Cyclophanes. Part LII: Ethynyl[2.2]paracyclophanes - New building blocks for molecular scaffolding

Article abstract of DOI:10.1055/s-2004-834872

The synthesis of seven ethynyl[2.2]paracyclophanes is described. The five diethynyl derivatives 4,5-diethynyl[2.2]paracyclophane (12), pseudo-gem-(13), pseudo-ortho-(14), pseudo-meta-(15), and pseudo-para-diethynyl[2.2] paracyclophane (16), the tetraethynyl compound 4,7,13,16-tetraethynyl[2.2] paracyclophane (17), and for comparison the mono-ethynylated hydrocarbon 4-ethynyl[2.2]paracyclophane (11) have been prepared. The structures of these new building blocks for carbon rich systems were determined by the usual analytical and spectroscopic methods.

Full text of DOI:10.1055/s-2004-834872

SPECIAL TOPIC
2751
Cyclophanes. Part LII:1 Ethynyl[2.2]paracyclophanes – New Building Blocks
for Molecular Scaffolding
E
thynyl[2.2]par
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acyclo
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phane
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– Ne
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i
Build
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Scaffolding ondarenko, Ina Dix, Heino Hinrichs, Henning Hopf*
Institute of Organic Chemistry, Technical University Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
Fax +49(531)3915388; E-mail: H.Hopf@tu-bs.de
Received 28 March 2004
Dedicated to Karsten Krohn on the occasion of his 60th birthday
Abstract: The synthesis of seven ethynyl[2.2]paracyclophanes is
described. The five diethynyl derivatives 4,5-diethynyl[2.2]paracy-
clophane (12), pseudo-gem- (13), pseudo-ortho- (14), pseudo-meta-
(15), and pseudo-para-diethynyl[2.2]paracyclophane (16), the tet-
raethynyl compound 4,7,13,16-tetraethynyl[2.2]paracyclophane
(17), and for comparison the mono-ethynylated hydrocarbon 4-
ethynyl[2.2]paracyclophane (11) have been prepared. The struc-
tures of these new building blocks for carbon rich systems were de-
termined by the usual analytical and spectroscopic methods.
Key words: ethynyl[2.2]paracyclophanes, oligoacetylenes, molec-
ular scaffolding
Di- and oligoacetylenes with terminal triple bonds are
valuable building blocks for extended carbon-rich sys-
tems,2 since their ethynyl functions can easily be connect-
ed by various coupling reactions. These monomers may
be categorized into three distinct groups: linear and rela-
tively flexible systems such as 1,5-hexadiyne (1), the most
important building block in Sondheimer’s annulene
chemistry;3 flat and rigid systems such as Diederich’s tet-
Figure 1
raethynylethene (2, TEE)4 or Vollhardt’s hexaethynylben-
zene (3),5 and all the ethynylbenzenes with a smaller
all, the synthesis of the corresponding octamethyl-
number of triple bonds, all the the way ‘down’ to 1,2-di-
ethynylbenzene (4);6 and three-dimensional molecules,
with Feldman’s tetraethynylmethane (5)7 serving as the
prototype. As far as the latter hydrocarbons are concerned,
in principle many other hydrocarbon or carbon cores
could be used. For example, the saturated carbon atom in
5 could be replaced by a cubane nucleus as in octaethynyl-
cubane (6),8 or by an adamantane core as illustrated by the
known9 tetraethynyladamantane (7) (Figure 1).
[2.2]paracyclophane was described by us several years
ago.10 Compared to many other core units, the [2.2]para-
cyclophane unit offers many advantages because of its hy-
brid chemical character: since the molecule consists of
aromatic and aliphatic parts, both types of chemistries are
applicable for synthetic transformations, the typical reac-
tions of aromatic chemistry for the rings, and those of ali-
phatic chemistry for the bridges.
In this paper we describe the preparation of the five di-
ethynyl[2.2]paracyclophanes 12–16 as well as the
‘crossed’ tetraethynyl derivative 17. For comparison, we
also needed the monosubstituted derivative 11 (Figure 2).
In our opinion, the [2.2]paracyclophane unit represents a
particularly valuable core system. Not only are many of
the lower ethynylogs chiral – see for example the diethy-
nyl derivatives 8 and 9 or 14 – but because of the 16 dif-
ferent positions which could carry a triple bond, an
extremely broad spectrum of structural variations should
be possible. While it seems unlikely that the fully ethyn-
ylated [2.2]paracyclophane will become available in
amounts allowing to study at least some reactions, the
synthesis of a hydrocarbon such as 10 in which the two ar-
omatic rings are fully ethynylated appears feasible. After
Beginning with the monosubstituted derivative 4-ethy-
nyl[2.2]paracyclophane (11), this hydrocarbon is easily
prepared in near quantitative yield (95%) using Best-
mann’s acetylene synthesis11 by reacting the mono formyl
derivative 18 with dimethyl 1-diazo-2-oxopropylphos-
phonate (19, Scheme 1).
SYNTHESIS 2004, No. 16, pp 2751–2759
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Advanced online publication: 07.10.2004
DOI: 10.1055/s-2004-834872; Art ID: C04704SS
© Georg Thieme Verlag Stuttgart · New York

2752
L. Bondarenko et al.
SPECIAL TOPIC
Figure 2
fluoromethylsulfonyl)aniline (21) in Et3N furnished the
triflate 22 which, by Sonogashira coupling with trimethyl-
silylacetylene, was converted to the acetylenic aldehyde
23, the yields being acceptable for both steps. Reaction of
23 with 19 in the presence of Cs2CO3 provided the unpro-
tected diacetylene 12.
To arrive at the four diethynyl cyclophanes carrying one
acetylenic group per benzene ring, the hydrocarbons pseu-
do-gem- (13), pseudo-ortho- (14), pseudo-meta- (15), and
pseudo-para-di-ethynyl[2.2]paracyclophane (16), it is in
principle only necessary to treat the corresponding bis
formyl derivatives with the Bestmann reagent 19. These
precursors can all be prepared by the reaction of propiolic
aldehyde with 1,2,4,5-hexatetraene (biallenyl) as dis-
cussed below and shown by us many years ago.13 Howev-
er, this cycloaddition leads to a mixture of the four
dialdehydes, and although separable by recrystallization
and column chromatography (see below), this purification
is time consuming. We, hence, needed directed syntheses
of these isomeric dialdehydes. For the pseudo-geminal di-
aldehyde 24 this was accomplished by exploiting the
pseudo-gem directing effect observed in monosubstituted
[2.2]paracyclophanes carrying a carbonyl group-contain-
ing substituent. Since we have described this methodolo-
gy in detail recently14 this transformation is not repeated
here.
Scheme 1
Traditionally, this valuable transformation, which in our
hands was superior to the Corey–Fuchs reaction in this
case, is carried out in the presence of K2CO3 as a base. We
have found that its replacement by Cs2CO3 (in MeOH) not
only results in a drastic yield increase but also provides a
much purer product. With K2CO3 the above transforma-
tion yields 11 in 66% yield only, accompanied by 22% of
the starting aldehyde 18. The monoacetylene was charac-
terized by the usual spectroscopic and analytical data re-
corded in the experimental section.
Reaction of 4,15-diformyl[2.2]paracyclophane (24)14
with 19 under optimized conditions (see above) provided
a product mixture consisting of the desired diacetylene 13
(31%), the mono ethynylated derivative 25 as the main
product (61%) and the ester alcohol 26 (8%, Scheme 2).
That 25 is a precursor of 13 was shown by treating it a sec-
ond time with 19 to provide the originally intended hydro-
carbon, although the conversion was again incomplete.
Derivative 26 is the result of a long known15 intramolecu-
lar Canizzaro reaction of 24. Its contribution to the prod-
uct mixture can be reduced by performing the
For the preparation of the ortho-disubstituted derivative
4,5-diethynyl[2.2]paracyclophane (12), 5-formyl-4-hy-
droxy[2.2]paracyclophane (20, FHPC)12 was used as the
starting material (Scheme 1). Its reaction with N,N-bis(tri-
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York

SPECIAL TOPIC
Ethynyl[2.2]paracyclophanes – New Building Blocks for Molecular Scaffolding
2753
Scheme 2
ethynylation in MeOH–MeCN (1:2) and using very anhy- aldehyde 31 was obtained in good yield and converted to
drous carbonate, i.e. a base containing only traces of hy- the diethynyl derivative 14 by treatment with 19 as de-
droxide.
scribed above. Again, the employed base turned out to be
critical. With K2CO3, besides 14 (52%) its precursor
mono acetylene derivative 32 was isolated in 48% yield.
With Cs2CO3, however, the hydrocarbon 14 was obtained
quantitatively. Finally, with the same base and MeOH–
CH2Cl2 as the solvent (ratio: 4:1) the reaction mixture
contained 64% of 32 and 28% of 14 after 2 days at 0 °C.
Thus either of the two intermediates can be made the main
product of the ethynylation procedure. Analogously, the
pseudo-meta dibromide 28 was first converted to the cor-
responding dialdehyde 33 (sec-BuLi in THF followed by
N-formyl-piperidine, 62%) and its subsequent reaction
with 19 (CH2Cl2–MeOH, Cs2CO3, r.t.) led to the pseudo-
meta diethynyl derivative 15 (88%, Scheme 3).
The pseudo-ortho and pseudo-meta dialdehydes were ob-
tained as follows. Bromination of the parent hydrocarbon
[2.2]paracyclophane (27) yielded a mixture of the pseudo-
meta and pseudo-para dibromides 28 and 29, respective-
ly, in roughly 1:1 ratio. These isomers could be separated
by recrystallization as described in the experimental sec-
tion. When 29 was heated to 216 °C (reflux) in triglyme it
equilibrated with the pseudo-ortho dibromide 30, the
product ratio being close to 1. After separation of 29 and
30, the thermal equilibration process was repeated and af-
ter a third or fourth cycle practically all of 29 had been
isomerized to 30. Its metalation with n-BuLi in Et2O was
then carried out and the formed dilithio derivative
quenched with N-formyl piperidine. The pseudo-ortho di-
Scheme 3
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York

2754
L. Bondarenko et al.
SPECIAL TOPIC
Except for several of the IR spectra, which were determined on a
Bruker Tensor 27 instrument, the instrumentation used for structure
determination has been described previously.18,19 Bestmann’s re-
agent [dimethyl 1-diazo-2-oxopropylphosphonate (19)] was pre-
pared according to literature procedure11,20 from the commercially
available dimethyl 2-oxo-propylphosphonate. The sample of pseu-
do-para-diformyl[2.2]paracyclophane (36) was available from a
previous addition experiment of propiolic aldehyde (35) to 1,2,4,5-
hexatetraene (34).13,21
To prepare the pseudo-para diethynyl derivative 16 a
sample of the corresponding dialdehyde 36 was used
which was still available from an earlier addition experi-
ment of propiolic aldehyde (35) to 1,2,4,5-hexatetraene
(34).13,14 As already mentioned (see above), 36 had to be
isolated from the product mixture by extensive column
chromatography/recrystallization to remove the other
three conceivable isomeric dialdehydes. The hydrocarbon
16 was then obtained in 86% yield by first carrying out a
Wittig reaction of 36 with bromomethyl triphenylphos-
phonium bromide using t-BuOK as the base in THF fol-
lowed by in situ dehydrobromination of the thus produced
vinylbromide intermediate.
4-Ethynyl[2.2]paracyclophane (11)
In anhyd MeOH (15 mL) were suspended 4-formyl[2.2]paracyclo-
phane (18, 118 mg, 0.5 mmol) and Cs2CO3 (ca. 1 g) and under vig-
orous stirring dimethyl 1-diazo-2-oxopropylphosphonate (19, 210
mg, 1.1 mmol) was added at r.t. After 12 h, additional Cs2CO3 (0.5
g) and 19 (100 mg, 0.45 mmol) were added. The reaction mixture
was stirred at r.t. until the starting material had been consumed [ca.
24 h, TLC monitoring on silica gel with pentane–CH2Cl2 (1:1)]. The
reaction mixture can be heated up to 40 °C if necessary. The color
changed from yellow to red-violet, and at the end CH2Cl2 and water
were added. The layers were separated, the water phase was washed
with CH2Cl2, and the combined organic solutions were washed with
brine, dried over MgSO4, and evaporated to dryness. The crude
product was filtered through silica gel with pentane–CH2Cl2 (1:1) to
afford 4-ethynyl[2.2]paracyclophane (11) as a colorless solid (110
mg, 95%; mp 124 °C).
For the synthesis of the ‘crossed’ tetraethynyl[2.2]paracy-
clophane (17), [2.2]paracyclophane (27) was brominated
under harsher conditions than above to yield the tetrabro-
mide 37 in 46% yield (Scheme 4).16 Sonogashira coupling
with trimethylsilylacetylene under similar conditions as
described for the conversion of 22 to 23 then provided the
protected tetraethynyl derivative 38c in acceptable yield
(considering that the coupling step had to be performed
four times). Besides this fully ethynylated derivative, the
partially converted dibromide 38a and the monobromide
38b were isolated as side products. The final deprotection
of 38c by treatment with K2CO3 in MeOH–CH2Cl2 to the
hydrocarbon 17 in quantitative yield, posed no problems.
IR (KBr): 3301 (s), 3011 (w), 2930 (s), 2099 (w), 1206 (m), 651
(vs), 585 (s) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.81–2.88 (m, 1 H, 2-H), 2.92–
2.98 (m, 1 H, 9-H), 2.99–3.11 (m, 4 H, 1-H, 9-H, 10-H), 3.18–3.25
(m, 1 H, 1-H), 3.26 (s, 1 H, 18-H) 3.51–3.61 (m, 1 H, 2-H), 6.43–
6.45 (m, 2 H, 8-H, 16-H), 6.48–6.50 (m, 2 H, 12-H, 13-H), 6.50–
We have incorporated the pseudo-ortho derivative 13 into
various annulenic systems already17 and will present
many more applications of building with the compounds
described herein soon.
6.52 (dd, 4J5,7 = 1.79 Hz, 3J7,8 = 7.81 Hz, 1 H, 7-H), 6.55 (d, 4J5,7
=
3
1.81 Hz, 1 H, 5-H), 6.78–7.00 (dd, J15,16 = 7.82 Hz, 4J15,13 = 1.73
Hz, 1 H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 34.09 (t, C-1), 34.20 (t, C-2),
35.06 (t, C-9), 35.40 (t, C-10), 80.25 (d, C-18), 83.90 (s, C-17),
123.71 (d, C-4), 129.89 (d, C-15), 132.49 (d, C-16), 132.69 (d, C-
12), 133.25 (d, C-7), 133.32 (d, C-13), 133.83 (d, C-8), 137.57 (d,
C-5), 139.33 (s, C-11), 139.50 (s, C-14), 139.66 (s, C-6), 142.95 (s,
C-3).
UV (MeCN): lmax (log e) = 204 (4.58), 224 (4.18, sh), 276 (3.07)
nm.
MS (70 eV): m/z (%) = 232 (77) [M+], 231 (16), 217 (16), 128 (99),
115 (5), 104 (100).
5-Formyl-4-trifluoromethylsulfonyloxy[2.2]paracyclophane
(22)
A solution of FHPC (20, 1.77 g, 7.0 mmol)12 and N,N-bis(trifluo-
romethylsulfonyl)aniline (21, 2.50 g (7.0 mmol)) in Et3N (50 mL)
was heated to reflux for 24 h. The solvent was removed in vacuo and
the residue purified by silica gel column chromatography with pen-
tane–CH2Cl2 (1:1, Rf 0.32) yielding 5-formyl-4-trifluoromethylsul-
fonyloxy[2.2]paracyclophane (22) as a colorless solid (2.12 g, 5.5
mmol, 79%; mp 72 °C). An analytically pure sample was obtained
by sublimation (85 °C, 10–2 mbar).
IR (KBr): 3072 (w), 3049 (w), 3017 (w), 2956 (m), 2933 (m), 1691
(vs), 1596 (m), 1542 (m), 1474 (m), 1424 (s), 1399 (s), 1223 (vs),
1208 (vs), 1180 (m), 1141 (vs), 1100 (m), 1004 (m), 947 (m), 909
(s), 883 (s), 844 (m), 830 (m), 810 (m), 801 (m), 786 (m), 762 (m),
719 (m), 659 (m), 639 (m) cm–1.
1H NMR (CDCl3): d = 2.85–2.96 (m, 2 H, 2-H, 9-H), 3.02–3.13 (m,
2 H, 1-H, 10-H), 3.18–3.29 (m, 2 H, 1-H, 10-H), 3.47 (ddd, 2J2s,2a
=
14.0 Hz, 3J2s,1s = 10.1 Hz, 3J2s,1a = 3.8 Hz, 1 H, 2-Hs), 4.02–4.08 (m,
1 H, 9-H), 6.40 (dd, 3J16,15 = 7.9, 4J16,12 = 1.9 Hz, 1 H, 16-H), 6.51
Scheme 4
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York

SPECIAL TOPIC
Ethynyl[2.2]paracyclophanes – New Building Blocks for Molecular Scaffolding
2755
(dd, 3J13,12 = 7.9, 4J13,15 = 1.9 Hz, 1 H, 13-H), 6.64 (dd, 3J12,13 = 7.9,
4J12,16 = 1.9 Hz, 1 H, 12-H), 6.71 (d, 3J7,8 = 8.0 Hz, 1 H, 7-H), 6.78
(dd, 3J15,16 = 7.9 Hz, 4J15,13 = 1.9 Hz, 1 H, 15-H), 6.81 (d, 4J8,7 = 8.0
Hz, 1 H, 8-H), 10.10 [s, 1 H, -C(O)H].
phase was dried with Na2SO4 and the organic solvents were evapo-
rated. Column chromatography on silica gel with pentane–CH2Cl2
(1:1, Rf = 0.67) gave 52 mg (0.2 mmol, 41%) of 12 as a colorless
solid (mp 98 °C).
13C NMR (CDCl3): d = 31.2 (t, C-2), 33.9, 33.9, 34.1 (t, C-1, C-9,
C-10), 117.0 (q, CF3), 129.3 (d, C-15), 129.6 (s, C-5), 131.4 (d, C-
16), 132.9 (d, C-12), 133.8 (d, C-13), 133.8 (s, C-3), 135.7 (d, C-7),
139.2 (s, C-14), 139.5 (s, C-11), 140.2 (d, C-8), 145.9 (s, C-6),
148.4 (s, C-4), 188.6 (d, CO).
IR (KBr): 3293 (vs), 3275 (vs), 2964 (m), 2935 (s), 2889 (m), 2853
(m), 1500 (s), 1458 (m), 1449 (m), 1411 (s), 1261 (m), 1255 (m),
1249 (m), 1243 (m), 1237 (m), 1230 (m), 1224 (m), 1220 (m), 1214
(m), 1208 (m), 1099 (m), 943 (m), 909 (m), 891 (m), 867 (m), 795
(m), 749 (m), 721 (s), 684 (s), 669 (s), 637 (vs), 618 (vs); 607 (s)
cm–1.
UV (MeOH): lmax (log e) = 208 (4.52), 292 (3.5), 220 (4.34), 234
(3.98), 248 (3.85), 260 (3.5), 276 (3.34), 310 (3.33) nm.
MS (EI): m/z (%) = 384 (56) [M+], 251 (41), 233 (13), 160 (14), 147
(59), 104 (100), 91 (13), 78 (13).
1H NMR (CDCl3): d = 2.80 (ddd, 2J2a,2s = 13.1 Hz, 3J2a,1a = 10.6 Hz,
2
3J2a,1s = 4.7 Hz, 2 H, 2-Ha, 9-Ha), 2.96 (ddd, J1a,1s = 13.1 Hz,
3
3J1a,2a = 10.6 Hz, J1a,2s = 3.0 Hz, 2 H, 1-Ha, 10-Ha), 3.14 (ddd,
2J1s,1a = 13.1 Hz, 3J1s,2s = 10.4 Hz, 3J1s,2a = 4.7 Hz, 2 H, 1-Hs, 10-Hs),
3.46 (s, 2 H, C≡CH), 3.48 (ddd, 2J2s,2a = 13.1 Hz, 3J2s,1s = 10.4 Hz,
3J2s,1a = 3.0 Hz, 2 H, 2-Hs, 9-Hs), 6.45 (m, 4 H, 7-H, 8-H, 12-H, 13-
H), 6.81–6.82 (m, 2 H, 15-H, 16-H).
Anal. Calcd for C18H15O4SF3 (388.37): C, 56.25; H, 3.93; F, 14.83;
S, 8.34. Found: C, 56.08; H, 3.78; S, 8.49.
5-Formyl-4-trimethylsilylethynyl[2.2]paracyclophane (23)
In a Schlenk tube 22 (384 mg, 1 mmol) was dissolved in THF (10
mL) and diisopropylamine (10 mL), and the solution was deoxy-
genated by bubbling Ar through it. Then Pd(PPh3)4 (116 mg, 0.1
mmol), CuI (19 mg, 0.1 mmol) and trimethylsilylacetylene (0.56
mL, 4 mmol) were added, the reaction flask was closed with a screw
cap, and the mixture was heated to 80 °C. After 12 h, the solvents
were removed and the residue purified by silica gel column chroma-
tography with pentane–CH2Cl2 (4:1, Rf 0.12) to give 23 (262 mg,
0.79 mmol, 79%) as a colorless solid (mp 81 °C).
13C NMR (CDCl3): d = 33.9 (t, C-1, C-10), 34.1 (t, C-2, C-9), 82.0
(s, C≡C-H), 84.4 (d, C≡C-H), 127.1 (s, C-4, C-5), 129.6 (d, C-15,
C-16), 132.9 (d, C-12, C-13), 133.4 (d, C-7, C-8), 139.2 (s, C-11, C-
14), 143.5 (s, C-3, C-6).
UV (CH3OH): lmax (log e) = 216 (4.71), 246 (4.1), 220 (4.31), 228
(4.15), 242 (4.07), 258 (3.84), 266 (3.74), 288 (3.49), 348 (2.82)
nm.
MS (EI): m/z (%) = 257 (20) [M+ + H], 256 (92) [M+], 255 (28), 241
(26), 152 (83), 151 (38), 104 (100).
IR (KBr): 3067 (w), 3036 (m), 3010 (m), 2959 (m), 2930 (s), 2891
(m), 2854 (m), 2817 (m), 2756 (m), 2147 (m), 1688 (vs), 1656 (m),
1649 (m), 1566 (m),1549 (m), 1500 (m), 1461 (m), 1448 (m), 1436
(m), 1411 (m), 1386 (m), 1249 (s), 1214 (m), 1029 (m), 942 (m),
908 (m), 871 (s), 846 (vs), 800 (m), 760 (s) cm–1.
2
Synthesis of pseudo-gem-Diethynyl[2.2]paracyclophane (13)
from pseudo-gem-Diformyl[2.2]paracyclophane (24)
In a dried flask was suspended 2414 (264 mg, 1 mmol) in anhyd
MeOH (10 mL) and anhyd MeCN (20 mL). Then Cs2CO3 (ca 1.5 g,
7.8 mmol) and 19 (700 mg, 3.6 mmol) were added under vigorous
stirring at r.t. After 1 h the starting material had been consumed
(TLC monitoring), anhyd MeOH (20 mL) was added, and the reac-
tion mixture was stirred for further 12 h. The color changed from
yellow to orange. For work-up CH2Cl2 and water were added. The
layers were separated, the water phase was washed thoroughly with
CH2Cl2, and the combined organic phases were washed with brine
and dried with MgSO4.The solvent was evaporated to dryness and
the crude mixture was chromatographed on silica gel (25 g) with
pentane–CH2Cl2 (1:1) to give 13 (80 mg, 31%). Elution with
CH2Cl2 yielded 4-formyl-15-ethynyl[2.2]paracyclophane (25, 160
mg, 61%) and finally with CH2Cl2–Et2O (1:1) 4-methoxycarbonyl-
15-hydroxymethyl[2.2]paracyclophane (26, 30 mg, 8%) was ob-
tained.
1H NMR (CDCl3): d = 0.34 [s, 9 H, Si(CH3)3], 2.81 (ddd, J9a,9s
=
12.6 Hz, 3J9a,10a = 10.2 Hz, 3J9a,10s = 6.6 Hz, 1 H, 9-Ha), 2.90 (ddd,
2J2a,2s = 13.1 Hz, 3J2a,1a = 10.7 Hz, 3J2a,1s = 4.6 Hz, 1 H, 2-Ha), 3.03–
3.25 (m, 4 H, 1-H, 10-H, 10-H, 1-H), 3.65 (ddd, 2J2s,2a = 13.2 Hz,
3J2s,1s = 10.4 Hz, 3J2s,1a = 3.0 Hz, 1 H, 2-Hs), 4.14 (ddd, 2J9s,9a = 12.6
Hz, 3J9s,10s = 10.0 Hz, 3J9s,10a = 2.3 Hz, 1 H, 9-Hs), 6.36 (dd, 3J16,15
=
4
3
7.8 Hz, J16,12 = 1.9 Hz, 1 H, 16-H), 6.46 (dd, J13,12 = 7.9 Hz,
4
4J13,15 = 1.9 Hz, 1 H, 13-H), 6.56 (dd, 3J12,13 = 7.9 Hz, J12,16 = 1.9
Hz, 1 H, 12-H), 6.57 (d, 3J7,8 = 7.8 Hz, 1 H, 7-H), 6.67 (d, 3J8,7 = 7.8
Hz, 1 H, 8-H), 6.85 [dd, 3J15,16 = 7.8 Hz, 4J15,13 = 1.9 Hz, 1 H, 15-H),
10.35 [s, 1 H, C(O)H].
13C NMR (CDCl3): d = –0.1 [q, Si(CH3)3], 33.6 (t, C-2), 33.7 (t, C-
1), 34.0 (t, C-10), 34.5 (t, C-9), 100.2 (s, C≡C-Si), 107.3 (s, C≡C-
Si), 129.3 (d, C-15), 129.7 (s, C-4), 131.4 (d, C-16), 132.6 (d, C-12),
133.5 (d, C-13), 135.4 (d, C-7), 136.6 (s, C-5), 137.5 (d, C-8), 139.1
(s, C-14), 139.9 (s, C-11), 142.6 (s, C-6), 144.3 (s, C-3), 194.1 (d,
C=O).
pseudo-gem-Diethynyl[2.2]paracyclophane (13)
Colorless crystals; mp 145 °C.
IR (KBr): 3328 (vs), 3035 (m), 2928 (m), 2099 (w), 1587 (m), 1480
(m), 797 (m), 657 (m) cm–1.
UV (CH3OH): lmax (log e) = 212 (4.42), 260 (4.18), 368 (3.29), 218
(4.29), 230 (4.14), 252 (4.12), 256 (4.18), 268 (4.04), 278 (3.89)
nm.
MS (EI): m/z (%) = 332 (100) [M+], 317 (10), 229 (38), 227 (68),
1H NMR (400.1 MHz, CDCl3): d = 2.91–2.99 (m, 6 H, 1-H, 2-H, 9-
H, 10-H), 3.04 (s, 2 H, 18-H, 20-H), 3.77–3.82 (m, 2 H, 1-H, 2-H),
6.40–6.42 (dd, 4J5,7 = 1.83 Hz, 3J7,8 = 7.81 Hz, 2 H, 7-H, 12-H), 6.47
(d, 3J7,8 = 7.83 Hz, 2 H, 8-H, 13-H), 6.67 (d, 4J5,7 = 1.89 Hz, 2 H, 5-
H, 16 H).
13C NMR (100.6 MHz, CDCl3): d = 33.43 (t, C-1, C-2), 34.84 (t, C-
9, C-10), 81.22 (d, C-18, C-20), 83.38 (s, C-17, C-19), 122.61 (d, C-
4, C-15), 133.54 (d, C-7, C-12), 133.98 (d, C-8, C-13), 136.21 (d,
C-5, C-16), 139.24 (s, C-6, C-11), 142.41 (s, C-3, C-14).
213 (28), 198 (14), 104 (87), 78 (12), 73 (35).
Anal. Calcd for C22H24SiO (332.50): C, 79.47; H, 7.27. Found: C,
79.20; H, 7.19.
4,5-Diethynyl[2.2]paracyclophane (12)
To a solution of 166 mg (0.5 mmol) of 23 in anhyd MeOH (5 mL),
diazophosphonate 19 (173 mg, 0.9 mmol) and Cs2CO3 (295 mg,
1.25 mmol) were added at 0 °C. After 30 min, the cooling bath was
removed and the reaction mixture was stirred at r.t. for 16 h; CH2Cl2
was added and the mixture was washed with brine. The organic
UV (MeCN): lmax (log e) = 214 (4.72), 248 (4.31) nm.
MS (70 eV): m/z (%) = 256 (96) [M+], 255 (76), 241 (66), 128 (100),
102 (23).
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L. Bondarenko et al.
SPECIAL TOPIC
Anal. Calcd for C20H16 (256.35): C, 93.71; H, 6.29. Found: C,
92.42; H, 6.33 (according to NMR analysis the hydrocarbon con-
tained traces of CH2Cl2, even after extended drying under vacuum).
pseudo-meta-Dibromo[2.2]paracyclophane (28) and pseudo-
para-Dibromo[2.2]paracyclophane (29)
To a solution of [2.2]paracyclophane (27, 25.0 g, 0.12 mol) in CCl4
(450 mL) was added bromine (40 mL, 124.8 g, 0.8 mol) at r.t., and
the mixture was heated at 60 °C for 3 h. The progress of the reaction
was monitored by TLC (silica gel, pentane–CH2Cl2, 9:1). A precip-
itate was formed, later shown to be 29 (see below). The mixture was
cooled in an ice bath and an aqueous solution of sodium bisulfite
was added (decolorization). The formed crystals were removed by
filtration, washed with water three times, followed by EtOH. After
air-drying this residue pseudo-para-dibromo[2.2]paracyclophane
(29, 14.5 g, 33%) was isolated as an off-white powder.
4-Formyl-15-ethynyl[2.2]paracyclophane (25)
Colorless crystals; mp 173 °C.
IR (KBr): 3232 (s), 3030 (w), 2932 (m), 1682 (vs), 1554 (w), 1482
(w), 730 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.96–3.19 (m, 7 H, 1-H, 2-H, 9-
H, 10-H), 3.30 (s, 1 H, 19-H), 3.64–3.69 (m, 1 H, 2-H), 6.53 (d,
3
4J12,16 = 1.51 Hz, 1 H, 16-H), 6.54 (d, J7,8 = 7.50 Hz, 1 H, 8-H),
4
6.57–6.61 (m, 2 H, 12-H, 13-H), 6.69–6.71 (dd, J5,7 = 1.95 Hz,
Mp 235 °C (lit. mp 248.5–250 °C22).
3J7,8 = 7.84 Hz, 1 H, 7-H), 7.10 (d, 4J5,7 = 2.00 Hz, 1 H, 5-H), 10.25
(s, 1 H, 17-H).
1H NMR (200 MHz, CDCl3): d = 2.83–3.10 (m, 4 H), 3.15–3.22 (m,
2 H), 3.43–3.54 (ps-t, 2 H), 6.43 (d, J = 7.8 Hz, 2 H), 6.51 (s, 2 H),
7.13 (d, J = 7.5 Hz, 2 H).
13C NMR (50 MHz, CDCl3): d = 32.8 (t), 35.4 (t), 127.0 (s), 128.2
(d), 134.1 (d), 137.3 (d), 138.5 (s), 141.1 (s).
13C NMR (100.6 MHz, CDCl3): d = 31.24 (t, C-2), 33.57 (t, C-1),
34.71, 34.73 (t, C-9, C-10), 83.28 (s, C-18), 83.31 (d, C-19), 124.37
(s, C-15), 133.00 (d, C-12), 133.63 (d, C-13), 134.06 (d, C-5),
136.12 (d, C-8), 136.40 (s, C-4), 136.82 (d, C-16), 137.75 (d, C-7),
139.55 (s, C-11), 140.13 (s, C-6), 142.19 (s, C-14), 142.88 (s, C-3),
190.49 (d, C-17).
The filtrate was carefully washed with CH2Cl2, the organic layers
were combined, washed with water and sat. NaCl solution, and fi-
nally dried with MgSO4. After complete solvent removal the resi-
due was dissolved in CH2Cl2 and the solution cooled to 0 °C. The
crystals formed were shown to be a ca. 1:1-mixture of 28 and 29.
Recrystallization from CH2Cl2 and cooling of the solution to 0 °C
allowed the separation of the pseudo-para isomer 29. To the com-
bined filtrates an aqueous solution of EtOH was added (ca. 70%, 50
mL) and after standing at r.t. overnight pure 28 could be removed
by filtration (16.6 g, 38%).
UV (MeCN): lmax (log e) = 216 (4.60), 254 (4.21), 300 (3.33) nm.
MS (70 eV): m/z (%) = 260 (66) [M+], 231 (15), 128 (100), 104 (24),
102 (30).
Anal. Calcd for C19H16O (260.34): C, 86.48; H, 6.15. Found: C,
86.53; H, 6.18.
4-Methoxycarbonyl-15-hydroxymethyl[2.2]paracyclophane
(26)
Colorless crystals; mp 95 °C.
Colorless crystals; mp 115 °C (lit. mp 115–122 °C22).
1H NMR (200 MHz, CDCl3): d = 2.83–3.13 (m, 6 H), 3.22–3.38 (m,
2 H), 6.46 (dd, J1 = 1.7 Hz, J2 = 7.8 Hz, 2 H), 6.57 (d, J = 1.8 Hz, 2
H), 7.15 (d, J = 7.8 Hz, 2 H).
13C NMR (50 MHz, CDCl3): d = 33.5 (t), 34.6 (t), 127.5 (s), 130.2
(d), 130.8 (d), 136.7 (d), 138.9 (s), 141.1 (s).
IR (KBr): 3458 (OH, m), 3038 (w), 2925 (m), 1711, 1690 (vs), 1593
(w), 1437 (m), 1268 (s), 1075, 1014 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.04 (br s, 1 H, -OH), 2.91–2.98
(m, 1 H, 1-H), 3.01–3.16 (m, 5 H, 2-H, 9-H, 10-H), 3.29–3.37 (m, 1
H, 1-H), 3.89 (s, 3 H, CH3), 4.01–4.07 (m, 1 H, 2-H), 4.27, 4.50
(AB-q, 2J = 13.99 Hz, 2 H, 19-H), 6.51 (m, 2 H, 12-H, 13-H), 6.55
(d, 4J12,16 = 2.29 Hz, 1 H, 16-H), 6.56 (d, 3J7,8 = 7.88 Hz, 1 H, 8 H),
6.66–6.69 (dd, 4J5,7 = 1.96 Hz, 3J7,8 = 7.75 Hz, 1 H, 7-H), 7.13 (d,
4J5,7 = 1.96 Hz, 1 H, 5-H).
13C NMR (100.6 MHz, CDCl3): d = 31.82 (t, C-1), 33.65 (t, C-2),
34.76 (t, C-10), 34.79 (t, C-9), 52.03 (q, C-18), 62.88 (t, C-19),
128.88 (s, C-4), 130.16 (d, C-16), 131.77 (d, C-12), 134.24 (d, C-5),
134.63 (d, C-13), 136.12 (d, C-8), 136.38 (s, C-15), 136.92 (d, C-7),
139.59 (s, C-6), 139.79 (s, C-11), 140.96 (s, C-14), 141.81 (s, C-3),
168.52 (s, C-17).
pseudo-ortho-Dibromo[2.2]paracyclophane (30)
A mixture of 29 (14.5 g, 39.6 mmol) and triglyme (70 mL) was re-
fluxed (216 °C) for 4 h. After cooling to r.t. the reaction mixture was
cooled in an ice bath, the formed precipitate (29) was removed by
filtration, washed with a small amount of Et2O, and heated again in
triglyme (40 mL). After repeating the cycle two more times (in de-
creasing amounts of solvent: 20 mL and 10 mL of triglyme, respec-
tively), the filtrates were combined and 60% aq EtOH (300 mL) was
added dropwise under vigorous stirring. The precipitate was filtered
off on a Büchner funnel and after washing once with 70% aq EtOH
dried on air to yield pure 30 (10.6 g, 73%). An analytically pure
sample was obtained by recrystallization from pentane–CH2Cl2,
(1:1) as colorless crystals.
UV (MeCN): lmax (log e) = 206 (4.62), 230 (4.07), 276 (3.40) nm.
MS (70 eV): m/z (%) = 296 (100) [M+], 281 (12), 264 (86), 236 (38),
162 (62), 134 (58), 119 (82), 105 (86), 91 (76).
Mp 185–190 °C (lit. mp 200–207 °C22).
1H NMR (200 MHz, CDCl3): d = 2.72–2.90 (m, 2 H), 2.95–3.15 (m,
4 H), 3.35–3.55 (m, 2 H), 6.45–6.57 (m, 4 H), 7.18 (d, 2 H).
Anal. Calcd for C19H20O3 (296.37): C, 76.99; H, 6.81. Found: C,
76.98; H, 6.72.
13C NMR (50 MHz, CDCl3): d = 32.4 (t), 35.8 (t), 126.6 (s), 131.6
Synthesis of pseudo-gem-Diethynyl[2.2]paracyclophane (13)
from 4-Formyl-15-ethynyl[2.2]paracyclophane (25)
To a suspension of 25 (1.10 g, 4.23 mmol) in anhyd MeOH (60 mL)
were added 19 (750 mg, 4 mmol) and CsCO3 (ca 2.0 g, 10.4 mmol).
The mixture was vigorously stirred at r.t. for 12 h. After the usual
work up (see above) the mixture was chromatographed on silica gel
(60 g) with pentane–CH2Cl2 (1:1) to give 13 (337 mg, 31%). Further
elution with CH2Cl2 afforded the starting aldehyde 25 (751 mg,
68%). The hydrocarbon was identified by its spectral data (see
above).
(d), 132.7 (d), 135.0 (d), 138.7 (s), 141.3 (s).
Synthesis of pseudo-ortho-Diethynyl[2.2]paracyclophane (14)
from pseudo-ortho-Diformyl[2.2]paracyclophane (31)
To a stirred solution of 30 (1.47 g, 4.0 mmol) in anhyd Et2O (30 mL)
was added at 0 °C TMEDA (0.5 mL) followed by n-BuLi (5 mL) in
hexane (1.6 M, 8 mmol). The quality of the metal organic reagent
was found to be of crucial importance, i.e. the yields given here are
only realized when the n-BuLi solution is colorless (or pale yellow)
and clear. The reaction mixture turned orange-brown, and was
stirred for 30–60 min at r.t. to complete the metalation. When N-
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York

SPECIAL TOPIC
Ethynyl[2.2]paracyclophanes – New Building Blocks for Molecular Scaffolding
2757
formylpiperidine (1.02 g, 9.0 mmol) was added in anhyd Et2O (10
mL) the solution became clear. After stirring for 1 h at r.t. the reac-
tion was terminated by the addition of dilute HCl. The layers were
separated, the organic layer was washed with bicarbonate solution,
brine, and dried with MgSO4. Solvent removal yielded a residue,
which was purified by column chromatography on silica gel with
CH2Cl2 giving 31 (0.868 g, 81%) as colorless crystals (mp 200–205
°C).
organic phases were dried (MgSO4), and the solvent was removed
in vacuo. Column chromatography on silica gel with pentane–
CH2Cl2 (1:1) provided 14 (142 mg, 28%) and aldehyde 32 (326 mg,
64%) as an oil which soon solidified. Recrystallization from pen-
tane–CH2Cl2 (7:3) yielded colorless crystals (mp 118 °C).
IR (diamond ATR): 3255 (m), 2929 (w), 2766 (w), 1678 (s), 1587
(m), 650 (s) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.80–2.91 (m, 2 H), 2.95–3.09
(m, 1 H), 3.11–3.20 (m, 2 H), 3.22–3.33 (m, 1 H), 3.31 (s, 1 H, acet-
ylenic), 3.58–3.65 (m, 1 H), 4.12–4.18 (m, 1 H), 6.44 (d, J = 1.8 Hz,
2 H), 6.47 (d, J = 7.9 Hz, 2 H), 6.58 (dd, J1 = 1.7 Hz, J2 = 8.0 Hz, 2
H), 9.88 (s, 1 H, CHO).
13C NMR (100.6 MHz, CDCl3): d = 33.0 (t), 33.8 (t), 34.0 (t), 81.1
(d), 83.0 (s), 123.7 (s), 133.0 (d), 133.9 (d), 134.8 (d), 135.9 (d),
136.4 (s), 136.6 (d), 138.2 (d), 139.9 (s), 140.4 (s), 142.4 (s), 142.6
(s), 192.5 (d).
In anhyd MeOH (20 mL) were suspended 31 (200 mg, 0.75 mmol)
and Cs2CO3; under vigorous stirring diazophosphonate 19 (500 mg,
2.7 mmol) was added at r.t. and the reaction mixture was stirred at
r.t. until the starting material had been consumed (24 h, TLC moni-
toring). If necessary, the reaction mixture, the color of which
changed from yellow to red-violet, can be warmed. For work-up
CH2Cl2 and water were added and the layers were separated. The
aqueous phase was extracted with CH2Cl2, the organic phases were
combined, washed with brine, and dried with MgSO4. Removal of
solvent gave an oily residue (193 mg, 100%), which soon solidified
giving colorless crystals (mp 66 °C).
UV (EtOH): lmax (log e) = 216 (4.60), 283 (3.68) nm.
MS (70 eV): m/z (%) = 260 (35) [M+], 128 (100).
HRMS: m/z calcd for C19H16O: 260.1201; found: 260.1188.
pseudo-ortho-Diformyl[2.2]paracyclophane (31)
IR (KBr): 3028 (vw), 2927 (w), 1680 (vs), 1648 (m), 1552 (m),
1232 (m) cm–1.
pseudo-meta-Diethynyl[2.2]paracyclophane (15) from pseudo-
meta-diformyl[2.2]paracyclophane (33)
1H NMR (400.1 MHz, CDCl3): d = 2.87–2.94 (m, 2 H, 2-H, 10-H),
3.04–3.12 (m, 2 H, 1-H, 9-H), 3.26–3.32 (m, 2 H, 1-H, 9-H), 4.12–
4.18 (m, 2 H, 2-H, 10-H), 6.59 (d, 3J7,8 = 3J12,13 = 7.8 Hz, 2 H, 8-H,
12-H), 6.76–6.78 (dd, 4J5,7 = 4J13,15 = 1.9 Hz, 3J7,8 = 3J12,13 = 7.8 Hz,
To a stirred solution of the dibromide 28 (3.66 g, 10.0 mmol) in an-
hyd THF (25 mL) was added at –75 °C s-BuLi (15.5 mL, 1.3 M in
hexane, 20 mmol); the solution turned olive-green and was stirred
for further 15 min. N-Formylpiperidine (3.0 mL, 27.0 mmol) in an-
hyd THF (20 mL) was added at –60 °C, and the reaction mixture
was allowed to warm to r.t. Dilute HCl acid was added, the layers
were separated, the organic phase was washed with bicarbonate and
brine, and dried with MgSO4. After solvent removal in vacuo the
residue was chromatographed on silica gel with CH2Cl2 to give 33
(1.65 g, 62%) as colorless crystals; mp 163–164 °C. As a side prod-
uct, 4-bromo-13-formyl[2.2]paracyclophane (1.24 g, 39%) was iso-
lated.
4
2 H, 7-H, 13-H), 6.84 (d, 4J5,7 = J13,15 = 1.9 Hz, 2 H, 5-H, 15-H),
9.80 (s, 2 H, 17-H, 18-H).
13C NMR (100.6 MHz, CDCl3): d = 33.77 (t, C-1, C-9), 34.11 (t, C-
2, C-10), 136.07 (d, C-8, C-12), 136.13 (d, C-5, C-15), 136.30 (s, C-
4, C-16), 137.81 (d, C-7, C-13), 140.60, 142.48 (s, C-3, C-6, C-11,
C-14), 191.96 (d, C-17, C-18).
UV (MeCN): lmax (log e) = 216 (4.53), 296 (3.95) nm.
MS (70 eV): m/z (%) = 264 (100) [M+], 132 (98), 104 (92).
HRMS: m/z calcd for C18H16O2: 264.115; found: 264.115.
In anhyd CH2Cl2 (15 mL) and anhyd MeOH (40 mL) were dis-
solved 33 (1.530 g, 5.80 mmol) and Cs2CO3 (ca. 3 g, 9.2 mmol). Un-
der vigorous stirring was added diazophosphonate 19 (2.1 g, 10.9
mmol), and after one additional day were added Cs2CO3 (ca. 1.0 g,
3.1 mmol) and 19 (0.7 g, 3.6 mmol). The reaction mixture was
stirred at r.t. until the starting material had been consumed (ca. 50
h) as monitored by TLC control (silica gel, CH2Cl2). The color of
the reaction mixture changed from yellow to red-violet. For work-
up, CH2Cl2 and water were added. The layers were separated, the
water phase was extracted with CH2Cl2, and the combined organic
solutions were washed with brine and dried with MgSO4. Evapora-
tion to dryness yielded 15 (1.310 g, 88%).
pseudo-ortho-Diethynyl[2.2]paracyclophane (14)
IR (KBr): 3291 (s), 3008 (w), 2928 (m), 2098 (w), 1479 (m), 1432
(m), 1404 (m), 877 (m), 655 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.78–2.91 (m, 2 H, 2-H, 10-H),
3.00–3.06 (m, 2 H, 1-H, 9-H), 3.14–3.21 (m, 2 H, 1-H, 9-H), 3.34
(s, 2 H, 18-H, 20-H), 3.58–3.64 (m, 2 H, 2-H, 10-H), 6.45–6.53 (m,
4 H, 7-H, 8-H, 12-H, 13-H), 7.14 (m, 2 H, 5-H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 33.07 (t, C-1, C-9), 33.92 (t, C-
2, C-10), 80.40 (d, C-18, C-20), 83.22 (s, C-17, C-19), 123.39 (s, C-
4, C-16), 133.29, 133.34 (d, C-7, C-8, C-12, C-13), 134.19 (d, C-5,
C-15), 139.34 (s, C-6, C-14), 142.51 (s, C-3, C-11).
pseudo-meta-diformyl[2.2]paracyclophane (33)
IR (KBr): 2936 (w), 1678 (s), 1588 (w), 1487 (w), 1229 (m), 1141
(w), 900 (w), 778 (m), 719 (m) cm–1.
UV (MeCN): lmax (log e) = 196 (4.29), 214 (4.73), 236 (4.09), 282
(3.82) nm.
MS (70 eV): m/z (%) = 256 (36) [M+], 241 (20), 228 (6), 128 (100),
102 (22).
1H NMR (400.1 MHz, CDCl3): d = 2.96–3.03 (m, 2 H, 1-H, 2-H),
3.05–3.13 (m, 2 H, 9-H, 10-H), 3.21–3.28 (m, 2 H, 9-H, 10-H),
4.06–4.14 (m, 2 H, 1-H, 2-H), 6.47 (d, 3J7,8 = 3J15,16 = 7.82 Hz, 2 H,
4
8-H, 15-H), 6.61–6.64 (dd, 4J5,7 = J12,16 = 1.95 Hz, 3J7,8 = 3J15,16
=
Anal. Calcd for C20H16 (256.35): C, 93.71; H, 6.29. Found: C,
93.50; H, 6.09.
7.82 Hz, 2 H, 7-H, 16-H), 7.02 (d, 4J5,7 = 4J12,16 = 1.96 Hz, 2 H, 5-
H, 12-H), 9.95 (s, 2 H, 17-H, 18-H).
13C NMR (100.6 MHz, CDCl3): d = 33.62 (t, C-1, C-2), 34.56 (t, C-
9, C-10), 134.81 (d, C-8, C-15), 136.05 (d, C-5, C-12), 136.85 (s, C-
4, C-13), 137.39 (d, C-7, C-16), 140.48, 143.09 (s, C-3, C-6, C-11,
C-14), 191.59 (d, C-17, C-18).
4-Formyl-16-ethynyl[2.2]paracyclophane (32)
In anhyd CH2Cl2 (10 mL) and MeOH (40 mL) were dissolved 31
(518 mg, 2 mmol) and Cs2CO3 (ca. 1 g, 3.1 mmol). The diazophos-
phonate 19 (450 mg, 2.4 mmol) was added, and the reaction mixture
was left in a refrigerator at 0 °C until the starting 31 had been con-
sumed completely (several days, monitoring by TLC). For work-up
CH2Cl2 and water were added, the layers were separated and the
aqueous phase was washed thoroughly with CH2Cl2. The combined
UV (MeCN): lmax (log e) = 214 (4.54), 296 (3.95) nm.
MS (70 eV): m/z (%) = 264 (82) [M+], 236 (17), 207 (9), 132 (66),
104 (100).
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2758
L. Bondarenko et al.
SPECIAL TOPIC
pseudo-meta-Diethynyl[2.2]paracyclophane (15)
IR (KBr): 3273 (vs), 3042 (w), 2926 (m), 2094 (w), 1479 (w), 1403
(w), 898 (m), 657 (vs), 625 (s), 606 (s) cm–1.
(92 mg, 0.08 mmol) and CuI (30 mg, 0.16 mmol) were added and
the reaction mixture was heated to 40–50 °C. A solution of trimeth-
ylsilyl acetylene (0.88 mL, 6 mmol) in deoxygenated THF (5 mL)
was added with a syringe pump over a period of 8 h. After heating
for 2 d, the solvents were removed in vacuo and the residue was pu-
rified by column chromatography on silica gel with pentane to yield
4,7-dibromo-13,16-bis(trimethylsilylethynyl)[2.2]paracyclophane
[(38a, 58 mg, 0.1 mmol (10%); Rf 0.26; colorless solid; mp 210 °C],
4-bromo-7,13,16-tris(trimethylsilylethynyl)[2.2]paracyclophane
[38b; 95 mg 0.16 mmol (16%); Rf 0.18; colorless solid; mp 108 °C],
and 4,7,13,16-tetrakis(trimethylsilylethynyl)[2.2]paracyclophane
[38c, 267 mg, 0.45 mmol (45%); Rf 0.12; colorless solid; mp 118
°C].
1H NMR (400.1 MHz, CDCl3): d = 2.89–2.97 (m, 2 H, 9-H, 10-H),
3.03–3.11 (m, 4 H, 1-H, 2-H, 9-H, 10-H), 3.28 (s, 2 H, 18-H, 20-H),
4
3.46–3.53 (m, 2 H, 1-H, 2-H), 6.48–6.50 (dd, 4J5,7 = J12,16 = 1.76
Hz, 3J7,8 = 3J15,16 = 7.89 Hz, 2 H, 7-H, 16-H), 6.58 (d, 4J5,7 = 4J12,16
=
1.74 Hz, 2 H, 5-H, 12-H), 6.99 (d, 3J7,8 = 3J15,16 = 7.89 Hz, 2 H, 8-
H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 32.57 (t, C-1, C-2), 34.76 (t, C-
9, C-10), 80.43 (d, C-18, C-20), 83.67 (s, C-17, C-19), 124.23 (s, C-
4, C-13), 130.39 (d, C-8, C-15), 132.68 (d, C-7, C-16), 137.11 (d,
C-5, C-12), 139.38 (s, C-6, C-11), 142.94 (s, C-3, C-14).
38a
UV (MeCN): lmax (log e) = 214 (4.70), 234 (4.14, sh), 284 (3.86)
nm.
IR (diamond ATR): 2956 (m), 2937 (m), 2897 (w), 2851 (w), 2152
(m), 1479 (m), 1461 (m), 1448 (w), 1431 (w), 1410 (w), 1390 (m),
1353 (m), 1247 (s), 1206 (m), 1180 (m), 1044 (s), 966 (w), 896 (m),
835 (vs), 756 (s), 692 (s), 625 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 0.32 (s, 18 H, SiMe3), 2.88–3.00
(m, 4 H, 1-H, 2-H, 9-H, 10-H), 3.22–3.29 (m, 2 H, 2-H, 9-H), 3.32–
3.39 (m, 2 H, 1-H, 10-H), 7.02 (s, 2 H, 5-H, 8-H), 7.15 (s, 2 H, 12-
H, 15-H).
MS (70 eV): m/z (%) = 256 (84) [M+], 241 (43), 128 (100), 102 (20).
Even after extended drying under vacuum the sample still contained
traces of CH2Cl2 (NMR analysis), causing the carbon value of the
elementary analysis to be too low (91.21 rather than 93.71%).
pseudo-para-Diethynyl[2.2]paracyclophane (16)
To a solution of bromomethyl triphenylphosphonium bromide (4.80
g, 11.0 mmol) in anhyd THF (50 mL) was added under stirring at
–80 °C t-BuOK (2.95 g, 26.3 mmol) in one portion. The suspension
was stirred for 40 min at –80 °C and during 30 min a solution of
pseudo-para-diformyl[2.2]paracyclophane (36, 1.32 g, 5.0 mmol)12
in anhyd THF (80 mL) was added. The reaction mixture was al-
lowed to warm to r.t. slowly, and was stirred for a further 2 h period.
Another portion of t-BuOK (2.18 g, 19.4 mmol) was added and the
mixture refluxed for 2.25 h. After stirring at r.t. overnight, water
was added followed by sat. aq NH4Cl for neutralization. The organ-
ic phase was separated, washed with 1 N HCl acid solution and
brine, and dried with MgSO4. The residue obtained after solvent re-
moval was purified by flash chromatography (flash silica gel,
CH2Cl2–pentane, 1:2) providing 16 (1.10 g, 86%) as colorless crys-
tals (mp 192 °C, sublimation).
13C NMR (100.6 MHz, CDCl3): d = 0.0 (q, SiMe3), 31.6 (t, C-1, C-
10), 33.2 (t, C-2, C-9), 100.2 (s, C≡CSiMe3), 104.4 (s, C≡CSiMe3),
125.2 (s, C-13, C-16), 125.3 (s, C-4, C-7), 133.8 (d, C-12, C-15),
134.9 (d, C-5, C-8), 140.6 (s, C-3, C-6), 141.8 (s, C-11, C-14).
UV (CH2Cl2): lmax (log e) = 228 (4.45), 250 (4.14), 305 (4.34), 318
(4.40) nm.
MS (70 eV): m/z (%) = 557 (7) [M+], 559 (15) [M+], 561 (8) [M+],
556 (18) [M+], 558 (41) [M+], 560 (24) [M+], 562 (2) [M+], 296
(100), 281 (27), 223 (20), 73 (39).
38b
IR (diamond ATR): 2956 (m), 2935 (m), 2896 (w), 2852 (w), 2149
(m), 1469 (w), 1447 (w), 1391 (w), 1368 (w), 1247 (s), 1206 (w),
1183 (w), 1140 (m), 1114 (w), 902 (m), 831 (vs), 756 (s), 724 (m),
698 (s), 671 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 0.31 (s, 9 H, SiMe3), 0.32 (s, 18
H, SiMe3), 2.84–3.02 (m, 4 H, 1-H, 2-H, 9-H, 10-H), 3.21–3.30 (m,
1 H, 2-H), 3.32–3.41 (m, 3 H, 1-H, 9-H, 10-H), 6.99 (s, 1 H, 8-H),
7.02 (s, 1 H, 5-H), 7.04 (s, 1 H, 12-H), 7.10 (s, 1 H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 0.0 (q, SiMe3), 31.6 (t, C-1),
31.9 (t, C-9), 32.1 (t, C-10), 33.3 (t, C-2), 98.7 (s), 99.6 (s), 100.0
(s), 104.2 (s), 104.6 (s), 124.2 (s, C-7), 125.1 (s, C-13), 125.2 (s, C-
16), 127.0 (s, C-4), 133.5 (d, C-15), 134.0 (d, C-5), 134.7 (d, C-3),
135.5 (d, C-8), 138.9 (s, C-3), 142.0 (s, C-11 or C-14), 142.0 (s, C-
11 or C-14), 143.9 (s, C-6).
MS (70 eV): m/z (%) = 575 (3), 577 (3), 574 (6) [M+], 576 (7) [M+],
495 (9), 486 (10), 488 (11), 407 (15), 334 (15), 296 (16), 281 (17),
223 (12), 73 (100).
IR (KBr): 3294 (s), 3045 (w), 2929 (m), 2098 (w), 1481 (w), 1405
(w), 899 (m), 874 (m), 723 (s), 656 (s), 626 (s) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.84–2.90 (m, 2 H, 2-H, 10-H),
2.94–3.01 (m, 2 H, 1-H, 9-H), 3.15–3.22 (m, 2 H, 1-H, 9-H), 3.27
(s, 2 H, 18-H, 20-H), 3.55–3.61 (m, 2 H, 2-H, 10-H), 6.44 (d, 3J7,8
=
3J15,16 = 7.89 Hz, 2 H, 8-H, 16-H), 6.56 (d, 4J5,7 = 4J13,15 = 1.79 Hz,
4
4
3
2 H, 5-H, 13-H), 6.99–7.02 (dd, J5,7 = J13,15 = 1.87 Hz, J7,8
=
3J15,16 = 7.88 Hz, 2 H, 7-H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 33.60 (t, C-1, C-9), 33.73 (t, C-
2, C-10), 83.82 (d, C-18, C-20), 123.50 (s, C-4, C-12), 133.19 (d, C-
8, C-15), 137.77 (d, C-5, C-13), 139.47 (s, C-6, C-14), 142.58 (s, C-
3, C-11).
UV (MeCN): lmax (log e) = 212 (4.69), 246 (4.30), 252 (4.25, sh)
nm.
MS (70 eV): m/z (%) = 256 (40) [M+], 241 (15), 128 (100), 102 (17).
38c
Even after extended drying under vacuum the sample still contained
traces of dichloromethane (NMR analysis), causing the carbon val-
ue of the elementary analysis to be too low (91.82% rather than
93.71%).
IR (KBr): 2958 (m), 2934 (m), 2897 (w), 2852 (w), 2150 (s), 1478
(w), 1449 (w), 1392 (w), 1249 (s), 1204 (m), 1178 (w), 907 (m), 878
(vs), 841 (vs), 727 (m), 697 (m), 827 (m) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 0.31 (s, 36 H, SiMe3), 2.87–2.95
(m, 4 H, 1-H, 2-H, 9-H, 10-H), 3.34–3.42 (m, 4 H, 1-H, 2-H, 9-H,
10-H), 6.98 (s, 4 H, 5-H, 8-H, 12-H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 0.0 (q, SiMe3), 32.1 (t, C-1, C-
2, C-9, C-10), 99.4 (s, C≡CSiMe3), 104.7 (s, C≡CSiMe3), 125.1 (s,
C-4, C-7, C-13, C-16), 134.4 (d, C-5, C-8, C-12, C-15), 142.2 (s, C-
3, C-6, C-11, C-14).
Synthesis of 4,7,13,16-Tetraethynyl[2.2]paracyclophane (17)
from 4,7,13,16-Tetrakis(trimethylsilylethynyl)[2.2]paracyclo-
phane (38c)
A solution of 4,7,13,16-tetrabromo[2.2]paracyclophane (37, 524
mg, 1 mmol), prepared from the parent hydrocarbon 27 according
to ref.16 in THF (5 mL) and diisopropylamine (10 mL) was deoxy-
genated by passing a stream of Ar through it for 30 min; Pd(PPh3)4
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York

SPECIAL TOPIC
Ethynyl[2.2]paracyclophanes – New Building Blocks for Molecular Scaffolding
2759
UV (CH2Cl2): lmax (log e) = 232 (4.72), 264 (4.35), 290 (4.31), 306
(6) For a summary see: Hopf, H. Classics in Hydrocarbon
(4.46), 324 (4.48) nm.
Chemistry; Wiley-VCH: Weinheim, 2000, Chap. 15.2, 457–
472.
(7) Feldman, K. S.; Kraebel, C. M.; Parvez, M. J. Am. Chem.
Soc. 1993, 115, 3846–3847.
MS (70 eV): m/z (%) = 592 (1) [M+], 504 (3), 438 (13), 436 (14),
357 (100), 311 (8), 309 (9), 230 (18), 103 (27).
(8) For the preparation of several lower ethynylogs of 6 see:
Eaton, P. E.; Galoppini, E.; Gilardi, R. J. Am. Chem. Soc.
1994, 116, 7588.
4,7,13,16-Tetraethynyl[2.2]paracyclophane (17)
A suspension of 38c (195 mg, 0.33 mmol) and K2CO3 (456 mg, 3.3
mmol) in CH2Cl2 (10 mL) and MeOH (10 mL) was stirred at r.t. for
24 h. The reaction mixture was diluted with CH2Cl2 and washed
with sat. NH4Cl solution. The organic layer was dried with Na2SO4
and the solvents evaporated to yield 17 as a colorless solid [96 mg,
0.32 mmol (97%); mp 143 °C).
(9) Naemura, K.; Hokura, Y.; Nakazaki, M. Tetrahedron 1986,
42, 1763.
(10) Hopf, H.; Allmann, R.; Nagel, M.; El-Tamany, S. Chem.
Ber. 1982, 115, 3203.
(11) (a) Müller, S.; Liepold, B.; Roth, G. J.; Bestmann, H.-J.
Synlett 1996, 521. (b) Ohira, S. Synth. Commun. 1989, 19,
561.
(12) (a) Rozenberg, V.; Kharitonov, V.; Antonov, D.; Sergeeva,
E.; Aleshkin, A.; Ikonnikov, N.; Orlova, S.; Belokon’, Y.
Angew. Chem., Int. Ed. Engl. 1994, 33, 91; Angew. Chem.
1994, 106, 106. (b) Hopf, H.; Barrett, D. G. Liebigs Ann.
Chem. 1995, 449.
IR (KBr): 3296 (vs), 3284 (vs), 3042 (w), 3037 (w), 3013 (w), 2969
(w), 2934 (m), 2885 (w), 2851 (w), 2098 (m), 1475 (m), 1447 (m),
1431 (m), 1248 (m), 1207 (w), 1193 (m), 1166 (w), 936 (w), 907 (s),
865 (m), 725 (w), 676 (m), 661 (m), 650 (s) cm–1.
1H NMR (400.1 MHz, CDCl3): d = 2.95–3.06 (m, 4 H, 1-H, 2-H, 9-
H, 10-H), 3.37 (s, 4 H, C≡CH), 3.39–3.46 (m, 4 H, 1-H, 2-H, 9-H,
10-H), 7.05 (s, 4 H, 5-H, 8-H, 12-H, 15-H).
13C NMR (100.6 MHz, CDCl3): d = 31.9 (t, C-1, C-2, C-9, C-10),
82.0 (C≡CH), 82.7 (C≡CH), 124.4 (s, C-4, C-7, C-13, C-16), 134.8
(d, C-5, C-8, C-12, C-15), 142.5 (s, C-3, C-6, C-11, C-14).
(13) Hopf, H.; Raulfs, F.-W.; Schomburg, D. Tetrahedron 1986,
42, 1655; and references cited therein.
(14) (a) Aly, A. A.; Hopf, H.; Ernst, L. Eur J. Org. Chem. 2000,
3021. (b) Zitt, H.; Dix, I.; Hopf, H.; Jones, P. G. Eur. J. Org.
Chem. 2001, 2298. (c) For a summary of the literature on
this reaction see: Hopf, H. In Modern Cyclophane
Chemistry; Gleiter, R.; Hopf, H., Eds.; Wiley-VCH:
Weinheim, 2004, 198.
(15) (a) Cram, D. J.; Truesdale, E. A. J. Org. Chem. 1980, 45,
3974. (b) Cram, D. J.; Hornby, R. B.; Truesdale, E. A.;
Reich, H. J.; Delton, M. H.; Cram, J. M. Tetrahedron 1974,
30, 1757.
(16) König, B.; Knieriem, B.; de Meijere, A. Chem. Ber. 1993,
126, 1643.
(17) Boydston, A. J.; Bondarenko, L.; Dix, I.; Weakley, T. J.;
Hopf, H.; Haley, M. M. Angew. Chem. Int. Ed. 2001, 40,
2986; Angew. Chem. 2001, 113, 3074.
UV (CH2Cl2): lmax (log e) = 232 (4.53), 254 (4.19), 290 (4.21), 298
(4.22), 308 (4.28) nm.
MS (70 eV): m/z (%) = 303 (74) [M+], 304 (50) [M+], 305 (11) [M+],
289 (59), 287 (26), 265 (18), 152 (100), 151 (89), 150 (35), 126
(18).
Acknowledgment
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for the continuous support of our work.
References
(18) Savinsky, R.; Hopf, H.; Dix, I.; Jones, P. G. Eur. J. Org.
Chem. 2001, 4595.
(19) Zitt, H.; Dix, I.; Hopf, H.; Jones, P. G. Eur. J. Org. Chem.
(1) For Part LI see: El Shaieb, K.; Narayanan, V.; Hopf, H.; Dix,
I.; Fischer, A.; Jones, P. G.; Ernst, L.; Ibrom, K. Eur. J. Org.
Chem. 2003, 567.
2001, 2298.
(20) (a) Callant, P.; D’Haenens, L.; Vandewalle, M. Synth.
Commun. 1984, 14, 155. (b) Colvin, E. W.; Hamill, B. J. J.
Chem. Soc., Chem. Commun. 1973, 151. (c) Colvin, E. W.;
Hamill, B. J. J. Chem. Soc., Perkin Trans. 1 1977, 869.
(21) Dix, I. Ph.D. Dissertation; Technical University
Braunschweig: Germany, 2002.
(22) (a) Reich, H. J.; Cram, D. J. J. Am. Chem. Soc. 1969, 91,
3527. (b) Braddock, D. C.; MacGilp, I. D.; Perry, B. G. J.
Org. Chem. 2002, 67, 8679.
(2) Carbon-Rich Compounds II, Topics in Current Chemistry,
Vol. 201; de Meijere, A., Ed.; Springer: Berlin, 1999, and
references cited therein.
(3) For reviews see: (a) Sondheimer, F. Pure Appl. Chem. 1971,
28, 331. (b) Sondheimer, F. Acc. Chem. Res. 1972, 5, 81.
(4) Rubin, Y.; Knobler, C. B.; Diederich, F. Angew. Chem., Int.
Ed. Engl. 1991, 30, 698; Angew. Chem. 1991, 103, 708.
(5) Diercks, R.; Armstrong, J. D.; Boese, R.; Vollhardt, K. P. C.
Angew. Chem., Int. Ed. Engl. 1986, 25, 268; Angew. Chem.
1986, 98, 270.
Synthesis 2004, No. 16, 2751–2759 © Thieme Stuttgart · New York