derivative 7 was
produced only when 6 was treated with BaMnO4,8 which
is known to be a useful oxidant of primary allylic alcohols
to aldehydes, in CH2Cl2 (Scheme 2). Due to its instabil-
ity, the aldehyde 7 was immediately treated with
Ph3PdCHCO2Et without purification to give the desired
Considerable attention has recently been focused on
carbocyclic nucleosides because of their biological impor-
tance.4 We previously performed chemical modifications
of neplanocin A (NPA, 1),5 a carbocyclic nucleoside
(3) For examples of oxidation of allycil alcohols, see: (a) Ebenezer,
W. J .; Wighy, P. In Comprehensive Organic Functional Group Tras-
formations; Katritzky, A. R., Methi-Cohn, O., Rees, C. W., Eds.;
Pergamon Press: Oxford, 1995; Vol 3; pp 57 and 215. (b) Procter, G.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 7, pp 305-325.
(4) (a) Marquez, V. E. Carbocyclic nucleosides. In Advances in
Antiviral Drug Design; J AI Press: Greenwich, CT, 1996; Vol 2, p 89-
146. (b) Borthwick, A. D.; Biggadike, K. Tetrahedron 1992, 48, 571-
623. (c) Agrofoglio, L.; Suhas, E.; Farese, A.; Condom, R.; Challand, S.
R.; Earl, R. A.; Guedj, R. Tetrahedron 1994, 50, 10611-10670.
(5) (a) Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi,
M.; Otani, M. J . Antibiot. 1981, 34, 359-366. (b) Hayashi, M.;
Yaginuma, S.; Yoshioka, H.; Nakatsu, K. J . Antibiot. 1981, 34, 675-
680.
(6) (a) Shuto, S.; Obara, T.; Toriya, M.; Hosoya, M.; Snoeck, R.;
Andrei, G.; Balzarini, J .; De Clercq, E. J . Med. Chem. 1992, 35, 324-
331. (b) Shuto, S.; Obara, T.; Saito, Y.; Andrei, G.; Snoeck, R.; De
Clercq, E.; Matsuda, A. J . Med. Chem. 1996, 39, 2392-2399. (c) Obara,
T.; Shuto, S.; Saito, Y.; Snoeck, R.; Andrei, G.; Balzarini, J .; De Clercq,
E.; Matsuda, A. J . Med. Chem. 1996, 39, 3847-3852. (d) Shuto, S.;
Obara, T.; Yaginuma, S.; Matsuda, A. Chem. Pharm. Bull. 1997, 45,
138-142. (e) Shuto, S.; Obara, T.; Saito, Y.; Yamashita, K.; Tanaka,
M.; Sasaki, T.; Andrei, G.; Snoeck, R.; Neyts, J .; Padalko, E.; Balzarini,
J .; De Clercq, E.; Matsuda, A. Chem. Pharm. Bull. 1997, 45, 1163-
1168.
antibiotic, to develop potent antiviral agents.6 In these
studies, we found that some 6′-modified analogues of
neplanocin A, e.g., (6′R)-6′-C-methylneplanocin A (RM-
(7) For example, Swern, Moffatt, Pr4NRuO4, and PDC oxidations
of 6 were tried, but no 7 was obtained.
* Corresponding author. Tel: 81-11-706-3228. Fax: 81-11-706-4980.
E-mail: matuda@pharm.hokudai.ac.jp.
(8) BaMnO4 is easy to handle and requires no activation, which
makes it particulary useful for large-scale reactions; see: (a) Firouza-
badi, H.; Ghaderi, E. Tetrahedron Lett. 1978, 839-840. (b) Fatiadi, A.
J . Synthesis 1987, 85-127. (c) Kim, K. S.; Chung, S.; Cho, I. H.; Hahn,
C. S. Tetraherdon Lett. 1989, 30, 2559-2562.
(1) This paper constitutes Part 169 of Nucleosides and Nucleotides;
Part 168: Ueno, Y.; Kumagai, I.; Haginoya, M.; Matsuda, A. Nucleic
Acids Res. 1997, 25, 3777-3782.
(2) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863-927.
S0022-3263(97)01374-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/30/1998

4490 J . Org. Chem., Vol. 63, No. 13, 1998
Ta ble 1. On e-P ot Syn th esis of Dien e Der iva tives 10-12 fr om Cin n a m yl Alcoh ol (9)a
Notes
% isolated
entry
oxidant
ylide
solvent
CH2Cl2
CH2Cl2
CH2ClCH2Cl
toluene
DMF
CH2Cl2
toluene
CH2Cl2
toluene
temp
rt
reflux
reflux
reflux
100 °C
rt
time (h)
product
yield (E/ Zb)
1
2
3
4
5
6
7
8
2
BaMnO4
BaMnO4
BaMnO4
BaMnO4
BaMnO4
CMD
CMD
BaMnO4
BaMnO4
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCO2Et
Ph3PdCHCOCH3
Ph3PdCHCN
24
4
1.5
1
1.5
24
24
21
0.8
10
10
10
10
10
10
10
11
12
99 (5.8)
98 (6.5)
99 (7.3)
93 (7.5)
98 (7.6)
38 (4.5)c
94 (5.3)
81 (E only)
89 (3.4)
reflux
reflux
reflux
a
Reactions were carried out in 0.2 M substrate solution in the presence of oxidant (1.5 equiv) and ylide (1.3 equiv). bDetermined by
c
HPLC. Starting material was recovered in 57% yield.
Sch em e 3
the recovery of 9 (57%) after 24 h (entry 6). The reaction
with CMD was much faster under reflux in toluene, and
it was completed after 24 h to give the diene 10 in 94%
yield (E/ Z ) 5.3, entry 7). We then investigated the
reaction with other stable phosphorus ylides. When 9
was heated with Ph3PdCHCOMe in the presence of
BaMnO4 under reflux in CH2Cl2, the corresponding diene
11 (E only) was obtained in 81% yield. Similarly,
cyanomethylene diene derivative 12 was also synthesized
in high yield when Ph3PdCHCN was used as a stable
ylide. These results suggest that various stable phos-
phorus ylides can be used in this reaction system. It has
been shown that a large excess of oxidant is usually
required to complete the oxidation reactions by BaMnO4
and MnO2.8,10,11a Thus, it is noteworthy that only 1.5
equiv of BaMnO4 was needed for this oxidation-Wittig
reaction.
Next, the reaction was examined with a variety of
R,â-unsaturated alcohols as substrates, and the results
are summarized in Table 2. The reactions were carried
out with BaMnO4 (1.5 equiv) as the oxidant and
Ph3PdCHCO2Et (1.3 equiv) as the stable phosphorus
ylide. The reaction of geraniol was performed under
reflux in toluene to give the desired Wittig reaction
product in 55% yield (entry 1). When CHCl3 was used
as solvent, the yield was significantly improved and the
product was obtained in 92% yield without epimerization
of the C-C bond (entry 2). Similar results were obtained
with nerol as a substrate, giving the Wittig product
without epimerization (entries 3 and 4). BaMnO4 is an
effective oxidant not only for allylic alcohols but also for
other R,â-unsaturated alcohols such as benzyl alcohols.
Accordingly, treatment of benzyl alcohol under conditions
similar to those in entry 1 gave ethyl trans-cinnamate
quantitatively, as expected (entry 5). Although 2-py-
ridinemethanol has been shown to be oxidized by acti-
vated MnO210c or CMD11c to give 2-pyridinecarbaldehyde,
the yields were moderate. The corresponding Wittig
product of 2-pyridinecarbaldehyde was readily obtained
in high yield from 2-pyridinemethanol in this reaction
system (entry 6). Thiophene- and furanemethanols were
also good substrates to give the desired products (entries
7 and 8). Thus, thienyl and pyridinyl groups, which are
sensitive to a variety of oxidating agents, survived under
diene 8 in low yield (37% from 6). Therefore, we decided
to develop more efficient procedures for converting allylic
alcohols (I), including 6, as well as similar “activated”
alcohols such as benzylic alcohols into the corresponding
dienes (III).
We tested reactions with cinnamyl alcohol (9) as a
substrate under various reaction conditions and found
that 9 is readily converted into diene 10 by treatment
with BaMnO4 in the presence of Ph3PdCHCO2Et (Scheme
3).9 This reaction is very convenient because isolation
of the intermediary aldehyde is not necessary. The
reaction of 9 as a substrate was therefore investigated
in more detail, and the results are summarized in Table
1. The reactions were performed with 1.5 equiv of an
oxidant and 1.3 equiv of a stable ylide. Entries 1-5 are
reactions with BaMnO4 and Ph3PdCHCO2Et. When the
reaction was carried out in CH2Cl2 at room temperature
for 24 h, the diene 10 was isolated quantitatively as a
mixture of (E)- and (Z)-isomers (E/ Z ) 5.8, entry 1). This
reaction proceeded in a variety of polar and nonpolar
solvents to give 10 almost quantitatively, and the reac-
tion rate was significantly increased at a higher temper-
ature (entries 2-5). Activated manganese dioxide (MnO2)
is one of the mildest and most used oxidant for allylic
alcohols.3,10 While various methods for preparing acti-
vated MnO2 have been reported,10 Shioiri and co-workers
recently reported that chemical manganese dioxide (CMD),
an industrial product used in making batteries, was a
more effective oxidizing reagent compared with MnO2
activated by previous methods.11 Therefore, we compared
CMD with BaMnO4 in this reaction and found that CMD
also functioned as an oxidant in this reaction system.
However, the reaction was slower than that with
BaMnO4; the reaction carried out under the same condi-
tions as indicated in entry 1, except that BaMnO4 was
replaced by CMD, gave a 38% yield of diene 10 along with
(9) Although we investigated other oxidating agents in this reaction
system, these were unsuccessful. For example, when 9 was treated
with Dess-Martin reagent or PDC in the presence of Ph3PdCHCO2-
Et, no 10 was obtained.
(10) (a) Cahiez, G.; Alami, M. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; 1995; Vol 5 (L-M), pp 3229-
3235. (b) Papadopoulos, E. P.; J arrar, A.; Issidorides, C. H. J . Org.
Chem. 1966, 31, 615-616. (c) Goldman, I. M. J . Org. Chem. 1969, 34,
1979-1981.
(11) The yields of MnO2 oxidation sometimes vary, since the
reactivity of activated MnO2 depends on the method of preparation,
and commercially available activated MnO2 is not efficient for all of
the desired oxidation reactions (see ref 8a). Shioiri reported that CMD
has a constant efficiency as an oxidant: (a) Hamada, Y.; Shibata, M.;
Sugiura, T.; Kato, S.; Shioiri, T. J . Org. Chem. 1987, 52, 1252-1255.
(b) Matsubara, J .; Nakao, K.; Hamada, Y.; Shioiri, T. Tetrahedron Lett.
1992, 33, 4187-4190. (c) Shioiri, T.; Aoyama, T.; Hamada, Y. Wako
J unyaku J ihou 1997, 65, 12-14.

Notes
J . Org. Chem., Vol. 63, No. 13, 1998 4491
Ta ble 2. Rea ction of “Activa ted ” Alcoh ols w ith
Ta ble 3. Step w ise Rea ction w ith Ba Mn 4O a n d
P h 3P dCHCO2Et-Ba Mn O4 System a
P h 3P dCHCO2Eta
a
Substrate was heated under reflux in CHCl3 in the presence
of 1.5 equiv of BaMnO4 for the same time as the corresponding
entry in Table 2 or until the substrate disappeared on TLC, and
then insoluble oxidant was filtered off. The filtrate was evaporated,
and the residual aldehyde was treated with 1.3 equiv of
b
Ph3PdCHCO2Et in CHCl3 until it disappeared on TLC. Deter-
mined from the 1H NMR spectrum. c The corresponding Wittig
reaction product was also not obtained at all when CH2Cl2 was
used as a solvent for the oxidation reaction.
Sch em e 4
a
Substrate was heated under reflux in the indicated solvent
in the presence of 1.5 equiv of BaMnO4 and 1.3 equiv of
Ph3PdCHCO2Et until both substrate alcohol and its intermediary
b
aldehyde disappeared on TLC, except for entry 10. After 66 h,
obtained as a mixture with phenyl methyl ketone, and the yield
was determined from the 1H NMR spectrum.
strates and compared the results with those of the above
one-pot method. The reactions were carried out with
BaMnO4 (1.5 equiv) and Ph3PdCHCO2Et (1.3 equiv), and
the results are summarized in Table 3. Substrates were
heated with BaMnO4 under reflux in CHCl3, and the
resulting aldehyde, which was not isolated, was then
treated with Ph3PdCHCO2Et in the same solvent. As a
result, the yields were lower than those of the corre-
sponding one-pot reactions. Thus, the effectiveness of the
one-pot method was clearly demonstrated.
Finally, this one-pot method was applied to the syn-
thesis of 6′-methylene derivatives of NPA. When 2′,3′-
O-isopropylideneneplanocin A (6) was heated in the
presence of BaMnO4 and Ph3dCHCO2Et in CH2Cl2, the
desired (E)-6′-ethoxycarbonylmethylene derivative 8 was
isolated in 85% yield (Scheme 4). Similarly, 6′-cyanom-
ethylene derivative 13 was readily obtained in good yield
as a mixture of E/ Z isomers in a ratio of 3.6:1.
these reaction conditions. This reaction system also
converted cyclopropanemethanol12 into the cyclopropyl
alkene derivative quantitatively (entry 9). Thus, all of
the primary “activated” alcohols tested were effective
substrates in this reaction system, and the corresponding
C2-elongated products were obtained in very high yields
(entries 5-9). However, this reaction system was not
effective for a secondary benzylic alcohol (entry 10), which
could be predicted from the known insufficient reactivity
of stable phosphorus ylides to ketones.13
We next investigated the reactions by a stepwise
oxidation-Wittig reaction procedure with several sub-
(12) Cyclopropylmethanols have been reported to have allylic alcohol-
like reactivity: Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.
Chem. Rev. 1989, 89, 165-198.
(13) (a) Trippett, S.; Walker, D. M. J . Chem. Soc. 1961, 1266-1272.
(b) Sakai, T.; Seko, K.; Tsuji, A.; Utaka, M.; Takeda, A. J . Org. Chem.
1982, 47, 1101-1106.
We studied the reaction with various alcohols and all
of the reactions gave (E)-alkenes selectively, which is

4492 J . Org. Chem., Vol. 63, No. 13, 1998
Notes
Anal. Calcd for C11H9N: C, 85.13; H, 5.85; N, 9.03. Found C,
85.00; H, 6.11; N, 8.91.
consistent with known stereoselectively of the Wittig
reaction with stable ylides.14
Eth yl 5,9-Dim eth yl-2,4,8-d eca tr ien oa te (Ta ble 2, En tr ies
As described above, the overall yields of the stepwise
oxidation and Wittig reaction were lower than those of
the one-pot system. This may be, at least in some cases,
due to instability of the R,â-unsaturated aldehyde (II),
which would decrease the isolate yield, especially in the
oxidation step.15 Although this one-pot reaction also
occurs via unstable R,â-unsaturated aldehydes (II), these
would be quickly converted into the corresponding Wittig
reaction products (III), which are generally stable com-
pared to the corresponding aldehydes (II). In addition,
in previous BaMnO4 and MnO2 oxidations, a large excess
of the oxidant is often required to complete the reaction,8a,10
and the absorption of compounds to polar sites of the
surface of the oxidation reagent has been presumed.10a
This may also decrease the yield of the BaMnO4 and
MnO2 oxidations. Accordingly, the excellent yields in this
reaction system may also be due to the reactions to be
completed using only a slight excess of BaMnO4.
In conclusion, we developed an efficient one-pot method
for elongating the carbon skeleton of R,â-unsaturated
primary alcohols. This method can be effectively used
in synthetic organic chemistry.
1, 2). (2E,4E)-Isom er :16 EI-MS m/z 222 (M+). Anal. Calcd for
C
14H22O2‚0.1H2O: C, 75.03; H, 9.98. Found: C, 75.17; H, 10.08.
(2Z,4E)-Isom er :16 EI-MS m/z 222 (M+). Anal. Calcd for
C
14H22O2: C, 75.63; H, 9.97. Found: C, 75.29; H, 10.01.
Eth yl 5,9-d im eth yl-2,4,8-d eca tr ien oa te (Ta ble 2, en tr ies
3
a n d 4)16 was obtained as
a mixture of (2E,4Z)- and
(2Z,4Z)-isomers: EI-MS m/z 222 (M+). Anal. Calcd for
C14H22O2‚0.4H2O: C, 73.26; H, 10.01. Found: C, 73.17; H, 9.70.
Eth yl cin n a m a te (Ta ble 2, en tr y 5)20 was obtained as an
E/ Z mixture: EI-MS m/z 176 (M+). Anal. Calcd for C11H12O2:
C, 74.98; H, 6.86. Found: C, 74.80; H, 6.97.
Eth yl 3-(2-p yr id yl)-2-p r op en oa te (Ta ble 2, en tr y 6)21,22
was obtained as an E/ Z mixture: EI-MS m/z 177 (M+). Anal.
Calcd for
Found: C, 67.17; H, 6.41; N, 7.67.
C10H11NO2‚0.1H2O: C, 67.10; H, 6.31; N, 7.82.
Eth yl 3-(3-F u r a n yl)-2-p r op en oa te (Ta ble 2, en tr y 7). (E)-
Isom er :23 EI-MS m/z 166 (M+).
Anal. Calcd for
C9H10O3‚0.2H2O: C, 63.67; H, 6.17. Found: C, 63.72; H, 5.98.
1
(Z)-Isom er : H NMR (CDCl3) δ 8.13 (s, 1 H), 7.41 (d, 1 H, J )
1.8 Hz), 6.94 (d, 1 H, J ) 1.8 Hz), 6.71 (d, 1 H, J ) 12.5 Hz),
5.80 (d, 1 H, J ) 12.5 Hz), 4.22 (q, 2 H, J ) 7.0 Hz), 1.31 (t, 3 H,
J ) 0.70 Hz); HRMS (EI) calcd for C9H10O3 166.0630, found
166.0625.
Eth yl 3-(2-th ien yl)p r op en oa te (Ta ble 2, en tr y 8)24 was
obtained as an E/ Z mixture: EI-MS m/z 182 (M+). Anal. Calcd
for C9H10O2S: C, 53.92; H, 5.53. Found: C, 59.25; H, 5.58.
Eth yl 3-cyclop r op yl-2-p r op en oa te (Ta ble 2, en tr y 9)25
was obtained as an E/ Z mixture: EI-MS m/z 140 (M+). Anal.
Calcd for C8H12O2: C, 68.55; H, 8.63. Found: C, 68.38; H, 8.62.
Eth yl 3-p h en yl-2-bu ten oa te (Ta ble 2, en tr y 10)26,27 was
obtained as an E/ Z mixture: EI-MS m/z 140 (M+). Anal. Calcd
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.64; H, 7.58.
Gen er a l P r oced u r e for Step w ise Oxid a tion -Wittig Re-
a ction . A mixture of a substrate (1.00 mmol) and BaMnO4 (384
mg, 1.5 mmol) in CHCl3 (5 mL) was heated under the conditions
indicated in Table 3. The insoluble material was filtered off on
Celite, and the filtrate was evaporated in vacuo. A mixture of
the resulting residue and Ph3PdCHCO2Et (1.3 mmol) in CHCl3
(5 mL) was stirred under the conditions indicated in Table 3.
The solvent was evaporated in vacuo, and and the residue was
purified by silica gel column chromatography (EtOAc/hexane).
The ratio of (E)- and (Z)-isomer was determined from the 1H
NMR spectrum.
(E )-6′-E t h oxyca r b on ylm e t h yle n e -2′,3′-O-isop r op yli-
d en en ep la n ocin A (8). A. Step w ise Meth od . A mixture of
6 (307 mg, 1.0 mmol) and BaMnO4 (4.5 g, 17.6 mmol) in CH2Cl2
(50 mL) was heated under reflux for 40 h. After MeOH (40 mL)
was added, the mixture was cooled to room temperature, and
the insoluble material was filtered off. the filtrate was evapo-
rated to dryness in vacuo to give crude 7 as a foam. To the foam
was added MeCN (10 mL) and Ph3PdCHCO2Et (383 mg, 1.1
mmol) and the mixture was stirred at room temperature for 1
h. The solution was evaporated in vacuo, and the residue was
partitioned between CHCl3 and saturated aqueous NaCl. The
organic layer was evaporated in vacuo and the residue was
purified by silica gel column chromatography (MeOH/CHCl3
1:100, then 1:40) to give 8 (138 mg, 37%) as a white form: 1H
NMR (DMSO-d6) δ 8.11 and 8.04 (each s, each 1 H), 7.45 (d, 1
Exp er im en ta l Section
Melting points are uncorrected. NMR spectra were recorded
at 270 or 500 MHz (1H) and at 125 MHz (13C) and are reported
in ppm downfield from TMS. Mass spectra were obtained by
electron ionization (EI) or fast atom bombardment (FAB)
method. Thin-layer chromatography was done on Merck coated
plate 60F254. Silica gel chromatography was done with Merck
silica gel 5715.
Rea ction w ith
a Sta ble P h osp h or u s Ylid e-Ba Mn O4
System (Gen er a l P r oced u r e). A mixture of a substrate (1.00
mmol), a stable phosphorus ylide (1.30 mmol), and BaMnO4 (384
mg, 1.5 mmol) in the corresponding solvent (5 mL) was stirred
under the conditions indicated in Table 1 or 2. The insoluble
material was filtered off on Celite, and the filtrate was evapo-
rated in vacuo. The resulting residue was purified by silica gel
column chromatography (EtOAc/hexane). All of the products
were obtained as an oil, and the ratio of (E)- and (Z)-isomer was
determined by HPLC (YMC R-ODS-5-A, 75% aqueous MeOH,
1
1.0 mL/min, 254 nm) for Table 1 or from the H NMR spectrum
for Tables 2 and 3.
Eth yl 5-P h en yl-2,4-p en ta d ien oa te (10). (2E,4E)-Isom er :
16
EI-MS m/z 202 (M+). Anal. Calcd for C13H14O2: C, 77.20; H,
6.98. Found: C, 76.94; H, 7.08. (2Z,4E)-Isom er :17 EI-MS m/z
202 (M+). Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found:
C, 76.82; H, 7.05.
(E,E)-6-P h en yl-3,5-h exa d ien -2-on e (11):18 EI-MS m/z 172
(M+). Anal. Calcd for C12H12O‚0.2H2O: C, 81.97; H, 7.11.
Found: C, 82.08; H, 7.03.
1-Cya n o-4-p h en yl-1,3-bu ta d ien e (12)19 was obtained as a
mixture of (1E,3E)- and (1Z,3E)-isomers: EI-MS m/z 155 (M+).
(14) (a) Ronald, R. C.; Wheeler, C. J . J . Org. Chem. 1983, 48, 138-
139. (b) Climent, M. S.; Marinas, J . M.; Mouloungui, Z.; Bigot, Y. L.;
Delmas, M.; Gaset, A.; Sinisterra, J . V. J . Org. Chem. 1989, 54, 3695-
3701.
(19) Huang, Y.-Z.; Shen, Y.; Chen, C. Synth. Commun. 1989, 19,
83-90.
(20) Aldrich FT-NMR Spectra; Aldrich: Milwaukee, WI, Vol. 1,
1232C.
(15) For example, Marko and co-workers obtained the corresponding
R,â-unsaturated aldehydes of cinnamyl alcohol, geraniol, nerol, and
thiophene-2-methanol, which were also used as substrates in our study,
by an novel ruthenium-catalyzed oxidation in 60-80% isolated yields,
while they described the conversion yields as almost quantitative:
Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Urch, C.
J .; Brown, S. M. J . Am. Chem. Soc. 1997, 119, 12661-12662.
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Notes
J . Org. Chem., Vol. 63, No. 13, 1998 4493
H, J ) 16.0 Hz), 7.25 (br s, 2 H), 6.39 (d, 1 H, J ) 2.1 Hz), 6.21
(d, 1 H, J ) 16.0 Hz), 5.64 (d, 1 H, J ) 5.9 Hz), 5.60 (d, 1 H, J
) 2.1 Hz), 4.81 (d, 1 H, J ) 5.9 Hz), 4.17 (q, 2 H, J ) 7.0 Hz),
1.36 and 1.32 (each s, each 3 H), 1.24 (t, 3 H, J ) 7.0 Hz); EI-
MS m/z 371 (M+). Anal. Calcd for C18H21N5O4‚0.7H2O: C, 57.03;
H, 6.09; N, 17.78. Found: C, 57.43; H, 5.92; N, 17.58.
B. On e-P ot Meth od . A mixture of 6 (92 m g, 0.3 mmol),
Ph3PdCHCO2Et (115 mg, 0.33 mmol), and BaMnO4 (769 mg,
3.00 mmol) in CH2Cl2 (6 mL) was stirred at reflux for 24 h. The
insoluble material was filtered off on Celite, and the filtrate was
evaporated in vacuo. The resulting residue was purified by silica
gel column chromatography (CHCl3/MeOH 1:50) to give 8 (95
mg, 85%) as a white form.
isomer was determined from the 1H NMR spectrum: EI-MS m/z
324 (M+); HRMS calcd for C16H16N6O2 324.1335, found 324.1322.
1H NMR (CDCl3) δ (E)-isomer, 8.33 (s, 1 H), 7.68 (s, 1 H), 7.21
(d, 1 H, J ) 16.5 Hz), 6.09 (d, 1 H, J ) 2.6 Hz), 5.94 (d, 1 H, J
) 16.5 Hz), 5.67-5.56 (m, 4 H), 4.88-4.85 (m, 1 H), 1.46 (s, 3
H), 1.38 (s, 3 H); (Z)-isomer, 8.36 (s, 1 H), 7.73 (s, 1 H), 6.88 (d,
1 H, J ) 12.5 Hz), 6.45 (d, 1 H, J ) 2.6 Hz), 5.82 (d, 1 H, J ) 5.3
Hz), 5.67-5.56 (m, 4 H), 4.88-4.85 (m, 1 H), 1.50 (s, 3 H), 1.41
(s, 3 H).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
8 and 13 (2 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.
6′-Cya n om eth ylen e-2′,3′-O-isop r op ylid en en ep la n ocin A
(13). Compound 13 was prepared as described for 8, with
Ph3PdCHCN instead of Ph3PdCHCO2Et. After purification by
silica gel column chromatography, 13 was obtained as an E/ Z
mixture (white foam, 85 mg, 87%). The ratio of (E)- and (Z)-
J O971374M