CoCl(PPh3)3 as Cyclotrimerization Catalyst for Functionalized Triynes under Mild Conditions

Article abstract of DOI:10.1021/acs.joc.5b01623

The ubiquitary Co(I) complex CoCl(PPh₃)₃ was found to be a convenient catalyst for the [2 + 2 + 2] cycloaddition of functionalized triynes under mild reaction conditions and devoid of any additional additive, yielding the substituted

Full text of DOI:10.1021/acs.joc.5b01623

Note
pubs.acs.org/joc
CoCl(PPh3)3 as Cyclotrimerization Catalyst for Functionalized Triynes
under Mild Conditions
Phillip Jungk, Fabian Fischer, Indre Thiel, and Marko Hapke*
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock (LIKAT), Albert-Einstein-Str. 29a, D-18059 Rostock, Germany
̈
̈
S
* Supporting Information
ABSTRACT: The ubiquitary Co(I) complex CoCl(PPh3)3 was
found to be a convenient catalyst for the [2 + 2 + 2]
cycloaddition of functionalized triynes under mild reaction
conditions and devoid of any additional additive, yielding the
substituted arene compounds. Successful development of
synthetic routes to various triynes and the subsequent cyclo-
trimerization key step gave systematic access to a variety of
different bi- and triaryls with good to excellent yields for the
cyclization.
yclotrimerization reactions have flourished in an impres-
latter has been identified as a suitable catalyst for cyclo-
trimerizations already by the work of Grigg et al. in the
cyclization of acetylenes and diynes, and its application has
prospered since.13 Initial experiments with CoCl(PPh3)3 (1) as
catalyst without any additive proved its high activity in
intramolecular cyclization reactions from simple triynes 2 and
3 to yield 4 and 5 in high to excellent yields after a short
reaction time at room temperature (Scheme 1). Complex 1 is
C
sive manner,1 especially as a synthetic tool for the
assembly of carbo- and heterocyclic cores of complex organic
molecules from structurally simple precursors.2 However, the
investigation of novel catalyst systems or reassessment of
known precatalysts can still open the door for either novel
synthetic applications and substrate classes or exceptionally
mild reaction conditions. For the diverse cyclopentadienyl (Cp)
cobalt complex chemistry, several recent examples exemplify
the potential in the area of CpCo(I) (pre)catalyst development
and uncovering of catalyst activation processes.3 Recent
examples of novel CpCo(I) precatalysts were reported by
Gandon et al.4 as well as by our group.5 Further development
led to the synthesis of air-stable and recyclable precatalysts like
[CpCo{P(OR)3}(trans-MeO2CHCCHCO2Me)].6 Molecu-
lar defined phosphine complexes like [Co(H)(PMe3)4] have
been applied by Amatore, Aubert, and Petit et al. for the
cycloaddition of enediynes, providing access to bicyclic trienes.7
Another approach is the in situ generation of the catalytically
active Co(I) species. Okamoto et al. used Co(II) salts together
with either bisphosphines, 2-iminomethylpyridines, or N-
heterocyclic carbenes (NHC) in the presence of zinc as
reductant for the synthesis of substituted benzenes and
pyridines.8 The group of Hilt introduced bisimines and
substituted 1,2-dithioethanes as ligands for the in situ catalysis
with Co(II) salts.9 The addition of zinc(II) salts proved to be
beneficial for the catalytic reaction, as recent mechanistic
investigations corroborated for Diels−Alder-type reactions.10
Cheng et al. applied [CoI2(dppe)] (dppe = 1,2-bis(diphenyl-
phosphino)ethane) in the presence of zinc for the synthesis of
pyridines, benzolactones, and benzolactames.11
Scheme 1. Initial Triyne Cyclizations Using CoCl(PPh3)3
(1) as the Catalyst
commercially available or can be conveniently synthesized from
CoCl2 and PPh3.14 It is our intention to bring this easy to
prepare and rather “cheap” CoCl(PPh3)3 (1) to the wider
attention of the community involved in organic synthesis,
especially as an alternative for the rather “expensive” Wilkinson
catalyst in cyclotrimerizations.
To the best of our knowledge, only single reports for the
application of 1 in cyclotrimerizations exist, as exemplified by a
work by Butenschon et al., who transformed three molecules of
̈
tolane into hexaphenylbenzene in 97% yield.16 The only more
detailed investigations into the reactivity of 1 in cyclo-
trimerizations was performed by Chung et al. and Field et al.,
who found that monosubstituted alkynes possessing electron-
deficient substituents can be reacted at ambient temperatures,
Since we are interested in the synthesis of novel biaryl
systems by [2 + 2 + 2] cycloadditions, we focus on the
development of both novel cyclization substrates as well as
catalysts. We have now investigated the catalytic activity of the
molecular cobalt analogue CoCl(PPh3)3 (1) of the Wilkinson
complex, RhCl(PPh3)3, toward its catalytic properties.12 The
Received: July 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b01623
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Note
Scheme 2. Synthetic Studies toward Unsymmetrical Substituted Triynes, Exemplified for 14
Reaction conditions: (a) Pd(PPh3)4 (2 mol %), CuI (6 mol %), 1.3 equiv 2-propyn-1-ol, NEt3, 50 °C, 15 h. (b) 1.5 equiv CBr4, PPh3, CH2Cl2, 0 °C,
1 h. (c) (1) 1.2 equiv NaH, 15 (pathway A) or 17 (pathway C), THF, 25 °C, 1 h; (2) 8, 25 °C, 15 h. (d) p-TSA (2 mol %), MeOH, 0−25 °C, 68 h.
(e) (1) 1.03 equiv NaH, THF, 0 °C, 1 h; (2) 1-bromo-2-butyne, 25 °C, 18 h. (f) 5 equiv KOH, 5 equiv 11, 1-propyne, 0−25 °C, 20 h. (g)
Pd(PPh3)4 (5 mol %), CuI (15 mol %), 6 (pathway B) or 12 (pathway D), NEt3/THF, 25−100 °C, 22 h. (h) 1.09 equiv dihydropyrane, pyridine-p-
TSA (11 mol %), 40 °C, 1 h, ref 15. (i) p-TSA 0.6 equiv, MeOH, 50 °C, 18 h.
Scheme 3. Synthetic Access to Malonate-Bridged Unsymmetrical Triynes Like 36 and Derivatives
Reaction conditions: (a) (1) 1.01 equiv NaH, THF, 0−25 °C, 1 h; (2) bromoalkyne, 0.5 equiv NaI, 65 °C, 15 h, ref 19. (b) Pd(PPh3)4 (5 mol %),
CuI (15 mol %), R-I, NEt3/THF, 50−60 °C, 18 h. (c) (1) 1.05 equiv NaH, THF, 25 °C, 1 h; (2) 2.5 equiv 1,4-dibromo-2-butyne, THF, 25 °C, 17 h.
(d) (1) 1.05 equiv NaH, THF, malonylalkyne, 25 °C, 1 h, then 35, 15 h. (e) (1) 1.03 equiv NaH, 33, THF, 0 °C, 1 h; (2) 1,4-dibromo-2-butyne,
25 °C, 2 h; (3) 1.03 equiv NaH, 37, THF, 0 °C, 1 h, then addition to reaction mixture, 25 °C, 15 h.
whereas disubstituted alkynes require the addition of NaBPh4
for a successful transformation.17 We report here the systematic
preparation of novel triynes and their subsequent cyclo-
trimerization catalyzed by 1, yielding highly substituted bi-
and triaryls.
The study set out with the preparation of the triynes required
for the reactivity study. We initially chose symmetrical triynes
first synthesized by Otsuka et al. and adopted their synthetic
procedures.18 Furthermore, with the intention to identify the
most efficient synthetic route, we investigated several pathways
to construct unsymmetrical aryltriynes, as exemplified for
compound 14 (Scheme 2). The potential cyclization products
would thus obtain only one chiral biaryl axis. Scheme 2
represents four different approaches for the synthesis of triyne
14. It is interesting to note that pathway A and C requiring
more steps are more efficient than the conciser routes B and D.
In the latter cases, this can be attributed to the low-yielding
Sonogashira cross-coupling with the aryl iodide 6. In pathway
B, the synthesis of 12 is complicated by the concurrent
formation of the not easily separable triyne byproduct. In
addition, the final cross-coupling product still contains Pd
residues even after column chromatography. In pathways A and
C, the cross-coupling takes place in an early stage of the
synthesis, followed by convenient operations like bromination
or etherification during the later stages, which commonly occur
in good to very good yields. Interestingly, the reaction of the
deprotonated arylpropargylic alcohol 7 with 1,4-dibromobut-2-
yne to 18 in pathway A did not work. A possible explanation
B
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Note
would be that the aryl group on the propargylic alcohol is
hampering the nucleophilic substitution by stabilizing the
negative charge at the alcoholate through the aromatic ring.
Circumventing this problem, we brominated the propargylic
alcohol 7 to 8 and used the easily accessible partially THP-
protected 2-butyn-1,4-diol (15) for the nucleophilic substitu-
tion. Deprotection of the THP group and one additional
nucleophilic substitution furnished the unsymmetrical triyne 14
with the highest overall yield of all investigated routes (Scheme
2, pathway A).
Table 1. Cyclotrimerization of Ether-Bridged Triynes
Applying the developed optimized procedures, we were able
to construct a significant library of symmetrical and unsym-
metrical ether-bridged triynes 19−31 in mostly good overall
yields. We furthermore adopted this procedure to construct a
smaller library of unsymmetrical malonate-bridged triynes by
using 1,4-dibromobut-2-yne as a key building block (Scheme
3).
Starting from 33 and 37, we were able to develop a basically
one-pot procedure for the synthesis of triyne 38. Interestingly,
this is only possible starting from 33 and 37 for the malonate-
bridged triynes, but not for the synthesis of ether-bridged
triynes by using the related 2-butyn-1,4-diol (11).20
Having this substrate library in hand, we started investigating
the catalytic potential of CoCl(PPh3)3 (1) in the cyclization
reactions (Table 1). The screening of reaction conditions with
the triynes 14 and 19−31 quickly showed that 1 is highly suited
for the carbocyclization of these substrates in THF solution
already at 25 °C and a catalyst loading of 4−10 mol %. For
nearly all ether-bridged triynes, good to high yields of the
corresponding products were obtained under rather mild
conditions, including heteroaryl-substituted triynes like 26
and 27 (Table 1, entries 8 and 9). Only for substrate 20 with a
methoxy substituent in the 2-position of the naphthalene
(Table 1, entry 2), no conversion was observed, presumably
result from steric hindrance, because the reactions performed
with unsymmetrical triynes 14 and 30 with a smaller second
terminal substituent were successful.
Experiments showed that, for the cyclization of the malonate-
bridged triynes 36a−h, higher temperatures (>65 °C) were
required (Table 2). Only the triyne 36e (entry 5) proved to be
unreactive under any reaction condition tested. We have
reproduced these experiments several times but cannot give an
comprehensible explanation for this surprising observation of
different reactivity of 36e and 36f. We also tested a catalyst
system based on a cobalt(II) salt, after reducing with zinc and
zinc(II) iodide (like in Table 2, entry 3 (36c); see footnote),
but the product was not observed either.
We also synthesized and cyclized two examples of triynes
exhibiting different bridging units between the alkyne moieties
(54 and 56, Scheme 4). While 54 included silanol- as well as
ether-bridged alkyne moieties, triyne 56 contained alkyl- as well
as ether-linked alkyne units. The cyclization of triyne 54 to
biaryl 55 worked in acceptable yields already at room
temperature. The cyclization of 56 required a longer reaction
time to observe the good yield of 74% of the interesting biaryl
57 with the newly formed saturated five- as well as six-
membered backbone ring. An alternative reaction, the
cyclization of a diyne and alkyne, is complicated by the fact
that 1 can also catalyze the addition of terminal C−H bonds to
unsaturated functions like other alkynes. The test reaction
between internal diynes (like trideca-4,9-diyne) and an internal
alkyne (3-hexyne) with 1 as catalyst gave only rather little
a
b
A catalyst loading of 4−5 mol % 1 was applied. CoBr2 (5 mol %),
Zn, and ZnI2 used as catalyst system, because 1 gave a very low yield.
amounts of the expected substituted arene as well as
homocoupling byproducts.
To further investigate the role of the anionic ligand at the
cobalt center, we used chiral anions usually applied in
asymmetric counteranion-directed catalysis (ACDC) to eval-
uate a potential application for asymmetric [2 + 2 + 2]
cycloadditions (Scheme 5).21 As a screening substrate, we used
C
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Table 2. Cyclotrimerization of Malonate-Bridged Triynes
Scheme 5. Screening of Catalytic Activity for 1 in
Combination with Selected Chiral Anion
making it a suitable model compound for such experiments
being configurationally stable even at higher temperatures.22
Although we did not observe any enantioselectivity, the
application of the TRIP anions 58 and 59 improved the
overall yield significantly from 59% using 1 without additives to
up to 94% yield using TRIP derivative 58 in just 1 h reaction
time (Scheme 5).23 This phenomenon has been observed and
reported earlier applying NaBPh4 as additive in cyclizations
with 1.17 The possible explanation of raising available
coordination space around the Co center by the abstraction
of Cl from the metal center can be transferred to the present
case. However, we think that the proximity of the tested chiral
anion to the metal center is not close enough for providing
enantioselectivity beside the observed higher reactivity.
In summary, we presented a study of the systematic access to
ether- and malonate-bridged triynes and their conversion under
mild conditions to the corresponding biaryl and triaryl products
in mostly good to excellent yields. While different possibilities
for the preparation of the triynes were investigated, the
synthetic differences with respect to the bridging of the alkyne
moieties (ether vs malonate) were identified. Furthermore, the
commercially available and well-known, albeit for cyclo-
trimerizations rarely investigated, Co(I) complex CoCl(PPh3)3
(1) has been identified as an excellent catalyst without the
requirement of preactivation or the necessity of additional
additives. The use of chiral counterions as additives did not
induce chirality but showed to improve the reaction rate and
yield.
a
At first CoBr2, Zn, and ZnI2 were used with basically no conversion;
then CoCl(PPh3)3 (1, 5 mol %) was added as catalyst.
EXPERIMENTAL SECTION
■
Scheme 4. Cyclotrimerization of Triynes 54 and 56
General Experimental Details. All reactions were carried out
under an inert gas atmosphere (argon) in flame-dried Schlenk tubes or
flasks if not mentioned otherwise. The used chemicals were stored
under argon and used as received from the suppliers without further
purification. The anhydrous solvents (tetrahydrofuran, toluene,
dichloromethane) for the reactions were filtered through 2 columns
filled with activated alumina D-201 5 × 8 in a Solvent Purification
System. Triethylamine and diisopropylamine were dried over P2O5
and distilled under inert conditions and stored under argon. Column
chromatography was performed on silica gel with eluent mixtures of
cyclohexane (c-hex), ethyl acetate (EE), petrol ether (PE),
tetrahydrofuran (THF), n-hexane (n-hex), diethyl ether (DE), and
acetone. Compounds first appearing in the Supporting Information or
not numbered in the paper are enumerated with SI. High-resolution
mass spectroscopy (HRMS) analyses were performed using an
electron spray ionization time-of-flight (ESI-TOF) method or an
electron ionization (EI) with a sector field analyzer.
Syntheses of Building Blocks for Ether-Bridged Triynes. 1-(3-
Bromoprop-1-yn-1-yl)-2-methoxynaphthalene (8). Under an argon
atmosphere, 7 (2.12 g, 10 mmol, 1.0 equiv) was dissolved in 30 mL of
CH2Cl2 and cooled to 0 °C. Then, solid PPh3 (3.93 g, 15 mmol, 1.5
equiv) and CBr4 (4.97 g, 15 mmol, 1.5 equiv) were added, and the
mixture was stirred at 0 °C for 1 h. The solvent was removed under
reduced pressure, and the crude product was purified by column
chromatography with c-hex/EE (10:1). Alkyne 8 (2.58 g, 94%) was
received as a colorless solid.
triyne 19 in combination with a chiral anionic ligand salt in the
presence of NEt3. Compound 19 was used before in
asymmetric iridium-catalyzed [2 + 2 + 2] cycloadditions by
the group of Shibata,18 and we, therefore, used it as reference
for the attempted asymmetric induction experiments. The
biaryl has a sufficiently large activation barrier for racemization,
D
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Note
1H NMR (CDCl3, 400 MHz): δ = 4.03 (s, 3H), 4.40 (s, 2H), 7.24
(d, J = 9.1 Hz, 1H), 7.39 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.56 (ddd, J =
8.4, 6.8, 1.2 Hz, 1H), 7.78 (dt, J = 8.1, 0.8 Hz, 1H), 7.84 (d, J = 8.7 Hz,
1H), 8.22 (dq, J = 8.4, 0.8 Hz, 1H) ppm.
25 °C for 17 h. After flash chromatography with cyclohexane, the
product SI-VI (1.43 g, 81%) was obtained as a slightly yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.48−1.68 (m, 4H), 1.69−1.89
(m, 2H), 3.54 (dddd, J = 11.2, 5.8, 3.6, 2.0 Hz, 1H), 3.85 (ddd, J =
11.5, 8.7, 3.3 Hz, 1H), 4.31 (dt, J = 15.7, 1.8 Hz, 1H), 4.39 (dt, J =
15.7, 1.8 Hz, 1H), 4.46 (t, J = 1.8 Hz, 2H), 4.64 (s, 2H), 4.84 (t, J =
3.3 Hz, 1H), 7.42 (dd, J = 8.3, 7.1 Hz, 1H), 7.48−7.62 (m, 2H), 7.69
(dd, J = 7.2, 1.2 Hz, 1H), 7.81−7.88 (m, 2H), 8.32 (dd, J = 8.1, 1.0 Hz,
1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 16.1, 56.7, 81.7, 93.6, 105.1,
112.5, 124.4, 125.0, 127.7, 128.2, 128.5, 130.9, 134.8, 159.5 ppm.
HRMS-EI (C14H11BrO): calcd: 273.9987; found: 273.9984.
EA: calcd: C 61.11, H 4.03, Br 29.04; found: C 61.09, H 3.87, Br
30.49.
Mp. 76−77 °C.
13C NMR (CDCl3, 75 MHz): δ = 19.1, 25.4, 30.3, 54.3, 57.0, 57.6,
62.1, 81.3, 83.2, 84.9, 89.1, 96.9, 120.1, 125.2, 126.1, 126.5, 126.9,
128.3, 129.1, 130.8, 133.1, 133.3 ppm.
2-((4-((3-(2-Methoxynaphthalen-1-yl)prop-2-yn-1-yl)oxy)but-2-
yn-1-yl)oxy)tetrahydro-2H-pyran (9). To a cooled solution of sodium
hydride (0.17 g, 4.4 mmol, 1.2 equiv, 60 wt % in oil) in 5 mL of THF
was slowly added compound 15 (0.61 g, 3.6 mmol, 1.0 equiv)
dissolved in 5 mL of THF using a dropping funnel. The solution was
stirred for 1 h until the hydrogen evolution ceased. Then, a solution of
compound 8 (1.0 g, 3.6 mmol, 1.0 equiv) in 5 mL of THF was slowly
added, and the resulting mixture was stirred at 25 °C for 15 h. The
reaction was monitored by TLC. After no more observable changes,
the reaction was quenched with water and extracted with ethyl acetate.
The organic phases were washed with brine and dried over sodium
sulfate, and the solvent was removed under reduced pressure. The
crude product was purified by flash chromatography with c-hex/EE
(20:1), and the starting material 8 (0.24 g, 24%) was reisolated and
product 9 (0.78 g, 82%) was obtained as a yellow oil.
HRMS-EI (C22H22O3): calcd: 334.1564, found: 334.1558.
4-((3-(Naphthalene-1-yl)prop-2-yn-1-yl)oxy)but-2-yn-1-ol (SI-
VII). Following the above procedure for 10 (pathway A), compound
SI-VI (1.38 g, 4.13 mmol, 1.0 equiv) and p-TSA (15 mg, 0.08 mmol, 2
mol %) in 30 mL of methanol were stirred at 25 °C for 3 days. After
workup and flash chromatography with c-hex/EE (10:1), the product
SI-VII (0.92 g, 89%) was obtained as a slightly yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.69 (s, 1H), 4.35 (t, J = 1.8 Hz,
2H), 4.45 (t, J = 1.8 Hz, 2H), 4.64 (s, 2H), 7.43 (dd, J = 8.3, 7.2 Hz,
1H), 7.49−7.62 (m, 2H), 7.69 (dd, J = 7.2, 1.2 Hz, 1H), 7.81−7.88
(m, 2H), 8.30−8.34 (m, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 51.2, 57.0, 57.7, 81.2, 85.0, 85.3,
89.0, 120.1, 125.2, 126.1, 126.5, 126.9, 128.4, 129.2, 130.9, 133.1, 133.3
ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.48−1.88 (m, 6H), 3.54 (dtd, J
= 11.2, 4.2, 1.8 Hz, 1H), 3.85 (ddd, J = 11.2, 8.4, 3.3 Hz, 1H), 4.02 (s,
3H), 4.26−4.43 (m, 2H), 4.48 (t, J = 1.8 Hz, 2H), 4.69 (s, 2H), 4.83
(dd, J = 3.8, 2.8 Hz, 1H), 7.25 (d, J = 8.7 Hz, 1H), 7.38 (ddd, J = 8.1,
6.8, 1.2 Hz, 1H), 7.54 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.78 (dd, J = 8.1,
0.7 Hz, 1H), 7.83 (d, J = 8.9 Hz, 1H), 8.23 (dd, J = 8.4, 1.0 Hz, 1H)
ppm.
HRMS-ESI (TOF) (C17H14O2): calcd: 251.1067 [M + H]+,
273.0886 [M + Na]+; found: 251.1067 [M + H]+, 273.0888 [M +
Na]+.
4-((3-Phenylprop-2-yn-1-yl)oxy)but-2-yn-1-ol (SI-VIII). Following
the procedures for the nucleophilic substitution and the deprotection
of the crude product, sodium hydride (1.35 g, 33.8 mmol, 1.1 equiv, 60
wt % in oil), compound 15 (5.24 g, 30.8 mmol, 1.0 equiv), and SI-III
(6.0 g, 30.8 mmol, 1.0 equiv) suspended in 120 mL of THF were
stirred at 25 °C for 17 h. The crude product and p-TSA (0.25 g, 1.33
mmol, 4 mol %) were stirred in 130 mL of methanol at 40 °C for 16 h.
Workup and flash chromatography with c-hex/EE (3:1) delivered the
product SI-VIII (4.32 g, 65% over two steps) as a colorless oil.
The spectral data are in accordance with the literature.24
Syntheses of Ether-Bridged Triynes. 1-(3-((4-(But-2-yn-1-
yloxy)but-2-yn-1-yl)oxy)prop-1-yn-1-yl)-2-methoxynaphthalene
(14). Pathway A or D. Following the above procedure for compound
9, sodium hydride (0.04 g, 1.0 mmol, 1.2 equiv, 60 wt % in oil),
compound 10 (0.237 g, 0.85 mmol, 1.0 equiv), and 1-bromo-2-butyne
(0.07 mL, 0.85 mmol, 1.0 equiv) were reacted in 5 mL of THF under
stirring at 25 °C for 17 h. The product 14 (0.20 g, 71%) was obtained
as a yellow oil after flash chromatography with c-hex/EE (4:1).
1H NMR (CDCl3, 400 MHz): δ = 1.86 (t, J = 2.3 Hz, 3H), 4.02 (s,
3H), 4.22 (q, J = 2.3 Hz, 2H), 4.31 (t, J = 1.8 Hz, 2H), 4.48 (t, J = 1.8
Hz, 2H), 4.69 (s, 2H), 7.25 (d, J = 9.1 Hz, 1H), 7.38 (ddd, J = 8.1, 6.8,
1.2 Hz, 1H), 7.54 (ddd, J = 8.3, 6.8, 1.2 Hz, 1H), 7.78 (dt, J = 8.2, 0.8
Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 8.23 (dd, J = 8.4, 1.0 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 3.6, 56.5, 56.6, 56.7, 57.2, 57.8,
74.3, 81.4, 82.2, 82.3, 83.2, 93.7, 105.4, 112.5, 124.2, 125.1, 127.5,
128.1, 128.4, 130.5, 134.6, 159.3 ppm.
13C NMR (CDCl3, 75 MHz): δ = 19.1, 25.3, 30.2, 54.3, 56.6, 56.8,
57.8, 62.0, 81.3, 81.5, 82.9, 93.8, 96.9, 105.4, 112.5, 124.2, 125.2, 127.5,
128.1, 128.5, 130.4, 134.6, 159.2 ppm.
HRMS-ESI (TOF) (C23H24O4): calcd: 387.1567 [M + Na]+;
found: 387.1568 [M + Na]+.
4-((3-(2-Methoxynaphthalen-1-yl)prop-2-yn-1-yl)oxy)but-2-yn-1-
ol (10). Pathway A. Compound 9 (0.76 g, 2.18 mmol, 1.0 equiv) was
dissolved in 15 mL of methanol and cooled to 0 °C, and para-
toluenesulfonic acid monohydrate (p-TSA, 17 mg, 0.08 mmol, 4 mol
%) was added. The reaction mixture stirred at 25 °C for 3 days. The
reaction was stopped with 3 mL of sat. aqueous NaHCO3 sol., and the
solvent was evaporated. The aqueous phase was extracted with ethyl
acetate, and the combined organic phases were washed with brine and
dried over sodium sulfate. Purification by column chromatography
with c-hex/EE (2:1) as eluent gave product 10 (0.47 g, 76%) as a
colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 1.64 (sbr, 1H), 4.03 (s, 3H), 4.34
(sbr, 2H), 4.48 (t, J = 1.8 Hz, 2H), 4.69 (s, 2H), 7.25 (d, J = 9.1 Hz,
1H), 7.38 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.54 (ddd, J = 8.4, 6.8, 1.2
Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.84 (d, J = 9.1 Hz, 1H), 8.23 (dd, J
= 8.5, 1.0 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 51.2, 56.6, 56.8, 58.0, 81.5 (2×),
85.1, 93.7, 105.5, 112.6, 124.3, 125.2, 127.5, 128.1, 128.5, 130.5, 134.6,
159.3 ppm.
HRMS-ESI (TOF) (C22H20O3): calcd: 333.1485 [M + H]+,
355.1305 [M + Na]+; found: 333.1490 [M + H]+, 355.1309 [M +
Na]+.
HRMS-EI (C18H16O3): calcd: 280.1094, found: 280.1091.
EA: calcd: C 77.12, H 5.75; found: C 77.02, H 5.85.
Pathway C. Following the above procedure for 9, sodium hydride
(0.14 g, 3.5 mmol, 1.07 equiv, 60 wt % in oil), compounds 17 (0.45 g,
3.26 mmol, 1.0 equiv) and 8 (0.90 g, 3.26 mmol, 1.0 equiv) dissolved
in 5 mL of THF were stirred at 25 °C for 19 h. After flash
chromatography with c-hex/EE (6:1), the starting material 8 (0.10 g,
12%) was reisolated as well as product 14 (0.71 g, 78%) was obtained
as a yellow oil.
Pathway D. Following the procedure for 34a, complex Pd(PPh3)4
(0.23 g, 0.20 mmol, 5 mol %), CuI (0.12 g, 0.60 mmol, 15 mol %), and
6 (1.14 g, 4.02 mmol, 1.0 equiv) as solution in 23 mL of NEt3 and 12
(0.50 g, 4.02 mmol, 1.0 equiv) dissolved in 4 mL of THF were mixed
and stirred at 50 °C for 19 h. After flash chromatography with n-hex/
EE (4:1, 2:1, 1:1), product 10 (0.27 g, 24%) was obtained as a
colorless oil.
Pathway B. Following the procedure for 34a, catalyst Pd(PPh3)4
(46 mg, 0.04 mmol, 2 mol %), CuI (23 mg, 0.12 mmol, 6 mol %), and
compound 6 (0.65 g, 2.2 mmol, 1.1 equiv) as reaction mixture in 7 mL
of NEt3 and 13 (0.35 g, 2.0 mmol, 1.0 equiv) dissolved in 3 mL of
THF were mixed and stirred at 25 °C for 18 h and finally at 100 °C for
2-((4-((3-(Naphthalen-1-yl)prop-2-yn-1-yl)oxy)but-2-yn-1-yl)oxy)-
tetrahydro-2H-pyran (SI-VI). Following the above synthetic proce-
dure for compound 9, a mixture of sodium hydride (0.27 g, 6.6 mmol,
1.2 equiv, 60 wt % in oil), compound 15 (0.90 g, 5.3 mmol, 1.0 equiv),
and SI-V (1.3 g, 5.3 mmol, 1.0 equiv) in 25 mL of THF was stirred at
E
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
4 h. After flash chromatography with n-hex/EE (4:1), product 14 (0.19
g, 24%) was obtained as a yellow oil.
13C NMR (CDCl3, 75 MHz): δ = 20.7, 56.7, 57.5, 82.3, 85.8, 87.9,
122.2, 125.5, 128.6, 129.4, 132.2, 140.3 ppm.
1,4-Bis((3-(2-methoxynaphthalen-1-yl)prop-2-yn-1-yl)oxy)but-2-
yne (20). Following the procedure for compound 23, catalyst
Pd(PPh3)4 (0.36 g, 0.31 mmol, 10 mol %), CuI (0.12 g, 0.62 mmol,
20 mol %), and compound 6 (1.76 g, 6.2 mmol, 2.0 equiv) as solution
in 40 mL of toluene beside added 2 (0.5 g, 3.10 mmol, 1.0 equiv) and
N,N-diisopropylamine (2.20 mL, 15.5 mmol, 5.0 equiv) were stirred at
25 °C for 18 h. After workup and flash chromatography with c-hex/EE
(1:1), triyne 20 (0.41 g, 50%) was obtained as a yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 4.01 (s, 6H), 4.54 (s, 4H), 4.74
(s, 4H), 7.22 (d, J = 9.5 Hz, 2H), 7.37 (ddd, J = 8.1, 6.8, 1.2 Hz, 2H),
7.55 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.81 (d, J
= 9.0 Hz, 2H), 8.26 (d, J = 9.0 Hz, 2H) ppm.
HRMS-ESI (TOF) (C24H22O2): calcd: 343.1693 [M + H]+,
365.1512 [M + Na]+; found: 343.1694 [M + H]+, 365.1512 [M +
Na]+.
1,4-Bis((3-(2-isopropylphenyl)prop-2-yn-1-yl)oxy)but-2-yne (24).
Following the above procedure for 23, catalyst Pd(PPh3)4 (0.36 g,
0.31 mmol, 10 mol %), CuI (0.12 g, 0.62 mmol, 20 mol %), and 1-
iodo-2-isopropylbenzene (1.15 mL, 6.82 mmol, 2.2 equiv) dissolved in
20 mL of toluene as well as added 2 (0.5 g, 3.10 mmol, 1.0 equiv) and
N,N-diisopropylamine (2.20 mL, 15.5 mmol, 5.0 equiv) were stirred at
25 °C for 17 h. After flash chromatography with c-hex/EE (20:1),
triyne 24 (1.03 g, 83%) was obtained as a yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.24 (d, J = 6.9 Hz, 12H), 3.42
(sept, J = 6.9 Hz, 2H), 4.39 (s, 4H), 4.52 (s, 4H), 7.10 (ddd, J = 7.6,
6.5, 2.2 Hz, 2H), 7.23−7.28 (m, 4H), 7.40 (dt, J = 7.6, 1.0 Hz, 2H)
ppm.
13C NMR (CDCl3, 75 MHz): δ = 56.6, 56.8, 57.9, 81.5, 82.5, 93.8,
105.4, 112.5, 124.3, 125.2, 127.6, 128.1, 128.5, 130.5, 134.7, 159.3
ppm.
13C NMR (CDCl3, 75 MHz): δ = 23.2, 31.5, 56.7, 57.5, 82.2, 85.7,
87.6, 121.2, 124.9, 125.5, 128.9, 132.7, 150.7 ppm.
HRMS-EI (C32H26O4): calcd: 474.1826; found: 474.1823.
1,4-Bis((3-(phenanthren-9-yl)prop-2-yn-1-yl)oxy)but-2-yne (21).
Following the procedure for 23, catalyst Pd(PPh3)4 (0.81 g, 0.70
mmol, 10 mol %), CuI (0.27 g, 1.40 mmol, 20 mol %), and 2 (1.14 g,
7.0 mmol, 1.0 equiv) as solution in 50 mL of NEt3 and a solution of 9-
bromophenanthrene (3.84 g, 14.4 mmol, 2.05 equiv) in 20 mL of THF
were combined and stirred at 50 °C for 2 h and an additional 47 h at
25 °C. After flash chromatography with toluene/CH2Cl2 (1:1), 9-
bromophenanthrene (1.35 g) was reisolated and triyne 21 (1.58 g,
67%) was obtained as a brown solid.
HRMS-ESI (TOF) (C28H30O2): calcd: 399.2319 [M + H]+,
421.2138 [M + Na]+; found: 399.2321 [M + H]+, 421.2136 [M +
Na]+.
Dimethyl-2,2′-((but-2-yne-1,4-diylbis(oxy))bis(prop-1-yne-3,1-
diyl))dibenzoate (25). Following the above procedure for 23
Pd(PPh3)4 (0.36 g, 0.31 mmol, 10 mol %), CuI (0.12 g, 0.62 mmol,
20 mol %), methyl 2-iodobenzoate (1.15 mL, 6.82 mmol, 2.2 equiv) in
20 mL of toluene, 2 (0.5 g, 3.10 mmol, 1.0 equiv), and N,N-
diisopropylamine (2.20 mL, 15.5 mmol, 5.0 equiv) were stirred at 25
°C for 24 h. After flash chromatography with c-hex/EE (4:1, 2:1),
triyne 25 (1.30 g, 97%) was obtained as a yellow oil.
The spectral data are in accordance with the literature.18
HRMS-EI (C38H26O2): calcd: 514.1927; found: 514.1918.
EA: calcd: C 88.69, H 5.09; found: C 88.52, H 5.03.
1H NMR (CDCl3, 300 MHz): δ = 3.92 (s, 6H), 4.45 (s, 4H), 4.55
(s, 4H), 7.37 (td, J = 7.3, 1.1 Hz, 2H), 7.46 (td, J = 7.6, 1.1 Hz, 2H),
7.56 (d, J = 7.6 Hz, 2H), 7.93 (d, J = 7.8 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 52.2, 56.8, 57.4, 82.4, 85.5, 89.5,
122.9, 128.2, 130.4, 131.7, 131.9, 134.3, 166.4 ppm.
Mp. 93.5−94.5 °C.
1,4-Bis((3-(4-methylnaphthalen-1-yl)prop-2-yn-1-yl)oxy)but-2-
yne (22). In a flame-dried Schlenk flask, Pd(PPh3)4 (0.76 g, 0.66
mmol, 5 mol %) and CuI (0.38 g, 1.97 mmol, 15 mol %) were
suspended in 40 mL of NEt3. Then, compound 2 (1.06 g, 6.56 mmol,
1.0 equiv) and 1-bromo-4-methylnaphthalene (2.9 g, 13.1 mmol, 2.0
equiv) dissolved in 5 mL of THF were added. The solution was stirred
at 25 °C for 18 h and monitored by TLC. After completion, the
reaction mixture was quenched with aqueous sat. NH4Cl sol., and the
aqueous phase was extracted several times with ethyl acetate. The
organic phase was washed with brine, dried over Na2SO4, evaporated,
and purified by column chromatography with n-hex/EE (4:1). 1-
Bromo-4-methylnaphthalene (1.51 g) was reisolated, and triyne 22
(0.65 g, 46%) was obtained as a yellow oil.
HRMS-ESI (TOF) (C26H22O6): calcd: 431.1489 [M + H]+,
453.1309 [M + Na]+; found: 431.1491 [M + H]+, 453.1306 [M +
Na]+.
1,4-Bis((3-(quinolin-4-yl)prop-2-yn-1-yl)oxy)but-2-yne (26). Fol-
lowing the above procedure for 23, Pd(PPh3)4 (0.53 g, 0.46 mmol, 10
mol %), CuI (0.17 g, 0.92 mmol, 20 mol %), SI−I (2.0 g, 9.6 mmol,
2.1 equiv) in 40 mL of toluene, 2 (0.74 g, 4.6 mmol, 1.0 equiv), and
N,N-diisopropylamine (3.2 mL, 22.9 mmol, 5.0 equiv) were stirred at
50 °C for 23 h. After workup and flash chromatography with n-hex/
THF (1:1, 0.5% NEt3) and recrystallization from acetone, triyne 26
(1.36 g, 71%) was obtained as a yellow solid.
1H NMR (CDCl3, 300 MHz): δ = 2.70 (s, 6H), 4.49 (s, 4H), 4.66
(s, 4H), 7.26 (dd, J = 7.3, 1.1 Hz, 2H), 7.51−7.63 (m, 6H), 7.96−8.04
(m, 2H), 8.33−8.39 (m, 2H) ppm.
1H NMR (CDCl3, 300 MHz): δ = 4.48 (s, 4H), 4.66 (s, 4H), 7.50
(d, J = 4.5 Hz, 2H), 7.62 (ddd, J = 8.2, 6.9, 1.3 Hz, 2H), 7.75 (ddd, J =
8.4, 6.9, 1.5 Hz, 2H), 8.12 (d, J = 8.2 Hz, 2H), 8.24 (ddd, J = 8.4, 1.5,
0.7 Hz, 2H), 8.87 (d, J = 4.5 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 19.7, 56.9, 57.7, 82.4, 85.3, 88.4,
118.3, 124.4, 126.1, 126.3, 126.5, 126.7, 130.7, 132.3, 133.3, 135.9
ppm.
HRMS-ESI (TOF) (C32H26O2): calcd: 443.2006 [M + H]+,
465.1825 [M + Na]+; found: 443.2005 [M + H]+, 465.1826 [M +
Na]+.
13C NMR (CDCl3, 75 MHz): δ = 57.3, 57.5, 82.4, 82.7, 93.6, 124.0,
125.8, 127.4, 127.6, 128.8, 129.9, 130.0, 148.1, 149.8 ppm.
HRMS-EI (C28H20N2O2): calcd: 416.1519; found: 416.1516.
EA: calcd: C 80.75, H 4.84, N 6.73; found: C 80.74, H 4.86, N 6.46.
Mp. 146.5−147.5 °C.
1,4-Bis((3-(o-tolyl)prop-2-yn-1-yl)oxy)but-2-yne (23). In a flame-
dried Schlenk flask, Pd(PPh3)4 (0.36 g, 0.31 mmol, 10 mol %) and CuI
(0.12 g, 0.62 mmol, 20 mol %) were suspended in 9 mL of toluene.
Then, 1-iodo-2-methylbenzene (0.89 mL, 6.82 mmol, 2.20 equiv),
compound 2 (0.5 g, 3.10 mmol, 1.0 equiv) dissolved in 9 mL of
toluene, and N,N-diisopropylamine (2.20 mL, 15.5 mmol, 5.0 equiv)
were added, and the solution was stirred at 25 °C for 17 h. The
reaction was monitored by TLC, and after completion, the reaction
mixture was quenched with aqueous sat. NH4Cl sol. and filtered
through a pad of Celite. The aqueous phase was extracted several
times with ethyl acetate, and the combined organic phase was washed
with brine, dried over Na2SO4, evaporated, and purified by column
chromatography with c-hex/EE (10:1). Triyne 23 (0.79 g, 74%) was
obtained as a yellow oil.
1,4-Bis((3-(isoquinolin-4-yl)prop-2-yn-1-yl)oxy)but-2-yne (27).
Following the above procedure for 23, catalyst Pd(PPh3)4 (0.53 g,
0.46 mmol, 10 mol %), CuI (0.17 g, 0.92 mmol, 20 mol %), and 4-
bromoisoquinoline (2.0 g, 9.6 mmol, 2.1 equiv) suspended in 40 mL
of toluene as well as added 2 (0.74 g, 4.6 mmol, 1.0 equiv) and N,N-
diisopropylamine (3.2 mL, 22.9 mmol, 5.0 equiv) were stirred at 75 °C
for 38 h. After workup and flash chromatography with n-hex/THF
(1:1, 0.5% NEt3) and recrystallization from acetone triyne, 27 (0.41 g,
22%) was obtained as a yellow solid.
1H NMR (CDCl3, 300 MHz): δ = 4.48 (s, 4H), 4.66 (s, 4H), 7.64
(ddd, J = 8.2, 6.8, 1.2 Hz, 2H), 7.78 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H),
7.97 (dt, J = 8.2, 1.0 Hz, 2H), 8.21 (dq, J = 8.4, 1.0 Hz, 2H), 8.69 (s,
2H), 9.19 (s, 2H) ppm.
1H NMR (CDCl3, 300 MHz): δ = 2.49 (s, 6H), 4.46 (s, 4H), 4.59
(s, 4H), 7.18 (td, J = 7.2, 2.2 Hz, 2H), 7.20−7.34 (m, 4H), 7.47 (dd, J
= 7.4, 1.5 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 57.1, 57.6, 82.1, 82.4, 91.6, 115.1,
124.9, 127.7, 127.9, 128.6, 131.3, 132.0, 146.9, 152.4 ppm.
F
DOI: 10.1021/acs.joc.5b01623
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The Journal of Organic Chemistry
Note
HRMS-ESI (TOF) (C28H20N2O2): calcd: 417.1598 [M + H]+,
439.1417 [M + Na]+; found: 417.1600 [M + H]+, 439.1420 [M +
Na]+.
EA: calcd: C 80.75, H 4.84, N 6.73; found: C 80.68, H 4.82, N 6.30.
Mp. 116−117 °C.
13C NMR (CDCl3, 75 MHz): δ = 56.6, 56.8, 57.0, 57.6, 57.9, 81.5,
82.2, 82.7, 85.0, 89.1, 93.7, 105.4, 112.5, 120.1, 124.2, 125.1, 125.2,
126.1, 126.5, 126.9, 127.5, 128.1, 128.3, 128.4, 129.1, 130.5, 130.8,
133.1, 133.3, 134.6, 159.3 ppm.
HRMS-EI (C31H24O3): calcd: 444.1720; found: 444.1712.
Syntheses of Building Blocks for Malonate-Bridged Triynes.
Diethyl-2-(3-(naphthalen-1-yl)prop-2-yn-1-yl)malonate (34a). In a
flame-dried Schlenk flask, Pd(PPh3)4 (0.58 g, 0.50 mmol, 5 mol %)
and CuI (0.28 g, 1.5 mmol, 15 mol %) were suspended in 50 of mL
NEt3. 1-Iodonaphthalene (1.46 mL, 10 mmol, 1.0 equiv) was added
via syringe, followed by the addition of compound 33a (1.98 g, 10
mmol, 1.0 equiv) dissolved in 20 mL of THF. The solution was heated
to 50 °C for 15 h. The reaction was monitored by TLC, and after
completion, aqueous sat. NH4Cl sol. was used to quench the reaction.
The aqueous phase was extracted several times with ethyl acetate,
washed with brine, dried over Na2SO4, and purified by column
chromatography with n-hex/EE (10:1). Alkyne 34a (3.17 g, 98%) was
obtained as a slightly yellow oil.
1-(3-((4-(But-2-yn-1-yloxy)but-2-yn-1-yl)oxy)prop-1-yn-1-yl)-
naphthalene (28). Following the above procedure for 9, sodium
hydride (0.08 g, 1.98 mmol, 1.1 equiv, 60 wt % in oil), SI-VII (0.45 g,
1.79 mmol, 1.0 equiv), and 1-bromo-2-butyne (0.24 g, 0.85 mmol, 1.0
equiv) suspended in 10 mL of THF were stirred at 25 °C for 12 h.
After flash chromatography with c-hex/EE (20:1), product 28 (0.46 g,
85%) was obtained as a slightly yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 1.86 (t, J = 2.3 Hz, 3H), 4.23 (q,
J = 2.3 Hz, 2H), 4.32 (t, J = 1.8 Hz, 2H), 4.46 (t, J = 1.8 Hz, 2H), 4.64
(s, 2H), 7.42 (dd, J = 8.3, 7.1 Hz, 1H), 7.52 (ddd, J = 8.1, 6.8, 1.4 Hz,
1H), 7.58 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.69 (dd, J = 7.1, 1.1 Hz,
1H), 7.85 (ddd, J = 7.4, 3.3, 2.3 Hz, 2H), 8.32 (dd, J = 8.3, 1.1 Hz, 1H)
ppm.
13C NMR (CDCl3, 100 MHz): δ = 3.6, 56.6, 56.9, 57.2, 57.5, 74.3,
81.9, 82.5, 83.2, 84.9, 89.0, 120.0, 125.1, 126.0, 126.4, 126.9, 128.3,
129.1, 130.8, 133.1, 133.3 ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.29 (t, J = 7.1 Hz, 6H), 3.17 (d,
J = 7.7 Hz, 2H), 3.77 (t, J = 7.7 Hz, 1H), 4.27 (qd, J = 7.1, 1.5 Hz,
4H), 7.39 (dd, J = 8.3, 7.2 Hz, 1H), 7.44−7.61 (m, 2H), 7.60 (d, J =
7.2 Hz, 1H), 7.76−7.86 (m, 2H), 8.27 (d, J = 8.6 Hz, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 19.8, 51.6, 61.8, 80.6, 90.4,
120.9, 125.2, 126.2, 126.3, 126.6, 128.2, 128.5, 130.3, 133.1, 133.5,
168.1 ppm.
HRMS-ESI (TOF) (C21H18O2): calcd: 303.1380 [M + H]+,
325.1199 [M + Na]+; found: 303.1397 [M + H]+, 325.1201 [M +
Na]+.
1-(3-((4-((3-Phenylprop-2-yn-1-yl)oxy)but-2-yn-1-yl)oxy)prop-1-
yn-1-yl)naphthalene (29). Following the above procedure for 9,
sodium hydride (0.29 g, 7.3 mmol, 1.1 equiv, 60 wt % in oil), SI-VIII
(1.32 g, 6.6 mmol, 1.0 equiv), and 8 (1.62 g, 6.6 mmol, 1.0 equiv) as
reaction mixture in 40 mL of THF were stirred at 25 °C for 20 h. After
workup and flash chromatography with c-hex/EE (6:1), triyne 29
(1.80 g, 75%) was obtained as a yellow oil.
HRMS-EI (C20H20O4): calcd: 324.1356; found: 324.1361.
Diethyl-2-(3-(2-methoxynaphthalen-1-yl)prop-2-yn-1-yl)-
malonate (34b). Following the above procedure for 34a, catalyst
Pd(PPh3)4 (1.16 g, 1.0 mmol, 1 mol %), CuI (0.40 g, 2.04 mmol, 2
mol %), and compound 6 (2.85 g, 10 mmol, 1.0 equiv) dissolved in 50
mL of NEt3 as well as a solution of 33a (2.0 g, 10 mmol, 1.0 equiv) in
10 mL of THF were combined and stirred at 50 °C for 15 h. After
workup and flash chromatography with n-hex/EE (10:1), the alkyne
product 34b (3.05 g, 87%) was obtained as a slightly yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.29 (t, J = 7.1 Hz, 6H), 3.24 (d,
J = 7.8 Hz, 2H), 3.81 (t, J = 7.8 Hz, 1H), 4.00 (s, 3H), 4.27 (qd, J =
7.1, 2.4 Hz, 4H), 7.22 (d, J = 9.1 Hz, 1H), 7.36 (ddd, J = 8.1, 6.8, 1.2
Hz, 1H), 7.51 (ddd, J = 8.5, 6.8, 1.2 Hz, 1H), 7.77 (t, J = 8.1 Hz, 2H),
8.18 (dd, J = 8.4, 1.0 Hz, 1H) ppm.
1H NMR (CDCl3, 300 MHz): δ = 4.44 (dt, J = 20.4, 1.8 Hz, 4H),
4.50 (s, 2H), 4.65 (s, 2H), 7.28−7.34 (m, 3H), 7.39−7.48 (m, 3H),
7.52 (ddd, J = 8.2, 6.8, 1.5 Hz, 1H), 7.58 (ddd, J = 8.4, 6.8, 1.5 Hz,
1H), 7.70 (dd, J = 7.2, 1.2 Hz, 1H), 7.85 (ddd, J = 7.5, 3.0, 1.6 Hz,
2H), 8.30−8.34 (m, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 56.9, 57.0, 57.5, 57.6, 82.3, 82.4,
84.2, 85.0, 86.9, 89.1, 120.1, 122.5, 125.2, 126.1, 126.5, 126.9, 128.3,
128.4, 128.6, 129.1, 130.9, 131.9, 133.1, 133.3 ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 20.2, 51.8, 56.6, 61.8, 76.8,
95.2, 106.3, 112.7, 124.1, 125.3, 127.2, 128.0, 128.5, 129.8, 134.8,
158.9, 168.2 ppm.
HRMS-EI (C26H20O2): calcd: 364.1458; found: 364.1451.
2-Methoxy-1-(3-((4-((3-phenylprop-2-yn-1-yl)oxy)but-2-yn-1-yl)-
oxy)prop-1-yn-1-yl)naphthalene (30). Following the above proce-
dure for 9, sodium hydride (0.29 g, 7.3 mmol, 1.1 equiv, 60 wt % in
oil), SI-VIII (1.32 g, 6.6 mmol, 1.0 equiv), and 8 (1.82 g, 6.6 mmol,
1.0 equiv) were suspended in 40 mL of THF, and the mixture was
stirred at 25 °C for 17 h. After workup and flash chromatography with
c-hex/EE (4:1), triyne 30 (2.49 g, 96%) was obtained as a yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 4.02 (s, 3H), 4.40 (t, J = 1.8 Hz,
2H), 4.49−4.52 (m, 4H), 4.71 (s, 2H), 7.25 (d, J = 8.9 Hz, 1H), 7.31
(dd, J = 5.1, 2.0 Hz, 3H), 7.37 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.42−
7.47 (m, 2H), 7.54 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 7.78 (d, J = 8.4 Hz,
1H), 7.83 (d, J = 9.1 Hz, 1H), 8.23 (dd, J = 8.4, 0.9 Hz, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 56.6, 56.8, 56.9, 57.4, 57.9, 81.5,
82.2, 82.6, 84.3, 86.9, 93.7, 105.4, 112.5, 122.4, 124.3, 125.2, 127.5,
128.1, 128.3, 128.5, 128.6, 130.5, 131.9, 134.6, 159.3 ppm.
HRMS-EI (C27H22O3): calcd: 394.1564; found: 394.1560.
2-Methoxy-1-(3-((4-((3-(naphthalen-1-yl)prop-2-yn-1-yl)oxy)but-
2-yn-1-yl)oxy)prop-1-yn-1-yl)naphthalene (31). Following the above
procedure for 9, sodium hydride (0.07 g, 1.65 mmol, 1.1 equiv, 60 wt
% in oil), compound 10 (0.42 g, 1.51 mmol, 1.0 equiv), and SI-V (0.37
g, 1.51 mmol, 1.0 equiv) as reaction mixture in 15 mL of THF were
stirred at 25 °C for 18 h. After workup and flash chromatography with
c-hex/EE (6:1, 1:1), the triyne product 31 (0.51 g, 76%) was obtained
as a yellow oil.
HRMS-ESI (TOF) (C21H22O5): calcd: 355.1540 [M + H]+,
377.1359 [M + Na]+; found: 355.1546 [M + H]+, 377.1362 [M +
Na]+.
Diethyl-2-(4-(2-methoxynaphthalen-1-yl)but-3-yn-1-yl)malonate
(34c). Following the above procedure for 34a, catalyst Pd(PPh3)4
(0.27 g, 0.24 mmol, 10 mol %), CuI (0.09 g, 0.47 mmol, 20 mol %),
and compound 6 (0.67 g, 10 mmol, 1.0 equiv) dissolved in 15 mL of
NEt3 and a solution of 33b (0.50 g, 2.4 mmol, 1.0 equiv) in 2 mL of
THF were mixed and stirred at 50 °C for 17 h. After workup and flash
chromatography with n-hex/EE (10:1), alkyne 34c (0.85 g, 98%) was
obtained as a slightly yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.28 (t, J = 7.1 Hz, 6H), 2.33 (q,
J = 7.2 Hz, 2H), 2.75 (t, J = 7.0 Hz, 2H), 3.83 (t, J = 7.4 Hz, 1H), 4.02
(s, 3H), 4.23 (qd, J = 7.1, 1.3 Hz, 4H), 7.24 (d, J = 9.1 Hz, 1H), 7.37
(ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.52 (ddd, J = 8.3, 6.8, 1.2 Hz, 1H),
7.77 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 9.0 Hz, 1H), 8.24 (dd, J = 8.5, 1.0
Hz, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 18.2, 28.1, 50.8, 56.6, 61.5,
76.2, 97.8, 112.7, 124.1, 125.3, 127.2, 128.0, 128.5, 129.5, 134.7, 144.0,
158.8, 169.3 ppm.
HRMS-EI (C22H24O5): calcd: 368.1618; found: 368.1616.
Diethyl-2-(3-phenylprop-2-yn-1-yl)malonate (SI-IX). Following
the above procedure for 34a, catalyst Pd(PPh3)4 (0.57 g, 0.49
mmol, 5 mol %), CuI (0.28 g, 1.5 mmol, 15 mol %), and 1-
iodobenzene (1.1 mL, 9.8 mmol, 1.0 equiv) dissolved in 60 mL of
NEt3 as well as a solution of 33a (1.93 g, 9.75 mmol, 1.0 equiv) in 5
mL of THF were combined and stirred at 50 °C for 17 h. After
1H NMR (CDCl3, 300 MHz): δ = 4.02 (s, 3H), 4.51 (dt, J = 10.6,
1.8 Hz, 4H), 4.66 (s, 2H), 4.72 (s, 2H), 7.25 (d, J = 9.1 Hz, 1H) 7.31−
7.48 (m, 2H), 7.45−7.63 (m, 3H), 7.69 (d, J = 7.2, 1.2 Hz, 1H), 7.75−
7.80 (m, 1H), 7.81−7.87 (m, 3H), 8.24 (dq, J = 8.4, 0.9 Hz, 1H), 8.32
(ddt, J = 8.4, 1.4, 0.8 Hz, 1H) ppm.
G
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
workup and flash chromatography with n-hex/EE (10:1), product SI-
IX (2.59 g, 97%) was obtained as a slightly yellow oil.
equiv), and SI-II (0.53 g, 2.5 mmol, 1.0 equiv) as reaction mixture in
30 mL of THF were stirred at 25 °C for 21 h. After workup and
purification by flash chromatography with c-hex/EE (10:1), triyne 36a
(1.54 g, 88%) was obtained as a yellow oil.
The spectral data are according to those reported in the literature.25
Diethyl-2-(4-bromobut-2-yn-1-yl)-2-(3-(naphthalen-1-yl)prop-2-
yn-1-yl)malonate (35a). Following the procedure for 35b, sodium
ethanolate (0.34 g, 5.0 mmol, 1.04 equiv), 34a (1.55 g, 4.79 mmol, 1.0
equiv), and SI−II (1.06 g, 5.0 mmol, 1.04 equiv) suspended in 50 mL
of THF were stirred at 25 °C for 16 h. After workup and flash
chromatography with c-hex/EE (10:1), diyne 35a (1.10 g, 51%) was
obtained as a yellow oil and triyne 36a (0.69 g, 21%) was isolated as a
yellow oil.
1H NMR (CDCl3, 400 MHz): δ = 1.26 (t, J = 7.1 Hz, 12H), 3.13 (s,
4H), 3.38 (s, 4H), 4.27 (q, J = 7.1 Hz, 8H), 7.37 (dd, J = 8.3, 7.2 Hz,
2H), 7.48 (ddd, J = 8.0, 6.8, 1.3 Hz, 2H), 7.55 (ddd, J = 8.3, 6.8, 1.3
Hz, 2H), 7.60 (dd, J = 7.2, 1.1 Hz, 2H), 7.78 (dt, J = 8.4, 1.1 Hz, 2H),
7.82 (d, J = 8.0 Hz, 2H), 8.27 (d, J = 8.4 Hz, 2H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 14.1, 23.3, 23.9, 56.9, 62.1, 78.0,
81.6, 89.2, 120.9, 125.2, 126.2, 126.3, 126.7, 128.2, 128.4, 130.5, 133.1,
133.4, 169.0 ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.29 (t, J = 7.1 Hz, 6H), 3.19 (t, J
= 2.4 Hz, 2H), 3.36 (s, 2H), 3.90 (t, J = 2.4 Hz, 2H), 4.28 (q, J = 7.1
Hz, 4H), 7.39 (dd, J = 8.3, 7.2 Hz, 1H), 7.50 (ddd, J = 8.1, 6.8, 1.5 Hz,
1H), 7.53−7.63 (m, 2H), 7.82 (ddd, J = 9.3, 8.2, 1.1 Hz, 2H), 8.26
(dd, J = 8.2, 0.8 Hz, 1H) ppm.
HRMS-EI (C44H42O8): calcd: 698.2874; found: 698.2872.
Tetraethyl-1,12-bis(2-methoxynaphthalen-1-yl)dodeca-1,6,11-
triyne-4,4,9,9-tetracarboxylate (36b). Following the above procedure
for 35b, a mixture consisting of sodium hydride (0.18 g, 4.44 mmol,
2.1 equiv, 60 wt % in oil), 34b (1.5 g, 4.23 mmol, 2.0 equiv), and SI-II
(0.45 g, 2.1 mmol, 1.0 equiv) dissolved in 60 mL of THF was stirred at
25 °C for 18 h. After flash chromatography with c-hex/EE (4:1), triyne
36b (0.71 g, 45%) was obtained as a yellow oil.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 14.7, 23.5, 24.1, 56.8, 62.2,
78.6, 81.9, 82.1, 88.8, 120.7, 125.2, 126.1, 126.3, 126.7, 128.2, 128.6,
130.5, 133.1, 133.4, 168.8 ppm.
HRMS-ESI (TOF) (C24H23BrO4): calcd: 455.0853 [M + H]+,
477.0672 [M + Na]+; found: 455.0851 [M + H]+, 477.0670 [M +
Na]+.
1H NMR (CDCl3, 300 MHz): δ = 1.25 (t, J = 7.1 Hz, 12H), 3.16 (s,
4H), 3.42 (s, 4H), 3.97 (s, 6H), 4.26 (q, J = 7.1 Hz, 8H), 7.20 (d, J =
9.1 Hz, 2H), 7.33 (ddd, J = 8.1, 6.8, 1.2 Hz, 2H), 7.51 (ddd, J = 8.5,
6.8, 1.2 Hz, 2H), 7.70−7.81 (m, 4H), 8.19 (dd, J = 8.5, 1.0 Hz, 2H)
ppm.
Diethyl-2-(4-bromobut-2-yn-1-yl)-2-(3-(2-methoxynaphthalen-1-
yl)prop-2-yn-1-yl)malonate (35b). A solution of 34b (1.0 g, 2.82
mmol, 1.0 equiv) in 5 mL of THF was added dropwise to a cooled
solution of sodium hydride (0.12 g, 2.96 mmol, 1.05 equiv, 60 wt % in
oil) in 20 mL of THF at 0 °C. The solution was allowed to warm to 25
°C and stirred for 1 h, until the hydrogen evolution ceased. The
resulting mixture was slowly added to a solution of SI-II (1.6 g, 7.05
mmol, 2.5 equiv) in 5 mL of THF and stirred at 25 °C for 18 h. The
reaction was monitored by TLC, and after completion, the reaction
was quenched with water and extracted with ethyl acetate. The organic
phases were washed with brine and dried over Na2SO4, and the solvent
was removed under reduced pressure. The crude product was purified
by flash chromatography with c-hex/EE (4:1), and product 35b (1.07
g, 79%) was obtained as a yellow oil.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 23.2, 24.2, 56.6, 57.0, 61.9,
77.8, 78.0, 93.8, 106.5, 112.8, 124.0, 125.4, 127.2, 127.9, 128.4, 129.6,
134.7, 159.1, 169.1 ppm.
HRMS-EI (C46H46O10): calcd: 758.3086; found: 758.3074.
Tetraethyl-1-(naphthalen-1-yl)trideca-1,6,11-triyne-4,4,9,9-tetra-
carboxylate (36c). Following the above procedure for 34a, catalyst
Pd(PPh3)4 (58 mg, 0.05 mmol, 5 mol %), CuI (29 mg, 0.15 mmol, 15
mol %), and 1-iodonaphthalene (0.18 mL, 1.2 mmol, 1.2 equiv)
dissolved in 5 mL of NEt3 and a solution of compound 38 (0.46 g, 1.0
mmol, 1.0 equiv) in 1 mL of THF were combined and stirred at 25 °C
for 15 h. After flash chromatography with n-hex/acetone (10:1), the
triyne product 36c (0.48 g, 81%) was obtained as a colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 1.23 (t, J = 7.1 Hz, 6H), 1.28 (t, J
= 7.1 Hz, 6H), 1.74 (t, J = 2.5 Hz, 3H), 2.91 (q, J = 2.4 Hz, 2H), 2.95
(t, J = 2.3 Hz, 2H), 3.08 (t, J = 2.3 Hz, 2H), 3.33 (s, 2H), 4.21 (q, J =
7.1 Hz, 4H), 4.27 (q, J = 7.1 Hz, 4H), 7.38 (dd, J = 8.2, 7.2 Hz, 1H),
7.49 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.56 (ddd, J = 8.3, 6.8, 1.3 Hz,
1H), 7.60 (dd, J = 7.2, 1.2 Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.82 (dd,
J = 8.1, 0.6 Hz, 1H), 8.24-.8.28 (m, 1H) ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.28 (t, J = 7.1 Hz, 6H), 3.24 (t, J
= 2.4 Hz, 2H), 3.41 (s, 2H), 3.90 (t, J = 2.3 Hz, 2H), 4.00 (s, 3H), 4.27
(q, J = 7.1 Hz, 4H), 7.22 (d, J = 9.1 Hz, 1H), 7.36 (ddd, J = 8.1, 6.8,
1.2 Hz, 1H), 7.53 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.73−7.81 (m, 2H),
8.17 (dd, J = 8.4, 1.0 Hz, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 14.9, 23.4, 23.5, 56.6, 56.9,
62.1, 78.1, 78.5, 82.4, 93.4, 106.3, 112.8, 124.1, 125.3, 127.3, 128.0,
128.5, 129.8, 134.7, 159.2, 168.9 ppm.
13C NMR (CDCl3, 75 MHz): δ = 3.5, 14.0 (2×), 22.8, 23.2, 23.8,
56.8, 56.9, 61.8, 62.0, 73.2, 77.2, 77.6, 78.1, 78.8, 81.5, 89.2, 120.9,
125.1, 126.2, 126.3, 126.6, 128.1, 128.4, 130.4, 133.1, 133.4, 168.9,
169.0 ppm.
HRMS-ESI (TOF) (C25H25BrO5): calcd: 485.0958 [M + H]+,
507.0778 [M + Na]+; found: 485.0964 [M + H]+, 507.0775 [M +
Na]+.
Diethyl-2-(4-bromobut-2-yn-1-yl)-2-(4-(2-methoxynaphthalen-1-
yl)but-3-yn-1-yl)malonate (35c). Following the procedure for 35b,
sodium hydride (0.14 g, 3.4 mmol, 1.05 equiv, 60 wt % in oil), 34c
(1.2 g, 3.26 mmol, 1.0 equiv), and SI-II (1.73 g, 8.2 mmol, 2.5 equiv)
dissolved in 50 mL of THF were stirred at 25 °C for 18 h. After
workup and flash chromatography with c-hex/EE (4:1), product 35c
(1.48 g, 79%) was obtained as a yellow oil.
Because of signal overlaps, not all expected carbon atoms could be
assigned.
HRMS-ESI (TOF) (C35H38O8): calcd: 587.2639 [M + H]+,
609.2459 [M + Na]+; found: 587.2640 [M + H]+, 609.2463 [M +
Na]+.
Tetraethyl-1-(2-methoxynaphthalen-1-yl)trideca-1,6,11-triyne-
4,4,9,9-tetracarboxylate (36d). Following the above procedure for
34a, Pd(PPh3)4 (57 mg, 0.05 mmol, 5 mol %), CuI (28 mg, 0.15
mmol, 15 mol %), and 6 (0.31 g, 1.07 mmol, 1.1 equiv) in 11 mL of
NEt3 and compound 38 (0.45 g, 0.98 mmol, 1.0 equiv) in 3 mL of
THF were stirred at 50 °C for 18 h. After flash chromatography with
n-hex/EE (4:1), triyne 36d (0.50 g, 83%) was obtained as a colorless
oil.
1H NMR (CDCl3, 300 MHz): δ = 1.27 (t, J = 7.1 Hz, 6H), 2.47−
2.60 (m, 2H), 2.59−2.72 (m, 2H), 3.01 (t, J = 2.4 Hz, 2H), 3.87 (t, J =
2.4 Hz, 2H), 4.02 (s, 3H), 4.22 (qd, J = 7.1, 4.5 Hz, 4H), 7.23 (d, J =
9.1 Hz, 1H), 7.37 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.53 (ddd, J = 8.4,
6.8, 1.2 Hz, 1H), 7.76 (dd, J = 7.3, 0.9 Hz, 1H), 7.78 (d, J = 9.1 Hz,
1H), 8.25 (dd, J = 8.5, 0.9, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.0, 14.8, 15.7, 23.6, 31.7, 56.6,
61.9, 75.3, 78.5, 82.2, 98.2, 106.6, 106.8, 112.6, 124.1, 125.4, 127.2,
128.0, 128.5, 129.5, 134.8, 158.6, 169.8 ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.24 (dt, J = 12.9, 7.1 Hz, 12H),
1.73 (t, J = 2.5 Hz, 3H), 2.90 (q, J = 2.3 Hz, 2H), 2.94 (t, J = 2.3 Hz,
2H), 3.11 (t, J = 2.3 Hz, 2H), 3.38 (s, 2H), 3.98 (s, 3H), 4.13−4.32
(m, 8H), 7.21 (d, J = 9.1 Hz, 1H), 7.35 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H),
7.52 (ddd, J = 8.5, 6.8, 1.2 Hz, 1H), 7.76 (dd, J = 8.5, 6.6 Hz, 2H),
8.15−8.20 (m, 1H) ppm.
HRMS-ESI (TOF) (C26H27BrO5): calcd: 499.1115 [M + H]+,
521.0934 [M + Na]+; found: 499.1118 [M + H]+, 521.0934 [M +
Na]+.
Syntheses of Malonate-Bridged Triynes. Tetraethyl-1,12-
di(naphthalen-1-yl)dodeca-1,6,11-triyne-4,4,9,9-tetracarboxylate
(36a). Following the above procedure for 35b, sodium hydride (0.20
g, 5.0 mmol, 2.0 equiv, 60 wt % in oil), 34a (1.62 g, 5.0 mmol, 2.0
13C NMR (CDCl3, 75 MHz): δ = 3.5, 14.1, 22.8, 23.2, 24.2, 56.6,
56.8, 57.0, 61.8, 61.9, 73.3, 77.8, 78.0, 78.9, 93.8, 106.5, 112.9, 124.1,
125.4, 127.2, 127.9, 128.5, 129.6, 134.7, 159.1, 169.0, 169.1 ppm.
H
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Because of signal overlaps, not all expected carbon atoms could be
assigned.
1H NMR (CDCl3, 300 MHz): δ = 1.23 (dt, J = 9.2, 7.1 Hz, 12H),
2.47−2.68 (m, 4H), 2.96 (dt, J = 30.1, 2.4 Hz, 4H), 3.17 (s, 2H), 4.00
(s, 3H), 4.13−4.29 (m, 8H), 7.20−7.25 (m, 4H), 7.31−7.38 (m, 3H),
7.52 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.79 (d, J
= 9.0 Hz, 1H), 8.27 (dd, J = 8.4 Hz, 1H) ppm.
HRMS-ESI (TOF) (C36H40O9): calcd: 617.2745 [M + H]+,
639.2565 [M + Na]+; found: 617.2758 [M + H]+, 639.2571 [M +
Na]+.
Tetraethyl-1-(naphthalen-1-yl)-12-phenyldodeca-1,6,11-triyne-
4,4,9,9-tetracarboxylate (36e). Following the above procedure for
35b, sodium hydride (93 mg, 2.3 mmol, 1.05 equiv, 60 wt % in oil), SI-
IX (0.60 g, 2.2 mmol, 1.0 equiv), and compound 35a (1.0 g, 2.2 mmol,
1.0 equiv) as reaction mixture in 20 mL of THF were stirred at 25 °C
for 18 h. After workup and flash chromatography with c-hex/EE (4:1),
triyne 36e (1.33 g, 94%) was obtained as a yellow oil.
13C NMR (CDCl3, 75 MHz): δ = 14.1 (2×), 15.7, 23.0, 23.3, 23.5,
31.5, 56.6, 61.8, 61.9, 75.2, 77.8, 77.9, 83.5, 84.2, 98.4, 106.8, 112.7,
123.2, 124.1, 125.5, 127.2, 127.9, 128.1, 128.4, 129.4, 131.7, 134.8,
158.6, 168.9, 170.0 ppm. Because of signal overlaps, not all expected
carbon atoms could be assigned.
HRMS-EI (C42H44O9): calcd: 692.2980; found: 692.2985.
Tetraethyl-trideca-1,6,11-triyne-4,4,9,9-tetracarboxylate (38). To
a suspension of sodium hydride (0.20 g, 5.1 mmol, 1.04 equiv, 60 wt %
in oil) in 10 mL of THF was slowly added compound 33a (1.0 g, 5.04
mmol, 1.0 equiv) dissolved in 10 mL of THF via a dropping funnel,
and the mixture was stirred at 25 °C for 40 min, until the hydrogen
evolution had ceased. This solution was added dropwise over a period
of 1 h to a solution of 1,4-dibromobut-2-yne (1.07 g, 5.04 mmol, 1.0
equiv) in 10 mL of THF and stirred for an additional 2 h. Meanwhile,
to a suspension of sodium hydride (0.20 g, 5.1 mmol, 1.04 equiv, 60 wt
% in oil) in 10 mL of THF was slowly added a solution of compound
33b (1.1 g, 5.04 mmol, 1.0 equiv) in 10 mL of THF, and the mixture
was stirred for 40 min, until the hydrogen evolution had ceased. The
latter solution was then slowly added to the first solution, and the
mixture was stirred at 25 °C for an additional 15 h. The reaction was
monitored by TLC, quenched with water, and extracted with ethyl
acetate. The organic phases were washed with brine and dried over
sodium sulfate, and the solvent was removed under reduced pressure.
The crude product was purified by bulb-to-bulb distillation, and triyne
38 (1.46 g, 63%) was obtained as a colorless oil.
1H NMR (CDCl3, 300 MHz): δ = 1.26 (q, J = 7.0 Hz, 12H), 3.03
(t, J = 2.2 Hz, 2H), 3.10 (t, J = 2.3 Hz, 2H), 3.20 (s, 2H), 3.35 (s, 2H),
4.25 (dq, J = 8.3, 7.1 Hz, 8H), 7.24−7.28 (m, 3H), 7.34−7.41 (m,
3H), 7.45−7.63 (m, 3H), 7.77−7.84 (m, 2H), 8.17−8.31 (m, 1H)
ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 23.1, 23.2, 23.5, 23.8, 56.9
(2×), 62.0 (2×), 77.9, 78.0, 81.6, 84.2, 89.2, 120.9, 124.9, 125.2, 126.2,
126.3, 126.7, 128.0, 128.2, 128.4, 130.5, 131.7, 133.1, 133.4, 168.9,
169.0 ppm. Because of signal overlaps, not all expected carbon atoms
could be assigned.
HRMS-EI (C40H40O8): calcd: 648.2718; found: 648.2708.
Tetraethyl-1-(2-methoxynaphthalen-1-yl)-12-phenyldodeca-
1,6,11-triyne-4,4,9,9-tetracarboxylate (36f). Following the above
procedure for 35b, sodium hydride (30 mg; 0.74 mmol, 1.05 equiv,
60 wt % in oil), SI-IX (0.19 g, 0.7 mmol, 1.0 equiv), and compound
35b (0.34 g, 0.7 mmol, 1.0 equiv) as reaction solution in 10 mL of
THF were stirred at 25 °C for 18 h. After workup and flash
chromatography with c-hex/EE (4:1), the triyne product 36f (0.30 g,
99%) was obtained as a yellow oil.
The spectral data are in accordance with the literature.26
1H NMR (CDCl3, 300 MHz): δ = 1.25 (tdd, J = 7.1, 6.1, 0.5 Hz,
12H), 3.03 (t, J = 2.3 Hz, 2H), 3.14 (t, J = 2.4 Hz, 2H), 3.20 (s, 2H),
3.40 (s, 2H), 3.98 (d, J = 0.4, 3H), 4.18−4.31 (m, 8H), 7.21 (d, J = 9.1
Hz, 1H), 7.23−7.29 (m, 3H), 7.30−7.39 (m, 3H), 7.52 (ddd, J = 8.3,
6.8, 1.3 Hz, 1H), 7.72−7.80 (m, 2H), 8.18 (dd, J = 8.6, 0.7 Hz, 1H)
ppm.
Syntheses of the Two Different Triynes. Diisopropyl((2-
methoxynaphthalen-1-yl)ethynyl)silane (SI-X). To a cooled solution
of 1-ethynyl-2-methoxynaphthalene (1.37 g, 7.5 mmol, 1.0 equiv) in
25 mL of THF was slowly added n-butyllithium (4.92 mL, 7.88 mmol,
1.05 equiv), and the mixture was stirred at −78 °C for 2 h. Then,
chlorodiisopropylsilane (1.56 mL, 9.0 mmol, 1.2 equiv) was added at
−78 °C, and the reaction mixture warmed to 25 °C and stirred for an
additional 2 h. The reaction was monitored by TLC and stopped by
the addition of diethyl ether. The organic phase was washed twice with
aqueous sat. NH4Cl sol. and subsequently with brine, dried with
MgSO4, filtered, and evaporated. The crude product was purified by
flash chromatography with PE/EE 50:1, and product SI-X (1.98 g,
89%) was obtained as a colorless oil.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 23.1, 23.2, 23.5, 24.3, 56.6,
56.9, 57.0, 62.0, 77.8, 78.0, 83.5, 84.3, 93.8, 106.5, 112.9, 122.2, 123.3,
124.1, 125.4, 127.2, 127.9, 128.2, 128.5, 129.6, 131.7, 134.7, 159.1,
168.9, 169.1 ppm. Because of signal overlaps, not all expected carbon
atoms could be assigned.
HRMS-EI (C41H42O9): calcd: 678.2823; found: 678.2813.
Tetraethyl-1-(2-methoxynaphthalen-1-yl)tetradeca-1,7,12-
triyne-5,5,10,10-tetracarboxylate (36g). Following the above proce-
dure for 35b, sodium hydride (45 mg, 1.11 mmol, 1.01 equiv, 60 wt %
in oil), 37 (0.23 g, 1.1 mmol, 1.0 equiv), and compound 35c (0.55 g,
1.1 mmol, 1.0 equiv) dissolved in 15 mL of THF were stirred at 25 °C
for 18 h. After workup and flash chromatography with c-hex/EE (4:1),
triyne 36g (0.54 g, 79%) was obtained as a yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 1.14−1.27 (m, 14H), 3.99 (sbr,
1H), 4.02 (s, 3H), 7.23 (d, J = 9.1 Hz, 1H), 7.38 (ddd, J = 8.1, 6.8, 1.2
Hz, 1H), 7.55 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.77 (dt, J = 8.1, 0.9 Hz,
1H), 7.82 (d, J = 9.1 Hz, 1H), 8.29 (dd, J = 8.4, 0.9 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 11.1, 18.5, 18.7, 56.8, 98.1,
101.9, 106.4, 112.9, 124.2, 125.3, 127.5, 128.1, 128.5, 130.5, 134.8,
160.0 ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.23 (dt, J = 9.2, 7.1 Hz, 12H),
1.70 (t, J = 2.5 Hz, 3H) 2.47−2.68 (m, 4H), 2.89 (t, J = 2.4 Hz, 4H),
2.93 (t, J = 2.1 Hz, 2H), 4.00 (s, 3H), 4.13−4.29 (m, 8H), 7.20−7.25
(m, 1H), 7.31−7.38 (m, 1H), 7.52 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 7.75
(d, J = 8.2 Hz, 1H), 7.79 (d, J = 9.0 Hz, 1H), 8.27 (dd, J = 8.6, 1.0 Hz,
1H) ppm.
29Si NMR (CDCl3, 79 MHz): δ = −15.4 ppm.
HRMS-EI (C19H24OSi): calcd: 296.1593; found: 296.1591.
Diisopropyl((2-methoxynaphthalen-1-yl)ethynyl)((4-((3-phenyl-
prop-2-yn-1-yl)oxy)but-2-yn-1-yl)oxy)silane (54). In a flame-dried
Schlenk flask, SI-X (1.49 g, 5.0 mmol, 1.0 equiv) was dissolved in 25
mL of CH2Cl2, N-bromosuccinimide (1.38 g, 7.76 mmol, 1.5 equiv)
was added as solid, and the solution was stirred at 60 °C for 6 h. The
resulting solution was then added to a solution of SI-VIII (0.90 g, 4.5
mmol, 0.9 equiv), N,N-dimethylaminopyridine (DMAP, 0.06 g, 0.50
mmol, 0.1 equiv), and NEt3 (0.7 mL, 5.0 mmol, 1.0 equiv) in 23 mL of
CH2Cl2, and the mixture was stirred at 25 °C for 16 h. After that time,
the mixture was in addition heated to 40 °C for 4 h. Additional DMAP
(0.06 g, 0.5 mmol, 0.1 equiv) and NEt3 (0.7 mL, 5.0 mmol, 1.0 equiv)
were added, and the solution was stirred at 25 °C for 3 days and finally
followed by heating to 40 °C for 8 h. The solvent was removed under
reduced pressure, and the crude product was purified with PE/EE
25:1. The expected triyne 54 was obtained as a yellow oil in 35% yield
(0.79 g).
13C NMR (CDCl3, 75 MHz): δ = 3.5, 14.0, 15.6, 22.8, 22.9, 23.3,
31.5, 56.6, 56.8, 61.7, 61.8, 73.2, 75.1, 77.6, 78.1, 78.9, 98.4, 106.8,
112.7, 124.1, 125.5, 127.2, 127.9, 128.5, 129.4, 134.8, 158.7, 169.1,
169.9 ppm. Because of signal overlaps, not all expected carbon atoms
could be assigned.
HRMS-EI (C37H42O9): calcd: 630.2823; found: 630.2815.
Tetraethyl-13-(2-methoxynaphthalen-1-yl)-1-phenyltrideca-
1,6,12-triyne-4,4,9,9-tetracarboxylate (36h). Following the above
procedure for 35b, sodium hydride (90 mg, 2.2 mmol, 1.05 equiv, 60
wt % in oil), SI-IX (0.59 g, 2.1 mmol, 1.0 equiv), and compound 35c
(1.0 g, 2.1 mmol, 1.0 equiv) as reaction mixture in 20 mL of THF were
stirred for 22 h at 25 °C. After workup and flash chromatography with
c-hex/EE (4:1), triyne 36h (1.05 g, 72%) was obtained as a yellow oil.
I
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1H NMR (CDCl3, 400 MHz): δ = 1.20 (d, J = 1.8 Hz, 14H), 4.02
(s, 3H), 4.37 (t, J = 1.8 Hz, 2H), 4.46 (s, 2H), 4.68 (t, J = 1.8 Hz, 2H),
7.24 (d, J = 9.1 Hz, 1H), 7.28−7.33 (m, 3H), 7.37 (ddd, J = 8.1, 6.8,
1.2 Hz, 1H), 7.41−7.44 (m, 2H), 7.56 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H),
7.78 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.9 Hz, 1H), 8.28 (dq, J = 8.5, 0.9
Hz, 1H) ppm.
and the resulting mixture was stirred overnight at 25 °C or heated to
temperatures up to 95 °C (see below at the individual products for the
reaction temperature). The reaction was monitored by TLC, and after
completion, the solvent was removed and the crude product was
purified by flash chromatography with c-hex/EE. The cyclotrimeriza-
tion products were obtained as colorless to yellow solids.
For every compound in parentheses: (amount of substrate, catalyst
loading, solvent if not THF, reaction temperature, time, eluent for
column chromatography, yield, d/l:meso ratio, aggregation state).
4,5-Di(naphthalen-1-yl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]-
difuran (39). (0.15 mmol, 10 mol % CoCl(PPh3)3, 25 °C, 36 h, c-hex/
EE (4:1); 57 mg (92%), 1:1.1 (d/l:meso ratio), colorless solid).
The spectral data are according to the literature.18
13C NMR (CDCl3, 75 MHz): δ = 13.3, 17.2, 17.3, 53.2, 56.7, 56.9,
57.2, 77.3, 80.2, 84.4, 85.7, 86.6, 97.7, 102.2, 112.8, 122.6, 124.3, 125.2,
127.7, 128.2, 128.3, 128.4, 128.5, 130.8, 131.8, 134.7, 160.4 ppm.
29Si NMR (CDCl3, 79 MHz): δ = 0.91 ppm.
HRMS-EI (C32H34O3Si): calcd: 494.2272; found: 494.2263.
9-(Naphthalen-1-yl)nona-2,8-diyn-1-ol (SI-XI). In a flame-dried
Schlenk flask, a suspension of PdCl2(PPh3)2 (0.11 g, 0.16 mmol, 2.5
mol %) and CuI (0.09 g, 0.48 mmol, 7.5 mol %) in 16 mL of N,N-
diisopropylethylamine was prepared, and a solution of 2,8-nonadiyn-1-
ol (0.96 g, 7.06 mmol, 1.1 equiv) in 5 mL of NEt3 was added dropwise,
followed by the addition of 1-iodonaphthalene (0.94 mL, 6.4 mmol,
0.9 equiv) via syringe. The solution was stirred at 25 °C for 17 h and
then heated for 30 min to 40 °C. The reaction mixture was quenched
with aqueous sat. NH4Cl sol., and the aqueous phase was extracted
with ethyl acetate. The combined organic phases were washed with
brine, dried over sodium sulfate, and evaporated. After flash
chromatography with PE/DE (1:1), the product SI-XI (1.47 g,
87%) was obtained as a slightly yellow oil.
4,5-Bis(2-methoxynaphthalen-1-yl)-1,3,6,8-tetrahydrobenzo[1,2-
c:3,4-c′]difuran (40). (0.1 mmol, 10 mol % CoCl(PPh3)3, 25 °C, 24 h,
no product isolated).
4,5-Di(phenanthren-9-yl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]-
difuran (41). (0.14 mmol, 10 mol % CoCl(PPh3)3, 25 °C, 17 h, c-hex/
EE (4:1); 60 mg (86%), (d/l:meso ratio could not be assigned),
colorless solid).
The spectral data are according to the literature.18
4,5-Bis(4-methylnaphthalen-1-yl)-1,3,6,8-tetrahydrobenzo[1,2-
c:3,4-c′]difuran (42). (0.10 mmol, 10 mol % CoCl(PPh3)3, 25 °C, 24
h, c-hex/EE (4:1); 45 mg (94%), 1.1:1 (d/l:meso ratio, GC area)
colorless solid).
1H NMR (CDCl3, 300 MHz): δ = 1.57 (s, 1H), 1.70−1.90 (m, 4H),
2.34 (tt, J = 6.7, 2.2 Hz, 2H), 2.55−2.67 (m, 2H), 4.27 (t, J = 2.2 Hz,
2H), 7.40 (dd, J = 8.3, 7.1 Hz, 1H), 7.50 (ddd, J = 8.3, 6.8, 1.6 Hz,
1H), 7.56 (ddd, J = 8.3, 6.8, 1.6 Hz, 1H), 7.62 (dd, J = 7.1, 1.2 Hz,
1H), 7.78 (dt, J = 8.3, 1.1 Hz, 1H), 7.81−7.86 (m, 1H), 8.33 (ddt, J =
8.3, 1.4, 0.8 Hz, 1H) ppm.
Meso and d/l forms are not separable by column chromatography.
1H NMR (CDCl3, 300 MHz): δ = 2.51 (dd, J = 3.9, 0.8 Hz, 12H),
4.69 (ddt, J = 12.0, 3.5, 2.0 Hz, 8H), 5.15−5.31 (m, 8H), 6.73−6.86
(m, 4H), 7.06−7.32 (m, 8H), 7.41−7.55 (m, 4H), 7.60−7.67 (m, 2H),
7.68−7.79 (m, 4H), 7.88−7.97 (m, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 19.4 (2×), 73.0 (2×), 73.8 (2×),
124.2, 124.5, 125.0, 125.2, 125.3, 125.4, 125.5, 125.7, 125.8, 126.0,
126.2, 126.4, 127.8, 130.9, 131.0, 131.1, 131.6, 132.4 (2×), 133.6,
133.7, 133.8, 134.3, 135.8, 140.0, 140.1 ppm.
13C NMR (CDCl3, 75 MHz): δ = 18.4, 19.3, 27.8, 28.0, 51.5, 78.8,
79.0, 86.1, 94.8, 121.6, 125.0, 125.3, 126.3, 126.6, 128.0, 128.3, 130.1,
133.2, 133.5 ppm.
HRMS-EI (C19H18O): calcd: 262.1352; found: 262.1347.
1-(9-(But-2-yn-1-yloxy)nona-1,7-diyn-1-yl)naphthalene (56). Fol-
lowing the above procedure for 9, a mixture of sodium hydride (0.15 g,
3.85 mmol, 1.1 equiv, 60 wt % in oil), SI-XI (0.92 g, 3.50 mmol, 1.0
equiv), and 1-bromo-2-butyne (0.51 g, 3.85 mmol, 1.0 equiv) in 20 mL
of THF was stirred at 25 °C for 16 h. After workup and flash
chromatography with PE/DE (3:1), 56 (0.83 g, 75%) was obtained as
a slightly yellow oily product.
HRMS-EI (C32H26O2): calcd: 442.1927; found: 442.1924.
EA: calcd: C 86.85, H 5.92; found: C 86.59, H 5.84.
Mp. 229.5−230.5 °C.
4,5-Di-o-tolyl-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]difuran (43).
(0.26 mmol, 5 mol % CoCl(PPh3)3, THF, 25 °C, 36 h, c-hex/EE
(4:1); 69 mg (78%), 1:1.1 (d/l:meso ratio, GC area), colorless solid).
The meso and d/l forms are not separable by column
chromatography.
1H NMR (CDCl3, 300 MHz): δ = 1.72−1.84 (m, 4H), 1.85 (t, J =
2.3 Hz, 3H), 2.34 (tt, J = 6.6, 2.1 Hz, 2H), 2.57−2.65 (m, 2H), 4.20
(q, J = 2.3 Hz, 2H), 4.23 (t, J = 2.1 Hz, 2H), 7.40 (dd, J = 8.3, 7.1 Hz,
1H), 7.50 (ddd, J = 8.1, 6.8, 1.5 Hz, 1H), 7.56 (ddd, J = 8.3, 6.8, 1.6
Hz, 1H), 7.62 (dd, J = 7.2, 1.2 Hz, 1H), 7.78 (dt, J = 8.3, 1.1 Hz, 1H),
7.81−7.86 (m, 1H), 8.33 (ddt, J = 8.3, 1.5, 0.8 Hz, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 3.7, 18.5, 19.3, 27.8, 28.0, 57.0,
57.1, 74.6, 75.8, 78.9, 82.9, 86.9, 94.8, 121.6, 125.3, 126.3, 126.6, 126.6,
128.0, 128.2, 130.1, 133.2, 133.5 ppm.
1H NMR (CDCl3, 300 MHz): δ = 2.06 (s, 8H), 2.09 (s, 4H), 4.70−
4.83 (m, 8H), 5.11−5.21 (m, 8H), 6.90−6.95 (m, 2H), 6.96−7.02 (m,
6H), 7.03−7.07 (m, 8H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 19.5, 19.9, 72.8, 72.9, 73.7, 73.8,
125.0, 125.3, 127.3, 127.3, 127.5, 128.1, 129.8, 129.9, 130.6, 130.8,
133.9, 134.0, 135.1, 135.3, 137.2, 137.9, 138.8, 139.1 ppm.
HRMS-EI (C24H22O2): calcd: 342.1614; found: 342.1611.
EA: calcd: C 84.18, H 6.48; found: C 84.03, H 6.00.
Mp. 154.5−155.5 °C.
HRMS-ESI (TOF) (C23H22O): calcd: 315.1743 [M + H]+,
337.1563 [M + Na]+; found: 315.1737 [M + H]+, 337.1569 [M +
Na]+.
Cyclization Products. 1,3,6,8-Tetrahydrobenzo[1,2-c:3,4-c′]-
difuran (4) and 4,5-Diphenyl-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-
c′]difuran (5). Procedure for the cyclotrimerization of either 2 or 3
with catalytic amounts of CoCl(PPh3)3 (1, 5 mol %):
4,5-Bis(2-isopropylphenyl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]-
difuran (44). (0.35 mmol, 4 mol % CoCl(PPh3)3, THF, 25 °C, 36 h, c-
hex/EE (4:1); 99 mg (72%), 1.3:1 (d/l:meso ratio, GC area), colorless
solid).
Meso and d/l forms are not separable by column chromatography.
1H NMR (CDCl3, 300 MHz): δ = 0.87 (d, J = 6.8 Hz, 4H), 0.94 (d,
J = 6.8 Hz, 12H), 1.16 (d, J = 6.8 Hz, 8H), 2.70 (sept, J = 6.9 Hz, 2H),
2.81 (sept, J = 6.9 Hz, 2H), 4.67 (d, J = 12.5 Hz, 2H), 4.74 (d, J = 11.7
Hz, 2H), 4.89−4.97 (m, 4H), 5.11−5.21 (m, 8H), 6.90 (dd, J = 8.0,
7.7, 1.6 Hz, 2H), 6.95−7.00 (m, 2H), 7.05−7.12 (m, 5H), 7.15−7.23
(m, 7H) ppm.
In a flame-dried Schlenk tube, CoCl(PPh3)3 (1, 5 mol %) was
suspended in THF (6 mL/mmol triyne). The triyne (2, 1.23 mmol, or
3, 0.58 mmol) was added as a solution in THF, and the resulting
mixture was stirred at 25 °C. The TLC showed complete reaction
within 3 h. The solvent was removed, and the crude product was
purified by flash chromatography with n-hex/EE (1:1). The cyclo-
trimerization products were obtained as colorless (4, 195 mg, 98%) to
light yellow (5, 156 mg, 85%) solids.
13C NMR (CDCl3, 75 MHz): δ = 22.5, 24.1, 25.4, 25.8, 29.6, 30.0,
72.8, 73.0, 73.9, 74.1, 124.9, 125.2, 125.3, 125.8, 127.8, 128.1, 129.7,
131.0, 131.1, 131.6, 133.8, 134.1, 135.9, 136.1, 139.1, 139.9, 146.0,
146.6 ppm.
The spectral data are according to the literature.8b
General Procedure for the Cyclotrimerization with Catalytic
Amounts of CoCl(PPh3)3 (1). In a flame-dried Schlenk tube,
CoCl(PPh3)3 (1, 10 mol %) was suspended in THF (1 mL). The
triyne (0.125−0.25 mmol) was added as solid or as a solution in THF,
HRMS-EI (C28H30O2): calcd: 398.2240; found: 398.2239.
Mp. 159−160 °C.
Dimethyl-2,2′-(1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]difuran-4,5-
diyl)dibenzoate (45). (0.33 mmol, 5 mol % CoCl(PPh3)3, THF, 25
J
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
°C, 36 h, c-hex/EE (4:1); 72 mg (51%), 2:1 (d/l:meso ratio), colorless
solid).
1H NMR (CDCl3, 400 MHz): δ = 1.85 (s, 3H), 3.87 (s, 3H), 4.54
(d, J = 12.3 Hz, 1H), 4.71 (d, J = 12.3 Hz, 1H), 5.12 (s, 2H), 5.18 (dd,
J = 7.2, 2.4 Hz, 4H), 7.19−7.23 (m, 1H), 7.31−7.36 (m, 2H), 7.38 (d,
J = 9.1 Hz, 1H), 7.82−7.87 (m, 1H), 7.92 (d, J = 9.1 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 15.9, 56.4, 72.9, 73.2, 73.5, 73.6,
113.2, 120.5, 123.7, 124.2, 126.9, 128.2, 128.8, 129.0, 129.3, 129.7,
129.9, 130.9, 132.5, 138.4, 139.7, 153.7 ppm.
1H NMR (CDCl3, 300 MHz): δ = 3.75 (d, J = 2.6 Hz, 6H), 4.76 (s,
4H), 5.14 (s, 4H), 7.12−7.16 (m, 2H), 7.17−7.23 (m, 2H), 7.25−7.32
(m, 2H), 7.76 (ddd, J = 7.7, 2.9, 1.6 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 52.1, 73.0, 73.5, 127.4, 129.5,
129.9, 130.6, 130.9, 131.7, 132.7, 137.7, 139.9, 167.1 ppm.
1H NMR (CDCl3, 300 MHz): δ = 3.71 (d, J = 2.2 Hz, 6H), 4.75
(dd, J = 11.3, 1.3 Hz, 2H), 4.91 (dd, J = 11.3, 2.2 Hz, 2H), 5.17 (q, J =
11.4 Hz, 4H), 7.02 (dt, J = 7.7, 1.8 Hz, 2H), 7.19 (tdd, J = 7.5, 2.3, 1.3
Hz, 2H), 7.26−7.32 (m, 2H), 7.73 (ddd, J = 7.9, 2.2, 1.2 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 51.9, 72.9, 73.8, 127.4, 129.9,
130.2, 130.3, 131.0, 131.8, 132.8, 138.5, 138.9, 166.6 ppm.
HRMS-ESI (TOF) (C26H22O6): calcd: 431.1489 [M + H]+,
453.1309 [M + Na]+; found: 431.1495 [M + H]+, 453.1317 [M +
Na]+.
HRMS-ESI (TOF) (C22H20O3): calcd: 333.1485 [M + H]+,
355.1305 [M + Na]+; found: 333.1472 [M + H]+, 355.1304 [M +
Na]+.
EA: calcd: C 79.50, H 6.06; found: C 79.40, H 6.12.
Mp. 214−215 °C.
4-(Naphthalen-1-yl)-5-phenyl-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-
c′]difuran (50). (0.14 mmol, 10 mol % CoCl(PPh3)3, THF, 25 °C, 17
h, c-hex/EE (4:1); 50 mg (96%), colorless solid).
1H NMR (CDCl3, 300 MHz): δ = 4.62−4.76 (m, 2H), 4.97 (d, J =
12.6 Hz, 1H), 5.11 (d, J = 13.6 Hz, 1H), 5.20 (dt, J = 7.3, 1.7 Hz, 4H),
6.93−7.04 (m, 5H), 7.10 (dd, J = 7.1, 1.3 Hz, 1H), 7.27−7.32 (m,
1H), 7.35−7.47 (m, 2H), 7.54−7.59 (m, 1H), 7.70 (dt, J = 8.3, 1.1 Hz,
1H), 7.80 (dd, J = 7.4, 2.2 Hz, 1H) ppm.
Mp. 162.5−163.5 °C.
4,5-Di(quinolin-4-yl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]difuran
(46). (0.125 mmol, 10 mol % CoCl(PPh3)3, THF, 25 °C, 18 h, n-hex/
THF (1:1, 0.5% NEt3); 48 mg (94%), 1.9:1 (d/l:meso ratio), yellow
solid).
13C NMR (CDCl3, 75 MHz): δ = 72.8, 72.9, 73.6, 73.8, 124.9 (2×),
125.1, 125.5, 125.8, 126.3, 126.9, 127.6, 127.7, 127.8, 128.4, 128.6,
131.0, 131.6, 132.3, 135.4, 136.0, 138.8, 139.8, 139.9 ppm.
HRMS-EI (C26H20O2): calcd: 364.1458; found: 364.1452.
Mp. 163.5−164.5 °C.
1H NMR (CDCl3, 300 MHz): δ = 4.69 (dt, J = 3.5, 1.9 Hz, 4H),
5.17−5.29 (m, 4H), 6.76 (d, J = 4.4 Hz, 2H), 7.57 (ddd, J = 8.3, 6.7,
1.2 Hz, 2H), 7.66−7.76 (m, 4H), 8.06 (dt, J = 8.3, 1.2 Hz, 2H), 8.45
(d, J = 4.4 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 72.8, 73.3, 120.6, 120.9, 125.1,
126.5, 127.3, 129.7, 130.2, 132.8, 139.6, 144.1, 148.1, 149.7 ppm.
1H NMR (CDCl3, 300 MHz): δ = 4.66−4.84 (m, 4H), 5.17−5.30
(m, 4H), 7.16 (d, J = 4.4 Hz, 2H), 7.24 (ddd, J = 8.3, 6.9, 1.3 Hz, 2H),
7.51 (ddd, J = 8.4, 6.9, 1.3 Hz, 2H), 7.55−7.60 (m, 2H), 7.90 (dt, J =
8.4, 0.9 Hz, 2H), 8.72 (d, J = 4.4 Hz, 2H) ppm.
4-(2-Methoxynaphthalen-1-yl)-5-phenyl-1,3,6,8-tetrahydro-
benzo[1,2-c:3,4-c′]difuran (51). (0.13 mmol, 10 mol % CoCl(PPh3)3,
THF, 25 °C, 17 h, c-hex/EE (4:1); 44 mg (85%), colorless solid).
1H NMR (CDCl3, 300 MHz): δ = 3.68 (s, 3H), 4.67 (qt, J = 12.3,
2.1 Hz, 2H), 5.05 (q, J = 12.6 Hz, 2H), 5.20 (d, J = 2.1 Hz, 4H), 6.94−
7.02 (m, 5H), 7.11 (d, J = 9.1 Hz, 1H), 7.29 (dt, J = 7.8, 1.9 Hz, 1H),
7.33−7.39 (m, 2H), 7.70−7.76 (m, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 72.8, 73.3, 122.4, 125.2, 125.7,
126.6, 129.5, 129.9, 130.2, 132.9, 139.6, 143.8, 148.2, 149.3 ppm.
HRMS-EI (C28H20N2O2): calcd: 416.1519; found: 416.1511.
Mp. 126−127 °C.
13C NMR (CDCl3, 75 MHz): δ = 56.1, 72.9, 73.0, 73.7, 73.8, 112.6,
120.6, 123.5, 124.4, 124.9, 126.7, 126.8, 127.5, 128.1, 128.2, 128.3,
129.6, 131.2, 131.8, 132.7, 136.0, 138.5, 138.7, 140.2, 153.6 ppm.
HRMS-EI (C27H22O3): calcd: 394.1564; found: 394.1566.
Mp. 170−171 °C.
4,5-Di(isoquinolin-4-yl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-c′]-
difuran (47). (0.125 mmol, 10 mol % CoCl(PPh3)3, THF, 25 °C, 18 h,
n-hex/THF (1:1, 0.5% NEt3); 48 mg (92%), 1.1:1 (d/l:meso ratio),
yellow solid).
4-(2-Methoxynaphthalen-1-yl)-5-(naphthalen-1-yl)-1,3,6,8-tetra-
hydrobenzo[1,2-c:3,4-c′]difuran (52). (0.1 mmol, 10 mol % CoCl-
(PPh3)3, THF, 25 °C, 24 h, c-hex/EE (6:1); 40 mg (90%), colorless
solid).
1H NMR (CDCl3, 300 MHz): δ = 4.65−4.81 (m, 4H), 5.17−5.33
(m, 4H), 7.53−7.67 (m, 2H), 7.64−7.76 (m, 4H), 7.90 (dt, J = 8.2, 1.0
Hz, 2H), 7.93 (s, 2H), 8.95 (s, 2H) ppm.
Two diastereomers were isolated, which account together for the
13C NMR (CDCl3, 75 MHz): δ = 72.9, 73.4, 124.2, 127.5, 128.0,
128.2, 129.0, 130.1, 131.2, 132.5, 134.1, 140.5, 142.0, 152.4 ppm.
1H NMR (CDCl3, 300 MHz): δ = 4.67−4.88 (m, 4H), 5.19−5.32
(m, 4H), 7.33−7.44 (m, 4H), 7.50−7.59 (m, 2H), 7.69−7.82 (m, 2H),
8.34 (s, 2H), 8.96 (s, 2H) ppm.
total yield.
1
First Fraction. H NMR (CDCl3, 400 MHz): δ = 3.09 (s, 3H),
4.63−4.85 (m, 4H), 5.18−5.31 (m, 4H), 6.78−6.86 (m, 2H), 6.92 (dd,
J = 8.2, 7.1 Hz, 1H), 7.31 (ddd, J = 8.1, 6.8, 1.3 Hz, 1H), 7.37−7.47
(m, 3H), 7.52 (dd, J = 8.4, 1.0 Hz, 2H), 7.59 (d, J = 8.9 Hz, 1H),
7.68−7.75 (m, 2H), 7.77−7.81 (m, 1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 72.9, 73.5, 124.3, 127.1, 127.9,
128.6, 130.1, 130.2, 132.6, 133.4, 140.6, 143.9 144.0, 152.2 ppm.
HRMS-EI (C28H20N2O2): calcd: 416.1519; found: 416.1519.
EA: calcd: C 80.75, H 4.84, N 6.73; found: C 80.80, H 5.03, N 6.08.
Mp. decomp. > 190.5 °C.
13C NMR (CDCl3, 100 MHz): δ = 55.1, 72.9, 73.1, 73.8, 73.9,
112.2, 120.3, 123.3, 124.6, 124.7, 125.4, 125.5, 126.1, 126.5, 126.8,
127.4, 128.1, 128.2, 128.4, 129.3, 131.0, 131.2, 131.4, 132.2, 133.1,
133.3, 134.3, 136.0, 139.7, 140.5, 153.3 ppm.
1
Second Fraction. H NMR (CDCl3, 400 MHz): δ = 3.89 (s, 3H),
4-Methyl-5-(naphthalen-1-yl)-1,3,6,8-tetrahydrobenzo[1,2-c:3,4-
c′]difuran (48). (0.15 mmol, 10 mol % CoCl(PPh3)3, THF, 25 °C, 36
h, c-hex/EE (4:1); 44 mg (96%), colorless solid).
4.61−4.83 (m, 4H), 5.17−5.31 (m, 4H), 7.07 (dt, J = 6.4, 3.4 Hz, 2H),
7.12 (d, J = 9.1 Hz, 1H), 7.16−7.23 (m, 2H), 7.24−7.28 (m, 1H), 7.31
(dd, J = 7.1, 1.3 Hz, 1H), 7.35−7.41 (m, 1H), 7.47−7.55 (m, 2H),
7.57−7.62 (m, 2H), 7.66 (dt, J = 8.2, 0.9 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 55.9, 73.0, 73.1, 73.8, 73.8,
112.1, 120.5, 123.3, 124.6, 124.7, 125.4, 125.5, 125.7, 126.1, 126.4,
127.6 (2×), 128.0, 128.5, 129.5, 129.6, 130.7, 131.4 (2×), 132.2, 133.2,
134.2, 135.8, 139.9, 140.5, 153.6 ppm.
HRMS-EI (C31H24O3): calcd: 444.1720; found: 444.1719.
Mp. 234.5−235.5 °C.
Tetraethyl-4,5-di(naphthalen-1-yl)-1,3,6,8-tetrahydro-as-inda-
cene-2,2,7,7-tetracarboxylate (53a). (0.125 mmol, 10 mol %
CoCl(PPh3)3, toluene, 80 °C, 18 h, c-hex/EE (4:1); 70 mg (81%),
2.6:1 (d/l:meso ratio, GC area), colorless solid).
1H NMR (CDCl3, 300 MHz): δ = 1.87 (s, 3H), 4.55 (dd, J = 12.5,
2.2 Hz, 1H), 4.78 (dd, J = 12.5, 2.2 Hz, 1H), 5.11 (s, 2H), 5.18 (s,
4H), 7.29 (dd, J = 7.0, 1.2 Hz, 1H), 7.37−7.43 (m, 2H), 7.46−7.57
(m, 2H), 7.84−7.97 (m, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 16.1, 72.8, 73.1, 73.4, 73.5, 125.3,
125.6, 126.0, 126.3, 126.4, 127.9, 128.5, 129.3, 129.4, 130.9, 131.3,
132.9, 133.7, 136.3, 138.5, 139.3 ppm.
HRMS-ESI (TOF) (C21H18O2): calcd: 303.1380 [M + H]+,
325.1199 [M + Na]+; found: 303.1374 [M + H]+, 325.1202 [M +
Na]+.
Mp. 153.5−154.5 °C.
4-(2-Methoxynaphthalen-1-yl)-5-methyl-1,3,6,8-tetrahydro-
benzo[1,2-c:3,4-c′]difuran (49). (0.25 mmol, 5 mol % CoBr2,10 mol
% Zn, ZnI2, THF, 65 °C, 18 h, c-hex/EE (4:1); 75 mg (90%), colorless
solid).
Meso and d/l forms are not separable by column chromatography.
1H NMR (CDCl3, 300 MHz): δ = 1.15−1.24 (m, 24H), 3.03−3.20
(m, 8H), 3.58−3.82 (m, 8H), 4.06−4.26 (m, 16H), 6.75−6.97 (m,
K
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
6H), 7.07−7.25 (m, 4H), 7.40−7.47 (m, 6H), 7.50 (dt, J = 8.2, 1.0 Hz,
4H), 7.52−7.58 (m, 2H), 7.64−7.77 (m, 6H) ppm.
(m, 7H), 4.04−4.27 (m, 8H), 6.95 (s, 4H), 7.08 (d, J = 9.1 Hz, 1H),
7.21−7.34 (m, 4H), 7.68 (d, J = 8.6 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.0, 22.7, 29.4, 29.7 (2×), 31.9,
39.3, 39.4, 40.2, 40.3, 60.1, 61.7, 124.6, 125.0, 125.2, 125.3, 125.4,
125.8, 126.0, 126.1, 126.2, 127.0, 127.8, 128.1, 131.2, 131.9, 133.1,
133.2, 134.6, 134.7, 135.3, 135.4, 136.6, 137.1, 139.6, 139.7, 171.6,
171.7, 171.8 ppm. Because of signal overlaps, not all expected carbon
atoms could be assigned.
13C NMR (CDCl3, 75 MHz): δ = 13.9, 14.0, 14.1, 39.4, 39.5, 40.1,
40.6, 56.0, 60.1, 60.2, 61.6, 61.8, 62.0, 112.8, 121.9, 123.2, 125.0, 126.2,
126.3, 127.1, 127.8, 127.9, 128.6, 128.7, 129.0, 130.2, 131.7, 133.1,
134.5, 134.9, 138.0, 138.2, 139.7, 139.8, 153.6, 171.6, 171.8 (2×),
171.9 ppm.
HRMS-EI (C41H42O9): calcd: 678.2823; found: 678.2812.
Tetraethyl-5-(2-methoxynaphthalen-1-yl)-4-methyl-1,6,7,9-tetra-
hydro-2H-cyclopenta[a]naphthalene-2,2,8,8(3H)-tetracarboxylate
(53g). (0.11 mmol, 10 mol % CoCl(PPh3)3, toluene, 80 °C, 20 h, c-
hex/EE (4:1); 14 mg (20%), colorless solid).
HRMS-EI (C44H42O8): calcd: 698.2874; found: 698.2856.
Mp. 149.5−150.5 °C.
Tetraethyl-4,5-bis(2-methoxynaphthalen-1-yl)-1,3,6,8-tetra-
hydro-as-indacene-2,2,7,7-tetracarboxylate (53b). (0.1 mmol, 10
mol % CoCl(PPh3)3, toluene, 80 °C, 20 h, c-hex/EE (4:1); 73 mg
(96%), (no meso form detectable), colorless solid).
1H NMR (CDCl3, 400 MHz): δ = 1.15 (t, J = 7.1 Hz, 3H), 1.22 (t, J
= 7.1 Hz, 3H), 1.30 (td, J = 7.1, 2.1 Hz, 6H), 1.73 (s, 3H), 1.95−2.06
(m, 1H), 2.05−2.14 (m, 2H), 2.20−2.33 (m, 1H), 3.12 (d, J = 16.4
Hz, 1H), 3.25 (d, J = 16.4 Hz, 1H), 3.62 (s, 2H), 3.68 (s, 2H), 3.82 (s,
3H), 4.07−4.16 (m, 2H), 4.12−4.22 (m, 2H), 4.26 (qd, J = 7.1, 4.6
Hz, 4H), 7.05 (dt, J = 8.3, 0.7 Hz, 1H), 7.25 (ddd, J = 8.3, 6.8, 1.6 Hz,
1H), 7.30 (ddd, J = 8.1, 6.7, 1.4 Hz, 1H), 7.36 (d, J = 9.1 Hz, 1H), 7.81
(dd, J = 8.3, 1.2 Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 14.0, 14.1, 16.4, 24.2, 28.1, 32.6,
39.8, 40.2, 53.4, 56.3, 59.5, 61.3 (2×), 61.8 (2×), 113.4, 122.8, 123.5,
124.5, 126.5, 126.9, 127.9, 128.9, 129.1, 130.5, 132.7, 133.1, 134.0,
136.6, 137.4, 153.5, 171.4, 171.7, 172.1, 172.2 ppm. Because of signal
overlaps, not all expected carbon atoms could be assigned.
HRMS-EI (C37H42O9): calcd: 630.2823; found: 630.2810.
Mp. 56−57 °C
1H NMR (CDCl3, 300 MHz): δ = 1.19 (dt, J = 12.4, 7.1 Hz, 12H),
3.16 (d, J = 16.2 Hz, 2H), 3.39 (d, J = 16.2 Hz, 2H), 3.61−3.82 (m,
10H), 4.09−4.23 (m, 8H), 6.93 (ddd, J = 8.3, 6.7, 1.5 Hz, 2H), 6.97−
7.04 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.41−7.45 (m, 2H), 7.48 (d, J
= 9.0 Hz, 2H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.0, 14.1, 39.6, 40.5, 55.9, 59.9,
61.5, 61.6, 112.0, 121.6, 122.8, 125.2, 125.8, 127.2, 128.2, 128.6, 132.0,
132.2, 134.9, 140.5, 153.8, 171.7, 172.2 ppm. Because of signal
overlaps, not all expected carbon atoms could be assigned.
HRMS-EI (C46H46O10): calcd: 758.3086; found: 758.3068.
EA: calcd: C 72.81, H 6.11; found: C 72.76, H 6.17.
Mp. 196−197 °C.
Tetraethyl-4-methyl-5-(naphthalen-1-yl)-1,3,6,8-tetrahydro-as-
indacene-2,2,7,7-tetracarboxylate (53c). (0.25 mmol, 10 mol %
CoCl(PPh3)3, THF, 65 °C, 21 h, c-hex/EE (10:1); 140 mg (95%),
yellow oil).
Tetraethyl-5-(2-methoxynaphthalen-1-yl)-4-phenyl-1,6,7,9-tetra-
hydro-2H-cyclopenta[a]naphthalene-2,2,8,8(3H)-tetracarboxylate
(53h). (0.1 mmol, 10 mol % CoCl(PPh3)3, toluene, 80 °C, 22 h, 95
°C, 2 h, c-hex/EE (4:1); 63 mg (92%), colorless syrup).
1H NMR (CDCl3, 300 MHz): δ = 1.18 (t, J = 7.1 Hz, 3H), 1.20−
1.32 (m, 9H), 2.06−2.33 (m, 4H), 3.15 (d, J = 16.7 Hz, 1H), 3.35−
3.54 (m, 3H), 3.65 (s, 3H), 3.70−3.82 (m, 2H), 4.09−4.29 (m, 8H),
6.53−6.97 (m, 3H), 7.06 (d, J = 9.1, 2H), 7.14−7.33 (m, 4H), 7.67
(ddt, J = 8.9, 2.6, 1.1 Hz, 2H) ppm.
1H NMR (CDCl3, 400 MHz): δ = 1.12 (t, J = 7.1 Hz, 3H), 1.19 (t, J
= 7.1 Hz, 3H), 1.30 (td, J = 7.1, 4.5 Hz, 6H), 1.83 (s, 3H), 2.90 (d, J =
16.7 Hz, 1H), 3.18 (d, J = 16.7 Hz, 1H), 3.48−3.62 (m, 4H), 3.64 (s,
2H), 4.02−4.17 (m, 4H), 4.26 (p, J = 7.2 Hz, 4H), 7.22−7.29 (m,
1H), 7.34−7.39 (m, 2H), 7.46 (ddd, J = 8.2, 5.3, 2.7 Hz, 1H), 7.52
(dd, J = 8.2, 7.0 Hz, 1H), 7.85 (d, J = 7.2 Hz, 1H), 7.89 (d, J = 8.3 Hz,
1H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.1, 24.4, 28.1, 32.8, 39.7, 40.5,
53.4, 55.8, 59.7, 61.4, 61.5, 61.7, 100.0, 112.6, 122.4, 123.2, 124.8,
126.1, 126.3, 127.0, 127.8, 128.5 (2×), 128.9, 129.1, 133.1, 133.5 (2×),
136.4, 136.9, 137.9, 139.9, 153.4, 171.2, 171.8, 171.9, 172.0 ppm.
Because of signal overlaps, not all expected carbon atoms could be
assigned.
HRMS-EI (C42H44O9): calcd: 692.2980; found: 692.2967.
3,3-Diisopropyl-4-(2-methoxynaphthalen-1-yl)-5-phenyl-1,3,6,8-
tetrahydro[1,2]oxasilolo[4,3-e]isobenzofuran (55). (0.125 mmol, 10
mol % CoCl(PPh3)3, THF, 25 °C, 17 h, PE/EE (6:1); 37 mg (60%),
yellow oil).
13C NMR (CDCl3, 100 MHz): δ = 13.9, 14.0, 14.1 (2×), 16.4, 39.1,
39.4, 39.9, 40.1, 59.9, 60.2, 61.5, 61.6, 61.8 (2×), 125.6, 125.7, 125.8,
126.0, 126.6, 127.4, 128.2, 131.2, 131.7, 132.4, 133.7, 134.4, 134.9,
137.7, 138.4, 139.0, 171.6, 171.7, 171.9, 188.9 ppm.
HRMS-ESI (TOF) (C35H38O8): calcd: 587.2639 [M + H]+,
609.2459 [M + Na]+; found: 587.2628 [M + H]+, 609.2450 [M +
Na]+.
Tetraethyl-4-(2-methoxynaphthalen-1-yl)-5-methyl-1,3,6,8-tetra-
hydro-as-indacene-2,2,7,7-tetracarboxylate (53d). (0.25 mmol, 10
mol % CoCl(PPh3)3, toluene, 60 °C, 18 h, 80 °C, 17 h, c-hex/EE
(4:1); 126 mg (82%), yellow oil).
1H NMR (CDCl3, 400 MHz): δ = 0.30 (d, J = 6.6 Hz, 3H), 0.32−
0.41 (m, 1H), 0.55 (d, J = 7.0 Hz, 3H), 0.62 (d, J = 7.0 Hz, 3H), 0.73−
0.85 (m, 1H), 0.86 (d, J = 6.5 Hz, 3H), 3.76 (s, 3H), 5.01 (ddt, J =
17.8, 12.9, 2.2 Hz, 2H), 5.12 (d, J = 2.0 Hz, 2H), 5.19 (s, 2H), 6.93−
6.97 (m, 3H), 7.00−7.04 (m, 2H), 7.22 (ddd, J = 8.0, 6.4, 1.8 Hz, 1H),
7.24−7.29 (m, 1H), 7.29−7.32 (m, 1H), 7.65 (dd, J = 7.5, 1.4 Hz,
1H), 7.69 (d, J = 9.1 Hz, 1H) ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.10 (td, J = 7.1, 1.2 Hz, 3H),
1.19 (td, J = 7.1, 1.2 Hz, 3H), 1.30 (tt, J = 7.1, 1.2 Hz, 6H), 1.82 (s,
3H), 2.89 (d, J = 16.7 Hz, 1H), 3.17 (d, J = 16.7 Hz, 1H), 3.50−3.60
(m, 2H), 3.63 (d, J = 13.6 Hz, 4H), 3.85 (d, J = 0.9 Hz, 3H), 3.99−
4.18 (m, 4H), 4.26 (dddq, J = 7.2, 4.5, 3.1, 1.6 Hz, 4H), 7.17 (dd, J =
6.8, 2.9 Hz, 1H), 7.25−7.33 (m, 2H) 7.37 (dd, J = 9.1, 1.3 Hz, 1H),
7.78−7.84 (m, 1H), 7.88 (d, J = 0.9 Hz, 1H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 12.9, 13.1, 15.8, 16.2, 16.5, 16.7,
55.1, 70.6, 72.9, 73.9, 111.6, 123.2, 124.5, 125.8, 125.9, 126.7, 127.3,
127.6, 128.0, 128.3, 129.2, 131.6, 133.8, 135.2, 135.7, 138.9, 139.2,
140.9, 143.3, 153.8 ppm. Because of signal overlaps, not all expected
carbon atoms could be assigned.
13C NMR (CDCl3, 75 MHz): δ = 13.9, 14.0, 14.1, 16.3, 39.2, 39.5,
40.0, 40.2, 56.5, 59.9, 60.2, 61.5, 61.7, 61.8, 113.6, 122.1, 123.5, 124.8,
126.5, 127.9, 129.1, 130.8, 131.7, 132.5, 132.9, 134.4, 138.4, 139.4,
153.8, 171.7, 171.9, 172.0, 172.2 ppm. Because of signal overlaps, not
all expected carbon atoms could be assigned.
29Si NMR (CDCl3, 79 MHz): δ = 32.2 ppm.
HRMS-ESI (TOF) (C36H40O9): calcd: 617.2745 [M + H]+,
639.2565 [M + Na]+; found: 617.2747 [M + H]+, 639.2569 [M +
Na]+.
HRMS-EI (C32H34O3Si): calcd: 494.2272, found: 494.2267.
4-Methyl-5-(naphthalen-1-yl)-1,3,6,7,8,9-hexahydronaphtho[1,2-
c]furan (57). (0.15 mmol, 10 mol % CoCl(PPh3)3, THF, 25 °C, 5 d, c-
hex/EE (4:1); 37 mg (78%), colorless solid).
Tetraethyl-4-(2-methoxynaphthalen-1-yl)-5-phenyl-1,3,6,8-tetra-
hydro-as-indacene-2,2,7,7-tetracarboxylate (53f). (0.1 mmol, 10
mol % CoCl(PPh3)3, toluene, 80 °C, 22 h, 95 °C, 2 h, c-hex/EE (4:1);
31 mg (46%), colorless oil).
1H NMR (CDCl3, 300 MHz): δ = 1.39−1.56 (m, 2H), 1.58−1.72
(m, 5H), 1.86 1. 98 (m, 1H), 2.16−2.29 (m, 1H), 2.54 (t, J = 6.4 Hz,
2H), 5.08 (s, 4H), 7.11−7.16 (m, 1H), 7.23−7.27 (m, 2H), 7.29−7.43
(m, 2H), 7.44 (dd, J = 8.2, 7.0 Hz, 1H), 7.80 (dt, J = 8.2, 1.0 Hz, 1H)
ppm.
1H NMR (CDCl3, 300 MHz): δ = 1.13 (t, J = 7.1 Hz, 3H), 1.19 (t, J
= 7.1 Hz, 3H), 1.25 (td, J = 7.1, 3.1 Hz, 6H), 2.97 (d, J = 16.9 Hz,
1H), 3.17 (d, J = 16.9 Hz, 1H), 3.45 (q, J = 16.9 Hz, 2H), 3.59−3.75
L
DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
13C NMR (CDCl3, 75 MHz): δ = 16.7, 22.6, 23.3, 27.1, 27.9, 73.9,
74.1, 125.4, 125.8, 125.9, 126.1, 126.9, 127.3, 128.1, 128.4, 132.0,
133.8, 135.2, 135.3, 136.8, 138.4, 138.9 ppm. Because of signal
overlaps, not all expected carbon atoms could be assigned.
HRMS-EI (C23H22O): calcd: 314.1671; found: 314.1665.
Mp. 78−79 °C.
(11) (a) Chang, H.-T.; Jeganmohan, M.; Cheng, C.-H. Chem.
Commun. 2005, 4955. (b) Chang, H.-T.; Jeganmohan, M.; Cheng, C.-
H. Org. Lett. 2007, 9, 505.
(12) The bromide analogue of 1, CoBr(PPh3)3, was initially studied
by the group of Kotora, who demonstrated the use in partial
intramolecular [2 + 2 + 2]-cycloadditions of ether-bridged diynes with
ferrocenyl- as well as alkynylpurines. This reaction was only suitable
for ether-bridged diynes, while the reaction with malonate-bridged
ASSOCIATED CONTENT
* Supporting Information
■
̌
́ ̌ ́ ̌
L.; Císarova, I.; Stepnicka, P.; Kotora, M.
diynes failed. (a) Dufkova,
Eur. J. Org. Chem. 2003, 2003, 2882. (b) Turek, P.; Kotora, M.;
Tislerova, I.; Hocek, M.; Votruba, I.; Císarova, I. J. Org. Chem. 2004,
69, 9224. (c) Turek, P.; Novak, P.; Pohl, R.; Hocek, M.; Kotora, M. J.
Org. Chem. 2006, 71, 8978. (d) Turek, P.; Kotora, M.; Hocek, M.;
Císarova, I. Tetrahedron Lett. 2003, 44, 785.
S
Schemes of all molecules synthesized, references for
literature-known products, further results for cyclizations
̌
́
̌
́
́
1
with chiral anions, and H and 13C NMR spectra for all
̌
́
new synthesized compounds. The Supporting Informa-
tion is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.5b01623 (PDF)
(13) (a) Grigg, R.; Scott, R.; Stevenson, P. J. Chem. Soc., Perkin Trans.
1 1988, 1357. (b) Grigg, R.; Scott, R.; Stevenson, P. J. Chem. Soc.,
Perkin Trans. 1 1988, 1365. (c) Grigg, R.; Scott, R.; Stevenson, P.
Tetrahedron Lett. 1982, 23, 2691.
AUTHOR INFORMATION
Corresponding Author
*E-mail: marko.hapke@catalysis.de.
(14) Baysdon, S. L.; Liebeskind, L. S. Organometallics 1982, 1, 771.
After our experience, the complex can be handled in air for short
periods of time.
■
(15) Tamura, S.; Doke, S.; Murakami, N. Tetrahedron 2010, 66, 8476.
Notes
(16) Angermund, K. P.; Betz, P.; Butenschon, H. Chem. Ber. 1993,
̈
The authors declare no competing financial interest.
126, 713.
(17) (a) Rhyoo, H.-Y.; Lee, B. Y.; Yu, H. K. B.; Chung, Y. K. J. Mol.
Catal. 1994, 92, 41. (b) Field et al. showed that cyclotrimerization of
symmetrical alkynes bearing electron-withdrawing groups (like esters)
with CoCl(PPh3)3 (1) proceeded in good yields after short reaction
times as well as unsymmetrical alkynes after 24 h, with a preference for
1,2,4-benzenes: Field, L. D.; Ward, A. J.; Turner, P. Aust. J. Chem.
1999, 52, 1085.
(18) Shibata, T.; Tsuchikama, K.; Otsuka, M. Tetrahedron: Asymmetry
2006, 17, 614.
(19) Sautier, B.; Lyons, S. E.; Webb, M. R.; Procter, D. J. Org. Lett.
ACKNOWLEDGMENTS
■
We thank Prof. Uwe Rosenthal for his enduring support and
helpful discussions. We thank the LIKAT and the Leibniz-
Gemeinschaft for financial support. The excellent technical
support from the analytical department is gratefully acknowl-
edged.
DEDICATION
■
2012, 14, 146.
This work is dedicated to Prof. Dr. Rudiger Beckhaus on the
occasion of his 60th birthday.
̈
(20) Here, the utilization of the cross-coupling reaction as the last
step in the construction of the malonate-bridged triynes is possible
because these triynes are easily separated from residual palladium
species by column chromatography.
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DOI: 10.1021/acs.joc.5b01623
J. Org. Chem. XXXX, XXX, XXX−XXX