Ring size effects in the C2-C6 biradical cyclisation of enyne-allenes and the relevance for neocarzinostatin

Article abstract of DOI:10.1039/b102380m

The regioselectivity of the thermal cyclisations of enyne-allenes 1 can be toggled as a function of the ring size of the cycloalkene. With a cyclopentene as the ene moiety the Myers-Saito (C²-C⁷) cycloaromatisation product is formed, whereas with six- and seven-membered cycloalkenes the novel C²-C⁶ cyclisation is observed. DFT calculations are used to rationalise these changes. The implications of these findings for alternative thermal biradical cyclisations of neocarzinostatin are discussed.

Full text of DOI:10.1039/b102380m

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2
6
Ring size effects in the C –C biradical cyclisation of enyne–
allenes and the relevance for neocarzinostatin
a
a
a
b
b
Michael Schmittel,* Jens-Peter Steffen, Michael Maywald, Bernd Engels,* Holger Helten
and Patrick Musch
b
2
a
FB 8 - OC1 (Chemie - Biologie), Universität GH Siegen, Adolf-Reichwein-Str,
D-57068 Siegen, Germany. E-mail: schmittel@chemie.uni-siegen.de
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg,
Germany. E-mail: bernd@chemie.uni-wuerzburg.de
b
Received (in Cambridge, UK) 12th March 2001, Accepted 18th May 2001
First published as an Advance Article on the web 15th June 2001
The regioselectivity of the thermal cyclisations of enyne–allenes 1 can be toggled as a function of the ring size of the
cycloalkene. With a cyclopentene as the ene moiety the Myers–Saito (C –C ) cycloaromatisation product is formed,
whereas with six- and seven-membered cycloalkenes the novel C –C cyclisation is observed. DFT calculations are
used to rationalise these changes. The implications of these findings for alternative thermal biradical cyclisations of
neocarzinostatin are discussed.
2
7
2
6
Introduction
evidence has been presented for the intermediate benzofulvene
6 2 6
biradical in the C –C cyclisation, it is the intramolecular
follow-up reaction of the biradical intermediate to formal ene
and Diels–Alder type products that renders this process so
efficient. In contrast, intermolecular trapping of the benzo-
1
Cycloaromatisations of enediynes (Bergman cyclisation) and
2
2
7
enyne–allenes (Myers–Saito cyclisation, C –C ) have received
3
large interest over the last decade since the intervening bi-
radicals constitute key intermediates in the mode of action of
natural enediyne antitumor antibiotics. However, while the
above cyclisations may be regarded as electrocyclic reactions
6c
fulvene biradical is synthetically rather unsatisfying.
4
2
6
As the novel C –C cyclisation has recently moved into the
10
11
focus of theoretical, DNA cleavage, and synthetic studies
13
leading to aromatic biradicals via in-plane aromatic transition
12
(
e.g. towards the kinamycin
and the neocryptolepine
5
2
6
6
states the novel C –C cyclisation of enyne–allenes (Scheme 1)
family), it seemed to be important to learn more about the
various factors controlling the regioselectivity of a thermal
biradical cyclisation. Up to now the influence of ring size effects
on the regioselectivity has not been investigated systematically,
14
although a few isolated examples may indicate some effect.
15
Herein, we would like to disclose that the switch between the
2
7
2
6
C –C and the C –C cyclisation can be initiated simply by ring
size effects.
Results
Preparation of cyclic enyne–allenes 1a–f
Enyne–allenes 1a–f are available in a four-step synthesis from
the corresponding cycloalkanones via the cycloalkene carbalde-
16
hydes. The latter are reacted using a Sonogashira coupling
with two acetylides, either nBuC᎐CMgBr or [(PhC᎐C) -
᎐
᎐
2
17
AlH ]Na, the second being prepared from phenylacetylene
2
and SDDA ([Et AlH ]Na). The resultant propargyl (prop-2-
2
2
ynyl) alcohols 3a–f were treated with ClPPh thus providing the
2
18
diphenylphosphane oxide substituted enyne–allenes
1a–f
Scheme 1
after a [2,3]-sigmatropic rearrangement (Scheme 2). Enyne–
allenes were isolated by column chromatography or HPLC. The
structures were identified by IR, H NMR, C NMR and high
leads to an intermediate benzofulvene biradical in a 5-exo-dig
fashion reminiscent of the regioselectivity of mono radical
cyclisations. Our studies have shown that the proper choice of
1
13
6
resolution mass spectrometry. During isolation of enyne–allene
1
f the follow-up product 13f was also obtained.
substituents R at the alkyne terminus allows the regioselectivity
of thermal enyne–allene biradical cyclisations to be steered
Thermolysis of 1a–f
2
7
2
6
away from the Myers–Saito (C –C ) towards the C –C path-
way. Moreover, the switch from R = H towards R = aryl likewise
led to analogue regiocontrol of the biradical cyclisations of
Enyne–allenes 1a–f experience thermal cyclisation over a wide
19
temperature range as demonstrated by the onset temperature
7–9
enyne–carbodiimides and enyne–ketenimines.
from DSC experiments (1a: 145 ЊC, 1b: 110 ЊC, 1c: 92 ЊC, 1d:
70 ЊC, 1e: 61 ЊC, 1f: 40 ЊC). Thermolyses of enyne–allene 1a
in toluene and of 1b in mesitylene at reflux temperature in
the presence of an excess of cyclohexa-1,4-diene (1,4-CHD)
2
6
In many examples described so far the C –C reaction pro-
ceeds in rather high yields, in particular when compared to
other thermal biradical cyclisations. As ample mechanistic
DOI: 10.1039/b102380m
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339
This journal is © The Royal Society of Chemistry 2001
1331

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furnished the cyclisation products 4a (15%) and 4b (31%)
Scheme 3). In addition, some other follow-up products (5a, 6a
and 7b) were found, which were structurally characterised using
NMR techniques such as DEPT, H,H- and C,H-COSY and
HMBC measurements.
the radical 10a, because it can be stabilised either through
hydrogen donation to another radical or through C–P bond
cleavage (a phenylogous β-fragmentation). For the benzylic
radical 9b cyclisation is less of an option because it is a less
reactive benzhydryl radical, but it can nevertheless combine in
the para position with benzyl radicals (from the solvent) to
form the α,para combination product whose rearrangement
furnishes 7b (Scheme 4).
(
Products 4a–6a, 4b, 7b can be explained directly from the
2
7
intermediate Myers–Saito (C –C ) biradical 8a,b (Scheme 4).
While the more reactive σ-radical site readily abstracts one
hydrogen from toluene–cyclohexadiene to afford 9a,b, the
benzylic π-radical is less reactive and additionally shielded to
some extent against intermolecular reactions. Hence, only some
of the 9a,b undergoes a second hydrogen abstraction to 4a,b.
Alternatively, radical 9a (R = nBu) may undergo a cyclisation to
In contrast, thermolysis of enyne–allenes 11d,f afforded the
2
6
C –C cyclisation products, as demonstrated by formation of
the formal Diels–Alder products 13d (80%, 110 ЊC, 3 h, 20 eq.
of 1,4-CHD) and 13f (85%, 110 ЊC, 3 h, 20 eq. of 1,4-CHD).
These products are exactly those that we expect from an
intermediate fulvene biradical 11d,f after intramolecular ring
closure (Scheme 5).
Thermolyses (5 min at 80 ЊC, DMSO, without 1,4-CHD) of
2
6
the enyne–allenes 1c,e also led to C –C cyclisation products.
1
Detailed investigations by H NMR (see Experimental section)
showed the intermediate formation of the ene products 12c,e
through intramolecular hydrogen transfer from 11c,e.
Unfortunately, 12c,e are not stable enough to be isolated, as
they contain a vinyl fulvene as a structural motif that is prone
Scheme 2 Synthesis of the enyne–allenes 1a–f.
Scheme 4 Thermolyses of enyne–allenes 1a,b.
Scheme 3
1
332
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339

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Table 1 ‡ Summary of the calculated data for the transition state ener-
2
6
2
7
gies ∆G (298 K) of C –C and Myers–Saito (C –C ) cyclisation of
Ϫ1
model compound 15. The energies are given in kcal mol with respect
to those of the corresponding enyne–allenes
2
3
‡
2
6
‡
2
7
n
Substituent R
∆G (C –C )
∆G (C –C )
1
1
1
1
1
1
5a
5b
5c
5d
5e
5f
1
2
3
1
2
3
H
H
H
Ph
Ph
Ph
+34.1
+27.8
+26.6
+30.3
+24.2
+22.2
+25.0
+22.3
+20.6
+30.9
+28.1
+26.1
the unrestricted approach does not reveal an existing instability
of the closed shell solution possibly found. Corrections to
the pure singlet state were not performed since all optimised
stationary points under consideration possess no or only minor
spin contamination (〈S 〉 ≤ 0.2). The computational results on
the enyne–allenes and the transition states of both biradical
Scheme 5 Thermolysis of enyne–allenes 1c–f.
2
20,21
to dimerisations or polymerisations.
Indeed, prolonged
heating caused decomposition of 12c,e to unidentifiable
products. Even when using different conditions for the therm-
olysis (various temperatures, flash pyrolysis, different solvents)
complex mixtures were always furnished.
cyclisations are depicted in Tables 1 and 2.
Discussion
Calculations
Ring strain effects and cyclisation mode
Knowing that aryl groups at the alkyne terminus redirect the
Our original reasoning about the dramatic switch from the
2
7
2
6
2
6
C –C to the C –C cyclisation as a function of the substituent
course of enyne–allene cyclisations towards the C –C mode a
14
at the alkyne terminus was based on the assumption that the
transition state (TS) of the C –C cyclisation would already
show some biradical character. As a consequence, a phenyl
group should stabilise the forming vinyl radical center and
recent result of Wang et al. was quite surprising. Thermolysis
of the cyclopentene based enyne–allene 1g only furnished the
2
6
2
7
C –C cyclisation product 14 and not 13g (Scheme 6). Another
2 7
2
2
example of the C –C cyclisation of a cyclopentene based
enyne–allene derivative with an attached aryl group at the
acetylene terminus was presented by Nakatani et al. in the
2
6
thus the TS of the C –C cyclisation could fall beneath that of
6c
2
7
the C –C cycloaromatisation. Recent calculations by Engels
10a
30
and by Schreiner, however, have indicated clearly that the
TS of the C –C cyclisation possesses mainly a closed-shell
electronic structure. Nevertheless, the calculations indicate a
lower activation barrier for the C –C than for the C –C cyclis-
biradical cyclisation of enyne–ketenes.
2
6
A much more detailed picture now emerges from our experi-
mental results on the thermolyses of enyne–allenes 1a–f which
are summarised in Schemes 3 and 5. Accordingly, with cyclo-
2
6
2
7
Ϫ1
2
6
ation (29 vs. 30 kcal mol ). The reason for that is a resonance
hexene and cycloheptene derived enyne–allenes the novel C –C
2
6
stabilisation of the C –C cyclisation TS as evidenced by a sig-
cyclisation is observed as controlled through the presence of a
7
phenyl
nificant C –C
bond shortening (1.411 Å) when compared
phenyl group at the acetylene terminus, but the Myers–Saito
2
7
2
7
to the C –C TS (1.454 Å).
(C –C ) cycloaromatisation is the predominant pathway for the
cyclopentene based enyne–allenes. Obviously, the aryl group
at the alkyne cannot override a particular ring size effect that
Analogue quantum chemical calculations were now used to
2
6
2
7
get an insight into ring size effects on the C –C and C –C
2
3
2
7
cyclisations. The geometries of all stationary points were
optimised using analytical energy gradients within the density
25
for a 5-membered ring prefers the C –C cyclisation.
To understand this ring size effect we have carried out calcu-
lations on the two competing biradical cyclisations using
24
functional theory (DFT) approach employing the B3LYP
2
6
2
6
hybrid functional in conjunction with the 6-31G(d) basis
set. Optimised stationary points were characterised as minima
or transition states by the computation of the correspond-
ing vibrational frequencies. The influence of nuclear motion
and temperature effects were incorporated in the standard
enyne–allene 15 as a model. Neither the distances d(C –C ) and
2 7
d(C –C ) nor the dihedral angles ꢀ and θ (Table 2) reveal a clear
trend with ring size in enyne–allene 15 or with transition state
free energies (Table 1) for both cyclisation modes. This is quite
in contrast to Nicolaou’s postulate (revised later by Maier)
relating the corresponding cd-distance in enediynes with their
27
approach.
All calculations were performed with the
2
8
3a
Gaussian98 package.
thermal activation barriers. It is clear, however, that the
6
c,d,10a
Former studies
showed, that DFT is sufficiently
geometrical reorganisation along d when going from the enyne–
2
7
accurate to describe the barriers of activation correctly if a
spatial and spin unrestricted ansatz (e.g. UB3LYP) is employed
and no or only small spin contamination occurs for the trans-
ition states along the biradical pathways. In order to test for
the biradical nature of the transition states, an additional check
of the stability of the wavefunctions was performed and the
wavefunction as well as the geometry were reoptimised if an
instability was encountered. This additional check of the
wavefunction is necessary since in many cases the simple use of
allene to the transition state is much larger for the C –C
2 6
(∆d ≈ 150–165 pm) than for the C –C (∆d ≈ 110–120 pm)
cyclisation.
The energetics, as summarised in Table 1, are more inform-
ative indicating that the size of the embedded cycloalkene unit
has a remarkable leverage on the transition state energy of the
two cyclisation modes. For both hydrogen and phenyl substitu-
29
‡
ents at the alkyne (i.e. for 15a–c vs. 15d–f) the decrease of ∆G
2
6
with increasing ring size is stronger for the C –C cyclisation
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339 1333

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1
4
Scheme 6 Unexpected cyclisation pathway of enyne–allene 1g as shown by Wang et al.
2
6
2
7
Table 2 Structural data (from calculations) for enyne–allene 15 and the corresponding C –C and C –C transition states (TS)
2
6
2
7
TS C –C
Enyne–allene
TS C –C
a
2
6
ꢀb
θc
a
2
6
a
2
7
θc
a
2
7
ꢀb
θc
Comp.
n
d (C –C )
d (C –C )
d (C –C )
d (C –C )
1
1
1
1
1
1
5a
5b
5c
5d
5e
5f
1
2
3
1
2
3
192.0
190.6
191.9
193.7
192.8
194.2
12.1
13.6
14.0
18.1
19.2
20.9
318.5
303.0
300.6
319.0
302.6
300.6
373.8
355.6
354.3
375.1
356.0
355.2
208.4
205.7
208.0
207.3
204.1
206.3
39.4
43.5
43.2
39.5
42.7
41.8
56.5
65.5
62.9
0.1
2.2
17.2
61.4
61.3
61.6
a
2
6
2
7
b
3
2
1
1
c
6
7
Ph
Ph + 1
The distance d(C –C ) or d(C –C ) is provided in pm. Dihedral angle (in Њ) for C –C –C –H . Dihedral angle (in Њ) for C –C –C –C
.
Ϫ1
2
7
(
ca. 8 kcal mol ) than for the C –C cyclisation (ca. 5 kcal
Ϫ1
mol ). For R = H (15a–c) ring size effects are too small to
cause a change in the regioselectivity of the cyclisation for
2
7
2
6
systems; C –C cyclisation is clearly favoured over C –C cyclis-
‡
ation for all three calculated model compounds (∆∆G = 6–9
kcal mol ) as corroborated by a few experimental results from
the literature. A different situation is found for the phenyl
substituted systems. In agreement with earlier calculations the
phenyl group increases the barrier for the C –C cyclisation by
approximately 5.5–6 kcal mol while it decreases the one for
C –C cyclisation by 4 ± 0.5 kcal mol . For 15e and 15f the
C –C cyclisation is now clearly favoured over C –C cyclisation
Ϫ1
31
6c
2
7
Ϫ1
2
6
Ϫ1
2
6
2
7
Ϫ1
by about 4 kcal mol , in good agreement with the observed
experimental data for 1c–f. For the cyclopentenyne–allene 15d
both cyclisations have a similar activation free energy. However,
2
6
while the calculated data slightly favour the C –C cyclisation
‡
Ϫ1
(
∆∆G = 0.6 kcal mol ) the thermolysis of 1a,b led to the
2 7
formation of C –C cyclisation products. This close energetic
situation as obtained through the calculations led us to care-
fully reinvestigate the products from the thermolysis of 1a and
1
b. Indeed for 1b we could identify as a minor side product 13b
Scheme 7
2 6
from the C –C pathway among a large excess of Myers–Saito
products (4b, 7b). Compound 13b was unequivocally identified
by its spectral data and by comparison with analogous systems.
Despite major efforts, only 4a, 5a, and 6a but no 12a could be
detected in the thermolysis of 1a, but this may be due to the
aforementioned thermal lability of vinylfulvenes (Scheme 7).
At this point, the calculations on 15d and the experimental
results on 1a,b show some minor deviation in the regioselec-
tivity of the biradical cyclisation. This discrepancy may simply
be related to the fact that different systems are being used for
the experimental and the theoretical investigation. On the other
hand, one might argue that for the five-membered ring system
the product distribution is no longer exclusively controlled
by the kinetic competition of the two biradical cyclisations,
but—because of the unfavourable thermodynamics of the
and their follow-up reactions are too time consuming as density
function theory would not be adequate any more.
Finally, after knowing about ring size effects it seemed
reasonable to ask whether the neocarzinostatin chromophore
2
7
uses the cyclopentene unit to favour C –C (leading to 18) over
2
6
C –C cyclisation (leading to biradical 17). Calculations by
10a
Schreiner indicate that smaller cyclic enyne–allenes (8- and
2
6
9-membered systems) prefer kinetically the C –C cyclisation
pathway and one could imagine that this preference also should
be valid for the cyclic 9-membered enyne–cumulene 16 as
found at the heart of the neocarzinostatin cycloaromatisation
3
2
(Scheme 8).
2
7
The C –C biradical mode in 19 has been evaluated recently
2
6
33
C –C biradical—by the kinetics of the follow-up reaction.
using BPW91/cc-pVDZ quantum mechanical calculations
Unfortunately, reliable theoretical calculations on the biradicals
without addressing alternative pathways. Our UB3LYP DFT
1
334
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339

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Table 3 Comparison of differential energies for 21a–c vs. 22a–c and of
the differential free activation energies for 15a–c
‡
2
6
2
7
n
∆∆G (C –C vs. C –C ) for 15a–c
∆∆E (21–22)
a
b
c
1
2
3
9.1
5.5
6.0
+38.5
+32.8
+33.3
Conclusion
Ring size effects can be used to control the regioselectivity
of thermal enyne–allene cyclisations, allowing either the
2
6
Myers–Saito (with cyclopentenyne–allenes) or C –C cyclis-
ation products (with larger cycloalkenyne–allenes) to be
accessed. This toggle is in line with calculations on the DFT
level. Neocarzinostatin also seems to make use of the annulated
2
7
cyclopentene ring to control its Myers–Saito (C –C ) cyclis-
ation to 18, since in the parent 9-membered cyclic enyne–
2
6
cumulene the C –C biradical is kinetically favoured over the
C –C cyclisation.
Scheme 8
2
7
2
6
calculations on 19 now reveal that the C –C cyclisation path-
‡
Ϫ1
way (∆G = 17.6 kcal mol ) is kinetically favoured over the
Experimental
2
7
‡
Ϫ1
C –C mode (∆G = 20.8 kcal mol ). As 68% of the products
in the neocarzinostatin cycloaromatisation are derived from
biradical 18, one has to assume that nature uses the annulated
cyclopentene ring in 16 to control the regioselectivity of the
biradical cyclisations!
Preamble
All J values are given in Hz. SDDA = sodium diethyldihydro-
aluminate. In almost all cases purification was achieved by
standard column chromatography; in such cases only the
solvent (mixture) is provided. For details about the equipment
used please consult ref. 6b. Compound 2a was synthesised
according to ref. 31a.
Compound 2c. To a mixture of cyclohexene–bromocarb-
aldehyde (5.00 g, 26.4 mmol) (prepared analogously to Arnold
16
and Holý ) and phenylacetylene (3.10 g, 30.4 mmol) in
3
Further calculations, in particular with regard to the cyclis-
ation modes of 20 with n = 1, 2, are currently under way in our
laboratories to clarify this point of interest. So far, calculations
from other groups have solely focused on the straightforward
triethylamine (100 cm ) were added PdCl (PPh ) (278 mg, 396
2
3 2
µmol) and CuI (125 mg, 655 µmol). After stirring the black
solution for 16 h at room temperature it was quenched with a
3
mixture of saturated aqueous ammonium chloride (200 cm )
2
7
33,34
3
C –C cyclisation of enyne–cumulenes,
while experimental
and n-pentane (200 cm ). After filtration the aqueous layer was
3
investigations on neocarzinostatin models follow the natural
washed with n-pentane (2 × 100 cm ). The combined organic
35
bicyclic[7.3.0] system or—because of thermal stability—
layers were dried (MgSO ) and evaporated under reduced
4
36
operate with increased ring size of the larger ring. At present,
pressure to furnish a brown oil. After purification by column
chromatography (silica gel, n-pentane–diethyl ether = 10 : 1)
carbaldehyde 2c (4.45 g, 80%) was isolated as a brown oil
(Found: C, 85.93; H, 6.95. C H O requires C, 85.67; H,
no experimental data on the parent nine-membered enyne–
[
3]cumulene are available to prove or disprove an alternative
2 6
C –C cyclisation. But it is clear from literature reports on
1
5
14
Ϫ1
related systems that competitive biradical cyclisations may be
6.72%); ν
˜ max(film)/cm 3056, 2935, 2860, 2732, 2199, 1673,
31c,34,37
quite reasonable options.
The kinetically controlled switch in the regioselectivity
1603, 1489, 1442, 758 and 689; δ (200 MHz; CDCl ; Me Si)
H
3
4
1.63–1.64 (4 H, m), 2.20–2.30 (2 H, m), 2.40–2.50 (2 H, m),
7.28–7.45 (3 H, m), 7.40–7.45 (2 H, m), 10.28 (1 H, s, CHO);
δ (50 MHz; CDCl ; Me Si) 21.5, 22.3, 22.5, 32.7, 86.7, 98.9,
2
6
between the Myers–Saito and the C –C cyclisation as a func-
tion of the ring size is most likely due to ring strain that already
materialises partly in the transition state and that is substantial
in the biradicals. To estimate the differential strain in the
C
3
4
122.7, 128.9, 129.9, 135.1, 140.4, 143.0, 193.3.
2
6
Myers–Saito vs. the C –C biradicals depending on the ring size
we have determined the relative energy differences ∆∆E (21–22)
Compound 2e. Analogously to 2c a mixture of cycloheptene–
bromocarbaldehyde (2.00 g, 9.85 mmol), phenylacetylene (1.14
38
3
employing DFT. The data in Table 3 reveal clearly a parallel
trend for both the differential activation data and ∆∆E (21–22).
In both sets of data an increase is observed when going
from the unstrained systems b,c (with 6- and 7-membered rings)
to a (5-membered ring). Since the increase is much more pro-
g, 11.2 mmol) in triethylamine (35 cm ), PdCl (PPh ) (104 mg,
2
3 2
148 µmol), and CuI (46.6 mg, 244 µmol) were allowed to react.
After stirring the black solution for 72 h at room temperature it
was worked up as described above. The purification of the
remaining brown oil via column chromatography on silica gel
with a mixture of petroleum ether–diethyl ether (10 : 1)
‡
2
6
2
7
nounced for ∆∆E (21–22) than for ∆∆G (C –C vs. C –C )
only a part of the strain in the biradicals is already found in the
transition states.
afforded the carbaldehyde 2e (1.62 g, 73%) as a yellow oil
Ϫ1
(Found: 224.1197. C H O requires 224.1201); ν
˜
max(film)/cm
16
16
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339
1335

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3
055, 2922, 2850, 2189, 1669, 1599, 1588, 1489, 757 and 670;
(4 H, m, CH CH CH ), 1.50–1.72 (4 H, m, cyclo-CH CH ),
2
2
3
2
2
δ (250 MHz; CDCl ; Me Si) 1.40–1.50 (2 H, m), 1.68–1.74 (2
2.20 (2 H, td, J 7.2, J 2.0, C᎐CCH CH ), 2.11–2.31 (2 H, m,
H
3
4
᎐
2
2
H, m), 1.80–1.83 (2 H, m), 2.52–2.57 (2 H, m), 2.68–2.73 (2 H,
m), 7.33–7.37 (2 H, m), 7.45–7.47 (1 H, m), 7.49–7.50 (2 H, m)
cyclo-CH ), 2.32–2.40 (2 H, m, cyclo-CH ), 2.70 (1 H, s, OH),
2
2
5.72 (1 H, t, J 2.0, HOCHC᎐C), 7.24–7.28 (3 H, m), 7.38–7.41
(2 H, m); δ (63 MHz; CDCl ; Me Si) 14.0, 18.9, 22.4, 22.5, 22.7,
1
2
1
0.30 (1 H, s, CHO); δ (63 MHz; CDCl ; Me Si) 24.4, 25.8,
C 3 4
C
3
4
5.9, 32.4, 37.6, 87.8, 100.4, 122.5, 128.6, 129.3, 131.8, 145.9,
23.9, 30.6, 31.1, 64.7, 79.1, 86.6, 88.5, 93.6, 118.0, 123.8, 128.4,
+
+
48.7, 192.4; m/z 224 (M , 64%), 195 (30), 167 (100).
128.7, 131.8, 144.4; m/z 292 (M , 8%), 275 (14), 211 (100).
Compound 3a. At room temperature a solution of hex-1-yne
452 mg, 5.50 mmol) in dry diethyl ether (5 cm ) was added to
Compound 3d. As described for 3c, phenylacetylene (2.47
3
3
(
cm , 22.5 mmol) was allowed to react with a 2 M SDDA solu-
3
a solution of ethylmagnesium bromide (prepared from ethyl
bromide (600 mg, 5.51 mmol) and magnesium turnings (134
tion in toluene (5.25 cm , 10.5 mmol) and with 2c (1.85 g, 8.77
3
mmol) in toluene (5 cm ). After work-up the remainder was
3
mg, 5.51 mmol) in dry diethyl ether (5 cm )) and heated under
purified by column chromatography (silica gel, n-pentane–
diethyl ether = 4 : 1) to afford propargyl alcohol 3d (2.4 g, 87%)
as a red oil (Found: 312.1503. C H O requires 312.1514);
reflux for 3 h. Carbaldehyde 2a (800 mg, 4.08 mmol) dissolved
3
in diethyl ether (5 cm ) was added to the Grignard solution at
2
3
20
Ϫ1
room temperature and stirred at this temperature for 16 h. It
ν˜
(film)/cm 3374, 3079, 2930, 2848, 2212, 2202, 1597, 1571,
was then quenched with aqueous saturated ammonium chloride
1487, 754 and 690; δ (250 MHz; CDCl ; Me Si) 1.71 (4 H, br s,
cyclo-CH ), 2.33 (2 H, br s, cyclo-CH ), 2.47 (2 H, br s, cyclo-
2 2
H
3
4
3
(
10 cm ). After extraction of the aqueous layer with diethyl
3
ether (3 × 10 cm ) the combined organic layers were dried
MgSO ), filtered and concentrated to furnish a brown oil,
CH ), 2.83 (1 H, s, OH), 5.98 (1 H, s, HOCHC᎐C), 7.29–7.32
2
(
(6 H, m), 7.41–7.48 (4 H, m); δ (50 MHz; CDCl ; Me Si) 22.6,
4
C
3
4
which was purified by column chromatography (silica gel,
n-pentane–dichloromethane–diethyl ether = 5 : 5 : 1). Propargyl
24.2, 27.4, 30.7, 65.1, 85.9, 88.5, 88.7, 94.0, 118.9, 123.1, 123.8,
128.6, 128.7, 128.8, 128.9, 131.9, 132.3, 143.7; m/z 312 (M ,
43%), 295 (37), 294 (100).
+
alcohol 3a (930 mg, 82%) was afforded as a yellow oil (Found:
Ϫ1
2
3
1
78.1666. C H O requires 278.1671); ν˜ max(film)/cm 3374,
20 22
080, 3049, 2956, 2933, 2871, 2274, 2219, 1596, 1489, 1442,
379, 1124, 1009, 954, 756, 732 and 691; δ (200 MHz; CDCl ;
Compound 3e. As described above for 3c, hex-1-yne (850
3
mm , 7.44 mmol) was allowed to react with 2 M SDDA (1.74
H
3
3
3
Me Si) 0.90 (3 H, t, J 7.1, CH CH ), 1.30–1.57 (4 H, m), 1.94
cm , 3.47 mmol) in toluene (10 cm ) and to this mixture was
added 2e (650 mg, 2.9 mmol). After stirring for 17 h at ambient
temperature and work-up the residue was purified by column
chromatography (petroleum (bp 40–60 ЊC)–diethyl ether = 4 : 1)
4
2
3
(
2 H, quintet, J 8.0, cyclo-CH CH CH ), 2.22 (2 H, td, J 6.9,
2 2 2
J 1.9, C᎐CCH CH ), 2.45 (1 H, s, OH), 2.62 (2 H, tt, J 8.0,
᎐
2
2
J 2.3, cyclo-CH -CH -CH ), 2.66 (2 H, tt, J 8.0, J 2.3, cyclo-
2
2
2
CH -CH -CH ), 5.52 (1 H, t, J 1.9, HOCHC᎐C), 7.26–7.32 (3
to furnish propargyl alcohol 3e (750 mg, 85%) as a yellow oil
2
2
2
Ϫ1
H, m), 7.42–7.46 (2 H, m); δ (63 MHz; CDCl ; Me Si) 13.4,
(Found: 306.1977. C H O requires 306.1983); ν˜ (film)/cm
C
3
4
22 26
1
1
8.3, 21.8, 22.1, 30.5, 31.3, 36.8, 60.0, 78.6, 84.4, 86.2, 94.8,
20.6, 123.1, 128.0, 128.1, 131.3, 149.0.
3390, 3054, 2924, 2851, 2275, 2220, 1596, 1480, 755 and 690;
δ (250 MHz; CDCl ; Me Si) 0.90 (3 H, t, J 7.0, CH CH ),
H
3
4
2
3
1
.36–1.50 (4 H, m, cyclo-CH ), 1.51–1.67 (4 H, m, CH CH -
2
2
2
Compound 3b. As described above for the synthesis of 3a
CH ), 1.74–1.87 (2 H, m, cyclo-CH ), 2.06 (1 H, s, OH), 2.23
(2 H, td, J 7.0, J 1.8, C᎐CCH ), 2.46–2.51 (4 H, m, cyclo-CH ),
2 2
3
2
phenylacetylene (562 mg, 5.50 mmol) in dry diethyl ether
3
(
5 cm ) was allowed to react with ethylmagnesium bromide,
5.71 (1 H, d, J 1.8, HOCHC᎐C), 7.28–7.30 (2 H, m), 7.32–7.35
(1 H, m), 7.41–7.44 (2 H, m); δ (63 MHz; CDCl ; Me Si) 13.6,
prepared from ethyl bromide (600 mg, 5.51 mmol) and
C
3
4
magnesium turnings (134 mg, 5.51 mmol) in dry diethyl ether
18.3, 21.9, 26.2, 27.2, 28.8, 30.7, 32.5, 34.9, 65.3, 79.0, 86.4,
89.5, 93.8, 123.3, 123.6, 128.0, 128.3, 131.3, 149.4; m/z 306 (M ,
67%), 289 (100), 229 (28).
3
+
(
5 cm ), and the resulting Grignard reagent was treated with
3
2
a (800 mg, 4.08 mmol), dissolved in dry diethyl ether (5 cm ).
After work-up, purification by column chromatography (silica
gel, n-pentane–dichloromethane–diethyl ether = 5 : 5 : 1) fur-
Compound 3f. As described above for the synthesis of 3c,
3
nished propargyl alcohol 3b as an orange oil (953 mg, 78%)
phenylacetylene (820 mm , 7.44 mmol) was allowed to react
+
3
3
(
Found: 297.1272. C H O (M Ϫ 1) requires 297.1279);
with 2 M SDDA (1.74 cm , 3.47 mmol) in toluene (10 cm ) and
with 2e (650 mg, 2.90 mmol). After stirring for 17 h at ambient
temperature it was worked up as described before. Purification
(silica gel, petroleum (bp 40–60 ЊC)–diethyl ether = 4 : 1)
22
17
Ϫ1
ν
˜
max(film)/cm 3347, 3056, 2955, 2849, 2223, 2196, 1597, 1490,
442, 1177, 1036, 990, 932, 756, 733 and 690; δ (200 MHz;
1
H
CDCl ; Me Si) 1.98 (2 H, quintet, J 7.6, CH CH CH ), 2.65
3
4
2
2
2
(
2 H, tt, J 7.6, J 2.2, CH CH CH ), 2.70 (1 H, br s, OH), 2.77
afforded propargyl alcohol 3f (783 mg, 83%) as a yellow oil
2
2
2
Ϫ1
(
2 H, tt, J 7.6, J 2.2, CH CH CH ), 5.79 (1 H, HOCHC᎐C),
(Found: 326.1663. C H O requires 326.1670); ν˜ (film)/cm
2
2
2
24 22
7
.28–7.32 (6 H, m), 7.44–7.50 (4 H, m); δ (63 MHz; CDCl ;
3375, 3054, 2922, 2850, 2226, 2195, 1596, 1569, 1480, 754 and
C
3
Me Si) 22.1, 31.3, 36.9, 60.3, 84.4, 85.3, 87.6, 95.2, 121.4, 122.4,
690; δ (250 MHz; CDCl ; Me Si) 1.63–1.68 (4 H, m, cyclo-
4
H
3
4
1
23.0, 128.1, 128.2 (2 C), 128.3, 131.4, 131.7, 148.2.
CH CH ), 1.79–1.83 (2 H, m, cyclo-CH ), 2.24 (1 H, s, OH),
2
2
2
2
.50–2.61 (4 H, m, cyclo-CH ), 5.97 (1 H, s, HOCHC᎐C), 7.30–
2
3
Compound 3c. Hex-1-yne (2.75 cm , 22.5 mmol) was added
7.34 (6 H, m), 7.43–7.48 (4 H, m); δ (63 MHz; CDCl ; Me Si)
26.1, 27.2, 29.0, 32.5, 35.0, 65.6, 85.5, 88.1, 89.4, 94.1, 122.7,
123.5, 124.1, 128.1, 128.2, 128.3, 128.5, 131.4, 131.8, 148.7; m/z
326 (M , 81%), 308 (100), 249 (12).
C 3 4
3
dropwise to a solution of 2 M SDDA (5.25 cm , 10.5 mmol) in
toluene (25 cm ). The mixture was stirred for 3 h at ambient
temperature until gas evolution stopped. At 0 ЊC a mixture of
c (1.85 g, 8.77 mmol) in toluene (5 cm ) was added slowly.
3
+
3
2
After stirring at room temperature for 3 h the reaction mixture
was quenched with saturated aqueous ammonium chloride (40
Compound 1a. Propargyl alcohol 3a (218 mg, 783 µmol) and
triethylamine (87.6 mg, 866 µmol) were dissolved in THF (10
3
3
cm ). After the aqueous layer had been extracted with ethyl
cm ). After cooling to Ϫ80 ЊC chlorodiphenylphosphane (192
3
acetate (4 × 40 cm ), the combined organic layers were dried
mg, 870 µmol) was added dropwise during 15 min under vigor-
ous stirring. After stirring at Ϫ80 ЊC for another 10 minutes the
suspension was allowed to warm up slowly to room temper-
(
MgSO ), filtered and concentrated. Purification by column
4
chromatography (silica gel, n-pentane–diethyl ether = 8 : 1)
3
3
afforded propargyl alcohol 3c (2.06 g, 80%) as a red oil (Found:
ature (2 h). Then water (10 cm ) and dichloromethane (10 cm )
were added, the organic layer was separated, and the aqueous
Ϫ1
2
92.1826. C H O requires 292.1827); ν˜ (film)/cm 3373, 3055,
21 24
3
2
930, 2860, 2302, 2276, 1597, 1483, 1442, 755 and 690; δ (250
layer was extracted with dichloromethane (2 × 10 cm ). The
H
MHz; CDCl ; Me Si) 0.88 (3 H, t, J 7.0, CH CH ), 1.31–1.47
combined organic layers were dried (MgSO ), filtered and con-
3
4
2
3
4
1
336
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339

View Article Online
centrated in vacuo. Purification of the residue (silica gel, diethyl
ether) afforded enyne–allene 1a (326 mg, 90%) as a yellow oil
that crystallised on standing (Found: 462.2110. C H OP
CH ), 6.85 (1 H, d, J 10.6, CHC=C=C), 7.21–7.40 (6 H, m),
2
7.44–7.55 (8 H, m), 7.65–7.72 (6 H, m); δ (50 MHz; CDCl ;
C
3
Me Si) 22.3, 22.6, 27.0, 31.0, 89.3, 95.3, 99.9 (d, J 11.7), 105.5
32
31
4
requires 462.2113); mp 98 ЊC (differential scanning calorimetry
(d, J 99.1), 119.1, 127.5, 127.6, 127.9, 128.0, 128.3 (d, J 11.7),
128.6, 128.7, 131.3 (d, J 12.4), 131.7 (d, J 5.1), 132.0, 132.1 (d,
J 108.4), 132.4, 135.5, 214.4 (d, J 4.8); δ (162 MHz; CDCl ;
Ϫ1
(
DSC)); ν
925, 1488, 1438, 1194, 1117, 1101, 831, 760, 724, 701 and 692;
δ (250 MHz; CDCl ; Me Si) 0.84 (3 H, t, J 7.2, CH CH ),
˜ (film)/cm 3078, 3059, 2958, 2928, 2870, 2852, 2186,
1
P
3
H PO ) 28.6 (s).
H
3
4
2
3
3
4
1
1
.25–1.39 (2 H, m, cyclo-CH ), 1.44–1.57 (2 H, m, cyclo-CH ),
2
2
.70–1.90 (2 H, m, cyclo-CH ), 1.95–2.39 (4 H, m, CH CH -
Compound 1e. As described for 1a, propargyl alcohol 3e
(200 mg, 654 µmol) was reacted with chlorodiphenylphosphane
(173 mg, 788 µmol) and triethylamine (79 mg, 784 µmol). After
stirring for 30 min at 0 ЊC and 1 h at ambient temperature
standard work-up was followed. The purification (silica gel,
petroleum (bp 40–60 ЊC)–ethyl acetate = 1 : 1) afforded 1e (290
mg, 90%) as a yellow oil (Found: C, 83.01; H, 7.05. C H OP
2
2
2
CH ), 2.47–2.57 (2 H, m, C=C=CCH CH ), 6.42 (1 H, td,
J 11.0, J 3.2, CHC=C=C), 7.24–7.34 (3 H, m), 7.36–7.54 (8 H,
m), 7.65–7.80 (4 H, m); δ (100 MHz; CDCl ; Me Si) 13.7, 22.3,
3
2
2
C
3
4
22.4, 28.0 (d, J 5.7), 30.6 (d, J 5.7), 33.3, 37.0, 85.4 (d, J 2.9),
93.3 (d, J 14.3), 96.5 (d, J 1.9), 101.3 (d, J 99.2), 121.5 (d, J 4.8),
123.3, 128.1, 128.1 (d, J 12.4), 128.2, 128.3 (d, J 12.4), 131.3,
131.5 (d, J 9.5), 131.5 (d, J 9.5), 131.7 (d, J 2.9), 131.8 (d,
34
35
Ϫ1
requires C, 83.22; H, 7.20%); ν˜ (film)/cm 3056, 2927, 2853,
J 103.0), 131.9 (d, J 2.9), 131.9 (d, J 105.0), 141.7 (d, J 9.5),
11.6 (d, J 5.7); δ (162 MHz; CDCl ; H PO ) 28.6 (s).
2184, 1919, 1591, 1488, 1194, 1117, 755, 722 and 690; δ (200
H
2
MHz; CDCl ; Me Si) 0.84 (3 H, t, J 7.3, CH CH ), 1.06–1.42
P
3
3
4
3
4
2
3
(
4 H, m, CH CH CH ), 1.43–1.70 (6 H, m, cyclo-CH ), 2.10–
2
2
3
2
Compound 1b. Propargyl alcohol 3b was reacted as described
2.18 (2 H, m, cyclo-CH ), 2.26–2.43 (4 H, cyclo-CH ,
C=C=CCH ), 6.67 (1 H, td, J 3.1, J 3.1, CHC=C=C), 7.26–7.32
(3 H, m), 7.37–7.48 (8 H, m), 7.62–7.82 (4 H, m); δ (63 MHz;
2
2
for 1a. Accordingly, 3b (273 mg, 915 µmol), triethylamine (102
2
3
mg, 1.01 mmol), both dissolved in THF (15 cm ), were treated
C
with chlorodiphenylphosphane (222 mg, 1.01 mmol). After
purification (silica gel, diethyl ether) enyne–allene 1b was
isolated as a yellow oil (385 mg, 87%) which crystallised on
standing (Found: 481.1716. C H OP (M Ϫ 1) requires
CDCl ; Me Si) 13.9, 22.4, 26.0, 26.4, 28.1, 30.4, 30.6, 33.4, 35.1,
3
4
90.8, 95.6, 100.0 (d, J 14.3), 102.5 (d, J 99.6), 123.2, 127.9, 128.1
(d, J 12.2), 128.4, 131.1, 131.5 (d, J 9.2), 131.7, 131.8 (d, J 3.1),
131.9 (d, J 103.7), 142.4, 210.7 (d, J 5.7); δ (162 MHz; CDCl ;
34
26
P
3
Ϫ1
4
2
1
1
81.1721); mp 56 ЊC (DSC); ν
197, 1913, 1719, 1708, 1596, 1490, 1438, 1176, 1119, 1098,
˜
(film)/cm 3057, 2957, 2840,
H PO ) 30.7 (s).
3 4
071, 757, 726, 693 and 546; δ (250 MHz; CDCl ; Me Si) 1.69–
H
3
4
Compound 1f. As described above for 1a, propargyl alcohol
3f (200 mg, 612 µmol) was treated with chlorodiphenylphos-
phane (162 mg, 739 µmol) and triethyamine (75.0 mg, 741
µmol). After stirring for 30 min at 0 ЊC and for 1 h at ambient
temperature the work-up followed that described above. Purifi-
cation (silica gel, petroleum (bp 40–60 ЊC)–ethyl acetate = 1 : 1)
.95 (2 H, m, CH ), 2.08–2.20 (2 H, m, CH ), 2.48–2.57 (2 H,
2
2
m, CH ), 6.56 (1 H, d, J 10.7, CHC=C=C), 7.14–7.30 (6 H, m),
2
7
.33–7.52 (8 H, m), 7.59–7.62 (2 H, m), 7.68–7.81 (4 H, m);
δ (100 MHz; CDCl ; Me Si) 22.5, 33.3, 37.0, 85.2 (d, J 2.8),
C
3
4
9
1
4.2 (d, J 12.8), 97.0, 103.9 (d, J 99.2), 122.9 (d, J 4.8), 123.1,
27.8, 128.2 (d, J 12.4), 128.2, 128.3, 128.3 (d, J 11.4), 128.3 (d,
afforded enyne–allene 1f (218 mg, 70%) as a pale-red oil
J 4.8), 128.6, 131.3, 131.6 (d, J 9.5), 131.7 (d, J 9.5), 131.8 (d,
J 2.9), 132.0 (d, J 2.9), 132.1 (d, J 106.8), 132.1 (d, J 105.9),
Ϫ1
(
Found: 510.2105. C H OP requires 510.2112); ν˜ (film)/cm
36 31
3
056, 2924, 2852, 2202, 1911, 1594, 1490, 1182, 1117, 759 and
1
32.1 (d, J 5.7), 140.5 (d, J 8.6), 215.1 (d, J 4.8); δ (162 MHz;
P
694; δ (250 MHz; CDCl ; Me Si) 1.18–1.39 (2 H, m, CH ),
H
3
4
2
CDCl ; H PO ) 28.9 (s).
3
3
4
1.44–1.79 (4 H, CH ), 2.10–2.27 (2 H, CH ), 2.36–2.49 (2 H,
2 2
CH ), 6.85 (1 H, d, J 10.4, CHC=C=C), 7.19–7.37 (6 H, m),
2
Compound 1c. As described above for 1a, propargyl alcohol
c (400 mg, 1.36 mmol) was allowed to react with chlorodi-
phenylphosphane (356 mg, 1.64 mmol) and triethylamine (271
mg, 1.64 mmol). Purification of the crude product (silica gel,
petroleum (bp 40–60 ЊC)–acetone = 4 : 1) afforded the enyne–
7
.39–7.53 (8 H, m), 7.55–7.65 (2 H, m), 7.72–7.81 (4 H, m);
3
δ (63 MHz; CDCl ; Me Si) 26.0, 28.9, 29.6, 33.3, 34.9, 86.4,
C
3
4
9
1
2.9, 105.4 (d, J 98.8), 109.9 (d, J 105.2), 124.3, 127.3, 127.8,
28.0, 128.2, 128.3, 128.5, 128.6 (d, J 12.2), 131.1, 131.3 (d,
J 95.5), 131.6 (d, J 9.2), 131.8, 131.9, 139.1, 210.7 (d, J 5.7);
δ (162 MHz; CDCl ; H PO ) 28.9 (s).
allene 1c (565 mg, 87%) as a yellow oil (Found: 476.2258.
P
3
3
4
Ϫ1
C H OP requires 476.2258); ν˜ (film)/cm 3054, 2929, 2197,
3
3
33
1
920, 1590, 1484, 1438, 1195, 1117, 754, 721 and 692; δ (200
H
Thermolysis of enyne–allenes 1a–f
MHz; CDCl ; Me Si) 0.85 (3 H, t, J 7.0, CH CH ), 1.24–1.43 (4
3
4
2
3
H, m, CH CH CH ), 1.47–1.55 (4 H, m, cyclo-CH ), 1.62–1.75
All enyne–allenes were thermolysed in toluene or mesitylene
in the presence of 20 equivalents of the cyclohexa-1,4-diene.
For solvent, duration, temperature and yields see Table 4. After
several hours the solvent was removed under reduced pressure
and the mixture was purified by column chromatography if
2
2
3
2
(
1 H, br s, cyclo-CH ), 1.90–2.05 (1 H, br s, cyclo-CH ), 2.18–
2
2
2
.30 (2 H, m, cyclo-CH ), 2.35 (2 H, tdd, J 17.6, J 7.7, J 3.2,
2
C=C=CCH ), 6.66 (1 H, dt, J 11.2, J 3.2, CHC=C=C), 7.29–
2
7
.34 (2 H, m), 7.36–7.52 (9 H, m), 7.63–7.83 (4 H, m); δ (63
C
38
MHz; CDCl ; Me Si) 14.2, 22.4, 22.7, 22.8, 26.9, 28.5, 31.0,
necessary.
3
4
3
1
1.1, 89.5, 95.0, 99.0 (d, J 14.2), 102.6 (d, J 99.1), 118.3, 123.9,
28.5 (d, J 11.3), 128.7, 128.9, 132.1 (d, J 4.5), 132.3 (d,
Compound 4a. Column chromatography on silica gel with
petroleum (bp 40–60 ЊC)–ethyl acetate (1 : 1) as eluent provided
J 105.9), 132.4, 134.8 (d, J 12.2), 136.4, 210.3 (d, J 5.7); δ (162
P
MHz; CDCl ; H PO ) 29.1 (s).
the cyclisation product 4a as a yellow oil (Found: 464.2270.
3
3
4
Ϫ1
C H OP requires 464.2269); ν˜ (film)/cm 3056, 3023, 2955,
32
33
Compound 1d. As described above for 1a, the enediyne 3d
360 mg, 1.15 mmol) was brought to reaction with chlorodi-
2932, 2861, 1480, 1437, 1185, 1116, 1101, 1072, 1028, 885, 722
(
and 698; δ (600 MHz; CDCl ; Me Si) 0.72 (3 H, t, J 7.2,
H
3
4
phenylphosphane (338 mg, 1.54 mmol) and triethylamine (158
mg, 1.53 mmol). Purification of the crude product (silica gel,
petroleum (bp 40–60 ЊC)–acetone–dichloromethane = 5 : 1 : 2)
CH CH ), 1.05–1.13 (3 H, m, CH CH CH ), 1.22–1.28 (1 H,
2 3 2 2 3
m, CH CH CH ), 1.72–1.79 (1 H, m, CHCH CH ), 2.12–2.17
2
2
3
2
2
(3 H, m, cyclo-CH , CHCH CH ), 2.85–2.94 (2 H, cyclo-CH ),
2
2
2
2
afforded enyne–allene 1d (410 mg, 71%) as a yellow oil (Found:
2.95–3.00 (m, 1H, cyclo-CH ), 3.05–3.10 (1 H, m, cyclo-CH ),
2
2
Ϫ1
4
2
96.1944. C H OP requires 496.1945); ν
˜
(film)/cm 3056,
3.62 (1 H, ddd, J 11.4, J 8.1, J 3.2, CHCH CH ), 6.00 (2 H, br
2 2
35
29
933, 2860, 2198, 1911, 1592, 1490, 1437, 1195, 1117, 737, 724
s), 6.87 (1 H, s), 7.01 (2 H, dd, J 11.1, J 7.1), 7.14–7.17 (2 H, m),
7.20–7.29 (2 H, br s), 7.28 (1 H, t, J 7.3), 7.35 (1 H, t, J 7.4),
7.44–7.47 (2 H, m), 7.52 (1 H, t, J 7.4), 7.57 (2 H, dd, J 11.0,
and 693; δ (200 MHz; CDCl ; Me Si) 1.55 (4 H, br s, CH ),
H
3
4
2
1
.70 (1 H, br s, CH ), 2.02 (1 H, br s, CH ), 2.24 (2 H, br s,
2
2
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339
1337

View Article Online
Table 4 Reaction conditions and products of thermolyses of enyne–allenes 1a–f
Enyne–allene
Conditions
Products
1a
1b
1c
1d
1e
1f
20 eq. 1,4-CHD, mesitylene, reflux, 1 h
20 eq. 1,4-CHD, toluene, reflux, 18 h
20 eq. 1,4-CHD, toluene, reflux, 5 min
20 eq. 1,4-CHD, toluene, reflux, 3 h
20 eq. 1,4-CHD, toluene, reflux, 5 min
20 eq. 1,4-CHD, toluene, reflux, 3 h
4a (15%), 5a (25%), 6a (34%)
4b (31%), 7b (33%), 13b (1%)
3
9
[12c]
13d (80%)
3
9
[12e]
13f (85%)
J 7.8), 7.77 (1 H, s); δ (151 MHz; CDCl ; Me Si) 13.7, 22.5,
47.4, 116.1, 119,7, 120.5, 124.6, 126.5, 127.2, 140.2, 142.1,
143.1, 143.5, 146.5, 148.2.
C
3
4
25.5, 30.0 (d, J 12.6), 30.3 (d, J 1.1), 32.6, 32.8, 41.6 (d, J 67.7),
124.5 (d, J 4.6), 125.5 (d, J 1.7), 126.6, 127.7, 127.7 (d, J 11.5),
128.5 (d, J 11.5), 129.6, 131.1 (d, J 2.9), 131.2 (d, J 102.7), 131.4
Compound 7b. Column chromatography (silica gel,
dichloromethane–diethyl ether = 20 : 1) gave product 7b as a
colourless oil (Found: 574.2416. C H OP requires 574.2426);
(
d, J 5.7), 131.5 (d, J 9.2), 131.5 (d, J 8.0), 131.6, 132.9 (d,
J 97.5), 141.3 (d, J 7.5), 141.7 (d, J 1.2), 142.7 (d, J 2.9), 143.9
d, J 2.3); δ (162 MHz; CDCl ; H PO ) 34.8 (s).
4
1
35
Ϫ1
(
ν˜
(film)/cm 3058, 3026, 2949, 2846, 1712, 1598, 1482, 1437,
P
3
3
4
1
314, 1270, 1180, 1114, 1028, 997, 910, 730 and 698; δ (600
H
Compound 4b. Column chromatography (silica gel,
dichloromethane–diethyl ether = 20 : 1) afforded product 4b as
MHz; CDCl ; Me Si) 2.02–2.08 (2 H, m, cyclo-CH ), 2.80–2.84
(2 H, m, cyclo-CH ), 2.92–3.00 (2 H, cyclo-CH ), 3.86 (2 H, s,
2 2
3
4
2
colourless oil (Found: 484.1946. C H OP requires 484.1956);
ArCH Ph), 4.76 (1 H, d, J 9.7, (Ph )P(O)CH), 6.90 (2 H, br s),
34
29
2
2
Ϫ1
ν
˜
(film)/cm 3057, 3026, 2951, 2844, 1599, 1493, 1479, 1437,
265, 1201, 1178, 1117, 1072, 1030, 998, 920, 888, 733 and 698;
δ (600 MHz; CDCl ; Me Si) 2.02–2.09 (2 H, m, CH ), 2.78–
6.91 (1 H, s), 6.95 (2 H, d, J 8.0), 7.08 (2 H, d, J 7.0), 7.16–7.21
(5 H, m), 7.24 (2 H, t, J 6.7), 7.28–7.37 (8 H, m), 7.39 (1 H, m),
7.41–7.44 (2 H, m), 8.35 (1 H, s); δ (151 MHz; CDCl ; Me Si)
1
H
3
4
2
C
3
4
2
.87 (2 H, m, cyclo-CH ), 2.93–3.03 (2 H, m, cyclo-CH ), 4.79
25.4, 32.5, 32.9, 41.4, 48.3 (d, J 65.4), 125.8, 125.9, 126.1 (d,
J 5.2), 127.0, 127.8, 127.9 (d, J 11.5), 128.0 (d, J 11.5), 128.3,
128.8 (d, J 1.7), 128.8, 129.7, 130.1 (d, J 5.7), 131.1 (d, J 2.9),
131.2 (d, J 2.9), 131.3 (d, J 8.6), 131.4 (d, J 9.2), 132.3 (d,
J 98.1), 132.3 (d, J 3.4), 132.4 (d, J 96.9), 134.6 (d, J 5.2), 139.2
(d, J 2.3), 140.4 (d, J 8.6), 141.1, 141.8, 142.9 (d, J 1.7), 144.0 (d,
J 1.7); δ (162 MHz; CDCl ; H PO ) 32.6 (s).
2
2
(
1 H, d, J 9.5, CH), 6.88 (2 H, br s), 6.92 (1 H, m), 7.09 (1 H, t,
J 7.2), 7.11–7.14 (2 H, m), 7.19–7.22 (2 H, m), 7.24–7.26 (2 H,
m), 7.28–7.32 (3 H, m), 7.33–7.37 (5 H, m), 7.40 (1 H, t, J 7.4),
7
.44 (2 H, dd, J 11.0, J 7.6), 8.37 (1 H, s); δ (151 MHz; CDCl ;
C
3
Me Si) 25.3, 32.4, 32.8, 48.7 (d, J 65.4), 125.8, 126.1 (d, J 5.7),
4
1
1
26.5 (d, J 2.3), 127.0, 127.9, 127.9 (d, J 11.5), 128.1 (d, J 11.5),
28.1 (d, J 2.3), 129.6, 130.0 (d, J 5.7), 131.1 (d, J 2.3), 131.2 (d,
P
3
3
4
1
J 2.3), 131.2 (d, J 8.6), 131.3 (d, J 9.2), 132.2 (d, J 99.1), 132.2
d, J 4.0), 132.6 (d, J 97.0), 136.9 (d, J 5.2), 140.4 (d, J 8.6),
Compounds 12c,e. The thermolysis was followed by H NMR.
(
After 5 min (d -DMSO, 80 ЊC) signals could be observed that
6
1
41.8, 142.9 (d, J 1.7), 144.0 (d, J 1.1); δ (162 MHz; CDCl ;
are indicative of 12c and 12e as judged by characteristic signals
P
3
6,11
H PO ) 32.4 (s).
of similar cyclisation products. After prolonged heating 12c
and 12e finally decomposed. 12c: δ (200 MHz; CDCl ; Me Si)
3
4
H
3
4
Compound 5a. Column chromatography (silica gel, petrol-
eum (bp 40–60 ЊC)–ethyl acetate = 1 : 1) furnished product 5a
as a pale yellow oil (Found: 462.2121. C H OP requires
5.53 (1 H, d, J 3.5), 6.48 (1 H, s). 12e: δ (200 MHz; CDCl ;
H
3
Me Si) 5.68 (1 H, d, J 3.5), 6.62 (1 H, s).
4
32
31
Ϫ1
4
62.2113); ν
˜
(film)/cm 3059, 3011, 2954, 2864, 1439, 1314,
Compound 13b. Column chromatography (silica gel,
dichloromethane–diethyl ether = 5 : 1) furnished Diels–Alder
1
179, 1110, 1027, 999, 911, 730, 698 and 643; δ (600 MHz;
H
CDCl ; Me Si) 0.41–0.53 (2 H, m, cyclo-CH ), 0.64 (3 H, t,
product 13b as a yellow fluorescent oil (Found: 482.1800.
3
4
3
Ϫ1
J 7.4, CH CH ), 1.12 (2 H, qt, J 7.4, J 7.5, CH CH ), 2.09 (2 H,
C H OP requires 482.1800); ν˜ (film)/cm 3057, 2961, 2928,
2
3
2
3
34 27
tt, J 7.5, J 7.4, CH CH CH ), 2.60–2.66 (1 H, cyclo-CH ),
2862, 1937, 1747, 1707, 1597, 1490, 1438, 1262, 1183, 1113,
2
2
3
2
2
2
7
7
.69–2.76 (1 H, cyclo-CH ), 2.81–2.90 (2 H, m, cyclo-CH ),
1026, 801, 756, 726 and 697; δ (250 MHz; CDCl ; Me Si)
2
2
H
3
4
.92 (2 H, t, J 7.4, CCH CH ), 7.00 (1 H, s), 7.13 (1 H, t, J 7.5),
1.84 (2 H, br s, cyclo-CH ), 2.11 (2 H, tt, J 7.4, J 6.9, cyclo-
2
2
2
.19–7.27 (5 H, m), 7.28 (1 H, d, J 7.5), 7.30–7.35 (3 H, m),
CH CH CH ), 2.41 (2 H, t, J 6.9, cyclo-CH ), 3.23 (2 H, s,
2
2
2
2
.36–7.43 (3 H, m), 7.43 (1 H, s), 7.51 (1 H, d, J 7.5); δ (151
CH ), 7.15 (1 H, t, J 7.6), 7.23–7.30 (2 H, m), 7.34–7.38 (2 H,
C
2
MHz; CDCl ; Me Si) 13.7, 22.8, 24.8 (d, J 10.2), 25.5, 31.3 (d,
J 1.5), 32.6, 32.7, 58.2 (d, J 61.5), 115.4 (d, J 1.5), 119.1 (d,
J 1.5), 121.7 (d, J 2.9), 125.6 (d, J 2.9), 126.1 (d, J 2.4), 127.5
m), 7.41–7.58 (9 H, m), 7.72–7.81 (4 H, m), 8.27 (1 H, d, J 8.5);
δ (162 MHz; CDCl ; H PO ) 30.6 (s).
3
4
P
3
3
4
(
2 C, d, J 10.7), 127.6 (d, J 1.9), 130.2 (d, J 95.0), 130.3 (d,
Compound 13d. Column chromatography (silica gel, petrol-
J 95.0), 131.3 (2 C, d, J 2.9), 132.1 (d, J 7.8), 132.2 (d, J 8.2),
eum (bp 40–60 ЊC)–acetone = 2 : 1) gave Diels–Alder product
13d as a yellow fluorescent oil (Found: 496.1956. C H OP
1
1
3
40.6 (d, J 4.9), 141.3 (d, J 1.9), 142.4 (d, J 4.9), 143.3 (d, J 2.4),
35
29
Ϫ1
43.4 (d, J 2.4), 144.1 (d, J 2.4); δ (162 MHz; CDCl ; H PO )
requires 496.1947); ν˜ (film)/cm 3054, 2918, 1591, 1482, 1165,
P
3
3
4
3.0 (s).
1119, 821, 733 and 691; δ (250 MHz; CDCl ; Me Si) 1.61–1.80
H
3
4
(
4 H, br s, cyclo-CH ), 2.57–2.65 (2 H, br s, cyclo-CH ), 2.81–
2 2
Compound 6a. Column chromatography (silica gel, petrol-
eum (bp 40–60 ЊC)–ethyl acetate = 1 : 1) gave product 6a as a
2.90 (2 H, m, cyclo-CH ), 3.32 (2 H, s, CH ), 6.97–7.22 (4 H,
2
2
m), 7.28–7.58 (8 H, m), 7.63–7.89 (4 H, m), 7.91–7.98 (2 H, m),
8.08 (1 H, d, J 9.1); δ (63 MHz; CDCl ; Me Si) 23.2, 24.3, 26.5,
colourless oil that is not stable standing in air for a long time
C
3
4
Ϫ1
(
2
7
Found: 262.1723. C H requires 262.1722); ν
˜
(film)/cm 3010,
30.1, 45.2, 123.2, 124.8, 125.2, 126.9, 127.5, 128.2, 128.9 (d,
J 12.1), 129.4, 129.5, 130.6, 130.9, 131.8 (d, J 2.9), 132.1, 132.7,
(d, J 11.4), 134.5 (d, J 69.8), 136.1 (d, J 102.2), 140.1, 143.2,
144.9, 151.1; δ (162 MHz; CDCl ; H PO ) 33.4 (s); m/z 496
20
22
955, 2928, 2857, 1606, 1452, 1317, 1260, 1096, 1022, 875, 803,
40 and 700; δ (250 MHz; C D ; Me Si) 0.80 (3 H, t, J 6.7,
H
6
6
4
CH CH ), 1.05–1.27 (4 H, m, CH CH CH ), 2.01 (2 H, tt,
2
3
2
2
3
P
3
3
4
+
J 7.3, J 7.3, cyclo-CH CH CH ), 1.95–2.27 (2 H, m, CHCH -
(M , 100%), 295 (100).
2
2
2
2
CH ), 2.90 (4 H, t, J 7.3, cyclo-CH ), 3.94 (1 H, t, J 5.7,
2
2
CHCH CH ), 7.31 (1 H, t, J 7.3), 7.37 (1 H, s), 7.40 (1 H, t,
Compound 13f. Column chromatography (silica gel, petrol-
eum (bp 40–60 ЊC)–acetone = 3 : 1) gave product 13f as a red
2
2
J 7.3), 7.49 (1 H, d, J 7.3), 7.65 (1 H, s), 7.81 (1 H, d, J 7.3);
δ (63 MHz; C D ; Me Si) 14.0, 23.4, 26.2, 27.9, 32.9, 33.1, 33.3,
fluorescent oil (Found: 510.2112. C H OP requires 510.2112);
C
6
6
4
36 31
1
338
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339

View Article Online
Ϫ1
ν
˜
(film)/cm 3056, 2922, 1588, 1484, 1185, 1117, 758 and 695;
19 S. Zeman, Thermochim. Acta, 1997, 302, 11.
2
0 K. Hafner, K. H. Häfner, C. König, M. Kreuder, G. Ploss,
δ (250 MHz; CDCl ; Me Si) 1.17–1.44 (2 H, m, cyclo-CH ),
.49–1.85 (4 H, m, cyclo-CH ), 2.13–2.22 (2 H, m, cyclo-CH ),
2 2
.28–2.42 (2 H, m, cyclo-CH ), 3.45 (2 H, s, CH ), 7.09–7.20
1 H, m), 7.30–7.56 (11 H, m), 7.69–7.84 (4 H, m), 7.89–7.97
2 H, m), 8.13 (1 H, m); δ (63 MHz; CDCl ; Me Si) 26.7, 27.2,
H
3
4
2
G. Schulz, E. Sturm and K. H. Vöpel, Angew. Chem., 1963, 75, 35;
1
2
(
M. Neuenschwander, Pure Appl. Chem., 1987, 58, 55.
1 A. Pauli, H. Kolshorn and H. Meier, Chem. Ber., 1987, 120, 1611.
2 J. E. Bennett and J. A. Howard, Chem. Phys. Lett., 1971, 9, 460.
2
2
2
2
(
23 For all calculated transition states the normal mode of the
imaginary frequency points into the direction of the ring closures
C
3
4
3
1
1
1
0.0, 30.4, 31.3, 44.7, 124.7, 125.2, 125.7, 127.1, 127.8, 128.3,
29.0 (d, J 12.2), 129.3, 129.6, 130.2, 130.9, 132.1 (d, J 3.2),
32.2, 132.3, (d, J 10.7), 135.0 (d, J 70.2), 135.3 (d, J 102.2),
39.5, 143.6, 145.0, 150.8; δ (162 MHz; CDCl ; H PO ) 30.6 (s);
2
7
2
6
(
either C –C or C –C cyclisation).
2
4 (a) R. G. Parr and W. Yang, Density Functional Theory, Oxford
University Press, Oxford, 1989; (b) R. M. Dreizler and E. K. U.
Gross, Density Functional Theory, Springer, Berlin, 1990; (c) K.
Burke, Density Functional Theory and the Meaning of Life,
Department of Chemistry, Rutgers University, 610 Taylor Rd,
Piscataway, NJ 08854, 2000.
P
3
3
4
+
m/z 510 (M , 100%), 433 (12), 201 (26).
Acknowledgements
2
5 (a) A. D. Becke, J. Chem. Phys., 1993, 98, 5648; (b) C. Lee, W. Yang
We are very much indebted to the Deutsche Forschungsgemein-
schaft, the Volkswagenstiftung and the Fonds der Chemischen
Industrie for continuous support. Michael Maywald thanks the
Graduiertenkolleg “Struktur und Reaktivität” in Siegen for a
stipend and D. Auer for technical assistance.
and R. G. Parr, Phys. Rev. B, 1988, 37, 785.
2
6 (a) W. J. Hehre, R. Ditchfield and J. A. Pople, J. Chem. Phys., 1972,
5
6, 2257; (b) R. Krishnan, J. S. Binkley, R. Seeger and J. A. Pople,
J. Chem. Phys., 1980, 72, 650; (c) M. J. Frisch, J. A. Pople and J. S.
Binkley, J. Chem. Phys., 1984, 80, 3265.
2
2
7 J. B. Foresman and A. Frisch, Exploring Chemistry with Electronic
Structure Methods, Gaussian Inc., Pittsburgh, PA 15213, USA,
1
993.
Notes and references
8 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, R. E.
Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels,
K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M.
Cossi, R. Cammi, B. Mennucci, C. Pomelli, A. Adamo, S. Clifford,
J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma,
D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman,
J. Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu, A. Liashenko,
P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson,
W. Chen, M. W. Wong, J. L. Andres, M. Head-Gordon, E. S.
Replogle and J. A. Pople, Gaussian 98 (Revision A.7), 1998,
Gaussian, Inc., Pittsburgh, PA.
1
2
3
4
(a) R. R. Jones and R. G. Bergman, J. Am. Chem. Soc., 1972, 94,
60; (b) T. P. Lockhart, P. B. Comita and R. G. Bergman, J. Am.
Chem. Soc., 1981, 103, 4082.
(a) A. G. Myers, E. Y. Kuo and N. S. Finney, J. Am. Chem. Soc.,
989, 111, 8057; (b) R. Nagata, H. Yamanaka, E. Okazaki and
I. Saito, Tetrahedron Lett., 1989, 30, 4995.
Recent reviews: (a) M. E. Maier, Synlett, 1995, 13; K. K. Wang,
Chem. Rev., 1996, 96, 207; (b) J. W. Grissom, G. U. Gunawardena,
D. Klingberg and D. Huang, Tetrahedron, 1996, 52, 6453.
K. C. Nicolaou and W.-M. Dai, Angew. Chem., 1991, 103, 1453;
K. C. Nicolaou and W.-M. Dai, Angew. Chem., Int. Ed. Engl., 1991,
6
1
3
0, 1387; Enediyne Antibiotics as Antitumor Agents, eds D. B.
Borders and T. W. Doyle, Dekker, New York, 1995.
5
6
I. Morao and F. P. Cossío, J. Org. Chem., 1999, 64, 1868.
29 (a) R. Seeger and J. A. Pople, J. Chem. Phys., 1977, 66, 3045; (b)
R. Bauernschmitt and R. Ahlrichs, J. Chem. Phys., 1996, 104, 9047.
30 K. Nakatani, S. Isoe, S. Maekawa and I. Saito, Tetrahedron Lett.,
1994, 35, 605.
31 (a) K. K. Wang, B. Liu and Y.-D. Lu, Tetrahedron Lett., 1995, 36,
3785; (b) P. A. Wender and M. J. Tebbe, Tetrahedron, 1994, 50, 1419;
(c) K. Fujiwara, H. Sakai and M. Hirama, J. Org. Chem., 1991, 56,
1688.
32 A. G. Myers and P. J. Proteau, J. Am. Chem. Soc., 1989, 111, 1146.
33 C. J. Cramer and R. R. Squires, Org. Lett., 1999, 1, 215.
34 F. Ferri, R. Brückner and R. Herges, New J. Chem., 1998, 531.
35 A. G. Myers, J. Liang, M. Hammond, P. M. Harrington, Y. S. Wu
and E. Y. Kuo, J. Am. Chem. Soc., 1998, 120, 5319; T. Takahashi,
H. Tanaka, H. Yamada, T. Matsumoto and Y. Sugiura, Angew.
Chem., 1997, 109, 1570; T. Takahashi, H. Tanaka, H. Yamada,
T. Matsumoto and Y. Sugiura, Angew. Chem., Int. Ed. Engl., 1997,
36, 1524; I. Sato, K. Toyama, T. Kikuchi and M. Hirama, Synlett,
1998, 1308.
(a) M. Schmittel, M. Strittmatter and S. Kiau, Angew. Chem., 1996,
1
08, 1952; M. Schmittel, M. Strittmatter and S. Kiau, Angew.
Chem., Int. Ed. Engl., 1996, 35, 1843; (b) M. Schmittel, M. Keller,
S. Kiau and M. Strittmatter, Chem. Eur. J., 1997, 3, 807; (c) B. Engels
and M. Hanrath, J. Am. Chem. Soc., 1998, 120, 6356; (d ) B. Engels,
C. Lennartz, M. Hanrath, M. Schmittel and M. Strittmatter, Angew.
Chem., 1998, 110, 2067; B. Engels, C. Lennartz, M. Hanrath,
M. Schmittel and M. Strittmatter, Angew. Chem., Int. Ed., 1998, 37,
1
060.
7
(a) M. Schmittel, J.-P. Steffen, M. Á. Wencesla Ángel, B. Engels,
C. Lennartz and M. Hanrath, Angew. Chem., 1998, 110, 1633;
M. Schmittel, J.-P. Steffen, M. Á. Wencesla Ángel, B. Engels,
C. Lennartz and M. Hanrath, Angew. Chem., Int. Ed., 1998, 37,
1
562; (b) M. Schmittel, J.-P. Steffen, B. Engels, C. Lennartz and
M. Hanrath, Angew. Chem., 1998, 110, 2531; M. Schmittel, J.-P.
Steffen, B. Engels, C. Lennartz and M. Hanrath, Angew. Chem., Int.
Ed., 1998, 37, 2371.
8
9
(a) C. Shi and K. K. Wang, J. Org. Chem., 1998, 63, 3517; (b) C. Shi,
Q. Zhang and K. K. Wang, J. Org. Chem., 1999, 64, 925.
See also Moore cyclisation: (a) L. D. Foland, J. O. Karlsson, S. T.
Perri, R. Schwabe, S. L. Xu, S. Patil and H. W. Moore, J. Am. Chem.
Soc., 1989, 111, 975; (b) H. W. Moore and B. R. Yerxa, Chemtracts,
36 G. Rodríguez, D. Rodríguez, M. López, L. Castedo, D. Domínguez
and C. Saá, Synlett, 1998, 1282; J. Suffert, E. Abraham, S. Raeppel
and R. Brückner, Liebigs Ann., 1996, 447; M. Eckhardt and
R. Brückner, Liebigs Ann., 1996, 473; K. Toshima, K. Ohta,
K. Yanagawa, T. Kano, M. Nakata, M. Kinoshita and
S. Matsumura, J. Am. Chem. Soc., 1995, 117, 10825; S. Kawata,
T. Oishi and M. Hirama, Tetrahedron Lett., 1994, 35, 4595;
M. Hirama, T. Gomibuchi, K. Fujiwara, Y. Sugiura and M. Uesugi,
J. Am. Chem. Soc., 1991, 113, 9851.
1
992, 273.
0 (a) P. R. Schreiner and M. Prall, J. Am. Chem. Soc., 1999, 121, 8615;
b) P. G. Wenthold and M. A. Lipton, J. Am. Chem. Soc., 2000, 122,
1
(
9
2
265; (c) B. Engels, M. Hanrath and C. Lennartz, Comput. Chem.,
001, 25, 15.
37 R. Brückner and J. Suffert, Synlett, 1999, 6, 657; S. W. Scheuplein,
R. Machinek, J. Suffert and R. Brückner, Tetrahedron Lett., 1993,
34, 6549.
1
1
1 (a) M. Schmittel, S. Kiau, T. Siebert and M. Strittmatter,
Tetrahedron Lett., 1996, 37, 7691; (b) M. Schmittel, M. Maywald
and M. Strittmatter, Synlett, 1997, 165.
38 For these computations we employed the BLYP functional in
3
8a
2 Ó. de Frutos and A. M. Echavarren, Tetrahedron Lett., 1997, 38,
combination with
a
SVP basis set.
The calculations were
38b
7
941.
performed with the TurboMole programm package
using the
3
8c
1
1
3 M. Alajarín, P. Molina and A. Vidal, J. Nat. Prod., 1997, 60, 747.
4 B. Liu, K. K. Wang and J. L. Petersen, J. Org. Chem., 1996, 61,
RI-approach. (a) K. Eichkorn, O. Treutler, H. Öhm, M. Häser and
R. Ahlrichs, Chem. Phys. Lett., 1995, 242, 652; (b) R. Ahlrichs,
M. Bär, H.-P. Baron, R. Bauernschmitt, S. Böcker, M. Ehrig,
K. Eichkorn, S. Elliott, F. Haase, M. Häser, H. Horn, C. Huber,
U. Huniar, M. Kattannek, C. Kölmel, M. Kollwitz, C. Ochsenfeld,
H. Öhm, A. Schäfer, U. Schneider, O. Treutler, M. von Arnim,
F. Weigend, P. Weis, H. Weiss, Quant. Chem. Group, University
of Karlsruhe, Germany since 1988; (c) F. Weigend, M. Häser,
H. Patzelt and R. Ahlrichs, Chem. Phys. Lett., 1998, 294, 143.
39 As described in the synthetic part the ene products of the enyne–
allenes 1c,e are not stable at room temperature.
8
503.
1
1
1
1
5 Preliminary communication: M. Schmittel, J.-P. Steffen, D. Auer
and M. Maywald, Tetrahedron Lett., 1997, 38, 6177.
6 Z. Arnold and A. Holý, Collect. Czech. Chem. Commun., 1961, 26,
3
059.
7 J. H. Ahn, M. J. Joung and N. M. Yoon, J. Org. Chem., 1995, 60,
6
173.
8 K. C. Nicolaou, P. Maligres, J. Shin, E. de Leon and D. Rideout,
J. Am. Chem. Soc., 1990, 112, 7825.
J. Chem. Soc., Perkin Trans. 2, 2001, 1331–1339
1339