Diastereoselective approach to 11-aryl steroid skeletons through a cobalt(I)-mediated [2+2+2] cyclization of allenediynes

Article abstract of DOI:10.1016/j.tet.2006.05.091

The cobalt(I)-mediated [2+2+2] cycloaddition reactions of allenediynes of yne-allene-yne type bearing an aryl group on the allene are described. The cyclizations are totally chemo- and regioselective and show low diastereoselectivities. η⁴-Comp

Full text of DOI:10.1016/j.tet.2006.05.091

Tetrahedron 62 (2006) 10582–10593
Diastereoselective approach to 11-aryl steroid skeletons through
a cobalt(I)-mediated [2D2D2] cyclization of allenediynes
*
Marc Petit, Corinne Aubert and Max Malacria
*
´
Universite Pierre et Marie Curie-Paris 6, Laboratoire de Chimie Organique (UMR CNRS 7611), Institut de Chimie Moleculaire
´
(FR 2769), Case 229, 4 place Jussieu, F-75252 Paris cedex 05, France
Received 18 February 2006; revised 1 May 2006; accepted 22 May 2006
Available online 8 August 2006
Abstract—The cobalt(I)-mediated [2+2+2] cycloaddition reactions of allenediynes of yne-allene-yne type bearing an aryl group on the allene
are described. The cyclizations are totally chemo- and regioselective and show low diastereoselectivities. h4-Complexed tricyclic (6,6,6) com-
pounds were obtained in good yields as mixtures of endo/exo diastereomers. The cyclization is also compatible with an oxyfunctionality at C3.
By designing an allenediyne having a preexisting D ring, we succeeded in building skeletons of 11-aryl steroids in one step and in a totally
diastereoselective manner and with simultaneous introduction of an angular methyl group at C10 and an aryl substituent at C11.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Our strategy depicted in Scheme 1 would allow in one step
the creation of the ABC ring system and most interestingly,
the simultaneous introduction of the substituents at both C11
and C10. Indeed, tetracyclic complex 2 could be reached
from the intramolecular [2+2+2] cyclization of allenediyne
3 incorporating a preexisting D ring. Subsequent transforma-
tions of 2 might lead to 11b-aryl steroids 1.
In the last two decades, the synthesis, biological evaluation,
and clinical applications of a new class of antiprogestational
steroids, which present an 11b-aryl unit have been stud-
ied.1,2 Due to their relevant pharmacological properties,
a large number of synthetic efforts aimed at producing
new compounds has been reported.3 However the synthesis
of such steroids is still in need of the development of new
synthetic methods.
O
11
Ar
O
Ar
9
In the context of our interests in metal-catalyzed or radical
cyclizations cascades directed toward the construction of
basic skeletons of natural products,4 we have explored the
feasibility of building 11-aryl steroid frameworks by using
an intramolecular cobalt(I)-mediated [2+2+2] cycloaddition
reaction of allenediynes.
10
R
R
R
R
O
CoCp
O
2
1
Ar
O
•
R
R
3a R, R =
O
3b R, R = H
Transition metal-catalyzed cyclizations have already been
used in the synthesisof the steroid nucleus.5,6 As for an exam-
ple, the cobalt(I) synthesis of racemic oestrone is probably
the most spectacular illustration of the potency of such an
approach.7 In addition, intramolecular cyclizations of
enediynes that allow the simultaneous formation of either the
BCD or ABCD ring systems have been proposed.8 Although
11-trimethylsilyl-substituted steroid frameworks have been
described,9 only one example of a low yielding access to
11-a-heterosubstituted steroid skeleton has been reported.
Scheme 1.
In this paper, after having presented the cyclizations of
allenediynes of yne-allene-yne type, we will document and
discuss the above approach that was achieved in our
laboratory.10
2. Results and discussion
2.1. Cobalt(I)-mediated cyclizations of allenediynes of
yne-allene-yne type
Allenes, which present cumulated C–C bonds are highly
appealing candidates for the transition metal-catalyzed
* Corresponding authors. Tel.: +33 14427 3586; fax: +33 14427 7360;
e-mail: max.malacria@upmc.fr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.091

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10583
OH
Ar
reactions. Over the last years, their reactivity in presence of
various catalysts in a large variety of cyclizations and subse-
quently, their synthetic applications have been extensively
investigated.11,12 Although allenes are good ligands in or-
ganometallic complexes, only few examples involving this
unsaturated component in [2+2+2] cycloaddition reactions
have been reported.13 Previously, it was discovered in our
group that allenes are relevant partners for intramolecular
[2+2+2] cocyclizations to alkynes.14 For instance, upon
treatment with CpCo(CO)2, allenediynes of yne-yne-allene
type furnished the corresponding cycloadducts in high yields
and in a complete chemo-, regio-, and diastereoselective
manner.15 Moreover, with optically active allenes, the pro-
cess can be performed with a total transfer of chirality
(Scheme 2).
path a
Ar
A
HO
path b
B
Scheme 4.
tertiary alcohol 7 (Ar¼Ph) (Scheme 5). However, its conver-
sion into the corresponding mesylate failed and the enediyne
8 was obtained in 76%. Several attempts to carry out the SN20
reaction with the corresponding methylether, even in pres-
ence of Lewis acid, were unsuccessful, the ether remaining
unchanged.
CpCo
CpCo(CO)2
•
H
O
R
THF, hν, ∆
R
PPh2
Ph2P
O
OH
O
R = Ph
e.e. > 95%
98%
74%
e.e. > 95%
e.e. > 95%
(a)
(b), (c)
Ph
R = t -Bu e.e. > 95%
Me3Si
Scheme 2.
6
Me3Si
OH
Ph
However, under the same conditions the allenediyne 4 with
tetrasubstituted internal allene led chemo- and regioselec-
tively to the corresponding h4-complexed tricyclic com-
pound 5 as a 7:3 diastereomeric mixture in moderate yield
(Scheme 3).
(d), (e)
3
7
8
Me3Si
Me3Si
Scheme 5. (a) n-BuLi, octa-1,7-diyne, THF, ꢀ78 ꢁC, 76%; (b) PCC, Al2O3,
CH2Cl2, rt, 75%; (c) PhLi, THF, ꢀ78 ꢁC, 86%; (d) n-BuLi, THF, ꢀ78 ꢁC,
MsCl; and (e) K2CO3, MeOH, rt, 76% from 7.
CpCo(CO)2
•
(1 equiv)
xylenes
∆, hν
CoCp
42%
5, endo:exo = 7:3
4
In contrast, the allenediynes 16a–d were obtained from the
mesylates derived from alcohols 14 and 15 of type B,
Scheme 3.
prepared from 8-(trimethylsilyl)-oct-7-yn-2-oney
9 or
Before starting the synthesis of 2, we initially decided to
investigate the behavior of different allenediynes of yne-
allene-yne type bearing an aryl group on the allene and to
evaluate the influence of such substituent on the course of
the cyclization.
5-methoxy-oct-7-yn-2-one 13, which is readily prepared from
4-(tert-butyldimethylsilyloxy)-butyraldehyde19 as described
in Scheme 6.
Addition of the lithio derivative of hepta-1,6-diyne with the
ketone 9 furnished the corresponding alcohol 14 in 70%.
Then, the sequence—mesylation, SN20 with arylcopper re-
agent, deprotection of the triple bond—led to the allene-
diynes 16a–c. Starting from the ketone 13, the whole
sequence, which was carried out without purifying the inter-
mediates led to 16d in 36% overall yield.
2.1.1. Preparation of the allenediynes. The preparation of
allenic compounds has been widely investigated and highly
useful methods have been developed for obtaining numerous
substituted allenes.16 In this study, we chose to introduce the
allene unit via a copper(I) salt SN20 displacement of propar-
gylic sulfonate group.17 Therefore, the allenediynes were
prepared following the general sequence: (1) preparation
of the requisite triyne and (2) introduction of the allene in
the last step. However, it was possible to envision for this
last step the addition of either methylcopper or arylcopper
reagent onto the mesylates derived from the alcohol of
type A or B, respectively (path a or b) (Scheme 4).
2.1.2. Cobalt(I)-mediated cyclizations of the allenediynes
16a–d. Exposure of 16a–d to a stoichiometric amount of
CpCo(CO)2 in refluxing xylenes under irradiation (300 W
visible lamp, 50% of its power) led to the complexed tri-
cyclic compounds 17a–d in 60–65% yield as a nearly 1:1
Thus, considering path a the addition of monolithiated octa-
1,7 diyne to 6-trimethylsilyl-5-hexynal18 furnished the cor-
responding alcohol 6, which is readily transformed to the
y
8-(Trimethylsilyl)-oct-7-yn-2-one was prepared by using the same reac-
tions as for the parent compound 7-(trimethylsilyl)-hept-6-yn-2-one,
see Ref. 18.

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M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
OMe
Ph
OMe
Ph
O
(d)
(a), (b), (c)
O
OH
cat. CpCo(CO)2
xylenes,
3
3
hν, ∆
OSiMetBu
R2
12
13
quantitative
18
8
O
R2
OH
Scheme 8.
2
(f), (g)
(e)
2
R1
2.2. Diastereoselective approach to 11-aryl steroid
skeletons
R1
1 = SiMe3; R2 = H
R1 = H; R2 = OMe
9
14
15
R
13
Since an aryl group was compatible with the conditions of
the cyclization, we undertook the preparation of 3b (R¼H
and Ar¼Ph) starting from the commercially available
2-methyl-2-cyclopenten-1-one. Conjugate addition of (tri-
methylsilyl)ethynyl copper(I) reagent in the presence of
iodotrimethylsilane provided the corresponding silyl enol
ether 19 in 95% yield.21 Subsequent acid hydrolysis fur-
nished the ketone 20 in 85% yield.
Ar
•
Ar = Ph, 16a
R2 = H
Ar = p-CF3Ph, 16b
Ar = p-MeOPh, 16c
Ar = Ph, 16d
R2
R2 = OMe
Scheme 6. (a) HC^CCH2MgBr, THF, ꢀ30 ꢁC, 10: 85%; (b) NaH, THF, rt,
MeI, 11: quantitative; (c) n-Bu4NF, THF, 0 ꢁC–rt, 12: 86%; (d) 1. (COCl)2,
DMSO, NEt3, ꢀ78 ꢁC to rt, CH2Cl2; 2. MeMgBr, THF; 3. (COCl)2, DMSO,
NEt3, CH2Cl2, ꢀ78 ꢁC to rt, 13: 75% from 12; (e) n-BuLi, hepta-1,6-diyne,
THF, ꢀ78 ꢁC, 14: 70%; (f) 1. n-BuLi, THF, ꢀ78 ꢁC, MsCl; 2. ArMgBr/
Me2S$CuBr/LiBr (1.5 equiv), THF, ꢀ50 ꢁC, 16d: 36% from 13; and (g)
K2CO3, MeOH, rt, 16b: 72%; 16c: 51%; 16d: 33%.
Different methods at effecting the alkylation of 19 were
quite unsuccessful; the use of MeLi or NaNH2 in THF/
HMPA resulted in decomposition of the starting material
whereas the use of NaH led to a complex mixture of the ke-
tone 20 and mono- and trialkylated adducts albeit in low
yields (10–12%). The expected alkylated adduct was ob-
tained from 19 with a slightly modified Nicholas reaction22
(Scheme 9).
mixture of endo/exo diastereomers (Scheme 7). The
endo/exo stereochemical assigments and ratios were de-
termined by H NMR on the basis of the chemical shift
1
and integration of Cp-, dienic protons, and the angular
CH3, which is deshielded when located syn to cobalt
and shielded when located anti (dCH3 endo¼1.80 ppm;
dCH3 exo¼1.20 ppm).14b,20
OTMS
O
O
(a)
(b)
19
20
Ar
Ar
Ar
TMS
TMS
•
(a)
R2
OTMS
+
O
O
R2
R2
CoCp
(c), (d), (e)
(f)
CpCo
endo
exo
19
23
55
17a, 60% 45
17b, 65% 47
17c, 62% 39
16a, Ar = Ph
TMS
TMS
16b, Ar = p-CF3Ph R2 = H
16c, Ar = p-MeOPh
53
61
65
HO
TMS
O
O
17d, 62% 35
16d, Ar = Ph, R2= OMe
Ph
O
O
(g), (h), (i)
Scheme 7. CpCo(CO)2 (1 equiv), xylenes, hn, D.
•
24
25cis
TMS
Several features in these cyclizations are noteworthy: (i) they
are totally regioselective and lead only to the (6,6,6) tricyclic
cycloadducts; (ii) the yields are higher compared to the cy-
clization of allenediyne 4 due to an increase in the stability
of the isolated complexes since they could be purified with
non-degassed solvents on silica gel; (iii) the endo/exo dia-
stereoselectivity is independent of the substitution on the
allene; and (iv) the cyclization is compatible with an oxygen-
ated functionality at C3.
Scheme 9. (a) n-BuLi, Me3SiC^CH, TMSI, CuI, THF, ꢀ78 to ꢀ30 ꢁC, 19:
95%; (b) 1 M HCl, 20: 85%; (c) MeOCH2–C^CH$Co2(CO)6, Et2O$BF3,
CH2Cl2, rt, 21: 95%; (d) CAN, acetone, rt, 22: 78%; (e) 5 mol % PTSA,
ethylene glycol (2 equiv), benzene (0.01 M), 23cis/trans: 95%; (f) n-BuLi,
ꢀ78 ꢁC, THF, CH3C(O)(CH2)4C^CSiMe3, 24cis: 60%; 24trans: 50%;
(g) n-BuLi; MsCl, THF, ꢀ78 ꢁC; (h) Me2S$CuBr, PhMgCl, LiBr, THF,
ꢀ50 ꢁC, 10%; and (i) K2CO3, MeOH, rt, 25cis: quantitative.
Indeed the following sequence—addition of 19 at rt to a
solution of (propargyl)dicobalt hexacarbonyl cation, demeta-
lation,23 and acetalizationz of the corresponding adducts—
furnished a 2:1 mixture of the ketals 23cis/trans. The cis
Having in hands the diyne-ene-yne 8, we checked its behav-
ior in presence of a catalytic amount of CpCo(CO)2 under
the same conditions as above. The cycloadduct 18 was ob-
tained in quantitative yield showing that the cyclotrimeriza-
tion of the three alkynes is favored over the [2+2+2]
cycloaddition of the enediyne moiety (Scheme 8).
z
The acetalization proceeded in excellent yield only if the following con-
ditions are respected: 10ꢀ2 M in benzene, 5 mol % PTSA, and 2 equiv of
ethylene glycol.

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10585
relationship between the ethynyl and the propargyl groups
for the major diastereomer was assigned by NOE NMR ex-
periments. Alkylation of the lithium acetylide of 23cis/trans
with 8-trimethylsilyl-oct-7-yn-2-one provided the corre-
sponding alcohols 24cis/trans in 66% and 50% yields, re-
spectively. Almost all attempts in generating the allenes
through the sequence—mesylation of the alcohols followed
by a SN20 with copper(I)reagents—were unsuccessful. Only
the addition of phenylcopper(I) reagent on 24cis furnished
the corresponding allene in 10% yield whereas under the
same conditions 24trans (or the mesylate) was recovered.
Subsequent quantitative deprotection of the triple bonds
afforded the allenediyne 25cis.
The cobalt(I)-mediated cyclizations were carried out in the
presence of a stoichiometric amount of CpCo(CO)2 in boil-
ing xylenes under irradiation and depending on the stereo-
chemical relationship (cis or trans) between the ethynyl
group and the chain incorporationg the allene, we disclosed
two different trends. Indeed, the allenediyne 25cis afforded
the bicyclic yne-trienic compound 30 as a mixture of diaste-
reomers in 66% yield. This cycloadduct could result from
a formal Alder ene type reaction between the ethynyl group
and the double bond of the allene bearing the methyl group
(Scheme 11).
O
O
O
O
Ph
(a)
•
Ph
Since the allene formation occurred only for the cis adduct in
poor yield, we decided to study another synthetic path to the
allene 25. As alkylation of the ketone 20 with propargyl bro-
mide furnished the corresponding adduct in 60% yield, we
checked the feasibility of such an alkylation with the mesyl-
ate 28 derived from the alcohol 27.
66%
3
30
25cis
- elim.
β
reductive elim.
O
O
O
The starting material of this sequence was the alcohol 26,
which was generated from the addition of the lithium deriv-
ative of the tetrahydropyranyl propargyl ether with 8-tri-
methylsilyl-oct-7-yn-2-one (Scheme 10). Smooth formation
of the allene and acid hydrolysis of the ether provided the al-
cohol 27 in 94% overall yield. The addition of the correspond-
ing mesylate 28 to the potassium enolate of 20 afforded, after
desilylation of the triple bonds, the allenediyne 29trans as
a 5:4 mixture of two diastereomers in 50% yield over the
three steps (mesylation, alkylation, and desilylation).
O
Ph
•
Ph
4
CpCo
Co
Cp
3
Scheme 11. (a) CpCo(CO)2 (1 equiv), xylenes, hn, D.
Such an Alder ene reaction, which had already been ob-
served by our group24 occurs competitively with the
[2+2+2] cyclization when the latter is disfavored for geomet-
rical reasons. In the present case, molecular models show
that both of the unsaturations can be easily brought closer
together, thus allowing a straightforward complexation of
cobalt. After oxidative coupling, b-elimination followed
by reductive elimination furnished compound 30.
OH
Ph
RO
(a), (b), (c)
(d)
•
4
4
OTHP
26
TMS
27, R = H
28, R = Ms
TMS
O
In contrast, the allenediyne 29transM in presence of
a stoichiometric amount of the cobalt(I) mediator gave the
expected fused tetracyclic complex 31 in 60% yield as
a single diastereomer (Scheme 12). On the basis of 1H
NMR spectrum, the cis relationship between CpCo and the
A/B angular methyl was established (d¼1.75 ppm). The
structure of 31 was secured by a single crystal X-ray analy-
sis,{ which showed an endo stereochemistry between CpCo
and the vicinal methyl group and a trans relationship be-
tween the two angular methyl groups. The free ligand 32
could be readily obtained in 90% yield upon the treatment
of the complex 31 with silica gel. Therefore, the cyclization
and decomplexation sequence could also be carried out with-
out purifying the complex to allow the formation of 11-aryl
steroid skeleton in 48% overall yield.
O
Ph
Ph
(e), (f)
•
20
+
5 : 4
29transM
29transm
Scheme 10. (a) n-BuLi, MsCl, THF, ꢀ78 ꢁC; (b) Me2S$CuBr, PhMgBr,
LiBr, ꢀ50 ꢁC; (c) cat. PTSA, MeOH, rt, 94% from 26; (d) Et3N, cat.
4-DMAP, MsCl, ꢀ40 ꢁC, CH2Cl2; (e) KHMDS, ꢀ15 ꢁC, THF; ꢀ50 ꢁC, 28,
THF; and (f) K2CO3, MeOH, 50%.
The assigned stereochemistry of the major 29transM, which
was obtained pure after flash chromatography and crystalli-
zation, was unambiguously established by X-ray analysis.x
In addition, NMR experiments also showed the trans rela-
tionship between the ethynyl group on the five-membered
ring and the chain incorporating the allene for the minor
29transm diastereomer. However, we were unable to sepa-
rate it from the major diastereomer and we got a 41:59 mix-
ture of 29trans(M/m).
Although the minor allenediyne 29transm was not obtained
pure, it appears interesting to check if it could exhibit the
same reactivity as the major diastereomer. Thus, a mixture
of 29trans(M/m) (41:59)k was exposed to the usual
{
Crystal structure of 31 has been deposited at the Cambridge Crystallo-
graphic Data Centre with the following deposition number: CCDC
245954; see Ref. 10.
The ratio 29trans(M/m) (41:59) was determined by GC and 31:33 (61:39)
x
Crystal structure of 29trans has been deposited at the Cambridge Crystal-
lographic Data Centre with the following deposition number: CCDC
245955; see Ref. 10 supporting information.
k
by 1H NMR on the basis of the integration of Cp-protons.

10586
M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
O
deliver the fused tetracyclic complex (Scheme 14). Due to
O
Ph
Ph
the presence of the five-membered ring, the intermediate co-
baltacyclopentadienes C31 and C33 are quite rigid. For C31,
the most favored approach of the polyunsaturated partners in
which the non-bonded interactions are minimized is the
endo approach relatively to the chain, which would lead to
the endo complex 31. On the contrary for C33, the exo ap-
proach relatively to the chain would be the favored one.
•
(a)
60%
CoCp
29transM
31
O
Ph
(b)
32
90%
Cp
Scheme 12. (a) CpCo(CO)2 (1 equiv), xylenes, hn, D and (b) SiO2,
CH2Cl2, rt.
31
O
Co
O
Co
Cp
conditions of cyclization and this led to (61:39) mixture of
complexes 31 and 33 in 35% yield, which reveals to be the
exo complex (Scheme 13).
C31, endo approach
Cp
O
O
Ph
Ph
33
•
O
+
Co
O
Co
Cp
C33, exo approach
29transM
41 : 59
O
29transm
Scheme 14.
O
Ph
Ph
Thus, the diastereoselectivity of the cyclization for such
allenediynes appears to be controlled by the stereochemistry
of the allene.
(a)
+
35%
CoCp
CoCp
31
61 : 39
33
3. Conclusion
O
O
Ph
Ph
In summary, we reported that the cobalt(I)-mediated
[2+2+2] cyclizations of allenediynes of yne-allene-yne
type bearing an aryl group on the allene are totally chemo-
and regioselective and show low diastereoselectivities.
h4-Complexed tricyclic (6,6,6) compounds were obtained
in good yields as mixtures of endo/exo diastereomers, which
are independent of the substitution of the allene. The cycli-
zation is also compatible with an oxyfunctionality at C3.
(b)
+
90%
32
61 : 39
34
Scheme 13. (a) CpCo(CO)2 (1 equiv), xylenes, hn, D and (b) SiO2,
CH2Cl2, rt.
The results were unexpected: the yield is inferior to the cy-
clization of 29transM and the ratio of the cycloadducts is
different from the starting material one meaning that 33
could be less stable than 31 or/and the cyclization of 29m
is more difficult than the cyclization of 29M leading to deg-
radation. Indeed, besides 31 and 33, intractable materials
were formed. In addition, a third compound was isolated,
which may potentially result from an unanticipated side re-
action of 29transm, but we were unable to unambiguously
identify its structure. Based upon similarities of spectral
data, it seems to exhibit the steroid framework, which has
been modified by several double bond migrations.
Having disclosed that aryl substituted allenes are relevant
partners for these cyclizations, we carefully designed an al-
lenediyne having a preexisting D ring. We observed that, de-
pending on the stereochemical relationship (cis or trans)
between the ethynyl group on the five-membered ring and
the chain incorporating the allene, two different trends
occurred in the cobalt(I)-mediated cyclizations. If trans-
11-aryl steroids have been built in one step and in a totally
diastereoselective manner, with simultaneous introduction
of an angular methyl group at C10 and an aryl substituent at
C11 in 48% overall yield. In contrast, if cis then the allene-
diyne 25cis furnished a bicyclic yne-trienic compound in
66% yield resulting from a formal Alder ene reaction be-
tween the ethynyl group and the double bond of the allene
bearing the methyl group.
Finally, the mixture of 31 and 33 underwent efficient decom-
plexation with silica gel to furnish the free ligands 32 and 34
in 90%, the ratio 61:39 remaining unchanged.
The total diastereoselectivity observed for the cyclization of
both diastereomers 29trans could be explained by the most
probable mechanism of the [2+2+2], which may involve
a cobaltacyclopentadiene.15 The latter could react with the
double bond of the allene bearing the methyl group via an
intramolecular [4+2] cycloaddition process, which will
Interestingly we also observed that the diyne-ene-yne 8 fur-
nished in a quantitative yield the corresponding cycloadduct
bearing an aryl substituent at C11. This result could open
a new synthetic pathway to the steroid nucleus by designing
a judiciously functionalized unsaturated precursor.

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10587
4. Experimental
(PE/EE¼85/15) led to the alcohol 7 (1.33 g, 86%). IR (neat)
1
3450, 3060, 2970, 2850, 2200, 1630, 1440, 1240 cmꢀ1. H
4.1. General
NMR (400 MHz, CDCl3) d 7.58ꢀ7.28 (m, 5H), 2.43 (t,
J¼6.4 Hz, 2H), 2.27 (m, 2H), 2.19 (m, 2H), 1.99 (t,
J¼2.8 Hz, 1H), 2.10–1.90 (m, 2H), 1.75 (m, 6H), 0.09 (s,
9H). 13C NMR (100 MHz, CDCl3) d 141.7 (IV), 127.9
(2C, III), 127.5 (III), 126.4 (2C, III), 107.0 (IV), 88.5 (IV),
84.3 (IV), 83.8 (IV), 79.8 (IV), 79.0 (IV), 68.5 (III), 44.0
(II), 27.5 (II), 27.4 (II), 23.9 (II), 19.6 (II), 18.2 (II), 17.8
(II), 0.0 (3C, I).
Reactions were carried out under argon in flame-dried glass-
ware, with magnetic stirring and degassed anhydrous sol-
vents. All commercially available reagents were used
without further purification unless otherwise noted. All sol-
vents were reagent grade and distilled under positive pres-
sure of dry nitrogen before use. THF was distilled from
sodium/benzophenone. Xylenes and benzene were distilled
from CaH2. Solid reagents were dried in vacuo (0.5–
0.1 mmHg). Thin layer chromatography (TLC) was per-
formed on Merck 60 F254 silica gel. Merck Geduran SI
4.1.2. 1-Trimethylsilyl-6-phenyl-tetradec-5-ene-1,7,13-
triyne (8). Step 1. To a cooled (ꢀ78 ꢁC) solution of 7
(1.07 g, 3.1 mmol), in THF (20 mL) was added a solution
of n-BuLi (2.2 M in hexane, 3.1 mmol). After being stirred
for 10 min at ꢀ78 ꢁC, mesyl chloride (0.24 mL, 3.1 mmol)
was added. The mixture was stirred for additional 30 min
and neutralized with a saturated solution of NH4Cl, brine,
dried over magnesium sulfate, filtered, and concentrated in
vacuo. The crude residue was used without further purifica-
tion in the next step.
˚
60 A silica gel (35–70 mm) was used for column chromato-
graphy. PE and EE refer to petroleum ether and Et2O.
Chemical shifts are reported in parts per million referenced
to the residual proton resonances of the solvents (d¼7.26 for
CDCl3; d¼7.16 for C6D6). Coupling constants (J) are given
in hertz (Hz). The terms m, s, d, t, q, and quint refer to mul-
tiplet, singlet, doublet, triplet, quartet, and quintet; br means
that the signal is broad. Coupling constants are expressed in
hertz. We use (I), (II), (III), and (IV) to characterize primary,
secondary, tertiary, and quaternary carbons.
Step 2. At rt, to a solution of the previously prepared com-
pound in MeOH (5 mL) was added K2CO3 (3.43 g,
24.8 mmol, 8 equiv). The mixture was stirred until TLC in-
dicated the completion of the reaction. Then, the reaction
mixture was diluted with Et2O, washed successively with
a saturated solution of NH4Cl, brine, dried over magnesium
sulfate, filtered, and concentrated in vacuo. Purification by
flash chromatography (PE/EE¼95/5) gave 8 (0.605 g,
76%). IR (neat) 3060, 2970, 2850, 1640, 1440,
ꢀ
Elemental analyses were performed by the Service Regional
de Microanalyse de l’Universite Pierre et Marie Curie—low
ꢀ
resolution mass spectra (MS) and high resolution mass spec-
ꢀ
tra (HRMS) were measured by Service de spectrometrie de
masse de l’ICSN-CNRS, Gif-sur-Yvette. Infrared spectra
(IR) were recorded on a Bruker Tensor 27 spectrometer
(ATR diamond spectrometer). Absorbance frequencies are
850 cmꢀ1 1H NMR (400 MHz, CDCl3) d 7.62–7 (m,
.
2H), 7.34 (m, 2H), 7.27 (m, 1H), 6.42 (t, J¼7.4 Hz, 1H),
2.70 (m, 2H), 2.50 (m, 2H), 2.42 (m, 2H), 2.29 (m, 2H),
2.01 (t, J¼3.5 Hz, 1H), 1.99 (t, J¼3.5 Hz, 1H), 1.77 (m,
4H). 13C NMR (100 MHz, CDCl3) d 144.6 (IV), 137.2
(IV), 132.2 (IV), 128.6 (2C, III), 128.3 (III), 127.1 (2C,
III), 85.2 (IV), 85.0 (IV), 84.7 (IV), 84.2 (IV), 68.3 (III),
67.9 (III), 32.0 (II), 29.9 (II), 29.5 (II), 24.9 (II), 23.5
(II), 22.5 (II).
given at maximum of intensity in cmꢀ1
.
4.1.1. 6-Phenyl-1-(trimethylsilyl)-tetradeca-1,7,13-triyn-
6-ol (7). To a solution of alcohol 6 (1.85 g, 6.74 mmol) in
CH2Cl2 (65 mL) were successively added neutral alumina
(10 g) and pyridinium chlorochromate (PCC, 2 g,
9.44 mmol, 1.4 equiv). The mixture was stirred until com-
pletion of the reaction by TLC and then, was filtered on
Celite pad. The filtered solution was successively washed
with a saturated solution of NH4Cl, brine, dried over magne-
sium sulfate, filtered, and concentrated in vacuo. The residue
was purified by flash chromatography (PE/EE¼90/10) and
furnished the ketone (1.37 g, 75%). IR (neat) 3060, 2970,
4.1.3. 7-(tert-Butyldimethylsilyloxy)-hept-1-yn-4-ol (10).
At ꢀ30 ꢁC, to a solution of 4-(tert-butyldimethylsilyloxy)-
butyraldehyde (15.46 g, 76.4 mmol) in Et2O (80 mL) was
slowly added a solution of propargylic magnesiumbromide
(80 mmol, 1.05 equiv). The resulting solution was warmed
up to rt and stirred for 2 h. Then, the mixture was diluted
with Et2O, washed successively with a saturated solution
of NH4Cl, brine, dried over magnesium sulfate, filtered,
and concentrated in vacuo. Purification by flash chromato-
graphy (PE/EE¼80/20) led to 10 (15.8 g, 85%). IR (neat)
2850, 2200, 1630, 1440, 1240 cmꢀ1. H NMR (400 MHz,
1
CDCl3) d 2.42 (t, J¼7.1 Hz, 2H), 2.37 (t, J¼7.1 Hz, 2H),
2.18 (m, 2H), 2.10 (t, J¼7.1 Hz, 2H), 1.85 (t, J¼2.5 Hz,
1H), 1.69–1.57 (m, 4H), 1.40 (qt, J¼7.1, 7.1 Hz, 2H),
ꢀ0.00 (s, 9H). 13C NMR (100 MHz, CDCl3) d 187.1 (IV),
106.6 (IV), 92.6 (IV), 84.7 (IV), 82.5 (IV), 81.0 (IV), 69.3
(III), 44.7 (II), 27.6 (II), 26.3 (II), 22.9 (II), 19.4 (II), 17.7
(II), 17.4 (II), 0.0 (3C, I). HRMS calcd for C17H24OSi
(272.46) (MH+) 273.160. Found 273.167.
3450, 2950, 2200, 1450 cmꢀ1
.
1H NMR (400 MHz,
CDCl3) d 3.77–3.62 (m, 2H), 3.23 (br s, 1H), 2.39 (dd,
J¼3.2, 2.8 Hz, 2H), 2.03 (t, J¼2.43 Hz, 1H), 1.80–1.78
(m, 2H), 1.69–1.65 (m, 2H), 0.89 (s, 9H), 0.07 (s, 6H). 13C
NMR (100 MHz, CDCl3) d 81.3 (IV), 70.4 (III), 69.8 (III),
63.4 (II), 33.6 (II), 29.1 (II), 27.2 (II), 25.9 (3C, I), 18.3
(IV), ꢀ5.3 (2C, I).
To a cooled (ꢀ78 ꢁC) solution of the previously prepared ke-
tone (1.37 g, 5.1 mmol) in Et2O (20 mL) was added a solu-
tion of phenyllithium (1.8 M in THF, 6.72 mmol, 1.2 equiv).
The mixture was stirred until completion of the reaction by
TLC and diluted with Et2O, washed with a saturated solution
of NH4Cl, brine, dried over magnesium sulfate, filtered, and
concentrated in vacuo. Purification by flash chromatography
4.1.4. 1-(tert-Butyldimethylsilyloxy)-4-methoxy-hept-6-
yne (11). At 0 ꢁC, to a suspension of sodium hydride (60%
in mineral oil, 1 g, 24 mmol, 1.2 equiv) in THF (60 mL)
was added a solution of alcohol 10 (4.85 g, 20 mmol) in

10588
M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
THF (60 mL). After 30 min at rt, iodomethane (6.2 mL,
14.2 g, 100 mmol, 5 equiv) was added. After being stirred
for 2 h, the resulting mixture was diluted with Et2O, washed
successively with a saturated solution of NH4Cl, brine, dried
over magnesium sulfate, filtered, and concentrated in vacuo.
The crude residue was purified by flash chromatography
(PE/EE¼95/5) to furnish the ether 11 (5.12 g, quantitative).
4.1.7. 7-Methyl-1-(trimethylsilyl)-tetradeca-1,8,13-triyn-
7-ol (14). At ꢀ78 ꢁC n-BuLi (2.1 M in hexane, 29.1 mL,
61.1 mmol, 1.2 equiv) was added dropwise to a solution of
hepta-1,6-diyne (10 g, 102 mmol, 2 equiv) in THF
(300 mL). After being stirred at ꢀ78 ꢁC for 30 min, a solu-
tion of 8-(trimethylsilyl)-oct-7-yn-2-one
9
(10 g,
50.9 mmol, 1 equiv) in THF (50 mL) was added. The reac-
tion mixture was warmed up at rt, stirred for 2 h and was di-
luted with Et2O, washed successively with a saturated
solution of NH4Cl, brine, dried over magnesium sulfate, fil-
tered, and concentrated in vacuo. Purification by flash chro-
matography (PE/EE¼90/10) furnished 14 (10.28 g, 70%).
IR (neat) 2950, 2200, 1450 cmꢀ1 1H NMR (400 MHz,
.
CDCl3) d 3.74 (m, 1H), 3.64–3.61 (m, 2H), 3.37 (s, 3H),
2.42–2.38 (m, 2H), 1.98 (t, J¼2.48 Hz, 1H), 1.68–1.55 (m,
4H), 0.89 (s, 9H), 0.04 (s, 6H). 13C NMR (100 MHz,
CDCl3) d 81.0 (IV), 79.0 (I), 69.9 (III), 63.1 (II), 57.0
(III), 29.8 (II), 28.5 (II) 26.0 (3C, I), 23.2 (II), 18.4 (IV),
ꢀ5.2 (2C, I).
IR (neat) 3400, 3300, 2240, 2180, 1240, 840 cmꢀ1 1H
.
NMR (400 MHz, CDCl3) d 2.34–2.25 (m, 4H), 2.23 (m,
2H), 1.96 (t, J¼2.6 Hz, 1H), 1.70 (qt, J¼7.04 Hz, 2H),
1.68–1.54 (m, 6H), 1.44 (s, 3H), 0.13 (s, 9H). 13C NMR
(100 MHz, CDCl3) d 107.4, (IV), 84.8 (IV), 84.6 (IV),
82.5 (2C, IV), 68.9 (III), 68.2 (IV), 57.0 (III), 43.4 (II),
30.1 (I), 28.8 (II), 27.6 (II), 24.1 (II), 19.9 (II), 17.7 (II),
17.6 (II), 0.2 (3C, I). Anal. Calcd for C26H32O2Si
(288.50): C, 74.94; H, 9.78. Found: C, 75.08; H, 9.66.
4.1.5. 4-Methoxy-hept-6-yn-1-ol (12). At 0 ꢁC, to a solution
of 11 (5.12 g, 20 mmol) in THF (100 mL) was added drop-
wise a 1 M solution in THF of TBAF (20 mL, 20 mmol).
The reaction was stirred at rt until TLC indicated the com-
pletion of the reaction. Then, it was diluted with Et2O,
washed successively with a saturated solution of NH4Cl,
brine, dried over magnesium sulfate, filtered, and concen-
trated in vacuo. Purification by flash chromatography (PE/
AcOEt¼60/40) led to 12 (2.44 g, 86%). IR (neat) 3450,
4.2. General procedure for the preparation of allene-
diynes 16a–c
1
2970, 2200, 1450, 870 cmꢀ1. H NMR (400 MHz, CDCl3)
d 3.74 (m, 1H), 3.63–3.60 (m, 2H), 3.35 (s, 3H), 2.42–2.38
(m, 2H), 1.98 (t, J¼2.48 Hz, 1H), 1.68–1.55 (m, 4H). 13C
NMR (100 MHz, CDCl3) d 81.1 (IV), 79.5 (I), 70.5 (IV),
63.0 (II), 57.0 (III), 30.4 (II), 28.8 (II), 23.3 (II).
A THF solution of arylmagnesium chloride or bromide
(2.6 mmol, 1.5 equiv) was added dropwise at ꢀ50 ꢁC to
a suspension of Me2S$CuBr (0.535 g, 2.6 mmol, 1.5 equiv)
and LiBr (0.224 g, 2.6 mmol, 1.5 equiv) in THF (20 mL)
and the resulting mixture was stirred at ꢀ50 ꢁC for 15 min.
4.1.6. 5-Methoxy-oct-7-yn-2-one (13). Step 1. To a cooled
solution (ꢀ78 ꢁC) of oxalyl chloride (4 mL, 46 mmol,
1.3 equiv) in CH2Cl2 (130 mL) was added dropwise a solu-
tion of DMSO (6.5 mL, 91 mmol, 2.6 equiv) in CH2Cl2
(70 mL). After 5 min, a solution of 12 (5 g, 35 mmol) in
CH2Cl2 (50 mL) was added dropwise and after being stirred
for an additional 15 min, triethylamine (24 mL, 175 mmol,
5 equiv) was added. The mixture was allowed to warm to
rt, diluted with Et2O, washed successively with a saturated
solution of NH4Cl, brine, dried over magnesium sulfate, fil-
tered, and concentrated in vacuo. The crude residue was used
without further purification in the next step.
At ꢀ78 ꢁC, a 2.1 M solution of n-BuLi in hexane (0.82 mL,
1.73 mmol, 1 equiv) was added dropwise to a solution of the
alcohol 14 (0.50 g, 1.73 mmol). After being stirred for
5 min, pure mesyl chloride (0.15 mL, 1.90 mmol, 1.1 equiv)
was added. The resulting solution was stirred for 5 min and
transferred via a cannula into a solution of the previously
prepared copper(I) reagent. After stirring for 30 min at
ꢀ50 ꢁC, the temperature was allowed to warm up at rt.
The reaction mixture was hydrolyzed with a saturated solu-
tion of NH4Cl/NH4OH (2/1) and partitioned with Et2O. The
organic layer was washed with brine, dried over MgSO4, fil-
tered, and concentrated in vacuo to give the corresponding
allenediynes. The crude mixture was used in the next step
without any further purification.
Step 2. At 0 ꢁC, to a solution of the preceding aldehyde in
Et2O (40 mL) was added a solution of methylmagnesium
bromide (3 M in Et2O, 12.8 mL, 1.1 equiv). The mixture
was warmed up to rt, stirred until TLC indicated the comple-
tion of the reaction. Then, it was diluted with Et2O, washed
successively with a saturated solution of NH4Cl, brine, dried
over magnesium sulfate, filtered, and concentrated in vacuo.
The crude residue was used without further purification in
the next step.
K2CO3 (1.88 g, 13.6 mmol, 8 equiv) was added to a solution
of previously prepared crude compound in MeOH (10 mL)
and the resulting mixture was stirred until TLC had indicated
the completion of the reaction. The mixture was diluted with
Et2O, washed with a saturated solution of NH4Cl and brine,
dried over MgSO4, filtered, and concentrated. Purification
by flash chromatography (PE/EE¼9/1) led to the allene-
diynes 16a–c.
Step 3. The previously prepared alcohol was oxidized fol-
lowing the same procedure as described for step 1. Purifi-
cation by flash chromatography (PE/EE¼90/10) gave the
ketone 13 (4.07 g, 75% from 12). IR (neat) 3300, 2970,
4.2.1. (3-Methyl-1-pent-4-ynyl-nona-1,2-dien-8-ynyl)-
benzene (16a). 0.344 g, 72%. IR (neat) 2950, 2210, 2180,
1960, 1440, 950 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 7.44
(m, 2H), 7.37 (m, 2H), 7.25 (m, 1H), 2.61 (t, J¼7.3 Hz,
2H), 2.36 (dt, J¼4.6, 2.4 Hz, 2H), 2.24 (m, 2H), 2.17 (m,
2H), 2.05 (t, J¼2.44 Hz, 1H), 2.01 (t, J¼2.5 Hz, 1H), 1.87
(s, 3H), 1.84 (m, 2H), 1.82 (m, 4H). 13C NMR (100 MHz,
CDCl3) d 201.2 (IV), 138.0 (IV), 128.4 (2C, III), 126.3
2200, 1650, 1450, 870 cmꢀ1
.
1H NMR (400 MHz,
CDCl3) d 3.74 (m, 1H), 3.37 (s, 3H), 2.42–2.38 (m, 4H),
2.10 (s, 3H), 1.98 (t, J¼2.48 Hz, 1H), 1.80–1.76 (m, 2H).
13C NMR (100 MHz, CDCl3) d 209.2 (IV), 81.1 (IV),
79.5 (I), 70.5 (III), 57.0 (III), 47.3 (I), 31.4 (II), 28.7 (II),
23.3 (II).

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10589
(III), 125.9 (2C, III), 103.9 (IV), 103.1 (IV), 84.5 (2C, IV),
68.6 (2C, III), 33.9 (II), 29.3 (II), 28.4 (II), 27.0 (II), 26.8
(II), 19.8 (II), 18.9 (I), 18.2 (II). HRMS calcd for C21H24
(276.42) (MH+) 277.188. Found: 277.187.
17a endo: 1H NMR (400 MHz, C6D6) d 7.83 (m, 2H), 7.46
(m, 3H), 5.24 (d, J¼3.9 Hz, 1H), 4.37 (s, 5H), 4.36 (d,
J¼3.9 Hz, 1H), 2.45–2.42 (m, 2H), 2.2–2.05 (m, 2H),
1.96–1.95 (m, 2H), 1.81 (s, 3H), 1.57–1.56 (m, 4H), 1.33–
1.31 (m, 4H). 13C NMR (100 MHz, C6D6) d 150.3 (IV),
142.3 (IV), 126.0 (IV), 129–125 (5C, III), 81.7 (5C, III),
76.9 (III), 73.5 (IV), 72.8 (III), 65.2 (IV), 48.2 (IV), 36.9
(II), 36.5 (II), 35.0 (II), 31.8 (II), 27.5 (I), 26.4 (II), 25.0
(II), 24.7 (II).
4.2.2. 1-(3-Methyl-1-pent-4-ynyl-nona-1,2-dien-8-ynyl)-
4-trifluoromethyl-benzene (16b). 0.303 g, 51%. IR (neat)
1
2950, 2210, 2180, 1960, 1440 cmꢀ1. H NMR (400 MHz,
CDCl3) d 7.57 (d, J¼8.0 Hz, 2H), 7.50 (d, J¼8.0 Hz, 2H),
2.56 (t, J¼7.6 Hz, 2H), 2.34–2.30 (m, 2H), 2.22–2.18 (m,
2H), 2.16–2.13 (m, 2H), 2.01 (t, J¼1.6 Hz, 1H), 1.96 (t,
J¼2.4 Hz, 1H), 1.84 (s, 3H), 1.81–1.77 (m, 2H), 1.59 (m,
4H). 13C NMR (100 MHz, CDCl3) d 202.1 (IV), 144.2 (q,
J¼81 Hz, IV), 142.0 (IV), 126.3 (q, J¼140 Hz, IV), 127.7
(III), 126.0 (2C, III), 125.2 (III), 103.9 (IV), 103.5 (IV),
84.2 (2C, IV), 68.7 (III), 68.4 (III), 33.7 (II), 29.1 (II),
28.2 (II), 26.9 (II), 26.7 (II), 18.8 (I), 18.3 (II), 18.1 (II).
1
17a exo: H NMR (400 MHz, C6D6) d 7.32–7.23 (m, 5H),
4.91 (d, J¼3.9 Hz, 1H), 4.64 (s, 5H), 4.47 (d, J¼3.9 Hz,
1H), 2.35–2.22 (m, 2H), 2.2–2.05 (m, 2H), 1.88–1.83 (m,
2H), 1.57–1.56 (m, 4H), 1.55–1.45 (m, 4H), 1.21 (s, 3H).
13C NMR (100 MHz, C6D6) d 146.3 (IV), 144.2 (IV),
126.0 (IV), 129–125 (5C, III), 80.9 (5C, III), 78.0 (III),
77.5 (IV), 76.0 (III), 65.3 (IV), 48.2 (IV), 40.9 (II), 37.7
(II), 37.4 (II), 35.6 (II), 30.8 (II), 26.1 (II), 24.3 (I), 22.7
(II). HRMS calcd for C26H29Co (400.44) (MH)+ 401.168.
Found: 401.165.
4.2.3. 1-Methoxy-4-(3-methyl-1-pent-4-ynyl-nona-1,2-
dien-8-ynyl)-benzene (16c). 0.175 g, 33%. IR (neat) 2980,
2200, 2180, 1960, 1440 cmꢀ1
.
1H NMR (400 MHz,
CDCl3) d 7.34 (m, 2H), 6.89 (m, 2H), 3.82 (s, 3H), 2.52 (t,
J¼7.3 Hz, 2H), 2.33–2.29 (m, 2H), 2.22–2.20 (m, 2H),
2.12 (m, 2H), 2.01 (t, J¼2.5 Hz, 1H), 1.97 (t, J¼2.5 Hz,
1H), 1.82 (s, 3H), 1.80–1.79 (m, 2H), 1.61–1.60 (m, 4H).
13C NMR (100 MHz, CDCl3) d 200.6 (IV), 158.3 (IV),
132.2 (IV), 127.0 (2C, III), 113.8 (2C, III), 103.6 (IV),
102.8 (IV), 84.5 (2C, IV), 68.6 (III), 68.4 (III), 55.3 (I),
33.9 (II), 29.5 (II), 28.3 (II), 27.0 (II), 26.8 (II), 19.1 (I),
18.3 (II), 18.2 (II).
4.3.2. Cycloadduct (17b). 0.268 g, 65% (endo/exo¼53/47).
17b endo: 1H NMR (400 MHz, C6D6) d 7.48 (d, J¼8.2 Hz,
2H), 7.13 (d, J¼8.2 Hz, 2H), 5.2 (d, J¼3.9 Hz, 1H), 4.33
(d, J¼3.9 Hz, 1H), 4.26 (s, 5H), 2.35–2.25 (m, 2H), 2.2–
2.05 (m, 2H), 1.91–1.85 (m, 2H), 1.67 (s, 3H), 1.57–1.56
(m, 4H), 1.49–1.45 (m, 2H), 1.33–1.31 (m, 2H). 13C NMR
(100 MHz, C6D6) d 150.3 (2C, IV), 142.3 (2C, IV), 126.0
(IV), 129–125 (4C, III), 81.6 (5C, III), 77.0 (III), 73.5
(IV), 72.7 (III), 65.2 (IV), 48.2 (IV), 37.1 (II), 36.8 (II),
36.2 (II), 31.5 (II), 27.6 (I), 26.3 (II), 24.4 (II), 24.2 (II).
4.2.4. (6-Methoxy-3-methyl-1-pent-4-ynyl-nona-1,2-
dien-8-ynyl)-benzene (16d). It was obtained using the
same procedure as for the preparation of 14 (the intermediate
alcohol was not purified) followed by the sequence de-
scribed for 16a–c. 0.303 g, 36% overall yield. IR (neat)
1
17b exo: H NMR (400 MHz, C6D6) d 7.48 (d, J¼8.2 Hz,
2H), 7.13 (d, J¼8.2 Hz, 2H), 4.90 (d, J¼3.9 Hz, 1H), 4.63
(s, 5H), 4.44 (d, J¼3.9 Hz, 1H), 2.35–2.25 (m, 2H), 2.2–
2.05 (m, 2H), 1.91–1.85 (m, 2H), 1.57–1.56 (m, 4H),
1.49–1.45 (m, 2H), 1.33–1.31 (m, 2H), 1.06 (s, 3H). 13C
NMR (100 MHz, C6D6) d 150.3 (2C, IV), 143.0 (2C, IV),
126.0 (IV), 129–125 (4C, III), 81.6 (5C, III), 78.1 (III),
76.0 (III), 73.5 (IV), 65.2 (IV), 48.2 (IV), 40.8 (II), 35.5
(II), 34.8 (II), 30.7 (II), 25.9 (II), 24.2 (I), 22.6 (II), 22.5
(II). IR (neat): 3250, 2950, 2920, 1950, 1630, 1470, 1450,
1350, 850 cmꢀ1. HRMS calcd for C27H28CoF3 (468.44)
(MH)+ 469.148. Found: 469.154.
1
2950, 2210, 2180, 1960, 1440 cmꢀ1. H NMR (400 MHz,
CDCl3) d 7.42 (m, 2H), 7.33 (m, 2H), 7.25 (m, 1H), 3.72
(m, 1H), 3.35 (s, 3H), 2.61 (t, J¼7.4 Hz, 2H), 2.36 (dt,
J¼4.7, 2.5 Hz, 2H), 2.24 (m, 2H), 2.17 (m, 2H), 2.05 (t,
J¼2.5 Hz, 1H), 2.01 (t, J¼2.5 Hz, 1H), 1.87 (s, 3H), 1.84
(m, 2H), 1.82 (m, 2H). 13C NMR (100 Hz, CDCl3) d 201.2
(IV), 138.0 (IV), 128.4 (2C, III), 126.3 (III), 125.9 (2C,
III), 103.9 (IV), 103.1 (IV), 84.5 (2C, IV), 78.7 (I), 68.6
(2C, III), 57.1 (III), 33.9 (II), 29.3 (II), 28.4 (II), 26.8 (II),
19.8 (II), 18.9 (I), 18.2 (II).
4.3.3. Cycloadduct (17c). 0.152 g, 62% (endo/exo¼61/39).
4.3. General procedure for the preparation of the
cycloadducts 17a–d
17c endo: 1H NMR (400 MHz, C6D6) d 7.16 (m, 2H), 6.85
(m, 2H), 5.25 (d, J¼3.9 Hz, 1H), 4.38 (s, 5H), 4.37 (d,
J¼3.9 Hz, 1H), 3.57 (s, 3H), 2.52–2.48 (m, 2H), 2.2–2.05
(m, 2H), 1.99–1.87 (m, 4H), 1.84 (s, 3H), 1.57–1.56 (m,
2H), 1.47–1.36 (m, 4H). 13C NMR (100 MHz, C6D6)
d 158.0 (IV), 142.5 (IV), 129.9 (IV), 128.1 (2C, III), 127.2
(IV), 112.1 (2C, III), 81.6 (5C, III), 76.9 (III), 73.3 (IV),
72.7 (III), 64.4 (IV), 54.6 (I), 48.2 (IV), 36.9 (II), 36.6 (II),
35.1 (II), 31.8 (II), 27.5 (I), 26.4 (II), 25.0 (II), 24.6 (II).
Cyclopentadienyldicarbonylcobalt(I) (1.2 equiv) was added
to a boiling solution of allenediyne 16a–d (1 equiv) in
xylenes degassed by three freeze-pump-thaw cycles and
was irradiated (light from projector lamp; ELW, 300 W,
50% of its power). The reaction was monitored by TLC
and after completion, the reaction mixture was concentrated
in vacuo. The crude oil was purified by flash chromato-
graphy (the solvents of chromatography were not degassed)
either on deactivated alumina with 3% H2O (PE) or on silica
gel neutralized with NEt3 and dried (PE/EE 95/5) to furnish
17a–d as an inseparable endo/exo mixture.
16c exo: 1H NMR (400 MHz, C6D6) d 7.75 (m, 2H), 7.09 (m,
2H), 4.93 (d, J¼3.9 Hz, 1H), 4.65 (s, 5H), 4.48 (d, J¼3.9 Hz,
1H), 3.37 (s, 3H), 2.52–2.48 (m, 2H), 2.2–2.05 (m, 2H),
1.99–1.87 (m, 4H), 1.57–1.56 (m, 2H), 1.47–1.36 (m, 4H),
1.27 (s, 3H). 13C NMR (100 MHz, C6D6) d 157.9, 142.3,
4.3.1. Cycloadduct (17a). 0.180 g, 60% (endo/exo¼55/45).

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M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
129.9, 129.8 (2C), 127.2, 113.4 (2C), 80.9 (5C), 78.0 (III),
76.0 (III), 74.8 (IV), 65.5 (IV), 54.5 (I), 46.7 (IV), 40.9
(II), 37.9 (II), 37.4 (II), 35.6 (II), 30.9 (II), 26.2 (II), 24.2
(I), 22.8 (II). HRMS calcd for C27H31CoO (MH)+ 431.179.
Found: 431.177.
1.02 (s, 3H), 0.13 (s, 9H). 13C NMR (100 MHz, CDCl3)
d 218.4 (IV), 104.9 (IV), 88.2 (IV), 80.4 (IV), 71.0 (III),
51.3 (IV), 36.7 (III), 36.6 (II), 25.9 (II), 25.2 (II), 18.0 (I),
0.2 (3C, I). EIMS (m/z, %) 233 (100), 217 (35).
22trans: 1H NMR (400 MHz, CDCl3) d 2.87 (t, J¼13.8 Hz,
1H), 2.44–2.00 (m, 6H), 1.97 (t, J¼2.4 Hz, 1H), 1.14 (s, 3H),
0.12 (s, 9H). 13C NMR (100 MHz, CDCl3) d 218.4 (IV),
105.0 (IV), 89.2 (IV), 80.5 (IV), 70.5 (III), 51.2 (IV), 39.8
(III), 35.5 (II), 25.7 (II), 23.7 (II), 20.7 (I), 0.0 (3C, I).
EIMS (m/z, %) 233 (100), 217 (35).
4.3.4. Cycloadduct (17d). 0.077 g, 62% (endo/exo¼65/35).
This cyclization led to the formation of an inseparable mix-
ture of four diastereomers endo/exo and it was impossible to
fully describe the compounds particularly the 13C NMR
spectra were unexploitable. Only the characteristic data in
1H NMR are given.
4.3.7. Trimethyl-(6-methyl-6-prop-2-ynyl-1,4-dioxa-
spiro[4,4]non-7-ylethynyl)-silane (23). A solution of
ketone 22cis/trans (0.313 g, 1.35 mmol), ethylene glycol
(0.15 mL, 2.7 mmol, 2 equiv) and PTSA (0.01 g,
0.07 mmol, 0.05 equiv) in benzene (13 mL) was refluxed
with a Dean–Stark apparatus for 12 h. After being cooled
at rt, the reaction mixture was diluted with Et2O, washed
successively with a 2:1 saturated solution of NH4Cl/
NH4OH and brine, dried over MgSO4, filtered, and concen-
trated in vacuo. Filtration through silica gel (PE/EE¼9/1)
gave the acetals 23cis/trans (0.355 g, cis/trans¼2/1, 95%).
17d endo (two diastereomers): 7.60 (m, 4H), 7.46 (m, 6H),
5.62 (d, J¼3.9 Hz, 1H), 5.35 (d, J¼3.9 Hz, 1H), 4.33 (s,
5H), 4.31 (s, 5H), 4.65 (d, J¼3.9 Hz, 1H), 4.41 (d,
J¼3.9 Hz, 1H), 3.38 (s, 3H), 3.36 (m, 2H), 3.35 (s, 3H),
2.45–1.3 (m, 24H), 1.54 (s, 3H), 1.45 (s, 3H).
17d exo (two diastereomers): 7.60 (m, 4H), 7.46 (m, 6H),
5.02 (d, J¼3.9 Hz, 1H), 4.99 (d, J¼3.9 Hz, 1H), 4.76 (s,
5H), 4.67 (s, 5H), 4.66 (d, J¼3.9 Hz, 1H), 4.5 (d,
J¼3.9 Hz, 1H), 3.32 (m, 2H), 3.30 (s, 3H), 3.28 (s, 3H),
2.45–1.3 (m, 24H), 1.02 (s, 3H), 0.96 (s, 3H).
23cis: Mp 62–64 ꢁC. 1H NMR (400 MHz, CDCl3) d 3.89 (m,
4H), 2.69 (t, J¼17.7 Hz, 1H), 2.51–2.26 (m, 2H), 1.98–1.88
(m, 3H), 1.79–1.66 (m, 2H), 1.09 (s, 3H), 0.10 (s, 9H). 13C
NMR (100 MHz, CDCl3) d 118.0 (IV), 107.2 (IV), 87.8
(IV), 83.2 (IV), 69.0 (III), 65.5 (II), 64.8 (II), 48.9 (IV),
40.2 (III), 33.6 (II), 26.7 (II), 23.0 (II), 19.7 (I), 0.2 (3C, I).
Anal. Calcd for C16H24O2Si: C, 69.51; H, 8.75. Found: C,
69.33; H, 8.95.
4.3.5. 5-Phenyl-1,2,3,4,7,8-hexahydro-phenanthrene
(18). 0.150 g, quantitative. IR (neat) 3060, 2970, 2850,
1630, 1440, 850 cmꢀ1 1H NMR (400 MHz, CDCl3)
.
d 7.35–7.31 (m, 2H), 7.28–7.25 (m, 3H), 7.09 (d,
J¼7.6 Hz, 1H), 7.00 (d, J¼7.6 Hz, 1H), 6.28 (t, J¼5.1 Hz,
1H), 2.79 (t, J¼6.6 Hz, 2H), 2.71 (t, J¼7.1 Hz, 2H), 2.29–
2.24 (m, 2H), 2.01 (t, J¼6.2 Hz, 2H), 1.66 (m, 2H), 1.48
(m, 2H). 13C NMR (100 MHz, CDCl3) d 144.6 (IV), 141.2
(IV), 137.2 (IV), 136.6 (IV), 135.0 (IV), 134.8 (IV), 132.2
(III), 128.6 (2C, III), 128.3 (III), 127.1 (2C, III), 126.6
(III), 125.0 (III), 31.0 (II), 30.6 (II), 30.1 (II), 23.9 (II),
23.5 (II), 22.9 (II).
23trans: 1H NMR (400 MHz, CDCl3) d 4.00–3.85 (m, 4H),
2.69 (t, J¼17.7 Hz, 1H), 2.29 (m, 2H), 1.99–1.87 (m, 3H),
1.79–1.62 (m, 2H), 1.16 (s, 3H), 0.12 (s, 9H). 13C NMR
(100 MHz, CDCl3) d 118.0 (IV), 107.1 (IV), 87.4 (IV),
82.5 (IV), 69.5 (III), 65.1 (II), 64.6 (II), 48.4 (IV), 39.0
(III), 33.2 (II), 26.0 (II), 23.7 (II), 16.6 (I), 0.2 (3C, I).
Anal. Calcd for C16H24O2Si: C, 69.51; H, 8.75. Found: C,
69.33; H, 8.95.
4.3.6. 2-Methyl-2-prop-2-ynyl-3-(trimethylsilylethynyl)-
cyclopentanone (22). To a cooled (ꢀ78 ꢁC) solution of
(propargyl)methyl ether hexacarbonyl dicobalt complex
(0.69 g, 1.92 mmol, 1.03 equiv) in CH2Cl2 (8 mL) was
added Et2O$BF3 (0.5 mL, 1.92 mmol, 1.03 equiv). After
warming up at rt, the reaction mixture was stirred for
15 min and silyl enol ether 1921 (0.50 g, 1.87 mmol) was
added. After being stirred at rt until completion of the reac-
tion (TLC), the reaction mixture was diluted with Et2O,
washed with a saturated solution of NH4Cl and brine, dried
over MgSO4, filtered, and concentrated in vacuo to furnish
the ketones 21. The crude mixture was used in the next
step without any further purification.
4.3.8. Methyl-1-[6-methyl-7-(trimethylsilylethynyl)-1,4-
dioxa-spiro[4,4]non-6-yl]-10-trimethylsilyl-deca-2,9-
diyn-4-ol (24). To a cooled (ꢀ78 ꢁC) solution of 23 (0.50 g,
1.81 mmol) in THF (10 mL) was added dropwise n-BuLi
(2.5 M in hexane, 0.72 mL, 1.81 mmol). After being stirred
at ꢀ78 ꢁC for 30 min, a solution of 8-(trimethylsilyl)-oct-7-
yn-2-one (0.355 g, 1.81 mmol) in THF (5 mL) was added.
The temperature was allowed to warm up at rt, the mixture
was stirred until TLC had indicated the completion of the re-
action. The reaction was diluted with Et2O, washed with
a saturated solution of NH4Cl, brine, dried over MgSO4, fil-
tered, and concentrated in vacuo. Purification by flash chro-
matography (PE/EE¼85/15) afforded the alcohols 24cis and
24trans.
To a solution of the previously prepared ketones 21 in
acetone (250 mL) was added portionwise CAN (8.2 g,
14.96 mmol, 8 equiv). After being stirred for 5 min at rt,
the reaction mixture was diluted with Et2O (1 L), washed
successively with H2O and brine, dried over MgSO4, fil-
tered, and concentrated in vacuo. Flash chromatography
(PE/EE¼95/5) of the residue furnished the ketones 22cis/
trans (0.318 g, cis/trans¼2/1, 74% over the two steps).
24cis: 0.564 g, 66%. IR(neat) 3610, 2980, 2950, 2290, 2000,
1470, 1390, 1350 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 3.90
(m, 4H), 2.70 (t, J¼17.7 Hz, 1H), 2.45 (m, 2H), 2.30–2.24
(m, 4H), 1.81–1.69 (m, 2H), 1.60–1.59 (m, 6H), 1.44 (s,
3H), 1.08 (s, 3H), 0.13 (s, 9H), 0.12 (s, 9H). 13C NMR
(100 MHz, CDCl3) d 118.1 (IV), 107.3 (2C, IV), 87.6
1
22cis: H NMR (400 MHz, CDCl3) d 3.28 (dd, J¼11.2,
6.8 Hz, 1H), 2.49–2.05 (m, 6H), 1.96 (t, J¼2.4 Hz, 1H),

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10591
(IV), 84.4 (IV), 82.5 (2C, IV), 68.2 (IV), 65.5 (II), 64.8 (II),
49.1 (IV), 43.3 (II), 40.2 (III), 33.7 (II), 30.0 (I), 28.8 (II),
26.7 (II), 24.1 (II), 23.2 (II), 20.3 (II), 19.9 (I), 0.28 (3C,
I), 0.22 (3C, I). Anal. Calcd for C27H44O3Si2: C, 68.59; H,
9.38. Found: C, 68.44; H, 9.57.
38.0 (III), 33.7 (II), 32.8 (II), 32.2 (II), 28.3 (II), 26.9 (II),
26.5 (II), 20.7 (I), 18.7 (II), 18.3 (I).
4.3.10. 4-Methyl-1-(tetrahydropyran-2-yloxy)-10-tri-
methylsilyl-deca-2,9-diyn-4-ol (26). To a cooled (ꢀ78 ꢁC)
solution of 8-trimethylsilyl-oct-7-yn-2-one (1.19 g,
6.04 mmol, 1 equiv) in THF (10 mL) was added at ꢀ78 ꢁC
the lithium acetylide derived from tetahydropyranyl prop-
argyl ether (0.6 M in THF, 6.04 mmol, 1 equiv). After warm-
ing up at rt, the reaction mixture was stirred until TLC
indicated the completion, diluted with Et2O, washed with
a saturated solution of NH4Cl, brine, dried over MgSO4, fil-
tered, and concentrated invacuo. Flash chromatography (PE/
EE¼9/1) of the residue furnished the alcohol 26 (1.93 g,
24trans: 0.43 g, 50%. IR(neat) 3610, 2980, 2950, 2290,
1
2000, 1470, 1390, 1350 cmꢀ1. H NMR (200 MHz, C6D6)
d 3.77–3.50 (m, 2H), 3.46–3.35 (m, 2H), 2.90 (t,
J¼18.7 Hz, 1H), 2.54 (br s, 2H), 2.11 (t, J¼13.7 Hz, 2H),
1.92–1.52 (m, 10H), 1.46 (s, 3H), 1.44 (s, 3H), 0.22 (s,
9H), 0.18 (s, 9H). 13C NMR (50 MHz, C6D6) d 119.0 (IV),
108.9 (2C, IV), 88.5 (IV), 87.1 (IV), 85.6 (IV), 82.4 (IV),
68.9 (IV), 66.0 (II), 65.6 (II), 49.9 (IV), 44.7 (II), 40.6 (III),
34.4 (II), 31.2 (I), 30.2 (II), 26.6 (II), 25.6 (II), 25.4 (II),
21.2 (II), 18.3 (I), 1.3 (6C, I). Anal. Calcd for
C27H44O3Si2: C, 68.59; H, 9.38. Found: C, 68.44; H, 9.57.
95%). IR(neat) 3400, 2950, 2100, 1250, 930 cmꢀ1 1H
.
NMR (400 MHz, CDCl3) d 4.78 (t, J¼3.2 Hz, 1H), 4.24 (d,
J¼8.4 Hz, 2H), 3.82–3.76 (m, 1H), 3.52–3.47 (m, 1H),
2.20 (t, J¼6.4 Hz, 2H), 1.77–1.48 (m, 12H), 1.43 (s, 3H),
0.09 (s, 9H). 13C NMR (100 MHz, CDCl3) d 107.4 (IV),
96.6 (III), 89.9 (IV), 84.6 (IV), 79.0 (IV), 67.9 (IV), 61.9
(II), 54.3 (II), 43.0 (II), 30.2 (II), 28.7 (II), 29.7 (I), 25.4
(II), 24.0 (II), 19.8 (II), 18.9 (II), 0.2 (3C, I). Anal. Calcd
for C19H32O3Si: C, 67.81; H, 9.58. Found: C, 68.03; H, 9.67.
4.3.9. 7-Ethynyl-6-methyl-6-(4-methyl-2-phenyl-deca-
2,3-diene-9-ynyl)-1,4-dioxa-spiro[4,4]nonane (25cis). A
1.5 M THF solution of phenylmagnesium chloride
(1.28 mL, 1.92 mmol, 1.5 equiv) was added dropwise at
ꢀ50 ꢁC to a suspension of Me2S$CuBr (1.92 mmol,
1.5 equiv) and LiBr (0.167 g, 1.92 mmol, 1.5 equiv) in
THF (20 mL) and the resulting mixture was stirred at
ꢀ50 ꢁC for 15 min.
At ꢀ78 ꢁC, a 2.1 M solution of n-BuLi in hexane (0.61 mL,
1.28 mmol) was added dropwise to a solution of the alcohol
24cis (0.61 g, 1.28 mmol). After being stirred for 5 min,
pure mesyl chloride (0.12 mL, 1.53 mmol, 1.2 equiv) was
added. The resulting solution was stirred for 5 min and
transferred via a cannula into a solution of the previously
prepared copper(I) reagent. After stirring for 30 min at
ꢀ50 ꢁC, the temperature was allowed to warm up at rt.
The reaction mixture was hydrolyzed with a saturated solu-
tion of NH4Cl/NH4OH (2/1) and partitioned with Et2O. The
organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated in vacuo. The crude mixture was
used in the next step without any further purification.
4.3.11. 4-Methyl-2-phenyl-10-trimethylsilyl-deca-2,3-
dien-9-yn-1-ol (27). To a cooled (ꢀ50 ꢁC) THF (50 mL)
suspension of Me2S$CuBr (1.82 g, 8.85 mmol, 1.5 equiv)
and LiBr (0.77 g, 8.85 mmol, 1.5 equiv) was added dropwise
a solution of phenylmagnesium bromide (2.7 M in Et2O,
8.85 mmol, 1.5 equiv). The resulting mixture was stirred
for 15 min (during this period a yellow precipitate ap-
peared).
At ꢀ78 ꢁC, n-BuLi (2.4 M in hexane, 2.46 mL, 5.9 mmol,
1 equiv) was added to a solution of alcohol 26 (2 g,
5.9 mmol, 1 equiv) in THF (20 mL) and after 5 min, pure
mesyl chloride (0.51 mL, 6.49 mmol, 1.1 mmol) was added.
The resulting solution was stirred for 5 min and was added
to the previously prepared copper(I) reagent. After being
stirred at ꢀ50 ꢁC for 30 min, the reaction mixture was
allowed to warm to rt. Then, the reaction was hydrolyzed
with a 2:1 saturated solution of NH4Cl/NH4OH, diluted
with Et2O, washed with brine, dried over MgSO4, filtered,
and concentrated in vacuo. The crude residue was used in
the next step without any further purification.
K2CO3 (1.42 g, 10.24 mmol, 8 equiv) was added to the pre-
viously prepared silylated allenediyne in MeOH (10 mL)
and the resulting mixture was stirred until TLC had indicated
the completion of the reaction. The mixture was diluted with
Et2O, washed with a saturated solution of NH4Cl and brine,
dried over MgSO4, filtered, and concentrated. The crude resi-
due was purified by flash chromatography (PE/EE¼9/1) to
yield allenediyne 25cis (two diastereomers, 0.05 g, 10%).
To a solution of the previously prepared crude mixture in
MeOH (30 mL) was added PTSA (0.118 g, 0.6 mmol,
0.1 equiv). After being stirred at rt until TLC had indicated
the completion of the reaction, the mixture was diluted
with Et2O, washed successively with a saturated solution
of NaHCO3, brine, dried over MgSO4, filtered, and concen-
trated in vacuo. Purification by flash chromatography (PE/
EE¼85/15) afforded 27 (1.73 g, 94% over the two steps).
IR(neat) 3100, 2970, 2150, 2010, 1470 cmꢀ1 1H NMR
.
(400 MHz, CDCl3) d 7.39 (m, 2H), 7.27 (m, 2H), 7.17 (m,
1H), 3.95 (t, J¼8.8 Hz, 2H), 3.86 (t, J¼8.8 Hz, 2H), 3.14–
3.04 (m, 1H), 2.80 (m, 1H), 2.43–2.33 (m, 1H), 2.17–2.12
(m, 6H), 1.94–1.92 (m, 4H), 1.79 (s, 3H), 1.60–1.56 (m,
4H), 1.07 (s, 3H). 13C NMR (100 MHz, CDCl3) d (25cis,
major) 203.2 (IV), 140.2 (IV), 128.0 (2C, III), 126.3 (2C,
III), 125.9 (III), 119.1 (IV), 103.2 (IV), 101.8 (IV), 87.2
(IV), 79.0 (IV), 70.3 (III), 68.2 (III), 64.8 (2C, II), 49.7
(IV), 37.8 (III), 33.9 (II), 32.9 (II), 32.4 (II), 28.3 (II), 26.8
(II), 26.6 (II), 20.7 (I), 18.7 (II), 18.3 (I). d (25cis, minor)
203.2 (IV), 140.2 (IV), 128.0 (2C, III), 126.3 (2C, III),
125.9 (III), 119.1 (IV), 103.2 (IV), 101.7 (IV), 87.2 (IV),
79.0 (IV), 70.5 (III), 68.3 (III), 64.8 (2C, II), 49.7 (IV),
IR(neat) 3400, 2950, 2200, 1640, 1240, 930 cmꢀ1 1H
.
NMR (400 MHz, CDCl3) d 7.41–7.21 (m, 5H), 4.53 (br s,
2H), 2.25–2.16 (m, 4H), 1.86 (s, 3H), 1.67–1.37 (m, 4H),
0.14 (s, 9H). 13C NMR (100 MHz, CDCl3) d 199.6 (IV),
135.5 (IV), 128.6 (2C, III), 126.8 (III), 126.0 (2C, III)
115.4 (IV), 107.3 (IV), 106.1 (IV), 84.7 (IV), 61.8 (II),
33.7 (II), 28.1 (II), 26.6 (II), 19.7 (II), 19.0 (I), 0.2 (3C, I).
Anal. Calcd for C20H28OSi: C, 76.86; H, 9.03. Found: C,
76.86; H, 9.21.

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M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
1
4.3.12. 3-Ethynyl-2-methyl-2-(4-methyl-2-phenyl-deca-
2,3-dien-9-ynyl)-cyclopentanone (29trans). To a cooled
(ꢀ50 ꢁC) THF (50 mL) solution of KHMDS (1.10 g,
5.54 mmol) was added a solution of ketone 2021(1.29 g,
6.65 mmol, 1.2 equiv) in THF (50 mL). After warming up
at ꢀ15 ꢁC, the reaction mixture was stirred for 45 min.
Then, after being cooled to ꢀ50 ꢁC a solution of the mesyl-
ate (2.16 g, 5.54 mmol, 1 equiv) [generated from alcohol
27] in THF (10 mL) was added. After stirring for 30 min
at ꢀ50 ꢁC, the temperature was allowed to warm up at rt.
The reaction mixture was hydrolyzed with a saturated solu-
tion of NH4Cl/NH4OH (2/1) and partitioned with Et2O. The
organic layer was washed with brine, dried over MgSO4, fil-
tered, and concentrated in vacuo. The crude mixture was
used in the next step without any further purification.
1640, 930 cmꢀ1. H NMR (400 MHz, CDCl3) d 7.23–7.15
(m, 5H), 5.11–4.77 (m, 3H), 3.94–3.88 (m, 4H), 2.6–2.5
(m, 2H), 2.17–1.67 (m, 8H), 1.57 (s, 3H), 1.42–1.32 (m,
4H), 0.98 (s, 3H). 13C NMR (100 MHz, CDCl3) d 144.1
(IV), 133.8 (IV), 128.4 (2C, III), 128.0 (IV), 127.9 (IV),
127.6 (2C, III), 127.4 (IV), 126.4 (III), 119.9 (IV), 116.0
(III), 113.7 (II), 84.7 (IV), 68.2 (III), 65.3 (II), 64.4 (II),
49.2 (III), 45.5 (IV), 37.8 (II), 36.1 (II), 34.2 (II), 29.8 (II),
28.2 (II), 27.6 (II), 26.4 (I), 17.8 (I). HRMS Calcd for
C27H32O2 (388.54) (MH)+ 389.248. Found: 389.248.
4.3.14. Cycloadduct (31). The procedure is identical as the
one described for (30). The cyclization was carried out with
CpCo(CO)2 (27 mL, 0.19 mmol, 1.2 equiv) and a solution
of 29transM (0.054 g, 0.16 mmol) in degassed xylenes
(10 mL). Purification by flash chromatography (PE/EE
9/1) gave 31 (0.045 g, 60%) as a red solid. Mp 68–70 ꢁC.
1H NMR (400 MHz, C6D6) d 7.26–7.21 (m, 2H), 7.18–7.11
(m, 3H), 5.04 (d, J¼4.2 Hz, 1H), 4.59 (s, 5H), 4.46 (d,
J¼4.2 Hz, 1H), 2.41 (d, J¼17.4 Hz, 1H), 2.29–2.22 (m,
1H), 2.15 (d, J¼17.4 Hz, 1H), 1.98–1.89 (m, 4H), 1.75 (s,
3H), 1.60–1.15 (m, 8H), 0.83 (s, 3H). 13C NMR
(100 MHz, C6D6) d 218.0 (IV), 145.9 (IV), 144.8 (IV),
129.6 (IV), 128.2 (2C, III), 127.8 (III), 125.9 (2C, III),
80.8 (5C, III), 77.6 (IV), 75.1 (III), 73.5 (III), 63.7 (IV),
50.0 (III), 48.0 (IV), 47.2 (IV), 46.1 (II), 41.0 (II), 35.8
(II), 35.7 (II), 30.8 (II), 27.7 (I), 22.5 (II), 21.3 (II), 14.7
(I). HRMS Calcd for C30H33CoO (468.52) (MH)+ 469.194.
Found: 469.194.
To a solution of the crude allenediyne previously prepared in
MeOH (20 mL) was added K2CO3 (6.15 g, 44.3 mmol,
8 equiv) at rt. The reaction was stirred at rt until TLC had
indicated the completion of the reaction. The mixture was
diluted with Et2O, washed successively with a saturated
solution of NH4Cl and brine, dried over MgSO4, filtered,
and concentrated in vacuo. Purification by flash chromato-
graphy (PE/EE 9/1) furnished a 5:4 mixture of 29trans
(0.954 g, 50%).
Successive recrystallization in pentane allowed the isolation
of pure major 29transM (0.300 g). IR(neat) 2970, 2900,
1
2100, 1675, 1640, 930 cmꢀ1. H NMR (400 MHz, CDCl3)
d 7.38–7.36 (m, 2H), 7.31–7.28 (m, 2H), 7.21–7.17 (m,
1H), 3.38 (m, 1H), 2.94 (d, J¼15.6 Hz, 1H), 2.64 (d,
J¼15.6 Hz, 1H), 2.41–2.16 (m, 4H), 1.98–1.92 (m, 4H),
1.72 (s, 3H), 1.54 (m, 6H), 1.16 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 218.8 (IV), 203.0 (IV), 138.0 (IV),
128.3 (2C, III), 126.6 (III), 126.3 (2C, III), 103.2 (IV),
100.8 (IV), 84.2 (IV), 83.6 (IV), 68.6 (III), 68.3 (III), 51.3
(IV), 36.3 (II), 34.3 (III), 33.8 (II), 28.2 (II), 26.4 (II), 25.7
(II), 20.7 (I), 18.3 (I), 18.2 (II). HRMS calcd for C25H28O
(MH)+ 345.214. Found: 345.222.
4.3.15. Compound (32). A solution of complex 31 (0.08 g,
0.17 mmol) in CH2Cl2 (5 mL) was stirred in presence of sil-
ica gel at rt. The reaction was monitored by TLC and after
completion, the reaction mixture was filtered and furnished
32 (0.052 g, 90%). IR (neat) 2970, 2900, 2100, 1675,
1
1640, 930 cmꢀ1. H NMR (400 MHz, CDCl3) d 7.28–7.18
(m, 3H), 7.11 (m, 2H), 5.63 (m, 2H), 2.56–2.45 (m, 3H),
2.32–2.23 (m, 3H), 2.09–2.06 (m, 2H), 1.88 (m, 1H), 1.65
(m, 2H), 1.45 (m, 1H), 1.27 (s, 3H), 1.25–1.23 (m, 3H),
0.93 (s, 3H). 13C NMR (100 MHz, CDCl3) d 220.8 (IV),
147.4 (IV), 146.2 (IV), 140.2 (IV), 134.7(IV), 132.1 (IV),
128.3 (III), 128.2 (III), 127.4 (III), 126.0 (2C, III), 118.1
(III), 116.0 (III), 47.3 (II), 46.8 (III), 46.5 (IV), 43.0 (IV),
39.8 (II), 36.3 (II), 33.1 (II), 27.3 (II), 26.1 (I), 23.2 (II),
21.1 (II), 14.3 (I). HRMS Calcd for C25H28O (344.49)
(MH)+ 345.214. Found: 345.221.
1
29transm: H NMR (400 MHz, CDCl3) d 7.38–7.36 (m,
2H), 7.31–7.28 (m, 2H), 7.21–7.17 (m, 1H), 3.38 (m, 1H),
2.97 (d, J¼15.5 Hz, 1H), 2.63 (d, J¼15.6 Hz, 1H), 2.41–
2.16 (m, 4H), 1.98–1.92 (m, 4H), 1.79 (s, 3H), 1.54 (m,
6H), 1.16 (s, 3H). 13C NMR (100 MHz, CDCl3) d 218.8
(IV), 202.9 (IV), 137.9 (IV), 128.2 (2C, III), 126.6 (III),
126.2 (2C, III), 103.4 (IV), 100.6 (IV), 84.2 (IV), 83.6
(IV), 71.5 (III), 68.6 (III), 51.2 (IV), 36.3 (II), 34.4 (III),
33.9 (II), 28.2 (II), 26.6 (II), 25.7 (II), 20.8 (I), 18.3 (2C, II
and I), 18.2 (II).
4.3.16. Cycloadduct (33). The procedure is the same as the
one described for (31). The cyclization was carried out with
a 41:59 mixture of 29trans(M/m) (0.200 g, 0.59 mmol) and
CpCo(CO)2 (100 mL, 0.70 mmol, 1.2 equiv) in degassed
xylenes (10 mL). Purification by flash chromatography
(PE/EE 9/1) gave a 61:39 mixture of 31 and 33 (0.097 g,
35%). Besides 0.0264 g of unidentified compound was iso-
4.3.13. Cycloadduct (30). CpCo(CO)2 (20 mL, 0.16 mmol,
1.2 equiv) was added to a boiling solution of 25cis
(0.049 g, 0.13 mmol) in xylenes (10 mL) degassed by three
freeze-pump-thaw cycles and was irradiated (light from pro-
jector lamp; ELW, 300 W, 50% of its power). The reaction
was monitored by TLC and after completion, the reaction
mixture was concentrated in vacuo. The crude oil was puri-
fied by flash chromatography (the solvents of chromato-
graphy were not degassed) either on deactivated alumina
with 3% H2O (PE) or on silica gel neutralized with NEt3
and dried (PE/EE 95/5) to furnish 30 (0.033 g, 66%) as
a mixture of diastereomers. IR(neat) 3300, 2950, 2100,
1
lated. (33): H NMR (400 MHz, CDCl3) d 7.26–7.21 (m,
2H), 7.18–7.11 (m, 3H), 4.98 (d, J¼4.2 Hz, 1H), 4.64 (s,
5H), 4.54 (d, J¼4.2 Hz, 1H), 2.41 (d, J¼17.4 Hz, 1H),
2.29–2.22 (m, 1H), 2.15 (d, J¼17.4 Hz, 1H), 1.98–1.89
(m, 4H), 1.60–1.15 (m, 8H), 1.01 (s, 3H), 0.80 (s, 3H).
13C NMR (100 MHz, CDCl3) d 218.1 (IV), 146.4 (IV),
145.5 (IV), 129.6 (IV), 128.2 (2C, III), 127.8 (III), 125.9
(2C, III), 80.8 (5C, III), 77.6 (IV), 75.1 (III), 73.5 (III),
64.0 (IV), 50.5 (III), 46.9 (IV), 46.3 (IV), 45.5 (II), 39.1 (II),

M. Petit et al. / Tetrahedron 62 (2006) 10582–10593
10593
9. Clinet, J. C.; Dun˜ach, E.; Vollhardt, K. P. C. J. Am. Chem. Soc.
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10. Petit, M.; Aubert, C.; Malacria, M. Org. Lett. 2004, 6, 3937–
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11. For a recent review on allenes, see: (a) Ma, S. Chem. Rev. 2005,
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Acknowledgements
M.M. is a member of IUF. Financial support was provided
by CNRS, MRES, and IUF. M.P. thanks Sanofi-Aventis
for his grant (BDI co-financed by CNRS).
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