Ruthenium alkylidene-catalyzed reaction of 1,6-heptadiynes with alkenes

Article abstract of DOI:10.1021/jo5028084

Ruthenium carbene catalysts are able to catalyze cross [2 + 2 + 2] cyclotrimerizations of 1,6-diynes with cyclic and acyclic double bonds. A plausible mechanistic competition is described in which electron-deficient alkenes follow similar pathways as thos

Full text of DOI:10.1021/jo5028084

Note
pubs.acs.org/joc
Ruthenium Alkylidene-Catalyzed Reaction of 1,6-Heptadiynes with
Alkenes
Silvia Alvarez, Sandra Medina, Gema Domínguez, and Javier Perez-Castells*
́
Facultad de Farmacia, Departamento Química y Bioquímica, Universidad San Pablo CEU, Urb. Montepríncipe, ctra. Boadilla km
5,300 Boadilla del Monte, 28668 Madrid, Spain
S
* Supporting Information
ABSTRACT: Ruthenium carbene catalysts are able to catalyze cross [2 + 2 + 2] cyclotrimerizations of 1,6-diynes with cyclic and
acyclic double bonds. A plausible mechanistic competition is described in which electron-deficient alkenes follow similar
pathways as those of other ruthenium catalysts previously utilized and produce mixtures of trienes and cyclohexadienes. On the
contrary, allylethers give different isomers of the same final products, suggesting that a metathetic cascade pathway operates in
these cases.
etal-catalyzed [2 + 2 + 2] cyclotrimerization of alkynes is
Ma feasible approach to construct densely functionalized
aromatic compounds in an atom-efficient and group-tolerant
way.1−9 Aromatic and nonaromatic heterocycles have also been
obtained by cross reactions between alkynes and carbon−
heteroatom multiple bonds, such as nitriles to give pyridines10
or heterocumulenes which give access to 2-pyridones.11,12 The
participation of carbon−carbon double bonds in [2 + 2 + 2]
cyclizations is possible, but this has been much less developed
owing to the lack of generality. The reaction of two alkyne units
with an alkene gives, in principle, substituted cyclohexadiene
derivatives, which are valuable synthetic intermediates. Several
metal complexes are able to mediate these kinds of trans-
formations. Stoichiometric reactions were reported using
cobalt-based systems.13,14 Catalytic versions have been
developed using rhodium,15−17 iridium,18 cobalt,19,20 nick-
el,21,22 and niobium complexes.23 Catalytic enantioselective [2
+ 2 + 2] cycloadditions of one alkyne unit and two alkenes
were described using cobalt24 and nickel catalysis.25 Intra-
molecular reactions with dienynes catalyzed by rhodium
complexes allowed the synthesis of fused polycyclic com-
pounds.26−28
Ruthenium catalysts such as [Cp*RuCl(cod)] have been
used for the reaction of 1,6-diynes with alkenes. The [2 + 2 +
2] cycloaddition was found to compete with double cyclo-
propanation processes, which showcased the double carbenic
nature of the metallacyclopentadiene intermediate.29 A recent
study focused on the regio- and stereochemical outcome of the
reaction, which depends on the substitution of the 1,6-diyne
and the nature of the alkene. With cyclic alkenes, the expected
cyclohexadiene is formed and a tandem [2 + 2 + 2]/[4 + 2]
cycloaddition is also observed. When acyclic alkenes were used,
a cascade process that behaves as a formal Ru(II)-catalyzed [2 +
2 + 2] cycloaddition took place. Initially, a Ru-catalyzed linear
coupling occurs to give open 1,3,5-trienes, which, after a
thermal disrotatory 6e− π-electrocyclization, led to the final 1,3-
cyclohexadienes.30
The mechanism of the [2 + 2 + 2] alkyne cyclotrimerization
is well-established, and its basic features have been studied
mainly through computational procedures.31 Independently,
the groups of Vollhardt32 and Saa33
studied, by DFT
́
computations, the mechanism of the cobalt- and ruthenium-
mediated [2 + 2 + 2] cycloaddition of two alkynes to one
alkene to give 1,3-cyclohexadienes, respectively.
Blechert reported for the first time the use of Grubbs’ first-
generation catalyst [Ru]-I for the intramolecular cyclo-
trimerization of triynes and he proposed a cascade metathetic
mechanism.34 We35 and other groups36−38 have shown that
[Ru]-I, [Ru]-II, and Hoveyda−Grubbs’ complex [Ru]-III can
mediate [2 + 2 + 2] cyclotrimerization reactions for the
synthesis of benzene rings. Recently, we used [Ru]-III for the
efficient synthesis of pyridines39 and 2-pyridones.40 These latter
cases showed a similar behavior in terms of scope and
limitations as that of other Ru catalysts, suggesting a possible
transformation of the carbenic initial complex into a different
species able to follow a metallacyclopentadiene-based reaction
pathway.
We present here a study on the behavior of ruthenium
carbene catalysts in the reaction of diverse kinds of alkenes with
1,6-diynes. As a starting point, we selected diyne 1a and ethyl
acrylate to optimize the reaction conditions, the results of
which are summarized in Table 1.
Received: December 11, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/jo5028084
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 1. Selection of Conditions for the Reaction of 1a with
Ethyl Acrylate
Scheme 1. Cyclotrimerization of Cyclic Alkenes with 1,6-
Diynes
a
yield (%)
temp.
(°C)
time
(h)
cat.
(mol %)
entry
solvent
1a
2a
3a
4a
1
toluene
toluene
CH3CN
THF
rt
48
3
5
60
16
11
arising from the reaction of 6 with a second equivalent of
dihydrofurane. When using methyl maleimide, the latter 2:1
adducts were the only reaction products, and the yield was
good with 1a, whereas it was moderate with diynes 1b and 1c.42
During the study on the scope of the reaction, we realized
that allyl ethers produced, under our conditions, different
products from those described previously.30 In particular,
reaction of 1a with allyl phenylether produced a sluggish
mixture of an open triene identified as 9b (22%), cyclo-
hexadiene 3b (15%), and cycloisomer 10 (13%, entry 1,
conditions A, Table 2). Product 9b is an isomer of 2a isolated
in the reactions shown in Table 1, which indicates a possible
b
2
110
5
25
32
32
b
3
82
1
5
45
32
b
4
66
1
5
13
40
23
45
43
27
51
5
DMF
DCM
DCE
140
1
5
b
6
40
2
5
8
28
35
36
16
13
b
7
90
2
5
12
17
45
26
b
8
DCE
90
2
10
5
c
9
DCE
100
0.5
1
c
10
11
12
DCE
100
5
c
DCE
100
1
10 [Ru]-I 61
5 [Ru]-II
c
DCE
100
1
21
38
15
a
Reactions were conducted at 0.07 M diyne with 5 equiv of ethyl
b
acrylate and catalyst [Ru]-III except for entries 11 and 12. Refluxing
conditions. Conducted in a sealed tube.
Table 2. Cyclization Reactions of 1,6-Diynes 1 with Allyl
Ethers
c
The reactions were carried out with catalyst [Ru]-III except
for entries 11 and 12 and with 5 equiv of ethyl acrylate. The
initial attempts conducted in toluene showed that heating was
needed to observe the cross reaction. A mixture of 2a and 3a,
both in moderate yields, was observed under refluxing toluene
(entry 2, Table 1), resulting in the isolation of small amounts of
dimerization product 4a. Other solvents were tested (entries
3−7), and with DCE the total conversion of the starting diyne
into a mixture of 2a, 3a, and 4a was observed. It is noteworthy
that in the case of DMF at 140 °C only cyclized product 3a was
observed, albeit in moderate yield (entry 5). Very similar results
were observed with 5 and 10 mol % catalyst loading (entries 7
and 8). The reaction was then performed in a sealed tube
because we had observed that this method was favorable when
developing the reaction of diynes with nitriles.39 Under these
conditions, the global yield improved and the ratio 3a/2a
increased with longer reaction times (entries 9 and 10). Next,
we used the latter conditions (conditions A) with [Ru]-I and
[Ru]-II as the catalysts (entries 11 and 12). First-generation
catalyst gave no final products, possibly due to decomposition
under the reaction conditions. Using [Ru]-II resulted in yields
that were slightly below those achieved with [Ru]-III, which
was used for the rest of the study.
a
no. diyne
Z
R1
H
R2 cond.
yield (%)
1
1a
C(CO2Bn)2
Ph
A
9b: 22; 3b: 15;
10 : 13
b
2
1a
1a
1a
1d
1d
1d
1e
1f
C(CO2Bn)2
C(CO2Bn)2
C(CO2Bn)2
NTs
H
Ph
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
Ph
B
A
B
A
B
B
9b: 73; 11b: 10
c
3
H
9c: 19; 12 : 26
4
H
9c: 62; 11c: 15
9d: 27
5
H
6
NTs
H
9d: 55
7
NTs
H
9e: 45
d
8
O
H
B
A
B
B
9f: 38
9
NTs
Me
Me
Me
9g: 16; 3g: 32
9g: 61
10
11
1f
NTs
e
1g
C(CO2Bn)2
9h/3h (4:1) 45
a
Conditions A: DCE 0.07 M, 5 equiv of allyl ether, sealed tube, 100
°C, 1 h. Conditions B: CHCl3 0.07 M, 5 equiv of allyl ether, rt, 16 h.
b
10:
Our next aim was to establish the scope of the process by
reacting diynes 1a−c with different cyclic alkenes (Scheme
1).41 Norbornene reacted poorly because a great amount of
norbornene polymer was formed. Compound 5 could be
isolated in low yield using 10 equiv of this alkene. This type of
dicyclopropane was described previously by Itoh using other
diynes.29 Reaction with dihydrofurane gave a mixture of the
expected [2 + 2 + 2] product, 6, and a Diels−Alder adduct, 7,
c
12:
d
e
Concentration: 1.1 mM. A 4:1 mixture (calculated from integration
of well-resolved signals) of 9g and 3g that could not be separated.
B
DOI: 10.1021/jo5028084
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The Journal of Organic Chemistry
Note
Scheme 2. Reaction Pathways for Cyclization Reactions
change in the reaction pathway. The result of this reaction was
substantially improved when we carried it out at room
temperature for 16 h (conditions B, entry 2). In this case,
the major product was 9b (73%), and a new product assigned
to 11b was also obtained in 10% yield. The reaction of 1a with
allyl butyl ether under conditions A gave a poor result,
although, interestingly, a new product, 12, was isolated in low
yield. This compound shares the structure of 2a (Table 1), but
the conjugated olefinic system is shifted (entry 3). On the other
hand, reaction under conditions B gave 9c (62%) and 11c
(15%, entry 4). In view of this result, we selected some diynes
and carried out their reaction with the allyl ethers. It was
observed that conditions A gave worse results and allowed the
formation of products 3 in a similar way as the reaction with
ethyl acrylate (entries 1 and 9). On the contrary, milder
conditions B allowed the formation of products 9 and 11 in
moderate to good global yields (entries 2, 4, 6−8, 10, and 11).
With unsymmetrical diynes 1f and 1g, the reaction was totally
regioselective, with the formation of products 9g−h and 3g and
no detection of other possible regioisomers (entries 9−11).
Our results show that ruthenium carbenes such as [Ru]-III
are able to catalyze cyclizations of 1,6-diynes with different
alkenes. However, it appears that two reaction pathways may be
operating in these reactions. A first possible mechanism consists
of a transformation of the ruthenium complex under strong
reaction conditions (conditions A) into a different species,
which could catalyze the cycloaddition in a similar way as that
with other ruthenium catalysts (Scheme 2, path a). This
pathway explains the formation of compounds 2, which may
evolve into 3 through a 6π-electrocyclization that completes a
formal [2 + 2 + 2] cyclotrimerization. Transformation of
ruthenium carbenes into other species able to catalyze
nonmetathetic transformations has been described by us43
and others.44 In particular, we showed a case in which the
modified species was unable to catalyze metathesis reactions.43
After coordination with the metal to give C,46 the unsym-
metrical olefin inserts in the C−Ru bond with both orientations
(D), but it does so with substituent X preferably being away
from the bulky metal complex. After rearrangement of D into
E, a mixture of 2 and 2′ (major) is formed from F. However, 2′
was not detected, as it undergoes an electrocyclization to give 3.
In a previous work by Saa, the parent compound to 2, obtained
́
when reacting a nonterminal diyne with an allyl ether, could be
isolated only when the reaction was performed at room
temperature, as it underwent electrocyclization at 50 °C with
no catalyst needed.30 In our case, it was observed that the
isomer 2 did not cyclize and could be isolated, whereas its
isomer, 2′, was not detected. In the case of cyclic alkenes, direct
[2 + 2 + 2] cycloaddition from D leads to E′, which gives
products like 6 that can further undergo a Diels−Alder
cycloaddition onto 7 or 8 (Scheme 1). On the other hand,
with allyl ethers, although this pathway still operates if the same
strong conditions are applied, a metathetic cascade process
would be possible if the ruthenium species is not transformed
and allowed to react for a longer period. Thus, following cycle b
in Scheme 2, successive metatheses produce intermediates H
and J. This latter carbene reacts with allyl ether to give 9, which
might continue reacting with the catalysts and the excess alkene
to produce 11 through intermediate L. Neither 9 nor 11 give
cyclized products. Previous reports have shown the need for
harsh thermal conditions or photochemical mediation to
produce 6π-cyclizations with these products.45 Interestingly,
when using unsymmetrically substituted diynes 1g−h, the
reactions behave in a completely regioselective manner. Thus,
no other isomers could be detected, which is possibly due to
steric reasons in the coordination step of the alkene (from B to
C). The selectivity in the metathesis pathway may be due to
equilibration from reaction intermediates, as it has been shown
that the metal has higher affinity for terminal alkynes.47
However, the formation of intermediate K would possibly be
sterically precluded if R1 is attached to the ruthenacyclobutane
and equilibration possibly leads to the observed isomer.
To obtain more information on these processes, we
1
monitorized some of the reactions by H NMR, observing
the evolution of the carbenic signal (see the Supporting
Information). Thus, the reaction of 1a with ethyl acrylate in the
presence of 25 mol % of [Ru]-III at 100 °C showed the rapid
disappearance of the carbenic signal (16.390 ppm), suggesting
the transformation of the catalyst. If the same reaction is carried
out at rt, then the carbene remains unaltered and no reaction is
C
DOI: 10.1021/jo5028084
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The Journal of Organic Chemistry
Note
The flask was sealed and introduced in a 100 °C bath, and the
resulting mixture was stirred during 1 h. After cooling the flask to
room temperature, the reaction mixture was filtered through Celite,
the solvent was eliminated under reduced pressure, and the residue
was purified by silica-gel flash column chromatography with solvent
mixtures (EtOAc/hexanes 1:20 → 1:1 v/v).
observed. In the reaction of 1a with allyl phenyl ether at rt, a
new carbenic signal appears during the reaction (15.807 ppm).
This new carbene could correspond to J in Scheme 2.48 No
other intermediates containing carbenic hydrogens appear in
the proposed reaction pathways.
In conclusion, we have shown a new nonmetathetic
application of ruthenium carbenes as catalysts for cross
diyne−alkene cyclizations. Different cyclization products are
isolated depending on the reaction conditions and the nature of
the alkene, suggesting a competition between two reaction
pathways.
Dibenzyl 3,3a,7,8a-Tetrahydro-1H-indeno[5,6-c]furan-6,6-
(5H)dicarboxylate, 6. Following general procedure the reaction of
cyclic alkenes, diyne 1a (100 mg, 0.28 mmol) and 2,5-dihydrofuran
(98 mg, 1.40 mmol) afforded 31 mg (26%) of 6 as a light yellow syrup
(Rf 0.08 (EtOAc/hexanes 1:6)) and 62 mg (44%) of 7 as a yellow
syrup (Rf 0.07 (EtOAc/hexanes 1:6)). 1H NMR (400 MHz, CDCl3): δ
2.92−3.05 (m, 6H), 3.45 (dd, 2H, J1 = 8.1 Hz, J2 = 6.2 Hz), 4.12 (t,
2H, J = 7.8 Hz), 5.12 (s, 2H), 5.13 (s, 2H), 5.41 (s, 2H), 7.23−7.24
(m, 4H), 7.30−7.31 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ
38.68, 38.74, 58.9, 67.2, 75.2, 117.4, 127.9, 128.0, 128.3, 128.50,
128.52, 134.7, 135.41, 135.44, 170.9, 171.0; IR (NaCl): 2960, 2928,
2857, 1736, 1552 cm−1; Anal. Calcd for C27H26O5: C, 75.33; H, 6.09.
Found: C, 75.58; H, 6.12.
EXPERIMENTAL SECTION
■
Reaction of Diyne 1a with Ethyl Acrylate. (Table 1, entry 10,
conditions A.) A solution of Ru-[III] (9 mg, 0.014 mmol) in 1,2-
dichloroethane (2 mL) was added to a solution of the diyne 1a (100
mg, 0.28 mmol) and the ethyl acrylate (140 mg, 0.15 mL, 1.40 mmol)
in the same solvent (2 mL) contained in a pressure flask. The flask was
sealed, introduced in a 100 °C bath and the resulting mixture was
stirred during 1 h. After cooling the flask to room temperature the
reaction mixture was filtered through Celite, the solvent was
eliminated under reduced pressure and the residue was purified by
silica-gel flash column chromatography with solvent mixtures (EtOAc/
hexanes 1:9 v/v). Evaporation of solvent afforded 34 mg (26%) of 2a,
66 mg (51%) of 3a and 26 mg (13%) of 4a. If the reaction time was
shortened to 30 min (Table 1, entry 9) the reaction gave 58 mg (45%)
of 2a, 35 mg (27%) of 3a, and 32 mg (16%) of 4a.29
1
Compound 7. H NMR (400 MHz, CDCl3): δ 1.63−1.65 (m,
2H), 1.71−1.72 (m, 4H), 2.76 (s, 4H), 3.71 (d, 4H, J = 8.2 Hz), 3.88
(d, 4H, J = 8.4 Hz), 5.10 (s, 4H), 7.21−7.24 (m, 4H), 7.30−7.32 (m,
6H); 13C{1H} NMR (100 MHz, CDCl3): δ 19.2, 23.4, 41.0, 57.3, 67.3,
69.7, 128.0, 128.3, 128.5, 130.4, 135.4, 171.5; IR (NaCl): 2964, 2924,
2852, 1736, 1547 cm−1; Anal. Calcd for C31H32O6: C, 74.38; H, 6.44.
Found: C, 74.25; H, 6.31.
Compound 8a. Following general procedure the reaction of cyclic
alkenes, diyne 1a (100 mg, 0.28 mmol) and N-methylmaleimide (155
mg, 1.40 mmol) afforded 139 mg (85%) of 8a as a yellow syrup (Rf
1
(Z)-Dibenzyl 3-((E)-4-Ethoxy-4-oxobut-2-enylidene)-4-meth-
ylenecyclopentane-1,1-dicarboxylate, 2a. Yellow oil. Rf 0.21
(EtOAc/hexanes 1:6). 1H NMR (400 MHz, CDCl3): δ 1.29 (t, 3H, J =
7.2 Hz), 3.09 (s, 2H), 3.20 (s, 2H), 4.19 (q, 2H, J = 7.2 Hz), 5.12 (s,
4H), 5.17 (d, 1H, J = 10.5 Hz), 5.28 (s, 1H), 5.34 (s, 1H), 5.67 (d, 1H,
J = 10.9 Hz), 7.10 (t, 1H, J = 11.6 Hz), 7.22−7.24 (m, 4H), 7.29−7.31
(m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 14.3, 42.0, 42.4, 57.2,
60.0, 67.4, 115.0, 118.0, 121.7, 128.0, 128.3, 128.5, 135.3, 139.8, 143.5,
145.8, 166.6, 170.7; IR (NaCl): 2924, 2852, 1736, 1637 cm−1; Anal.
Calcd for C28H28O6: C, 73.03; H, 6.13. Found: C, 73.14; H, 6.32.
2,2-Dibenzyl 5-Ethyl 6,7-dihydro-1H-indene-2,2,5(3H)-tricar-
0.11 (EtOAc/hexanes 1:3)). H NMR (400 MHz, CDCl3): δ 2.76 (s,
6H), 2.88 (s, 4H), 3.00 (s, 4H), 3.81 (s, 2H), 5.02 (s, 4H), 7.15−7.18
(m, 4H), 7.29−7.31 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ
24.7, 35.1, 42.1, 43.5, 58.6, 67.4, 127.9, 128.4, 128.6, 135.1, 136.7,
170.7, 176.3; IR (NaCl): 2924, 1732, 1700 cm−1; Anal. Calcd for
C33H30N2O8: C, 68.03; H, 5.19, N, 4.81. Found: C, 68.25; H, 5.01, N,
4.72.
Compound 8b. Following general procedure the reaction of cyclic
alkenes, diyne 1b (100 mg, 0.26 mmol) and N-methylmaleimide (144
mg, 1.30 mmol) afforded 87 mg (55%) of 8b as a yellow syrup (Rf 0.07
(EtOAc/hexanes 1:3)). 1H NMR (400 MHz, CDCl3): δ 1.91 (s, 6H),
2.67 (s, 4H), 2.77 (s, 6H), 2.89 (s, 4H), 5.02 (s, 4H), 7.15−7.18 (m,
4H), 7.29−7.31 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 17.3,
24.7, 40.6, 41.2, 50.0, 58.3, 67.5, 128.0, 128.4, 128.6, 135.1, 138.3,
170.8, 175.1; IR (NaCl): 2924, 1732, 1700 cm−1; Anal. Calcd for
C35H34N2O8: C, 68.84; H, 5.61; N, 4.59. Found: C, 68.80; H, 5.58, N,
4.61.
Compound 8c. Following general procedure the reaction of cyclic
alkenes, diyne 1c (75 mg, 0.27 mmol) and N-methylmaleimide (151
mg, 1.36 mmol) afforded 70 mg (52%) of 8c as a yellow syrup (Rf 0.05
(EtOAc/hexanes 1:3)).1H NMR (400 MHz, CDCl3): δ 1.86 (s, 6H),
2.41 (s, 3H), 2.59 (s, 6H), 2.68 (s, 4H), 3.96 (s, 4H), 7.35 (d, 2H, J =
8.2 Hz), 7.64 (d, 2H, J = 8.2 Hz); 13C{1H} NMR (100 MHz, CDCl3):
δ 16.8, 21.4, 24.6, 40.5, 49.9, 54.4, 127.5, 129.9, 133.3, 136.5, 143.7,
174.5 ppm; IR (NaCl): 2916, 2853, 1710, 1551 cm−1; Anal. Calcd for
C25H27N3O6S: C, 60.35; H, 5.47; N, 8.45; S, 6.44. Found: C, 60.41; H,
5.38, N, 8.51.
General Procedure for the Reaction of Diynes with Allyl
Ethers. Conditions A, Table 2. A solution of Ru-[III] (9 mg, 0.014
mmol) in 1,2-dichloroethane (2 mL) was added to a solution of the
diyne (0.28 mmol) and the allyl ether (1.40 mmol) in the same solvent
(2 mL) contained in a pressure flask. The flask was sealed and
introduced in a 100 °C bath, and the resulting mixture was stirred
during 1 h. After cooling, it was filtered through Celite. The solvent
was eliminated under reduced pressure, and the residue was purified
by silica-gel flash column chromatography with solvent mixtures
(EtOAc/hexanes 1:20 → 1:6 v/v).
1
boxylate, 3a. Colorless oil. Rf 0.15 (EtOAc/hexanes 1:6). H NMR
(300 MHz, CDCl3) δ 1.28 (t, 3H, J = 7.1 Hz), 2.24 (t, 2H, J = 9.9 Hz),
2.54 (t, 2H, J = 9.9 Hz), 3.11 (bs, 4H), 4.19 (q, 2H, J = 7.1 Hz), 5.12
(s, 4H), 6.94 (s, 1H), 7.22−7.26 (m, 4H), 7.30−7.32 (m, 6H);
13C{1H} NMR (75 MHz, CDCl3) δ 14.4, 22.1, 23.5, 40.9, 43.4, 58.8,
60.4, 67.4, 126.9, 128.1, 128.4, 128.6, 130.4, 131.4, 135.4, 140.9, 167.3,
171.5; IR (NaCl): 2966, 2928, 1740 cm−1; Anal. Calcd for C28H28O6:
C, 73.03; H, 6.13. Found: C, 73.15; H, 6.21.
Compound 5. A solution of Ru-[III] (9 mg, 0.014 mmol) in 1,2-
dichloroethane (2 mL) was added to a solution of diyne 1a (100 mg,
0.28 mmol) and norbornene (263 mg, 2.80 mmol) in the same solvent
(2 mL) contained in a pressure flask. The flask was sealed and
introduced in a 100 °C bath, and the resulting mixture was stirred
during 16 h. After cooling the flask to room temperature, the reaction
mixture was filtered through Celite, the solvent was eliminated under
reduced pressure, and the residue was purified by silica-gel flash
column chromatography with solvent mixtures (EtOAc/hexanes 1:20
→ 1:6 v/v). Evaporation of solvent afforded 38 mg (25%) of 5.
1H NMR (400 MHz, CDCl3): δ 0.65 (d, 2H, J = 10.6 Hz), 0.87 (d,
4H, J = 2.5 Hz), 1.05 (d, 2H, J = 10.5 Hz), 1.22−1.25 (m, 4H), 1.43−
1.45 (m, 4H), 1.61 (t, 2H, J = 2.8 Hz), 2.29 (s, 4H), 2.70 (s, 4H), 5.08
(s, 4H), 7.21−7.23 (m, 4H), 7.29−7.31 (m, 6H); 13C{1H} NMR (100
MHz, CDCl3): δ 12.8, 22.0, 28.2, 29.5, 36.0, 41.1, 57.5, 67.1, 128.0,
128.2, 128.5, 131.4, 135.6, 171.7; IR (NaCl): 2961, 2921, 2849, 1735,
1577 cm−1; Anal. Calcd for C37H40O4: C, 80.99; H, 7.35. Found: C,
81.15; H, 7.21.
General Procedure for the Reaction of Diynes with Cyclic
Alkenes. A solution of Ru-[III] (9 mg, 0.014 mmol) in 1,2-
dichloroethane (2 mL) was added to a solution of the diyne and the
cyclic alkene in the same solvent (2 mL) contained in a pressure flask.
Conditions B, Table 2. A solution of Ru-[III] (9 mg, 0.014
mmol) in CHCl3 (2 mL) was added to a solution of the diyne (0.28
mmol) and the allyl ether (1.40 mmol) in the same solvent (2 mL).
D
DOI: 10.1021/jo5028084
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
The mixture was stirred for 16 h, and the same work up as that under
the previous conditions was followed.
128.2, 128.5, 131.3, 135.6, 136.4, 150.5, 171.5; IR (NaCl): 2964, 2932,
1734, 1622 cm−1; Anal. Calcd for C30H34O5: C, 75.92; H, 7.22. Found:
C, 75.84; H, 7.09.
Reaction of 1a with Allyl Phenyl Ether. Following conditions A,
diyne 1a (100 mg) and allyl phenyl ether (188 mg) afforded 30 mg
(22%) of 9b as a yellow oil (Rf 0.16 (EtOAc/hexanes 1:6)), 21 mg
(15%) of 3b as a colorless oil (Rf 0.17 (EtOAc/hexanes 1:6)
impurified with 9b), and 24 mg (13%) of 10 as a yellow oil (Rf 0.51
(EtOAc/hexanes 1:6)). Following conditions B, 101 mg (73%) of 9b
and 17 mg (10%) of 11b as a colorless syrup (Rf 0.36 (EtOAc/hexanes
1:6)).
Dibenzyl 3,4-Bis((E)-3-butoxyprop-1-enyl)cyclopent-3-ene-
1
1,1-dicarboxylate, 11c. H NMR (400 MHz, CDCl3): δ 0.92 (t,
6H, J = 7.4 Hz), 1.34−1.41 (m, 4H), 1.54−1.59 (m, 4H), 3.27 (s, 4H),
3.43 (t, 4H, J = 6.6 Hz), 4.05 (d, 4H, J = 5.9 Hz), 5.12 (s, 4H), 5.72
(dt, 2H, J1 = 15.6 Hz, J2 = 5.9 Hz), 6.65 (d, 2H, J = 15.7 Hz), 7.23−
7.31 (m, 10H); 13C{1H} NMR (100 MHz, CDCl3): δ 14.0, 19.4, 31.9,
41.3, 57.1, 67.4, 70.3, 71.4, 124.6, 128.0, 128.3, 128.5, 128.6, 134.1,
135.4, 171.5; IR (NaCl): 2920, 2847, 1736, 1583 cm−1; Anal. Calcd for
C35H44O6: C, 74.97; H, 7.91. Found: C, 74.87; H, 7.82.
(E)-Dibenzyl 3-(3-Phenoxyprop-1-enyl)-4-vinylcyclopent-3-
1
ene-1,1-dicarboxylate, 9b. H NMR (400 MHz, CDCl3): δ 3.29
Reaction of 1d with Allyl Phenyl Ether. Following conditions B,
diyne 1d (70 mg) and allyl phenyl ether (188 mg) afforded 59 mg
(55%) of 9d as a yellow oil (Rf 0.12 (EtOAc/hexanes 1:6)).
(s, 2H), 3.31 (s, 2H), 4.61 (d, 2H, J = 5.6 Hz), 5.12 (s, 4H), 5.18 (d,
1H, J = 17.7 Hz), 5.19 (d, 1H, J = 10.1 Hz), 5.85 (dt, 1H, J1 = 15.7 Hz,
J2 = 5.6 Hz), 6.72−6.82 (m, 2H), 6.90−6.97 (m, 3H), 7.22−7.30 (m,
12H); 13C{1H} NMR (100 MHz, CDCl3): δ δ40.9, 41.3, 57.0, 67.4,
68.5, 114.7, 116.3, 120.9, 125.4, 126.7, 128.0, 128.3, 128.5, 129.1,
129.5, 134.0, 135.4, 135.9, 158.5, 171.5; IR (NaCl): 2930, 2853, 1733,
1546 cm−1; Anal. Calcd for C32H30O5: C, 77.71; H, 6.11. Found: C,
77.57; H, 6.25.
(E)-3-(3-Phenoxyprop-1-en-1-yl)-1-tosyl-4-vinyl-2,5-dihydro-
1
1H-pyrrole, 9d. H NMR (400 MHz, CDCl3): δ 2.43 (s, 3H), 4.31
(s, 4H), 4.60 (dd, 2H, J1 = 5.4 Hz, J2 = 1.1 Hz), 5.09 (d, 1H, J = 17.4
Hz), 5.24 (d, 1H, J = 10.8 Hz), 5.75 (dt, 1H, J1 = 15.9 Hz, J2 = 5.5 Hz),
6.63 (dd, 1H, J1 = 17.4 Hz, J2 = 10.8 Hz), 6.67 (d, 1H, J = 15.9 Hz),
6.90 (dd, 2H, J1 = 8.8 Hz, J2 = 1.0 Hz), 6.96 (t, 1H, J = 7.4 Hz), 7.29
(dd, 2H, J1 = 8.8 Hz, J2 = 7.4 Hz), 7.32 (d, 2H, J = 8.0 Hz), 7.75 (d,
2H, J = 8.2 Hz); 13C{1H} NMR (100 MHz, CDCl3): δ 21.5, 55.0,
55.2, 68.0, 114.7, 117.4, 121.1, 122.7, 126.9, 127.5, 127.9, 129.6, 129.9,
131.3, 132.8, 133.8, 143.7, 158.3; IR (NaCl): 2925, 2853, 1587 cm−1;
Anal. Calcd for C22H23NO3S: C, 69.26; H, 6.08; N, 3.67; S, 8.41.
Found: C, 69.02; H, 6.16; N, 3.75
Reaction of 1d with Allyl Butyl Ether. Following conditions B,
diyne 1d (70 mg) and allyl butyl ether (160 mg) afforded 46 mg
(45%) of 9e as a yellow oil (Rf 0.11 (EtOAc/hexanes 1:6)).
(E)-3-(3-Butoxyprop-1-en-1-yl)-1-tosyl-4-vinyl-2,5-dihydro-
1H-pyrrole, 9e. 1H NMR (400 MHz, CDCl3): δ 0.92 (t, 3H, J = 7.4
Hz), 1.33−1.42 (m, 2H), 1.53−1.60 (m, 2H), 2.43 (s, 3H), 3.43 (t,
2H, J = 7.8 Hz), 4.03 (dd, 2H, J1 = 5.7 Hz, J2 = 1.0 Hz), 4.29 (s, 4H),
5.06 (d, 1H, J = 17.4 Hz), 5.22 (d, 1H, J = 17.4 Hz), 5.63 (dt, 1H, J1 =
15.8 Hz, J2 = 5.7 Hz), 6.54 (d, 1H, J = 15.8 Hz), 6.63 (dd, 1H, J1 =
17.4 Hz, J2 = 10.9 Hz), 7.32 (d, 2H, J = 8.0 Hz), 7.74 (d, 2H, J = 8.2
Hz); 13C{1H} NMR (100 MHz, CDCl3): δ 13.9, 19.3, 21.5, 31.8, 55.0,
55.3, 70.6, 70.9, 116.9, 121.8, 127.0, 127.5, 129.9, 130.0, 131.6,
132.0,133.8, 143.6; IR (NaCl): 2925, 2850 cm−1; Anal. Calcd for
C20H27NO3S: C, 66.45; H, 7.53; N, 3.87; S, 8.87. Found: C, 66.22; H,
7.69; N, 3.64.
Dibenzyl 6-(Phenoxymethyl)-4,5-dihydro-1H-indene-
2,2(3H)-dicarboxylate, 3b. Data Obtained from a Mixture of
1
3b and 9b. H NMR (400 MHz, CDCl3): δ 2.20−2.25 (m, 2H),
2.31−2.36 (m, 2H), 3.06 (bs, 4H), 4.47 (s, 2H), 5.11 (s, 4H), 5.93 (s,
1H), 6.90−6.97 (m, 3H), 7.23−7.31 (m, 12H); 13C{1H} NMR (100
MHz, CDCl3): δ 23.2, 24.7, 41.3, 43.2, 58.7, 67.2, 71.1, 114.8, 119.8,
120.8, 128.0, 128.2, 128.5, 129.4, 129.9, 132.4, 133.5, 135.5, 158.8,
171.8.
Dibenzyl 3,4-Bis((E)-3-phenoxyprop-1-enyl)cyclopent-3-
1
ene-1,1-dicarboxylate, 11b. H NMR (400 MHz, CDCl3): δ 3.31
(s, 4H), 4.63 (d, 4H,J = 5.5 Hz), 5.12 (s, 4H), 5.87 (dt, 2H, J1 = 15.7
Hz, J2 = 5.7 Hz), 6.79 (d, 2H, J = 15.7 Hz), 6.90−6.97 (m, 6H), 7.22−
7.31 (m, 14H); 13C{1H} NMR (100 MHz, CDCl3): δ 41.3, 57.1, 67.5,
68.5, 114.7, 121.0, 125.3, 127.0, 128.1, 128.3, 128.6, 129.5, 134.6,
135.3, 158.5, 171.4; IR (NaCl): 2931, 2852, 1735, 1620 cm−1; Anal.
Calcd for C39H36O6: C, 77.98; H, 6.04. Found: C, 77.89; H, 6.19.
Dibenzyl 3,4-Divinylcyclopent-3-ene-1,1-dicarboxylate, 10.
1H NMR (400 MHz, CDCl3): δ 3.28 (s, 4H), 5.13 (s, 4H), 5.16 (d,
2H, J = 17.1 Hz), 5.18 (d, 2H, J = 11.0 Hz), 6.76 (dd, 2H, J1 = 17.1
Hz, J2 = 11.0 Hz), 7.23−7.25 (m, 4H), 7.30−7.32 (m, 6H); 13C{1H}
NMR (100 MHz, CDCl3): δ 40.9, 56.9, 67.4, 116.0, 128.0, 128.3,
128.5, 129.2, 135.3, 135.4, 171.6; IR (NaCl): 2930, 2853, 1733, 1546
cm−1; Anal. Calcd for C25H24O4: C, 77.30; H, 6.23. Found: C, 77.14;
H, 6.12.
Reaction of 1e with Allyl Butyl Ether. A solution of Ru-[III] (9
mg, 0.014 mmol) in CHCl3 (10 mL) was added to a solution of diyne
1e (100 mg, 1.06 mmol) and allyl butyl ether (604 mg, 5.30 mmol) in
the same solvent (10 mL). The mixture was stirred for 16 h, cooled,
and filtered through Celite. The solvent was eliminated under reduced
pressure, and the residue was purified by silica-gel flash column
chromatography with solvent mixtures (EtOAc/hexanes 1:20 → 1:6 v/
v). Evaporation of solvent afforded 84 mg (38%) of 9f as a yellow oil
(Rf 0.11 (EtOAc/hexanes 1:6)).
Reaction of 1a with Allyl Butyl Ether. Following conditions A,
diyne 1a (100 mg) and allyl butyl ether (160 mg) afforded 25 mg
(19%) of 9c as a yellow oil (Rf 0.15 (EtOAc/hexanes 1:6)) and 35 mg
(26%) of 12 as a colorless oil (Rf 0.14 (EtOAc/hexanes 1:6)).
Following conditions B, 82 mg (62%) of 9c and 24 mg (15%) of 11c
were afforded as colorless syrups (Rf 0.19 (EtOAc/hexanes 1:6)).
(E)-Dibenzyl 3-(3-Butoxyprop-1-enyl)-4-vinylcyclopent-3-
1
1
ene-1,1-dicarboxylate, 9c. H NMR (400 MHz, CDCl3) 0.92 (t,
(E)-3-(3-Butoxyprop-1-enyl)-4-vinyl-2,5-dihydrofuran, 9f. H
3H, J = 7.4 Hz), 1.33−1.43 (m, 2H), 1.54−1.61 (m, 2H), 3.27 (s,
2H,), 3.28 (s, 2H), 3.43 (t, 2H, J = 6.6 Hz,), 4.05 (d, 2H, J = 5.9 Hz),
5.12 (s, 4H), 5.16 (d, 1H, J = 18.3 Hz), 5.17 (d, 1H, J = 9.7 Hz), 5.73
(dt, 1H, J1 = 15.6 Hz, J2 = 6.0 Hz), 6.65 (d, 1H, J = 15.7 Hz), 6.76 (dd,
1H, J1 = 17.1 Hz, J2 = 11.0 Hz), 7.22−7.24 (m, 4H), 7.30−7.31 (m,
6H); 13C{1H} NMR (100 MHz, CDCl3): δ 13.9, 19.4, 31.9, 40.8, 41.4,
57.0, 67.4, 70.4, 71.3, 115.8, 124.5, 128.0, 128.3, 128.5, 128.8, 129.2,
134.4, 135.1, 135.4, 171.5; IR (NaCl): 3034, 2972, 2960, 2853, 1736,
1618 cm−1. Anal. Calcd for C30H34O5: C, 75.92; H, 7.22. Found: C,
75.78; H, 7.39.
Dibenzyl 3-((1E, 3E)-4-Butoxybuta-1,3-dienyl)-4-methylcy-
clopent-3-ene-1,1-dicarboxylate, 12. 1H NMR (400 MHz,
CDCl3): δ 0.93 (t, 3H, J = 7.4 Hz), 1.37−1.43 (m, 2H), 1.55 (s,
3H), 1.63−1.65 (m, 2H), 2.97 (s, 2H), 3.01 (s, 2H), 3.68 (t, 2H, J =
6.5 Hz), 5.11 (s, 4H), 5.31−5.34 (m, 1H), 5.37 (t, 1H, J = 12.2 Hz),
5.76 (d, 1H, J = 11.2 Hz), 6.52 (d, 1H, J = 10.5 Hz), 7.22−7.25 (m,
4H), 7.29−7.31 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 13.8,
17.5, 19.1, 31.2, 41.5, 41.7, 56.4, 67.1, 69.3, 106.0, 119.8, 120.8, 128.0,
NMR (400 MHz, CDCl3): δ 0.93 (t, 3H, J = 7.4 Hz), 1.34−1.42 (m,
2H), 1.55−1.61 (m, 2H), 3.45 (t, 2H, J = 6.6 Hz), 4.06 (dd, 2H, J1 =
5.8 Hz, J2 = 1.2 Hz), 4.85 (s, 4H), 5.02 (d, 1H, J = 17.4 Hz), 5.23 (d,
1H, J = 10.8 Hz), 5.59 (dt, 1H, J1 = 15.9 Hz, J2 = 5.8 Hz), 6.62 (d, 1H,
J = 15.9 Hz), 6.72 (dd, 1H, J1 = 17.5 Hz, J2 = 10.8 Hz); 13C{1H} NMR
(100 MHz, CDCl3): δ 12.9, 18.3, 30.8, 69.5, 70.2, 75.0, 75.3, 115.3,
120.7, 125.7, 128.3, 132.1, 132.7; IR (NaCl): 2960, 2929, 2852 cm−1;
Anal. Calcd for C13H20O2: C, 74.96; H, 9.68. Found: C, 74.89; H, 9.79
Reaction of 1f with Allyl Phenyl Ether. Following conditions A,
diyne 1f (73 mg) and allyl phenyl ether (188 mg) afforded 18 mg
(16%) of 9g as a yellow oil (Rf 0.15 (EtOAc/hexanes 1:6) and 35 mg
(32%) of 3g as a yellow oil (Rf 0.13 (EtOAc/hexanes 1:6)). Following
conditions B afforded 67 mg (61%) of 9g.
(E)-3-(3-Phenoxyprop-1-en-1-yl)-4-(prop-1-en-2-yl)-1-tosyl-
1
2,5-dihydro-1H-pyrrole, 9g. H NMR (400 MHz, CDCl3): δ 1.86
(s, 3H), 2.43 (s, 3H), 4.27 (d, 2H, J = 3.8 Hz), 4.30 (d, 2H, J = 3.8
Hz), 4.58 (d, 2H, J = 5.4 Hz), 4.86 (s, 1H), 5.07 (s, 1H), 5.73 (dt, 1H,
J1 = 16.0 Hz, J2 = 5.5 Hz), 6.72 (d, 1H, J = 16.0 Hz), 6.88 (dd, 2H, J1 =
E
DOI: 10.1021/jo5028084
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
8.8 Hz, J2 = 1.0 Hz), 6.95 (t, 1H, J = 7.4 Hz), 7.27 (t, 2H, J = 7.3 Hz),
7.33 (d, 2H, J = 8.2 Hz), 7.74 (d, 2H, J = 8.2 Hz); 13C{1H} NMR (100
MHz, CDCl3): δ 21.5, 22.4, 55.6, 57.2, 68.1, 114.7, 117.8, 121.1, 125.1,
127.51, 127.53, 129.4, 129.5, 129.9, 133.9, 135.8, 137.2, 143.6, 158.3;
IR (NaCl): 2921, 2857, 1592 cm−1; Anal. Calcd for C23H25NO3S: C,
69.84; H, 6.37; N, 3.54; S, 8.11. Found: C, 70.05; H, 6.26; N, 3.61
4-Methyl-6-(phenoxymethyl)-2-tosyl-2,3,4,5-tetrahydro-1H-
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1
isoindole, 3g. H NMR (400 MHz, CDCl3): δ 0.98 (d, 3H, J = 6.8
Hz), 2.01 (dd, 1H, J1 = 16.1 Hz, J2 = 10.1 Hz), 2.37−2.43 (m, 2H),
2.43 (s, 3H), 4.01−4.24 (m, 4H), 4.47 (s, 2H), 5.87 (s, 1H), 6.88 (dd,
2H, J1 = 8.8 Hz, J2 = 1.0 Hz), 6.92−6.96 (m, 1H, J = 7.4 Hz), 7.26 (dd,
2H, J1 = 8.7 Hz, J2 = 7.4 Hz), 7.32 (d, 2H, J = 8.0 Hz), 7.72 (d, 2H, J =
8.2 Hz); 13C{1H} NMR (100 MHz, CDCl3): δ 18.1, 21.5, 27.6, 33.2,
55.0, 55.1, 70.6, 114.8, 116.4, 121.0, 127.4, 127.7, 129.5, 129.8, 134.2,
134.4, 135.1, 143.4, 158.6; IR (NaCl): 2962, 2921, 2853, 1546 cm−1;
Anal. Calcd for C23H25NO3S: C, 69.84; H, 6.37; N, 3.54; S, 8.11.
Found: C, 70.11; H, 6.30; N, 3.78
Reaction of 1g with Allyl Phenyl Ether. Following conditions B,
diyne 1g (105 mg) and allyl phenyl ether (188 mg) afforded 64 mg
(45%) of a 4:1 mixture (calculated from integration of well-resolved
signals) of 9h and 3h as a yellow oil that could not be separated (Rf
0.16 (EtOAc/hexanes 1:6)).
Data Obtained from the Mixture: (E)-Dibenzyl 3-(3-phenox-
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127, 12466−12467.
1
boxylate, 9h. H NMR (400 MHz, CDCl3): δ 1.86 (s, 3H), 3.25 (s,
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2H), 3.28 (s, 2H), 4.58 (d, 2H, J = 5.8 Hz), 4.87 (s, 1H), 5.04 (d, 1H, J
= 1.8 Hz), 5.12 (s, 4H), 5.82 (dt, 1H, J1 = 15.8 Hz, J2 = 6.0 Hz), 6.79
(d, 1H, J = 15.9 Hz), 6.89−6.96 (m, 3H), 7.22−7.31 (m, 12H).
Dibenzyl 4-Methyl-6-(phenoxymethyl)-4,5-dihydro-1H-in-
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1
(18) Kezuka, S.; Okado, T.; Niou, E.; Takeuchi, R. Org. Lett. 2005, 7,
1711−1714.
dene-2,2(3H)-dicarboxylate, 3h. H NMR (400 MHz, CDCl3): δ
0.98 (d, 3H, J = 6.8 Hz), 1.68−1.72 (m, 1H), 2.00−2.04 (m, 1H),
2.38−2.44 (m, 2H), 2.97−3.17 (m, 4H), 4.49 (s, 2H), 5.12 (s, 4H),
5.92 (s, 1H), 6.89−6.96 (m, 3H), 7.22−7.31 (m, 12H). 13C{1H} NMR
(100 MHz, CDCl3): δ 18.1, 22.3, 29.1, 33.4, 41.31, 41.37, 41.4, 43.8,
57.1, 58.7, 67.2, 67.4, 68.7, 71.1, 114.7, 114.8, 114.9, 116.5, 119.5,
120.79, 120.83, 126.0, 127.95, 127.97, 127.99, 128.00, 128.01, 128.03,
128.26, 128.30, 128.5, 128.6, 129.3, 129.4, 129.5, 131.6, 133.43,
135.41, 135.51, 135.53, 137.3, 139.7, 158.6, 158.8, 171.5, 171.8.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
(26) Sagae, H.; Noguchi, K.; Hirano, M.; Tanaka, K. Chem. Commun.
2008, 3804−3806.
Copies of H and 13C NMR spectra for new compounds.
Figure S1: Evolution of carbenic signals for the reaction of 1a
with ethyl acrylate or allyl phenyl ether. This material is
available free of charge via the Internet at http://pubs.acs.org.
(27) Shibata, T.; Kurokawa, H.; Kanda, K. J. Org. Chem. 2007, 72,
6521−6525.
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11767.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jpercas@ceu.es.
■
(29) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.;
Tatsumi, K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310−4319.
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J. 2008, 14, 9772−9778.
(31) Review: Varela, J. A.; Saa,
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C. Chem.Eur.
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C. J. Organomet. Chem. 2009, 694,
The authors declare no competing financial interest.
143−149.
(32) Gandon, V.; Agenet, N.; Vollhardt, K. P. C.; Malacria, M.;
ACKNOWLEDGMENTS
Funding of this project by Spanish MINECO (no. CTQ2012-
31063/BQU) and FUSP-CEU (PC17/14) is acknowledged.
■
Aubert, C. J. Am. Chem. Soc. 2006, 128, 8509−8520.
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(33) Varela, J. A.; Rubin, S. G.; Castedo, L.; Saa, C. J. Org. Chem.
2008, 73, 1320−1332.
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S.M. thanks the Fundacion San Pablo-CEU and S.A. thanks
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The Journal of Organic Chemistry
Note
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cycloadditions with alkynes; see ref 35.
(42) The [2 + 2 + 2]/[4 + 2] adducts were still the major product
(7) or the only reaction product (8a−c) when using 2 equiv of alkene,
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DOI: 10.1021/jo5028084
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