Alkyne versus allene activation in platinum- and gold-catalyzed cycloisomerization of hydroxylated 1,5-allenynes

Article abstract of DOI:10.1002/chem.200701522

Chemo- and stereoselective transformations of 3-hydroxy-1,5-allenynes 1 into a variety of new and potentially useful cyclic compounds have been achieved. Substrates bearing a silyl group at the alkyne moiety undergo purely thermal or Lewis acid catalyzed Alder-ene type transformations into 2-methylene-3-vinylcyclopent-3-enol derivatives 2. When heated in the presence of a catalytic amount of PtCl₂ or PtCl₄, these incipient cyclopentenols could be further transformed into 3-vinylcyclopent-2-enones 3. On the other hand, alkyl-substituted 3-hydroxy-1,5-allenynes proved to be stable under refluxing conditions. Nevertheless, PtCl₂ and PtCl₄ could selectively activate the alkyne moiety of these substrates toward intramolecular nucleophilic attack of the internal aliene double bond to yield unprecedented 6-methylenebicyclo[3.1.0]hexan-3-one derivatives 4. With gold-based catalysts, provided that the reaction is carried out in dichloromethane, both Au^I and Au^III complexes selectively activate the aliene fragment of the substrates toward intramolecular nucleophilic attack of the hydroxyl group to yield 2-ethynyl-3,6-dihydro-2H- pyrans 5. Compounds of type 4 can also be formed with Au¹ and Au ^III complexes if the reaction is carried out in toluene. The reactivity of these new compounds has been partially investigated, and polycyclic ketones were obtained after oxidation under mild conditions or goldcatalyzed cycloisomerization.

Full text of DOI:10.1002/chem.200701522

DOI: 10.1002/chem.200701522
Alkyne versus Allene Activation in Platinum- and Gold-Catalyzed
Cyclo
N
N
Riadh Zriba, Vincent Gandon, Corinne Aubert, Louis Fensterbank,* and
Max Malacria*[a]
Abstract: Chemo- and stereoselective
transformations of 3-hydroxy-1,5-alle-
nynes 1 into a variety of new and po-
tentially useful cyclic compounds have
been achieved. Substrates bearing a
silyl group at the alkyne moiety under-
go purely thermal or Lewis acid cata-
lyzed Alder-ene type transformations
allenynes proved to be stable under re-
fluxing conditions. Nevertheless, PtCl2
and PtCl4 could selectively activate the
alkyne moiety of these substrates
toward intramolecular nucleophilic
attack of the internal allene double
bond to yield unprecedented 6-
out in dichloromethane, both AuI and
AuIII complexes selectively activate the
allene fragment of the substrates
toward intramolecular nucleophilic
attack of the hydroxyl group to yield 2-
ethynyl-3,6-dihydro-2H-pyrans 5. Com-
pounds of type 4 can also be formed
with AuI and AuIII complexes if the re-
action is carried out in toluene. The re-
activity of these new compounds has
been partially investigated, and poly-
cyclic ketones were obtained after oxi-
dation under mild conditions or gold-
catalyzed cycloisomerization.
methylenebicyclo[3.1.0]hexan-3-one de-
A
into
2-methylene-3-vinylcyclopent-3-
rivatives 4. With gold-based catalysts,
provided that the reaction is carried
enol derivatives 2. When heated in the
presence of a catalytic amount of PtCl2
or PtCl4, these incipient cyclopentenols
could be further transformed into 3-vi-
nylcyclopent-2-enones 3. On the other
hand, alkyl-substituted 3-hydroxy-1,5-
Keywords: cyclization
· gold ·
homogeneous catalysis · platinum ·
synthetic methods
Introduction
and trienes (N).[3] In contrast, cycloisomerization of 1,5-alle-
nynes has remained underexplored in the fields of gold and
platinum catalysis.[3a,4,5] Here we describe in detail our find-
ings concerning the cycloisomerization of 3-hydroxy-1,5-alle-
nynes in the presence of PtII, PtIV, AuI, and AuIII salts.
It is now well established that gold and platinum salts can
activate alkynes, alkenes, and allenes toward nucleophilic
attack.[1] In the case of 1,6-enynes, electrophilic activation of
the alkyne triggers nucleophilic attack by the alkene to give
a metallacyclopropyl carbene intermediate that can evolve
along different pathways to give various types of dienes
(Scheme 1, A–E ) or bicyclic derivatives (F–H).[1e,g] 1,5-
Enynes, on the other hand, were selectively transformed
Results and Discussion
Starting compounds 1a–n (see Tables 1 and 2) were pre-
pared by addition of lithium acetylide to b-allenyl aldehydes.
These precursors were obtained via Claisen–Cope rear-
rangement of propargyl vinyl ethers derived from p-toluene-
sulfonic acid-catalyzed condensation of aldehydes to prop-
argyl alcohols, as described in the literature.[6]
into bicyclo
G
G
ones (J) when starting from 3-hydroxylated substrates.[2] 1,6-
Allenynes were also successfully converted into valuable
cyclic compounds including vinylallenes (K, L), dienes (M),
[a] Dr. R. Zriba, Dr. V. Gandon, Dr. C. Aubert,
Prof. Dr. L. Fensterbank, Prof. Dr. M. Malacria
Laboratoire de Chimie Organique UMR 7611
Institut de Chimie MolØculaire FR2769
UniversitØ Pierre et Marie Curie
Cycloisomerization to 2-methylene-3-vinylcyclopent-3-enol
or 3-vinylcyclopent-2-enone derivatives: We found that
some of the allenynes could be cycloisomerized without cat-
alyst (Table 1). Silylated allenynes 1a (R=SiMe3, Table 1,
entry 1), 1d (R=SitBuMe2, Table 1, entry 7), 1e (R=
SiPhMe2, Table 1, entry 9), 1 f (R=SiPh3, Table 1, entry 11),
and 1g (R=SiiPr3, Table 1, entry 13) were converted in high
Tour 44-54, 4 place Jussieu 75252 Paris (France)
Fax : (+33)144-277-3-60
E-mail: louis.fensterbank@upmc.fr
max.malacria@upmc.fr
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Chem. Eur. J. 2008, 14, 1482 – 1491

FULL PAPER
Scheme 1. Typical cycloisomerizations of 1,6-enynes, 1,5-enynes, and 1,6-allenynes under gold and platinum catalysis.
the exocyclic vinylic proton and
the methylene fragment. These
unprecedented products pre-
sumably result from thermal
Alder-ene cycloisomerizations,
which are quite unusual at such
a low temperature. With alkyl
groups at the alkyne moiety
(1h–l, Table 1, entries 15–19),
Table 1. Thermal or platinum-catalyzed cycloisomerization of hydroxylated 1,5-allenynes to cyclopentenols or
cyclopentenones (yields of isolated products).
Entry
Substrate
R
R’
R’’
Catalyst
Yield [%]
(2/3)
AHCTREUNG
thermal
transformation
no
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
1a
1a
1a
1b
1b
1c
1d
1d
1e
1e
1 f
1 f
1g
1g
1h
1i
SiMe3
SiMe3
SiMe3
SiMe3
SiMe3
SiMe3
H
H
H
H
H
Me
Me
Me
H
none
PtCl4
PtCl2
PtCl4
PtCl2
PtCl4
none
PtCl4
none
PtCl4
none
PtCl4
none
PtCl4
none
none
none
none
none
98/0
0/98
0/79
0/48
0/79
0/79
89/0
0/65
86/0
0/79
67/0
67/0
95/0
95/0
0/0
longer took place. The ease
with which silylated compounds
transform could be explained
H
by the well-known silicon
b
A
effect:[7] if the pericyclic reac-
Si
Si
C
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
tion proceeds in an asynchro-
nous manner (i.e., the C1 H
bond is formed early in the
transition state),
SiPhMe2
SiPhMe2
SiPh3
SiPh3
SiiPr3
À
a
positive
charge developing at C2 would
SiiPr3
CH2Ph
CH2iPr
CH2OMe
CH2OMe
nC6H13
0/0
0/0
0/0
0/0
1j
1k
1l
Me
Me
yields to 2-methylene-3-vinylcyclopent-3-enol derivatives 2a
and 2d–g within 2 h in refluxing toluene. The stereochemis-
try was proposed on the basis of the NOE effect between
be stabilized by silyl groups
(Scheme 2).
Scheme 2. Postulated
chronous Alder-ene transition
state.
asyn-
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1483

M. Malacria, L. Fensterbank et al.
With the exception of the sterically crowded allenynes 1 f
and 1g (Table 1, entries 12 and 13), the thermally labile sily-
lated substrates 1a, 1d, and 1e could be transformed into
another type of compound: when refluxed in the presence
of 5 mol% of PtCl2 or PtCl4, 3-vinylcyclopent-2-enone deriv-
atives 3a, 3d, and 3e (Table 1, entries 2–6, 8, 10) were ob-
tained in good yields. These reactions are also possible with
standard Lewis acids such as ZnCl2 or AlCl3, but the reac-
tion rates are much lower. As shown by the stepwise trans-
formation of compound 1a into first 2a and then 3a
(Scheme 3), cyclopentenols seem indeed to be likely precur-
sors to the cyclopentenones.
Scheme 4. Lewis acid (LA) catalyzed rearrangement of cyclopentenols 2
to cyclopentenones 3.
entry 3) and 1k (Table 2, entry 6) were transformed into 4i
and 4k in 87 and 80% yield of isolated product, respective-
ly.[9] Remarkably, this reaction tolerates the presence of an-
À
other C C triple bond (1m,
Table 2, entry 9).
As expected, these com-
pounds were obtained as single
diastereomers of cis configura-
tion at the ring junction, as con-
firmed by NOE experiments.
Scheme 3. Stepwise transformation of allenyne 1a into cyclopentenone 3a.
Although most of these prod-
ucts were obtained as oils, we
Thus, Lewis acids promote rearrangement of the unsatu-
rated framework to yield conjugated compounds. The first
step could be an exocyclic/endocyclic migration of the sily-
lated double bond to give a cy-
were able to obtain single crystals of the trityl derivative 4n
and carry out an X-ray diffraction study, which confirmed
the proposed structure (Scheme 5).[10]
Table 2. Platinum- and gold-catalyzed cycloisomerization of hydroxylated 1,5-allenynes to bicyclic ketones or
dihydropyrans (yields of isolated products).
clopentadienol
intermediate
(Scheme 4). Keto/enol tauto-
merism would then lead to a
b,g-unsaturated cyclopentenone.
Finally,
a
proton-shift would
produce
a
a,b,g,d-unsaturated
cyclopentenone as thermody-
namic product.
Entry Substrate
R
R’ R’’ Conditions
Yield [%]
The next step of our investi-
gation was to evaluate the reac-
tivity of the thermally stable
alkyl-substituted hydroxylated
allenynes 1h–m in the presence
of gold and platinum complexes
(vide infra).
(4/5)
1
2
3
4
5
6
7
8
9
1h
1h
1i
1i
1j
1k
1k
1l
CH2Ph
CH2Ph
CH2iPr
CH2iPr
CH2OMe
CH2OMe
CH2OMe
nC6H13
Me Me PtCl4 (5 mol%), toluene, reflux, 36 h
Me Me PtCl2 (5 mol%), toluene, reflux, 36 h
Me Me PtCl4 (5 mol%), toluene, reflux, 36 h
Me Me PtCl2 (5 mol%), toluene, reflux, 36 h
75/0
55/0
87/0
87/0
85/0[a]
80/0
70/0
66/0
68/0
70/0
0/96
Me
H
PtCl4 (5 mol%), toluene, reflux, 36 h
Me Me PtCl4 (5 mol%), toluene, reflux, 36 h
Me Me PtCl2 (5 mol%), toluene, reflux, 36 h
Me Me PtCl4 (5 mol%), toluene, reflux, 24 h
1m
ACHTREUNG
Cycloisomerization
to
6-
10 1m
11 1a
ACHTREUNG
methylenebicyclo[3.1.0]hexan-
ACHTREUNG
SiMe3
Me Me
Me
(CH2)5
C
G
3-one or 2-ethynyl-3,6-dihydro-
2H-pyran derivatives: Efficient
cycloisomerization of allenynes
1h–m was achieved by using a
catalytic amount of PtCl2 or
PtCl4 (Table 2, entries 1–10). In-
stead of cyclopentenols of type
2 or cyclopentenones of type 3,
12 1b
13 1c
14 1i
15 1k
16 1k
SiMe3
H
0/48[b]
0/45
SiMe3
G
CH2iPr
CH2OMe
CH2OMe
Me Me
Me Me
Me Me
C
N
0/72
0/73
unprecedented
methylenebicyclo
6-
ACHTREUNG
17 1k
18 1k
19 1k
20 1k
CH2OMe
CH2OMe
CH2OMe
CH2OMe
Me Me AuCl (2 mol%), CH2Cl2, RT, 6 h
Me Me AuCl3 (2 mol%), CH2Cl2, RT, 6 h
Me Me AuCl (2 mol%), toluene, reflux, 6 h
Me Me AuCl3 (2 mol%), toluene, reflux, 6 h
0/41
0/55
45/0
58/0
one derivatives 4h–m were iso-
lated in good yields after 24–
36 h in refluxing toluene.[8] For
instance, allenynes 1i (Table 2, [a] Separated mixture of E/Z isomers (1.7/1). [b] Inseparable mixture of isomers (1/1).
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Cycloisomerization of Hydroxylated 1,5-Allenynes
FULL PAPER
pound 6n in 93% yield. On the
other hand, diketone 6k was re-
gioselectively obtained in 95%
yield from the less sterically
crowded substrate 4k. The ring
junction proton resonates at d=
3.27 ppm, which supports the
proposed regiochemistry. It
seems likely that, in this case,
the spiranic framework is also
formed but, due to a lack of ki-
Scheme 5. Synthesis of 4n and structure obtained from X-ray diffraction analysis.
It seems clear that these bicyclic compounds arise from
the activation of the triple bond by the platinum catalyst fol-
lowed by intramolecular nucleophilic attack of the internal
allene double bond, as in the case of hydroxylated 1,5-enyn-
es.[2e] Although similar reactivity was expected with gold cat-
alysts, a different outcome ensued: on using a catalytic
amount of [Au
A
ACHTREUNG
into 2-ethynyl-3,6-dihydro-2H-pyran derivatives 5i (Table 2,
entry 14) and 5k (Table 2, entry 15) in 72 and 73% yield, re-
spectively.[11] The corresponding transformations were re-
ported in the b-hydroxyallene series.[12]
These reactions came to completion within 1 h in CH2Cl2
at room temperature. The yield of 5k was significantly low-
ered in toluene instead of CH2Cl2 (Table 2, entry 16, 55%).
AuCl and AuCl3 proved to be less efficient catalysts: 5k was
obtained in 41 and 55% yield, respectively, after 6 h at
room temperature in CH2Cl2 (Table 2, entries 17 and 18). In-
terestingly, when the reaction was carried out in toluene in-
stead of CH2Cl2, AuCl and AuCl3 led to 4k in 45 and 58%
yield, respectively (Table 2, entries 19 and 20). Clearly,
Scheme 6. Mechanistic interpretation (x=2, 4).
whereas [Au
(PPh3)]+ remains a well-defined species in both
G
toluene and CH2Cl2 due to the presence of a stabilizing
phosphane ligand, the“low-tech”[13] gold salts AuCl and
AuCl3 may give rise to different active species depending on
the solvent and the temperature of the reaction mixture.
Thus, hydroxylated 1,5-allenynes behave like hydroxylated
1,5-enynes or b-hydroxyallenes depending on the reaction
conditions.[14] However, in spite of potential competition be-
tween the two nucleophilic sites (i.e., the OH group and the
internal allene double bond), we encountered only chemo-
specific transformations in which [Au
A
Scheme 7. Reaction of compounds of type 4 with mCPBA.
tivated the allene moiety, whereas PtClx (x=2,4) activates
only the triple bond (Scheme 6).[15]
netic stabilization, subsequent rearrangement into a cyclobu-
tanone takes place.[16]
Synthetic applications of compounds 4: Although many new
compounds were formed from hydroxylated 1,5-allenynes,
as far as synthetic applications are concerned, the peculiar
framework of compounds 4 appeared the most fascinating.
We thus started to evaluate these intriguing compounds as
potential precursors to more complex molecules. First, we
found that the alkene fragment is highly reactive toward m-
chloroperbenzoic acid (mCPBA; Scheme 7). Ketone 4n un-
derwent selective epoxidation to give tricyclic spiro com-
We next envisaged treating compounds 4 with halogenat-
ing agents. Hydroxyalkyl derivatives 4o–q were prepared by
PtCl4-catalyzed cycloisomerization of allenynes 1o–q fol-
lowed by fluorodesilylation (Scheme 8). Treatment of 4o
with N-iodosuccinimide (NIS) produced tricyclic 7o in 97%
yield as a single regio- and diastereomer arising from 5-endo
cyclization. The stereochemical assignment of this product
was ascertained by X-ray diffraction.[17] With longer methyl-
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1485

M. Malacria, L. Fensterbank et al.
Scheme 8. Iodoalkoxylation of the 6-methylene bond.
ene spacers, the same reaction conditions led to 7p in 85%
yield, but only to degradation in the case of 4q.
Since the hydroxylated ketones 4o–q display both a meth-
ylenecyclopropane fragment and a nucleophilic site, we fig-
ured that these substrates could also be good candidates for
gold-catalyzed transformations. Pertinent to this idea was
the recently described gold(I)-catalyzed hydroamination of
methylenecyclopropanes.[18] We found that the outcome of
the reaction of compounds of type 4 with gold(I) was criti-
cally dependent on the length of the methylene spacer
(Table 3). For instance with n=1 (Table 3, entry 1), 4o was
selectively transformed into cyclohexadienone 8o in 77%
yield in the presence of 2 mol% of [Au
(PPh3)]+. On the
G
other hand, with n=2 (Table 3, entry 2), products arising
from attack of the alcohol at the double bond (9p, 42%) or
at the cyclopropane moiety (10p, 30%) were obtained.
Spiro compound 10q was formed as sole product for n=3
(Table 3, entry 3). A different product distribution was ob-
tained on using AuCl with n=1 and n=2 (Table 3, entries 4
and 5), but 10q was still obtained selectively with n=3
(Table 3, entry 6). It is note worthy that compounds of type
9 and 10 were formed as single diastereomers.[19,20]
The formation of 8o can be summarized as follows
(Scheme 9): electron depletion of the methylenecyclopro-
pane moiety induced by gold coordination promotes elimi-
nation of an allylic proton and hence formation of a hydro-
nium cation. Elimination of water and opening at the ring
junction leads to a gold-complexed 5-methylenecyclohex-3-
Scheme 9. Mechanistic rationale for AuI-catalyzed transformations of 4o
into 8o.
enone intermediate. After regeneration of the catalyst, this
compound rearranges into the more stable a,b,g,d-unsaturat-
ed ketone 8o.
With a longer tether (n=2 or 3; Scheme 10), nucleophilic
attack of the double bond, or of the cyclopropyl ring, by the
alkoxyl group becomes faster than proton elimination. In
the latter case, this transformation leads to a vinylgold spe-
cies that includes a spiranic moiety. Elimination of H+ fol-
À
lowed by acidic cleavage of the C Au bond regenerates the
catalyst and delivers 10p,q.
Conclusion
Table 3. Gold-catalyzed transformations of compounds 4o-q (yields of isolated products).
We have shown that hydroxy-
lated 1,5-allenynes can be cy-
cloisomerized in the presence
of platinum- and gold-based
catalysts to yield distinct prod-
ucts.
methylenebicyclo
Among
them,
6-
Entry Substrate
n
Conditions
[AuCl
[AuCl
[AuCl
AuCl (5 mol%), CH2Cl2, reflux, 2 h
AuCl (5 mol%), CH2Cl2, reflux, 2 h
AuCl (5 mol%), CH2Cl2, reflux, 2 h
Yield [%] (8/9/10)
AHCTREUNG
1
2
3
4
5
6
4o
4p
4q
4o
4p
4q
1
2
3
1
2
3
G
ACHTREUNG
ones were formed on using
PtCl2 or PtCl4, whereas 2-ethyn-
yl-3,6-dihydro-2H-pyrans were
G
ACHTREUNG
E
(PPh3)] (2 mol%), AgSbF6 (2 mol%), CH2Cl2, reflux, 1 h 0/0/74
54/38/0[a]
0/44/0
0/0/80
obtained with [Au
(PPh3)]+.
A
Thus, platinum salts show an
extensive degree of alkynophi-
[a] Separated.
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Cycloisomerization of Hydroxylated 1,5-Allenynes
FULL PAPER
was purified by flash chromatography on silica gel (petroleum ether/
AcOEt 9/1).
1a (prepared from trimethylsilylacetylene and 2,2,5-trimethyl-3,4-hexa-
dienal, 96%): Colorless oil; 1H NMR (CDCl3): d=0.19 (s, 9H), 1.09 (s,
3H), 1.10 (s, 3H), 1.72 (d, J=3.0 Hz, 6H), 4.07 (s, 1H), 5.01 ppm (sept,
J=3.0 Hz, 1H), OH unobserved; 13C NMR (CDCl3): d=0.03 (CH3), 20.8
(2C, CH3), 24.1 (2C, CH3), 27.0 (C), 70.8 (CH), 90.2 (C), 95.3 (C), 97.1
(C), 105.4 (CH), 201.2 ppm (C); IR (neat): n˜ =1725, 2171, 3396 cmÀ1
1b (prepared from trimethylsilylacetylene and 2,2-dimethyl-3,4-hexadi-
enal, 67%): Colorless oil; 1H NMR (CDCl3): d=0.15 (s, 9H), 1.06 (s,
.
AHCTREUNG
3H), 1.08 (s, 3H), 1.65 (dd, J=6.8, 3.3 Hz, 3H), 2.18 (brs, OH), 4.04 (s,
1H), 5.08–5.21 ppm (m, 2H); 13C NMR (CDCl3): d=À0.11 (CH3), 14.6
(CH3), 23.6 (CH3), 23.9 (CH3), 40.2 (C), 70.7 (CH), 87.7 (CH), 90.4 (C),
96.5 (CH), 104.9 (C) 204.0 ppm (C); IR (neat): n˜ =1960, 2171, 3378 cmÀ1
HRMS(ES +) calcd for C13H22OSiNa: 245.1338; found: 245.1332.
;
1c (prepared from trimethylsilylacetylene and 4-cyclohexylidene-2,2-di-
methyl-3-butenal, 34%): Colorless oil; 1H NMR (CDCl3): d=0.19 (s,
9H), 1.10 (s, 3H), 1.12 (s, 3H), 1.41–1.62 (m, 6H), 2.09–2.22 (m, 4H),
4.08 (d, J=6.8 Hz, 1H), 5.02 ppm (sept, J=2.3 Hz, 1H), OH unobserved;
13C NMR (CDCl3): d=0.03 (CH3), 23.8 (CH3), 24.4 (CH3), 26.2 (2C,
CH2), 27.0 (C), 27.6 (2C, CH2), 31.9 (CH2), 40.7 (C), 70.9 (CH), 90.5 (C),
94.9 (CH), 104.9 (C), 197.9 ppm (C); IR (neat): n˜ =1958, 2171,
Scheme 10. Mechanistic rationale for AuI-catalyzed transformations of
4p,q into 9p,q and 10p,q.
3402 cmÀ1
299.1798.
; HRMS(ES +) calcd for C17H28OSiNa: 299.1807; found:
licity, as opposed to[Au
ACHTREUNG
stantially allenophilic. 6-Methylenebicyclo
AHCTREUNG
1d (prepared from tert-butyldimethylsilylacetylene and 2,2,5-trimethyl-
3,4-hexadienal, 68%): Colorless oil; 1H NMR (CDCl3): d=0.09 (s, 6H),
0.92 (s, 9H), 1.06 (s, 3H), 1.08 (s, 3H), 1.68 (d, J=3.0 Hz, 6H), 4.06 (d,
J=6.5 Hz, 1H), 5.04 ppm (sept, J=3.0 Hz, 1H), OH unobserved;
13C NMR (CDCl3): d=À4.50 (CH3), 16.6 (C), 20.7 (CH3), 20.8 (CH3),
23.7 (CH3), 24.3 (CH3), 26.2 (CH3), 40.8 (C) 70.9 (CH), 88.7 (C), 95.3
(CH), 97.5 (C) 105.8 (C), 201.3 ppm (C); IR (neat): n˜ =1968, 2170,
ones were oxidized by mCPBA or NISto give polycyclic
compounds regio- and diastereoselectively. On the other
hand, [Au
(PPh3)]+ allowed the formation of tricyclic or
T
spiro derivatives from hydroxyalkyl-substituted substrates
depending on the tether length. Overall, these compounds
were obtained in three steps from hydroxylated allenynes by
a unique sequence of platinum- and then gold-catalyzed
transformations.
3400 cmÀ1
301.1964.
; HRMS(ES +) calcd for C17H30OSiNa: 301.1958; found:
1e (prepared from dimethylphenysilylacetylene and 2,2,5-trimethyl-3,4-
hexadienal, 63%): Colorless oil; 1H NMR (CDCl3): d=0.43 (s, 3H), 0.44
(s, 3H), 1.11 (s, 3H), 1.13 (s, 3H), 1.71 (d, J=3.0 Hz, 6H), 4.14 (d, J=
1.3 Hz, 1H), 5.04 (sept, J=3.0 Hz, 1H), 7.36–7.41 (m, 3H), 7.61–
7.68 ppm (m, 2H), OH unobserved; 13C NMR (CDCl3): d=À0.71 (CH3),
20.7 (CH3), 20.8 (CH3), 23.8 (CH3), 24.3 (CH3), 40.8 (C), 71.0 (CH), 88.5
(C), 95.2 (CH), 97.5 (C), 107.0 (C), 127.9, 129.5, 133.7 (CHarom), 136.9
(C), 201.3 ppm (C); IR (neat): n˜ =1967, 2170, 3438 cmÀ1; HRMS(ES +)
calcd for C19H26OSiNa: 321.1654; found: 321.1651.
Experimental Section
General methods: Reactions were carried out under argon in oven-dried
glassware. THF was distilled over sodium benzophenone ketyl. Toluene
was distilled from CaH2. Thin-layer chromatography (TLC) was per-
formed on Merck 60 F254 silica gel. Merck Gerudan SI 60 Š silica gel
(35–70 mm) was used for column chromatography. NMR spectra (1H, 13C,
DEPT, 1H,1H and 1H,13C COSY) were recorded at room temperature on
a 400 MHz Bruker ARX400 spectrometer. Chemical shifts are given in
parts per million, referenced to the residual proton resonance of the sol-
vents (d=7.26 ppm for CDCl3) or to the residual carbon resonance of
the solvent (d=77.16 ppm for CDCl3) When possible, 1H and 13C signals
were assigned mostly on the basis of DEPT and 2D NMR (COSY,
HMBC) experiments. In the description of the 13C NMR spectra, a
number at the beginning of the information in parentheses refers to acci-
dentally isochronous carbon atoms. Elemental analyses were performed
by the Service RØgional de Microanalyse de lꢁUniversitØ Pierre et Marie
Curie-Paris 6. High-resolution mass spectra (HRMS) were measured by
the Service de SpectromØtrie de Masse de lꢁUniversitØ Pierre et Marie
Curie-Paris 6. Infrared (IR) spectra were recorded on a Bruker Tensor
27 spectrometer. Melting points were obtained on a Büchi capillary appa-
ratus and were not corrected.
1 f (prepared from triphenylsilylacetylene and 2,2,5-trimethyl-3,4-hexa-
1
dienal, 49%): Pale yellow oil; H NMR (CDCl3): d=1.16 (s, 3H), 1.19 (s,
3H), 1.68 (d, J=3.0 Hz, 6H), 4.24 (d, J=6.0 Hz, 1H), 5.09 (sept, J=
3.0 Hz, 1H), 7.59–7.74 ppm (m, 15H), OH unobserved; IR (neat): n˜ =
1967, 2170, 3400 cmÀ1; HRMS(ES +): calcd for C29H30OSiNa: 445.1964;
found: 445.1958.
1g (prepared from triisopropylsilylacetylene and 2,2,5-trimethyl-3,4-hexa-
dienal, 60%): Colorless oil; 1H NMR (CDCl3): d=1.07 (s, 3H), 1.08 (d,
J=5.5 Hz, 18H), 1.09 (s, 3H), 1.10–1.20 (m, 3H), 1.70 (d, J=2.2 Hz,
6H), 4.08 (d, J=6.5 Hz, 1H), 5.03 ppm (sept, J=3.0 Hz, 1H), OH unob-
served; 13C NMR (CDCl3): d=18.5 (CH3), 18.7 (CH), 20.8 (CH3), 20.9
(CH3), 23.6 (CH3), 24.5 (CH3), 40.9 (C), 71.0 (CH), 86.6 (C), 94.8 (C),
95.4 (CH), 97.5 (C), 201.3 ppm (C); IR (neat): n˜ =2172, 3387 cmÀ1
1h (prepared from 3-phenyl-1-propyne and 2,2,5-trimethyl-3,4-hexadi-
enal, 58%): Colorless oil; 1H NMR (CDCl3): d=1.12 (s, 3H), 1.14 (s,
.
AHCTREUNG
3H), 1.72 (d, J=2.9 Hz, 6H), 3.62 (s, 2H), 4.15 (s, 1H), 5.05 (sept, J=
3.0 Hz, 1H), 7.36–7.49 ppm (m, 5H), OH unobserved; 13C NMR
(CDCl3): d=20.6 (CH3), 20.7 (CH3), 23.8 (CH3), 24.2 (CH3), 25.2 (CH2),
40.8 (C), 70.8 (CH), 81.7 (C), 83.7 (C), 95.4 (CH), 97.3 (C), 126.6 (CH),
127.9 (CH), 128.5 (CH), 136.7 (C), 201.2 ppm (C); IR (neat): n˜ =1967,
2220, 3406 cmÀ1; HRMS(ES +) calcd for C18H22ONa: 277.1568; found:
277.1565.
Synthesis of the precursors allenynes: general procedure for preparation
of 1a–q: nBuLi (5.6 mL, 2.3m in hexanes, 13 mmol) was added to a solu-
tion of the alkyne (10 mmol) in dry THF (14 mL) at À788C. After
20 min, a solution of the allene aldehyde (9.9 mmol, 1 equiv) in dry THF
(14 mL) was added. The mixture was then allowed to warm to room tem-
perature. The mixture was quenched with saturated NH4Cl solution and
extracted with diethyl ether. The combined organic layers were washed
with brine, dried over MgSO4, and evaporated to give a crude oil, which
1i (prepared from 4-methyl-1-pentyne and 2,2,5-trimethyl-3,4-hexadienal,
69%): Colorless oil; 1H NMR (CDCl3): d=0.94 (s, 3H), 0.96 (s, 3H),
1.04 (s, 3H), 1.05 (s, 3H), 1.67 (d, J=2.9 Hz, 6H), 1.70–1.85 (m, 1H),
Chem. Eur. J. 2008, 14, 1482 – 1491
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1487

M. Malacria, L. Fensterbank et al.
2.10 (dd, J=6.3, 2.0 Hz, 2H), 4.04 (s, 1H), 4.99 ppm (sept, J=3.0 Hz,
1H), OH unobserved; 13C NMR (CDCl3): d=20.7 (CH3), 20.8 (CH3),
22.1 (CH3), 23.7 (CH3), 24.3 (CH3), 28.0 (CH), 28.1 (CH2), 40.8 (C), 70.7
(CH), 80.2 (C), 85.3 (C), 95.4 (CH), 97.2 (C), 201.2 ppm (C); IR (neat):
n˜ =1968, 2222, 3390 cmÀ1; HRMS(ES +) calcd for C15H24ONa: 243.1725;
found: 243.1719.
3433 cmÀ1
345.2221.
;
HRMS(ES +) calcd for C19H34O2SiNa: 345.2226; found:
1q (prepared from tert-butyl(dimethyl)(4-pentynoxy)silane and 2,2,5-tri-
A
methyl-3,4-hexadienal, 69%): Colorless oil; 1H NMR (CDCl3): d=0.04
(s, 6H), 0.88 (s, 9H), 1.05 (s, 3H), 1.07 (s, 3H), 1.70 (d, J=3.1 Hz, 6H),
1.61–1.73 (m, 2H), 2.25–2.35 (m, 2H), 3.68 (t, J=6.0 Hz, 2H), 4.09 (br d,
1H), 4.98 ppm (sept, J=3.1 Hz, 1H), OH unobserved; 13C NMR
(CDCl3): d=À5.3 (CH3), 15.2 (CH2), 18.4 (C), 20.8 (2C, CH3), 23.7
(CH3), 24.3 (CH3), 25.9 (CH3), 31.8 (CH2), 40.8 (C), 61.7 (CH2), 70.7
(CH), 81.9 (C), 86.0 (C), 95.3 (CH), 97.3 (C), 201.3 ppm (C); IR (neat):
1j (prepared from methyl propargyl ether and 2,2-dimethyl-3,4-hexadi-
enal, 47%): Colorless oil; 1H NMR (CDCl3): d=1.08 (s, 3H), 1.10 (s,
3H), 1.75 (d, J=2.8 Hz, 6H), 3.38 (s, 3H), 4.10 (d, J=2.8 Hz, 1H), 4.15
(d, J=1.5 Hz, 2H), 5.00 ppm (sept, J=2.8 Hz, 1H); 13C NMR (CDCl3):
d=20.7 (CH3), 23.8 (CH3), 24.1 (CH3), 40.7 (C), 57.5 (CH3), 59.9 (CH2),
70.5 (CH), 81.5 (C), 86.0 (C), 95.3 (CH), 97.4 (C), 201.2 ppm (C); IR
(neat): n˜ =1720, 1968, 3405 cmÀ1; HRMS(ES +) calcd for C12H18O2Na:
217.1204; found: 217.1199.
n˜ =1967, 2225, 3449 cmÀ1
.
General procedure for thermal Alder-ene cycloisomerization reactions:
A stirred solution of allenyne in dry toluene (c=0.05m) was heated
under reflux for 1 h. After cooling to room temperature, the mixture was
filtered through a short pad of silica gel and concentrated in vacuo.
1k (prepared from methyl propargyl ether and 2,2,5-trimethyl-3,4-hexa-
dienal, 89%): Colorless oil; 1H NMR (CDCl3): d=1.07 (s, 3H), 1.08 (s,
3H), 1.64 (d, J=3.5 Hz, 6H), 3.35 (s, 3H), 4.10 (brs, 1H), 4.14 (s, 2H),
5.07–5.21 ppm (m, 1H), OH unobserved; 13C NMR (CDCl3): d=14.6
(CH3), 23.6 (CH3), 23.7 (CH3), 24.0 (CH3), 40.3 (C), 57.6 (CH3), 59.9
(CH2), 70.5 (CH), 81.6 (C), 85.8 (C), 87.9 (CH), 96.6 (CH), 204.1 ppm
General procedure for PtCl2- and PtCl4-catalyzed cycloisomerization:
The platinum catalyst was added to a stirred solution of allenyne in dry
toluene (c=0.05m) under argon, and the solution was heated under
reflux for 2–36 h. After cooling to room temperature, the mixture was fil-
tered through a short pad of silica gel and concentrated in vacuo.
(C); IR (neat): n˜ =1725, 1961, 3418 cmÀ1
; HRMS(ES +) calcd for
Compounds 4o–q were obtained after a cycloisomerization step as de-
scribed previously, followed by treatment with 1.5 equiv of a 1m solution
of tetra-n-butylammonium fluoride (TBAF) in THF and purification by
flash chromatography on silica gel (petroleum ether/AcOEt 1/1).
C13H20O2Na: 231.1361; found: 231.1357.
1l (prepared from 1-octyne and 2,2,5-trimethyl-3,4-hexadienal, 61%):
1
Colorless oil; H NMR (CDCl3): d=0.88 (t, J=7.0 Hz, 3H), 1.05 (s, 3H),
1.07 (s, 3H), 1.21–1.49 (m, 6H), 1.45–1.56 (m, 2H), 1.69 (d, J=2.8 Hz,
6H), 2.21 (td, J=7.0, 2.0 Hz, 2H), 4.04 (td, J=3.8, 2.0 Hz, 1H), 4.99 ppm
(sept, J=2.8 Hz, 1H), OH unobserved; 13C NMR (CDCl3): d=14.1-
General procedure for AuCl- and AuCl3-catalyzed cycloisomerization re-
actions: The gold catalyst was added to a stirred solution of allenyne in
dry CH2Cl2 (c=0.05m) under argon, and the solution was heated under
reflux for 2 h. After cooling to room temperature, the mixture was fil-
tered through a short pad of silica gel and concentrated in vacuo.
A
(CH3), 28.6 (CH2), 28.7 (CH2), 31.4 (CH2), 40.8 (C), 70.7 (CH), 79.2 (C),
86.5(C), 95.4 (CH), 97.3 (C), 201.2 ppm (C); IR (neat): n˜ =1714, 2224,
3397 cmÀ1
271.2032.
; HRMS(ES +) calcd for C17H28ONa: 271.2038; found:
General procedure for [Au(PPh3)]SbF6-catalyzed cycloisomerization re-
A
actions: Allenyne (0.45 mmol) in CH2Cl2 (9 mL) was added to a solution
formed by adding 2 mol% of ClAuPPh3 and 2 mol% of AgSbF6 to
CH2Cl2. The mixture was stirred under reflux for 2 h. After cooling to
room temperature, the mixture was filtered through a short pad of silica
gel and concentrated in vacuo.
1m (prepared from hepta-1,6-diynyltrimethylsilane and 2,2,5-trimethyl-
3,4-hexadienal, 58%): Colorless oil; 1H NMR (CDCl3): d=0.14 (s, 9H),
1.06 (s, 3H), 1.07 (s, 3H), 1.65–1.79 (m, 8H), 2.26–2.39 (m, 4H), 4.03 (d,
J=6.5 Hz, 1H), 4.98 ppm (sept, J=2.7 Hz, 1H), OH unobserved;
13C NMR (CDCl3): d=0.11 (CH3), 17.8 (CH2), 19.0 (CH2), 20.6 (2C,
CH3), 23.7 (2C, CH3), 27.7 (CH2), 40.7 (C), 60.3 (C), 70.6 (CH), 80.1 (C),
85.1 (C), 95.5 (CH), 97.0 (C), 106.1 (C), 201.1 ppm (C); IR (neat): n˜ =
1717, 2173, 3410 cmÀ1; HRMS(ES +) calcd for C19H30OSiNa: 325.1964;
found: 325.1958.
2a: Colorless oil; 1H NMR (CDCl3): d=0.18 (s, 9H), 1.07 (s, 6H), 1.89
(s, 3H), 4.24 (d, J=6.0 Hz, 1H), 5.09 (s, 1H), 5.10 (s, 1H), 5.75 (s, 1H),
5.80 ppm (s, 1H), OH unobserved; 13C NMR (CDCl3): d=0.52 (CH3),
21.3 (CH3), 22.9 (CH3), 27.1 (CH3), 45.8 (C), 81.8 (CH), 115.0 (CH2),
123.1 (CH), 132.2 (C), 138.3 (C), 142.8 (CH), 161.2 ppm (C); IR (neat):
n˜ =3420 cmÀ1
.
1n (prepared from 3-O-(triphenylmethyl)prop-1-yn-3-ol and 2,2,5-tri-
methyl-3,4-hexadienal, 65%): Colorless oil; 1H NMR (CDCl3): d=1.13
(s, 3H), 1.15 (s, 3H), 1.75 (d, J=2.8 Hz, 6H), 3.38 (d, J=1.5 Hz, 2H),
4.13 (brs, 1H), 5.06 (sept, J=2.8 Hz, 1H), 7.33–7.39 (m, 10H), 7.47–
7.58 ppm (m, 5H), OH unobserved; 13C NMR (CDCl3): d=20.75 (CH3),
20.78 (CH3), 23.8 (CH3), 24.1 (CH3), 40.7 (C), 53.2 (CH2), 70.5 (CH), 82.4
(C), 84.7 (C), 87.4 (C), 95.2 (CH), 97.3 (C), 127.1 (CHarom), 127.9
(CHarom), 128.6 (CHarom), 143.5 (C), 201.2 ppm (C); IR (neat): n˜ =1737,
1
2 f: Colorless oil; H NMR (CDCl3): d=0.95 (s, 3H), 0.98 (s, 3H), 1.95 (s,
3H), 4.02 (d, J=5.0 Hz, 1H), 5.17 (s, 1H), 5.26 (s, 1H), 5.91 (s, 1H), 6.29
(s, 1H), 7.21–7.46 (m, 10H), 7.55–7.69 ppm (m, 5H); 13C NMR (CDCl3):
d=15.3 (CH3), 21.5 (CH3), 26.5 (CH3), 45.7 (C), 82.2 (CH), 114.6 (CH),
115.5 (CH2), 128.0 (CHarom), 129.5 (CHarom), 130.1 (CHarom), 135.1 (C),
138.2 (C), 142.9 (C), 143.9 (CH), 165.2 ppm (C).
1
1967 cmÀ1
459.2294.
;
HRMS(ES +) calcd for C31H32O2Na: 459.2297; found:
2g: Colorless oil; H NMR (CDCl3): d=1.08 (d, J=7.3 Hz, 18H), 1.21 (s,
3H), 1.23 (s, 3H), 1.28–1.38 (m, 3H), 1.91 (s, 3H), 4.14 (d, J=7.6 Hz,
1H), 5.10 (s, 1H), 5.12 (s, 1H), 5.69 (s, 1H), 5.79 ppm (s, 1H), OH unob-
served; 13C NMR (CDCl3): d=12.4 (CH), 18.7 (CH3), 21.1 (CH3), 22.8
(CH3), 27.1 (CH3), 46.2 (C), 82.3 (CH), 115.1 (CH2), 118.7 (CH), 138.6
1o (prepared from tert-butyl
ACHTREUNG
methyl-3,4-hexadienal, 87%): Colorless oil; 1H NMR (CDCl3): d=0.11
(s, 6H), 0.90 (s, 9H), 1.06 (s, 3H), 1.08 (s, 3H), 1.70 (d, J=3.5 Hz, 6H),
4.09 (brs, 1H), 4.35 (d, J=1.8 Hz, 2H), 4.99 ppm (sept, J=3.5 Hz, 1H),
OH unobserved; 13C NMR (CDCl3): d=À5.0 (CH3), 18.3 (C), 20.8 (2C,
CH3), 23.7 (2C, CH3), 24.2 (CH3), 25.9 (CH3), 40.8 (C), 68.0 (CH), 81.9
(C), 84.5 (C), 95.2 (CH), 97.4 (C), 201.3 ppm (C); IR (neat): n˜ =
(C), 141.9 (CH), 143.7 (C), 161.8 ppm (C); IR (neat): n˜ =3420 cmÀ1
.
3a: Colorless oil; 1H NMR (CDCl3): d=À0.04 (s, 9H), 1.07 (s, 6H), 1.87
(s, 2H), 2.00 (s, 3H), 2.47 (s, 2H), 5.17 (s, 1H), 5.20 ppm (s, 1H);
13C NMR (CDCl3): d=À0.76 (C), 14.7 (CH2), 22.3 (CH3), 25.6 (CH3),
41.8 (C), 49.5 (CH2), 117.5 (CH2), 136.1 (C), 141.6 (C), 160.0, 214.1 ppm
(C); IR (neat): n˜ =1695 cmÀ1; HRMS(ES +) calcd for C14H24OsiNa:
259.1494; found: 259.1485.
3422 cmÀ1
331.2063.
;
HRMS(ES +) calcd for C18H32O2SiNa: 331.2069; found:
1p (prepared from tert-butyl
ACHTREUNG
3b: Colorless oil; 1H NMR (CDCl3): d=À0.05 (s, 9H), 1.09 (s, 6H), 1.73
(s, 2H), 2.48 (s, 2H), 5.38 (dd, J=10.6, 1.3 Hz, 1H), 5.58 (dd, J=17.4,
1.3 Hz, 1H), 6.80 ppm (dd, J=17.4, 10.7 Hz, 1H); 13C NMR (CDCl3): d=
À1.0 (CH3), 13.8 (CH2), 25.6 (CH3), 42.1 (C), 42.3 (CH2), 119.3 (CH2),
131.9 (CH), 137.7 (C), 156.2 (C), 213.8 ppm (C); IR (neat): n˜ =
methyl-3,4-hexadienal, 66%): Colorless oil; 1H NMR (CDCl3): d=0.06
(s, 6H), 0.88 (s, 9H), 1.05 (s, 3H), 1.06 (s, 3H), 1.70 (d, J=3.0 Hz, 6H),
2.44 (td, J=7.0, 1.8 Hz, 2H), 3.71 (t, J=7.3 Hz, 2H), 4.03 (d, J=7.0 Hz,
1H), 4.95–5.03 ppm (m, 1H), OH unobserved; 13C NMR (CDCl3): d=
À5.1 (CH3), 18.4 (C), 20.8 (CH3), 23.2 (CH2), 23.7 (CH3), 24.2 (CH3),
25.9 (CH3), 40.8 (C), 62.0 (CH2), 70.7 (CH), 80.4 (C), 83.2 (C); 95.3
(CH), 97.3 (C), 135.5 (C), 201.3 ppm (C); IR (neat): n˜ =1968, 2226,
1692 cmÀ1
245.1326.
; HRMS(ES +) calcd for C13H22OSiNa: 245.1338; found:
1488
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1482 – 1491

Cycloisomerization of Hydroxylated 1,5-Allenynes
FULL PAPER
1
3c: Colorless oil; H NMR (CDCl3): d=À0.03 (s, 9H), 1.07 (s, 6H), 1.56–
(neat): n˜ =1742 cmÀ1; HRMS(ES +) calcd for C17H28ONa: 271.2038;
found: 271.2035.
1.75 (m, 4H), 1.86 (s, 2H), 2.15–2.29 (m, 4H), 2.46 (s, 2H), 6.04 ppm (m,
1H); 13C NMR (CDCl3): d=À0.7 (CH3), 14.6 (CH2), 21.9 (CH2), 22.7
(CH2), 25.6 (CH3), 25.9 (CH2), 27.8 (CH2), 41.7 (C), 45.6 (CH2), 129.8
(CH), 134.2 (C), 135.6 (C), 161.5 (C), 214.2 ppm (C); IR (neat): n˜ =
1691 cmÀ1; HRMS(ES +, M+H): calcd for C17H29OSi: 277.1988; found:
277.1982.
4m: Colorless oil; 1H NMR (CDCl3): d=0.14 (s, 9H), 1.03 (s, 3H), 1.14
(s, 3H), 1.51–1.68 (m, 4H) 1.74 (s, 1H), 1.75 (s, 3H), 1.77 (s, 3H), 2.19–
2.29 (m, 2H), 2.28 (d, A of AB, J=17.9 Hz, 1H), 2.69 ppm (d, B of AB,
J=17.9 Hz, 1H); 13C NMR (CDCl3): d=0.29 (CH3), 20.2 (CH2), 22.0
(CH3), 22.3 (CH3), 22.7 (CH3), 24.9 (C), 26.5 (CH2), 26.6 (CH3), 33.3
(CH2), 34.3 (CH), 43.2 (CH2), 50.2 (C), 85.0 (C), 107.1 (C), 125.5 (C),
127.2 (C), 220.4 ppm (C); IR (neat): n˜ =1741, 2173 cmÀ1; HRMS(ES +)
calcd for C19H30OSiNa: 325.1964; found: 325.1958.
4n: White solid; m.p. 118–1208C; 1H NMR (CDCl3): d=1.13 (s, 3H),
1.30 (s, 3H), 1.78 (s, 4H), 1.81 (s, 3H), 2.37 (d, A of AB, J=18.2 Hz,
1H), 3.12 (d, B of AB, J=18.2 Hz, 1H), 3.14 (d, A of AB, J=9.6 Hz,
1H), 3.42 (d, B of AB, J=9.6 Hz, 1H), 7.25–7.38 (m, 8H), 7.42–7.53 ppm
(m, 7H); 13C NMR (CDCl3): d=21.9 (CH3), 22.4 (CH3), 22.5 (CH3), 25.3
(C), 26.4 (CH3), 34.3 (CH), 41.4 (CH2), 50.1 (C), 65.6 (CH2), 86.2 (C),
125.0 (C), 126.7 (C), 127.0 (CHarom), 128.3 (CHarom), 130.1 (CHarom), 144.2
(C), 220.4 ppm (C); IR (neat): n˜ =1741 cmÀ1; HRMS(ES +) calcd for
C31H32O2Na: 459.2297; found: 459.2295; elemental analysis calcd (%) for
C31H32O2: C 85.27, H 7.39; found: C 85.31, H 7.25.
3d: Colorless oil; 1H NMR (CDCl3): d=À0.13 (s, 6H), 0.84 (s, 3H), 0.89
(s, 9H), 1.09 (s, 6H), 1.89 (s, 2H), 2.01 (s, 3H), 2.48 (s, 2H), 5.15–
5.24 ppm (m, 2H); 13C NMR (CDCl3): d=À5.4 (CH3), 10.3 (CH2), 17.0
(C), 25.6 (2C, CH3), 26.4 (CH3), 41.9 (C), 46.1 (CH2), 117.3 (CH2), 136.2
(C), 141.8 (C), 160.0 (C), 214.1 ppm (C); IR (neat): n˜ =1697 cmÀ1
.
3e: Colorless oil; 1H NMR (CDCl3): d=0.29 (s, 6H), 1.07 (s, 6H), 1.87
(s, 3H), 2.12 (s, 2H), 2.45 (s, 2H), 5.08–5.15 (m, 2H), 7.31–7.42 ppm (m,
5H); 13C NMR (CDCl3): d=À2.2 (CH3), 14.1 (CH2), 22.0 (CH3), 25.5
(CH3), 41.9 (C), 46.1 (CH2), 117.3 (CH2), 127.7 (CHarom), 129.0 (CHarom),
133.8 (CHarom), 135.5 (C), 138.6 (C), 141.6 (C), 163.2 (C), 214.0 ppm (C);
IR (neat): n˜ =1698 cmÀ1
.
4h: Colorless oil; 1H NMR (CDCl3): d=0.97 (s, 3H), 1.04 (s, 3H), 1.75
(s, 3H), 1.79 (s, 4H), 2.26 (d, A of AB, J=17.9 Hz, 1H), 2.67 (d, B of
AB, J=17.9 Hz, 1H), 2.80 (d, A of AB, J=13.6 Hz, 1H), 3.02 (d, B of
AB, J=13.6 Hz, 1H), 7.13–7.39 ppm (m, 5H); 13C NMR (CDCl3): d=
21.9 (CH3), 22.3 (CH3), 22.7 (CH3), 26.1 (CH3), 26.5 (C), 34.7 (CH), 39.9
(CH2), 42.5 (CH2), 50.3 (C), 126.1 (C), 126.8 (CH), 128.6 (C), 128.7
4o: Colorless oil; 1H NMR (CDCl3): d=1.05 (s, 3H), 1.15 (s, 3H), 1.76
(s, 3H), 1.79 (s, 4H), 2.31 (d, A of AB, J=18.2 Hz, 1H), 2.96 (d, B of
AB, J=18.2 Hz, 1H), 3.57 (d, A of AB, J=11.4 Hz, 1H), 3.88 ppm (d, B
of AB, J=11.4 Hz, 1H), OH unobserved; 13C NMR (CDCl3): d=21.9
(CH3), 22.5 (CH3), 22.6 (CH3), 26.4 (CH3), 27.4 (C), 33.7 (CH), 40.6
(CH2), 50.1 (C), 65.2 (CH2), 124.6 (C), 127.1 (C), 220.1 ppm (C); IR
(CH), 129.8 (CH), 139.5 (C), 220.1 ppm (C); IR (neat): n˜ =1740 cmÀ1
HRMS(ES +) calcd for C18H22ONa: 277.1568; found: 277.1566.
;
(neat): n˜ =1730, 3401 cmÀ1
; HRMS(ES +) calcd for C12H18O2Na:
4i: Colorless oil; 1H NMR (CDCl3): d=0.91 (d, J=6.5 Hz, 3H), 0.97 (d,
J=6.5 Hz, 3H), 1.02 (s, 3H), 1.15 (s, 3H), 1.30–1.49 (m, 1H), 1.65–1.67
(m, 1H), 1.69–1.89 (m, 2H), 1.76 (s, 3H), 1.77 (s, 3H), 2.30 (d, A of AB,
J=17.9 Hz, 1H), 2.73 ppm (d, B of AB, J=17.9 Hz, 1H); 13C NMR
(CDCl3): d=22.0 (CH3), 22.1 (CH3), 22.7 (CH3), 22.8 (CH3), 24.3 (CH3),
24.4 (C), 26.2 (CH3), 27.2 (CH), 35.4 (CH), 43.7 (CH2), 43.9 (CH2), 49.9
217.1204; found: 217.1199.
4p: Colorless oil; 1H NMR (CDCl3): d=1.04 (s, 3H), 1.15 (s, 3H), 1.72
(s, 1H), 1.78 (s, 6H), 1.93 (t, J=7.0 Hz, 2H), 2.33 (d, A of AB, J=
18.2 Hz, 1H), 2.78 (d, B of AB, J=18.2 Hz, 1H), 3.74 ppm (t, J=7.0 Hz,
2H), OH unobserved; 13C NMR (CDCl3): d=21.7 (CH3), 22.0 (CH3),
22.5 (2C, CH3 and C), 22.6 (CH3), 34.3 (CH), 36.7 (CH2), 43.4 (CH2),
50.0 (C), 61.2 (CH2), 125.6 (C), 126.7 (C), 220.6 ppm (C); IR (neat): n˜ =
1734, 3384 cmÀ1; HRMS(ES +) calcd for C13H20O2Na: 231.1361; found:
231.1356.
4q: Colorless oil; 1H NMR (CDCl3): d=1.01 (s, 3H), 1.11 (s, 3H), 1.52–
1.69 (m, 4H), 1.60 (s, 1H), 1.73 (s, 3H), 1.74 (s, 3H), 2.26 (d, A of AB,
J=18.2 Hz, 1H), 2.68 (d, B of AB, J=18.2 Hz, 1H), 3.56–3.71 ppm (m,
2H), OH unobserved; 13C NMR (CDCl3): d=21.9 (CH3), 22.3 (CH3),
22.7 (CH3), 25.8 (C), 26.5 (CH3), 30.2 (CH2), 30.6 (CH2), 34.1 (CH), 43.1-
(C), 125.1 (C), 127.4 (C), 220.8 ppm (C); IR (neat): n˜ =1741 cmÀ1
HRMS(ES +) calcd for C15H24ONa: 273.1467; found: 273.1463.
;
4j (E isomer): Colorless oil; 1H NMR (CDCl3): d=1.07 (s, 3H), 1.19 (s,
3H), 1.79 (d, J=6.5 Hz, 3H), 1.80 (s, 1H), 2.28 (d, A of AB, J=17.9 Hz,
1H), 2.94 (d, B of AB, J=17.9 Hz, 1H), 3.37 (s, 3H), 3.38 (d, A of AB,
J=10.3 Hz, 1H), 3.51 (d, B of AB, J=10.3 Hz, 1H), 5.94 ppm (qd, J=
6.5, 1.5 Hz, 1H); 13C NMR (CDCl3): d=17.3 (CH3), 22.0 (CH3), 25.1 (C),
26.4 (CH3), 33.4 (CH), 41.9 (CH2), 50.3, (C), 58.8 (CH3), 75.3 (CH2),
117.6 (CH), 131.3 (C), 219.7 ppm (C); IR (neat): n˜ =1741 cmÀ1; HRMS
(ES+) calcd for C12H18O2Na: 217.1204; found: 217.1199.
(CH2), 50.2 (C), 62.9 (CH2), 125.4 (C), 127.1 (C), 220.7 ppm (C); IR
(neat): n˜ =1737, 3394 cmÀ1
; HRMS(ES +) calcd for C14H22O2Na:
4j (Z isomer): Colorless oil; 1H NMR (CDCl3): d=1.04 (s, 3H), 1.16 (s,
3H), 1.74 (dd, J=6.5, 1.8 Hz, 3H), 1.79 (d, J=2.2 Hz, 1H), 2.32 (d, A of
AB, J=18.1 Hz, 1H), 2.97 (d, B of AB, J=18.1 Hz, 1H), 3.35 (d, A of
AB, J=10.4 Hz, 1H), 3.38 (s, 3H), 3.67 (d, B of AB, J=10.4 Hz, 1H),
5.89 ppm (qd, J=6.5, 1.0 Hz, 1H); 13C NMR (CDCl3): d=17.1 (CH3),
21.3 (CH3), 24.9 (C), 26.2 (CH3), 34.1 (CH), 41.4 (CH2), 49.6 (C), 59.1
(CH3), 74.8 (CH2), 118.1 (CH), 131.2 (C), 219.7 ppm (C); IR (neat): n˜ =
245.1517; found: 245.1512.
5a: Colorless oil; 1H NMR (CDCl3): d=0.17 (s, 9H), 0.98 (s, 3H), 1.09
(s, 3H), 1.24 (s, 3H), 1.28 (s, 3H), 4.19 (s, 1H), 5.42 (d, J=10.1 Hz, 1H),
5.48 ppm (d, J=10.1 Hz, 1H); 13C NMR (CDCl3): d=0.19 (CH3), 22.6
(CH3), 25.5 (2C, CH3), 29.7 (CH3), 35.2 (C), 70.4 (CH), 73.9 (C), 90.3
(C), 103.5 (C), 132.3 (CH), 133.7 ppm (CH).
1
5b (major isomer): Colorless oil; H NMR (CDCl3): d=0.17 (s, 9H), 0.98
1741 cmÀ1
217.1199.
;
HRMS(ES +) calcd for C12H18O2Na: 217.1204; found:
(s, 3H), 1.12 (s, 3H), 1.24 (d, J=6.6 Hz, 3H), 4.08 (s, 1H), 4.18–4.26 (m,
1H), 5.45 (dd, J=10.2, 1.3 Hz, 1H), 5.57 ppm (dd, J=10.2, 2.0 Hz, 1H);
13C NMR (CDCl3): d=0.01 (CH3), 21.4 (CH3), 23.2 (CH3), 25.2 (CH3),
35.2 (C), 71.8 (CH), 74.8 (CH), 91.0 (C), 102.2 (C), 128.3 (CH),
1
4k: Colorless oil; H NMR (CDCl3): d=1.7 (s, 3H), 1.18 (s, 3H), 1.78 (s,
3H), 1.81 (s, 4H), 2.30 (d, A of AB, J=17.9 Hz, 1H), 2.96 (d, B of AB,
J=17.9 Hz, 1H), 3.30 (d, A of AB, J=10.3 Hz, 1H), 3.39 (s, 3H),
3.66 ppm (d, B of AB, J=10.3 Hz, 1H); 13C NMR (CDCl3): d=21.9
(CH3), 22.3 (CH3), 22.6 (CH3), 25.7 (C), 26.3 (CH3), 34.4 (CH), 41.1
(CH2), 50.1 (C), 59.0 (CH3), 75.1 (CH3), 124.8 (C), 126.8 (C), 220.2 ppm
(C); IR (neat): n˜ =1741 cmÀ1; HRMS(ES +) calcd for C13H20O2Na:
231.1361; found: 231.1355.
135.1 ppm (CH); IR (neat): n˜ =2181 cmÀ1
; HRMS(ES +) calcd for
C13H22OSiNa: 245.1338; found: 245.1335.
1
5b (minor isomer): Colorless oil; H NMR (CDCl3): d=0.17 (s, 9H), 1.06
(s, 3H), 1.07 (s, 3H), 1.24 (d, J=6.8 Hz, 3H), 4.22 (s, 1H), 4.39–4.46 (m,
1H), 5.45 (dd, J=10.2, 1.3 Hz, 1H), 5.57 ppm (dd, J=10.2, 2.0 Hz, 1H);
13C NMR (CDCl3): d=0.17 (CH3), 20.2 (CH3), 23.7 (CH3), 27.1 (CH3),
35.0 (C), 67.6 (CH), 71.3 (CH), 98.0 (C), 102.3 (C), 128.2 (CH),
4l: Colorless oil; 1H NMR (CDCl3): d=0.82–0.99 (m, 3H), 1.01 (s, 3H),
1.11 (s, 3H), 1.20–1.39 (m, 8H), 1.45–1.65 (m, 2H), 1.55 (d, J=1.1 Hz,
1H), 1.74 (d, J=1.2 Hz, 3H), 1.75 (s, 3H), 2.25 (d, A of AB, J=17.9 Hz,
1H), 2.78 ppm (d, B of AB, J=17.9 Hz, 1H); 13C NMR (CDCl3): d=14.1
(CH3), 22.0 (CH3), 22.2 (CH3), 22.6 (CH2), 22.7 (CH3), 25.2 (C), 26.5
(CH3), 27.5 (CH2), 29.6 (CH2), 31.8 (CH2), 31.8 (CH2), 34.1 (CH2), 34.2
(CH), 43.1 (CH2), 50.1 (C), 124.9 (C), 127.6 (C), 220.8 ppm (C); IR
133.5 ppm (CH); IR (neat): n˜ =2181 cmÀ1
; HRMS(ES +) calcd for
C13H22OSiNa: 245.1338; found: 245.1335.
1
5c: Colorless oil; H NMR (CDCl3): d=0.20 (s, 9H), 1.00 (s, 3H), 1.12 (s,
3H), 1.31–1.80 (m, 10H), 4.23 (s, 1H), 5.52 (d, J=10.1 Hz, 1H),
5.58 ppm (d, J=10.1 Hz, 1H); 13C NMR (CDCl3): d=0.11 (CH3), 22.0
(CH2), 22.1 (CH2), 22.8 (CH3), 25.4 (CH3), 25.7 (CH2), 33.7 (C), 38.1 (2C,
Chem. Eur. J. 2008, 14, 1482 – 1491
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1489

M. Malacria, L. Fensterbank et al.
CH2), 69.6 (CH), 74.5 (C), 89.9 (C), 103.8 (C), 131.2 (CH), 134.2 ppm
(CH); IR (neat): n˜ =2180 cmÀ1
1660 cmÀ1
199.1093.
;
HRMS(ES +) calcd for C12H16ONa: 199.1099; found:
.
9o: Colorless oil; 1H NMR (CDCl3): d=0.90 (d, J=3.0 Hz, 1H), 1.01 (s,
3H), 1.14 (s, 3H), 1.20 (s, 3H), 1.22 (s, 3H), 1.40 (d, J=3.0 Hz, 1H), 2.37
(d, A of AB, J=18.2 Hz, 1H), 2.85 (d, B of AB, J=18.2 Hz, 1H), 3.90
(d, J=8.5 Hz, 1H), 3.93 ppm (d, J=8.5 Hz, 1H); 13C NMR (CDCl3): d=
20.3 (CH3), 24.5 (CH3), 25.9 (CH3), 27.0 (CH3), 29.6 (C), 32.7 (CH), 37.1
(CH), 38.0 (C), 47.6 (C), 67.7 (CH2), 81.2 (C), 218.8 ppm (C); IR (neat):
n˜ =1739 cmÀ1; HRMS(ES +) calcd for C12H18O2Na: 217.1204; found:
217.1200.
5i: Colorless oil; 1H NMR (CDCl3): d=0.97 (d, J=6.0 Hz, 6H), 0.98 (s,
3H), 1.09 (s, 3H), 1.24 (s, 3H), 1.27 (s, 3H), 1.83 (non, J=6.6 Hz, 1H),
2.10–2.19 (m, 2H), 4.18 (t, J=2.0 Hz, 1H), 5.41 (d, J=10.1 Hz, 1H),
5.48 ppm (d, J=10.1 Hz, 1H); 13C NMR (CDCl3): d=22.1 (2C, CH3),
22.6 (CH3), 25.44 (CH3), 25.45 (CH3), 28.1 (CH), 28.2 (CH2), 29.7 (CH3),
35.20 (C), 70.1 (CH), 73.6 (C), 78.5 (C), 85.1 (C), 132.2 (CH), 133.8 ppm
(CH); IR (neat): n˜ =2235 cmÀ1
.
5k: Colorless oil; 1H NMR (CDCl3): d=0.97 (s, 3H), 1.08 (s, 3H), 1.22
(s, 3H), 1.25 (s, 3H), 3.35 (s, 3H), 4.13 (s, 2H), 4.21 (s, 1H), 5.40 (d, J=
10.4 Hz, 1H), 5.45 ppm (d, J=10.4 Hz, 1H); 13C NMR (CDCl3): d=22.5
(CH3), 25.2 (CH3), 25.3 (CH3), 29.5 (CH3), 35.0 (C), 57.6 (CH3), 60.09
(CH2), 69.9 (CH), 73.7 (C), 81.4 (C), 84.0 (C), 132.0 (CH), 133.5 ppm
(CH); HRMS(ES +) calcd for C13H20O2Na: 231.1361; found: 231.1355.
9p: Colorless oil; 1H NMR (CDCl3): d=0.27 (d, J=4.0 Hz, 1H), 0.99 (s,
3H), 1.13 (s, 3H), 1.19 (s, 3H), 1.23 (d, J=4.0 Hz, 1H), 1.34 (s, 3H),
1.81–1.89 (A of ABm, 1H), 1.91–2.05 (B of ABm, 1H), 2.30 (d, A of AB,
J=18.4 Hz, 1H), 2.69 (d, B of AB, J=18.4 Hz, 1H), 3.44–3.53 (A of
ABm, 1H), 3.58–3.66 ppm (B of ABm, 1H); 13C NMR (CDCl3): d=19.9
(C), 20.54 (CH3), 25.2 (CH2), 26.6 (CH3), 27.4 (CH), 28.2 (CH), 32.5
(CH3), 24.7 (CH3), 45.8 (CH2), 48.5 (C), 57.7 (CH2), 69.5 (C), 220.7 ppm
General procedure for oxidation with mCPBA: A solution of 4k–n
(1.2 mmol) in dry CH2Cl2 (10 mL) was treated with NaHCO3 (192 mg,
2.2 mmol) and mCPBA (70%, 430 mg, 1.74 mmol). The mixture was
stirred at room temperature for 2 h, diluted with a saturated aqueous
NaHCO3 solution, vigorously stirred for 15 min, and extracted with
CH2Cl2. The combined organic layers were washed successively with
water and then brine, dried over MgSO4, filtered, and evaporated under
reduced pressure. 6k–n were purified by flash chromatography on silica
gel (petroleum ether/AcOEt 9/1).
(C); IR (neat): n˜ =1738 cmÀ1
.
10p: Colorless oil; 1H NMR (CDCl3): d=0.94 (s, 3H), 1.06 (s, 3H), 1.75
(s, 3H), 1.85 (d, J=1.0 Hz, 3H), 2.10–2.21 (m, 2H), 2.50–2.65 (m, 3H),
3.78–3.92 (m, 2H), 4.97 ppm (s, 1H); 13C NMR (CDCl3): d=17.1 (CH3),
18.1 (CH3), 20.0 (CH3), 27.8 (CH3), 31.2 (CH2), 40.8 (CH2), 42.2 (CH),
55.8 (C), 66.0 (CH2), 94.8 (C), 121.2 (CH), 138.2 (C), 221.1 ppm (C); IR
(neat): n˜ =1735 cmÀ1; HRMS(ES +) calcd for C13H20O2Na: 231.1361;
found: 231.1355.
10q: White solid; m.p. 146–1478C; 1H NMR (CDCl3): d=0.89 (s, 3H),
1.10 (s, 3H), 1.58–1.65 (m, 1H), 1.68 (d, J=1.3 Hz, 3H), 1.76 (d, J=
1.5 Hz, 3H), 1.85–1.96 (m, 2H), 2.01–2.10 (m, 1H), 2.42 (d, A of AB, J=
18.8 Hz, 1H), 2.53 (d, B of AB, J=18.8 Hz, 1H), 2.99 (d, J=11.0 Hz,
1H), 3.64–3.83 (m, 2H), 4.99–5.08 ppm (m, 1H); 13C NMR (CDCl3): d=
18.3 (CH3), 20.7 (CH3), 25.6 (CH3), 26.1 (CH2), 26.5 (CH3), 33.0 (CH2),
50.4 (C), 50.6 (CH2), 54.4 (CH), 67.0 (CH2), 87.2 (C), 120.0 (CH), 136.1
(C), 221.2 ppm (C); IR (neat): n˜ =1737 cmÀ1; HRMS(ES +) calcd for
C14H22O2Na: 245.1517; found: 245.1512.
6k: Colorless oil; 1H NMR (CDCl3): d=1.00 (s, 3H), 1.07 (s, 3H), 1.12
(s, 3H), 1.22 (s, 3H), 2.54 (d, J=19.2 Hz, 1H), 2.90 (d, J=19.2 Hz, 1H);
3.27 (s, 1H), 3.38 (s, 3H), 3.58 (d, J=9.6 Hz, 1H), 3.65 ppm (d, J=
9.6 Hz, 1H); 13C NMR (CDCl3): d=19.2 (CH3), 19.3 (CH3), 20.1 (CH3),
27.6 (CH3), 41.2 (CH2), 41.4 (C), 48.9 (C), 59.3 (CH3), 61.4 (C), 71.1
(CH), 75.8 (CH2), 214.7 (C), 220.7 ppm (C); IR (neat): n˜ =1736,
1770 cmÀ1
247.1304.
; HRMS(ES +) calcd for C13H20O3Na: 247.1311; found:
6n: Colorless oil; 1H NMR (CDCl3): d=1.12 (s, 3H), 1.27 (s, 3H), 1.28
(s, 3H), 1.40 (s, 3H), 1.70 (s, 1H), 2.41 (d, J=18.4 Hz, 1H), 2.98 (d, J=
18.4 Hz, 1H); 3.22 (d, J=9.6 Hz, 1H), 3.36 (d, J=9.6 Hz, 1H), 7.15–7.41
(m, 8H), 7.45–7.55 ppm (m, 7H); 13C NMR (CDCl3): d=20.1 (CH3), 22.4
(CH3), 22.5 (CH3), 24.0 (C), 27.1 (CH3), 30.0 (CH), 38.5 (CH2), 47.9 (C),
63.1 (CH2), 71.7 (C), 86.4 (C), 127.0 (C), 127.1 (CH), 127.8 (CH), 128.5
(CH), 143.8 (C), 218.3 ppm (C); IR (neat): n˜ =1743 cmÀ1; HRMS(ES +)
calcd for C31H32O3Na: 475.2249; found: 475.2243.
Acknowledgement
This work was supported by CNRS, MRES, IUF, and ANR BLAN 06-
2_159258. R.Z. is thankful to CNRSfor a grant. V.G. thanks Prof. Phil-
ippe Bertus for fruitful discussions.
General procedure for iodocyclization with NIS: A solution of 4o,p
(0.25 mmol) and NIS(68 mg, 0.3 mmol) in CH 3CN (1 mL) and H2O
(0.5 mL) was stirred for 1 h at 508C. The reaction was quenched with a
saturated aqueous solution of Na2S2O3, extracted with diethyl ether,
dried over MgSO4, and concentrated under reduced pressure. 7o,p were
purified by flash chromatography on silica gel (petroleum ether/AcOEt
9/1).
7o: White solid; m.p. 115–1168C; 1H NMR (CDCl3): d=1.11 (s, 3H),
1.27 (s, 3H), 1.28 (s, 3H), 1.40 (s, 3H), 1.44 (s, 1H), 2.32 (d, A of AB, J=
18.7 Hz, 1H), 3.00 (d, B of AB, J=18.7 Hz, 1H), 3.86 (d, A of AB, J=
8.9 Hz, 1H), 3.90 ppm (d, B of AB, J=8.9 Hz, 1H); 13C NMR (CDCl3):
d=18.1 (CH3), 22.3 (CH3), 28.6 (CH3), 29.0 (CH3), 33.4 (C), 35.0 (C),
36.3 (CH), 39.4 (CH2), 50.9 (C), 66.4 (CH2), 85.3 (C), 216.4 ppm (C);
HRMS(ES +) calcd for C12H17O2INa: 343.0171; found: 343.0165.
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126, 10858–10859; g) A. Fürstner, F. Stelzer, H. Szillat, J. Am.
7p: Colorless oil; 1H NMR (CDCl3): d=1.11 (s, 3H), 1.25 (s, 3H), 1.36
(s, 3H), 1.59 (s, 1H), 1.60 (s, 3H), 1.99–2.08 (m, 1H), 2.19–2.26 (m, 1H),
2.41 (d, A of AB, J=18.9 Hz, 1H), 2.78 (d, B of AB, J=18.9 Hz, 1H),
3.62–3.86 ppm (m, 2H); 13C NMR (CDCl3): d=19.2 (CH3), 24.2 (CH2),
26.1 (C), 26.6 (CH3), 27.9 (CH3), 28.5 (CH3), 37.8 (CH), 41.4 (C), 50.4
(CH2), 51.7 (C), 57.4 (CH2), 74.5 (C), 217.9 ppm (C); IR (neat): n˜ =
1739 cmÀ1
357.0324.
; HRMS(ES +) calcd for C13H19O2INa: 357.0327; found:
8o: Colorless oil; 1H NMR (CDCl3): d=1.16 (s, 6H), 1.89 (t, J=1.3 Hz,
3H), 2.03 (d, J=1.3 Hz, 3H), 4.80–4.83 (A of ABm, 1H), 5.03–5.06 (B of
ABm, 1H), 5.89 (s, 1H), 5.98 ppm (s, 1H); 13C NMR (CDCl3): d=21.3
(CH3), 24.3 (CH3), 25.6 (CH3), 46.1 (C), 115.6 (CH2), 124.1 (CH), 137.1
(C), 143.8 (C), 144.0 (CH), 153.9 (C), 205.4 ppm (C); IR (neat): n˜ =
1490
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Chem. Eur. J. 2008, 14, 1482 – 1491

Cycloisomerization of Hydroxylated 1,5-Allenynes
FULL PAPER
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cloisomerizations. Indeed, the reaction of an allenyne similar to 1k
without substituents at C4 led to the corresponding cyclopentenone
in 50% yield of isolated product under the same experimental con-
ditions.
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You, J. Am. Chem. Soc. 2002, 124, 15186–15187; for thermal, micro-
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nynes, see inter alia: i) H. Ohno, T. Mizutani, Y. Kadoh, K. Miya-
mura, T. Tanaka, Angew. Chem. 2005, 117, 5243–5245; Angew.
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[4] We thank Prof. F. D. Toste, UC-Berkeley, for sharing with us some
findings on that topic.
[10] CCDC-662257 contains 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.
[11] Examples of distinctly different behavior of platinum and gold cata-
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[12] a) B. Gockel, N. Krause, Org. Lett. 2006, 8, 4485–4488; for related
gold-catalyzed cycloisomerization of a-aminoallenes to 3-pyrrolines,
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[14] Protecting the hydroxyl group as an acetate led only to Alder-ene
cycloisomerization products with or without catalyst. Interestingly,
no acetate migration was observed (see ref. [1]).
[15] The reason for this chemoselectivity is not well understood at this
time.
[16] J. K. Crandall, W. W. Conover, J. Org. Chem. 1978, 43, 3533–3535.
[17] CCDC-662258 contains 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.
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iodine-containing compounds 7 and reduction products 9. The NMR
data of these products are identical to those obtained with NISfor 7
and by gold-catalyzed cycloisomerization for 9. Therefore, we be-
lieve that compounds of type 9 display the same stereochemical ar-
rangement as compounds 7.
[5] These compounds undergo thermal and molybdenum- or palladium-
catalyzed [2+2] cycloadditions to give bicyclo[3.2.0]hepta-1,5-
A
dienes; for examples, see: a) C. H. Oh, D. I. Park, S. H. Jung, V. R.
Reddy, A. K. Gupta, Y. M. Kim, Synlett 2005, 2092–2094. They also
give rise to Alder-ene-type cycloisomerizations to 5-methylene-1-vi-
nylcyclopent-1-enes mediated by titanium(II): b) T. Yamazaki, H.
Urabe, F. Sato, Tetrahedron Lett. 1998, 39, 7333–7336.
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[7] M. A. Brook in Silicon in Organic, Organometallic, and Polymer
Chemistry, Wiley, New York, 2000.
[20] Although the proposed stereochemistry of compounds 10 seems
likely, it was not established by NOE experiments.
[8] The unfunctionalized 6-methylenebicyclo[3.1.0]hexane framework is
G
known; see inter alia: J. J. Gajewski, S. K. Chou, J. Am. Chem. Soc.
1977, 99, 5696–5707.
[9] It is noteworthy that, although gem-dimethyl substitution in the
tether improves the yield, it is not a necessary feature for such cy-
Received: September 25, 2007
Published online: November 22, 2007
Chem. Eur. J. 2008, 14, 1482 – 1491
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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