Regioselective samarium diiodide induced couplings of carbonyl compounds with 1,3-diphenylallene and alkoxyallenes: A new route to 4-hydroxy-1-enol ethers

Article abstract of DOI:10.1002/chem.200400418

Since its introduction into synthetic organic chemistry, samarium diiodide has found broad application in a variety of synthetically important transformations. Herein, we describe the first successful intermolecular additions of samarium ketyls to typical allenes such as 1,3-diphenylallene (7), methoxyallene (12) and benzyloxyallene (25). Reaction of different samarium ketyls with 1,3-diphenylallene (7) occurred exclusively at the central carbon atom of the allene to afford products 9 in moderate to good yields. In contrast, reductive coupling of cyclic ketones to methoxyallene (12) regioselectively provided 4-hydroxy-1-enol ethers 13, which derive from addition to the terminal allene carbon atom of 12, in moderate to good yields. Whereas the E/Z selectivity with respect to the enol ether double bond is low, excellent diastereoselectivity has been observed in certain cases with regard to the ring configuration (e.g. compound 13 b). Studies with deuterated tetrahydrofuran and alcohol were performed to gain information about the reaction mechanism of this coupling process, which involves alkenyl radicals. The couplings of samarium ketyls derived from acyclic ketones and aldehydes gave lower yields, and in several cases cyclopentanols 20 are formed as byproducts. Branched acyclic ketones and conformationally more flexible cyclic ketones such as cycloheptanone led to a relatively high amount of cyclopentanol derivatives 20, whose formation involves an intramolecular hydrogen atom transfer through a geometrically favoured six-membered transition state followed by a cyclization step. The samarium diiodide mediated addition of 8b to benzyloxyallene (25) afforded the expected enol ethers 26, albeit in only low yield. Additionally, spirocyclic compounds 27 and 28 were obtained, which are formed by a cascade reaction involving an addition/cyclization sequence. In the novel coupling process described here methoxyallene (12) serves as an equivalent of acrolein. The 1,4-dioxygenated products obtained contain a masked aldehyde functionality and are therefore valuable building blocks in organic synthesis.

Full text of DOI:10.1002/chem.200400418

FULL PAPER
Regioselective Samarium Diiodide Induced Couplings of Carbonyl
Compounds with 1,3-Diphenylallene and Alkoxyallenes:
A New Route to 4-Hydroxy-1-enol Ethers
Alexandra Hölemann and Hans-Ulrich Reißig*[a]
Abstract: Since its introduction into
synthetic organic chemistry, samarium
diiodide has found broad application in
the enol ether double bond is low, ex-
cellent diastereoselectivity has been
observed in certain cases with regard
to the ring configuration (e.g. com-
pound 13b). Studies with deuterated
tetrahydrofuran and alcohol were per-
formed to gain information about the
reaction mechanism of this coupling
process, which involves alkenyl radi-
cals. The couplings of samarium ketyls
derived from acyclic ketones and alde-
hydes gave lower yields, and in several
cases cyclopentanols 20 are formed as
byproducts. Branched acyclic ketones
and conformationally more flexible
cyclic ketones such as cycloheptanone
led to a relatively high amount of cy-
clopentanol derivatives 20, whose for-
mation involves an intramolecular hy-
drogen atom transfer through a geo-
metrically favoured six-membered
transition state followed by a cycliza-
tion step. The samarium diiodide medi-
ated addition of 8b to benzyloxyallene
(25) afforded the expected enol ethers
26, albeit in only low yield. Additional-
ly, spirocyclic compounds 27 and 28
were obtained, which are formed by a
cascade reaction involving an addition/
cyclization sequence. In the novel cou-
pling process described here methoxy-
allene (12) serves as an equivalent of
acrolein. The 1,4-dioxygenated prod-
ucts obtained contain a masked alde-
hyde functionality and are therefore
valuable building blocks in organic syn-
thesis.
a
variety of synthetically important
transformations. Herein, we describe
the first successful intermolecular addi-
tions of samarium ketyls to typical al-
lenes such as 1,3-diphenylallene (7),
methoxyallene (12) and benzyloxyal-
lene (25). Reaction of different samari-
um ketyls with 1,3-diphenylallene (7)
occurred exclusively at the central
carbon atom of the allene to afford
products 9 in moderate to good yields.
In contrast, reductive coupling of cyclic
ketones to methoxyallene (12) regiose-
lectively provided 4-hydroxy-1-enol
ethers 13, which derive from addition
to the terminal allene carbon atom of
12, in moderate to good yields. Where-
as the E/Z selectivity with respect to
Keywords: allenes · cyclopentanols ·
enol ethers · radical reactions ·
samarium diiodide
Introduction
views.[2] One important class of samarium diiodide induced
reactions is the intermolecular or intramolecular coupling of
carbonyl compounds with carbon–carbon multiple bonds
(Scheme 1). Many reactions of different ketyls with alkenes
have been intensively studied by Molander and his group.[3]
In recent years, our group[4] has reported different cycliza-
tions of samarium ketyls with alkenyl,[5] alkynyl,[6,7] aryl[8]
and heteroaryl[9] units leading to highly functionalized car-
bocycles and heterocycles, often in good yields and with ex-
cellent diastereoselectivities.
Since the pioneering studies of Kagan and his co-workers in
the late 1970s,[1] samarium diiodide has attracted considera-
ble attention. It has rapidly been established as an excep-
tionally useful and versatile one-electron-transfer reductant
in organic synthesis, which promotes a variety of synthetical-
ly important transformations including sequential reactions.
The outstanding properties of this reagent, which include its
easy preparation, its applicability under mild and selective
conditions, and the possibility of tuning its reactivity and se-
lectivity by assistance of catalysts and additives, and its use-
fulness in organic synthesis have been outlined in several re-
However, reactions of samarium ketyls with a,b-unsatu-
rated aldehydes, in particular with acrolein, have rarely
[a] Dr. A. Hölemann, Prof. Dr. H.-U. Reißig
Institut für Chemie, Freie Universität Berlin
Takustrasse 3, 14195 Berlin (Germany)
Fax : (+49)30-83855367
E-mail: hans.reissig@chemie.fu-berlin.de
Scheme 1. Samarium diiodide promoted ketyl–olefin coupling reactions.
Chem. Eur. J. 2004, 10, 5493 – 5506
DOI: 10.1002/chem.200400418
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FULL PAPER
been studied. a,b-Unsaturated aldehydes have mainly been
used in samarium diiodide induced iodomethylations[10] and
Mukaiyama aldol reactions.[11] A few cyclizations of a,b-un-
saturated aldehydes to double and triple bonds have recent-
ly been reported.[12]
Intermolecular and intramolecular coupling reactions of
samarium ketyls with cumulated double bonds are also very
rare. Whereas intermolecular couplings with allenes have
not been studied at all, only a few examples of cyclizations
involving electron-deficient allenyl aldehydes leading to sub-
stituted cycloalkanols have been described by Gillmann.[13]
As part of our interest in samarium diiodide mediated
ketyl–olefin coupling reactions,[4–9] we therefore focussed
our attention[7] on intermolecular additions of ketyls to sub-
stituted allenes and recently published our preliminary re-
sults.[14] In principle, three electronically different carbon
atoms are available for the coupling process of a substituted
allene with the ketyl radical anion. Scheme 2 illustrates the
possible reaction pathways and the resulting addition prod-
ucts 6a–d which might be obtained by samarium diiodide
mediated coupling of ketyls 4 with monosubstituted allenes
5. The attack of the ketyl to the allene can occur at the a-
(6d), b- (6b,c) and g-positions (6a) to the substituent. To in-
vestigate the regiochemical and stereochemical features of
samarium ketyl additions we used 1,3-diphenylallene and
methoxyallene as typical model substrates.
Scheme 3. a) SmI2 (2.2 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight.
Table 1. Samarium diiodide induced coupling of 1,3-diphenylallene (7)
with carbonyl compounds 8.[a]
Entry Carbonyl compound Coupling product Yield [%] (E/Z)[b]
8
9
1
2
69 (>97:3)
8a
9a
45[c] (>97:3),
(dr>97:3)[d]
8b
8c
9b
9c
3
4
31 (>97:3)
21[e] (80:20)
8d
9d
[a] Conditions: 8 (1.0 equiv), 7 (1.1–1.2 equiv), SmI2 (2.2 equiv), HMPA
(18 equiv), tBuOH (2.0 equiv), THF, RT, overnight. [b] Yields for isolated
products after chromatography. E/Z ratios (according to 1H NMR spec-
troscopy) are given in parentheses. [c] trans-4-tert-Butylcyclohexanol
(19%) was obtained as byproduct. [d] Diastereoselectivity with respect
Scheme 2. Possible pathways of ketyl couplings with monosubstituted al-
lenes.
1
to the cyclohexane ring. [e] Purity >90% according to H NMR spectro-
scopy.
Results and Discussion
1
Reactions of samarium ketyls with 1,3-diphenylallene: Ex-
periments with different samarium ketyls were first per-
formed with 1,3-diphenylallene (7) which has only two dif-
ferent allene carbon atoms. In the presence of samarium
diiodide, HMPA (hexamethylphosphoramide) and tert-buta-
nol, allene 7 (1.1–1.2 equiv) was coupled with different car-
bonyl compounds 8 (Scheme 3, Table 1) to yield products 9,
which displayed characteristic 1H NMR signals at dꢀ
7.0 ppm. As expected, addition of the ketyl occurred exclu-
sively to the central allene carbon atom of 7, since the re-
sulting intermediate 11 is a highly stabilized allylic and ben-
zylic radical. A mixture of E and Z isomers of 1,3-diphenyl-
propene (10) was isolated as a byproduct (in ꢀ28% in the
case of 9a, >70% purity according to H NMR spectrosco-
py), which is the result of simple reduction of the allene
moiety.
Cyclic ketones such as cyclopentanone (8a, Table 1,
entry 1) and 4-tert-butylcyclohexanone (8b, entry 2) under-
went smooth coupling with 7 to afford products 9a and 9b
as single diastereomers (dr>97:3) with respect to the
double bond in 69 and 45% yield, respectively. In the case
of 8b, 4-tert-butylcyclohexanol was isolated in 19% as a by-
product. The configuration of the double bond was estab-
lished by NOESY spectroscopy. Only the E isomer was se-
lectively formed during this coupling process. In terms of
the relative stereochemistry at the cyclohexane ring, product
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SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
Table 2. Samarium diiodide induced coupling of methoxyallene (12) with
cyclopentanone (8a).[a]
9b was isolated as a single diastereomer. Although the con-
figuration of 9b has not been determined, it is highly likely
to be the trans isomer.[15]
Entry
Equiv
Equiv
Equiv
Yield of 13a [%]
(E/Z)[c]
[b]
12[b]
SmI2
HMPA[b]
Acyclic ketones such as acetone (8c, Table 1, entry 3) and
aldehydes such as heptanal (8d, entry 4) can also be used
for this coupling reaction; however, only low yields of 9c
and 9d could be obtained after chromatography. Further
products (e.g. pinacolic coupling products) could not be iso-
lated. As with the cyclic ketones, coupling product 9c was
obtained as the pure E isomer. In the case of heptanal, the
E/Z selectivity was lower, and an 80:20 mixture of the E
and Z isomers was isolated. The diastereoselectivity is appa-
rently controlled by the size of the added fragment derived
from the carbonyl compound.
1
2
3
4
1.0
2.0
2.0
2.0
2.2
2.2
2.2
1.0
18
18
–
65[d] (60:40)
85 (60:40)
–
18
38[e] (55:45)
[a] Conditions: 8a (1.0 equiv), 12, SmI2, HMPA, tBuOH (2.0 equiv),
THF, RT, overnight. [b] With respect to cyclopentanone (8a). [c] Yields
for isolated products after chromatography. E/Z ratios (according to
1H NMR spectroscopy) are given in parentheses. [d] Purity >90% ac-
cording to 1H NMR spectroscopy. [e] As a mixture with HMPA. Yield
1
was calculated according to the ratio determined by H NMR spectrosco-
py.
Reactions of samarium ketyls derived from cyclic ketones
with methoxyallene: Methoxyallene (12) (Scheme 4) is a
versatile C3 building block.[16] Reactions of this allene or
other alkoxyallenes in the presence of samarium diiodide
have generally not been reported. Methoxyallene itself has
only been applied to a samarium(ii)-induced [3+2] cycload-
dition with carbonyl ylides.[17]
As a model reaction, coupling of 12 with cyclopentanone
(8a) was studied under different conditions (Scheme 4,
Table 2). The samarium(ii)-induced reaction of 12 with 8a
green indicating that 12 itself slowly reacts with samarium
diiodide. Decomposition or oligomerisation of methoxyal-
lene (12) takes place, probably induced by the Lewis acidic
samarium(ii) or samarium(iii) species present or by an elec-
tron-transfer process.
In contrast to allene 7, coupling of 8a with 12 selectively
occurred at the terminal carbon atom of methoxyallene to
afford 4-hydroxy-1-enol ether 13a as an E/Z mixture
(Scheme 4). Formation of the samarium ketyls from the car-
bonyl functionality generates a nucleophilic radical which
selectively adds to the g-position with respect to the me-
thoxy group. Although alkoxyallenes appear to be nucleo-
philic components at first glance, their terminal double bond
has significant electrophilic character and can therefore
smoothly react with a nucleophilic radical such as the sama-
rium ketyl.[22] In this novel coupling process methoxyallene
(12) serves as an equivalent of acrolein (which is probably
too reactive for this kind of coupling) and it provides 4-hy-
droxy-1-enol ethers as products which bear a synthetically
useful masked aldehyde functionality. In principle, the over-
all process involves a formal umpolung[23] of reactivity (elec-
trophilic carbonyl compound!nucleophilic ketyl) which
allows for the construction of 1,4-dioxygenated compounds.
We propose the mechanism shown in Scheme 4. In ac-
cordance with literature reports,[3–9] ketyl radical anion 14 is
reversibly generated by electron transfer from samarium
diiodide to the carbonyl group. Subsequent addition of 14 to
12 affords alkenyl radical 15 which can be reduced by a
second equivalent of samarium diiodide to the correspond-
ing vinyl anion 16 (pathway A). Protonation by the additive
tert-butanol finally furnishes 13a. Since alkenyl radicals such
as 15 are highly reactive intermediates, the direct conversion
of 15 to 13a by abstraction of hydrogen from the solvent
THF (or the additive HMPA) has to be considered as mech-
anistic alternative (pathway B).[24]
was performed as above, and
a single product 13a
(Scheme 4) was isolated in 65% yield after chromatography
(entry 1). By using an excess of methoxyallene (12)
(2.0 equiv, entry 2) the yield of 13a could be increased to
85%. No reaction occurred in the absence of the additive
HMPA (entry 3). According to previous reports,[18,19] HMPA
is required for successful couplings, since this cosolvent sig-
nificantly increases the reduction power of samarium(ii).
Coupling of 12 with 8a in the presence of one equivalent of
samarium diiodide was also successful (entry 4); however,
only 38%[20] of 13a could be isolated showing that at least
two equivalents of samarium diiodide are necessary for an
efficient coupling process.[21]
To investigate the mechanistic details of the ketyl–me-
thoxyallene coupling, experiments were carried out with
deuterated THF as solvent and deuterated methanol as
proton source (Table 3). The percentage of deuterium in
13a was estimated from the ratio of the alkenyl protons de-
termined by 1H NMR spectroscopy.[25] In the presence of
[D8]THF and with tert-butanol as proton source (entry 1)
crude 13a was obtained with approximately 20–30% deute-
rium incorporation. However, using [D4]MeOH as proton
Scheme 4. a) SmI2, HMPA, tBuOH, THF, RT, overnight.
In a control experiment, methoxyallene (12) was treated
with samarium diiodide and HMPA in the absence of
ketone 8a. The colour of the reaction solution gradually
changed from deep violet (complex of SmI2 and HMPA) to
Chem. Eur. J. 2004, 10, 5493 – 5506
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H.-U. Reißig and A. Hölemann
FULL PAPER
source in normal THF (entry 2) only small amounts (ca.
5%) of deuterium were incorporated in 13a. Combination
of [D8]THF and [D4]MeOH (entry 3) resulted in the incor-
poration of approximately 20% deuterium.
Table 3. Mechanistic studies with 8a and 12 in the presence of deuterat-
ed THF and/or proton source.[a]
Entry
Solvent
Proton source
Yield [%]
H/D-13a
Content of deu-
terium [%] in 13a[b]
1
2
3
[D8]THF
THF
tBuOH
50
58
67
E isomer: 20
Z isomer: 30
E isomer: 5
Z isomer: 5
E isomer: 20
Z isomer: 20
[D4]MeOH
[D4]MeOH
Scheme 5. a) SmI2 (2.2 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight.
[D8]THF
[a] Conditions: 8a (1.0 equiv), 12 (2.0 equiv), SmI2 (2.2 equiv), HMPA
(18 equiv), proton source (2.0 equiv), solvent, RT, overnight. [b] Estimat-
ed according to the ratio of alkenyl protons determined by 1H NMR
spectroscopy of the crude mixture. The content of deuterium significantly
decreases to 4–15% during chromatography on aluminium oxide (activi-
ty III) probably as a result of proton exchange by protonation/deprotona-
tion.
pling reaction in more detail. Reductive couplings were gen-
erally performed by adding a THF solution of carbonyl
compound 8, methoxyallene (12) and tert-butanol to a solu-
tion of freshly prepared samarium diiodide and HMPA in
THF at room temperature. Several cyclic ketones were com-
bined with 12, and the results of these reactions are summar-
ized in Table 4. In general, products 13 were obtained as
mixtures of E and Z isomers in ratios of 50:50 to 65:35 (ac-
These results indicate that the solvent, but not the proton
source, has an important influence on the incorporation of
deuterium in 13a. As expected, alkenyl radicals such as 15
are highly reactive intermediates and only a fairly small
fraction is reduced to anion 16 by a second equivalent of sa-
marium diiodide (pathway A, Scheme 4) to give the proto-
nated or deuterated product. In accordance with Inana-
gaꢁs[26] and Curranꢁs[24,27] results, the direct conversion of al-
kenyl radical 15 to 13a by abstraction of hydrogen or deute-
rium from the solvent and/or the additive HMPA (path-
way B) is more favourable. Although available in high
concentration, only 20–30% of 13a is obtained by abstrac-
tion of deuterium from the solvent [D8]THF (entry 1). We
therefore assume that 13a is most probably formed by ab-
straction of hydrogen from the methyl groups of the additive
HMPA which is a far better hydrogen donor leading to a
well-stabilized radical.[28]
We envisaged that ketyl–alkene coupling of acrolein di-
methylacetal (17) with 8a in the presence of samarium diio-
dide and HMPA (Scheme 5) would also lead to a protected
aldehyde derivative. However, under standard conditions,
the expected coupling product 18 was not obtained, and 13a
was isolated in 51% yield as single product. Intermolecular
addition of ketyl 14 to the double bond of 17 affords radical
19, which is transformed into 13a by a second electron
transfer of samarium diiodide and subsequent b-elimination
of methanolate. Coupling of 8a with methoxyallene (12) is
therefore a more efficient reaction.
1
cording to H NMR spectroscopy). In almost all cases, the E
isomer was slightly preferred.
As with cyclopentanone (8a), similar cyclic ketones such
as cyclobutanone (8e, Table 4, entry 1) and cyclohexanone
(8 f, entry 2) afforded the addition products 13e and 13 f as
the only isolated products in good yields. In contrast, cou-
pling of 12 with cycloheptanone (8g, entry 3) under standard
conditions unexpectedly furnished two constitutional iso-
mers. Separation by chromatography gave the expected cou-
pling product 13g in 29% yield and bicyclic compound 20g
in 34% yield as a single diastereomer whose configuration
has not yet been determined. The latter product arises as a
result of the higher conformational flexibility of the cyclo-
heptane ring which leads, in a sequential reaction, to a
second carbon–carbon coupling step. Formation of bicyclic
derivatives 20 can thus be explained by an intramolecular
hydrogen atom transfer[30] to alkenyl radical 15 to afford
alkyl radical 21. The six-membered transition state involved
is geometrically very favoured (Scheme 6). Radical 21 sub-
sequently attacks the enol ether double bond in a 5-exo-trig
cyclization leading to stabilized radical 22. A second elec-
tron transfer of samarium diiodide followed by protonation
finally yields 20.
Substituted cycloalkanones (Table 4, entries 4–7) and a pi-
peridinone derivative (entry 8) can also be used in this
novel coupling reaction to give moderate to good yields of
the expected enol ethers. With 2-methylcyclohexanone (8h,
entry 4) as precursor the enol ether 13h was obtained in low
overall yield (35%). The decreased efficacy of this transfor-
mation is probably caused by the a-methyl substituent,
which sterically disfavours the attack of the ketyl to the
The first successful coupling of 8a and 12 and the versatil-
ity of building blocks 13 for further synthetic transforma-
tions, which has actually been demonstrated,[29] encouraged
us to investigate the scope and limitations of the new cou-
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SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
Table 4. Samarium diiodide induced coupling of methoxyallene (12) with cyclic ketones 8.[a]
(entry 3), the intramolecular
hydrogen atom transfer through
the six-membered transition
state (Scheme 6) can compete
because a more stabilized terti-
ary radical is involved in this
case.
Entry
Ketone 8
Addition product 13 [%][b]
Cyclization product 20[b]
The reaction of 12 with 4-
tert-butylcyclohexanone
(8b,
Table 4, entry 6) was more effi-
cient, and the expected cou-
pling product 13b was obtained
in 58% yield. In addition, start-
ing material 8b was recovered
in 41% yield after chromatog-
raphy. Apparently, conversion
of this ketone was incomplete,
which may also have occurred
in other experiments in which
unconsumed starting material
was not isolated owing to its
volatility. The reaction of 8b
and 12 was therefore carried
out with 4.2 equivalents of sa-
marium diiodide. Only traces of
starting material 8b were de-
tected in the crude mixture;
however, the yield of 13b was
1
2
8e (n=0)
8 f (n=2)
13e 65 (65:35)[c]
13 f 79 (60:40)
–
–
[d]
3
8g (n=4)
13g 29 (60:40)
20g 34 (dr>97:3)
4
–
8h
cis-13h 14 (50:50),
trans-13h 21 (55:45)
5
6
8i
13i 29 (60:40)
20i 43 (dr 60:40)
–
not
dramatically
increased
(62%). Addition of samarium
diiodide to a solution of 8b and
12 (i.e., reverse addition mode)
slightly improved the yield of
13b, albeit 16% of the starting
material was recovered. In all
experiments, 13b was obtained
as a single diastereomer (dr>
97:3) with respect to the cyclo-
hexane ring. The relative con-
figuration was determined by
transforming 13b into the cor-
responding g-lactone as descri-
bed previously.[14,29] By compar-
ing the data of this lactone with
the data of the cis and trans iso-
mers reported in the litera-
ture,[32] 13b was unambiguously
assigned as the trans isomer.
This selectivity can nicely be
explained by assuming that the
8b
13b 58 (60:40),[e]
dr>97:3[f]
7
8
–
8j
13j 54 (55:45)
[h]
–
8k13k
51 (50:50)[g]
[a] Conditions: 8 (1.0 equiv), 12 (2.0–3.0 equiv), SmI2 (2.2–2.5 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight. [b] Yield for isolated products after chromatography. E/Z ratios (according to 1H NMR
spectroscopy) are given in parentheses. [c] Purity >95% according to 1H NMR spectroscopy. [d] Traces of a
bicyclic compound related to 20g were detected in the crude mixture. [e] Starting material 8b was recovered
in 41%. [f] Only trans isomer was detected. [g] Isolation of 11% of secondary alcohol. [h] Small amounts of a
bicyclic compound related to 20g were obtained after chromatography.
allene. A low diastereoselectivity (60:40) in favour of the
trans isomer was recorded.[31]
sterically demanding samarium alkoxy and tert-butyl groups
of the intermediate ketyl prefer equatorial positions
(Scheme 7). As a consequence the attack of 12 takes place
in the axial position leading to the trans product.
Other substituents and even heteroatoms are tolerated in
the 4-position (Table 4, entries 7 and 8). Reaction of 8j with
12 under standard conditions afforded coupling product 13j
as the only isolated product in 54% yield. Coupling of Boc-
protected piperidinone 8k with methoxyallene (12) furnish-
Coupling of methoxyallene (12) with 3-tert-butylcyclohex-
anone (8i, Table 4, entry 5) also gave the desired coupling
product 13i in only low yield (29%), but as a single diaster-
eomer in this case. The bicyclic compound 20i was obtained
as the main product in 43% yield and as a 60:40 mixture of
diastereomers. Although the six-membered ring is confor-
mationally less flexible than the seven-membered ring
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major product was the expected coupling product 13m,
whereas the minor component was identified as cyclopenta-
nol derivative 20m. Branched ketones such as isopropylme-
thylketone (8n) and pinacolone 8o (entries 4 and 5) gave
the desired products 13 in even lower yields probably for
steric reasons; on the other hand they facilitated the forma-
tion of cyclopentanol derivatives 20 through intramolecular
hydrogen atom transfer according to Scheme 6. Starting
with 8n an 85:15 mixture of coupling product 13n and cyclo-
pentanol 20n was obtained in 24% yield. In the case of pi-
nacolone 8o, only traces of the desired product 13o were
isolated, and the cyclization product 20o was isolated as the
major component of this reaction in 21% yield. All cyclo-
pentanol derivatives were obtained as single diastereomers
with as yet unknown configurations. The Houk–Beckwith[33]
transition state model presented in Scheme 8 should be as-
sumed for the addition of the radical 21 to the enol ether
double bond, in which the sterically demanding samarium
group is located in an equatorial position. Cyclization
should then produce cyclopentanol derivatives 20 with cis-
orientated hydroxyl and CH2OMe groups.
Scheme 6. Proposed mechanism for the formation of cyclopentanols 20.
Scheme 7. Intermediate ketyl radical anion in the addition of 8b to 12.
ed the desired product 13k in
Table 5. Samarium diiodide induced coupling of methoxyallene (12) with acyclic ketones and aldehydes 8.[a]
moderate yield (51%); howev-
er, a bicyclic compound analo-
gous to 20g could be detected
in a mixture along with other
components.
Entry
1
Ketone 8
Addition product 13 [%][b,c]
Cyclization product 20[b]
Reactions of samarium ketyls
derived from acyclic ketones
and aldehydes with methoxyal-
lene: The successful results with
cyclic ketones motivated us to
study the reactions of methox-
yallene (12) with acyclic ke-
tones and aldehydes. This varia-
tion significantly diminished the
yields of coupling products 13
(Table 5) and cyclopentanol de-
rivatives 20 were formed to a
higher degree.
Reaction of 12 with acetone
(8c, Table 5, entry 1) and
butan-2-one (8l, entry 2) af-
forded the corresponding ad-
ducts 13c and 13l in 26% and
36% yield, respectively. The
low efficacies of these transfor-
mations may be due to the vol-
atility of the products (and by-
products). Performing the cou-
pling process with pentan-3-one
(8m, entry 3) significantly im-
proved the mass balance to give
52% overall yield; however, an
85:15 mixture of two isomeric
–
8c
8l
13c 26 (65:35)
13l 36 (60:40)
13m 44[d] (55:45)
2
3
–
8m
20m 8[d] (dr>97:3)
20n 4[d] (dr>97:3)
4
5
8n
13n 20[d] (55:45)
8o
8p
8d
13o 5[d] (60:40)
13p 53 (85:15)[e]
13d 43 (55:45)
20o 21[d] (dr>97:3)
6
7
–
–
[a] Conditions: 8 (1.0 equiv), 12 (2.0–3.0 equiv), SmI2 (2.2–2.5 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight. [b] Yield for isolated products after chromatography. [c] E/Z ratios (according to
1H NMR spectroscopy) are given in parentheses. [d] 13 and 20 were obtained as a mixture. Yield was calculat-
ed according to the ratio determined by 1H NMR spectroscopy. [e] As a mixture with 14% 4-phenylbutan-2-
1
compounds was obtained. The ol. Yield was calculated according to the ratio determined by H NMR spectroscopy.
5498
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 5493 – 5506

SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
Other 1-alkoxy-1,2-propadienes can also be applied to
this coupling reaction. When the reaction was performed
with benzyloxyallene (25) and 4-tert-butylcyclohexanone
(8b) the expected enol ether 26 was isolated in a mixture to-
gether with two other components in 67% overall yield
after chromatography. Separation by HPLC yielded (E)-26
(15%), (Z)-26 (12%) and two spirocyclic derivatives 27
(20%) and 28 (8%), respectively (Scheme 10). The struc-
tures of these compounds were unambiguously identified by
NMR spectroscopy. Compounds 26–28 were obtained in dia-
stereomerically pure form; however, the relative configura-
tion of the hydroxyl and tert-butyl groups at the cyclohexyl
ring could not be determined. Again, the configurations de-
picted in Scheme 10 are highly likely by analogy with the re-
sults obtained in the coupling of 8b with 12.
Scheme 8. Transition state and intermediate according to the Houk–
Beckwith model for cyclizations leading to 20.
Aryl-substituted carbonyl compounds such as acetophe-
none and benzaldehyde are unsuitable precursors for the sa-
marium diiodide induced coupling reactions with methoxyal-
lene (12). The resulting ketyl radicals are considerably
better stabilized by the aryl group and are therefore less re-
active. In addition, the increased bulk introduced with the
phenyl substituent may also hamper the reaction with 12.
Coupling of phenylacetone with 12 was also unsuccessful re-
sulting in the formation of a very complex mixture of prod-
ucts. In contrast, 4-phenylbutan-2-one (8p, Table 5, entry 6)
can successfully be coupled with methoxyallene (12) to
afford the desired coupling product 13p as an inseparable
mixture (85:15) with 4-phenylbutan-2-ol.
Samarium ketyls derived from aldehydes also undergo the
coupling process with methoxyallene (12). Reaction of hep-
tanal (8d) with 12 furnished the corresponding adduct 13d
in moderate yield (Table 5, entry 7). Ketyl radical anions
from aldehydes are less stabilized than those from ketones
and are therefore generally more prone to simple reduction
and/or to the pinacol coupling process, which apparently re-
duces the efficacy of the desired carbon–carbon bond-form-
ing process with the allene.
Scheme 10. a) SmI2 (2.2 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight.
Reactions of samarium ketyls with substituted methoxyal-
lene derivatives and other alkoxyallenes: We also studied
the reaction of carbonyl compounds with substituted me-
thoxyallene derivatives and other alkoxyallenes. When cy-
clopentanone (8a) was combined with 1-methoxydodeca-
1,2-diene[34] in the presence of samarium diiodide and
HMPA no reaction took place, and only starting material
was recovered after chromatography. Coupling of 8a with
different 1-substituted methoxyallene derivatives in most
cases led to the formation of rather complex product mix-
tures. However, the most simple compound of this series, 3-
methoxybuta-1,2-diene (23),[35] and 8a (Scheme 9) gave the
expected coupling product 24, albeit in disappointing yield
The formation of spirocyclic compounds 27 and 28 proba-
bly occurs in a similar manner to the ketyl–aryl cyclizations
previously reported by us and others.[8,9] These reactions fea-
ture dearomatization of the aryl ring leading to products
with cyclohexadienyl subunits. Similar samarium diiodide
promoted cyclizations of g-aryl-substituted ketyls to give
spirocyclic compounds have recently been described by
Berndt[36] and Tanaka.[37] However, in the case of 27 and 28
the precursor for the cyclization is an alkenyl radical which
is formed in situ by samarium diiodide induced coupling of
25 and 8b. The proposed mechanism for this cascade reac-
tion is presented in Scheme 11. Analogous to the coupling
with methoxyallene, ketyl radical 29 adds in g-position to
the alkoxy substituent to afford alkenyl radical 30. This in-
termediate is either converted into enol ether 26 by hydro-
gen abstraction or into pentadienyl radical 31 by 5-exo-trig
cyclization onto the ipso-position of the aromatic ring. The
conceivable 6-trig cyclization was not observed. Subsequent-
ly, radical 31 is reduced by a second equivalent of samarium
diiodide to the corresponding anion 32, which is finally pro-
tonated regioselectively to yield 27 and 28. By analogy with
the Birch reduction,[38] the 1,4-diene 27 is obtained as the
major product, whereas the thermodynamically more stable
conjugated 1,3-diene 28 represents only the byproduct.
1
(18%) and low purity according to H NMR spectroscopy.
As in the reaction of different samarium ketyls with me-
thoxyallene (12), the attack of the ketyl radical occurs selec-
tively in g-position to the methoxy group.
Although this reaction produced compounds in only mod-
erate yield, it nevertheless delivers products with a complex
Scheme 9. a) SmI2 (2.2 equiv), HMPA (18 equiv), tBuOH (2.0 equiv),
THF, RT, overnight.
Chem. Eur. J. 2004, 10, 5493 – 5506
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5499

H.-U. Reißig and A. Hölemann
FULL PAPER
products are obtained by umpolung of reactivity (electro-
philic carbonyl compound!nucleophilic ketyl). The 4-hy-
droxy-1-enol ethers 13 contain a masked aldehyde function-
ality and are valuable building blocks which have been con-
verted into g-lactones 33 or (via g-lactols) into highly substi-
tuted tetrahydrofuran derivatives 34 (Scheme 12).[29] Alter-
natively, aldehydes such as 35 are available after protection
of the hydroxyl group. Further synthetic applications of
compounds 13 are conceivable.
Scheme 11. Proposed mechanism of the coupling of 8b and 25.
functionality pattern. This transformation therefore deserves
further investigation and optimisation.
Conclusion
Scheme 12. Synthetic applications of 4-hydroxy-1-enol ethers 13.
We have successfully studied the first intermolecular addi-
tion of samarium ketyls to allenes. The reactions were ap-
plied to different ketyls and typical allenes such as 1,3-di-
phenylallene (7), methoxyallene (12) and benzyloxyallene
(25). The reductive coupling of different samarium ketyls
with 1,3-diphenylallene (7) afforded the expected E-config-
ured addition products 9 in moderate to good yields. The
attack of the ketyl radical exclusively occurred at the central
carbon atom of the allene owing to the formation of a stabi-
lized radical intermediate. In contrast, the reactions with
methoxyallene (12) regioselectively provide products 13 de-
rived from ketyl additions to the terminal position of the
allene. Several four-, five- and six-membered cycloalkanones
smoothly undergo this transformation to afford 13 in moder-
ate to good yields as E/Z mixtures. Samarium ketyls derived
from acyclic ketones and aldehydes are less suitable for this
kind of coupling reaction and give lower yields. A compet-
ing reaction leading to the formation of cyclopentanol deriv-
atives 20 occurs in certain cases, which reduces the efficacy
of the coupling process. Branched acyclic ketones and con-
formationally more flexible ketyl precursor such as cyclo-
heptanone led to the formation of compound 20, since the
intramolecular hydrogen atom transfer is possible through a
geometrically favoured six-membered transition state.
Experimental Section
General methods: Reactions were generally performed under argon in
flame-dried flasks, and the components were added by means of syringe.
Unless otherwise stated, materials were obtained from commercial sup-
pliers and were used without further purification. Hexamethylphosphora-
mide (HMPA, Fluka) was distilled and kept under argon over 4 Š molec-
ular sieves. Warning: HMPA has been identified as a carcinogenic re-
agent. Use of gloves is required during handling. Reactions and chroma-
tography
should
be
performed
in
a
well-vented
hood.
Tetrahydrofuran (THF) was freshly distilled from sodium/benzophenone
under argon for each of the SmI2 reactions. 1,2-Diiodoethane (Acros)
was dried in vacuo, sublimated before use and kept under argon at 08C.
Samarium (ꢀ40 mesh) was obtained from Acros and used as supplied.
Products were purified by flash chromatography on silica gel (230–
400 Mesh, Merck) or neutral alumina (activity III, Fluka). Unless other-
wise stated, yields refer to analytically pure samples. Isomer ratios were
derived from suitable 1H NMR integrals.
1H NMR [CDCl3 (7.25 ppm) or TMS (0.00 ppm) as internal standard]
and 13C NMR spectra [CDCl3 (77.0 ppm) as internal standard] were re-
corded on a Bruker AC250, AM270 or AC500 and Joel Eclipse500 in
CDCl3 solution at 258C. Missing signals are hidden by signals of the
second compound or they could not be unambiguously identified as a
result of low intensity. Integrals are in accordance with assignments; cou-
pling constants are given in Hz. The assignments refer to IUPAC nomen-
clature; primed numbers belong to the side chain. IR spectra were meas-
ured with an FTIR spectrophotometer Nicolet 5SXC (Perkin–Elmer).
MS and HRMS analyses were performed on Finnigan MAT711 (EI,
8 kV), MAT CH7A (EI, 3 kV) and CH5DF (FAB, 3 kV) at 80 eV. The
peak of the molecular ion (M +, if possible, otherwise a characteristic
fragment was chosen) and the peak with the highest intensity are given.
The complete set of peaks was collected elsewhere.[7] Elemental analysis
were recorded on a Perkin–Elmer elemental analyzer. Melting points
were measured on a Reichert apparatus and are uncorrected.
Aryl-substituted carbonyl compounds and a-phenyl car-
bonyl compounds provide only complex product mixtures.
Employment of 1- or 3-substituted methoxyallene deriva-
tives either led to recovery of starting material or to com-
plex mixtures. The samarium diiodide induced coupling of
8b with benzyloxyallene (25) afforded the expected enol
ethers 26 in only low yields, and a competing intermolecular
addition/spirocyclization sequence leads to the formation of
spirocyclic compounds 27 and 28.
General procedure for SmI2 induced couplings of carbonyl compounds
with allenes: Samarium powder (2.4–2.5 equiv) and 1,2-diiodoethane
(2.2 equiv) were suspended in freshly distilled anhydrous THF (10 mL
In this novel coupling reaction methoxyallene serves as an
equivalent of acrolein, and the resulting 1,4-dioxygenated
5500
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 5493 – 5506

SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
per g-atom samarium) under an argon atmosphere and stirred for 2 h at
room temperature. HMPA (18 equiv) was added to the resulting dark
blue solution. Carbonyl compound 8 (1.0 equiv), allene 7, 12 or 25 (1.1–
3.0 equiv) and tert-butanol (2.0 equiv) were dissolved in anhydrous THF
(15 mL per mmol 8) and then added to the deep violet solution. After
16–18 h the mixture was quenched with saturated aqueous sodium bicar-
bonate and water, the organic layer was separated, and the aqueous layer
was extracted three times with diethyl ether. The combined organic
layers were washed once with water and twice with brine, dried with an-
hydrous magnesium sulfate, filtered and evaporated. The resulting crude
oil was purified by column chromatography on silica gel or neutral alumi-
nium oxide (activity III) using n-hexane/ethyl acetate.
3J=6.9 Hz, 3H; 9-H); 13C NMR (126 MHz, CDCl3): E isomer: d=127.2
(d, C-1), 75.4 (d, C-3), 34.4 (t, CH2Ph), 36.3, 31.9, 29.3, 25.8, 22.7 (5t, C-
4, C-5, C-6, C-7, C-8), 14.1 ppm (q, C-9); Z isomer: d=129.7 (d, C-1),
70.4 (d, C-3), 37.3 (t, CH2Ph), 35.6, 31.8, 29.3, 26.0, 22.7 (5t, C-4, C-5, C-
6, C-7, C-8), 14.1 ppm (q, C-9); the following signals could not be unam-
biguously assigned to one of the isomers: d=144.0, 142.9, 140.3, 139.7,
137.4, 134.9 [6s, (E)/(Z)-C-2, (E)/(Z)-Ph], 129.7, 129.6, 128.8, 128.7,
128.6, 128.6, 128.5, 128.2, 126.8, 126.7, 126.3, 126.2 ppm [12d, (E)/(Z)-
ꢁ
ꢁ
ꢁ
Ph]; IR (film): n˜ =3385 (O H), 3080–3025 (=C H), 2955–2855 (C H),
1600–1495 cmꢁ1 (C=C); MS (EI, 1008C): m/z (%): 308 (5) [M +], 217
(100) [M +ꢁC7H7]; HRMS: m/z: calcd for C22H28O: 308.2140; found:
308.2152.
1H NMR and 13C NMR data of compounds 13 are presented in Tables 6
and 7, respectively.
1-[(E)-1-Benzyl-2-phenylethenyl]cyclopentan-1-ol (9a): The reaction was
performed according to the general procedure by using 1,3-diphenylal-
lene (7) (0.192 g, 1.00 mmol) and cyclopentanone (8a) (0.076 g,
0.90 mmol). Chromatography on silica gel with n-hexane/ethyl acetate
(95:5) gave a mixture of (E)- and (Z)-1,3-diphenylpropene 10 (0.054 g,
28%, purity >70%) as a yellow oil and 9a (0.173 g, 69%, E:Z>97:3) as
a colourless oil. 1H NMR data of 10 are in accordance with literature
data.[39] 9a: 1H NMR (500 MHz, CDCl3): d=7.29–7.23, 7.20–7.16 (2 m,
8H, 2H; Ph), 7.02 (s, 1H; 2’-H), 3.79 (s, 2H; CH2Ph), 1.88–1.78, 1.70–
1.64 (2m, 2”4H; 2-H, 3-H, 4-H, 5-H), 1.30 ppm (brs, 1H; OH);
13C NMR (126 MHz, CDCl3): d=144.0, 140.3, 137.5 (3s, Ph, C-1’), 128.5,
128.4, 128.3, 126.7, 126.0 (5d, Ph), 127.1 (d, C-2’), 85.6 (s, C-1), 39.9, 23.4
1-[(E)/(Z)-3-Methoxyprop-2-enyl]cyclopentan-1-ol (13a): Cyclopenta-
none (8a) (0.084 g, 1.00 mmol) and methoxyallene (12) (0.140 g,
2.00 mmol) were treated with SmI2 and HMPA according to the general
procedure. Chromatography on aluminium oxide (activity III) using n-
hexane/ethyl acetate (90:10 to 80:20) yielded a mixture of (E)-13a and
(Z)-13a (0.133 g, 85%, E:Z 60:40) as a colourless oil. IR (film): n˜ =3425
ꢁ1
ꢁ
ꢁ
ꢁ
(O H), 3060–3040 (=C H), 2955–2830 (C H), 1665–1655 cm (C=C);
MS (EI, 308C): m/z (%): 156 (2) [M +], 72 (100) [C4H8O+]; HRMS: m/z:
calcd for C9H16O2: 156.1150; found: 156.1163.
SmI2-induced coupling of cyclopentanone (8a) with 3,3-dimethoxyprop-
1-ene (17): Cyclopentanone (8a) (0.084 g, 1.00 mmol) and 3,3-dimethoxy-
prop-1-ene (17) (0.204 g, 2.00 mmol) were treated with SmI2 and HMPA
under the described conditions. Chromatography on aluminium oxide
(activity III) using n-hexane/ethyl acetate (90:10 to 75:25) gave a mixture
of (E)-13a and (Z)-13a (0.080 g, 51%, E:Z 60:40) as a colourless oil.
ꢁ
(2t, C-2, C-3, C-4, C-5), 34.6 ppm (t, CH2Ph); IR (film): n˜ =3420 (O H),
ꢁ1
ꢁ
ꢁ
3080–3025 (=C H), 2960–2870 (C H), 1600–1495 cm (C=C); MS (EI,
408C): m/z (%): 278 (1) [M +], 169 (100) [M +ꢁCH2C6H5ꢁH2O]; elemen-
tal analysis calcd (%) for C20H22O (278.4): C 86.29, H 7.97; found: C
86.51, H 7.81.
1-[(E)-1-Benzyl-2-phenylethenyl]-4-tert-butylcyclohexan-1-ol (9b): Com-
1-[(E)/(Z)-3-Methoxyprop-2-enyl]cyclobutan-1-ol (13e): The reaction
was performed according to the general procedure using cyclobutanone
(8e) (0.068 g, 0.97 mmol) and 12 (0.140 g, 2.00 mmol). Chromatography
on aluminium oxide (activity III) using n-hexane/ethyl acetate (90:10 to
75:25) yielded a mixture of (E)-13e and (Z)-13e (0.090 g, 65%, purity
pound
7 (0.190 g, 0.988 mmol) and 4-tert-butylcyclohexanone (8b)
(0.139 g, 0.901 mmol) were treated with SmI2 and HMPA according to
the general procedure. Chromatography on silica gel with n-hexane/ethyl
acetate (90:10 to 70:30) yielded 9b (0.140 g, 45%, E:Z>97:3, dr>97:3)
as a pale yellow oil and trans-4-tert-butylcyclohexanol (0.027 g, 19%, dr>
97:3) as a colourless oil. 1H NMR data of trans-4-tert-butylcyclohexanol
are in accordance with literature data.[40] 9b: 1H NMR (500 MHz,
CDCl3): d=7.39–7.18 (m, 10H; Ph), 7.01 (s, 1H; 2’-H), 3.85 (s, 2H;
CH2Ph), 2.36–2.33, 1.67–1.65, 1.55–1.50, 1.20–1.13 (4m, 2H, 2H, 3H, 3H;
2-H, 3-H, 4-H, 5-H, 6-H, OH), 0.87 ppm (s, 9H; C(CH3)3); 13C NMR
(126 MHz, CDCl3): d=141.2, 140.1, 137.7 (3s, Ph, C-1’), 130.2, 128.6,
128.6, 128.4, 128.3, 126.8 (6d, Ph), 126.0 (d, C-2’), 75.7 (s, C-1), 47.4 (d,
C-4), 37.5, 24.7 (2t, C-2, C-3, C-4, C-5), 33.5 (t, CH2Ph), 32.2, 27.5 ppm
according to 1H NMR spectroscopy >95%, E:Z 65:35) as a colourless
ꢁ1
ꢁ
ꢁ
ꢁ
oil. IR (film): n˜ =3400 (O H), 3060–2835 (=C H, C H), 1670–1655 cm
(C=C); MS (EI, 408C): m/z (%): 142 (17) [M +], 71 (100) [C4H7O+];
HRMS: m/z: calcd for C8H14O2: 142.0994; found: 142.0984.
1-[(E)/(Z)-3-Methoxyprop-2-enyl]cyclohexan-1-ol (13 f): Cyclohexanone
(8 f) (0.098 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) were treated with
SmI2 and HMPA under the described conditions. Chromatography on
aluminium oxide (activity III) using n-hexane/ethyl acetate (90:10 to
75:25) afforded a mixture of (E)-13 f and (Z)-13 f[41] (0.134 g, 79%, E:Z
ꢁ
ꢁ
(s, q, C(CH3)3); IR (film): n˜ =3385 (O H), 3080–3025 (=C H), 2950–
ꢁ1
ꢁ
ꢁ
60:40) as a colourless oil. IR (film): n˜ =3435 (O H), 3060–3040 (=C H),
ꢁ
2865 (C H), 1600–1495 cm (C=C); MS (EI, 408C): m/z (%): 348 (4)
ꢁ1
[M +], 257 (100) [M +ꢁC7H7]; HRMS: m/z: calcd for C25H32O: 348.2453;
ꢁ
3000–2855 (C H), 1665–1655 cm (C=C); MS (EI, 308C): m/z (%): 170
(2) [M +], 72 (100) [C4H8O+]; HRMS: m/z: calcd for C10H18O2: 170.1307;
found: 348.2462.
found: 170.1315.
(3E)-3-Benzyl-2-methyl-4-phenylbut-3-en-2-ol (9c): Acetone 8c (0.026 g,
0.45 mmol) and 7 (0.110 g, 0.572 mmol) were treated with SmI2 and
HMPA under the described conditions. Chromatography on silica gel
with n-hexane/ethyl acetate (95:5) afforded 9c (0.035 g, 31%, E:Z>97:3)
as a colourless oil. 1H NMR (500 MHz, CDCl3): d=7.31–7.18 (m, 10H;
Ph), 6.98 (s, 1H; 4-H), 3.81 (s, 2H; CH2Ph), 1.39 ppm (s, 6H; 1-H, 2-
CH3); OH signal not observed; 13C NMR (126 MHz, CDCl3): d=146.4,
140.6, 137.8 (3s, C-3, Ph), 128.8, 128.7, 128.5, 128.5, 126.9, 126.2 (6d, Ph),
126.8 (d, C-4), 74.8 (s, C-2), 34.4 (t, CH2Ph), 30.8 ppm (q, C-1, 2-CH3);
1-[(E)/(Z)-3-Methoxyprop-2-enyl]cycloheptan-1-ol (13g) and 7-(methox-
ymethyl)bicyclo[4.2.1]nonan-1-ol (20g): Cycloheptanone (8g) (0.112 g,
1.00 mmol) and 12 (0.140 g, 2.00 mmol) were treated with SmI2 and
HMPA according to the general procedure. Chromatography on alumini-
um oxide (activity III) using n-hexane/ethyl acetate (90:10 to 75:25 to
50:50) resulted in a mixture of (E)-13g and (Z)-13g (0.054 g, 29%, E:Z
60:40) and 20g (0.062 g, 34%, dr>97:3) as colourless oils. 13g: IR (film):
ꢁ1
ꢁ
ꢁ
ꢁ
n˜ =3435 (O H), 3060–3040 (=C H), 2995–2855 (C H), 1655 cm (C=
C); MS (EI, 308C): m/z (%): 184 (1) [M +], 72 (100) [C4H8O+]; HRMS:
m/z: calcd for C11H20O2: 184.1463; found 184.1483; elemental analysis
calcd (%) for C11H20O2 (184.3): C 71.70, H 10.94; found C 71.37, H 10.48.
20g: 1H NMR (500 MHz, CDCl3): d=3.30 (s, 3H; OCH3), AB part of
ꢁ
ꢁ
ꢁ
IR (film): n˜ =3400 (O H), 3080–3025 (=C H), 2975–2855 (C H), 1600–
1495 cmꢁ1 (C=C); MS (EI, 408C): m/z (%): 252 (54) [M +], 161 (100)
[M +ꢁC7H7]; HRMS: m/z: calcd for C18H20O: 252.1514; found: 252.1533.
(1E)- and (1Z)-2-Benzyl-1-phenylnon-1-en-3-ol (9d): The reaction was
carried out according to the general procedure by using 7 (0.104 g,
0.541 mmol) and heptanal (8d) (0.055 g, 0.48 mmol). Chromatography on
silica gel with n-hexane/ethyl acetate (100:0 to 95:5) afforded 9d
2
3
3
ABX system (dA =3.24, dB =3.19, JAB =8.9, JAX =7.5, JBX =6.5 Hz, each
1H; 7-CH2O), 2.07–2.04, 1.96–1.86, 1.83–1.75, 1.73–1.52, 1.48–1.32 ppm
(5m, 1H, 2H, 3H, 5H, 4H; 2-H, 3-H, 4-H, 5-H, 6-H, 7-H, 8-H, 9-H,
OH); 13C NMR (126 MHz, CDCl3): d=82.3 (s, C-1), 78.4 (t, 7-CH2O),
58.6 (q, OCH3), 46.5 (d, C-6), 37.6 (d, C-7), 43.8, 43.6, 41.2, 34.2, 24.9,
(0.031 g, 21%, E:Z 80:20) as
CDCl3): E isomer: d=7.38–7.16 (m, 10H; Ph), 6.84 (s, 1H; 1-H), 4.15
a
colourless oil. 1H NMR (500 MHz,
3
2
ꢁ
23.0 ppm (6t, C-2, C-3, C-4, C-5, C-8, C-9); IR (film): n˜ =3395 (O H),
(dd, J=4.5, 7.4 Hz, 1H; 3-H), 3.86 (d, J=15.5 Hz, 1H; CH2Ph), 3.57 (d,
2J=15.7 Hz, 1H; CH2Ph), 1.70–1.20 (m, 11H; 4-H, 5-H, 6-H, 7-H, 8-H,
OH), 0.88 ppm (t, 3J=6.9 Hz, 3H; 9-H); Z isomer: d=7.38–7.16 (m,
2920–2735 cmꢁ1 (C H); MS (EI, 60–808C): m/z (%): 184 (3) [M +], 111
ꢁ
(100); HRMS: m/z: calcd for C11H20O2: 184.1463; found 184.1473.
3
10H; Ph), 6.24 (s, 1H; 1-H), 4.72 (dd, J=5.6, 8.2 Hz, 1H; 3-H), AB part
cis- and trans-1-[(E)/(Z)-3-Methoxyprop-2-enyl]-2-methylcyclohexan-1-ol
(cis- and trans-13h): Allene 12 (0.210 g, 3.00 mmol) and 2-methylcyclo-
hexanone (8h) (0.112 g, 1.00 mmol) were treated with SmI2 and HMPA
of ABX system (dA =3.65, dB =3.53, 2JAB =15.7, 4JAX =1.1 Hz, each 1H;
CH2Ph), 1.70–1.20 (m, 11H; 4-H, 5-H, 6-H, 7-H, 8-H, OH), 0.88 ppm (t,
Chem. Eur. J. 2004, 10, 5493 – 5506
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5501

H.-U. Reißig and A. Hölemann
FULL PAPER
Table 6. 1H NMR data (500 MHz, CDCl3) of enol ethers 13.
ꢁ
ꢁ
ꢁ
Enol
ether
CH2CH=CHOMe
d [ppm] (td, J [Hz])
CH2CH=CHOMe
d [ppm] (td, J [Hz])
OMe
d [ppm]
CH2CH=CHOMe
d [ppm] (dd, J [Hz])
Other signals
d [ppm] (J [Hz])
(s)
(E)-13a
(Z)-13a
(E)-13e
(Z)-13e
(E)-13 f
(Z)-13 f
(E)-13g
(Z)-13g
cis-(E)-13h
6.38
4.78
3.55
3.60
3.52
3.57
3.54
3.59
3.55
3.59
3.54
2.19
1.85–1.76, 1.67–1.53 (2m, 3H, 6H; 2-H, 3-H, 4-H,
5-H, OH)
1.85–1.76, 1.67–1.53 (2m, 3H, 6H; 2-H, 3-H, 4-H,
5-H, OH)
3
3
(4J=1.1, J=12.6)
(3J=7.8, 12.6)
4.48
(4J=1.1, J=7.8)
6.06
2.36
(4J=1.3, J=6.3)
(3J=7.7, 6.3)
4.72
(4J=1.3, J=7.7)
3
3
6.38[a]
2.19
2.05–1.96, 1.74–1.64, 1.53–1.42 (3m, 2H, 2H, 2H;
(3J=12.6)
6.06
(3J=7.6, 12.6)
4.44
(3J=7.6)[a]
2.37
2-H, 3-H, 4-H)[b]
2.05–1.96, 1.74–1.64, 1.53–1.42 (3m, 2H, 2H, 2H;
2-H, 3-H, 4-H)[b]
1.65 (brs, 1H; OH), 1.61–1.33, 1.28–1.20 (2m, 9H,
1H; 2-H, 3-H, 4-H, 5-H, 6-H)
1.69 (brs, 1H; OH), 1.61–1.33, 1.28–1.20 (2m, 9H,
1H; 2-H, 3-H, 4-H, 5-H, 6-H)
1.69–1.35 (m, 13H; 2-H, 3-H, 4-H, 5-H, 6-H,
7-H, OH)
(4J=1.2, J=6.3)
(3J=7.6, 6.3)
4.76
(4J=1.2, J=7.6)
3
3
6.32
2.05
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
4.45
(4J=1.2, J=7.8)
3
3
6.06
2.23
(4J=1.3, J=6.3)
(3J=7.9, 6.3)
4.76
(4J=1.3, J=7.9)
3
3
6.33
2.07
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
4.46
(4J=1.2, J=7.9)
3
3
6.06
2.24
1.69–1.35 (m, 13H; 2-H, 3-H, 4-H, 5-H, 6-H,
7-H, OH)
(4J=1.3, J=6.3)
(3J=7.8, 6.3)
4.71
(4J=1.3, J=7.8)
3
3
6.30
2.11, 2.08[c,d]
1.68–1.16 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
(2JAB =13.8, JAX
/
0.89 (d, J=6.5, 3H; 2-CH3)
3
3
3
J
BX =7.9,
4JAY/JBY =1.2)
cis-(Z)-13h
6.01
4.39[d]
3.59
2.37[d]
1.68–1.16 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
0.91 (d, J=6.6, 3H; 2-CH3)
(4J=1.3, J=6.3)
(3J=6.3, 7.6, 8.1)
(4J=1.3, J=7.6,
3
3
3
2J=14.1)
2.17[d] (4J=1.3,
3J=8.1, J=14.1)
2
trans-(E)-13h
trans-(Z)-13h
(E)-13i
6.34
4.74
3.55
3.59
3.53
3.57
3.55
3.59
2.10, 2.01[c,d]
1.78–1.16 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
0.93 (d, J=7.0, 3H, 2-CH3)
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
(2JAB =14.3, JAX
/
3
3
3
4
J
BX =7.9, JAY =1.2)
6.07
4.45
2.26, 2.18[c,d]
1.78–1.16 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
(4J=1.4, J=6.3)
(3J=7.8, 6.3)
(2JAB =14.5, JAX
/
0.94 (d, J=7.0, 3H, 2-CH3)
3
3
3
4
J
BX =7.8, JAY =1.4)
6.31[a]
4.70
2.16, 2.09[c,d]
1.80–0.99 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
0.82 (s, 9H; C(CH3)3)
(3J=12.6)
(3J=7.8, 12.6)
(2JAB =14.4, JAX
/
3
4
J
BX =7.9, JAY =0.9)
(Z)-13i
6.05
4.41
2.32, 2.26[c,d]
1.80–0.99 (m, 10H; 2-H, 3-H, 4-H, 5-H, 6-H, OH),
0.81 (s, 9H; C(CH3)3)
(4J=1.2, J=6.3)
(3J=7.9, 6.3)
(2JAB =14.5, JAX
/
3
3
4
J
BX =7.9, JAY =0.9)
(E)-13b
6.34
4.74
2.14
1.61 (brs, 1H; OH), 1.81–1.75, 1.70–1.66, 1.42–1.34,
1.13–1.02 (4m, 2H, 2H, 2H, 3H; 2-H, 3-H, 4-H,
5-H, 6-H), 0.86 (s, 9H; C(CH3)3)
1.91 (brs, 1H; OH), 1.81–1.75, 1.70–1.66, 1.42–1.34,
1.13–1.02 (4m, 2H, 2H, 2H, 3H; 2-H, 3-H, 4-H,
5-H, 6-H), 0.86 (s, 9H; C(CH3)3)
3.92 (m, 4H; 2-H, 3-H), 1.91–1.84, 1.64–1.55 (2m,
2H, 6H; 6-H, 7-H, 9-H, 10-H), 1.41 (brs, 1H; OH)
3.92 (m, 4H; 2-H, 3-H), 1.91–1.84, 1.64–1.55 (2m,
2H, 6H; 6-H, 7-H, 9-H, 10-H), 1.69 (brs, 1H; OH)
3.79, 3.18 (m, 4H; 4H, 2-H, 6-H), 1.81, 1.78 (2brs,
1H, 1H; OH), 1.59–1.48 (m, 8H; 3-H, 5-H),
1.46, 1.45 (2s, 9H, 9H; C(CH3)3)[e]
(4J=1.1, J=12.6)
(3J=7.9, 12.6)
(4J=1.1, J=7.9)
3
3
(Z)-13b
6.08
4.45
2.31
(4J=1.3, J=6.3)
(3J=7.9, 6.3)
(4J=1.3, J=7.9)
3
3
(E)-13j
(Z)-13j
(E)-13k
6.31[a]
4.72
3.52
3.56
3.55
2.05
(3J=12.6)
6.05
(3J=7.9, 12.6)
4.42
(4J=1.1, J=7.9)
3
2.23
(4J=1.2, J=6.3)
(3J=8.0, 6.3)
4.73
(4J=1.2, J=8.0)
3
3
6.34[a]
2.07
(3J=12.6)
(3J=7.9, 12.6)
(4J=1.1, J=7.9)
3
(Z)-13k
(E)-13c
(Z)-13c
(E)-13l
6.08
4.43
3.60
3.55
3.59
3.55
2.24
3
3
(4J=1.2, J=6.2)
(3J=8.0, 6.2)
4.77
(4J=1.2, J=8.0)
6.32
2.07
1.53 (brs, 1H; OH), 1.20 (s, 6H; 1-H, 2-CH3)
1.75 (brs, 1H; OH), 1.21 (s, 6H; 1-H, 2-CH3)
1.69 (brs, 1H; OH), 1.53–1.44 (m, 2H; 2-H),
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
4.45
(4J=1.2, J=7.9)
3
3
6.04
2.25
(4J=1.3, J=6.3)
(3J=7.9, 6.3)
4.75
(4J=1.3, J=7.9)
3
3
6.33
2.07, 2.05[c,d]
(4J=1.2, J=12.6)
(3J=7.9, 12.6)
(2JAB =14.0, JAX
/
1.13 (s, 3H; 3-CH3), 0.91 (t, J=7.5, 3H; 1-H)
3
3
3
3JBX =7.9, JAY
/
4
J
BY =1.2)
(Z)-13l
6.04
4.43
3.59
3.52
2.25, 2.22[c,d]
1.75 (brs, 1H; OH), 1.53–1.44 (m, 2H; 2-H),
1.14 (s, 3H; 3-CH3), 0.91 (t, J=7.5, 3H; 1-H)
(4J=1.3, J=6.3)
(3J=7.8, 6.3)
(2JAB =14.2, JAX
/
3
3
3
3JBX =7.8, JAY
/
4
J
BY =1.3)
2.02
(4J=1.0, J=7.9)
(E)-13m
6.30
4.69
1.48–1.41 (m, 4H; CH2), 1.31 (brs, 1H; OH),
(4J=1.0, J=12.6)
(3J=7.9, 12.6)
0.85 (t, J=7.5, 6H; CH3)
3
3
3
5502
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 5493 – 5506

SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
Table 6. (Continued)
ꢁ
ꢁ
ꢁ
Enol
ether
CH2CH=CHOMe
d [ppm] (td, J [Hz])
CH2CH=CHOMe
d [ppm] (td, J [Hz])
OMe
d [ppm]
CH2CH=CHOMe
d [ppm] (dd, J [Hz])
Other signals
d [ppm] (J [Hz])
(s)
(Z)-13m
(E)-13n
6.01
4.38
3.57
2.19
1.60 (brs, 1H; OH), 1.48–1.41 (m, 4H; CH2),
0.85 (t, J=7.5, 6H; CH3)
3
3
3
(4J=1.3, J=6.3)
(3J=7.8, 6.3)
4.76
(4J=1.3, J=7.8)
6.33
3.55
2.11, 2.05[c,d]
1.75 (brs, 1H; OH), 1.76–1.60 (m, 1H; 2-H),
(4J=1.1, J=12.6)
(3J=7.8, 12.6)
(2JAB =14.1, JAX
/
1.06 (s, 3H; 3-CH3), 0.90, 0.90 (2d, J=6.8, each
3
3
3
3JBX =7.8, JBY =1.1)
3H;
4
1-H, 2-CH3)
1.76–1.60 (m, 1H; 2-H), 1.50 (brs, 1H; OH),
1.07 (s, 3H; 3-CH3), 0.94, 0.94 (2d, J=6.9, each
3H;
(Z)-13n
6.05
4.46
3.59
2.28, 2.23[c,d]
3
3
3
(4J=1.3, J=6.3)
(3J=7.8, 6.3)
(2JAB =14.3, JAX
/
4
3JBX =7.8, JBY =1.3)
1-H, 2-CH3)
[g]
(E)-13o[f]
(Z)-13o[f]
(E)-13p
6.27[a]
4.76
3.52
3.55
3.56
–
1.06, 1.05 (2s, each 3H; 3-CH3),
(3J=12.4)
6.03[a]
(3J=7.9, 12.4)
4.46
0.92, 0.91 (2s, each 9H; C(CH3)3)[e,b]
[g]
–
(3J=6.4)
6.37[a]
(3J=7.6, 6.4)
4.78
2.19–2.11[h]
7.31–7.28, 7.22–7.18 (2m, 2H, 3H; Ph),
2.80–2.65 (m, 2H; 1-H), 1.81–1.73 (m, 3H; 2-H,
OH),
(3J=12.6)
(3J=7.8, 12.6)
1.24 (s, 3H; 3-CH3)
7.29–7.25, 7.21–7.15 (2m, 2H, 3H; Ph), 2.75–2.65
(m, 2H; 1-H), 1.82–1.73 (m, 2H; 2-H),
(Z)-13p
(E)-13d
6.07
4.49
3.60
3.51
2.33, 2.29[c,d]
3
3
(4J=1.2, J=6.3)
(3J=7.9, 6.3)
(2JAB =14.1, JAX
/
3JBX =7.9,
4JAY/4JBY =1.2)
1.62 (brs, 1H; OH), 1.24 (s, 3H; 3-CH3)
3.52–3.47 (m, 1H; 4-H), 1.69 (d, J=3.7, 1H; OH),
1.45–1.23 (m, 10H; 5-H, 6-H, 7-H, 8-H, 9-H),
6.33[a]
4.68[d]
2.14[i]
3
(3J=12.6)
(3J=7.0, 8.2, 12.6)
(4J=1.2, J=4.2, 7.0,
3
2J=14.0),
3
1.95[i] (4J=0.7,
3J=7.7,
0.86 (t, J=6.9, 3H; 10-H)
2
8.2, J=14.0)
3
(Z)-13d
6.00
4.39
3.57
2.22–2.18[h]
3.61–3.56 (m, 1H; 4-H), 1.84 (d, J=4.0, 1H; OH),
(4J=1.3, J=6.3)
(3J=7.5, 6.3)
1.45–1.23 (m, 10H; 5-H, 6-H, 7-H, 8-H, 9-H),
3
3
0.86 (t, J=6.9, 3H; 10-H)
[a] Allylic coupling could not be detected. [b] The signal of the hydroxyl group was not observed. [c] AB part of ABXY system. [d] ddd. [e] The signals
could not be assigned to one of the isomers. [f] Mixture with 20o. These signals in the 1H NMR spectrum of the mixture can be assigned to compound
13o. [g] Signals are not observed. [h] Multiplet. [i] dddd.
according to the general procedure. Chromatography on aluminium
trans-4-(tert-Butyl)-1-[(E)/(Z)-3-methoxyprop-2-enyl]cyclohexan-1-ol
(13b): 4-tert-Butylcyclohexanone (8b) (0.463 g, 3.00 mmol) and 12
(0.630 g, 8.99 mmol) were treated with SmI2 and HMPA according to the
general procedure. The resulting crude oil was purified by column chro-
matography on aluminium oxide (activity III) using n-hexane/ethyl ace-
tate (90:10 to 70:30) to furnish 8b (0.188 g, 41%) and a mixture of (E)-
13b and (Z)-13b (0.397 g, 58%, E:Z 60:40, dr>97:3) as a colourless
oxide (activity III) with n-hexane/ethyl acetate (100:0 to 75:25) yielded
1
cis-13h (0.026 g, 14%, purity according to H NMR spectroscopy >90%,
E:Z 50:50) as a colourless oil and trans-13h (0.038 g, 21%, purity accord-
1
ing to H NMR spectroscopy >90%, E:Z 55:45) as a colourless oil.
3-tert-Butyl-1-[(E)/(Z)-3-methoxyprop-2-enyl]cyclohexan-1-ol (13i) and
5-tert-butyl-6-(methoxymethyl)bicyclo[3.2.1]octan-1-ol (20i): 3-tert-Butyl-
cyclohexanone (8i) (0.154 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) were
treated with SmI2 and HMPA under the described conditions. Chroma-
tography on silica gel using n-hexane/ethyl acetate (90:10 to 75:25, +1%
triethylamine) afforded a mixture of (E)-13i and (Z)-13i (0.066 g, 29%,
purity according to 1H NMR spectroscopy >70% E:Z 60:40) and 20i
(0.097 g, 43%, purity according to 1H NMR spectroscopy >80%, dr
ꢁ
ꢁ
solid. M.p. 49–508C; IR (KBr): n˜ =3410 (O H), 3060–3040 (=C H),
ꢁ1
ꢁ
2940–2865 (C H), 1655 cm (C=C); MS (EI, 308C): m/z (%): 226 (1)
[M +], 72 (100) [C4H8O+]; HRMS: m/z: calcd for C14H26O2: 226.1933;
found 226.1956; elemental analysis calcd (%) for C14H26O2 (226.4): C
74.29, H 11.58; found C 74.04, H 11.12.
8-[(E)/(Z)-3-Methoxyprop-2-enyl]-1,4-dioxaspiro[4.5]decan-8-ol
(13j):
The reaction was performed using 1,4-dioxaspiro[4.5]decan-8-one (8j)
(0.156 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) according to the general
procedure. Chromatography on aluminium oxide (activity III) using n-
hexane/ethyl acetate (85:15 to 70:30 to 50:50) yielded a mixture of (E)-
ꢁ
ꢁ
60:40) as colourless oils. 13i: IR (film): n˜ =3405 (O H), 3060–3040 (=C
ꢁ1
ꢁ
H), 2940–2865 (C H), 1665–1655 cm (C=C); MS (EI, 408C): m/z (%):
226 (1) [M +], 72 (100) [C4H8O+]; HRMS: m/z: calcd for C14H26O2:
226.1933; found: 226.1953. 20i: 1H NMR (500 MHz, CDCl3): isomer A:
d=3.72 (dd, 3J=3.8, 2J=8.0 Hz, 1H; 6-CH2O), 3.32 (s, 3H; OCH3), 3.23
(dd, 2J=8.0, 3J=10.4 Hz, 1H; 6-CH2O), 2.05–1.16 (m, 11H; 2-H, 3-H, 4-
H, 6-H, 7-H, 8-H, OH), 0.89 ppm (s, 9H; C(CH3)3); isomer B: d=3.53
(dd, 3J=4.1, 2J=9.1 Hz, 1H; 6-CH2O), 3.35 (dd, 2J=9.1, 3J=11.6 Hz,
1H; 6-CH2O), 3.29 (s, 3H; OCH3), 2.05–1.16 (m, 12H; 2-H, 3-H, 4-H, 6-
H, 7-H, 8-H, OH), 0.92 ppm (s, 9H; C(CH3)3); 13C NMR (126 MHz,
CDCl3): isomer A: d=86.2 (t, 6-CH2O), 58.8 ppm (s, OCH3); isomer B:
d=74.8 (t, 6-CH2O), 58.7 ppm (s, OCH3); because of the impurities the
13j and (Z)-13j (0.124 g, 54%, E:Z 55:45) as a colourless oil. IR (film):
ꢁ1
ꢁ
ꢁ
ꢁ
n˜ =3480 (O H), 3040–3020 (=C H), 2935–2885 (C H), 1655 cm (C=
C); MS (EI, 308C): m/z (%): 228 (3) [M +], 129 (100) [M +ꢁC5H7O2];
HRMS: m/z: calcd for C12H20O4: 228.1362; found 228.1383; elemental
analysis calcd (%) for C12H20O4 (228.3): C 63.14, H 8.83; found C 62.65,
H 8.56.
N-(tert-Butoxycarbonyl)-4-[(E)/(Z)-3-methoxyprop-2-enyl]piperidin-4-ol
(13k): Boc-protected piperidinone 8k (0.199 g, 1.00 mmol) and 12
(0.140 g, 2.00 mmol) were treated with SmI2 and HMPA under the descri-
bed conditions. Chromatography on aluminium oxide (activity III) using
n-hexane/ethyl acetate (70:30 to 50:50) gave N-tert-butoxycarbonylpiperi-
din-4-ol (0.023 g, 11%), a mixture of (E)-13k and (Z)-13k (0.137 g, 51%,
ꢁ
missing signals could not be assigned; IR (film): n˜ =3380 (O H), 2955–
2810 cmꢁ1 (C H); MS (EI, 408C): m/z (%): 226 (1) [M +], 153 (100) [M +
ꢁ
ꢁC4H9O]; HRMS: m/z: calcd for C14H24O [M +ꢁH2O]: 208.1827; found:
208.1834.
Chem. Eur. J. 2004, 10, 5493 – 5506
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5503

H.-U. Reißig and A. Hölemann
FULL PAPER
Table 7. 13C NMR data (500 MHz, CDCl3) of enol ethers 13.
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
Enol
CH2CH=
CHOMe
d [ppm] (d) d [ppm] (d) d [ppm] (s)
CH2CH=
CHOMe
HO CR3
OMe
CH2CH=
CHOMe
d [ppm] (t) d [ppm]
Other signals
ether
d [ppm] (q)
(E)-13a
(Z)-13a
(E)-13e
(Z)-13e
(E)-13 f
(Z)-13 f
(E)-13g
(Z)-13g
cis-(E)-13h
149.8
148.3
149.9
148.7
149.7
148.4
149.8
148.4
149.3
97.8
101.9
96.7
101.0
96.8
101.1
97.2
101.4
97.5
81.5
82.0
73.9
74.8
70.8
71.7
74.8
75.7
72.6
56.0
59.5
55.9
59.5
56.0
59.5
56.0
59.5
56.0
39.5
35.6
37.8
33.9
40.4
36.3
41.5
37.5
38.8
39.2, 39.1, 23.9 (3t, CH2)[a]
35.3, 35.0, 11.8 (3t, CH2)[a]
37.4, 37.2, 25.8, 25.8, 22.4, 22.2 (6t, CH2)[a]
40.9, 40.8, 29.8, 29.8, 22.4, 22.4 (6t, CH2)[a]
38.4, 37.9 (2d, C-2), 36.2, 36.2, 30.7, 30.6, 25.6, 25.6, 21.9, 21.7
(8t, CH2), 15.0, 14.9 (2q, 2-CH3)[a]
cis-(Z)-13h
trans-(E)-13h
147.9
149.5
101.6
96.5
73.4
73.3
59.5
56.0
35.1
32.4
40.9, 40.4 (2d, C-2), 36.2, 35.9, 31.0, 30.8, 24.1, 23.8, 23.2, 23.0
(8t, CH2), 15.2, 15.1 (2q, 2-CH3)[a]
trans-(Z)-13h
(E)-13i
(Z)-13i
148.4
149.7
148.6
149.8
101.0
96.6
101.1
96.7
74.3
73.7
71.7
71.4
59.5
56.1
59.6
56.0
28.6
35.5
32.3
34.8
[b]
[b]
(E)-13b
47.5 (d, C-4), 38.5, 38.2, 24.5, 24.3 (4t, C-2, C-3, C-5, C-6),
32.2, 27.6 (s, q, C(CH3)3)
(Z)-13b
148.6
101.1
72.5
59.5
31.1
47.6 (d, C-4), 38.5, 38.2, 24.5, 24.3 (4t, C-2, C-3, C-5, C-6),
36.1, 27.6 (s, q, C(CH3)3)
(E)-13j
(Z)-13j
(E)-13k
(Z)-13k
(E)-13c
(Z)-13c
(E)-13l
(Z)-13l
(E)-13m
(Z)-13m
(E)-13n
(Z)-13n
(E)-13p
105.1
148.7
150.2
148.8
149.8
149.3
149.7
148.3
149.6
148.2
149.6
148.3
149.8
96.5
100.7
95.8
99.9
97.7
101.8
97.4
101.5
97.2
101.4
97.2
101.4
97.1
69.7
70.8
56.1
59.5
56.9
59.5
56.1
59.5
56.0
59.5
56.1
59.5
56.0
59.5
56.0
40.6
36.5
41.0
36.8
41.9
38.1
39.5
35.7
36.7
33.0
37.9
34.2
40.3
108.9 (s, C-5), 64.2, 64.1 (2t, C-2, C-3)[c]
108.9 (s, C-5), 64.2, 64.1 (2t, C-2, C-3)[c]
154.8 (s, CO)[e]
[d]
–
–
[d]
154.8 (s, CO)[e]
28.8 (q, C-1, 2-CH3)
28.9 (q, C-1, 2-CH3)
33.9 (t, C-2), 25.8 (q, 3-CH3), 8.1 (q, C-1)
34.2 (t, C-2), 25.9 (q, 3-CH3), 8.3 (q, C-1)
30.8, 30.6 (2 t, CH2), 7.9, 7.8 (2q, CH3)[a]
70.2
71.0
72.2
73.1
74.0
75.0
74.0
75.0
71.9
36.4 (d, C-2), 22.4 (q, 3-CH3), 17.7, 17.6 (2q, C-1, 2-CH3)
36.8 (d, C-2), 22.5 (q, 3-CH3), 17.0, 16.9 (2q, C-1, 2-CH3)
142.5 (s, Ph), 128.3,[f] 125.7 (2d, Ph), 43.3 (t, C-2), 30.2
(t,C-1), 26.3 (q, 3-CH3)
(Z)-13p
148.5
101.2
72.9
59.6
36.3
142.8 (s, Ph), 128.3,[f] 125.6 (2d, Ph), 43.7 (t, C-2), 30.5
(t, C-1), 26.6 (q, 3-CH3)
(E)-13d
(Z)-13d
149.4
148.2
98.2
102.1
71.4
71.7
56.0
60.0
35.7
31.8
14.0 (q, C-10)[g]
14.0 (q, C-10)[g]
[a] The signals could not be assigned to one of the isomers. [b] Because of the impurities the missing signals could not be assigned. [c] The following sig-
nals could not be assigned to one of the isomers: d=34.6, 34.5, 30.6, 30.5 (4t, CH2). [d] The signals could not be assigned to one of the isomers: d=69.9,
68.9 (2s, C-4). [e] The following signals could not be assigned to one of the isomers: d=79.2, 79.1, 28.4, 28.4 (2s, 2q, C(CH3)3), 39.8 (brt, C-2, C-6), 36.5,
36.3 (2t, C-3, C-5). [f] Signal shows doubled intensity. [g] The following signals could not be assigned to one of the isomers: d=36.9, 36.5, 32.0, 31.8, 29.3,
29.3, 25.7, 25.6, 22.6 (9t, C-5, C-6, C-7, C-8, C-9).
E:Z 50:50) as a colourless oil and a mixture (0.053 g), which probably
afforded 13l (0.052 g, 36%, E:Z=60:40) as a colourless oil. IR (film):
ꢁ1
ꢁ
ꢁ
ꢁ
ꢁ
contains a bicyclic compound like 20g. 13k: IR (film): n˜ =3445 (O H),
n˜ =3425 (O H), 3060–3040 (=C H), 2955–2835 (C H), 1655 cm (C=
C); MS (EI, 308C): m/z (%): 144 (3) [M +], 72 (100) [C4H8O+]; HRMS:
m/z: calcd for C8H16O2: 144.1150; found 144.1173.
ꢁ1
ꢁ
ꢁ
3040–2830 (=C H, C H), 1695, 1670 cm (C=O, C=C); MS (EI, 808C):
m/z (%): 271 (4) [M +], 57 (100) [C4H9+]; HRMS: m/z: calcd for
C14H25NO4: 271.1784; found 271.1765; elemental analysis calcd (%) for
C14H25NO4 (271.4): C 61.97, H 9.29, N 5.16; found C 61.59, H 8.95, N
5.05.
(E)- and (Z)-3-Ethyl-6-methoxyhex-5-en-3-ol (13m): Diethylketone (8m)
(0.086 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) were treated with SmI2
and HMPA under the described conditions. Chromatography on alumini-
um oxide (activity III) using n-hexane/ethyl acetate (100:0 to 80:20) af-
forded a mixture of 13m (E:Z 55:45) and 1-ethyl-3-methoxymethylcyclo-
pentan-1-ol (20m) (dr>97:3) in a ratio of 85:15 (0.082 g, 52%, purity
(E)- and (Z)-5-Methoxy-2-methylpent-4-en-2-ol (13c): Acetone 8c
(0.058 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) were treated with SmI2
and HMPA according to the general procedure. Chromatography on alu-
minium oxide (activity III) using n-hexane/ethyl acetate (90:10 to 70:30)
yielded a mixture of (E)-13c and (Z)-13c (0.034 g, 26%, E:Z 65:35) as a
ꢁ
>90%) as a colourless oil. 13m: IR (film): n˜ =3460 (O H), 3060–3040
ꢁ1
ꢁ
ꢁ
(=C H), 2965–2830 (C H), 1665–1655 cm (C=C); MS (EI, 408C): m/z
(%): 158 (1) [M +], 72 (100) [C4H8O+]; HRMS: m/z: calcd for C9H18O2:
158.1307; found 158.1318. 20m: The following signals in the 1H NMR of
the mixture can be assigned to 20m: 1H NMR (500 MHz, CDCl3): d=
3.40 (s, 3H; OCH3), 3.39 (m, 2H; CH2OCH3), 3.07 (brs, 1H; OH),
ꢁ
ꢁ
ꢁ
yellow oil. IR (film): n˜ =3430 (O H), 2995–2915 (=C H, C H),
1655 cmꢁ1 (C=C); MS (EI, 308C): m/z (%): 130 (2) [M +], 59 (100)
[C3H7O+]; HRMS: m/z: calcd for C7H14O2: 130.0994; found 130.0986. An
elemental analysis could not be recorded due to the high volatility of the
compound.
3
0.99 ppm (t, J=7.5 Hz, 3H; CH3).
(E)- and (Z)-6-Methoxy-3-methylhex-5-en-3-ol (13l): The reaction was
carried out using 12 (0.140 g, 2.00 mmol) and butan-2-one (8l) (0.072 g,
1.00 mmol) according to the general procedure. Chromatography on alu-
minium oxide (activity III) with n-hexane/ethyl acetate (80:20 to 70:30)
(E)- and (Z)-6-Methoxy-2,3-dimethylhex-5-en-3-ol (13n) and 4-methoxy-
methyl-1,2-dimethylcyclopentan-1-ol (20n): The reaction was performed
according to the general procedure using 12 (0.140 g, 2.00 mmol) and 3-
methylbutan-2-one (8n) (0.086 g, 1.00 mmol). Chromatography on alumi-
5504
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 5493 – 5506

SmI2-Induced Carbonyl–Allene Couplings
5493 – 5506
nium oxide (activity III) with n-hexane/ethyl acetate (95:5 to 60:40) af-
forded a mixture of 13n (E:Z 55:45) and 20n (0.038 g, 24%, 13n:20n
afforded (E)-26 (0.044 g, 15%, purity >95%), 27 (0.061 g, 20%), 28
(0.024 g, 8%, dr>97:3) and (Z)-26 (0.036 g, 12%, dr>97:3) all as colour-
less solids. 27: m.p. 98–1008C; 1H NMR (500 MHz, CDCl3): d=6.34 (s,
1H; 3’-H), 5.84 (td, 3J=3.3, 10.2 Hz, 1H; 7’-H, 9’-H), 5.56 (td, 4J=2.1,
3J=10.2 Hz, 2H; 6’-H, 10’-H), 4.05 (s, 2H; 1’-H), 2.62 (m, 2H; 8’-H), 2.10
(s, 2H; 4’-CH2), 1.81–1.78, 1.63–1.60, 1.34–1.29, 1.06–0.99 (4m, 2H, 2H,
2H, 3H; 2-H, 3-H, 4-H, 5-H, 6-H), 1.77 (brs, 1H; OH), 0.82 ppm (s, 9H;
C(CH3)3); 13C NMR (126 MHz, CDCl3): d=142.8 (d, C-3’), 129.8 (d, C-6’,
C-10’), 125.4 (d, C-7’, C-9’), 116.2 (s, C-4’), 81.2 (t, C-1’), 71.7 (s, C-1),
50.4 (s, C-5’), 47.3 (d, C-4), 38.5, 24.5 (2t, C-2, C-3, C-5, C-6), 32.2, 27.5
(s, q, C(CH3)3), 30.3 (t, 4’-CH2), 26.0 ppm (t, C-8’); IR (film): n˜ =3340
ꢁ
85:15) as a colourless oil. 13n: IR (film): n˜ =3470 (O H), 3060–3040 (=
ꢁ1
ꢁ
ꢁ
C H), 2960–2830 (C H), 1655 cm (C=C); MS (EI, 308C): m/z (%): 158
(1) [M +], 72 (100) [C4H8O+]; HRMS: m/z: calcd for C9H18O2: 158.1307;
found 158.1322. The following signals in the 1H and 13C NMR spectra of
the mixture can be assigned to compound 20n: 1H NMR (500 MHz,
CDCl3): d=3.37 (s, 3H; OCH3), 3.32 (m, 2H; CH2OCH3), 3.11 (brs, 1H;
OH), 1.19 ppm (s, 3H; 1-CH3); 13C NMR (126 MHz, CDCl3): d=78.1 (s,
C-1), 76.3 (t, CH2OCH3), 58.9 (q, OCH3), 44.8, 35.0, 35.0 (2t, d, CH,
CH2), 24.4 (q, 1-CH3), 11.9 ppm (q, 2-CH3).
(O H), 3025–2815 (=C H, C H), 1660–1630 cmꢁ1 (C=C); MS (EI,
808C): m/z (%): 302 (1) [M +], 148 (100) [M +ꢁC10H18O]; HRMS: m/z:
calcd for C20H30O2: 302.2246; found 302.2240. 28: m.p. 117–1188C;
1H NMR (500 MHz, CDCl3): d=6.29 (s, 1H; 3’-H), 5.94 (dd, 3J=5.1,
9.6 Hz, 1H; 7’-H), 5.86–5.79, 5.74–5.67 (2m, each 1H; 8’-H, 9’-H), 5.51
(d, 3J=9.6 Hz, 1H; 6’-H), AB system (dA =4.06, dB =3.97, 2JAB =8.8 Hz,
each 1H; 1’-H), 2.55–2.46, 2.34–2.27 (2m, each 1H; 10’-H), 2.25 (s, 2H;
4’-CH2), 1.92–1.81, 1.67–1.60, 1.41–1.23, 1.07–0.97 (4m, 2H, 3H, 3H, 2H;
2-H, 3-H, 4-H, 5-H, 6-H, OH), 0.82 ppm (s, 9H; C(CH3)3); 13C NMR
(126 MHz, CDCl3): d=141.9 (d, C-3’), 130.7, 125.1, 124.5, 123.2 (4d, C-6’,
C-7’, C-8’, C-9’), 117.0 (s, C-4’), 80.9 (t, C-1’), 72.0 (s, C-1), 48.3 (s, C-5’),
47.4 (d, C-4), 39.5, 38.3, 24.6, 24.5 (4t, C-2, C-3, C-5, C-6), 33.8 (t, C-10’),
ꢁ
ꢁ
ꢁ
4-Methoxymethyl-1,2,2-trimethylcyclopentan-1-ol (20o) and (E)/(Z)-6-
methoxy-2,2,3-trimethylhex-5-en-3-ol (13o): Pinacolone (8o) (0.088 g,
1.00 mmol) and 12 (0.140 g, 2.00 mmol) were treated with SmI2 and
HMPA according to the general procedure. Chromatography on alumini-
um oxide (activity III) using n-hexane/ethyl acetate (90:10 to 70:30) gave
a mixture of 13o (E:Z 60:40) and 4-methoxymethyl-1,2,2-trimethylcyclo-
pentan-1-ol (20o) (dr>97:3) in a ratio of 20:80 (0.039 g, 26%) as a col-
ourless oil. 20o: 1H NMR (500 MHz, CDCl3): d=3.33 (s, 3H; OCH3),
3
AB part of ABX system (dA =3.29, dB =3.27, 2JAB =8.6, 3JAX =3.9, JBX
=
3.7 Hz, each 1H; 4-CH2), 3.05 (brs, 1H; OH), 2.31–2.23 (m, 1H; 4-H),
2.11 (dd, 3J=11.4, 2J=14.2 Hz, 1H; 5-H), 1.65 (dd, 3J=8.8, 2J=12.8 Hz,
3
2
3
2
1H; 3-H), 1.53 (dd, J=3.2, J=14.2 Hz, 1H; 5-H), 1.48 (dd, J=9.0, J=
12.8 Hz, 1H; 3-H), 1.08, 0.94, 0.83 ppm (3s, each 3H; 1-CH3, 2-CH3, 2-
CH3); 13C NMR (126 MHz, CDCl3): d=81.0 (s, C-1), 76.1 (t, 4-CH2), 58.9
(q, OCH3), 46.2 (s, C-2), 42.6 (t, C-5), 41.2 (t, C-3), 33.7 (d, C-4), 25.9,
ꢁ
30.5 (t, 4’-CH2), 32.2, 27.6 ppm (s, q, C(CH3)3); IR (film): n˜ =3340 (O
ꢁ1
ꢁ
ꢁ
H), 3050–2800 (=C H, C H), 1650 cm (C=C); MS (EI, 908C): m/z
(%): 302 (1) [M +], 148 (100) [M +ꢁC10H18O]; HRMS: m/z: calcd for
C20H28O [M +ꢁH2O]: 284.2140; found 284.2153. (E)-26: m.p. 64–658C;
1H NMR (500 MHz, CDCl3): d=7.38–7.28 (m, 5H; Ph), 6.36 (d, 2J=
12.6 Hz, 1H; 3’-H), 4.87 (td, 3J=7.9, 12.6 Hz, 1H; 2’-H), 4.77 (s, 2H;
OCH2), 2.13 (d, 3J=7.9 Hz, 2H; 1’-H), 1.73–1.62, 1.40–1.34, 1.10–0.98
(3m, 5H, 2H, 3H; 2-H, 3-H, 4-H, 5-H, 6-H, OH), 0.85 ppm (s, 9H;
C(CH3)3); 13C NMR (126 MHz, CDCl3): d=148.5 (d, C-3’), 137.0, 128.5,
127.9, 127.5 (s, 3d, Ph), 98.9 (d, C-2’), 71.4 (s, C-1), 71.2 (t, OCH2), 47.5
(d, C-4), 38.1, 24.2 (2t, C-2, C-3, C-5, C-6), 34.8 (t, C-1’), 32.2, 27.6 ppm
ꢁ
21.1, 20.4 ppm (3q, 1-CH3, 2-CH3, 2-CH3); IR (film): n˜ =3475 (O H),
2940–2870 cmꢁ1 (C H); MS (EI, 608C): m/z (%): 172 (6) [M +], 43 (100)
ꢁ
[C2H3O+]; HRMS: m/z: calcd for C10H20O2: 172.1463; found 172.1482.
(5E)- and (5Z)-6-Methoxy-3-methyl-1-phenylhex-5-en-3-ol (13p): 4-Phe-
nylbutan-2-one (8p) (0.148 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol)
were treated with SmI2 and HMPA under the described conditions. Chro-
matography on aluminium oxide (activity III) with n-hexane/ethyl ace-
tate (95:5 to 80:20) afforded an 85:15 mixture (0.137 g) of 13p (E:Z
85:15) and 4-phenylbutan-2-ol as a colourless oil. Separation using HPLC
[nucleosil 50-5, n-hexane/ethyl acetate (85:15), 128 mLminꢁ1, 112 bar]
yielded (Z)-13p (0.013 g, 6%) as a colourless oil and a mixture (0.094 g)
ꢁ
ꢁ
ꢁ
(s, q, C(CH3)3); IR (film): n˜ =3435 (O H), 3090–2865 (=C H, C H),
1670–1650 cmꢁ1 (C=C); MS (EI, 508C): m/z (%): 302 (1) [M +], 91 (100)
[C7H7+]; HRMS: m/z: calcd for C16H21O2 [M +ꢁC4H9]: 245.1541; found
245.1562. (Z)-26: m.p. 52–538C; 1H NMR (500 MHz, CDCl3): d=7.36–
7.28 (m, 5H; Ph), 6.23 (td, 4J=1.1, 3J=6.3 Hz, 1H; 3’-H), 4.80 (s, 2H;
OCH2), 4.51 (dt, 3J=7.8, 6.3 Hz, 1H; 2’-H), 2.36 (dd, 4J=1.1, 3J=7.8 Hz,
2H; 1’-H), 1.86 (brs, 1H; OH), 1.81–1.77, 1.65–1.62, 1.38–1.32, 1.15–1.06,
1.03–0.95 (5 m, 2H, 2H, 2H, 2H, 1H; 2-H, 3-H, 4-H, 5-H, 6-H),
0.83 ppm (s, 9H; C(CH3)3); 13C NMR (126 MHz, CDCl3): d=146.7 (d, C-
3’), 137.3, 128.5, 127.9, 127.4 (s, 3d, Ph), 101.9 (d, C-2’), 73.8 (t, OCH2),
72.6 (s, C-1), 47.5 (d, C-4), 38.5, 24.5 (2t, C-2, C-3, C-5, C-6), 31.3 (t, C-
of (E)-13p and 4-phenylbutan-2-ol in a ratio of 85:15. (Z)-13p: IR (film):
ꢁ1
ꢁ
ꢁ
ꢁ
n˜ =3450 (O H), 3085–2825 (=C H, C H), 1665–1495 cm (C=C); MS
(EI, 408C): m/z (%): 220 (2) [M +], 91 (100) [C7H7+]; HRMS: m/z: calcd
for C14H20O2: 220.1463; found: 220.1447. (E)-13p: IR (film): n˜ =3435
(O H), 3085–2835 (=C H, C H), 1670–1495 cmꢁ1 (C=C); MS (EI,
608C): m/z (%): 220 (1) [M +], 91 (100) [C7H7+]. The following signal
can be assigned to 4-phenylbutan-2-ol: d=3.82 ppm (m, 1H; 2-H).
ꢁ
ꢁ
ꢁ
ꢁ
1’), 32.2, 27.6 ppm (s, q, C(CH3)3); IR (film): n˜ =3330 (O H), 3090–2840
(E)- and (Z)-1-Methoxydec-1-en-4-ol (13d): The reaction was performed
with heptanal (8d) (0.114 g, 1.00 mmol) and 12 (0.140 g, 2.00 mmol) in
accordance with the general procedure. Chromatography on aluminium
oxide (activity III) using n-hexane/ethyl acetate (90:10 to 80:20) yielded
a mixture of (E)-13d and (Z)-13d (0.081 g, 43%, E:Z 55:45) as a colour-
ꢁ1
ꢁ
ꢁ
(=C H, C H), 1665 cm (C=C); MS (EI, 1008C): m/z (%): 302 (1)
[M +], 91 (100) [C7H7+]; HRMS: m/z: calcd for C20H30O2: 302.2246;
found 302.2262.
ꢁ
ꢁ
ꢁ
less oil. IR (film): n˜ =3440 (O H), 3040 (=C H), 2960–2830 (C H),
1655 cmꢁ1 (C=C); MS (EI, 308C): m/z (%): 186 (1) [M +], 101 (100) [M +
ꢁC5H9O2]; HRMS: m/z: calcd for C10H19O [M +ꢁOCH3]: 155.1436;
found 155.1453; elemental analysis calcd (%) for C11H22O2 (186.3): C
70.92, H 11.90; found C 70.94, H 11.65.
Acknowledgments
Generous support of this work from the Fonds der Chemischen Industrie
(KekulØ fellowship for A.H.), the Volkswagen-Stiftung, the Deutsche
Forschungsgemeinschaft, the Freie Universität Berlin and the Schering
AG is most gratefully acknowledged. We also thank Dr. R. Zimmer for
discussions and help during preparation of this manuscript.
1-(3-Methoxybut-2-enyl]cyclopentanol (24): Cyclopentanone (8a)
(0.084 g, 1.00 mmol) and 23 (0.126 g, 1.50 mmol) were treated with SmI2
and HMPA under the described conditions. Chromatography on alumini-
um oxide (activity III) using n-hexane/ethyl acetate (90:10 to 70:30) af-
forded 24 (0.031 g, 18%, purity >70%) as a colourless oil. 1H NMR
(270 MHz, CDCl3): d=4.40 (t, 3J=7.9 Hz, 1H; 2’-H), 3.47 (s, 3H;
OCH3), 2.22 (d, 3J=7.9 Hz, 2H; 1’-H), 1.87–1.50 (m, 9H; 2-H, 3-H, 4-H,
5-H, OH), 1.76 ppm (s, 3H; 4’-H).
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4-tert-Butyl-1-(2-oxaspiro[4.5]deca-3,6,9-trien-4-ylmethyl)cyclohexanol
(27), 4-tert-butyl-1-(2-oxaspiro[4.5]deca-3,6,8-trien-4-ylmethyl)cyclohexa-
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HPLC [nucleosil 50–5, n-hexane/isopropanol (98:2), 64 mLminꢁ1, 65 bar]
Chem. Eur. J. 2004, 10, 5493 – 5506
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5505

H.-U. Reißig and A. Hölemann
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Received: April 29, 2004
Published online: September 16, 2004
1
the ratio in H NMR spectra.
5506
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 5493 – 5506