Functional [6]pericyclynes: Synthesis through [14+4] and [8+10] cyclization strategies

Article abstract of DOI:10.1002/chem.200601191

Critical analysis of possible strategies for the synthesis of novel carbo-benzene derivatives suggests several [(18-n)+n] routes for the preparation of hexaoxy[6]pericyclyne precursors. Beyond the previously attempted [9 + 9] symmetrical scheme (n = 9), t

Full text of DOI:10.1002/chem.200601191

FULL PAPER
DOI: 10.1002/chem.200601191
Functional [6]Pericyclynes: Synthesis through [14+4] and [8+10]
Cyclization Strategies**
Catherine Saccavini, Christine Tedeschi, Luc Maurette, Christine Sui-Seng, Chunhai Zou,
Mich›le Soleilhavoup, Laure Vendier, and Remi Chauvin*[a]
Abstract: Critical analysis of possible
strategies for the synthesis of novel
carbo-benzene derivatives suggests sev-
eral [(18Àn)+n] routes for the prepa-
ration of hexaoxy[6]pericyclyne precur-
sors. Beyond the previously attempted
[9+9] symmetrical scheme (n=9), the
a priori most selective strategies are
those for which n=1, 4, 7, 10, 13, and
16. They involve a cyclizing double-
propargylation of a C18Àn w-bis-termi-
different substitution patterns. These
compounds were obtained in 7–15
steps as mixtures of stereoisomers.
Thus, by using dibenzoylacetylene as
the C4 electrophile, a [14+4] strategy
allowed the synthesis of two hexaphen-
yl representatives with two or four free
carbinol vertices. This approach also af-
forded tetraphenyl representatives in
which the two remaining carbinoxy ver-
tices were substituted with either two
alkynyl or one 4-anisyl and one 4-pyr-
idyl groups. By using the hexacarbonyl-
dicobalt complex of butynedial as the
C4 electrophile, a [14+4] strategy also
allowed the isolation of a tetraphenyl-
hexaoxy[6]pericyclyne with two adja-
cent unsubstituted carbinol vertices. A
regioisomer with two opposite unsub-
stituted carbinol vertices was obtained
through an [8+10] strategy and its oxi-
dation afforded the corresponding peri-
cyclynedione. Several attempts at syn-
thesizing
diphenylhexaoxy[6]pericy-
clynes with four unsubstituted carbi-
noxy vertices are described. Only an
[8+10] strategy allowed the generation
of a fragile diphenylhexaoxy[6]pericy-
clyne with four adjacent unsubstituted
carbinoxy vertices, which could be
partly characterized. These results
show that the synthesis of the nonsub-
stituted hexahydroxy[6]pericyclyne, the
ring carbo-mer of [6]cyclitol, is a diffi-
cult challenge.
nal-skipped
oligoyne
containing
(19Àn)/3 triple bonds with a Cn w-di-
carbonyl-skipped oligoyne containing
(nÀ1)/3 triple bonds. To complement
the previously used [11+7] strategy,
the [14+4] and [8+10] strategies were
thus explored. They proved to be effi-
cient, affording seven novel hexaox-
y[6]pericyclynes corresponding to six
Keywords: alkynes · butynedial ·
carbo-mers · cyclization · macro-
cycles · pericyclynes
Introduction
tion of C2 units into all symmetry-related bonds of the rele-
vant Lewis–Cram model of any molecule. Since the carbo-
mer model preserves the essential properties of the parent
model (connectivity, shape, symmetry, p resonance), one
may naturally wonder how related chemical properties
would be modified.[2] Aromaticity is such a property under-
lying many others, for which benzene stands as a paradigm.
Its ring carbo-mer C18H6 (“carbo-benzene”) is thus the sim-
plest molecule for the study of carbo-meric effects on aro-
maticity.[3] In 1995, the challenge of its synthesis and the first
four examples of aryl-substituted derivatives 1a–d were si-
multaneously reported by one of us[4] and by Kuwatani,
Ueda, and co-worker,[5] respectively (Scheme 1a).
In the age of nanoscience, macroscopic processes and devi-
ces are transposed to the molecular level. Within this con-
text, carbo-merization can be regarded as a “molecular in-
flation” through (di)carbon doping.[1] It involves the inser-
[a] Dr. C. Saccavini, Dr. C. Tedeschi, Dr. L. Maurette, Dr. C. Sui-Seng,
Dr. C. Zou, Dr. M. Soleilhavoup, L. Vendier, Prof. R. Chauvin
Laboratoire de Chimie de Coordination du CNRS, UPR 8241
205 Route de Narbonne 31077, Toulouse cedex 4 (France)
Fax : (+33)561-333-113
E-mail: chauvin@lcc-toulouse.fr
Both reports were based on the availability of functional
carbo-cyclohexane key precursors, namely hexaoxy-[6]peri-
cyclynes. These intriguing molecules were first exemplified
by molecules with the type 2 structure (Scheme 1a),[5] and
the goal here was to gain a systematic insight into the func-
[**] Series title, Part 1; for Part 2, see: C. Saccavini, C. Sui-Seng, L. Maur-
ette, C. Lepetit, S. Soula, C. Zou, B. Donnadieu, R. Chauvin, Chem.
Eur. J. 2007, 13, DOI: 10.1002/chem.200601193.
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4895

9, have been attempted previ-
ously,[4,5,8] whereas the even
strategies, n=4 and 10, are ad-
dressed herein (Scheme 2).
Results and Discussion
This section is divided into
three subsections. Before tack-
ling the study of the [14+4]
and [8+10] cyclization strat-
egies, the possibility of appeal-
ing alternative strategies is out-
lined. Their deceptive results
are briefly reported in a pre-
liminary subsection.
Attempted [6”3] and [3”6] se-
quential strategies to hexaox-
y[6]pericyclynes of type 2: The
most appealing route to highly
symmetrical hexaoxy[6]pericy-
clynes would be a cyclizing se-
Scheme 1. a) Exemplified hexaoxy[6]pericyclynes with a star-shaped alternating substitution pattern. These
molecules were devised as precursors of aryl-substituted carbo-benzene derivatives.[5] b) Targeted hexaoxy[6]-
pericyclynes with various substitution patterns, regarded as potential precursors of novel carbo-benzene deriv-
atives.
tional compatibility of hexaoxy-[6]pericyclynes in the alter-
native type 3 structure (Scheme 1b). The ultimate targets
were the corresponding carbo-benzene derivatives 4, which
display reduced symmetry compared with the three-fold
ideal symmetry of the known derivatives 1a–d
(Scheme 1b).[6] Since the ultimate aromatization step is de-
voted to the removal of all the stereochemical information
contained in the highly stereogenic [6]pericyclyne precursors
3, their stereochemical resolution was not required. In the
following, the term “isolated molecule” is defined regardless
of the stereochemistry.
Scheme 2. The seven [(18Àn)+n] cyclization schemes for the preparation
of [6]pericyclynes by cyclizing double alkynyl-propargyl coupling. The
dissymmetrical [3+15] and [6+12] schemes involving different ambiva-
lent nucleophilic/electrophilic reagents are nonselective and are not de-
picted. Underlined strategies have previously been investigated by
double alkynyl-oxopropargyl coupling;[4,5,8] italicized strategies are inves-
tigated herein.
In the pioneering work of Scott et al., the (nonfunctional)
dodecamethyl[6]pericyclyne
prototype
was
prepared
through a ring-closing strategy in which the 18 carbon atoms
of the ring were already present in the open-chain hexayne
precursor.[7] In contrast, the first hexaoxy[6]pericyclynes
were prepared through a cyclization strategy in which the 18
carbon atoms of the ring were brought together from either
two C9 w-ynal moieties[4] or from a C7 w-dialdehyde 5a–b
and a C11 w-diyne 6a–b (Scheme 1).[5,8] The latter [11+7]
strategy afforded the pivotal hexaoxy[6]pericyclynes 2d and
2e in 13 steps (2a–c were obtained from 2e via the pericy-
clynetrione 2 f). Both the attempted [9+9] and successful
[11+7] cyclization reactions relied on double alkynyl-oxo-
propargyl coupling (Scheme 1).[9] The same process also ena-
bled the synthesis of homologous pentaoxy[5]pericyclynes
through [(15Àn)+n] cyclization strategies from C15Àn w-
quential metathesis of six C3 1,3-dicarbyne units. The 2,5-
heptadiyne 7b can be prepared either directly from methyl
benzoate or from the known 1,4-diynes
8 and 7a
(Scheme 3).[10,11] However, attempts at metathesis of 7b
using the Mortreux instant catalyst under the original
(1358C) or modified (50/808C) conditions did not afford the
yet unknown pericyclyne 2a’.[12]
Alternatively, hexaoxy[6]pericyclynes could result from
cyclizing sequential alkynyl-propargyl coupling of three C6
heterodifunctional 1,4-diyne units. The 1,4-diynal brick 9
was thus generated by formylation of the 1,4-diyne 8, but an
attempt at in situ desilylation of 9 with KF in the presence
of [18]crown-6[13] failed to produce the known pericyclyne
2a by sequential condensation.[8]
diynes and Cn w-dicarbonyl compounds (n=4, 10).[10]
A
simple generalization led us to consider the homologous
[(18Àn)+n] strategy for the synthesis of hexaoxy[6]pericy-
clynes. Of the nine possibilities, the odd strategies, n=7 and
These disappointing results prompted us to resort to a
step-by-step construction of the C18 [6]pericyclyne ring.
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Functional [6]Pericyclynes
FULL PAPER
were obtained as oily mixtures
of diastereomers (six in theory)
with almost superimposable
TLC spots and NMR spectra.
Their resolution was not at-
tempted.
Formation of the hexaoxy[6]-
pericyclynes 3a and 3a’ resulted
from the double 1,4-attack of
dibenzoylacetylene (10) by the
tetra- and dilithium salts of
pentaynes 12a and 12a’, respec-
tively (Scheme 6). Although
Scheme 3. Attempted sequential processes [6”3] metathesis or [3”6] alkynyl-oxopropargyl coupling) for the
direct formation of symmetrical hexaoxy[6]pericyclynes.
A
hexaoxy[6]pericyclynes of type
3: The [14+4] strategy is envis-
aged for various C4 dielectro-
philes and C14 dinucleophiles
(Scheme 4).
Hexaphenylhexaoxy[6]pericy-
clynes 3a and 3a’: Owing to a
trade off between structural
and synthetic simplicity, hexa-
Scheme 5. Preparation of C14 tetraphenyltetraoxypentaynes.
Scheme 6. Formation of [6]pericyclynetetrol 3a and [6]pericyclynediol 3a’
through a [14+4] strategy.
Scheme 4. General [14+4] strategy for the generation of hexaoxy[6]peri-
cyclynes of type 3.
transient protection of the two hydroxy groups of 12a was
first envisioned through the bis(silyl ether) 13a (which will
be used for another purpose, see below), the poor solubility
of the tetralithium salt of 12a in THF was finally overcome
by simple dilution, giving the [6]pericyclynetetrol 3a in 39%
yield after chromatography. The dilithium salt of the bis-
(methyl ether) 12a’ was more soluble, but the [6]pericycly-
nediol 3a’ was isolated in a similar yield (40%).
phenyl-carbo-benzene 1a acts as a reference molecule. Its
hexaphenyl[6]pericyclyne precursor 2a was first prepared in
15 steps via 2e through an [11+7] strategy.[5,8] The alterna-
tive precursors 3a,a’ were targeted through a [14+4] strat-
egy using dibenzoylacetylene (10) as the C4 unit.[14] An obvi-
ous advantage of this route is its doubly convergent charac-
ter, as 10 can also serve as a precursor to the C14 unit.
The symmetric pentaynediol 11a was obtained by double
addition of 2 equiv of racemic monosilylated b-diyne 8 to di-
benzoylacetylene (10), which were prepared as previously
described in three[11] and two steps,[14] respectively. The hy-
droxy groups were methylated by treatment of the lithium
dialkoxides with an excess of MeI/DMSO to give 11a’. Desi-
lylation of 11a and 11a’ by treatment with K2CO3/MeOH
afforded the symmetrical C14 bis-terminal pentaynes 12a
and 12a’, respectively (Scheme 5). The pentaynes 12a,a’
The hexaoxy[6]pericyclyne 3a was obtained as an oily
mixture of at most 20 stereoisomers, corresponding to six
chiral and eight achiral diastereomers. Likewise, the hexaox-
y[6]pericyclyne 3a’ was obtained as an oily mixture of at
most 36 stereoisomers, corresponding to 16 chiral and 4
achiral diastereomers. While the diastereomeric mixtures of
the acyclic pentayne precursors 12a,a’ give almost degener-
1
ate H NMR signals for topographically equivalent protons,
the mixtures of the pericyclynes 3a and 3a’ give much more
complex NMR spectra. This is illustrated (Figure 1) for the
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4897

R. Chauvin et al.
ium salt of 14 afforded the lithium triyne ketolate intermedi-
ate 15a, which was converted in situ to the diether 16 in
46% yield (Scheme 7). The corresponding alcohol 15b
could also be isolated after treatment of the alkoxide 15a
with silica gel (simple hydrolysis resulted in decomposition).
Inspired by the sequence used for the synthesis of the
phenyl and anisyl homologues 8 and 14, the synthesis of pyr-
idyl-b-diyne 17 was first envisaged from bis(trimethylsilyl)a-
cetylene and isonicotinoyl chloride or its N-oxide in the
presence of AlCl3.[10] After several fruitless attempts, we fi-
nally resorted to an indirect route. Reaction of the Grignard
salt of trimethylsilylacetylene with pyridine-4-carbaldehyde
afforded the 4-pyridylcarbinol 18 in 95% yield. By using
either the Dess–Martin periodinane reagent or activated
MnO2, the alcohol was oxidized to the 4-pyridyl alknyl
ketone 19 in 85% yield.[17] Reaction of 19 with acetylene-
magnesium bromide afforded racemic (pyridyl)dialkynylcar-
binol 17 in 91% yield (Scheme 8). Monocrystals deposited
from a chloroform solution were suitable for X-ray diffrac-
Figure 1. 1H NMR spectrum of the stereoisomeric mixture of the pericy-
clynediol 3a’ (CDCl3, 250 MHz, 293 K).
pericyclynediol 3a’, which, in comparison with its precursor
12a’, exhibits significant broadening of the characteristic
ranges of the o-aromatic CH,
m,p-aromatic CH, OCH3, and
OH NMR signals, integrating
for 12, 18, 12, and 2 protons, re-
spectively. As previously re-
ported in the [5]pericyclyne
series,[10] averaging of the mag-
netic environment over the
NMR timescale is much less ef-
ficient in the locked cyclic
series than in the free-rotating
acyclic series.
Scheme 7. Preparation of the anisyltriynone 16 via desymmetrization of the C4 diketone 10.
The [14 +4] strategy thus af-
forded the novel hexaphenyl-
hexaoxy[6]pericyclynes 3a and
3a’ in eight and nine steps, and
12 and 11% overall yields, re-
spectively. By comparison, the
[11+7] strategy devised by Ku-
watani, Ueda, and co-workers
afforded the hexaphenylhex-
aoxy[6]pericyclyne 2a in 14
steps and 2.5% overall yield from commercially available
compounds.[8]
Scheme 8. Synthesis of (4-pyridyl)diethynylcarbinol 17.
tion analysis. The crystal structure of 17 (Figure 2, Tables 1
and 2), which is locally similar to that of the previously re-
ported anisyl homologue 14,[10] reveals a network of O
À
p-Anisyl-4-pyridyl-tetraphenyl-carbo-benzene 3b through a
[14+4] cyclization strategy: The success of the [14+4] strat-
egy for the synthesis of the hexaphenyl representatives 3a,a’
prompted us to investigate the generalization of this ap-
proach to another hexaaryl derivative, the dissymmetric het-
eroaryl[6]pericyclyne 3b. This target was indeed identified
as a potential precursor of the donor–acceptor carbo-ben-
zenic chromophore 4b,[15] studied at the theoretical level for
its nonlinear optical properties.[16] The first challenge was to
obtain a totally dissymmetric tetraaryl C14 pentayne bearing
both p-anisyl and 4-pyridyl substituents. The anisyl analogue
14 of the b-diyne 8 was prepared as previously described.[11]
Reaction of dibenzoylacetylene (10) with 1equiv of the lith-
H···N hydrogen bonds (H···N=1.82 Š). This feature is con-
sistent with the poor yields obtained in the attempted meth-
ylation of the hydroxy group of 17, which competes with the
methylation of the pyridyl nitrogen atom.
Nevertheless, double deprotonation of unprotected 17 and
subsequent addition of triynone 16 directly afforded crude
pentaynediol, which underwent desilylation to give pentay-
nediol 20a as a brown powder in 77% yield over two steps
(Scheme 9).
The spectroscopic simplicity of diastereomeric mixtures of
open-chain carbinol-skipped pentaynes, already noticed for
12a,a’ (six diastereomers), is dramatically illustrated with
the totally dissymmetric pentaynediol 20a (eight diastereo-
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Functional [6]Pericyclynes
FULL PAPER
Figure 2. ORTEP view (left) and hydrogen-bond packing (right) of the X-ray crystal structure of (4-pyridyl)diethynylcarbinol (17). Bond lengths and
angles are listed in Table 2.
Table 1. Crystallographic data for 17 (see Figure 2), 32 (see Figure 4, left), and 38 (see Figure 4, right).
did not afford the targeted
[6]pericyclyne. All attempts at
tuning the conditions (concen-
tration, temperature, and time)
resulted in partial desilylation
with retention of the terminal
alkynyl units (1H NMR signals
at d=2.7–2.8 ppm). The use of
a bulkier base, lithium diisopro-
17
32
38
formula
T [K]
C13H15NOSi
160(2)
C14H17OSi
180
C14H22O2Si2
293(2)
crystal system
space group
unit cell dimensions
a [Š]
b [Š]
c [Š]
monoclinic
P21/n
triclinic
P1
monoclinic
P21/n
¯
7.581(5)
18.956(5)
9.237(5)
90
97.927(5)
90
1314.7(12)
4
1.159
5.8139(10)
10.1083(15)
11.4864(17)
93.591(12)
95.348(13)
104.060(14)
649.42(18)
2
9.649(2)
7.9253(16)
24.007(6)
89.82(3)
92.81(3)
89.85(3)
1833.7(7)
4
a [8]
b [8]
pylamide (LDA), afforded
a
ꢀ
lower CH/OSi
A
g [8]
V [Š3]
nally,
deprotonation
4 equiv LiHMDS at À78/À208C
followed by addition of 10 led
to the total disappearance of
Z
1calcd [mgmÀ3
]
1.173
0.158
246
1.009
0.188
600
m [mmÀ1
(000)
]
0.159
488
F
A
ꢀ
the CH signals. Owing to the
crystal size [mm]
q range [8]
w range
0.30”0.25”0.12
2.47–26.23
–
0.375”0.125”0.075
3.57–32.06
–
excess base, partial desilylation
was, however, still observed.
Total desilylation of the crude
pericyclynediol was thus com-
pleted by treatment with tetra-
–
2.24–23.258
À10ꢁhꢁ0
À8ꢁkꢁ8
À26ꢁlꢁ26
10364/2644
index ranges
À9ꢁhꢂ9
À23ꢁkꢂ22
À11ꢁlꢂ11
9029/2583
À8ꢁhꢁ8
À11ꢁkꢁ14
À17ꢁlꢁ16
7051/4129
reflections collected/unique
butyl
ammonium
fluoride
[R
(int)=0.0436]
[R
U
[R(int)=0.1101]
N
completeness [%]
absorption correction
97.3 (2q=26.238)
empirical (DIFABS)
90.3 (q=32.068)
semi-empirical from
equivalents
0.995/0.9598
4129/0/149
0.785
R1 =0.0421
wR2 =0.0686
R1 =0.1010
wR2 =0.0787
0.266/À0.225
99.9 (q=23.258)
none
(TBAF) (Scheme 10). After
chromatography, the [6]pericy-
clynetetrol 3b was finally isolat-
ed as a brown powder in 14%
yield over two steps.
As previously noticed for
3a,a’, the diastereomeric mix-
ture of the totally dissymmetric
[6]pericyclynetetrol 3b exhibits
more complex or broader 13C
NMR signals than does the
max/min transmission
data/restraints/params
GOF on F2
0.979/0.953
2583/0/156
1.047
R1 =0.0356
wR2 =0.0869
R1 =0.0461
wR2 =0.0914
0.221/À0.264
–
2644/25/174
1.017
final R indices [I>2s(I)]
R1 =0.1189
wR2 =0.3108
R1 =0.2525
wR2 =0.3946
0.410/À0.429
R indices (all data)
À3
largest diff. peak/hole [eŠ
]
mers). Indeed, the Lewis structure of 20a counts 34 topo-
graphically distinct carbons all chemically nonequivalent in
the eight diastereomers. Therefore, 34”8=272 signals could
be a priori expected in the 13C NMR spectrum of 20a. In-
stead, exactly 34 sharp signals are found just as if the
sample contained a single diastereomer (Figure 3a).
mixture of the open-chain precursors. Despite the existence
of 32 diastereomers and 46 different topographical environ-
ments for the carbon atoms of each diastereomer (corre-
sponding to 1472 13C NMR signals at infinite resolution),
full functional assignment of the 13C NMR spectrum was
possible (Figure 3b).
An attempt at cyclization of the tetralithium salt of 20a
with dibenzoylacetylene (10) failed. The O-silylated sub-
strate 20b was thus prepared and isolated in 53% yield.
However, double deprotonation of the pentayne 20b with
nBuLi and subsequent addition of dibenzoylacetylene (10)
Dialkynyltetraphenylhexaoxy[6]pericyclyne 3c through
a
[14+4] cyclization strategy: The dialknyl[6]pericyclyne 3c
was also synthesized through a [14+4] strategy. Whereas
the tetraaryl C14 synthons 12a, 12a’, and 20b, were prepared
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R. Chauvin et al.
Table 2. Bond lengths [Š], angles [8], and hydrogen bonds for 17 (see Figure 2).
tives 23b’ and 23b’’, respective-
ly (Scheme 11). Alternatively,
oxidation with MnO2 afforded
the pentaynediones 24. Addi-
tion of acetylenemagnesium
bromide to dione 24a (obtained
in 68% yield from 22) gave
heptaynediol 25 in 71% yield.
The latter was finally converted
to tetraether 21 in 80% yield
(Scheme 11).
À
À
À
C1 O1
À
C1 C2
1.4143(17)
1.484(2)
1.4855(19)
1.5353(19)
1.186(2)
0.97(3)
1.204(2)
1.8463(16)
1.3796(19)
1.385(2)
C7 C9
1.387(2)
0.9500
1.383(2)
0.9500
1.3311(19)
0.9500
C11 H11B
0.9800
0.9800
1.8543(19)
0.9800
0.9800
À
À
C7 H7
C11 H11C
À
À
À
C1 C4
C8 C10
C12 Si1
À
À
À
C1 C6
C8 H8
C12 H12A
À
À
À
C2 C3
C9 N1
C12 H12B
À
À
À
C3 H3
C9 H9
C12 H12C
0.9800
À
À
À
C4 C5
C10 N1
1.3412(19) .853(2C) 13 Si11
À
À
À
C5 Si1
C10 H10
0.9500
1.857(2)
0.9800
C13 H13A
0.9800
0.9800
0.9800
À
À
À
C6 C7
C11 Si1
C13 H13B
À
À
À
C6 C8
C11 H11A
C13 H13C
À
O(12)H10.91
Heptayne 21 was then depro-
tonated with 2 equiv of nBuLi
and treated with dibenzoylace-
tylene (10) to give 3c in a satis-
factory yield for such a process
(43%, Scheme 12). The hexaox-
y[6]pericyclynediol 3c is theo-
retically obtained as a mixture
of 36 stereoisomers.
Indirect proof of the struc-
ture of 3c will be illustrated by
the X-ray crystal structure of its
aromatization product (carbo-
benzene 4c).[6]
O1-C1-C2
O1-C1-C4
C2-C1-C4
O1-C1-C6
C2-C1-C6
C4-C1-C6
C3-C2-C1
C2-C3-H3
C5-C4-C1
C4-C5-Si1
C7-C6-C8
C7-C6-C1
C8-C6-C1
C6-C7-C9
C6-C7-H7
C9-C7-H7
C10-C8-C6
C5-Si1-C11
110.49(11)
110.03(11)
109.42(11)
108.28(11)
109.06(11)
109.53(10)
177.44(16)
179.2(16)
176.54(15)
178.86(13)
118.82(12)
120.61(12)
120.56(12)
118.21(13)
120.9
C6-C7-H7
C9-C7-H7
C10-C8-C6
C10-C8-H8
C6-C8-H8
N1-C9-C7
N1-C9-H9
C7-C9-H9
120.9
120.9
118.97(13)
120.5
120.5
123.83(13)
118.1
118.1
122.81(14)
118.6
118.6
109.5
109.5
109.5
109.5
109.5
109.5
110.58(10)
Si1-C12-H12A
Si1-C12-H12B
H12A-C12-H12B
Si1-C12-H12C
H12A-C12-H12C
H12B-C12-H12C
Si1-C13-H13A
Si1-C13-H13B
H13A-C13-H13B
Si1-C13-H13C
H13A-C13-H13C
H13B-C13-H13C
C9-N1-C10
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
109.5
117.36(12)
106.5(13)
108.19(8)
107.38(8)
111.20(10)
111.17(10)
N1-C10-C8
N1-C10-H10
C8-C10-H10
Si1-C11-H11A
Si1-C11-H11B
H11A-C11-H11B
Si1-C11-H11C
H11A-C11-H11C
H11B-C11-H11C
C13-Si1-C11
C1-O1-H1
C5-Si1-C13
C5-Si1-C12
C13-Si1-C12
120.9
118.97(13)
108.18(8)
C12-Si1-C11
Tetraphenylhexaoxy[6]pericycl-
yne 3d: The unsubstituted an-
alogue of dibenzoylacetylene
(10) is acetylenedicarbaldehyde
(butynedial). This unstable mol-
ecule has been extensively
studied by Gorgues and co-
workers, who showed that it
can be stabilized by a hexacar-
bonyldicobalt moiety in com-
plex 26 (Scheme 13).[19] Despite
the introduction of six addition-
al electrophilic carbonyl cen-
ters, it has been shown that the
double-electrophilic reactivity
À
hydrogen bonds (with H···A<r(A)+2.000 Š and aD H···A>1108)
À
À
D H
d
A
d
G
aDHA
178.64
d
G
A
À
O1 H1
N1 [xÀ1,y,z]
Scheme 9. Preparation of totally dissymmetric C14 tetraarylpentaynes 20a,b.
through a C4 +2C5 process (see above), the dialkynyl C14
synthon 21 was synthesized through a stepwise [C4 +2C3]+
2C2 process. The triynedicarbaldehyde 22 was first prepared
according to a previously described method in five steps
from commercial compounds.[10] In order to improve the
yield of the production of the carbaldehyde functions
(acetal hydrolysis, 32%), alternative synthetic routes were
investigated (direct formylation and hydroxymethylation/ox-
idation). Rather disappointingly, all the methods gave simi-
lar yields (30–40%).[18]
Reaction of the C10 fragment 22 with 2 equiv of the
Grignard reagent of either trimethylsilylacetylene or acety-
lene gave the pentaynediol 23a or 23b, respectively (23a
could also be generated from the lithium salt of trimethyl-
silylacetylene). These unsubstituted diols were also charac-
terized as their dimethyl and bis(tetrahydropyranyl) deriva-
of the carbaldehyde centers of 26 is preserved.[20] In particu-
lar, anionic carbon nucleophiles such as lithium trimethylsi-
lylacetylide attack the CHO groups selectively over the car-
bonyl ligands.[21] In a cyclizing version, double attack of
complex 26 by the dilithium salts of C11 triynes afforded
pentaoxy[5]pericyclynes.[10] The analogous procedure was
thus attempted with the dilithium salts of the C14 pentaynes.
We found that after double deprotonation with nBuLi, the
above-described pentayne 13a (Scheme 5) reacts with 26 to
give the hexaoxy[6]pericyclyne complex 27 in 18% yield
(Scheme 13). Treatment of 27 with cerium ammonium ni-
trate (CAN) or TBAF resulted in simultaneous decomplexa-
tion and desilylation to give a stereoisomeric mixture of the
free tetraphenylhexaoxy[6]pericyclynetetrol 3d in 27 and
33% yields, respectively.[22] The presence of two adjacent
secondary carbinol vertices does not induce marked instabil-
4900
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Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
cessful
synthesis
of
3d
(Scheme 13), the butynedial
complex 26 was first envisioned
as a possible C4 synthon. The
missing secondary carbinol ver-
tices had then to be provided
by a suitable C14 pentayne. The
known pentayne cobalt com-
plex 28a was thus generated
from 26 and 2 equiv of the lithi-
um salt of 8[21] and treated
(without previous purification)
with CAN to give pentayne 29a
(Scheme 14). An attempt at the
C-desilylation of 29a with
TBAF failed, but protection of
the hydroxy groups with two
equivalents of 3,4-dihydro-2H-
pyran (DHP) in the presence of
p-toluenesulfonic acid (PTSA)
afforded 30a in 94% crude
yield and with acceptable
purity. As 30a decomposes on
silica gel, it was directly treated
with TBAF to afford bis-termi-
nal pentayne 30b in 34% yield
after chromatography. Never-
theless, reaction of the dilithi-
um salt of 30b with complex 26
did not afford any disubstituted
hexaoxy[6]pericyclyne.
Figure 3. Topographical assignment and ring-closure broadening effect in the 13C{1H} NMR spectra of diaste-
reomeric mixtures of acyclic pentayne 20a and cyclic hexayne 3b (CDCl3, 293 K). a) Sharp low-frequency
13C{1H} NMR spectrum (63 MHz) of pentayne 20a. Exactly 34 sharp signals (instead of 272) give the percep-
tion of
a
single diastereomer (instead of eight). b) Broadened high-frequency 13C{1H} NMR spectrum
(100 MHz) of [6]pericyclyne 3b. A functional assignment remains relevant.
These results seem to indi-
cate that the presence of at
least two adjacent propargylic
À
CH O vertices in the nucleo-
philic pentayne precursor is
precluded. Exploratory investi-
gations into the nucleophilic re-
activity of pentaynes 23b’ and
23b’’ (Scheme 11) showed that
À
Scheme 10. Formation of a totally dissymmetric heteroaryl-substituted hexaoxy[6]pericyclyne 3b.
ity with respect to the hexaphenyl homologue 3a containing
tertiary carbinol vertices only. This feature was previously
noticed in the pentaoxy[5]pericyclyne series.[10]
nonadjacent propargylic CH O vertices are problematic as
well. The [14+4] strategy was thus given up, but the chal-
lenge will be resumed through the alternative [8+10] cycli-
zation strategy (see below).
Similar to 3a’, the hexaoxy[6]pericyclynetetrol 3d is theo-
retically obtained as a mixture of 36 stereoisomers, 32 of
them being chiral and thus partitioned into 16 pairs of enan-
tiomers. In principle, 20 diastereomers could therefore be
distinguished by classical spectroscopy. No attempt at resolv-
ing the diastereomeric mixture was undertaken. The chemi-
cal proof of the topographical structure of 3d will be illus-
trated by the X-ray crystal structure of its aromatization
product (4d).[6]
Hexaoxy[6]pericyclynes through a [8+10] cyclization strat-
egy: Pursuing our efforts to synthesize hexaoxy[6]pericy-
clynes with secondary carbinol vertices (see above), the [8+
10] strategy was envisaged (Scheme 15).
Tetraphenylhexaoxy[6]pericyclyne 3e through a [10+8] cyc-
lization strategy: The C8 triynes 32 and 33 have previously
been prepared from 8[11] in two and three steps, respective-
ly.[10] Triyne 32 can also be prepared more directly from tri-
methylsilylacetylene and dibenzoylacetylene (10) in 65%
yield over two steps via the diol intermediate 31 (its isola-
tion was however not required: Scheme 16). Single crystals
Diphenylhexaoxy[6]pericyclynes—Attempted [14+4] route:
The challenge of the synthesis of a hexaoxy[6]pericyclyne
with four secondary carbinol vertices was first tackled
through a [14+4] cyclization strategy. Stimulated by the suc-
Chem. Eur. J. 2007, 13, 4895 – 4913
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4901

R. Chauvin et al.
ever, formed (see below) and
the mixture was used in subse-
quent steps.
The C10 dialdehyde 22 was
prepared as previously report-
ed.[10] Alternatively, it could
also be obtained from the C8
synthon through double formy-
lation or through hydroxyme-
thylation with formaldehyde
followed by MnO2 oxidation.[18]
The dilithium salt of the C8
triyne 33 was treated with 22
(Scheme 17). After protonation,
the integrated 1H NMR spec-
trum of the crude material (o-
ꢀ
CH/m,p-CH/OCH3/C CH
ꢃ2:3:3:0.13) revealed that the
carbaldehyde functions had dis-
appeared and that 87% of the
terminal alkynes had been con-
sumed. Three chromatographic
Scheme 11. Synthesis of bis-terminal carbinol-skipped heptaynes 25 and 21.
runs were required to purify
the hexaoxy[6]pericyclyne 3e in
12% yield. A slightly more polar product was also isolated
and assigned to the open nonaynediol structure 34a on the
1
basis of its H NMR spectrum. The pericyclyne 3e possesses
two nonadjacent secondary carbinol vertices and is therefore
compared with the less symmetrical pericyclyne 3d in which
1
the carbinol vertices are adjacent (see above). The H NMR
spectrum of 3e exhibits at least 23 different OCH3 signals
showing that the compound is obtained as a mixture of ste-
reoisomers. In theory, 3e, just as 3a, possesses 14 diastereo-
mers (six of them being chiral) corresponding to 32 chemi-
cally distinguishable OCH3 groups. Invoking possible over-
Scheme 12. Cyclization of a stereoisomeric mixture of the bis-terminal
heptayne tetraether 21 with dibenzoylacetylene (10) to the diethynyl[6]-
pericyclynediol 3c.
1
laps in the H NMR spectrum,
the sample of 3e was likely
close to a statistical mixture of
stereoisomers. This conclusion
was confirmed after oxidation
of the carbinol vertices.
Indeed, treatment of a mix-
ture of 3e and 34a with MnO2
led to [6]pericyclynedione 3 f (a
“closed” version of the pentay-
nedione 24a ; Scheme 11) and
nonaynedione 34b. Oxidation
of the carbonyl groups masks
two potentially stereogenic cen-
Scheme 13. Synthesis of a stable hexaoxy[6]pericyclyne 3d with adjacent secondary carbinol vertices using
Gorguesꢁ acetylenedicarbaldehyde cobalt complex 26.
of 32 (prepared by the original method)[10] were obtained
and submitted for X-ray diffraction analysis. It revealed a
meso configuration (Figure 4 (left), Tables 1and 3), as previ-
ously observed for the dianisyl derivative of 3[10] and here-
after reported for the unsubstituted derivative 38 (Figure 4
(right), Tables 1and 4). In this series, the meso isomers were
thus selectively crystallized with respect to the correspond-
ing (Æ) isomers. Both the meso and (Æ) isomers were, how-
ters, thus reducing both the number of stereoisomers from
1 4 in3e to five in 3 f, and the corresponding number of
chemically nonequivalent OCH3 groups decreases from 32
in 3e to eight in 3 f. The number of OCH3 signals distin-
guished in the 1H NMR spectrum of 3 f is exactly eight
(Figure 5, left). This shows that all the stereoisomers were
present in the mixture and confirms a posteriori that indeed
the (Æ) isomer was present in the starting material 32 along
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Functional [6]Pericyclynes
FULL PAPER
should be provided by the C8
synthon 35 (Scheme 18). The
parent octa-1,4,7-triyne-3,6-diol
was indeed described in 1961 as
a
sublimable solid prepared
from ethynylmagnesium bro-
mide and propiolaldehyde[24a]
and its 13C NMR spectrum was
later reported (without a refer-
ence to the preparative method
used).[24b] The bis(methyl ether)
Scheme 14. Preparation of skipped C14 pentaynes containing two adjacent secondary carbinoxy vertices, with a
view to a putative [14+4] cyclization with the C4 dicarbonylacetylenes 10 or 26.
Scheme 15. General [8+10] cyclization strategy for the synthesis of tar-
geted hexaoxy[6]pericyclynes of type 3 with secondary carbinol vertices.
The total retrosynthetic scheme may become doubly convergent for sym-
metrical targets (R=R’).
with the crystallizable meso isomer (Figure 4, right, Tables 1
and 3).
Permethyl[4]- and -[5]pericyclynones and a [10]pericycly-
nedione have been reported by Scott and Cooney,[23] and the
alternating [6]pericyclynetrione 2 f described by Kuwatani,
Ueda, and co-workers.[8] The series is completed here with
the [6]pericyclynedione 3 f, a ring carbo-mer of a 1,4-cyclo-
hexanedione. This molecule might serve as a pivotal electro-
phile in the synthesis of other pericyclynes of type 3, just as
does the trione 2 f in the synthesis of pericyclynes of type 2
(Scheme 1).[8]
Figure 4. ORTEP views of the meso isomers of 1,8-bis(trimethylsilyl)oc-
ta-1,4,7-triyne-3,6-diol derivatives. Left: Diphenyltriyne diether 32
(Scheme 16; reliablity factor (R)=0.042). Right: Unsubstituted triynediol
38 (Scheme 18; R=0.119). Bond lengths and angles are listed in Tables 3
and 4.
En route to diphenylhexaoxy[6]pericyclyne 3g through a
[10+8] cyclization strategy: The synthesis of a pericyclyne
with four secondary carbinol vertices could not be achieved
by the attempted [14+4] strategy (see above). Stimulated
by the successful preparation of 3e, the challenge was re-
sumed through an [8+10] strategy in which two CHOH ver-
tices are generated in the last cyclization step (Scheme 15).
Using the C10 synthon 22, the remaining CHOH vertices
35 was thus obtained from penta-1,4-diyn-3-ol 37, itself pre-
pared by the reaction of ethynylmagnesium bromide with
trimethylsilylpropiolaldehyde 36. Double deprotonation of
37 with EtMgBr and subsequent addition of 36 afforded
triynediol 38 in 42% yield (Scheme 17; use of the dilithium
salt of 37 was much less efficient).
X-ray diffraction analysis of
the white crystals selectively de-
posited from a diastereomeric
mixture of 38 indicated a meso
configuration (Figure 4, right).
This crystalline meso structure
can be compared with those of
diphenyl (32, Figure 4, left) and
Scheme 16. Synthesis of C8 triynes 32 and 33.
dianisyl derivatives.[10]
Chem. Eur. J. 2007, 13, 4895 – 4913
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4903

R. Chauvin et al.
Table 3. Bond lengths [Š] and angles [8] for 32 (see Figure 4, left).
An attempt at [8+10] cycli-
zation of 22 with doubly depro-
tonated triyne 35 (nBuLi) gave
erratic results. Nonetheless, two
À
À
À
C1 Si1
1.8454(18)
1.8489(16)
1.8418(16)
1.1975(18)
1.8495(15)
1.4977(18)
C6 O1
À
C6 C7
1.4253(16)
1.4885(19)
1.5294(19)
1.4263(17)
1.3820(19)
1.3906(19)
C10 C11
1.382(2)
1.373(2)
1.378(2)
1.384(2)
1.185(3)
À
À
C2 Si1
C11 C12
À
À
À
C3 Si1
C6 C9
C12 C13
À
À
À
C4 C5
C8 O1
C13 C14
successive
chromatographic
À
À
À
C4 Si1
C9 C14
C7 C7#1
runs allowed the pericyclyne 3g
to be partly characterized
(Scheme 19). As evidenced by
1H NMR spectroscopy, the final
À
À
C5 C6
C9 C10
C5-C4-Si1
C4-C5-C6
O1-C6-C7
O1-C6-C5
C7-C6-C5
O1-C6-C9
C7-C6-C9
C5-C6-C9
176.44(13)
176.46(16)
110.68(11)
110.84(11)
109.13(11)
106.44(10)
111.86(12)
107.84(11)
C14-C9-C10
C14-C9-C6
C10-C9-C6
C11-C10-C9
C12-C11-C10
C11-C12-C13
C12-C13-C14
C9-C14-C13
119.00(14)
120.67(13)
120.17(13)
119.89(14)
120.78(15)
119.62(15)
120.07(15)
120.64(14)
C6-O1-C8
C3-Si1-C1
C3-Si1-C2
C1-Si1-C2
C3-Si1-C4
C1-Si1-C4
C2-Si1-C4
C7#1-C7-C6
115.02(10)
112.48(10)
109.29(9)
109.00(9)
107.86(7)
106.78(7)
111.44(7)
177.5(2)
samples contained
a residual
terminal alkyne, but the DCI/
NH3 mass spectrum (DCI: de-
sorption chemical ionization)
exhibits the [M+NH4]+ signal
at m/z 550 as the main peak.
Both the 1H and 13C NMR
spectra indicate that the com-
pound was obtained as a mix-
ture of diastereomers (in theory
20, just as for 3a’, 3c, and 3d).
Despite the limited number
of steps (12) involved in the
[8+10] strategy, the above syn-
thesis is quite tedious, especial-
ly the preparation of the dialde-
hyde 22. It did however provide
evidence for the stability of a
hexaoxy[6]pericyclyne with four
adjacent secondary carbinol
vertices. All-secondary hexaox-
y[6]pericyclynes are the next
natural targets, the ultimate
goal being the nonethereal car-
Table 4. Bond lengths [Š] and angles [8] for 38 (Figure 4, right).
À
À
À
Si1 C11B
1.71(3)
O2 C6
1.350(11)
1.763(18)
1.762(18)
1.782(19)
1.918(16)
1.758(18)
1.764(18)
1.777(18)
Si2B C8
1.855(15)
1.189(10)
1.480(13)
1.489(11)
1.180(11)
1.488(12)
1.481(14)
1.174(12)
À
À
À
Si1 C1
1.827(10)
1.846(16)
1.853(18)
1.862(18)
1.858(17)
1.889(17)
1.442(9)
Si2A C13A
C5 C4
À
À
À
Si1 C10A
Si2A C14A
Si2A C12A
Si2A C8
C5 C6
C4 C3
C1 C2
C3 C2
C6 C7
C7 C8
À
À
À
Si1 C10B
À
À
À
Si1 C11A
À
À
À
Si1 C9B
Si2B C12B
À
À
À
Si1 C9A
Si2B C13B
À
À
À
O1 C3
Si2B C14B
C11B-Si1-C1
C11B-Si1-C10A
C1-Si1-C10A
C11B-Si1-C10B
C1-Si1-C10B
C10A-Si1-C10B
C11B-Si1-C11A
C1-Si1-C11A
C10A-Si1-C11A
C10B-Si1-C11A
C11B-Si1-C9B
C1-Si1-C9B
C10A-Si1-C9B
C10B-Si1-C9B
C11A-Si1-C9B
C11B-Si1-C9A
120.0(9)
119.5(15)
110.9(9)
99(2)
102.3(9)
36.9(11)
16.9(10)
103.1(7)
132.9(14)
105.5(17)
103(2)
114.7(11)
81.7(14)
117.0(13)
112.6(17)
97.8(19)
C1-Si1-C9A
102.4(8)
101.2(13)
137.2(12)
102.2(17)
20.3(11)
103.5(17)
119.4(18)
127.7(18)
110.9(12)
113.3(11)
79.2(12)
125.2(17)
99.2(16)
90.0(17)
114.0(13)
110.2(13)
C14B-Si2B-C8
C4-C5-C6
C5-C4-C3
C2-C1-Si1
O1-C3-C4
O1-C3-C2
C4-C3-C2
C1-C2-C3
O2-C6-C5
O2-C6-C7
C5-C6-C7
C8-C7-C6
C7-C8-Si2B
C7-C8-Si2A
Si2B-C8-Si2A
114.7(11)
174.1(10)
179.0(9)
175.6(10)
107.0(6)
111.8(7)
112.2(6)
178.5(10)
113.3(9)
112.9(8)
111.9(9)
174.9(11)
159.6(12)
164.7(12)
35.3(4)
C10A-Si1-C9A
C10B-Si1-C9A
C11A-Si1-C9A
C9B-Si1-C9A
C13A-Si2A-C14A
C13A-Si2A-C12A
C14A-Si2A-C12A
C13A-Si2A-C8
C14A-Si2A-C8
C12A-Si2A-C8
C12B-Si2B-C13B
C12B-Si2B-C14B
C13B-Si2B-C14B
C12B-Si2B-C8
C13B-Si2B-C8
bo[6]cyclitol,
a
symmetric
isomer of the skeletal carbo-
mer of glucose [C3H2O]6.
Conclusion
Regarding the synthetic meth-
odology, the [14+4] and [8+
Methylation of the secondary dialkynyl carbinol vertices
of 38 proved to be difficult. The classical procedure used to
methylate the tertiary counterparts did not work, but treat-
ment of the dilithium salt of 38 with methyl triflate in dieth-
yl ether below 08C afforded diether 39 in 95% crude yield.
This compound is quite unstable, but desilylation with
TBAF at À808C gave the bis(methyl ether) 35, which is
slightly more stable than 39, but still less stable than diol 38
and its desilylated derivative.[24] The peculiar reactivity of
triynediol 38 prompted us to attempt the oxidation of its
secondary carbinol vertices. Thus treatment of 38 with
MnO2 afforded the triynedione 40. Owing to poor separa-
tion by column chromatography, this fragile compound was
isolated in a very low yield (3%), but it was still unknown
despite its simplicity.
10] cyclization strategies proved to compete with the [11+
7] strategy of Kuwatani, Ueda, and co-workers.[5,8] Of
course, the remaining [13+5], [16+2], and [17+1] strat-
egies might be investigated as well. Nevertheless, the re-
markably short synthesis of pericyclynedione 3 f (eight
steps) and its potential pivotal role support the suitability of
the [8+10] route for a scale-up study, which is in prog-
ress.[25]
Regarding chemical diversity, the eight hexaoxy[6]pericy-
clynes 3a, 3a’, and 3b–3g correspond to six different substi-
tution patterns and enlarge the restricted family of known
homoconjugated cyclic C18 molecules.[26] At the very outset,
their intrinsic importance is limited by the fact that they
were obtained as mixtures of stereoisomers. This limitation
prompted us to tackle methodological studies for the stereo-
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Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
selective addition of terminal
alkynes to bis-oxopropargylic
substrates such as the butyne-
dial complex 26.[27] As stated in
the Introduction, however, the
stereochemical disorder can be
cancelled, either partly, through
oxidation of secondary carbinol
vertices (as in the pericyclyne-
dione 3 f),[27] or completely,
through reductive aromatiza-
tion to carbo-benzene deriva-
tives of type 4 (Scheme 1). This
is the topic of the following
paper.[6]
Experimental Section
General: THF and diethyl ether were
dried and distilled over sodium/benzo-
phenone, pentane and dichlorome-
thane over P2O5. Commercial solu-
tions of EtMgBr were 3m in diethyl
Scheme 17. Synthesis of the hexaoxy[6]pericyclyne 3e with two “opposite” secondary carbinol vertices, nonay-
nediol 34a (characterized by H NMR spectroscopy only), pericyclynedione 3 f, and nonaynedione 34b.
1
ether, those of nBuLi were 1.6 or 2.5m in hexane, and the effective con-
centrations of the latter were checked by titration with 2,2,2’-trimethyl-
propionanilide.[28] All other reagents were used as commercially avail-
able. In particular, activated MnO2 was purchased from Fluka (no.
446286/1) and solutions of nBu4NF (1m in THF) were purchased from
Aldrich. Previously described procedures were used for the preparation
of 7a,[10] 8,[11] 10,[15] 14,[10] 22,[10] 26,[19,21] 28a,b,[21] 32,[10] 33,[10] and 36.[8] All
reactions were carried out under nitrogen or argon using Schlenk and
vacuum line techniques. Column chromatography was carried out on
silica gel (60 Š, 70–200 mm). Silica gel thin-layer chromatography plates
(60F254, 0.25 mm) were revealed by treatment with an ethanolic solution
of phosphomolybdic acid (20%). The following analytical instruments
were used. IR: Perkin-Elmer GX FT-IR spectrometer, 0.1mm CaF 2 cell.
1H and 13C NMR: Bruker AC 200, WM 250, DPX 300, or AMX 400
spectrometer. X-ray diffraction: IPds STOE diffractometer. Mass spec-
trometry: Quadrupolar Nermag R10-10H spectrometer. Elemental analy-
ses: Perkin-Elmer 2400 CHN (flash combustion and detection by cathar-
ometry). All IR and NMR spectra were recorded in CDCl3 solutions. IR
absorption frequencies n˜ are in cmÀ1. NMR chemical shifts d are in ppm,
with positive values to high frequency relative to the tetramethylsilane
reference; coupling constants J are in Hz. As most compounds were iso-
lated as oily mixtures of diastereomers, characteristic assignments are
given to trace the analytical consistency within the homogeneous series
of compounds studied.
Figure 5. Resolved 1H (left) and 13C{1H} (right) NMR spectra of the dia-
X-ray crystallographic structure determinations (Table 1): Data were col-
lected on a Stoe Imaging Plate Dif-
stereomeric mixture of the tetramethoxypericyclynedione 3 f.
fraction System (IPDS) equipped with
an Oxford Cryosystems Cryostream
Cooler Device using graphite-mono-
chromated MoKa radiation (l=
0.71073 Š). The final unit cell parame-
ters were obtained by means of
a
least-squares refinement of a set of
well-measured reflections and crystal
decay was monitored during data col-
lection; no significant fluctuations in
intensity were observed. Structures
were solved by direct methods using
the SIR92 program[29] and refined by
least-squares procedures on F2 with
SHELXL-97.[30] All hydrogen atoms
Scheme 18. Preparation of the unsubstituted skipped octatriynediol diether 35.
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4905

R. Chauvin et al.
1,14-Bis(trimethylsilyl)-3,6,9,12-tetramethoxy-3,6,9,12-tetraphenyltetrade-
ca-1,4,7,10,13-pentayne (11a’):
A solution of pentayne 11a (131 mg,
0.18 mmol) in THF (5 mL) was treated with n-butyllithium (160 mL,
0.36 mmol) for 10 min at À788C. Iodomethane (120 mL, 1.8 mmol) was
added dropwise and the mixture was allowed to warm up to À258C.
DMSO (50 mL, 0.36 mmol) was added and stirring was continued for 1h
at À258C, then for 3 h at RT. After treatment with saturated aqueous
NH4Cl and extraction with Et2O, the organic layer was washed with
brine, dried with MgSO4, and concentrated under reduced pressure to
give crude 11a’ as a brown oil displaying satisfactory analytical data for
further use (127 mg, 95%). Rf ꢃ0.54 (heptane/acetone 7:3); 1H NMR
Scheme 19. Formation of hexaoxy[6]pericyclyne 3g with four adjacent
secondary carbinol vertices by [8+10] cyclization.
(CDCl3): d=0.22 (m, 18H; Si
7.35 (m, 12H; m-, p-CH), 7.73–7.76 ppm (m, 8H; o-CH); 13C{1H} NMR
(CDCl3): d=À0.44 (Si(CH3)3), 53.03 and 53.37 (OCH3), 71.79 and 71.92
(C(OMe)Ph), 83.60–84.99 ( C-COMe), 92.33 (C C-Si), 101.15 (C C-Si),
126.24–128.83 (o-, m-, p-CH), 139.48 ppm (ipso-C-C-OMe); IR (CDCl3):
(CH3)3), 3.47–3.58 (m, 12H; OCH3), 7.28–
AHCTREUNG
were located on a difference Fourier map, but introduced and refined by
using a riding model, except for OH hydrogen atoms, which were isotrop-
ically refined. All non-hydrogen atoms were anisotropically refined.
ꢀ
ꢀ
ꢀ
AHCTREUNG
À
À
À
ꢀ À
n˜ =3571(O H), 3065–2900 (C H), 2825 (OC H), 2069 (C C Si), 1601,
CCDC-638143 (17), CCDC-638145 (32), and CCDC-638144 (38) contain
the supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
À1
À
À
1490, 1450 (aromatic), 1251 (C Si), 1058 cm (C O).
3,12-Dimethoxy-3,6,9,12-tetraphenyltetradeca-1,4,7,10,13-pentayne-6,9-
diol (12a): A solution of pentayne 11a (10.60 g, 15 mmol) in methanol
(210 mL) was treated with potassium carbonate (1.02 g, 74 mmol) for 3 h
at RT. The solution was then filtered, concentrated under reduced pres-
sure, and diluted with Et2O. After extraction with water, the organic
layer was separated, dried with MgSO4, and evaporated to dryness. Pu-
rification by column chromatography on silica gel (hexane/EtOAc 6:4)
4-Methoxy-4-phenylhepta-2,5-diyne (7b): Compound 7a (4.08 g,
24 mmol) was dissolved in THF (50 mL) at À808C and nBuLi (19.2 mL,
48 mmol) was added. After stirring for 1h at À808C, iodomethane
(23.9 mL, 384 mmol) and DMSO (6.8 mL) were added. The solution was
allowed to warm up to RT, water was added, and the mixture extracted
in diethyl ether. The organic layer was separated, dried with MgSO4, and
evaporated to dryness to give crude 7b (3.62 g, 76%). 1H NMR
(250 MHz, CDCl3): d=1.95 (s, 3H; C-CH3), 3.43 (s, 3H; OCH3), 7.31–
7.40 (m, 3H; p-, m-CH), 7.70–7.77 ppm (m, 2H; o-CH); 13C{1H} NMR
(63 MHz, CDCl3): d=3.61(C- CH3), 53.22 (OCH3), 71.19 (COMe), 77.35,
gave 12a as a brown oil (5.60 g, 66%). Rf ꢃ0.39 (heptane/EtOAc 6:4);
1
ꢀ
H NMR (CDCl3): d=2.74 (m, 2H; C-H), 3.48 (m, 6H; OCH3), 3.64
(m, 2H; OH), 7.34–7.37 (m, 12H; m-, p-CH), 7.71–7.80 ppm (m, 8H; o-
CH); MS (DCI/NH3): m/z: 592 [M+NH4]+, 574 [M+NH4ÀH2O]+.
3,6,9,12-Tetramethoxy-3,6,9,12-tetraphenyltetradeca-1,4,7,10,13-pentayne
(12a’): A solution of pentayne 11a’ (127 mg, 0.17 mmol) in methanol
(5 mL) was treated with K2CO3 (117 mg, 0.85 mmol) for 3 h at RT. The
solution was then filtered, concentrated under reduced pressure, and di-
luted with Et2O. After treatment with water and extraction with Et2O,
the organic layers were combined, dried with MgSO4, and evaporated to
dryness. Purification by column chromatography on silica gel (hexane/
ꢀ
82.53 (C C), 126.31, 127.97, 128.18 (o-, m-, p-CH), 141.08 ppm (ipso-C);
MS (EI): m/z: 198 [M]+, 183 [MÀMe]+, 167 [MÀOMe]+.
6-Trimethylsilyl-4-phenyl-4-methoxyhexa-2,5-diynal (9): A solution of n-
butyllithium (2.5m in hexane, 8.26 mL, 20.6 mmol) was added through a
syringe to
a solution of 1-trimethylsilyl-3-phenyl-3-methoxypenta-1,4-
diyne (8) (5 g, 20.6 mmol) in THF (50 mL) at À408C. After stirring for
10 min, DMF (3.19 mL, 41.20 mmol, 2 equiv) was added and stirring was
continued at À408C for 15 min and then warmed to RT over 40 min. The
reaction mixture was poured into a mixture of diethyl ether (89 mL) and
aqueous 10% NaH2PO4 and 20% KCl (89 mL) at 08C. The organic layer
was separated and the aqueous layer extracted with diethyl ether. The
combined organic layers were washed with water and brine, dried with
MgSO4, and concentrated under reduced pressure. The product was iso-
lated as a brown oil and assigned to structure 9 on the basis of a NMR
analysis (6.294 g, quantitative). 1H NMR (CDCl3, 200 MHz): d=0.24 (s,
acetone 7:3) gave 12a’ as an orange oil (72 mg, 70%). Rf ꢃ0.25 (heptane/
1
ꢀ
acetone 8:2); H NMR (CDCl3): d=2.77 (s, 2H; C-H), 3.51–3.58 (m,
12H; OCH3), 7.34–7.39 (m, 12H; m-, p-CH), 7.74–7.79 ppm (m, 8H; o-
CH); 13C NMR (CDCl3): d=53.52 (q, JCH =142 Hz; OCH3), 71.93 (s; C-
1
(OMe)Ph), 75.66 (d, 1JCH =240 Hz; C-H), 80.81(d, 2JCH =50 Hz; C C-
ꢀ
ꢀ
ꢀ
H) 84.25–84.56 (m; C C), 125.84–129.75 (m; o-, m-, p-CH), 139.58 ppm
(s; ipso-C-C-OMe); IR (CDCl3): n˜ =3306 (C H), 3066–2903 (C H), 2827
(OC H), 2117 (C CH), 1600, 1490, 1450 (aromatic), 1068 cm (C O);
MS (DCI/NH3): m/z: 620 [M+NH4]+.
À
À
À1
À
ꢀ
À
9H; Si(CH3)3), 3.55 (s, 6H; OCH3), 7.36–7.44 (m, 3H, m-, p-CH), 7.72–
T
3,12-Dimethoxy-6,9-bis(trimethylsilyloxy)-3,6,9,12-tetraphenyltetradeca-
7.77 (m, 2H; o-CH), 9.28 ppm (s, 1H; CH(O)).
1,4,7,10,13-pentayne (13a):
A solution of pentayne 12a (2.10 g,
1,14-Bis(trimethylsilyl)-3,12-dimethoxy-3,6,9,12-tetraphenyltetradeca-
3.65 mmol) in THF (50 mL) was treated with n-butyllithium (3.40 mL,
7.48 mmol) for 10 min at À788C. Chlorotrimethylsilane (0.925 mL,
7.29 mmol) was then added dropwise and the solution was stirred for
30 min at À788C, then for 2 h 30 min at RT. After cooling back to
À788C, additional chlorotrimethylsilane (0.46 mL, 3.65 mmol) was added
to complete the reaction (TLC monitoring). The mixture was allowed to
warm up to RT and the stirring was continued for 1h at this temperature.
The solution was then concentrated to dryness and Et2O (30 mL) was
added, giving a white precipitate (LiCl). The solution was filtered, con-
centrated under reduced pressure, and the residue was purified by chro-
matography on silica gel (hexane/acetone 95:5) to afford 13a as a brown
oil (1.78 g, 68%). Rf ꢃ0.66 (heptane/EtOAc 7:3); 1H NMR (CDCl3): d=
ꢀ
1,4,7,10,13-pentayne-6,9-diol (11a):
A solution of diyne 8 (8.82 g,
36 mmol) in THF (300 mL) was treated with n-butyllithium (16.60 mL,
36 mmol) for 15 min at À788C. A solution of dibenzoylacetylene (10)
(4.26 g, 18 mmol) in THF (20 mL) was then added dropwise. After stir-
ring for 30 min at À788C, the mixture was allowed to warm up to RT
over 1.5 h and stirring was continued for another 30 min at this tempera-
ture. After treatment with saturated NH4Cl and extraction with Et2O, the
organic layer was washed with brine, dried with MgSO4, and evaporated
to dryness. The residue was then purified by chromatography through
silica gel (heptane/acetone 8:2) to afford 11a as a brown oil (10.60 g,
82%). Rf ꢃ0.52 (heptane/acetone 7.5:2.5); 1H NMR (CDCl3): d=0.25
(m, 18H; Si(CH3)3), 3.46–3.51(m, 6H; OC H3), 3.58 and 3.60 (2s, 2H;
R
0.19–0.24 (m, 18H; Si(CH3)3), 2.79 (m, 2H; CH), 3.53–3.56 (m, 6H;
OCH3), 7.36–7.40 (m, 12H; m-, p-CH), 7.74–7.79 ppm (m, 8H; o-CH);
A
OH), 7.33–7.36 (m, 12H; m-, p-CH), 7.73–7.75 ppm (m, 8H; o-CH).
13C{1H} NMR (CDCl3): d=À0.47 (Si
A
1
13C NMR (CDCl3): d=0.4 (q, 1JCH =139 Hz; Si
A
=
ꢀ
ꢀ
(C(OH)Ph), 71.3 (C(OMe)Ph), 80.9 (HOC-C C-COH), 84.6 (HOC-C
N
143 Hz; OCH3), 65.7 (s; C
C
C(OMe)Ph), 75.4 (d,
G
ꢀ
ꢀ
ꢀ
C-COMe), 87.7 ( C-COMe), 91.8 (C C-Si), 101.6 (C C-Si), 125.4–128.9
ꢀ
(o-, m-, p-CH), 139.4 (ipso-C-C-OMe), 142.4 ppm (ipso-C-C-OH); IR
ꢀ
À
À
À
ꢀ À
C C), 125.7–128.9 (m; o-, m-, p-CH), 139.7 (s; ipso-C-C-OMe), 142.9–
(CDCl3): n˜ =3571(O H), 3065–2901(C H), 2825 (OC H), 2069 (C C
143.0 ppm (s; ipso-C-C-OSiMe3); MS (DCI/NH3): m/z: 736 [M+NH4]+,
629 [MÀSiMe3O]+.
À1
À
À
Si), 1600, 1490, 1450 (aromatic), 1251 (C Si), 1060 cm (C O); MS
(DCI/NH3): m/z: 736 [M+NH4]+.
4906
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
By-product: 1,14-bis(trimethylsilyl)-3,12-dimethoxy-6,9-bis(trimethylsilyl-
10 min at À788C.
A
solution of dibenzoylacetylene (10) (2.5 g,
A
10.67 mmol) in THF (30 mL) was added dropwise and the mixture al-
lowed to warm up to À258C over a 3 h period. After cooling back to
À788C, iodomethane (5.3 mL, 85.13 mmol) was added and the mixture
allowed to warm up to À258C over 1h. DMSO (0.76 mL, 10.67 mmol)
was added and stirring was continued for 1h at À258C, then overnight
(17 h) at RT. After treatment with saturated NH4Cl and extraction with
Et2O, the organic layer was washed with brine, dried with MgSO4, and
concentrated to dryness. Purification of the residue by column chroma-
tography on silica gel (heptane/EtOAc 9:1) afforded 16 as an orange oil
(2.569 g, 46%). Rf ꢃ0.34 (heptane/EtOAc 8:2); 1H NMR (200 MHz,
Rf ꢃ0.80 (heptane/EtOAc 7:3); 1H NMR (CDCl3): d=0.20–0.28 (m,
36H; Si(CH3)3), 3.48–3.52 (m, 6H; OCH3), 7.31–7.36 (m, 12H; m-, p-
CH), 7.70–7.73 ppm (m, 8H; o-CH); 13C{1H} NMR (CDCl3): d=À 0.25,
1.45 (Si
ꢀ
ꢀ
82.9, 85.6, 86.9, 92.31( C C), 101.21 (C C-Si), 125.7–128.1 (o-, m-, p-CH),
139.9 (ipso-C-COMe), 143.1 ppm (ipso-C-COSiMe3); IR (CDCl3): n˜ =
À
À
ꢀ À
2960–2901(C H), 2825 (OC H), 2170 (C C Si), 1599, 1489, 1449 (aro-
matic), 1252 (C Si), 1066 cmÀ1 (C O); MS (DCI/NH3): m/z: 880
[M+NH4]+.
À
À
CDCl3): d=0.24 (s, 9H; Si(CH3)3), 3.53 (s, 3H; C(Ph)OCH3), 3.66 (s,
A
4,13-Dimethoxy-1,4,7,10,13,16-hexaphenylcyclooctadeca-2,5,8,11,14,17-
3H; C(An)OCH3), 3.80 (s, 3H; C6H4OCH3), 6.89 (d, 3JHH =8,46 Hz, 2H;
hexayn-1,7,10,16-tetrol (3a):
A solution of pentayne 12a (82 mg,
3
H-2 of 4-An), 7.41–7.85 (m, 10H; aromatic CH), 8.12 ppm (d, JHH
=
0.14 mmol) in THF (8 mL) was treated with n-butyllithium (0.26 mL,
0.56 mmol) for 30 min at À788C. A solution of dibenzoylacetylene (10)
(33 mg, 0.14 mmol) in THF (8 mL) was then added dropwise. The mix-
ture was stirred for 30 min at À788C and the mixture was allowed to
warm up to RT over a 2 h period. After treatment with saturated NH4Cl
and extraction with Et2O, the organic layer was washed with brine, dried
with MgSO4, and concentrated to dryness. Purification by column chro-
matography on silica gel (heptane/acetone 6:4) gave 3a as a brown oil
(49 mg, 39%). 1H NMR (CDCl3): d=3.35–3.39 (m, 6H; OCH3), 7.21–
6.98 Hz, 2H; o-H of Ph-C=O); 13C NMR (63 MHz, CDCl3): d=À0.24 (q,
1JCH =120 Hz; Si(CH3)3), 53.16, 53.88 (q, 1JCH =144 Hz; C(Ar)OCH3),
N
55.32 (q, 1JCH =144 Hz; C6H4-OCH3), 71.84, 73.41 (s; C(Ar)OMe),
1
ꢀ
101.21, 99.36, 89.91, 86.75, 83.24, 82.08 (s; C C), 113.73 (d, JCH =160 Hz;
C-2 of 4-An), 124.11–135.73 (m; aromatic C), 160.01 (s; C-1of 4-An),
177.15 ppm (s; C=O); IR (CDCl3): n˜ =3064, 3002, 2960, 2931, 2900 (C
À
À
H), 1646 (C=O), 1607, 1509, 1492, 1450, 1311 (aromatic), 1252 (C Si),
1063 cmÀ1 (C O); MS (DCI/NH3): m/z: 538 [M+NH4] , 521[ M+H] ,
489 [M+HÀMeOH]+; elemental analysis calcd (%) for C33H32O4Si: C
76.12, H 6.20; found: C 76.08, H 6.06.
+
+
À
7.31(m, 81H;
NMR (CDCl3): d=53.42 (OCH3), 64.98 ( C-C(OH)Ph-C ), 71.93 ( C-C-
m-, p-C6H5), 7.63–7.79 ppm (m, 12H; o-C6H5); 13C{1H}
ꢀ
ꢀ
ꢀ
3-(Trimethylsilyl)-1-(pyridin-4-yl)prop-2-yn-1-ol (18): After the treatment
of trimethylsilylacetylene (6.95 mL, 49.14 mmol) in THF (150 mL) with
EtMgBr (16.4 mL, 49.14 mmol) at 08C for 1h, a solution of pyridine-4-
carbaldehyde (4.7 mL, 49.14 mmol) in THF (100 mL) was added drop-
wise. After 1h at 0 8C, the mixture was warmed to RT and stirring was
continued for 15 min at this temperature. Saturated aqueous NH4Cl was
added and the mixture extracted with Et2O. The organic layer was
washed with brine, dried with MgSO4, and concentrated under reduced
pressure to give 18 as a pink powder (9.609 g, 95%). Rf ꢃ0.14 (heptane/
ꢀ
ꢀ
ACHTREUNG
À
À
À
n˜ =3570 (O H), 3000–2901(CC H), 2825 (OCC H), 1600, 1490 and
+
1449 (aromatic), 1067 cmÀ1 (C O); MS (DCI/NH3): m/z: 826 [M+NH4] .
À
4,7,10,13-Tetramethoxy-1,4,7,10,13,16-hexaphenylcyclooctadeca-
2,5,8,11,14,17-hexayn-1,16-diol (3a’):
A solution of pentayne 12a’
(248 mg, 0.41mmol) in THF (10 mL) was treated with n-butyllithium
(0.37 mL, 0.82 mmol) for 30 min at À788C. A solution of dibenzoylacety-
lene (10) (96 mg, 0.41mmol) in THF (8 mL) was then added dropwise.
The mixture was stirred for another 30 min at À788C, and the mixture
was allowed to warm up to RT over a 2 h period. After treatment with
saturated NH4Cl and extraction with Et2O, the organic layer was washed
with brine, dried with MgSO4, and concentrated to dryness. Purification
of the residue by column chromatography on silica gel (heptane/acetone
7:3) gave 3a’ as a brown oil (133 mg, 40%). Rf ꢃ0.25 (heptane/acetone
7:3); 1H NMR (CDCl3): d=3.07–3.13 (m, 2H; OH), 3.34–3.63 (m, 12H;
OCH3), 7.30–7.36 (m, 18H; m-, p-CH), 7.65–7.83 ppm (m, 12H; o-CH);
13C{1H} NMR (CDCl3): d=53.29 (OCH3), 64.86 (C(OH)Ph), 71.79 (C-
ꢀ
EtOAc (6:4)+1% MeOH); 1H NMR (200 MHz, CDCl3): d=0.15 (s,
3
9H; Si
C
=
Py); 13C NMR (63 MHz, CDCl3): d=À0.28 (q, 1JCH =120 Hz; Si
A
62.77 (d, 1JCH =146 Hz; CH(OH)), 91.26 (s; C CSi), 104.57 (s; C C-Si),
ꢀ
ꢀ
121.49 (d, 1JCH =164 Hz; C-3 of 4-Py), 149.07 (d, 1JCH =190 Hz; C-2 of 4-
À
Py), 153.04 ppm (s; C-4 of 4-Py); IR (CDCl3): n˜ =3595 (O H), 3081,
À
ꢀ
2960, 2900 (C H), 2175 (C CSi), 1601, 1558, 1493, 1411, 1335 (aromatic),
À1
+
À
À
1252 (C Si), 1044 cm (C O); MS (DCI/NH3): m/z: 206 [M+H] , 1 51
[M+NH4ÀSiMe3+H]+, 134 [M+HÀSiMe3+H]+.
A
3-(Trimethylsilyl)-1-(pyridin-4-yl)prop-2-yn-1-one (19)
À
(ipso-C-C-OMe), 140.51 ppm (ipso-C-C-OH); IR (CDCl3): n˜ =3571(O
À
À
Method 1: A solution of Dess–Martin periodinane (254 mg, 0.60 mmol) in
CH2Cl2 (10 mL) was added dropwise to a solution of alcohol 18 (98 mg,
0.48 mmol) in CH2Cl2 (4 mL). After stirring for 30 min at RT, the reac-
tion mixture was concentrated to 2 mL under reduce pressure, diluted
with Et2O (15 mL), and filtered before treatment with saturated
NaHCO3. The organic layer was then washed with brine, dried with
MgSO4, and concentrated under reduced pressure. Purification of the res-
idue by column chromatography on silica gel (heptane/EtOAc (6:4)+
1% MeOH) gave 19 as a yellow oil (8 mg, 8%).
H), 3065–2901(C H), 2826 (OC H), 1599, 1490, 1450 (aromatic),
+
1070 cmÀ1 (C O); MS (DCI/NH3): m/z: 854 [M+NH4] .
À
4-Hydroxy-7-methoxy-7-(4-methoxyphenyl)-9-(trimethylsilyl)-1,4-diphe-
nylnona-2,5,8-triyn-1-one (15b):
A solution of diyne 14 (150 mg,
0.55 mmol) in THF (2 mL) was treated with n-butyllithium (220 mL,
0.55 mmol) for 10 min at À788C. A solution of dibenzoylacetylene (10)
(129 mg, 0.55 mmol) in THF (5 mL) was added dropwise and stirring was
continued for 30 min at À788C. The mixture was then allowed to warm
up to RT over a 1.5 h period. The reaction mixture was concentrated to
2 mL and directly deposited onto a preparative silica gel TLC plate for
purification. After elution with a heptane/EtOAc mixture (8:2), subse-
quent extraction with Et2O, filtration, and evaporation gave 15b as an
orange oil (129 mg, 45%). Rf ꢃ0.50 (heptane/EtOAc 8:2); 1H NMR
Method 2: Activated MnO2 (34 g, 395 mmol) was added to a solution of
alcohol 18 (5.409 g, 26.3 mmol) in CH2Cl2 (200 mL). After stirring for 2 h
at RT, the reaction mixture was filtered through a small pad of Celite
and evaporated to dryness to give 19 as a yellow oil (4.536 g, 85%).
(200 MHz, CDCl3): d=0.24 (s, 9H; Si(CH3)3), 3.49 (s, 3H; CH3O-C-An),
T
Common analytical data: Rf ꢃ0.32 (heptane/EtOAc (6:4)+1% MeOH);
3.79 (s, 3H; CH3O-C6H4), 6.88 (d, 3JHH =9.1Hz, 2H; H-2 of An), 8.08–
8.54 (m, 10H; Har), 8.78 ppm (d, 3JHH =8.5 Hz, 2H; o-CH of Ph-C=O);
1H NMR (200 MHz, CDCl3): d=0.31(s, 9H; Si
A
=
3
6.06 Hz, 2H; H-3 of 4-Py), 8.84 ppm (d, 3JHH =6.06 Hz, 2H; H-2 of 4-
13C{1H} NMR (63 MHz, CDCl3): d=À0.24 (Si
G
Py); 13C NMR (63 MHz, CDCl3): d=À0.81(q, 1JCH =122 Hz; Si
A
99.78 (s; C CSi), 103.20 (s; C C-Si), 122.03 (d, 1JCH =164 Hz; C-3 of 4-
ꢀ
ꢀ
(C(Ph)OCH3),
55.33
(C6H4OCH3),
65.84
Py), 141.93 (s; C-4 of 4-Py), 150.89 (d, 1JCH =182 Hz; C-2 of 4-Py),
ꢀ
ꢀ
(C(An)OMe), 81.50, 84.50, 92.24, 92.50 (C C), 91.73 ( C-C=O), 101.12
ꢀ
À
ꢀ
( C-Si), 113.73 (C-2 of 4-An), 124.11–135.73 (aromatic C), 160.00 (C-1of
176.82 ppm (s; C=O); IR (CDCl3): n˜ =2963, 2920, 2852 (C H), 2155 (C
4-An), 177.51 ppm (C=O); MS (DCI/NH3): m/z: 475 [M+HÀMeOH]+.
CSi), 1651 (C=O), 1601, 1559, 1487, 1409, 1324 (aromatic), 1255 cmÀ1 (C
Si); MS (DCI/NH3): m/z: 221[ M+NH4]+, 204 [M+H]+.
À
4,7-Dimethoxy-7-(4-methoxyphenyl)-9-(trimethylsilyl)-1,4-diphenylnona-
2,5,8-triyn-1-one (16): A solution of diyne 14 (2.907 g, 10.67 mmol) in
THF (25 mL) was treated with n-butyllithium (4.27 mL, 10.67 mmol) for
1-(Trimethylsilyl)-3-(pyridin-4-yl)penta-1,4-diyn-3-ol (17): A saturated so-
lution of acetylene in THF (200 mL) at 08C was treated with EtMgBr
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4907

R. Chauvin et al.
ꢀ
(27 mL, 81mmol) for 1h at 0 8C and then pyridyl ketone 19 (8.15 g,
40 mmol) in THF (150 mL) was added dropwise. After stirring for 1 h at
08C, the reaction mixture was warmed to RT and stirring was continued
overnight (17 h) at this temperature. A saturated aqueous NH4Cl solution
was added and the mixture extracted with Et2O. The organic layer was
separated, washed with brine, dried with MgSO4, and concentrated under
reduced pressure to give 17 as a brown solid (8.343 g, 91%). M.p.
176.98C; Rf ꢃ0.13 (heptane/EtOAc (6:4)+1% MeOH); 1H NMR
ꢀ
CDCl3): d=0.20 (s, 18H; OSi
N
H-2 of 4-An), 7.31–7.74 (m, 14H; aromatic CH), 8.57 ppm (d, JHH
4.68 Hz, 2H; H-2 of Py); 13C NMR (63 MHz, CDCl3): d=1.35 (q, JCH
119 Hz; OSi
(CH3)3), 53.25, 53.53 (q, 1JCH =143 Hz; CH3O-C-Ar), 55.32
(q, 1JCH =144 Hz; OCH3O-C6H4), 64.53, 65.65 (s; Ar-C-OSi), 71.31, 71.93
(s; Ar-C-OMe), 74.54, 75.15 (d, JCH =253 Hz; C-H), 87.09, 86.41, 84.82,
84.06, 83.62, 82.95, 82.80, 80.83 (s; C-C C), 113.73 (d, 1JCH =156 Hz; C-2
(200 MHz, CD3OD): d=0.28 (s, 9H; Si
N
of 4-An), 120.34 (d, 1JCH =165 Hz; C-3 of 4-Py), 125.59–131.82 (m; aro-
matic CH), 139.62, 142.47, 142.60 (s; ipso-C of Ar=Ph, An), 149.93 (d,
1JCH =191 Hz; C-2 of 4-Py), 151.69 (s; C-4 of 4-Py), 160.03 ppm (s; C-1of
3JHH =6.27 Hz, 2H; H-2 of 4-Py); 13C NMR (63 MHz, CD3OD): d=
1
À0.99 (q, 1JCH =120 Hz; Si
G
=
4-An); IR (CDCl3): n˜ =3305 ( C H), 3062, 3026, 2958 (C H), 2826
(OC H), 1608, 1595, 1510, 1489, 1449, 1311 (aromatic), 1253 (C Si), 1175
(C OMe), 1067 cm (C OSi); MS (DCI/NH3): m/z: 750 [M+H] , 71 8
2
ꢀ
À
254 Hz; C C-H), 83.70 (d, JCH =51Hz; C CH), 89.90 (s; C CSi), 104.86
1
À1
(s; C C-Si), 121.65 (d, 1JCH =166 Hz; C-3 of 4-Py), 149.74 (d, JCH
=
ꢀ
À
À
191 Hz; C-2 of 4-Py), 153.48 ppm (s; C-4 of 4-Py); IR (CD3OD): n˜ =
[M+HÀMeOH]+,
678
646
3600–3100 (O H), 3309 ( C H), 2964 and 2903 (C H), 1601, 1564, 1480,
Me3+HÀMeOH]+, 606 [M+H+2HÀ2SiMe3]+.
À
ꢀ À
À
1413, 1327 (aromatic), 1253 cmÀ1 (C Si); MS (DCI/NH3): m/z: 230
À
13,16-Dimethoxy-13-(4-methoxyphenyl)-1,7,10,16-tetraphenyl-4-(pyridin-
4-yl)cyclooctadeca-2,5,8,11,14,17-hexayne-1,4,7,10-tetrol (3b)
[M+H]+.
Single crystals deposited from a chloroform solution were submitted to
an X-ray diffraction study, which confirmed the molecular structure
(Figure 2, Table 1).
Step 1: A solution of hexamethyldisilazane (0.354 mL, 1.68 mmol) in
THF (5 mL) was treated with n-butyllithium (1.16 mL, 1.68 mmol) for
25 min at À788C. A solution of pentayne 20b (300 mg, 0.4 mmol) in THF
(150 mL) was then added dropwise and the mixture was allowed to warm
up to À408C over a 45 min period. After warming up quickly to À208C,
the stirring was continued for 1h 30 min at À208C. After cooling back to
À788C, a solution of dibenzoylacetylene (10) (94 mg, 0.4 mmol) in THF
(15 mL) was added dropwise and the mixture was allowed to warm up to
RT over a 1h period. The stirring was continued overnight (17 h) at this
temperature. After treatment with a saturated NH4Cl solution and ex-
traction with Et2O, the organic layer was washed with brine, dried with
MgSO4, and concentrated under reduced pressure to give a brown oil
(439 mg, corresponding to a quantitative formal yield based on the ex-
pected bis-O-silylated hexaoxy[6]pericyclyne, but integrated 1H NMR
analysis suggested that partial desilylation occurred).
9,12-Dimethoxy-12-(4-methoxyphenyl)-6,9-diphenyl-3-(pyridin-4-yl)tetra-
deca-1,4,7,10,13-pentayne-3,6-diol (20a)
Step 1: A solution of pyridyl diyne 17 (4.003 g, 17.5 mmol) in THF
(50 mL) was treated with n-butyllithium (14 mL, 35 mmol) for 20 min at
À208C. A solution of triynone 16 (9.089 g, 17.5 mmol) in THF (30 mL)
was added dropwise and stirring was continued for 2 h at À208C, then
for 2 h at RT. After treatment with a saturated NH4Cl solution and ex-
traction with Et2O, the organic layer was washed with brine, dried with
MgSO4, and concentrated under reduced pressure to give a brown oil
(13.507 g, quantitative crude yield based on the expected 1,4-bis(trime-
thylsilyl) pentayne).
Step 2: A solution of the just obtained crude oil (13.507 g) in THF
(150 mL) was treated with a nBu4NF solution (THF, 36 mL, 36 mmol) for
10 min at À788C. The mixture was allowed to warm up to RT over a 3 h
period. The solution was then diluted with Et2O (50 mL) before water
was added. The organic layer was extracted with Et2O, dried with
MgSO4, and concentrated under reduced pressure. The residue was puri-
fied by column chromatography on silica gel (heptane/EtOAc (6:4)+1%
MeOH) to give 20a as a brown solid (8.131 g, 77% for the two steps). Rf
ꢃ0.14 (heptane/EtOAc (6:4)+1% MeOH); 1H NMR (250 MHz,
Step 2: A solution of the aforementioned brown oil (439 mg, 0.45 mmol)
in THF (40 mL) was treated with a solution of nBu4NF (THF, 1.11 mL,
1.11 mmol) for 10 min at À788C and the mixture was allowed to warm
up to RT over a 3 h period. The solution was then diluted with Et2O
(20 mL) before water was added. The organic layer was separated, dried
with MgSO4, concentrated under reduced pressure, and the residue puri-
fied by column chromatography on silica gel (heptane/EtOAc 4:6) to
afford 3b as a brown solid (47 mg, 14% over the two steps). Rf ꢃ0.53
(EtOAc); 1H NMR (400 MHz, CDCl3): d=3.19–3.43 (m, 6H; CH3O-C-
Ar), 3.60–3.76 (m, 3H, CH3O-C6H4), 6.65–6.77 (m, 2H; H-2 of An),
7.00–7.35, 7.39–7.80 (m, 24H; aromatic CH), 7.90–8.15 ppm (m, 2H; H-2
of 4-Py); 13C{1H} NMR (100 MHz, CDCl3; see Figure 3b): d=53.31, 53.79
(CH3O-C-Ar), 55.76 (CH3O-C6H4), 63.70, 64.09, 64.47, 64.87 (Ar-C-OH),
ꢀ
ꢀ
CDCl3): d=2.69 (s, 1H; An-C-C C-H), 2.76 (s, 1H; Py-C-C C-H), 3.44
(m, 6H; CH3O-C-Ar), 3.74 (s, 3H, CH3O-C6H4), 6.82 (d, 3JHH =8.57 Hz,
3
2H; H-2 of 4-An), 7.25–7.75 (m, 14H; aromatic CH), 8.27 ppm (d, JHH
=
4.78 Hz, 2H; H-2 of 4-Py); 13C NMR (63 MHz, CDCl3; see Figure 3a):
d=53.34, 53.58 (q, 1JCH =143 Hz; CH3O-C-Ar), 55.51(q, 1JCH =144 Hz;
CH3O-C6H4), 63.48, 64.53 (s; Ar-C-OH), 71.37, 72.03 (s; Ar-C-OMe),
ꢀ
71.96, 72.35 (Ar-C-OMe), 80.85–88.06 (C-C C-C), 114.18 (C-2 of 4-An),
74.50 (d, 1JCH =255 Hz; An-C-C C-H), 75.49 (d, 1JCH =254 Hz; Py-C-C
121.23 (C-3 of 4-Py), 126.28–129.53 (m; aromatic CH), 139.65–141.51
(ipso-C of An and Ph), 149.07 (C-2 of 4-Py), 151.50 (C-4 of 4-Py),
ꢀ
ꢀ
ꢀ
C-H), 87.73, 86.22, 84.90, 84.07, 83.50, 82.27, 82.05, 80.91(s; C- C C),
1
1
À
160.28 ppm (s; C-4 of 4-An); IR (CDCl3): n˜ =3390 (O H), 3066, 2934
113.94 (d, JCH =165 Hz; C-2 of 4-An), 120.92 (d, JCH =166 Hz; C-3 of 4-
Py), 124.63–130.61 (m; aromatic CH), 139.62, 141.22, 141.33 (s; ipso-C of
Ar=Ph, An), 149.00 (d, 1JCH =181 Hz; C-2 of 4-Py), 151.09 (s; C-4 of 4-
À
À
ꢀ
(C H), 2825 (OC H), 2048 (C C), 1602, 1509, 1490, 1450, 1312 (aro-
À1
À
À
matic), 1175 (C OMe), 1067 cm (C OH); MS (DCI/NH3): m/z: 840
[M+H]+, 808 [M+HÀMeOH]+.
À
ꢀ
Py), 160.14 ppm (s; C-1of 4-An); IR (CDCl 3): n˜ =3571(O H), 3304 (
À
À
À
C H), 3064, 2958, 2935 (C H), 2825 (OC H), 1602, 1510, 1490, 1450,
1,14-Bis(trimethylsilyl)-6,9-dimethoxy-6,9-diphenyltetradeca-1,4,7,10,13-
pentayne-3,12-diol (23a)
À1
À
À
À
1311 (aromatic), 1253 (C Si), 1175 (C OMe), 1068 cm (C OH); MS
(DCI/NH3): m/z: 606 [M+H]+, 574 [M+HÀMeOH]+.
From trimethylsilylacetylenelithium: A solution of n-butyllithium (2.5m in
hexane 0.82 mL, 1.2 mmol) was added through a syringe to a solution of
trimethylsilylacetylene (0.17 mL, 1.2 mmol) in THF (10 mL) at À808C.
After stirring for 40 min at À808C, then for 30 min at RT, a solution of
dialdehyde 22 (719 mg, 0.59 mmol) in THF (5 mL) was added. The mix-
ture was then stirred for 1h as it was warmed from À808C to RT. Diethyl
ether was added. The organic layer was then washed with a saturated
aqueous solution of NH4Cl and extracted with diethyl ether. The organic
layer was separated, washed with a saturated aqueous NH4Cl solution,
dried with MgSO4, and concentrated. The residue was purified by chro-
matography on silica gel (heptane/EtOAc 8:2). The product 23a was iso-
lated as an orange oil (144 mg, 43%) and was characterized by NMR
spectroscopy (see below).
4-[9,12-Dimethoxy-12-(4-methoxyphenyl)-6,9-diphenyl-3,6-bis(trimethyl-
silyloxy)tetradeca-1,4,7,10,13-pentayn-3-yl)pyridine (20b): A solution of
pentayne 20a (3.99 g, 6.59 mmol) in THF (30 mL) was treated with n-bu-
tyllithium (5.27 mL, 13.18 mmol) for 15 min at À788C and chlorotrime-
thylsilane (1.67 mL, 13.18 mmol) was then added dropwise. The mixture
was allowed to warm up to RT over a 1h 30 min period and the stirring
was continued for 30 min at this temperature. The solution was then con-
centrated to dryness and diluted in Et2O (30 mL). The white precipitate
formed (LiCl) was filtered and the solution concentrated under reduced
pressure. Purification by column chromatography on silica gel (heptane/
EtOAc (7:3)+1% MeOH) gave 20b as an orange oil (2.621g, 53%). Rf
ꢃ0.29 (heptane/EtOAc (7:3)+1% MeOH); 1H NMR (250 MHz,
4908
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
From trimethylsilylacetylenemagnesium bromide: A solution of trimethyl-
silylacetylene (1.6 mL, 5.6 mmol) in THF (50 mL) was treated with
EtMgBr (3.77 mL, 11.3 mmol) at 08C for 1h and then dialdehyde 22
(2.094 g, 5.6 mmol) dissolved in THF (30 mL) was added dropwise. Stir-
ring was continued for 1h at 0 8C, then for 2 h at RT. After addition of a
saturated aqueous NH4Cl solution and extraction with Et2O, the organic
layer was washed with brine, dried with MgSO4, and concentrated under
reduced pressure to give 23a as an orange oil (2.51g, 79%). The crude
product displayed satisfactory spectroscopic purity to be used as such in
the next step. Rf ꢃ0.41(heptane/EtOAc 5:5); 1H NMR (250 MHz,
3,12-Bis(tetrahydropyran-2-yloxy)-6,9-diphenyl-6,9-dimethoxytetradeca-
1,4,7,10,13-pentayne (23b’’): p-Toluenesulfonic acid (3 mg, 5.2”
10À3 mmol) was added to
a solution of pentaynediol 23b (179 mg,
0.13 mmol) and dihydropyran (77 mL, 0.26 mmol) in toluene (15 mL).
After stirring for 15 h at RT, the mixture was concentrated in vacuo and
the reaction quenched with one drop of triethylamine. Diethyl ether
(50 mL) and water (50 mL) were added. The organic layer was separated,
again washed with water, dried with MgSO4, and concentrated. The resi-
due was purified by chromatography on silica gel (heptane/EtOAc 8:2).
The product 23b’’ was isolated as an orange oil (47%). 1H NMR
4
(200 MHz, CDCl3): d=1.49–1.85 (m, 12H; CH2), 2.52, 2.56 (2d, JHH
=
CDCl3): d=0.18 (s, 18H; Si(CH3)3), 2.50 (s, 2H; OH), 3.52 (s, 6H;
G
ꢀ À
2.3 Hz, 2H; C H), 3.46–3.55 (s, 8H; OCH3 +CHH-O THP), 3.80–3.89
(m, 2H; CHH-O THP), 4.95–5.00 (m, 2H; CHO2 THP), 5.30, 5.32 (2d,
4JHH =2.3 Hz, 2H; CH-OTHP), 7.35–7.39 (m, 6H; p-, m-CH), 7.70–
7.78 ppm (m, 4H; m-CH); 13C{1H} NMR (60 MHz, CDCl3): d=15.09,
25.22, 29.91(C- CH2-C THP), 53.47 (OCH3), 54.39, 54.69 (CH-OTHP),
OCH3), 5.20 (s, 2H; CH(OH)), 7.35–7.41(m, 6H; m-, p-CH), 7.71–
7.76 ppm (m, 4H; o-CH); 13C{1H} NMR (63 MHz, CDCl3): d=À0.54 (Si-
A
ꢀ
ꢀ
ꢀ
90.01(C- C C-C), 90.92 (C C-Si), 101.01 ( C-Si), 126.43, 128.31 (o-, m-
À
CH), 128.88 (p-CH), 139.24 ppm (ipso-Ci); IR (CDCl3): n˜ =3585 (O H),
ꢀ À
61.93, 62.05 (CH2O THP), 71.82 (CPhOMe), 73.21, 73.62 ( C H), 78.52
À
À
ꢀ
3066, 3032, 2998, 2961, 2935, 2901 (C H), 2827 (OC H), 2179 (C CSi),
ꢀ
ꢀ
À1
(C CH), 81.45, 82.02, 82.24, 82.51, 84.25 (C-C C-C), 95.51, 95.89 (CHO2
À
À
1600, 1490, 1450, 1410 (aromatic), 1252 (C Si), 1063 cm (C O); MS
(DCI/NH3): m/z: 584 [M+NH4]+.
THP), 126.55, 126.63, 128.43, 128.93 (o-, m-CH), 128.93, 128.97 (p-CH),
139.54 ppm (ipso-C); IR (CDCl3): n˜ =3307 (spC H), 3066 (sp C H),
2
À
À
3,6,9,12-Tetramethoxy-6,9-diphenyltetradeca-1,4,7,10,13-pentayne (23b’)
3
À
À
ꢀ
2949(sp C H), 2827 (OC H), 2124 (C C), 1600, 1490, 1450 (aromatic),
A
1442, 1312, 1286, 1227, 1202, 1185, 1117, 1066 (C O), 1016 cmÀ1; MS
(DCI/NH3): m/z: 608 [M+NH4]+, 572 [MÀ2H2O+NH4]+, 559
[M+HÀMeOH]+, 524 [MÀDHPOH+NH4]+, 475 [MÀTHPOHÀ
MeOH+NH4]+.
Prepared via 1,14-bis(trimethylsilyl)-3,6,9,12-tetramethoxy-6,9-diphenylte-
tradeca-1,4,7,10,13-pentayne (23a’): A solution of n-butyllithium (2.5m in
hexane, 0.64 mL, 1.60 mmol) was added through a syringe to a solution
of pentaynediol 23a (454 mg, 0.80 mmol) and diethyl ether (6 mL) at
À808C. After stirring for 1min, methyl triflate (346 mL, 3.2 mmol) was
added, the mixture was allowed to warm up to À108C, and then stirred
between À10 and 08C over 15 h (CAUTION: above 08C, degradation
occurs). The mixture was then poured into a saturated aqueous K2CO3
solution and diethyl ether was added. The organic layer was separated,
washed again with saturated aqueous K2CO3, dried with MgSO4, and con-
centrated to give a crude product, assigned to the fragile structure 23a’,
as a dark oil. In order to avoid degradation, the crude material was used
in the next step.
À
6,9-Dimethoxy-1,14-bis(trimethylsilyl)-6,9-diphenyltetradeca-1,4,7,10,13-
pentayne-3,12-dione (24a): Manganese oxide (5.77 g, 66.4 mmol) was
added to a solution of crude pentayne 23a (2.51g, 4.4 mmol) in CH 2Cl2
(50 mL). After stirring at 08C for 1h, the mixture was allowed to warm
up to RT and stirring was continued for 1h. The solution was then fil-
tered and concentrated under reduced pressure to give 24a as a yellow
oil (2.13 g, 86%).
Rf ꢃ0.56 (heptane/EtOAc 8:2); 1H NMR (200 MHz, CDCl3): d=0.26 (s,
1 8 H; S(iCH3)3), 3.57 (s, 6H; OCH3), 7.39–7.43 (m, 6H; m-, p-CH),
C
7.70 ppm (m, 4H; o-CH); 13C NMR (63 MHz, CDCl3): d=À0.99 (q,
The crude diether 23a’ was dissolved in THF (8 mL) at À808C and a so-
lution of TBAF (1m in THF, 1.60 mL, 1.60 mmol) was added. After stir-
ring for 5 min at À808C, the mixture was poured into a mixture of water
and diethyl ether. The organic layer was separated, washed with water,
dried with MgSO4, and concentrated to give 23b’ as a dark oil. This sensi-
1JCH =124 Hz; Si(CH3)3), 53.91(q, 1JCH =144 Hz; OCH3), 71.91 (s; Ph-C-
T
ꢀ
ꢀ
OMe), 84.06 (s; PhC-C C-CPh), 85.28 (s; O=C-C C-CPh), 87.39 (s; O=
ꢀ
ꢀ
ꢀ
C-C C-CPh), 101.15 (s; O=C-C C-Si), 102.18 (s; C C-Si), 126.46 (d,
1JCH =168 Hz; m- or o-CH), 128.76 (d, 1JCH =159 Hz; o- or m-CH),
129.57 (d, JCH =161 Hz; p-CH), 137.99 (s; ipso-C), 159.55 ppm (s; C=O);
1
tive product was analyzed without further purification (338 mg, 94%
1
ꢀ
crude yield). H NMR (200 MHz, CDCl3): d=2.56 (s br., 2H; CH), 3.44
À
À
ꢀ
IR (CDCl3): n˜ =3066, 2961, 2935, 3903 (C H), 2829 (OC H), 2154 (C
(m, 6H; CHOCH3), 3.54 (m, 6H; CPhOCH3), 5.09 (m, 2H; CHOMe),
7.36–7.41(m, 6H; m-, p-CH), 7.72–7.76 ppm (m, 4H; o-CH); 13C{1H}
NMR (50 MHz, CDCl3): d=53.30, 54.39 (CPhOCH3 +CHOCH3), 59.36
À
CC(O)), 1634 (C=O), 1490, 1451, 1422 (aromatic), 1254 (C Si),
1070 cmÀ1 (C O); MS (DCI/NH3): m/z: 580 [M+NH4]+, 531
À
[M+HÀMeOH]+,
Me3+HÀMeOH]+,
508
[M+HÀSiMe3+NH4]+,
459
[M+HÀSi-
436
[M+H2À2SiMe3+NH4]+,
387
ꢀ À
ꢀ
(CHOMe), 67.78 (CPhOMe), 71.64 ( C H), 77.71( C CH), 81.44, 82.64,
[M+H2À2SiMe3+HÀMeOH]+.
ꢀ
84.18 (C-C C-C), 126.34, 128.30 (o-, m-CH), 128.85 (p-CH), 139.27 ppm
2
3
À
À
À
(ipso-C); IR (CDCl3): n˜ =3306 (spC H), 3065 (sp C H), 2934 (sp C H),
3,12-Dioxo-6,9-dimethoxy-6,9-diphenyltetradeca-1,4,7,10,13-pentayne
(24b): MnO2 (330 mg, 3.8 mmol) was added to a solution of pentayne
23b (107 mg, 0.25 mmol) in CH2Cl2 (20 mL) at 08C. After stirring for
10 min at 08C and then for 2 h at RT, the mixture was filtered through a
small pad of Celite, washed with ethyl acetate, and concentrated. The
dark oily residue was purified by chromatography on silica gel (heptane/
EtOAc 8:2, then 5:5) to afford a product assigned to structure 24b ac-
cording to NMR analysis (29 mg, 28%). 1H NMR (200 MHz, CDCl3):
ꢀ
À1
ꢀ
2122 (C C), 1654, 1490, 1450 cm (aromatic); MS (DCI/NH3): m/z: 468
[M+NH4]+, 436 [M+NH4ÀMeOH]+, 41 9 M[+HÀMeOH]+, 404
[M+NH4À2MeOH]+.
6,9-Diphenyl-6,9-dimethoxytetradeca-1,4,7,10,13-pentayne-3,12-diol
(23b):
A solution of ethynylmagnesium bromide (0.5m, 3.16 mL,
1.58 mmol) was added through a syringe to a solution of dialdehyde 22
(146 mg, 0.40 mmol) in diethyl ether (10 mL) at 08C. After stirring for
15 min at 08C, then for 1.5 h at RT, the mixture was poured into a mix-
ture of aqueous saturated NH4Cl and diethyl ether. The organic layer
was separated, washed with a saturated aqueous NH4Cl solution, dried
d=3.41(s, 2H;
C-H), 3.57 (s, 6H; OCH3), 7.36–7.43 (m, 6H; m-, p-
CH), 7.67–7.72 ppm (m, 4H; o-CH).
3,12-Diethynyl-6,9-dimethoxy-1,14-bis(trimethylsilyl)-6,9-diphenyltetrade-
ca-1,4,7,10,13-pentayne-3,12-diol (25): A solution of ethynylmagnesium
bromide (1.42 mL, 0.71 mmol) was added dropwise to a solution of crude
dione 24a (100 mg, 0.18 mmol) in THF (10 mL) at 08C. After stirring for
1 h at 08C and for 3 h at RT, the solution was treated with a saturated
NH4Cl solution. The organic layer was extracted with Et2O, washed with
brine, dried with MgSO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (heptane/
EtOAc 8:2) to give 25 as an orange oil (80 mg, 71%). Rf ꢃ0.25 (heptane/
with MgSO4, filtered, and concentrated to give 23b as an orange oil
1
ꢀ
(161 mg, 97%). H NMR (200 MHz, CDCl3): d=2.55 (s, 2H; CH), 3.50
(s, 6H; OCH3), 3.60 (s, 2H; OH), 5.18 (s, 2H; CH-OH), 7.34–7.40 (m,
6H; p-, m-CH), 7.70–7.74 ppm (m, 4H; o-CH); 13C{1H} NMR (60 MHz,
ꢀ À
CDCl3): d=51.85, 53.44 (OCH3 +CHOH), 71.82 (CPhOMe), 73.35 ( C
ꢀ
ꢀ
H), 80.18 (C CH), 81.46, 83.99–84.39 (C-C C-C), 126.57, 128.57 (o-, m-
À
CH), 129.13 (p-CH), 139.17 ppm (ipso-C); IR (CDCl3): n˜ =3585 (free O
À
À
À
À
H), 3408 (bound O H), 3306 (spC H), 3089–2903 (C H), 2827 (OC H),
EtOAc 7:3); 1H NMR (200 MHz, CDCl3): d=0.20 (s, 18 H; Si
(CH3)3),
G
ꢀ
2126 (C C), 1600, 1490, 1450 (aromatic), 1375, 1294, 1227, 1179, 1144,
1064 (C O), 1029 cmÀ1
;
MS (DCI/NH3): m/z: 440 [M+NH4+]), 408
2.68 (s, 2H; C C-H), 3.21(s, 2H; O H), 3.54 (s, 6H; OCH3), 7.35–7.39
À
ꢀ
[MÀMeOH+NH4]+, 391[ M+HÀMeOH]+, 376 [MÀ2MeOH+NH4]+.
(m, 6H; m-, p-CH), 7.71–7.77 ppm (m, 4H; o-C6H5); 13C NMR (63 MHz,
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4909

R. Chauvin et al.
CDCl3): d=À0.53 (q, 1JCH =121 Hz; Si
U
NMR (CDCl3): d=À0.08–0.31(m, 81H; Si
OCH3), 5.62–5.67 (m, 2H; CH(OH)), 7.27–7.41(m, 21H;
7.63–7.79 ppm (m, 8H; o-CH); 13C{1H} NMR (CDCl3): d=1.3 (Si
53.3 (OCH3), 63.6 (CH(OH)), 65.9 (CPh(OSiMe3)), 71.9 (CPh(OMe)),
ACHTREUNG
H), 79.97, 80.02 (2s; C-C C-C), 80.50 (d, 2JCH =57 Hz; C CH), 84.34 (s;
ꢀ
ACHTREUNG
C-C C-C), 89.09 (s; C CSi), 100.37 (C C-Si), 126.66 (d, 1JCH =167 Hz;
ꢀ
ꢀ
G
ACHTREUNG
m- or o-CH), 128.50 (d, 1JCH =165 Hz; o- or m-CH), 129.10 (d, JCH
ꢀ
82.17, 83.64, 85.87, 88.06, 93.88 (C C), 125.7–128.9 (o-, m-, p-CH), 139.5
161 Hz; p-CH), 139.15 ppm (s; ipso-C); IR (CDCl3): n˜ =3569 (O H),
ꢀ
(ipso-C-C-OMe), 142.5 (ipso-C-C-OSiMe3), 198.5 ppm (C O); IR
À
3306, 2961, 2931, 2900 (C H), 2825 (OC H), 2128 (C C), 1490, 1451,
À
À
ꢀ
(CDCl3): n˜ =2960–2901(C H), 2820 (OC H), 2100, 2065, 2037 (C O),
À1
À1
À
1408 (aromatic), 1252 (C Si), 1068 cm (C O); MS (DCI/NH3): m/z:
À
À
1559, 1489, 1449 (aromatic), 1253 (C Si), 1070 cm (C O); MS (ES, neg-
632 [M+NH4]+, 600 [M+NH4ÀMeOH]+.
3,12-Diethynyl-3,6,9,12-tetramethoxy-1,14-bis(trimethylsilyl)-6,9-diphe-
ative mode): m/z: 1083 [MÀ3H]À.
6,15-Dimethoxy-6,9,12,15-tetraphenylcyclooctadeca-1,4,7,10,13,16-hexa-
nyltetradeca-1,4,7,10,13-pentayne (21):
G
(100 mg, 0.16 mmol) in THF (8 mL) was treated with n-butyllithium
(117 mL, 0.29 mmol) for 20 min at À788C. Iodomethane (162 mL,
2.6 mmol) was added dropwise and the mixture was allowed to warm up
to À408C over a 30 min period. DMSO (23 mL, 0.32 mmol) was added
and stirring was continued for 1h at À08C, then overnight (17 h) at RT.
After treatment with a saturated NH4Cl solution and extraction with
Et2O, the organic layer was washed with brine, dried with MgSO4, and
concentrated under reduced pressure. Purification by column chromatog-
raphy on silica gel (heptane/EtOAc 8:2) gave 21 as an orange oil (82 mg,
80%). Rf ꢃ0.40 (heptane/EtOAc 7:3). 1H NMR (250 MHz, CDCl3): d=
ꢀ
(0.52 g, 0.48 mmol) in acetone (35 mL) was treated with ceric ammonium
nitrate (1.0 g, 1.91 mmol) at RT. After stirring for 3 h, IR monitoring in-
dicated the complete disappearance of the vibrational bands associated
with the carbonyl ligands of the [Co2(CO)6] unit. Water was added and
the mixture extracted with Et2O. The organic layer was separated, dried
with Na2SO4, and concentrated under reduced pressure. Purification of
the residue by column chromatography on silica gel (hexane/EtOAc 9:1)
gave 3d (98 mg, 33%) as a vitreous yellow solid. Rf ꢃ0.20 (heptane/
EtOAc 7:3); 1H NMR (CDCl3): d=3.29–3.61(m, 01H; OC H3 +OH),
5.05 (m, 2H; CH(OH)), 7.30–7.41(m, 12H; m-, p-CH), 7.62–7.69 ppm
(m, 8H; o-CH); 13C NMR (CDCl3): d=52.5 (q, 1JCH =142 Hz; OCH3),
51.5 (d, 1JCH =154 Hz; CH(OH)), 64.7 (s; CPh(OH)), 71.6 (s; CPh-
ꢀ
0.21(s, 18H; Si (CH3)3), 2.68 (s, 2H; C C-H), 3.49, 3.56 (2s, 12H; OCH3),
N
1
(63 MHz, CDCl3): d=À0.49 (q, 1JCH =120 Hz; Si
A
=
(OMe)), 81.3–86.8 (m; C C), 125.8–128.6 (m; o-, m-, p-CH), 138.6 (s;
ipso-C-C-OMe), 140.5 ppm (s; ipso-C6H5-C-OH); IR (CDCl3): n=3572
144 Hz; SiC CC-OCH3), 53.57 (q, 1JCH =144 Hz; PhC-OCH3), 60.61(s;
ꢀ
HC C-C-OMe), 71.82 (s; Ph-C-OMe), 72.75 (d, 1JCH =256 Hz; C C-H),
ꢀ
ꢀ
À
À
À
À
(free O H), 3376–3307 (H-bonded O H), 3066, 2936 (C H), 2827 (OC
2
ꢀ
ꢀ
78.57 (d, JCH =49 Hz; C CH), 81.32, 82.48, 84.28 (3s; C C), 90.07 (s; C
H), 1600, 1490, 1450 (aromatic), 1070 cmÀ1 (C O).
À
CSi), 98.46 (s; C C-Si), 126.60 (d, 1JCH =161 Hz; m- or o-CH), 128.47 (d,
ꢀ
1,14-Bis(trimethylsilyl)-3,12-dimethoxy-3,12-diphenyltetradeca-
1JCH =158 Hz; o- or m-CH), 129.07 (d, 1JCH =161 Hz; p-CH), 139.31 ppm
1,4,7,10,13-pentayne-6,9-diol (29): Complex 28 (127 mg, 0.15 mmol)[21]
was dissolved in acetone (6 mL) at 08C and cerium ammonium nitrate
(CAN, 192 mg, 0.35 mmol) was added. The mixture was stirred for
15 min at 08C and then for 1.5 h at RT until complete disappearance of
the CO stretching bands of 28 by IR monitoring. Water (15 mL) was
added and the mixture was extracted with diethyl ether. The organic
layer was separated, washed with water (2”10 mL), dried with MgSO4,
filtered, and evaporated to dryness. The residue was purified by chroma-
tography on silica gel (heptane/acetone 8:2) to afford 29 as a brown oil
(79 mg, 90%). Rf =0.17 (heptane/acetone 7:3); 1H NMR (CDCl3,
ꢀ À
(s; ipso-C); IR (CDCl3): n˜ =3306 ( C H), 3065, 3002, 2961, 2935, 2902
À
À
ꢀ
(C H), 2827 (OC H), 2124 (C C), 1490, 1450, 1408 (aromatic), 1252
À1
+
À
À
(C Si), 1061 cm (C O); MS (DCI/NH3): m/z: 660 [M+NH4] , 628
[M+NH4ÀMeOH]+, 61 1 M[ +HÀMeOH]+.
7,10,13,16-Tetramethoxy-7,16-bis[2-(trimethylsilyl)ethynyl]-1,4,10,13-tet-
raphenylcyclooctadeca-2,5,8,11,14,17-hexayne-1,4-diol (3c): A solution of
heptayne 21 (212 mg, 0.33 mmol) in THF (12 mL) was treated with n-bu-
tyllithium (0.264 mL, 0.66 mmol) for 25 min at À788C. The mixture was
allowed to warm up to À208C over a 15 min period. After cooling back
to À788C, a solution of dibenzoylacetylene (10) (77 mg, 0.33 mmol) in
THF (6 mL) was added dropwise and the mixture allowed to warm up to
RT over a 1h 30 min period. The stirring was continued for 2 h at this
temperature. After treatment with a saturated NH4Cl solution and ex-
traction with Et2O, the organic layer was washed with brine, dried with
MgSO4, and concentrated under reduced pressure. Purification by chro-
matography on silica gel (heptane/EtOAc 7:3) gave 3c as an orange oil
(126 mg, 43%). Rf ꢃ0.25 (heptane/EtOAc 7:3). 1H NMR (250 MHz,
200 MHz): d=0.22 (s, 18H; Si(CH3)3), 3.18 (s, 2H; OH), 3.46 (s, 6H;
E
OCH3), 5.23 (s, 2H; CHOH), 7.34–7.36 (m, 6H; p-, m-CH); 7.71–
7.75 ppm (m, 4H; o-CH); 13C NMR (CDCl3, 50 MHz): d=À0.40 (q,
1
1
1JCH =120 Hz; Si
(CH3)3), 51.90 (d, JCH =153 Hz; CH(OH)), 52.90 (q, JC-
A
ꢀ
H =143 Hz; OCH3), 71.71 (s; C(OMe)Ph), 81.11–82.66 (4s; C-C), 92.49
A
ꢀ
ꢀ
(s; C C-Si), 100.76 (s, C-Si), 126.46–128.74 (m; o-, m-, p-CH),
À
139.32 ppm (br; ipso-C); IR (CDCl3): n˜ =3674 (free O H), 3406 (bound
À
À
À
O H), 3064–2935 (C H), 2826 (OC H), 1490, 1449 (aromatic),
CDCl3): d=0.21(s, 18H; Si (CH3)3), 3.06 (m, 2H; OH), 3.42–3.62 (m,
G
1251 cmÀ1 (C Si); MS (DCI/NH3): m/z: 584 [M+NH4]+, 552
À
12H; OCH3), 7.33–7.40 (m, 12H; m-, p-CH), 7.66–7.81ppm (m, 8H; o-
[M+NH4ÀMeOH]+, 535 [MÀMeO]+, 520 [M+NH4À2MeOH]+, 503
CH); 13C{1H} NMR (63 MHz, CDCl3): d=À0.47 (Si
G
ꢀ
[MÀMeOÀMeOH]+.
ꢀ
1,14-Bis(trimethylsilyl)-6,9-bis(tetrahydropyran-2-yloxy)-3,12-diphenyl-
OH), 71.83 (Ph-C-OMe), 80.45, 81.58, 82.23, 83.59, 84.51, 84.56 (C C),
90.59 (C CSi), 98.23 (C C-Si), 125.35–129.10 (o-, m-, p-CH), 139.25
(ipso-C-C-OMe), 140.47 ppm (ipso-C-C-OH); IR (dilute CDCl3: C CSi
masked): n˜ =3570 (O H), 3064, 2960, 2934, 2900 (C H), 2827 (OC H),
ꢀ
ꢀ
3,12-dimethoxytetradeca-1,4,7,10,13-pentayne (30a):
A mixture of 29
(211 mg, 0.37 mmol), DHP (68 mL, 0.74 mmol), and p-toluenesulfonic
acid (3 mg, 1.49”10À3 mmol) in toluene (10 mL) was stirred for 5 h at
RT. The reaction was quenched by addition of triethylamine (2 mL) and
the solvent evaporated to dryness. Diethyl ether (75 mL) and water
(75 mL) were added to the crude residue and the organic layer was sepa-
rated, washed with water, dried with MgSO4, and concentrated to give
30a as a red-brown oil (259 mg, 94%). Rf =0.34 (heptane/acetone 7:3);
À
À
1600, 1490, 1450, 1408 (aromatic), 1252 (C Si), 1065 cm (C O); MS
(DCI/NH3): m/z: 894 [M+NH4]+, 845 [M+HÀMeOH]+.
Hexacarbonyl[7,10-bis(trimethylsilyloxy)-1,16-dihydroxy-4,13-dimethoxy-
A
4,7,10,13-tetraphenylcyclooctadeca-2,5,8,11,14,17-hexayne]dicobalt (27):
A solution of pentayne 13a (1.41 g, 1.97 mmol) in THF (120 mL) was
treated with n-butyllithium (1.80 mL, 3.93 mmol) for 30 min at À788C.
1H NMR (CDCl3, 250 MHz): d=0.22 (s; Si
(CH3)3), 1.54–1.90 (m, 12H;
U
C-CH2-C THP), 3.45–3.52 (m, 8H; OCH3 +CHH-O THP), 3.71–3.96 (m,
2H; CHH-O THP), 4.94–4.97 (m, 2H; CHO2 THP), 5.39–5.40 (m, 2H;
CHOTHP), 7.32–7.35 (m, 6H; p-, m-CH), 7.70–7.82 ppm (m, 4H; o-CH);
After addition of
a solution of butynedial complex 26 (800 mg,
2.16 mmol) in THF (40 mL), the stirring was continued for 30 min at
À788C and the mixture allowed to warm up to RT over a 1h 30 min
period. After treatment with a saturated NH4Cl solution and extraction
with Et2O, the organic layer was washed with brine, dried with MgSO4,
and concentrated under reduced pressure. The residue was purified by
chromatography through a silica gel column (heptane/acetone 9:1) to
13C{1H} NMR (CDCl3, 50.3 MHz): d=À0.43 (Si
C
ꢀ
ꢀ
OTHP), 71.71 (CPhOMe), 79.44–82.66 ( C-C), 91.94 (C C-Si), 94.49–
ꢀ
95.80 (CHO2 THP), 101.13 (C C-Si), 126.46, 126.52, 128.13, 128.59,
1
give 27 as a red oil (377 mg, 18%). Rf ꢃ0.35 (heptane/EtOAc 8.5:1.5); H
128.86 (aromatic CH), 139.60 ppm (ipso-C); IR (CDCl3): n˜ =2952, 2902,
4910
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
À1
À
ꢀ
À
2874, 2854 (C H), 2169 (C C), 1251 cm (C Si); MS (DCI/NH3): m/z
with Et2O, the organic layer was washed with brine, dried with MgSO4,
and concentrated under reduced pressure. Chromatography on silica gel
(heptane/EtOAc 7:3) gave 3e as a yellow powder (130 mg, 12%). Rf
ꢃ0.28 (heptane/EtOAc 5:5); 1H NMR (200 MHz, CDCl3): d=2.57–2.75
(m, 2H; OH), 3.34–3.57 (m, 12H; OCH3), 5.28–5.34 (m, 2H; CH-OH),
7.32–7.37 (m, 12H, m-, p-CH), 7.66–7.74 ppm (m, 8H; o-CH); 13C{1H}
NMR (50 MHz, CDCl3): d=52.10 (CHOH), 53.17 (PhC-OCH3), 71.58
(%): 752 (100) [M+NH4]+.
6,9-Bis(tetrahydropyran-2-yloxy)-3,12-diphenyl-3,12-dimethoxytetradeca-
1,4,7,10,13-pentayne (30b): A solution of TBAF (1m in hexane, 0.78 mL,
0.78 mmol) was added through a syringe to a solution of the silylated
pentayne 30a (0.198 g, 0.27 mmol) in THF (10 mL) at À788C. After stir-
ring for 1h at À788C the solution was poured into a mixture of diethyl
ether (70 mL) and saturated aqueous NH4Cl (100 mL). The organic layer
was separated, dried with MgSO4, filtered, and concentrated to give a
brown oil displaying satisfactory analytical data for 30b (137 mg, 85%
crude yield). It can however be purified by chromatography on silica gel
(CH2Cl2) to give 30b as a brown-orange oil in a much lower yield (34%).
Rf =0.16 (heptane/acetone 7:3). 1H NMR (CDCl3, 250 MHz): d=1.62–
ꢀ
(PhC-OCH3), 81.67, 83.31, 83.48, 84.08 (C C), 126.26–128.95 (o-, m-, p-
À
CH), 139.02 (ipso-C-C-OMe) ppm; IR (CDCl3): n˜ =3584 (O H), 2956–
À1
À
À
À
2935 (C H), 2826 (OC H), 1600, 1490, 1450 (aromatic), 1064 cm (C
O); MS (DCI/NH3): m/z: 702 [M+NH4]+, 653 [M+HÀMeOH]+.
Byproducts, each corresponding to a single TLC spot, were isolated and
À ꢀ À
À
ꢀ À
assigned to the general formula H C C CPh
G
ACHTREUNG
À ꢀ À
À ꢀ À
À ꢀ À
À ꢀ À
ꢀ
(OMe) C C CH(OH) C C CPh
N
1.87 (m, 12H; C-CH2-C THP), 2.75 (m, 2H; CH); 3.41–3.52 (m, 8H;
according to their 1H NMR spectrum and integration thereof. In particu-
lar for n=0 (33), n=1 (34a), and n=3: H NMR (250 MHz, CDCl3): d=
OCH3 +CHH-O THP), 3.80–3.85 (m, 2H; CHH-O THP), 4.95–4.97 (m,
2H; CHO THP), 5.37–5.40 (m, 2H; CHOTHP), 7.34–7.37 (m, 6H; p-, m-
CH), 7.71–7.78 ppm (m, 4H; o-CH); 13C{1H} NMR (CDCl3, 62.9 MHz):
d=18.63, 25.24, 29.93 (C-CH2-C THP), 53.22, 54.75 (OCH3 +CH2O
THP), 62.01( CH-OTHP), 71.53 (CPhOMe), 75.17 ( C-H), 80.73–83.65
( C-C), 95.59–95.90 (CHO2 THP), 126.44–128.90 (aromatic CH),
1
2.5–3.5 (m, 2nH; OH), 3.40–3.50 (m, 6
2nH; CH-OH), 7.20–7.35 (m, 6(2n+1)H; m-, p-CH), 7.65–7.75 ppm (m,
(2n+1)H; o-CH).
4,7,13,16-tetramethoxy-4,7,13,16-tetraphenylcyclooctadeca-2,5,8,11,14,17-
hexayne-1,10-dione (3 f): chromatographically purified sample of
(2n+1)H; OCH3), 5.15–5.25 (m,
AHCTREUNG
ꢀ
4
ACHTREUNG
ꢀ
À
À
139.54 ppm (ipso-C); IR (CDCl3): n˜ =3305 (spC H), 3065–2948 (C H),
A
À1
À
ꢀ
À
2828 (OC H), 2116 (C C), 1599, 1490, 1450 (aromatic), 1067 cm (C
[6]pericyclynediol 3e (70%, 85 mg, 0.076 mmol) and nonaynediol 34a
(30%, 0.033 mmol) was dissolved in CH2Cl2 (5 mL) and treated with
MnO2 (162 mg, 1.86 mmol) for 1 h at 08C. Stirring was continued for 1h
30 min at RT and then the solution was filtered and concentrated under
reduced pressure. Purification by flash chromatography on silica gel (hep-
tane/EtOAc 8:2) gave 3 f as a yellow oil (10 mg, 20%). Rf ꢃ0.44 (hep-
tane/EtOAc 6:4). 1H NMR (250 MHz, CDCl3): d=3.44–3.62 (m, 12H;
OCH3), 7.25–7.44 (m, 12H; m-, p-CH), 7.63–7.73 ppm (m, 8H: o-CH);
13C{1H} NMR (50 MHz, CDCl3): d=53.73 (OCH3), 71.78 (PhC-OCH3),
O); MS (DCI/NH3): m/z (%): 608 (67) [M+NH4]+.
1,8-Bis(trimethylsilyl)-3,6-diphenylocta-1,4,7-triyne-3,6-diol (31): A solu-
tion of n-butyllithium (8.13 mL, 17.07 mmol) was added dropwise to a so-
lution of trimethylsilylacetylene (2.53 mL, 17.9 mmol) in THF (20 mL) at
À788C. After stirring for 20 min at À788C, then for 20 min at RT, the
mixture was cooled back to À788C before addition of a solution of di-
benzoylacetylene (10) (2.0 g, 8.35 mmol) in THF (20 mL). The reaction
mixture was allowed to warm up to RT over 3 h and stirring was contin-
ued for 15 h. After addition of a saturated aqueous NH4Cl solution and
extraction with diethyl ether, the organic layer was separated, washed
with brine, dried with MgSO4, filtered, and evaporated under reduced
pressure. The residue was purified by chromatography on silica gel (hep-
tane: EtOAc 8:2) to afford 31 as a pale yellow solid (2.45 g, 67%). Rf
ꢃ0.58 (heptane/EtOAc 5:5); 1H NMR (250 MHz, CDCl3): d=0.21(s,
ꢀ
83.84, 83.96, 84.90, 88.51(C C), 126.28–128.69 (o-, m-, p-CH), 137.42
À
(ipso-C-C-OMe), 158.92 ppm (C=O); IR (CDCl3): n˜ =2956–2931(C H),
À1
À
À
2827 (OC H), 1638 (C=O), 1451 (aromatic), 1068 cm (C O); MS
(DCI/NH3): m/z: 698 [M+NH4]+, 649 [M+HÀMeOH]+.
3,6,12,15,21,24-Hexamethoxy-3,6,12,15,21,24-hexaphenyl-
1,4,7,10,13,16,19,22,25-nonayne-9,18-dione (34b): This compound was
produced from 34a in the above described procedure starting from a
70:30 3e/34a mixture. It was isolated as a pale yellow oil (23 mg, 70%).
Rf ꢃ0.35 (heptane/EtOAc 6:4); 1H NMR (250 MHz, CDCl3): d=2.79 (s,
18H; Si(CH3)3), 2.94 (s, 2H; OH), 7.36 (m, 6H; m-, p-CH), 7.78 ppm (m,
H
4H; o-CH); 13C{1H} NMR (63 MHz, CDCl3): d=À0.31(Si
A
ꢀ
ꢀ
ꢀ
(C-CPhOH), 84.89 (C-C C-C), 90.73 (C CSi), 103.76 ( C-SiMe3),
125.79–128.82 (o-, m-, p-CH), 141.06 ppm (ipso-C); IR (CDCl3): n˜ =3573
ꢀ
2H; C CH), 3.52–3.54 (m, 18H; OCH3), 7.34–7.40 (m, 18H; m-, p-CH),
7.65–7.76 ppm (m, 12H; o-CH); 13C{1H} NMR (63 MHz, CDCl3): d=
À
À
ꢀ
À
(O H), 2962 (C H), 2174 (C C), 1600, 1490, 1451 (aromatic), 1252 (C
Si), 1046 cmÀ1 (C O); MS (DCI/NH3): m/z: 430 [M+NH4ÀH2O] , 41 3
ꢀ
+
À
53.41, 53.86, 53.94 (OCH3), 71.65, 71.88 (PhC-OCH3), 75.78 (C CH),
[M+HÀH2O]+.
ꢀ
80.24, 81.94, 83.99, 84.68, 84.96, 86.38, 88.47, 89.25 (C C), 126.38–129.63
(o-, m, p-CH), 137.83, 138.09, 139.24 (ipso-C-C-OMe), 158.97 ppm (C=
1,8-Bis(trimethylsilyl)-3,6-dimethoxy-3,6-diphenylocta-1,4,7-triyne (32): A
solution de n-butyllithium (2.2 mL, 5.50 mmol) was added through a sy-
ringe to a solution of triynediol 31 (1.18 g, 2.75 mmol) in THF (20 mL) at
À788C. After stirring for 10 min at À788C, iodomethane (2.74 mL,
44 mmol) was added and the temperature allowed to reach À258C
before DMSO (0.4 mL, 5.5 mmol) was added. After 1h at À25/À208C,
stirring was continued for 15 h at RT. After addition of a saturated aque-
ous NH4Cl solution and extraction with Et2O, the organic layers were
combined, washed with brine, dried with MgSO4, filtered, and evaporated
to dryness. Compound 32 was thus obtained as a spectroscopically pure
orange oil (1.23 g, 97%). Rf ꢃ0.53 (heptane/acetone 8:2); MS (DCI/
NH3): m/z: 444 [M+NH4ÀMeOH]+, 427 [M+HÀMeOH]+; NMR analy-
À
À
À
O); IR (CDCl3): n˜ =3305 (spC H), 2958–2935 (C H), 2828 (OC H),
1640 (C=O), 1450 (aromatic), 1068 cmÀ1 (C O); MS (DCI/NH3): m/z:
À
1012 [M+NH4]+.
1-Trimethylsilylpenta-1,4-diyn-3-ol (37): A solution of acetylene in THF
(200 mL), saturated by prolonged bubbling at 08C, was treated with a so-
lution of EtMgBr (13 mL, 39 mmol). After stirring for 1 h at 48C, trime-
thylsilylpropynal (36) (5.00 g, 39 mmol) was added and stirring was con-
tinued for 17 h at RT. After addition of saturated aqueous NH4Cl
(30 mL) and Et2O (50 mL), the organic layer was separated and washed
with saturated aqueous NH4Cl (2”20 mL) and brine (10 mL). The com-
bined aqueous layers were again extracted with Et2O (2”15 mL) and the
combined organic layers dried with MgSO4, filtered, and concentrated to
dryness. Analytically pure product 37 was obtained (5.77 g, 98%). 1H
ꢀ
sis
was
consistent
with
previously
reported
data.[10]
Crystals slowly separated from the oily product and were analyzed by
means of X-ray crystallography (meso isomer, Figure 4, left).
NMR (CDCl3): d=0.16 (m, 9H; Si(CH3)3), 2.55 (2s, 1H; C-H), 2.63 (s,
C
1H; OH), 5.09 ppm (s, 1H; CH(OH)); 13C{1H} NMR (CDCl3): d=À0.58
4,7,13,16-Tetramethoxy-4,7,13,16-tetraphenylcyclooctadeca-2,5,8,11,14,17-
hexayne-1,10-diol (3e): A solution of triyne 33 (500 mg, 1.59 mmol) in
THF (200 mL) was treated with nBuLi (1.4 mL, 3.18 mmol) at À788C.
The solution was allowed to warm up to À208C over a 30 min period and
then stirring was continued for 15 min. After cooling back to À788C, a
solution of dialdehyde 22 (590 mg, 1.59 mmol) in THF (200 mL) was
added dropwise. Stirring was continued for 30 min at À788C and the tem-
perature allowed to rise to À208C over a 30 min period. Stirring was
then continued for 2 h at this temperature and finally for 30 min at RT.
After treatment with a saturated aqueous NH4Cl solution and extraction
ꢀ
ꢀ
ꢀ
(Si(CH3)3), 52.09 (CH(OH)), 72.72 ( C-H), 80.50 (C CH), 89.6 (C C-
G
ꢀ
À
SiMe3), 101.04 ppm ( C-SiMe3); IR (CDCl3): n˜ =3434 (O H), 3307 (spC-
À1
+
ꢀ
À
H), 2249 (C C), 1254 cm (C Si); MS (DCI/NH3): m/z: 187 [M+N2H7]
, 174 [M+NH4]+.
1,8-Bis(trimethylsilyl)octa-1,4,7-triyne-3,6-diol (38): A solution of diynol
37 (3.29 g, 21.64 mmol) in THF (50 mL) at À788C was treated with a so-
lution of EtMgBr (3m, 15.15 mL, 45.45 mmol). After stirring for 20 min
at À788C, then for 2 h at RT, the solution was cooled back to À788C and
a solution of trimethylsilylpropynal (36) (4.91g, 38.95 mmol) in THF
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4911

R. Chauvin et al.
(60 mL) was added. Stirring was continued overnight and saturated aque-
ous NH4Cl (100 mL) and Et2O (50 mL) were added. The organic layer
was separated and washed again with a saturated aqueous NH4Cl solu-
tion (3”60 mL). The combined aqueous layers were extracted with Et2O
(2”30 mL) and the combined organic layers dried with MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified by
chromatography on silica gel (heptane/EtOAc 9:1) to afford 38 as a
(200 MHz, CDCl3): d=3.39–3.60 (m, 12H; OCH3), 5.04 (m, 2H;
CHOMe), 5.25 (m, 2H; CHOH), 7.32–7.36 (m, 6H; m-, p-CH), 7.66–
7.73 ppm (m, 4H; o-CH); 13C NMR (50 MHz, CDCl3, high dilution: qua-
ternary carbon signals not unambiguously detected): d=52.21( CHOH),
53.44, 54.88 (OCH3), 59.63 (CHOMe), 126.48, 128.49, 129.07 ppm (o-, m-,
p-CH); MS (DCI/NH3): m/z: 550 [M+NH4]+.
brown oil (2.87 g, 47%). 1H NMR (CDCl3): d=0.14 (s, 9H; Si
4.15 (brs, 2H; OH), 5.17 ppm (brs, 2H; CHOH); 13C{1H} NMR (CDCl3):
(CH3)3),
ꢀ
ꢀ
d=À0.37 (Si
N
Acknowledgements
À
H), 2962, 2900 (sp C H), 2178 (C CSi), 1410, 1374, 1294, 1253 (Si C),
1135, 1042 cmÀ1 (C O); MS (DCI/NH3): m/z (%): 296 (100) [M+NH4] .
The authors thank the Centre National de la Recherche Scientifique and
the Minist›re de lꢁEducation Nationale de la Recherche et de la Techno-
logie for Ph.D. fellowships and the financial support of an Action Con-
certØe Incitative (ACI). The authors are also indebted to one of the refer-
ees whose critical reading and suggestions were very helpful.
Crystals slowly separated from the oily product and were analyzed by
means of X-ray crystallography (meso isomer, Figure 4, right).
1,8-Bis(trimethylsilyl)-3,6-dimethoxyocta-1,4,7-triyne (39): A solution of
n-butyllithium (2.5m in hexane, 0.29 mL, 0.719 mmol) was added through
a syringe to a solution of triynediol 38 (100 mg, 0.36 mmol) in Et2O
(2 mL) at À808C. After stirring for 1min, a solution of methyl triflate
(0.155 mL, 0.144 mmol) was added and stirring was continued overnight
at 08C. A saturated aqueous K2CO3 solution was added and the mixture
extracted with Et2O. The organic layer was washed with a saturated
aqueous K2CO3 solution, then with water, dried with MgSO4, and con-
centrated to leave crude 39 with acceptable purity (105 mg, 95%). 1H
[1] a) R. Chauvin, C. Lepetit, Acetylene Chemistry. Chemistry, Biology
and Material Sciences (Eds.: F. Diederich, P. J. Stang, R. R. Tykwin-
ski), Wiley, Weinheim, 2005, Chapter 1, pp. 1–50: b) V. Maraval, R.
Chauvin, Chem. Rev. 2006, 106, 5317–5343.
[2] R. Chauvin, Tetrahedron Lett. 1995, 36, 397–400.
[3] a) C. Godard, C. Lepetit, R. Chauvin, Chem. Commun. 2000, 1833–
1834; b) C. Lepetit, C. Godard, R. Chauvin, New J. Chem. 2001, 25,
572–580; c) C. Lepetit, B. Sivi, R. Chauvin, J. Phys. Chem. A 2003,
107, 464–473.
[4] R. Chauvin, Tetrahedron Lett. 1995, 36, 401–404.
[5] Y. Kuwatani, N. Watanabe, I. Ueda, Tetrahedron Lett. 1995, 36, 1 1 9–
122.
[6] C. Saccavini, C. Sui-Seng, L. Maurette, C. Lepetit, S. Soula, C. Zou,
B. Donnadieu, R. Chauvin, Chem. Eur. J. DOI: 10.1002/
chem.200601193.
[7] L. T. Scott, G. J. DeCicco, J. L. Hyunn, G. Reinhardt, J. Am. Chem.
Soc. 1985, 107, 6546–6555.
[8] R. Suzuki, H. Tsukude, N. Watanabe, Y. Kuwatani, I. Ueda, Tetrahe-
dron 1998, 54, 2477–2496.
[9] C. Tedeschi, C. Saccavini, L. Maurette, M. Soleilhavoup, R. Chauvin,
J. Organomet. Chem. 2003, 670, 151–169.
[10] L. Maurette, C. Tedeschi, E. Sermot, M. Soleilhavoup, F. Hussain, B.
Donnadieu, R. Chauvin, Tetrahedron 2004, 60, 10077—10098.
[11] L. Maurette, C. Godard, S. Frau, C. Lepetit, M. Soleihavoup, R.
Chauvin, Chem. Eur. J. 2001, 7, 1165–1170.
[12] a) V. Huc, R. Weihofen, I. Martin-Jimenez, P. OuliØ, C. Lepetit, G.
Lavigne, R. Chauvin, New J. Chem. 2003, 27, 1412–1414; b) V. Mar-
aval, C. Lepetit, A.-M. Caminade, J.-P. Majoral, R. Chauvin, Tetra-
hedron Lett. 2006, 47, 2155–2159.
[13] a) A. B. Holmes, C. L. D. Jennings-White, A. H. Schulthess, B.
Akinde, D. R. M. Walton, J. Chem. Soc., Chem. Commun. 1979,
840–842; b) E. Abele, K. Rubina, J. Popelis, I. Mazeika, E. Lukev-
ics, J. Organomet. Chem. 1999, 586, 184–190.
[14] Z. Z. Zhang, G. B. Schuster, J. Am. Chem. Soc. 1989, 111, 7149–
7155.
[15] J.-M. Ducere, C. Lepetit, P. G. Lacroix, J.-L. Heully, R. Chauvin,
Chem. Mater. 2002, 14, 3332–3338.
NMR (200 MHz, CDCl3): d=0.16 (s, +18H (slight excess); Si
3.40 (s, 6H; OCH3), 4.96 ppm (2m, 2H; CHOMe); 13C{1H} NMR
(50 MHz, CDCl3): d=À0.35 (Si(CH3)3), 54.66 (OCH3), 60.16 (CHOMe),
A
AHCTREUNG
ꢀ
ꢀ
ꢀ
80.24 (C-C C-C), 91.04 (C CSi), 98.79 ppm ( C-Si); IR (CDCl3): n˜ =
3
À1
À
À
ꢀ
À
2961, 2902 (sp C H), 2827 (OC H), 2176 (C CSi), 1463, 1252 cm (C
Si); MS (DCI/NH3): m/z: 324 [M+NH4]+.
3,6-Dimethoxyocta-1,4,7-triyne (35): A solution of TBAF (1m in THF,
4.06 mL, 4.06 mmol) was added through a syringe to a solution of triyne
39 (622 mg, 2.03 mmol) in THF (35 mL) at À808C. After stirring for
15 min, the mixture was quenched with water and extracted with diethyl
ether. The organic layer was separated, washed with water, dried with
MgSO4, and concentrated under reduced pressure to give crude 35 as a
black oil of acceptable purity (278 mg, 84%). 1H NMR (200 MHz,
ꢀ
CDCl3): d=2.54 (m, 2H; C-H), 3.39 (s, 12H; OCH3), 4.96 ppm (s, 2H;
CHOMe); 13C{1H} NMR (63 MHz, CDCl3): d=54.63 (OCH3), 59.40
ꢀ
ꢀ
(CHOMe), 74.10 ( C-H), 80.08 ppm (C-C ) + masked peak under the
3
ꢀ
À
ꢀ
CDCl3 signal; IR (CDCl3): n˜ =3306 (C CH), 2935 (sp C H), 2123 (C
CH), 1463 cmÀ1; MS (DCI/NH3): m/z: 180 [M+NH4]+.
1,8-Bis(trimethylsilyl)octa-1,4,7-triyne-3,6-dione (40): MnO2 (6.294 g,
72.34 mmol) was added to a solution of diol 38 (1.02 g, 3.6 mmol) in di-
chloromethane (150 mL) at 08C. After stirring for 30 min at 08C, then
for 1.5 h at RT, the reaction mixture was filtered through a small pad of
Celite. The filtrate was evaporated to dryness and the residue purified by
chromatography on silica gel (heptane/EtOAc 97:3). The product decom-
posed on silica gel (dragging spot), but minute quantities of pure com-
pound 40 were obtained as a brown oil (0.030 g, 3%). Rf =0.58 (heptane/
1
EtOAc 7:3); H NMR (CDCl3): d=0.27 ppm (s; Si
A
ꢀ
ꢀ
(CDCl3): d=À1,00 (Si
G
3
ꢀ
C), 1639 (C=O), 1254 (Si C), 1206 cmÀ1; MS (DCI/NH3): m/z (%): 292
(100) [M+NH4]+.
4,7-Diphenyl-4,7,13,16-tetramethoxycyclooctadeca-2,5,8,11,14,17-hexa-
[16] C. Lepetit, P. G. Lacroix, V. Peyrou, C. Saccavini, R. Chauvin, J.
Comput. Methods Sci. Eng. 2004, 4, 569–588.
A
0.45 mL, 1.25 mmol) was added through a syringe to a solution of triyne
35 (101 mg, 0.62 mmol) in THF (15 mL) at À808C. After stirring for
5 min, a solution of dialdehyde 22 (233 mg, 0.62 mmol) in THF (5 mL)
was added. The mixture was stirred at À808C for 1.5 h, then at 08C for
2.5 h, and finally poured into a mixture of saturated aqueous NH4Cl and
diethyl ether. The organic layer was separated, washed with saturated
aqueous NH4Cl, dried with MgSO4, and concentrated under reduced
pressure to give a brown residue which was purified by chromatography
twice on silica gel (first with heptane/EtOAc 6:4, secondly with heptane/
EtOAc 7:3). A fraction containing the pericyclyne 3g as the major prod-
[17] 2- and 3-pyridyl alknyl ketones have been described previously, see:
a) D. S. Holeman, R. M. Rasne, R. B. Grossman, J. Org. Chem.
2002, 67, 3149–3151; b) C. P. Sar, J. Jeko, P. Fajer, K. Hideg, Synthe-
sis 1999, 6, 1039–1045.
[18] C. Tedeschi, S. Soula, C. Saccavini, C. Zou, R. Chauvin, unpublished
results.
[19] a) A. Meyer, A. Gorgues, Y. Le Flocꢁh, Y. Pineau, J. Guilleviv, J. Y.
Le Marouille, Tetrahedron Lett. 1981, 22, 5181–5182; b) A. Meyer,
M. Bigorgne, Organometallics 1984, 3, 1112–1118.
[20] M. Soleilhavoup, L. Maurette, C. Lamirand, B. Donnadieu, M. J.
McGlinchey, R. Chauvin, Eur. J. Org. Chem. 2003, 9, 1652–1660.
uct was obtained as
a
pale yellow solid (5 mg, <2%). 1H NMR
4912
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 4895 – 4913

Functional [6]Pericyclynes
FULL PAPER
[21] C. Sui-Seng, M. Soleilhavoup, L. Maurette, C. Tedeschi, B. Donna-
dieu, R. Chauvin, Eur. J. Org. Chem. 2003, 9, 1641–1651.
[22] G. B. Jones, J. M. Wright, T. M. Rush, G. W. Plourde, T. F. Kelton,
J. E. Mathews, R. S. Huber, J. P. Davidson, J. Org. Chem. 1997, 62,
9379–9381.
[23] a) L. T. Scott, M. J. Cooney, “Macrocyclic homoconjugated polyace-
tylenes” in Modern Acetylene Chemistry (Eds.: P. J. Stang, F. Dieder-
ich), VCH, Weinheim, 1995, Chapter 9, p. 321; b) M. J. Cooney,
Ph.D. Dissertation, Nevada University, Reno, 1993.
[24] a) F. Wille, R. Strasser, Chem. Ber. 1961, 94, 1606–1611; b) M. T. X.
Hearn, Tetrahedron 1976, 32, 115–120.
[25] C. Zou, V. Maraval, C. Duhayon, R. Chauvin, unpublished results.
[26] S. Guiard, M. Santelli, J.-L. Parrain, Tetrahedron Lett. 2002, 43,
8099–8101.
[28] J. Suffert, J. Org. Chem. 1989, 54, 509–510.
[29] a) D. J. Watkin, C. K. Prout, J. R. Carruthers, P. W. Betteridge,
CRYSTALS Issue 10, Chemical Crystallography Laboratory,
Oxford, 1996; b) the SIR92 program was used for automatic solution
of crystal structures by direct methods: A. Altomare, G. Cascarano,
G. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli,
J. Appl. Crystallogr. 1994, 27, 435–436.
[30] a) J. R. Carruthers, D. J. Watkin, Acta Crystallogr. Sect. A 1979, 35,
698–699; b) SHELX97 (includes SHELXS97, SHELXL97, and
CIFTAB), Programs for Crystal Structure Analysis (Release 97.2),
G. M. Sheldrick, Institüt für Anorganische Chemie der Universität,
Gçttingen (Germany), 1998.
Received: August 16, 2006
Revised: November 4, 2006
Published online: March 19, 2007
[27] M. Li, C. Zou, C. Duhayon, R. Chauvin, Tetrahedron Lett. 2006, 47,
1047–1050.
Chem. Eur. J. 2007, 13, 4895 – 4913
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4913