Use of allyl, 2-tetrahydrofuryl, and 2-tetrahydropyranyl ethers as useful C3-, C4-, and C5-carbon sources: Palladium-catalyzed allylation of aldehydes

Article abstract of DOI:10.1002/chem.200500450

Palladium-diethylzinc or palladium-triethylborane catalytically promotes self-allylation of 2-(allyloxy)tetrahydrofurans, 2-(allyloxy)tetrahydropyrans, and their hydroxy derivatives on the rings (ribose, glucose, mannose, deoxyribose, deoxyglucose). All the reactions proceed at room temperature and provide polyhydroxyl products, sharing a structural motif of a homoallyl alcohol, in good to excellent yields with high levels of stereoselectivity. Useful Crunit elongation, which makes the best use of an allyl ether as a protecting group and a nucleophilic allylation agent, is demonstrated. Mechanisms for the umpolung reaction (of an allyl ether into an allylic anion) and stereoselectivity associated with allylation of aldehydes are discussed.

Full text of DOI:10.1002/chem.200500450

FULL PAPER
DOI: 10.1002/chem.200500450
Use of Allyl, 2-Tetrahydrofuryl, and 2-Tetrahydropyranyl Ethers as Useful
C3-, C4-, and C5-Carbon Sources: Palladium-Catalyzed Allylation of
Aldehydes
Masamichi Shimizu,[a] Masanari Kimura,[a] and Yoshinao Tamaru*[b]
Abstract: Palladium–diethylzinc or pal-
ladium–triethylborane catalytically pro-
motes self-allylation of 2-(allyloxy)te-
trahydrofurans, 2-(allyloxy)tetrahydro-
pyrans, and their hydroxy derivatives
on the rings (ribose, glucose, mannose,
deoxyribose, deoxyglucose). All the re-
actions proceed at roomtemperature
and provide polyhydroxyl products,
sharing a structural motif of a homoall-
yl alcohol, in good to excellent yields
with high levels of stereoselectivity.
Useful C3-unit elongation, which
makes the best use of an allyl ether as
a protecting group and a nucleophilic
allylation agent, is demonstrated.
Mechanisms for the umpolung reaction
(of an allyl ether into an allylic anion)
and stereoselectivity associated with al-
lylation of aldehydes are discussed.
Keywords:
allyl
compounds
allylation · asymmetric catalysis ·
palladium
Introduction
to render a hydroxy group a better leaving group, but also
as a reducing agent in the latter process, converting a cation-
ic p-allylpalladiumspecies into an anionic allylzinc species
and Pd0 (Umpolung).[4]
2-Tetrahydrofuryl (2-THF) and 2-tetrahydropyranyl (2-
THP) ethers[1] as well as allyl ethers[1,2] have been utilized
most widely as the useful protecting groups of a hydroxy
functionality. They are usually removed after the expected
transformations having been completed. Needless to say,
from practical, economical, and environmental view points,
it is beneficial if they could be utilized not only as protecting
groups, but also as carbon sources of target molecules.
Recently, we and others have developed efficient methods
that enable the direct use of allyl alcohols as allyl anion
equivalents under the catalysis of palladium.[3] The method
which uses a Pd/Et2Zn reaction systemrelies on the ability
of a palladium(0) species to undergo oxidative addition to
The same method has been successfully applied to the ac-
tivation of allyl ethers as allyl anion equivalents [Eq. (1)].[5]
Thus, the combination of a catalytic amount of Pd(OAc)2
and a stoichiometric amount of Et2Zn has nicely promoted
the conversion of 2-(allyloxy)tetrahydropyrans (1) and 2-(al-
lyloxy)tetrahydrofurans (3) into 7-octen-1,5-diols (2) and 6-
hepten-1,4-diols (4), respectively. Thus, the catalytic system
has enabled allyl, 2-tetrahydrofuryl and 2-tetrahydropyranyl
ethers to serve as C3-, C4-, and C5-carbon sources, respec-
tively. During this process, allyl ethers 1 or 3 might split into
two fragments: allylzincs and w-hydroxyaldehydes, which
combine to give 2 or 4, respectively.
ꢀ
the C O bond of an allyl alcohol and also the capability of
a p-allylpalladiumspecies, thus formed, to undergo transme-
tallation with Et2Zn giving rise to an allylzinc species. Dieth-
ylzinc serves not only as a Lewis acid in the former process
[a] Dr. M. Shimizu, Dr. M. Kimura
Graduate School of Science and Technology
Nagasaki University, 1-14 Bunkyo
Nagasaki 852-8521 (Japan)
[b] Prof. Y. Tamaru
This paper is a full account of our preliminary communi-
cation[5] and discloses a full scope of the reactivity, regiose-
lectivity, and stereoselectivity associated with the unique
self-allylation of 1 and 3 catalyzed by Pd/Et2Zn. The method
has been extended to 2-(allyloxy)-THF (6, 12 and 14) and 2-
Department of Applied Chemistry, Faculty of Engineering
Nagasaki University, 1-14 Bunkyo
Nagasaki 852-8521 (Japan)
Fax : (+81)95-819-2677
E-mail: tamaru@net.nagasaki-ac.jp
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(allyloxy)-THP derivatives (8 and 10) bearing hydroxy sub-
stituents on their five- and six-membered skeletons. A new
useful synthetic method that utilizes allyl alcohols both as
protecting groups and as allylating agents is demonstrated.
Some characteristic features of the catalytic self-allylation
promoted by Pd/Et3B, instead of Pd/Et2Zn, are also dis-
cussed.
[Eq. (2)], behave differently fromordinary enolizable ali-
phatic aldehydes and selectively undergo C1 allylation.
Results and Discussion
Table 2 outlines the scope of self-allylation of 1 and 3 under
Pd/Et3B catalysis, the conditions being identical to those ap-
plied in run 2, Table 1. Notably, all the reactions were clean
and provided diols 2 and 4 in good yields. Neither aldol con-
densation products nor Ca-allylation products were detected
at all.
The success of the self-allylation of 1 and 3 may be pri-
marily attributed to a unique mechanism that the reaction
follows. Under ordinary C1-allylation conditions, for exam-
ple, Table 1, an aldehyde is exposed to reagents all the time
and is susceptible to not only C1 allylation, but also Ca ally-
lation (and aldol and other reactions as well via enolization).
On the other hand, according to the mechanism shown in
Equation (2), the generation of w-hydroxyaldehyde synchro-
nizes with the generation of allylborane. This electrophile–
nucleophile pair might be generated in a small quantity
(never larger than the amount of the catalyst), and each
component would be present in close proximity to each
other so as to react as soon as formed.
In Scheme 1 is illustrated a plausible catalytic cycle for
the generation of allylborane and w-hydroxyaldehyde. A
palladium(0) species undergoes oxidative addition upon the
allyl–oxygen ether bond activated by coordination with
Et3B. A p-allyl–palladium species, thus formed, might under-
go allyl–ethyl exchange with BEt3 to give an ethyl–palladi-
umspecies, which undergoes b-H elimination regenerating a
palladium(0) species. During the final step are also formed
ethylene and an allyl(diethyl)borane–w-hydroxyaldehyde
complex, an active species for the self-allylation [Eq. (2)].
For the present self-allylation, both Ph3P and nBu3P work
with similar efficiency. For example, by the use of Ph3P in-
stead of nBu3P, 2a was obtained in 80% yield (258C, 30 h,
c.f., run 1, Table 2). For clarity, Table 2 lists only the results
obtained by the use of nBu3P.
Self-allylation of 2-(allyloxy)tetrahydropyrans (1) and 2-(al-
lyloxy)tetrahydrofurans (3) promoted by Pd0/Et2Zn or Pd0/
Et3B: In the past few years, Et2Zn and Et3B, which are
themselves feeble nucleophiles toward addition reaction to
carbonyl compounds, have been recognized to play unique
ꢀ
roles in the transition-metal catalyzed C C bond formation
reactions between carbonyl compounds and non-activated
alkenes and alkynes. For example, under nickel catalysis,[6]
Et2Zn and Et3B serve as a formal hydride donor or an alkyl
donor and activate dienes and alkynes as nucleophiles to
add to carbonyl compounds[7] and epoxides.[8]
Under palladiumcatalysis, Et Zn promotes allyl alcohols
2
to undergo nucleophilic allylation of a wide range of carbon-
yl compounds, encompassing aromatic and aliphatic alde-
hydes as well as the less reactive ketones. On the other
hand, Et3B is only capable of promoting the allylation of ar-
omatic aldehydes;[9] with this promoter, enolizable aliphatic
aldehydes undergo both nucleophilic allylation at the car-
bonyl carbon (C1 allylation) and electrophilic allylation at
the a-position of carbonyl groups (Ca allylation).[10] For ex-
ample, as illustrated in Table 1, the reaction of cyclohexane-
carboxaldehyde and cinnamyl alcohol provides a mixture of
1-cyclohexyl-2-phenyl-3-buten-1-ol (C1 allylation) and 1-
(trans-cinnamyl)cyclohexanecarboxaldehyde (Ca allylation)
in comparable amounts. The product distributions change
dramatically depending on additives and the kinds of phos-
phane ligands (Table 1). Selective a-allylation of aliphatic al-
dehydes has been achieved in the presence of additives,
LiCl/Et3N.[10]
Interestingly, in sharp contrast to these, under the cataly-
sis of Pd0/Et3B, 5-hydroxypentanal and 4-hydroxybutanal,
aliphatic aldehydes derived from 1 and 3, respectively
Table 2 also compiles the results obtained using Et2Zn as
a promoter. As was mentioned in our original paper,[5] the
reaction medium optimized is rather unique, which consists
of non-polar solvents: toluene (0.5–5.0 mL) and n-hexane
(3.6 mL, the solvent of Et2Zn) for 1 mmol scale experiments.
In general, there seemed to be a general trend that the
lower the polarity of the solvents, the better the yields of 2
or 4 (see below). Accordingly, the amount of toluene was
minimized so as to make the reaction mixture homogeneous
at the start at 08C. The progress of the reaction is indicated
visually by the increasing amount of white copious precipi-
tate due to zinc alkoxides (see Experimental Section).
Generally, Et2Zn promotes the allylation much faster and
provides 2 or 4 in better yields within shorter periods of re-
Table 1. Allylation of cyclohexanecarboxaldehyde with cinnamyl alcohol
promoted by Pd/Et3B catalytic system.
Phosphane
t [h]
C1 allylation (%)
Ca allylation (%)
1
2
Ph3P (20 mol%)
nBu3P (20 mol%)
4
23
39
21
30
51
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Allylation of Aldehydes
FULL PAPER
Table 2. Pd-catalyzed self-allylation of 2-(allyloxy)tetrahydropyrans 1 and 2-(allyloxy)tetrahydrofurans 3 promoted by Et3B or Et2Zn.
Run
1 or 3
Product
Et3B[a]
Et2Zn[b]
t [h]
Yield [anti,syn] (%)
t [h]
Yield [anti,syn] (%)
1
22
86
2
86
2
3
48
23
82 [4:1]
67 [4:1]
1
1
94 [2:1]
94 [2:1]
4
5
6
60[c]
48
74 [6:1]
66 [6:1]
73
3
2
3
90 [3:1]
85 [3:1]
72
31
7
16
56
2
87
8
43
83 [5:1]
71 [5:1]
70 [17:1]
67 [5:1]
1
1
2
2
78 [1:1]
68 [1:1]
70 [4:1]
87 [3:1]
9
34
10
11
32[c]
27
[a] 1 or 3 (1 mmol), Pd(OAc)2 (10 mol%), nBu3P (20 mol%), and Et3B (2.4 mmol, 1m in hexane) in dry THF (5 mL) at 258C under N2. [b] 1 or 3
(1 mmol), Pd(OAc)2 (10 mol%), nBu3P (40 mol%), and Et2Zn (3.6 mmol, 1m in hexane) in dry toluene (5 mL) at 258C under N2. [c] At 508C.
nents (TLC monitoring). Except for 1k (and 3i), these sub-
strates share a common structural feature bearing two sub-
stituents on the allyl ether skeleton. Judging fromthe reac-
tion times (Tables 2 and 3), these substituents significantly
slow down the reaction.
The self-allylation of 1g (run 1, Table 3) offers typical ex-
amples of the solvent polarity effects on the yields and reac-
tion times: THF (5 mL), hexane (3.6 mL), 34%, 64 h; tolu-
ene (5 mL), hexane (3.6 mL), 63%, 60 h; toluene (2 mL),
hexane (3.6 mL), 80%, 48 h; toluene (0.2 mL), hexane
(3.6 mL), 89%, 34 h.
Scheme 1. Plausible catalytic cycle for the generation of allylborane spe-
cies.
It is apparent, through Tables 2 and 3, that the allylation
action time than Et3B does. On the other hand, the reactions
promoted by Et3B have an advantage; they generally pro-
vide anti-diastereomers, that is anti-2 and anti-4, in much
higher selectivities.
In Table 3 the reactions are summarized using Et2Zn as a
promoter. Under the catalysis of Pd/Et3B, all the substrates
listed in this table did not react in an expected way and
either remained intact or provided, under forcing conditions,
intractable mixtures only including 2 or 4 as minor compo-
takes place regioselectively providing the most branched iso-
mers exclusively, irrespective of the substitution patterns of
the starting materials. For example, a-methylallyl ether 1b
(run 2, Table 2) and g-methylallyl ether 1c (run 3) provide
the same branched product 2b. Similar regioselectivities are
also observed in many examples listed in Table 3.
In almost all cases, the stereoselectivity is also independ-
ent to the substitution pattern of the starting materials. Only
one exception was observed for a pair of reactions of runs
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Y. Tamaru et al.
Table 3. Pd-catalyzed self-allylation of 1 and 3 bearing allyl ether groups of some structural complexity.[a]
ty, but provided the allylation
product 2c in the same selec-
tivity as 1e did under the Pd/
Et3B catalysis.
Run
1 or 3[b]
Product
t [h]
Yield (%)[c]
1
34
89 [2:1:2][d,e]
In a previous paper, we have
demonstrated that under Pd/
Et2Zn umpolung conditions,
trans-3-buten-2-yl benzoate[4b]
reacts with benzaldehydes and
provides one of the four possi-
ble diastereomers, (Z),anti-5a,
2
3
17
4
78 [2:1][d]
90 [12:1]
in
excellent
selectivity
(Table 4). Furthermore, the
benzoate even reacts with an
aliphatic aldehyde, providing
(Z),anti-5b with high stereose-
lectivity. In the light of these
precedents, the poor stereose-
lectivity observed for the self-
allylation of 1g is quite unex-
pected (run 1, Table 3).
In order to address the un-
usual stereoselectivity, we ex-
amined the reaction of 1g with
three equivalents of benzalde-
hyde and found that 1g also
furnished (Z),anti-5a exclu-
sively (Table 4). Similar results,
with somewhat lower stereose-
lectivity, are obtained for the
reaction with an aliphatic alde-
hyde.
4
5
9
1
73
92
7
27
17
5
80 [2:1:1][d,f]
90 [2:1][d]
98 [5:1]
82
8
9
10
1
[a] 1 or 3 (1 mmol), Pd(OAc)2 (10 mol%), nBu3P (40 mol%), and Et2Zn (3.6 mmol, 1m in hexane) in dry tolu-
ene (0.5 mL) at 258C under N2. [b] P and F stand for 2-tetrahydropyranyl and 2-tetrahydrofuryl groups, re-
spectively. [c] Isolated yields of spectroscopically homogeneous materials. Ratios of diastereomers in brackets
were determined on the basis of 1H NMR spectra (400 MHz). [d] The stereochemistry around C5–C6 (for 2)
or C4–C5 (for 4) are unknown. [e] (E)-2e/(E)-2e’/(Z)-2e. [f] (E)-4d/(E)-4d’/(Z)-4d.
The results observed in
Table 4 clearly indicate that 1)
1g shows better performance
10 and 11, Table 2. Under the Pd/Et3B catalysis, the sub-
strate 3d was so unreactive at 258C that it required heating
at 508C for the reaction to proceed at a reasonable rate.
Even under such conditions, 3d showed much higher selec-
tivity than 3e did at 258C. The reason for the unusual be-
havior on reactivity and stereoselectivity associated with 3d
is not clear at the moment.[11] It should be noted that corre-
sponding THP analogue 1d exhibited similarly low reactivi-
than benzoate regarding the yields of products,[14] 2) allyl-
zinc species generated fromdifferent sources (benzoate and
1g) might be regarded structurally similar to each other,
and 3) they intermolecularly react with aldehydes most
likely via a transition state I shown in Scheme 2. The special
structural feature associated with this six-membered chair-
like transition state I, leading to thermodynamically less
Table 4. Comparison of reactivity of 1g and its benzoic acid derivative.[a]
Aldehyde (R)
1g: X = 2-THP[a,c,d]
X = Bz[b,c]
1
2
Ph-
PhCH2CH2-
5a: 89 [100:0]
5b: 68 [83:17]
5a: 63 [100:0]
5b: 36 [94:6]
[a] a) Aldehyde (3 mmol), 1g (1 mmol), Pd(OAc)2 (10 mol%), nBu3P
(40 mol%), Et2Zn (3.6 mmol, 1m in hexane), dry toluene (0.5 mL) at
258C under N2. b) Aldehyde (1.0 mmol), benzoate (1.2 mmol), Pd(OAc)2
(10 mmol), nBu3P (40 mol%), Et2Zn (2.4 mmol, 1m in hexane), THF
(5 mL). c) Ratios of (Z),anti-5 to a mixture of other isomers [(Z),syn-,
(E),syn-, and (E),anti-5). d) No 2e was obtained.
Scheme 2. Plausible transition states for the self-allylation of 1.
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Allylation of Aldehydes
FULL PAPER
stable (Z)-isomers, is that the methyl group a to Zn occu-
pies a quasi-axial position so as to minimize the steric repul-
sion against the two ligands on Zn and hence, renders a
quasi-equatorial conformation of the methyl group g to Zn
most suitable.
The poor stereoselectivity associated with the intramolec-
ular self-allylation of 1g, on the other hand, might be attrib-
uted to the formation of a cyclic zinc w-formylalkanolate
species involving coordination of the aldehyde oxygen to
Zn, which forces an aldehyde to approach to an allyl anion
with its substituent in a quasi-axial position in such way as
depicted in transition states II-boat and II-chair (Scheme 2).
In these transition states, being characterized by a bicyclic
(Table 6), and 10 (Scheme 3) and a-deoxy-carbohydrates 12
and 14, were subjected to the self-allylation (Tables 7 and
8). As is evident fromthe results shown in Tables 7 and 8, a
series of a-deoxy ether derivatives did not show any prefer-
ences of all possible stereoisomers.[15] In sharp contrast to
this, a-oxy ether derivatives showed an interesting stereose-
lectivity at a synthetically useful level (Tables 5 and 6 and
Table 5. Self-allylation of 2-oxycarbohydrate derivative 6.[a]
ꢀ
[5.3.1] skeleton, both the aldehyde substituent and the Zn
alkoxide bond are forced to locate in quasi-diaxial positions.
Under such circumstances, II-chair might not be necessarily
preferred over II-boat. In fact, a transition state II-boat
leading to (E)-2e seems be slightly lower in energy than a
transitions state II-chair leading to (Z)-2e, as judged from
the product distribution, [(E)-2e + (E)-2e’]/(Z)-2e 3:2 (run
1, Table 3 and footnote [e]). The product mixture of 2e was
inseparable; however, the E/Z (3:2) ratio could be deduced
on the basis of the 1H NMR spectra of the mixture. Unfortu-
R
t [h]
Yield (%)
1
2
3
4
6a: R = H
6b: R = Me
6c: R = tBu
6d: R = Ph
2
2
5
2
7a: 91 [1:1]
7b: 88 [2:2:1:1]
7c: 85 [10:2:2:1]
7d: 76 [15:2:1:1]
[a] Conditions: 6 (1 mmol), Pd(OAc)2 (10 mol%), nBu3P (40 mol%), and
Et2Zn (3.6 mmol, 1m in hexane), dry toluene (2 mL) at 258C under N2.
ꢀ
nately the relative stereochemistry around C5 C6 could not
be determined.
Table 6. Self-allylation of 2-oxycarbohydrate derivative 8.[a]
The anti stereoselectivity generally observed for a series
of reactions of 1, all through Tables 2 and 3, might be ration-
alized similarly, supposing II-boat as the most favored tran-
sition state. The remarkably high anti-selectivity observed
for 1i (run 3, Table 3) might further lend support for a tran-
sition state II-boat. In this particular case, II-boat might pre-
dominate over II-chair, since II-chair suffers fromsubstan-
R
t [h]
Yield (%)
1
2
8a: R = H
8b: R = Ph
1.5
5
9a: 97 [12:1]
9b: 72 [single]
2
3
ꢀ
tial steric repulsion between R
clic C5 bridge.
R = (CH2)4 and the bicy-
[a] For reaction conditions, see Table 5; 1 mmol 8.
Self-allylation of carbohydrate derivatives 6, 8, 10, 12, and
14: The present self-allylation turned out to be successfully
applicable to the allylation of carbohydrate derivatives
(Tables 5–8 and Scheme 3). In all cases, the yields are satis-
factory and range from75 to 98% with one exception of
12b. Unsymmetrically substituted ethers reacted as usual,
providing the most branched isomers exclusively.
It might seem to be very challenging to examine the ster-
eoselection for these carbohydrate derivatives, since in addi-
tion to the metal–alkoxide control discussed in the foregoing
section (e.g., transition state II-chair or II-boat), the other
ether coordination controls (the so called “Cramcontrol”
due to a-ether and remote ether controls due to b- or g-
ethers) might become a subject to be taken into consider-
ation. However, the stereochemical outcomes turned out to
be much simpler than expected; among many transition
models, the Cram control was by far the most important and
the metal–alkoxide control was less important. The remote
ether groups seemed not to participate in controlling the
stereoselection to any appreciable extent.
Scheme 3).[16] The parent 6a did not show any diastereose-
lectivity and provided a mixture of 7a in a 1:1 ratio; howev-
er, surprisingly, as the steric size of allyl moieties increased,
the diastereofacial selectivity (around C4 stereocenter) as
well as the diastereoselectivity (around C5 stereocenter) in-
creased gradually, and finally (4R,5R)-7d was obtained pre-
dominantly over the other stereoisomers (run 4). In sharp
contrast to this, in the case of the glucose derivatives, even
the parent 8a exhibited a high level of diastereofacial selec-
tivity and provided (6R)-9a in excellent yield. Similarly high
diastereoselectivity was observed for the mannose derivative
10, where a mixture of (6S)-11/(6R)-11 was obtained in a
30:1 ratio in 90% yield.
In order to assess the abilities of the Cramcontrol, two
Scheme 3. Self-allylation of 2-oxycarbohydrate derivative 10 (for reaction
conditions, see Table 5; 1 mmol 10).
sets of substrates, a-oxy-carbohydrates
6 (Table 5), 8
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Y. Tamaru et al.
The contrasting stereoselectivity that 6a and a pair of 8a
and 10 display may be accounted for by supposing two types
of transitions states, a Cram-control transition state III and
a zinc–alkoxide control transition state IV (Scheme 4), the
In the cases of the self-allylation of 8 and 10, as compared
with 6, a zinc–alkoxide transition state such as IV would
become less favorable, since in these cases a tether connect-
ing zinc and aldehyde becomes longer by one carbon unit
(C5 bridge vs C4 bridge) and the repulsion between C5 and
C3 bridges becomes more serious; hence even the parent 8a
and 10 would selectively react through a Cramtransition
state such as III to furnish 9a and 11, respectively.
Structure determination of products: Fortunately, 7d formed
a nice crystalline solid and the structure of (4R,5R)-7d was
determined unequivocally by means of X-ray crystallograph-
ic analysis.[17] Chem3D perspective view of the crystal struc-
ture is shown in Figure 1.
Scheme 4. Plausible transition states for the self-allylation of 6.
latter having been invoked as a transition state for the self-
allylation of 1 and 3 in the previous section. A Cramtransi-
tion state III would give rise to (4R)-7, while a transition
state IV would lead to the other enantiomer, (4S)-7. In the
case of 6a, these two transition states might equally operate,
resulting in the formation of a 1:1 mixture of (4R)-7a and
(4S)-7a. Although the precise mechanism is not clear at the
moment, as the steric size of allyl ether moiety increases, a
Cramtransition state III would become favorable over a
zinc–alkoxide transition state IV. One reason for this may
be due to steric repulsion between the C4 and C3 bridges in
a transition state IV of a bicyclo[4.3.1] structure, which
might rapidly increase as the steric bulk of the C3 bridge in-
creases.
Figure 1. Chem3D presentation of X-ray structure of (4 R,5R)-7d. For
clarity, only relevant hydrogen atoms are shown.
The structures of 2b, 2g, 4c, 9a and 11 were deduced on
3
the basis of either coupling constants J(H,H) or increments
of area intensities by NOE experiments observed for the
1H NMR spectra of their cyclic derivatives, which were pre-
pared according to the standard procedures as outlined in
Scheme 5.
A Cramtransition state III creating a (4R) stereocenter is
correlated to the creation of a (5R) stereocenter (R¼H), as
evidenced by the selective formation of (4R,5R)-7d.
The transformation of 2g to 18 may deserve some com-
ments; reduction with NaBH4 of the cyclohexanone moiety
of the ozonolysis product of 2g took place selectively from
the axial side[18] and bicyclic carbonate 18 was obtained as a
single diastereomer. Two methyne protons Ha and Hc of 18
appeared separately and showed well-resolved absorptions
with splitting patterns, being characteristic of axial orienta-
tion of trans-fused bicyclo[4.4.0]decane with a chair-confor-
mation: Ha, 4.12 ppm(ddd, 3J(H,H)=2.7, 7.1, 10.2 Hz); Hc,
3.98 ppm(dt, 3J(H,H)=4.4, 11.0 Hz). The Ha and Hc protons
of the acetonide derivative of 18 give almost the same chem-
ical shifts and were give complex spectra in CDCl3 or in
C6D6.
Table 7. Self-allylation of 2-deoxy-d-ribose derivative 12.[a]
R
T [8C]/t [h]
Yield (%)
1
2
12a: R = H
12b: R = Ph
25/1
25/5
13a: 76 [1:1]
13b: 49 [3:2:1:1]
[a] For conditions, see footnote of Table 5; 1 mmol 12; the same amount
of Et2Zn was used, despite the presence of a hydroxy group.
An eight-membered cyclic acetonide such as 19 was pre-
pared also from 9b, however, no useful information to de-
termine the C7 configuration was obtained by extensive ex-
aminations of the 1H NMR spectra. Accordingly, the 7R
configuration of (6R,7R)-9b was tentatively assigned by
analogy with the stereoselectivity observed for (4R,5R)-7d.
Acetonization of (6S)-11 did not proceed at all under the
conditions applied to the conversion of (6R)-9a to 19, prob-
ably owing to steric repulsion of C4-allyl and C5-OBn
groups against one of the acetonide methyl group. A cyclic
carbonate 20 was prepared under rather forcing conditions
(see Experimental Section).
Table 8. Self-allylation of 2-deoxy-d-ribose derivative 14.[a]
R
T [8C]/t [h]
Yield (%)
1
1
14a: R = H
14b: R = Ph
25/3
25/5
15a: 98 [1:1]
15b: 98 [2:2:1:1]
[a] For conditions, see footnote of Table 5; 1 mmol 14.
6634
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 6629 – 6642

Allylation of Aldehydes
FULL PAPER
Scheme 6. C3 elongation of diols without protection–deprotection tech-
nique. i) NaH (210 mol%), allyl chloride (110 mol%), DMF, ii) pyridini-
um chlorochromate (200 mol%), AcONa (80 mol%), CH2Cl2; 21a (40%
overall), 21b (35% overall). iii) Pd(OAc)2 (10 mol%), nBu3P (40 mol%),
Et2Zn (240 mol%, 1m hexane), toluene (0.5 mL) at room temperature
under N2.
Self-allylation of 1a with reduced amounts of catalysts: All
the experiments examined so far have used 10 mol% of Pd-
(OAc)2. In Table 9 are summarized the results examined
using reduced amounts of Pd(OAc)2 together with the re-
sults examined under standard conditions for references
(runs 1 and 4).
In practice, the experimental runs 2, 3, 5, and 6 were un-
dertaken with fixed amounts of the catalyst/ligand (i.e.,
0.1 mmol/0.2 mmol for Et3B and 0.1 mmol/0.4 mmol for
Et2Zn), scaling up the amounts of 1a, Et3B or Et2Zn, and
the solvents. The reactions in runs 2 and 3 were not com-
plete after 22 h at 258C and the reactions were continued at
558C.
Scheme 5. Structure determination of products. i) O3/CH2Cl2 at ꢀ788C, ii)
NaBH4/MeOH-H2O, iii) excess Me2C(OMe)2, cat. p-toluenesulfonic acid,
iv) Ph3CCl, Et3N/CH2Cl2, v) (Imd)2CO/THF, vi) (Imd)2CO/NaH/dioxane.
Tr =triphenylmethyl, Imd=imidazolyl.
As the loading amounts of the catalyst decrease, the iso-
lated yields of 2a gradually decrease and reaction times get
Table 9. Self-allylation of 1a under reduced loading of the catalysts.[a]
C3 Unit elongation of diols in
shorter steps: A general strat-
egy for the C3-unit elongation
of diols may consists of 1)
semi-protection of diols to
formmono-alcohols, 2) oxida-
tion of the mono-alcohols to
aldehydes, 3) allylation of the
aldehydes with an appropriate
allylating agent, and 4) depro-
Pd(OAc)2(mol%)/nBu3P(mol%)
Scale [mmol]
EtnM
T [8C]/t [h]
Yield 2a (%)
1
2
3
4
5
6
10/20
3/6
1/2
10/40
3/12
1/4
1
3.4
10
1
3.4
10
Et3B
Et3B
Et3B
Et2Zn
Et2Zn
Et2Zn
25/2
86
77
61
91
84
63
25/22!55/10
25/22!55/24
25/1
25/3
25/8
[a] See footnote [a] and [b] (toluene, 0.5 mL instead of 5.0 mL) in Table 2 for reaction conditions. For larger
scale experiments, the amounts of EtnM and the solvent were increased proportionally.
tection. In this sequence, an allylating agent must be pre-
pared separately to performthe step 3. Accordingly, totally
five steps are necessary to achieve this transformation.
According to the sequence of reactions illustrated in
Scheme 6, the allylation of alcohol (step i) may be regarded
as a semi-protection step of a diol and as a step of prepara-
tion of allylating agent as well. Furthermore, with a single
step iii, can be achieved both nucleophilic allylation and de-
protection, the steps 3 and 4 mentioned above. Thus, as
compared with the existing general strategy, the process
shown in Scheme 6 is shorter in steps by 2 and might be
more efficient and economical. Both aromatic 21a and ali-
phatic aldehydes 21b undergo self-allylation smoothly at
roomtemperature and provide diols 22a and 22b in quanti-
tative yields, respectively.[19]
longer. Yet, even with 1 mol% of the catalyst, the yields of
2a still amount to about 60%.
Conclusion
A full scope of allylation of aldehydes using allyl ethers as
allyl nucleophiles is described. The reaction proceeds nicely
under very mild conditions, in almost all cases at ambient
temperature, under the catalysis of Pd/Et3B or Pd/Et2Zn.
The Pd/Et2Zn systemis applicable to a wide structural varie-
ty of allyl ethers 1, 3, 6, 8, 10, 12, 14, and 21. The success of
the reaction under the Pd/Et3B conditions is limited only to
allyl ethers 1 and 3 of structural simplicity, but this catalytic
systemshows higher diastereoselectivity than Pd/Et 2Zn
does. Under the Pd/Et2Zn conditions, a 2-oxy-THP group
Chem. Eur. J. 2005, 11, 6629 – 6642
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6635

Y. Tamaru et al.
ii) To
a
mixture of 2,3-O-isopropylidene-d-erythronolactol (1.0 g,
serves as a better leaving group than a benzoate group and
provides homoallyl alcohols in much better yields (Table 4).
The allyl group and 2-THF and 2-THP groups of 3 and 1
have been, so far, recognized as protecting groups; however,
through the present methodology, they have been proved to
be the useful C3-, C4-, and C5-building blocks, respectively.
The allylation methodology of carbohydrates disclosed here
may find wide application in chiral natural product synthe-
sis. The chiral homoallyl alcohols obtained here may also be
utilized for the chiral allyl group transfer via the 2-oxonium-
Cope rearrangement, the methodology developed recent-
ly.[20]
6.2 mmol) and NaH (0.3 g, 7.5 mmol) in dry DMF (10 mL) was added
dropwise a solution of allyl bromide (0.83 g, 6.9 mmol) in dry DMF
(10 mL) at 08C under N2. After stirring for 5 h at ambient temperature,
the mixture was quenched with MeOH/H2O (53 mL, 1:17) and extracted
with Et2O (2”200 mL). The combined extracts were dried (MgSO4) and
concentrated in vacuo to give an oil, which was purified by column chro-
matography on silica gel (AcOEt/hexane 1:10) to give 6a (770 mg, 62%).
1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.32 (s, 3H), 1.47 (s, 3H),
3.89 (dd, 3J(H,H)=10.4, 3.6 Hz, 1H), 3.95–4.01 (m, 2H), 4.13 (ddq, 3J
(H,H)=12.9, 5.2, 1.4 Hz, 1H), 4.58 (d, 3J(H,H)=5.8 Hz, 1H), 4.80 (dd,
3J(H,H)=5.8, 3.6 Hz, 1H), 5.08 (s, 1H), 5.19 (dd, 3J(H,H)=10.2, 1.4 Hz,
1H), 5.27 (dd, 3J(H,H)=17.3, 1.4 Hz, 1H), 5.95 (dddd, 3J(H,H)=17.3,
10.2, 5.2, 3.6 Hz, 1H); IR (neat): n˜ =3082, 2939, 2876, 1649, 1458, 1373,
1354, 1271, 1163, 1045, 1026, 995, 929, 858, 815, 764, 675 cmꢀ1. 6b–d were
prepared similarly.
Synthetic advantage using an allyl ether not only as a pro-
tecting group but also as an allyl nucleophile is demonstrat-
ed by short and high-yield C3-unit elongation reactions of
diols (Scheme 6).
2-(Allyloxy)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-
pyran (8a): i) Conc. H2SO4 (0.023 g, 0.28 mmol) at ambient temperature
was added to a solution of d-glucose (0.93 g, 5.2 mmol) in allyl alcohol
(8.46 g, 0.145 mol). The mixture was stirred at 858C for 3 h. The mixture
was neutralized with 28% aq. NH3 and volatile materials were removed
in vacuo at roomtemperature to give an oil.
Experimental Section
ii) To a mixture of the oil and NaH (1.10 g, 27.5 mmol) in dry DMF
(40 mL) was added dropwise
a solution of benzyl bromide (4.27 g,
25.0 mmol) in dry DMF (15 mL) at 08C under N2. After stirring for 24 h
at ambient temperature, the mixture was quenched with MeOH/H2O
(112 mL, 1:8) and extracted with Et2O (2”400 mL). The combined ex-
tracts were dried (MgSO4) and concentrated in vacuo to give an oil,
which was purified by column chromatography on silica gel (AcOEt/
hexane 1:8) to give 8a (1.68 g, 57%). 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=3.40–3.82 (m, 6H), 4.03 (m, 2H), 4.15 (dd, 3J(H,H)=13.4,
5.2 Hz, 1H), 4.42–5.06 (m, 8H), 5.20 (d, 3J(H,H)=11.3 Hz, 1H), 5.30 (d,
3J(H,H)=17.0 Hz, 1H), 5.95 (dddd, 3J(H,H)=17.0, 11.3, 6.1, 5.4 Hz,
1H); IR (neat): n˜ =3063, 3030, 2866, 1647, 1585, 1496, 1454, 1359, 1329,
1261, 1209, 1072, 1028, 928, 819, 737 cmꢀ1. Compound 8b was prepared
similarly.
Solvents and reagents: Tetrahydrofuran was dried and distilled fromben-
zophenone and sodium immediately prior to use under nitrogen atmos-
phere. Toluene was distilled over calciumhydride. Pd(OAc)
(purity
2
97.0%, Nakarai tesque), Ph3P (purity 97+ %, Wako), nBu3P (purity
90.0+ %, Tokyo Kasei), Et3B (1.0m hexane, KANTO), Et2Zn (1.0m
hexane, KANTO), allyl alcohol (KANTO), 2,3-O-isopropylidene-d-er-
ythronolactone (Aldrich), 2-deoxy-d-ribose (Tokyo Kasei), d-glucose
(Wako), d-mannose (Wako), triphenylmethyl chloride (Tokyo Kasei), o-
bis(hydroxymethyl)benzene (Tokyo Kasei), 2,2-dimethoxypropane
(Tokyo Kasei), NaH (purity 60.0+ %, Kishida Chemicals), p-toluenesul-
fonic acid (p-TsOH, Nakarai tesque), DIBAL (1.0m hexane, KANTO),
and dry DMF (purity 99.5%, water <0.005%, KANTO) were purchased
and used as received.
2-Allyloxy-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-
pyran (10): Conc. H2SO4 (50 mL, 1 mmol) at room temperature was
added to a solution of d-mannose (1.8 g, 10 mmol) in allyl alcohol
(10 mL, 147 mmol) and the mixture was stirred at 808C for 2 h. The mix-
ture was neutralized with 28% aq. ammonia (150 mL) and the excess
amount of allyl alcohol was removed under reduced pressure (708C/
0.1 mmHg). To the mixture of the residual oil and NaH (50% dispersion
in mineral oil; 2.4 g, 50 mmol) in dry DMF (80 mL) was added a solution
of benzyl bromide (6.0 mL, 50 mmol) dissolved in dry DMF (20 mL)
through a dropping funnel at 08C under nitrogen atmosphere. After stir-
ring for 6 h at room temperature, the reaction mixture was quenched
with aqueous methanol (100 mL; MeOH/water 1:8) and extracted with
Et2O (3”80 mL). The combined organic phase was dried (MgSO4) and
concentrated in vacuo to give a viscous oil, which was purified by column
chromatography on silica gel (AcOEt/hexane 1:8) to give 10 (3.29 g,
58%). 1H NMR (300 MHz, CDCl3, 258C, TMS): d=3.71–3.81 (m, 3H),
3.92–4.00 (m, 2H), 4.15 (m, 1H), 4.50 (brd, 3J(H,H)=10.8 Hz, 1H), 4.56
(brs, 1H), 4.62–4.77 (m, 4H), 4.87 (brd, 3J(H,H)=10.8 Hz, 1H), 4.92
(brs, 1H), 5.14 (brd, 3J(H,H)=10.5 Hz, 1H), 5.20 (brd, 3J(H,H)=
16.0 Hz, 1H), 5.84 (brddm, 3J(H,H)=10.5, 16.0 Hz, 1H), 7.16–7.45 (m,
20H); IR (neat): n˜ =3032 (s), 2862 (s), 1103 (s), 741 cmꢀ1 (s).
Preparation of starting materials
2-(Allyloxy)tetrahydrofurans (1a–k) and 2-(allyloxy)tetrahydropyrans
(3a–i): Tetrahydrofuran 1a as a typical example: 3,4-Dihydro-2H-pyran
(10 mL, 30 mmol) was added via syringe at 08C under N2 to a solution of
allyl alcohol (1.55 mL, 20 mmol) and p-TsOH (0.34 mg, 2.0 mmol) in dry
THF (10 mL). The mixture was stirred at ambient temperature overnight
and then diluted with AcOEt and washed with sat. NaHCO3 and brine,
and the organic phase was dried (MgSO4) and concentrated in vacuo to
give an oil, which was purified by Kugelrohr distillation (1008C at
30 mmHg) to give 1a (2.73 g, 96%). 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=1.50–1.90 (m, 6H), 3.52 (m, 1H), 3.89 (m, 1H), 3.99 (dd, 3J-
(H,H)=12.9, 6.1 Hz, 1H), 4.26 (dd, 3J(H,H)=12.9, 4.9 Hz, 1H), 4.66 (t,
3J(H,H)=3.4 Hz, 1H), 5.18 (d, 3J(H,H)=10.4 Hz, 1H), 5.30 (d, 3J-
(H,H)=16.9 Hz, 1H), 5.95 (dddd, 3J(H,H)=16.9, 10.4, 6.1, 4.9 Hz, 1H);
IR (neat): n˜ =3078, 2939, 2870, 1736, 1643, 1443, 1373, 1319, 1265, 1126,
1072, 1026, 995, 926, 871, 810, 748 cmꢀ1
.
4-(Allyloxy)-tetrahydro-2,2-dimethylfuro[3,4-d][1,3]dioxole (6a): i) A so-
lution of DIBAL (40.7 mmol, 1.0m hexane) was added dropwise over
0.5 h into a well-stirred solution of 2,3-O-isopropylidene-d-erythronolac-
tone (3.0 g, 19 mmol) in CH2Cl2 (60 mL) kept at ꢀ788C. After stirring
for 4 h at ꢀ788C, successively methanol (15 mL) and water (15 mL) were
added dropwise. After being allowed to warmto roomtemperature,
Et2O (150 mL) and MgSO4 were added. The mixture was filtrated and
the filter cake was washed with ether (60 mL). The filtrate was concen-
trated in vacuo and the residue was purified by column chromatography
on silica gel (AcOEt/hexane 1:16) to give 2,3-O-isopropylidene-d-eryth-
ronolactol (2.47 g, 81%). 1H NMR (300 MHz, CDCl3, 258C, TMS): d=
5-(Allyloxy)tetrahydro-2-(triphenylmethoxymethyl)furan-3-ol
(12a):
i) Conc. H2SO4 (0.07 g, 0.8 mmol) was added to a solution of 2-deoxy-d-
ribose (2.5 g, 18.6 mmol) in allyl alcohol (101.8 g, 1.7 mol) and the mix-
ture was stirred at 258C for 1.5 h. The mixture was neutralized with 28%
aq. NH3 and volatile materials were removed in vacuo to give an oil.
ii) To a mixture of the oil and Et3N (2.67 g, 26.4 mmol) in dry CH2Cl2
(50 mL) was added dropwise a solution of triphenylmethyl chloride
(6.58 g, 23.6 mmol) in dry CH2Cl2 (20 mL) at 08C under N2. After stirring
at ambient temperature for 21 h, the mixture was washed with 0.1m HCl,
sat. NaHCO3, and brine. The organic phase was dried (MgSO4) and con-
centrated in vacuo to give an oil, which was purified by column chroma-
3
1.33 (s, 3H), 1.47 (s, 3H), 3.53 (brs, 1H), 4.02 (d, J(H,H)=10.2 Hz, 1H),
3
3
4.07 (dd, J(H,H)=10.2, 3.3 Hz, 1H), 4.57 (d, J(H,H)=5.8 Hz, 1H), 4.84
(dd, 3J(H,H)=5.8, 3.3 Hz, 1H), 5.42 (s, 1H); IR (neat): n˜ =3425, 2986,
2947, 2885, 1458, 1380, 1335, 1211, 1165, 1072, 987, 910, 856 cmꢀ1
.
6636
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 6629 – 6642

Allylation of Aldehydes
FULL PAPER
tography on silica gel (AcOEt/hexane 1:7) to give 12a (4.57 g, 59%).
1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.87 (d, 3J(H,H)=4.4 Hz,
6-Methyloct-7-ene-1,5-diol (2b): 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=1.03 (d, 3J(H,H)=7.0 Hz, 3H), 1.37–1.65 (m, 6H), 2.42–3.12
(m, 2H), 2.20 (sext, 3J(H,H)=7.0 Hz, 1H, anti-isomer), 2.25 (sext, 3J
(H,H)=7.0 Hz, 1H, syn-isomer), 3.41 (m, 1H, anti-isomer), 3.46 (m, 1H,
syn-isomer), 3.65 (t, 3J(H,H)=6.0 Hz, 2H), 5.11 (d, 3J(H,H)=16.7 Hz,
1H), 5.12 (d, 3J(H,H)=10.8 Hz, 1H), 5.75 (ddd, 3J(H,H)=16.7, 10.8,
8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): anti-isomer: d=
16.2, 69.9, 32.6, 33.7, 44.2, 62.5, 74.7, 116.1, 140.4; syn-isomer: d=14.4,
22.0, 32.6, 33.7, 43.7, 62.5, 74.7, 115.1, 141.1; IR (neat): n˜ =3332, 3076,
2868, 1828, 1639, 1456, 1417, 1373, 1336, 912 cmꢀ1; HRMS (EI): m/z (%):
calcd for C9H18O2ꢀH2O: 140.1201, found: 140.1201 (2) [M +ꢀH2O], 103
(23), 85 (100), 67 (23).
3
1H), 2.05 (dd, 3J(H,H)=13.5, 5.2 Hz, 1H), 2.21 (ddd, J(H,H)=13.5, 6.6,
1.6 Hz, 1H), 3.17 (dd, 3J(H,H)=9.6, 6.6 Hz, 1H), 3.31 (dd, 3J(H,H)=9.6,
5.2 Hz, 1H), 3.87 (dd, 3J(H,H)=12.6, 6.6 Hz, 1H), 3.98 (q, 3J(H,H)=
3
5.5 Hz, 1H), 4.10 (m, 1H), 4.42 (m, 1H), 5.10 (d, J(H,H)=10.4 Hz, 1H),
3
3
5.15 (d, J(H,H)=17.3 Hz, 1H), 5.19 (m, 1H), 5.95 (dddd, J(H,H)=17.3,
10.4, 6.6, 5.5 Hz, 1H), 7.18–7.52 (m, 15H); IR (neat): n˜ =3460, 2924,
2870, 1491, 1448, 1223, 1080, 1001, 926, 900, 839, 763, 746, 705, 636 cmꢀ1
.
Compound 12b was prepared similarly.
6-(Allyloxy)tetrahydro-2,2-dimethyl-4H-furo[3,2-d][1,3]dioxine
(14a):
i) Conc. H2SO4 (0.04 g, 0.4 mmol) was added to a solution of 2-deoxy-d-
ribose (1.34 g, 10 mmol) in allyl alcohol (26.7 g, 0.46 mol) and the mixture
was stirred at 258C for 1.5 h. The mixture was neutralized with 28% aq.
NH3 and volatile materials were removed in vacuo to give an oil. ii) A so-
lution of the oil and p-TsOH (0.20 g, 1.1 mmol) in dry acetone (12 mL)
was stirred for 12 h at ambient temperature under N2. The mixture was
diluted with AcOEt and the mixture was washed with sat. NaHCO3 and
brine. The organic phase was dried (MgSO4) and concentrated in vacuo
to give an oil, which was purified by column chromatography on silica
gel (AcOEt/hexane 1:3) to give 14a (1.35 g, 63%). 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=1.35 (s, 3H), 1.52 (s, 3H), 1.84 (ddd, 3J(H,H)=
14.5, 6.1, 4.6 Hz, 1H), 2.17 (dt, 3J(H,H)=14.5, 4.6 Hz, 1H), 3.74 (dd,
3J(H,H)=12.9, 2.5 Hz, 1H), 3.74 (dd, 3J(H,H)=12.9, 3.0 Hz, 1H), 4.01
(m, 1H), 4.15 (dt, 3J(H,H)=7.0, 2.5 Hz, 1H), 4.24 (m, 1H), 4.46 (q,
3J(H,H)=7.0 Hz, 1H), 4.92 (dd, 3J(H,H)=6.1, 4.6 Hz, 1H), 5.19 (d,
3J(H,H)=10.2 Hz, 1H), 5.28 (d, 3J(H,H)=17.0 Hz, 1H), 5.91 (dddd,
3J(H,H)=17.0, 10.2, 6.1, 4.6 Hz, 1H); IR (neat): n˜ =2986, 2939, 2878,
2361, 1458, 1373, 1272, 1211, 1165, 1088, 995, 926, 864, 756 cmꢀ1. Com-
pound 14b was prepared similarly.
6-Phenyl-7-octene-1,5-diol (2c): 1H NMR (400 MHz, CDCl3, 258C,
TMS): anti-isomer: d=1.32–1.66 (m, 6H), 2.29–2.42 (m, 2H), 3.22 (brt,
3J(H,H)=8.4 Hz, 1H), 3.54 (brt, 3J(H,H)=3.5 Hz, 2H), 3.75–3.80 (m,
1H), 5.16 (dd, 3J(H,H)=17.2, 0.7 Hz, 1H), 5.20 (dd, 3J(H,H)=9.9,
1.5 Hz, 1H), 6.11 (ddd, 3J(H,H)=17.2, 9.9, 9.3 Hz, 1H), 7.18–7.28 (m,
5H); syn-isomer: d=1.32–1.66 (m, 6H), 2.29–2.42 (m, 2H), 3.28 (brt, 3J
3
(H,H)=8.4 Hz, 1H), 3.54 (brt, J(H,H)=3.5 Hz, 2H), 3.75–3.80 (m, 1H),
5.16 (dd, 3J(H,H)=17.2, 0.7 Hz, 2H), 5.20 (dd, 3J(H,H)=9.9, 1.5 Hz,
1H), 6.11 (ddd, 3J(H,H)=17.2, 9.9, 9.2 Hz, 1H), 7.18–7.28 (m, 5H);
13C NMR (100 MHz, CDCl3, 258C, TMS): anti-isomer: d=21.9, 32.4,
35.2, 57.5, 62.7, 73.8, 117.9, 126.6, 127.9, 128.1, 128.7, 129.2, 138.2, 141.4;
syn-isomer: d=22.0, 32.6, 35.4, 57.4, 62.3, 74.1, 116.8, 126.8, 128.0, 128.1,
128.8, 129.0, 138.4, 144.2; IR (neat): n˜ =3352, 3028, 2937, 2866, 1726,
1600, 1493, 1452, 1335, 1244, 916 cmꢀ1; HRMS (EI): m/z (%): calcd for
C14H20O2: 220.1463, found: 220.1442 (3) [M +], 147 (8), 118 (100), 103
(8), 85 (16).
7-Methyl-7-octene-1,5-diol (2d): 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=1.39–1.64 (m, 6H), 1.76 (s, 3H), 2.08–2.11 (m, 2H), 2.11 (dd,
3J(H,H)=13.5, 9.2 Hz, 1H), 2.21 (ddm, 3J(H,H)=13.5, 3.8 Hz, 1H), 3.65
(tm, 3J(H,H)=6.6 Hz, 2H), 3.73 (m, 1H), 4.80 (s, 1H), 4.88 (s, 1H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=21.9, 22.5, 32.6, 36.7, 46.2,
62.5, 68.9, 113.3, 142.9; IR (neat): n˜ =3333, 3074, 2935, 2864, 1651, 1452,
1375, 889 cmꢀ1; HRMS (EI): m/z (%):calcd for C9H18O2 158.1307, found:
158.1340 (1) [M +], 128 (1), 104 (3), 85 (100).
o-(Allyloxymethyl)benzaldehyde (21a): i) A solution of allyl chloride
(0.85 g, 11.1 mmol) in dry DMF (12 mL) was added dropwise at 08C
under N2 to
a mixture of o-bis(hydroxymethyl)benzene (1.39 g,
10.0 mmol) and NaH (0.85 g, 21.1 mmol) in dry DMF (20 mL). After stir-
ring for 24 h at ambient temperature, the mixture was quenched with
MeOH/H2O (48 mL, 1:3). The mixture was extracted with Et2O (2”
150 mL). The combined organic extracts were dried (MgSO4) and con-
centrated in vacuo to give an oil.
6-Methyl-7-nonene-1,5-diol (2e): 1H NMR (400 MHz, CDCl3, 258C,
3
3
TMS): d=0.99 (d, J(H,H)=6.5 Hz, 3H), 1.32–1.62 (m, 6H), 1.63 (dd, J-
(H,H)=5.1, 1.8 Hz, 3H), 2.01 (brs, 2H), 2.53 (dm, 3J(H,H)=7.0 Hz,
ii) To a solution of the oil in CH2Cl2 (30 mL) were added pyridinium
chlorochromate (4.33 g, 20 mmol) and sodium acetate (0.66 g, 8 mmol) at
room temperature. After stirring for 1 h at room temperature, the mix-
ture was diluted with ether. The organic extract was concentrated in
vacuo. The residue was purified by column chromatography on silica gel
(AcOEt/hexane 1:8) to give 21a (704 mg, 40% overall yield). 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=4.14 (dt, 3J(H,H)=5.5, 1.6 Hz, 2H),
4.94 (s, 2H), 5.23 (dd, 3J(H,H)=10.4, 1.6 Hz, 1H), 5.32 (dd, 3J(H,H)=
15.9, 1.6 Hz, 1H), 5.98 (ddt, 3J(H,H)=15.9, 10.4, 5.5 Hz, 1H), 7.26–7.88
(m. 5H), 10.22 (s, 1H); IR (neat): n˜ =2855, 2783, 2360, 1697, 1597, 1350,
1195, 1080, 995, 925, 856, 756 cmꢀ1. Compound 21b was prepared similar-
ly.
3
3
1H), 3.35 (m, 1H), 3.65 (tm, J(H,H)=5.7 Hz, 2H), 5.26 (ddq, J(H,H)=
10.3, 8.8, 1.8 Hz, 1H), 5.62 (dq, 3J(H,H)=10.6, 7.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=15.0, 16.8, 21.9, 33.7, 37.6, 43.2, 62.7,
74.9, 127.2, 133.0; IR(neat): n˜ =3344, 2935, 2869, 1726, 1454, 1375, 1259,
1055, 970, 921 cmꢀ1; HRMS (EI): m/z (%): calcd for C10H20O2 172.1463,
found: 172.1465 (10) [M +], 171(7), 155 (7), 142 (14), 137 (100), 136 (14).
1-(2-Cyclohexenyl)pentane-1,5-diol (2 f): a mixture in a ratio of 2:1;
1H NMR (400 MHz, CDCl3, 258C, TMS): d=1.34–1.47 (m, 2H), 1.68–
1.87 (m, 4H), 1.96–2.02 (m, 2H), 2.18–2.24 (m, 1H), 3.46 (ddm, 3J
(H,H)=8.4, 5.1 Hz, 1H), 3.56 (ddd, 3J(H,H)=5.8, 5.5, 4.8 Hz, 1H,
minor), 3.66 (t, 3J(H,H)=6.2, 1H), 5.69 (dm, 3J(H,H)=10.3 Hz, 1H),
5.55 (dm, 3J(H,H)=10.3 Hz, 1H, minor), 5.85 (ddm, 3J(H,H)=10.3,
6.6 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): major d=21.8,
22.3, 25.3, 25.9, 32.7, 33.4, 41.5, 62.8, 75.4, 126.9, 130.2; minor isomer: d=
21.5, 22.4, 22.9, 25.3, 32.7, 34.3, 41.5, 62.9, 74.5, 128.7, 130.5; IR (neat):
n˜ =3344, 3024, 2931, 2862, 1649, 1448, 1435, 1105, 1028 cmꢀ1; HRMS
(EI): m/z (%): calcd for C11H20O2 184.1463, found: 184.1460 (0.2) [M +],
167.1428 (0.4), 104 (100).
General procedure for the self-allylation of 1 or 3 (with Et2Zn, run 1,
Table 2): Compound 1a (142.2 mg, 1.0 mmol) and diethylzinc (3.6 mL,
1.0m in hexane) via syringe at 08C were added successively to a solution
of Pd(OAc)2 (22.6 mg, 0.1 mmol) and nBu3P (80.9 mg, 0.4 mmol) in dry
toluene (5 mL). The mixture was stirred at room temperature for 2 h
under N2 and then diluted with AcOEt, washed with 2m HCl, sat.
NaHCO3, and brine. The organic phase was dried (MgSO4) and concen-
trated in vacuo to give an oil, which was purified by column chromatog-
raphy on silica gel (AcOEt/hexane gradient 1:4 ! 4:1) to give 7-octene-
1-(2-Methylenecyclohexyl)pentane-1,5-diol (2g): a mixture in a ratio of
12:1; 1H NMR (400 MHz, CDCl3, 258C, TMS): d=1.38 (m, 1H), 1.43–
1.53 (m, 3H), 1.56–1.67 (m, 6H), 1.67–1.74 (m, 2H), 1.83 (s, 2H), 2.13
(dt, 3J(H,H)=9.9, 4.8 Hz, 1H), 2.17 (t, 3J(H,H)=6.2 Hz, 2H), 3.67 (t, 3J
(H,H)=6.2 Hz, 2H), 3.78 (ddd, 3J(H,H)=9.2, 8.8, 2.2 Hz, 1H), 4.75 (d,
3J(H,H)=2.2 Hz, 1H), 4.66 (s, 1H, minor), 4.86 (m, 1H), 4.73 (s, 1H,
minor); 13C NMR (100 MHz, CDCl3, 258C, TMS): major isomer: d=21.6,
22.4, 28.1, 29.0, 32.8, 33.0, 33.5, 50.1, 69.1, 70.2, 110.3, 149.8; minor
isomer: d=22.1, 23.1, 27.8, 28.5, 32.6, 34.6, 34.9, 49.5, 60.4, 70.2, 107.9,
150.5; IR (neat): n˜ =3342, 2932, 2858, 1645, 1447, 1058, 889 cmꢀ1; HRMS
1
1,5-diol (2a) in (123 mg, 86%). H NMR (400 MHz, CDCl3, 258C, TMS):
d=1.40–1.64 (m, 6H), 2.13–2.21 (m, 2H), 2.55 (brs, 2H), 3.62 (m, 1H),
3.63 (t, 3J(H,H)=6.2 Hz, 2H), 5.11 (d, 3J(H,H)=11.7 Hz, 1H), 5.12 (dm,
3J(H,H)=15.8 Hz, 1H), 5.83 (ddt, 3J(H,H)=15.8, 11.7, 7.7, 1H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=21.8, 32.4, 36.3, 42.0, 62.3,
70.7, 117.6, 135.0; IR (neat): n˜ =3331, 3076, 2936, 2864, 1641, 1435, 1340,
914 cmꢀ1; HRMS (EI): m/z (%): calcd for C8H16O2: 144.1150, found:
144.1098 (1) [M +], 126 (4), 116 (2), 71 (100).
Chem. Eur. J. 2005, 11, 6629 – 6642
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6637

Y. Tamaru et al.
(EI): m/z (%): calcd for C12H22O2ꢀH2O: 180.1514, found: 180.1208 (10)
[M +ꢀH2O], 179 (100).
1-(2-Cyclohexenyl)butane-1,4-diol (4e): a mixture of diastereomers in a
ratio of 2:1; 1H NMR (300 MHz, CDCl3, 258C, TMS): d= 1.39 (m, 1H),
1.48–1.58 (m, 2H), 1.60–1.81 (m, 6H), 1.96–2.02 (brs, 2H), 2.20–2.24 (m,
2H), 3.49 (m, 1H), 3.58 (m, 1H), 3.70 (tm, 3J(H,H)=5.6 Hz, 2H), 3.66
6,6-Dimethyl-7-octene-1,5-diol (2h): 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=1.00 (s, 6H), 1.25 (m, 1H), 1.36 (m, 1H), 1.45–1.56 (m, 2H),
1.58–1.70 (m, 2H), 3.25 (dd, 3J(H,H)=10.3, 1.7 Hz, 2H), 3.62 (t,
3J(H,H)=3.1 Hz, 2H), 5.03 (dd, 3J(H,H)=17.2, 1.5 Hz, 1H), 5.06 (dd,
3J(H,H)=11.0, 1.5 Hz, 1H), 5.82 (dd, 3J(H,H)=17.6, 11.0 Hz, 1H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=22.4, 22.9, 23.2, 31.0, 32.5,
62.5, 78.2, 113.1, 145.6; IR (neat): n˜ =3354, 3082, 2941, 2869, 1637, 1460,
3
(tm, J(H,H)=5.85 Hz, 2H), 5.69 (dm, 3J(H,H)=10.3 Hz, 1H), 5.55 (dm,
3J(H,H)=10.3 Hz, 1H), 5.84 (dm, 3J(H,H)=10.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3, 258C, TMS) major isomer: d= 21.7, 23.0, 25.3, 29.6,
31.7, 41.6, 63.0, 75.4, 126.8, 129.9; minor isomer: d= 21.4, 23.8, 25.7, 29.7,
30.9, 41.7, 63.0, 74.6, 128.3, 130.4; IR(neat): n˜ =3330, 3024, 2930, 2864,
2845, 1435, 1055, 1011, 970 cmꢀ1
; HRMS (EI): m/z (%): calcd for
1413, 1379, 1361, 912 cmꢀ1
; HRMS (EI): m/z (%): calcd for
C10H18O2: 170.1307, found: 170.1279 (3) [M +], 152 (24), 137 (100).
C10H20O2ꢀH2O: 155.1436, found: 155.1402 (47) [M +ꢀH2O], 139 (100),
1-(2-Methylenecyclohexyl)butane-1,4-diol (4 f): 1H NMR (300 MHz,
CDCl3, 258C, TMS): a mixture in a ratio of 5:1; d=1.38–1.56 (m, 4H),
1.60–1.68 (m, 2H), 1.69–1.82 (m, 3H), 1.88 (m, 1H), 2.13–2.20 (m, 2H),
137 (99), 124 (31).
6-Vinyl-7-octene-1,5-diol (2i): 1H NMR (400 MHz, CDCl3, 258C, TMS):
d=1.35–1.86 (m, 8H), 2.80 (brq, 3J(H,H)=7.4 Hz, 1H), 3.56 (m, 1H),
3.64–3.68 (m, 2H), 5.12 (dm, 3J(H,H)=10.1 Hz, 1H), 5.16 (dm,
3J(H,H)=15.5 Hz, 1H), 5.17 (dm, 3J(H,H)=15.1 Hz, 1H), 5.79 (ddd,
3J(H,H)=15.1, 10.7, 4.7 Hz, 1H), 5.85 (ddd, 3J(H,H)=15.5, 10.1, 5.2 Hz,
1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=22.0, 32.6, 33.8, 55.0,
62.8, 73.2, 116.9, 117.6, 137.0, 137.6; IR (neat): n˜ =3344, 3078, 2937, 2866,
2360, 2343, 1636, 1458, 1418, 1338, 1056, 1028, 1000, 912 cmꢀ1; HRMS
(EI): m/z (%): calcd for C10H18O2 170.1307, found: 170.1242 (1) [M +],
169.1293 (0.2), 153.1381 (0.3), 104 (100).
6-Heptene-1,4-diol (4a): 1H NMR (400 MHz, CDCl3, 258C, TMS): d=
1.39–1.73 (m, 4H), 2.17–2.31(m, 2H), 3.37 (brs, 2H), 3.60–3.72 (m, 2H),
5.11 (d, 3J(H,H)=11.0 Hz, 1H), 5.12 (d, 3J(H,H)=16.1 Hz, 1H), 5.82
(ddt, 3J(H,H)=16.5, 11.0, 7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=29.2, 33.8, 42.1, 62.9, 70.6, 118.0, 134.8; IR (neat): n˜ =
3333, 3076, 2935, 2634, 1641, 1435, 1344, 1057, 1011, 914 cmꢀ1; HRMS
(EI): m/z (%): calcd for C7H14O2 131.1099, found: 131.1080 (3) [M +],
115 (2), 112 (4), 89 (100).
3
2.17 (s, 1H), 2.78 (m, 1H), 3.66–3.73 (m, 2H), 3.82 (tm, J(H,H)=8.2 Hz,
1H), 4.67 (s, 1H, minor), 4.74 (s, 1H, minor), 4.78 (m, 1H), 4.88 (m,
1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): major isomer: d=22.3,
28.0, 29.0, 30.8, 32.9, 49.9, 63.0, 69.1, 110.4, 149.4; minor isomer: d=22.9,
28.4, 30.8, 32.4, 34.4, 49.6, 63.0, 70.2, 108.0, 150.3; IR(neat): n˜ =3344,
2932, 2856, 1447, 1055, 1007, 889 cmꢀ1; HRMS (EI): m/z (%): calcd for
C11H20O2: 184.1463, found: 184.1421 (3) [M +], 166 (58), 151(100).
5-Vinyl-6-heptene-1,4-diol (4g): 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=1.47 (m, 1H), 1.62–1.75 (m, 3H), 2.81 (brdt, 3J(H,H)=5.9,
7.7 Hz, 1H), 3.15 (brs, 2H), 3.54–3.70 (m, 3H), 5.12 (dm, 3J(H,H)=
17.2 Hz, 1H), 5.13 (dm, 3J(H,H)=10.6 Hz, 1H), 5.14 (dm, 3J(H,H)=
17.2 Hz, 1H), 5.18 (dm, 3J(H,H)=10.3 Hz, 1H), 5.81 (ddd, 3J(H,H)=
17.2, 10.6, 7.7 Hz, 1H), 5.84 (ddd, 3J(H,H)=17.2, 10.3, 8.1 Hz, 1H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=29.3, 31.3, 54.9, 62.7, 73.3,
116.8, 117.3, 137.1, 137.6; IR (neat): n˜ =3332, 3078, 2941, 2873, 1633,
1417, 1055, 999, 916 cmꢀ1; HRMS (EI): m/z (%): calcd for C9H16O2:
156.1150, found: 156.1135 (11) [M +], 138 (100).
5-Methyl-6-heptene-1,4-diol (4b): anti-isomer: 1H NMR (400 MHz,
CDCl3, 258C, TMS): d=1.03 (d, 3J(H,H)=7.0 Hz, 2H), 1.44 (m, 1H),
1.59–1.73 (m, 3H), 2.23 (dq, 3J(H,H)=8.1, 7.0 Hz, 1H), 3.29 (brs, 1H),
Intermolecular allylation of aldehydes with 1g: Allyl ether 1g (170.2 mg,
1.0 mmol), aldehyde (3.0 mmol), and diethylzinc (3.6 mL, 1.0m hexane)
were added successively via syringe at 08C under N2 to a solution of Pd-
(OAc)2 (22.6 mg, 0.1 mmol) and nBu3P (80.9 mg, 0.4 mmol) in dry tolu-
ene (0.5 mL). The mixture was allowed to warm to 258C and stirred at
the same temperature. The mixture was diluted with AcOEt and washed
with 0.2m HCl, sat. NaHCO3, and brine. The organic phase was dried
(MgSO4) and concentrated in vacuo to give an oil, which was purified by
column chromatography on silica gel (AcOEt/hexane 1:7).Compound 5a
was identified by comparison of the spectral data with those in literatur-
e.[4b]
(Z),anti-4-Methyl-1-phenyl-5-hepten-3-ol (5b): 1H NMR (400 MHz,
CDCl3, 258C, TMS): d=0.95 (d, 3J(H,H)=6.6 Hz, 3H), 1.65 (dd,
3J(H,H)=7.0, 1.8 Hz, 3H), 1.67–1.74 (m, 2H), 1.85 (ddq, 3J(H,H)=10.3,
9.9, 3.3 Hz, 1H), 2.56 (dquint, 3J(H,H)=10.3, 6.6 Hz, 1H), 2.67 (ddd,
3J(H,H)=13.6, 9.9, 6.6 Hz, 1H), 2.86 (dq, 3J(H,H)=13.6, 5.1 Hz, 1H),
3.36 (dt, 3J(H,H)=2.9, 8.1 Hz, 1H), 5.25 (ddq, 3J(H,H)=11.0, 10.1,
1.8 Hz, 1H), 5.62 (dq, 3J(H,H)=11.0, 6.6 Hz, 1H), 7.16–7.31 (m, 5H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=13.3, 16.9, 32.2, 36.0, 37.7,
74.7, 125.7, 126.2, 128.3, 128.4, 132.8, 154.5; IR (neat): n˜ =3418, 3026,
2930, 2870, 1497, 1454, 1036, 968, 700 cmꢀ1; HRMS (EI): m/z (%): calcd
for C12H16O: 204.1514, found: 204.1532(3) [M +], 135 (9), 69 (100).
3
3.45 (m, 1H), 3.58–3.70 (m, 2H), 5.09 (d, J(H,H)=18.3 Hz, 1H), 5.10 (d,
3
3J(H,H)=11.5 Hz, 1H), 5.76 (ddd, J(H,H)=8.1, 18.3, 11.5 Hz, 1H); syn-
isomer: d=1.04 (d, 3J(H,H)=7.0 Hz, 2H), 1.37–1.50 (m, 1H), 1.60–1.73
(m, 3H), 2.23 (dq, 3J(H,H)=8.1, 7.0 Hz, 1H), 3.29 (brs, 1H), 3.45 (m,
1H), 3.58–3.70 (m, 2H), 5.05 (d, 3J(H,H)=10.4 Hz, 1H), 5.06 (d,
3J(H,H)=17.4 Hz, 1H), 5.78 (ddd, 3J(H,H)=17.4, 10.4, 7.3 Hz, 1H);
13C NMR (CDCl3, 100 MHz): anti-isomer: d=16.2, 29.3, 31.1, 44.3, 62.8,
74.8, 116.1, 140.4; syn-isomer: d=14.7, 29.5, 31.3, 43.9, 62.8, 74.9, 115.1,
141.1; IR (neat): n˜ =3333, 3078, 2937, 2868, 1639, 1456, 1417, 1373, 1338,
912 cmꢀ1; HRMS (EI): m/z (%): calcd for C8H16O2: 144.1150, found:
144.1176 (6) [M +], 126 (100).
5-Phenyl-6-heptene-1,4-diol (4c): 1H NMR (400 MHz, CDCl3, 258C,
TMS): anti-isomer: d=1.36 (m, 1H), 1.52 (m, 1H), 1.60–1.66 (m, 2H),
2.87 (brs, 1H), 3.24 (brt, 3J(H,H)=8.2 Hz, 2H), 3.50–3.66 (m, 2H),
3.81(tm, 3J(H,H)=8.2 Hz, 1H), 5.18 (dm, 3J(H,H)=16.9 Hz, 1H), 5.20
(dm, 3J(H,H)=9.5 Hz, 1H), 6.12 (ddd, 3J(H,H)=16.9, 10.3, 9.5 Hz, 1H),
7.18–7.35 (m, 5H); syn-isomer: d=1.43 (m, 1H), 1.66–1.75 (m, 2H), 1.83
(m, 1H), 2.87 (brs, 1H), 3.30 (brt, 3J(H,H)=8.4 Hz, 2H), 3.50–3.66 (m,
2H), 3.88 (tm, 3J(H,H)=8.4 Hz, 1H), 5.11 (d, 3J(H,H)=11.4 Hz, 1H),
5.12 (d, 3J(H,H)=16.1 Hz, 1H), 6.02 (ddd, 3J(H,H)=16.1, 11.0, 9.5 Hz,
1H), 7.18–7.35 (m, 5H); 13C NMR (100 MHz, CDCl3, 258C, TMS): anti-
isomer: d=29.3, 31.5, 57.6, 63.0, 74.0, 118.0, 126.8, 128.0, 128.8, 138.4,
141.5; syn-isomer: d=29.3, 31.5, 57.6, 63.0, 74.3, 117.0, 127.0, 128.0, 128.5,
138.4, 140.9; IR (neat): n˜ =3344, 3028, 2873, 1637, 1601, 1492, 1452, 1001,
916 cmꢀ1; HRMS (EI): m/z (%): calcd for C13H18O2ꢀOH: 189.1279,
found: 189.1295 (1) [M +ꢀOH], 118 (100), 89 (10).
1-(5-Hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-buten-1-ol (7a): a
mixture in a ratio of 1:1, isomer 1: 1H NMR (300 MHz, CDCl3, 258C,
TMS): d=1.38 (s, 3H), 1.52 (s, 3H), 2.29–2.45 (m, 2H), 2.82–2.92 (m,
2H), 3.78–3.99 (m, 3H), 4.11 (dd, 3J(H,H)=6.9, 3.0 Hz, 1H), 4.23 (dt,
3J(H,H)=6.9, 5.0 Hz, 1H), 5.13 (dd, 3J(H,H)=10.2, 1.4 Hz, 1H), 5.16
(dd, 3J(H,H)=17.3, 1.4 Hz, 1H), 5.86 (ddt, 3J(H,H)=17.3, 10.2, 7.1 Hz
1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=25.02, 27.24, 39.58,
61.26, 68.58, 77.30, 78.39, 108.36, 118.05, 134.28; isomer 2: 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=1.36 (s, 3H), 1.41 (s, 3H), 2.21 (dt,
3J(H,H)=14.3, 8.4 Hz, 1H), 2.60–2.66 (m, 2H), 2.80 (brs, 1H), 3.76 (ddd,
3J(H,H)=11.7, 7.0, 5.1, 1H), 3.81–3.90 (m, 2H), 3.99 (dd, 3J(H,H)=9.2,
5-Methyl-6-octene-1,4-diol (4d): 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=1.00 (d, J=6.6 Hz, 1H), 1.43 (m, 1H), 1.62–1.76 (m, 7H), 2.25
3
(dddd, J(H,H)=0.7, 6.6, 8.8, 17.5 Hz, 1H), 2.79 (brs, 1H), 3.37 (m, 1H),
3.59–3.72 (m, 2H), 5.25 (ddq, 3J(H,H)=16.2, 11.0, 1.8 Hz, 1H), 5.61
13
(dddd, 3J(H,H)=0.7, 7.0, 11.0, 11.7 Hz, 1H);
C NMR (100 MHz,
3
3
CDCl3, 258C, TMS) d=15.3, 16.7, 29.3, 31.1, 42.9, 62.9, 75.0, 126.1, 132.9;
IR (neat): n˜ =3340, 2933, 2873, 1448, 1375, 1056, 977 cmꢀ1; HRMS (EI):
m/z (%): calcd for C9H18O2ꢀH2O: 141.1279, found: 141.1183 (1) [M +
ꢀH2O], 140 (1), 71 (100).
5.1 Hz, 1H), 4.32 (dt, J(H,H)=8.1, 5.1 Hz, 1H), 5.20 (dd, J(H,H)=14.7,
1.5 Hz, 1H), 5.21 (dd, 3J(H,H)=11.7, 1.5 Hz, 1H), 5.86 (dddd, 3J(H,H)=
14.7, 11.7, 8.4, 6.2 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d=25.34, 27.95, 38.84, 61.03, 68.54, 77.41, 79.36, 108.39, 119.21, 133.93;
6638
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 6629 – 6642

Allylation of Aldehydes
FULL PAPER
IR (neat): n˜ =3396, 3078, 2986, 2937, 2359, 2341, 1643, 1456, 1380, 1246,
1217, 1167, 1042, 918, 874, 797 cmꢀ1; HRMS (EI): m/z (%): calcd for
C10H19O4: 203.1302, found: 203.1283 (3) [M +], 188 (10), 187 (100), 171
(23), 169 (1).
2.92 (d, 3J(H,H)=5.5 Hz, 1H), 3.59–3.65 (m, 3H), 3.70 (dd, 3J(H,H)=
7.7, 1.8 Hz, 1H), 3.72 (dd, J(H,H)=7.0, 2.9 Hz, 1H), 4.05 (brs, 1H), 4.05
3
(dd, 3J(H,H)=7.7, 2.9 Hz, 1H), 4.51 (dd, 3J(H,H)=11.4, 2.9 Hz, 1H),
4.52–4.53 (m, 3H), 4.59 (dd, 3J(H,H)=11.4, 1.8 Hz, 1H), 4.63 (d,
3J(H,H)=11.4 Hz, 1H), 4.75 (d, 3J(H,H)=11.4 Hz, 1H), 4.86 (d,
3J(H,H)=11.4 Hz, 1H), 5.00 (dd, 3J(H,H)=17.2, 1.8 Hz, 1H), 5.01 (dd,
3J(H,H)=10.3, 1.1 Hz, 1H), 5.65 (ddt, 3J(H,H)=17.2, 10.3, 7.0 Hz, 1H),
7.23–7.36 (m, 20H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=38.84,
70.64, 71.34, 73.05, 73.52, 74.81, 75.00, 77.49, 79.44, 80.45, 117.46, 127.78,
127.96, 128.11, 128.31, 128.40, 134.94, 137.94, 138.15, 138.32; minor
isomer: 1H NMR (400 MHz, CDCl3, 258C, TMS): d=2.22 (dt, 3J(H,H)=
14.3, 8.1 Hz, 1H), 2.37 (m, 1H), 2.90 (d, 3J(H,H)=4.4 Hz, 1H), 3.62 (d,
1-(5-Hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-methyl-3-buten-1-
1
ol (7b): a mixture in a ratio of 2:2:1:1; H NMR (400 MHz, CDCl3, 258C,
2
3
TMS): an isomer corresponding to = : d=1.16 (d, J(H,H)=7.0 Hz, 3H),
6
1.34 (s, 3H), 1.41 (s, 3H), 2.57 (d, 3J(H,H)=5.5 Hz, 1H), 2.66 (m, 1H),
3
3
2.73 (t, J(H,H)=5.5 Hz, 1H), 3.68–3.89 (m, 3H), 4.07 (dd, J(H,H)=9.9,
5.5 Hz, 1H), 4.28 (ddd, 3J(H,H)=7.7, 5.5, 4.8 Hz, 1H), 5.16 (dd,
3J(H,H)=17.2, 1.8 Hz, 1H), 5.19 (dd, 3J(H,H)=10.6, 1.8 Hz, 1H), 5.89
(ddd, 3J(H,H)=17.2, 10.6, 7.7 Hz 1H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=16.66, 25.38, 28.02, 39.66, 61.14, 72.63, 77.41, 77.84,
3
3J(H,H)=4.4 Hz, 2H), 3.62–3.65 (m, 1H), 3.85 (dd, J(H,H)=6.6, 3.7 Hz,
1H), 3.90 (m, 1H), 3.94 (t, 3J(H,H)=4.2 Hz, 1H), 4.03 (m, 1H), 4.50 (d,
3J(H,H)=11.7 Hz, 1H), 4.53 (d, 3J(H,H)=7.9 Hz, 2H), 4.58 (d,
3J(H,H)=7.9 Hz, 2H), 4.63 (d, 3J(H,H)=11.0 Hz, 1H), 4.67 (d, 3J-
(H,H)=11.0 Hz, 1H), 5.05–5.08 (brs, 2H), 5.82 (dddd, 3J(H,H)=17.2,
9.9, 7.7, 6.6 Hz, 1H), 7.22–7.37 (m, 20H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=37.98, 71.11, 71.26, 71.26, 73.50, 73.99, 77.45, 78.78,
79.48, 117.35, 127.79, 128.05, 128.20, 128.48, 135.13, 137.62, 137.94,
138.09; IR (KBr): n˜ =3445, 3062, 3030, 3007, 2864, 1952, 1871, 1811,
1641, 1607, 1585, 1497, 1454, 1209, 1001, 916, 819, 698 cmꢀ1; HRMS (EI):
m/z (%): calcd for C37H42O6: 582.2981, found: 582.2966 (13) [M +],
492.2517 (40), 491.2459 (100).
108.32, 117.19, 138.05; an isomer corresponding to 2= : 1H NMR
6
(400 MHz, CDCl3, 258C, TMS): d=1.07 (d, 3J(H,H)=7.0 Hz, 3H), 1.36
(s, 3H), 1.42 (s, 3H), 2.38 (d, 3J(H,H)=2.9 Hz, 1H), 2.66 (m, 1H), 2.88
(dd, 3J(H,H)=7.3, 4.8 Hz, 1H), 3.68–3.89 (m, 3H), 4.12 (dd, 3J(H,H)=
9.2, 5.5 Hz, 1H), 4.33 (dt, 3J(H,H)=7.3, 5.1 Hz, 1H), 5.16 (dd, 3J(H,H)=
17.2, 1.8 Hz, 1H), 5.18 (dd, 3J(H,H)=10.6, 1.8 Hz, 1H), 5.92 (ddd,
3J(H,H)=17.2, 10.6, 6.2 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C,
TMS): d=10.90, 25.38, 28.02, 38.77, 61.03, 71.15, 76.83, 77.41, 108.32,
115.83, 140.97; an isomer corresponding to 1= : 1H NMR (400 MHz,
6
3
CDCl3, 258C, TMS): d=1.10 (d, J(H,H)=7.0 Hz, 3H), 1.38 (s, 3H), 1.51
(s, 3H), 2.41 (m, 1H), 2.48–2.80 (m, 2H), 3.57 (brs, 1H), 3.75–3.80 (m,
2H), 4.17–4.24 (m, 2H), 5.11 (d, 3J(H,H)=16.1 Hz, 1H), 5.12 (d,
3J(H,H)=9.9 Hz, 1H), 5.87 (ddd, 3J(H,H)=16.1, 9.9, 8.1 Hz, 1H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=16.62, 25.22, 27.36, 42.22,
61.50, 71.93, 76.52, 77.61, 108.36, 116.02, 139.99; an isomer corresponding
(2R,3R,4R,5S,6R,7R)-1,3,4,5-Tetrabenzyloxy-7-phenyl-8-nonene-2,6-diol
(9b): 1H NMR (400 MHz, CDCl3, 258C, TMS): d=2.09 (d, 3J(H,H)=
8.0 Hz, 1H), 2.93 (d, 3J(H,H)=5.2 Hz, 1H), 3.53 (dt, 3J(H,H)=10.2,
8.0 Hz, 1H), 3.63 (d, 3J(H,H)=4.7 Hz, 2H), 3.72 (dd, 3J(H,H)=6.6,
3.0 Hz, 1H), 3.93 (t, 3J(H,H)=8.0 Hz, 1H), 4.02–4.12 (m, 2H), 4.14 (dd,
3J(H,H)=8.0, 3.0 Hz, 1H), 4.49 (d, 3J(H,H)=11.4 Hz, 1H), 4.51 (d,
3J(H,H)=11.4 Hz, 1H), 4.54 (d, 3J(H,H)=12.5 Hz, 1H), 4.55 (d,
3J(H,H)=12.5 Hz, 1H), 4.60 (d, 3J(H,H)=11.3 Hz, 1H), 4.64 (d, 3J
to 1= : 1H NMR (400 MHz, CDCl3, 258C, TMS): d=1.12 (d, 3J(H,H)=
6
7.0 Hz, 3H), 1.36 (s, 3H), 1.51 (s, 3H), 2.41 (m, 1H), 2.48–2.80 (m, 2H),
3.48 (brs, 1H), 3.75–3.80 (m, 2H), 4.20 (m, 1H), 4.28 (dd, 3J(H,H)=7.0,
1.8 Hz, 1H), 5.06 (dd, 3J(H,H)=10.3, 1.8 Hz, 1H), 5.12 (d, 3J(H,H)=
16.9 Hz, 1H), 5.70 (ddd, 3J(H,H)=16.9, 10.3, 8.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=16.54, 24.91, 27.17, 43.24, 61.50,
71.93, 76.21, 77.22, 108.12, 115.83, 140.70; IR (neat): n˜ =3385, 3076, 2985,
2359, 2341, 1638, 1458, 1371, 1220, 1168, 1008, 918, 885, 796 cmꢀ1; HRMS
(EI): m/z (%): calcd for C11H21O4: 217.1471, found: 217.1440 (13) [M +],
216 (2), 199 (2), 186 (16), 185 (100), 183 (5).
3
3
(H,H)=11.3 Hz, 1H), 4.78 (d, J(H,H)=11.2 Hz, 1H), 4.91 (d, J(H,H)=
3
3
11.2 Hz, 1H), 4.90 (d, J(H,H)=16.8 Hz, 1H), 4.98 (d, J(H,H)=10.2 Hz,
1H), 5.76 (dt, 3J(H,H)=16.8, 10.2 Hz, 1H), 7.12–7.38 (m, 25H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=54.3, 70.5, 71.3, 72.8, 73.3,
73.4, 74.5, 74.7, 77.8, 78.0, 79.3, 116.9, 126.5, 127.5, 127.6, 127.7, 127.8,
127.9, 128.0, 128.2, 128.3, 128.4, 128.5, 137.8, 137.9, 138.0, 138.4, 138.5,
141.2; IR (KBr): n˜ =3447, 3062, 3030, 2866, 2361, 2341, 1716, 1600, 1585,
1497, 1454, 1361, 1261, 1211, 1070, 1028, 918, 734, 698, 667 cmꢀ1; HRMS
(EI): m/z (%): calcd for C43H46O6: 658.3294, found: 658.3357 (7) [M +],
568 (33), 538 (44), 537 (100), 524 (41).
2-tert-Butyl-1-(5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-
buten-1-ol (7c): a mixture of isomers in a ratio of 10:2:2:1; major isomer:
1H NMR (400 MHz, CDCl3, 258C, TMS): d=0.99 (s, 9H), 1.34 (s, 3H),
1.50 (s, 3H), 2.09 (dd, 3J(H,H)=10.3, 8.4 Hz, 1H), 2.47 (brs, 1H), 2.98
(brs, 1H), 3.71–3.78 (brs, 2H), 3.82 (dt, 3J(H,H)=1.5, 8.4 Hz, 1H), 4.16
(dt, 3J(H,H)=7.0, 5.1 Hz, 1H), 4.34 (dt, 3J(H,H)=7.0, 1.5 Hz, 1H), 5.07
(dd, 3J(H,H)=17.0, 2.2 Hz, 1H), 5.14 (dd, 3J(H,H)=10.3, 2.2 Hz, 1H),
(2R,3R,4R,5R,6S)-1,3,4,5-Tetrakis(benzyloxy)-8-nonene-2,6-diol
[(6S)-
11]: 1H NMR (400 MHz, CDCl3, 258C, TMS): d=2.30 (dt, 3J(H,H)=
13.9, 7.0 Hz, 1H), 2.37 (dt, 3J(H,H)=13.9, 7.0 Hz, 1H), 2.69 (d, 3J
(H,H)=5.6 Hz, 1H), 2.97 (d, 3J(H,H)=6.0 Hz, 1H), 3.62 (dd, 3J(H,H)=
5.6, 9.6 Hz, 1H), 3.67 (m, 1H), 3.68 (dd, 3J(H,H)=4.0, 9.6 Hz, 1H), 3.78
(dd, 3J(H,H)=4.0, 7.0 Hz, 1H), 3.95–4.06 (m, 3H), 4.49–4.59 (m, 4H),
4.61 (brs, 2H), 4.75 (brs, 2H), 5.03 (brd, 3J(H,H)=14.1 Hz, 1H), 5.05
(brd, 3J(H,H)=10.5 Hz, 1H), 5.78 (brddt, 3J(H,H)=10.5, 14.1, 7.0 Hz,
1H), 7.23–7.35 (m, 20H); 13C NMR (400 MHz, CDCl3 258C, TMS): d=
38.9, 70.4, 70.6, 71.1, 73.1, 73.3, 73.4, 74.6, 78.6, 79.4, 79.7, 117.2, 127.5,
127.6, 127.7, 127.9, 128.1, 128.2, 128.3, 135.0, 137.7, 137.8, 137.9, 138.1; IR
(neat): n˜ =3464 (s), 2870 (s), 1096 (s), 741 cmꢀ1 (s); HRMS (EI): m/z
(%): calcd for C37H42O6: 582.2981, found: 582.2987 (2) [M +], 491 (100),
433 (71).
3
5.61 (dt, J(H,H)=17.0, 10.3 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C,
TMS): d=24.91, 27.24, 29.15, 32.62, 59.16, 61.65, 68.89, 76.71, 77.80,
107.89, 118.44, 137.04; IR (KBr): n˜ =3406, 3074, 2954, 2908, 2872, 1639,
1467, 1419, 1381, 1369, 1244, 1217, 1163, 1105, 1072, 1040, 980, 916, 874,
862, 800 cmꢀ1; elemental analysis calcd (%) for C14H26O4 (258.4): C 65.09,
H, 10.14; found: C 65.30, H 10.29.
(2R,3S,4R,5R)-1-(5-Hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-
phenyl-3-buten-1-ol (7d): m.p. 91.0–92.0 (Et2O/hexane); 1H NMR
(400 MHz, CDCl3, 258C, TMS) d= 1.38 (s, 3H), 1.52 (s, 3H), 2.48 (brs,
1H), 2.83 (brs, 1H), 3.62 (dd, 3J(H,H)=9.2, 8.8 Hz, 1H), 3.78–3.84 (m,
2H), 4.02 (m, 1H), 4.20 (dt, 3J(H,H)=6.8, 5.1 Hz, 1H), 4.33 (dd,
3J(H,H)=6.8, 1.8 Hz, 1H), 5.18 (dd, 3J(H,H)=9.5, 1.5 Hz, 1H), 5.21 (dd,
3J(H,H)=16.9, 1.5 Hz, 1H), 6.03 (ddd, 3J(H,H)=16.9, 9.5, 9.2 Hz, 1H),
7.21–7.36 (m, 5H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d= 25.34,
27.95, 55.27, 61.50, 71.03, 75.70, 77.57, 108.23, 117.62, 128.28, 128.83,
137.97, 140.70; IR (KBr): n˜ =3330, 2989, 2893, 2345, 1633, 1602, 1454,
1379, 1261, 1211, 1164, 1123, 1043, 1022, 1005, 931, 899, 844, 700,
628 cmꢀ1; HRMS (EI): m/z (%): calcd for C16H23O4: 278.1520, found:
278.1518 (3) [M +], 263.13 (100), 262.15 (3), 260.14 (8), 247.13 (2),
220.132 (3).
(2R,3S)-1-Triphenylmethoxy-7-octene-2,3,5-triol (13a):
a mixture in a
ratio of 1:1, isomer 1: 1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.52
(ddd, 3J(H,H)=14.3, 8.2, 4.9 Hz, 1H), 1.63 (ddd, 3J(H,H)=14.3, 6.6,
4.9 Hz, 1H), 2.13–2.32 (m, 3H), 2.69 (d, 3J(H,H)=4.7 Hz, 1H), 2.88 (d,
3J(H,H)=5.5 Hz, 1H), 3.29 (dd, 3J(H,H)=9.6, 3.6 Hz, 1H), 3.42 (dd,
3
3J(H,H)=9.6, 3.8 Hz, 1H), 3.70 (dquint, J(H,H)=5.5, 4.7 Hz, 1H), 3.88–
4.00 (m, 2H), 5.12 (dd, 3J(H,H)=15.9, 0.9 Hz, 1H), 5.13 (dd, 3J(H,H)=
3
11.3, 0.9 Hz, 1H), 5.79 (dddd, J(H,H)=15.9, 11.8, 9.9, 6.9 Hz, 1H), 7.22–
7.45 (m, 15H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=38.02, 42.02,
64.65, 68.05, 70.39, 72.85, 87.05, 118.16, 126.99, 127.73, 128.36, 134.21,
143.35; isomer 2: 1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.40 (dt,
3J(H,H)=14.3, 9.9 Hz, 1H), 1.62 (dt, 3J(H,H)=14.3, 2.5 Hz, 1H), 2.16
(2R,3R,4R,5S,6R)-1,3,4,5-Tetrabenzyloxy-8-nonene-2,6-diol (9a): a mix-
ture in a ratio of 12:1, major isomer: 1H NMR (400 MHz, C6D6, 258C,
TMS): d=2.11 (dtd, 3J(H,H)=14.3, 7.3, 1.1 Hz, 1H), 2.21–2.29 (m, 2H),
Chem. Eur. J. 2005, 11, 6629 – 6642
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6639

Y. Tamaru et al.
(dt, 3J(H,H)=14.3, 7.2 Hz, 1H), 2.22 (dt, 3J(H,H)=14.3, 5.2 Hz, 1H),
2.76 (brs, 1H), 2.91 (brs, 1H), 3.32 (d, 3J(H,H)=5.2 Hz, 2H), 3.45 (brs,
1H), 3.67 (quint, 3J(H,H)=5.2 Hz, 1H), 3.82–3.96 (m, 2H), 5.10 (d,
3J(H,H)=16.8 Hz, 1H), 5.11 (d, 3J(H,H)=10.4 Hz, 1H), 5.76 (dddd,
3J(H,H)=16.8, 10.4, 7.2, 5.2 Hz, 1H), 7.22–7.45 (m, 15H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=37.67, 42.39, 64.31, 71.06, 72.84, 73.47,
87.01, 118.12, 126.97, 127.71, 128.36, 133.94, 143.36; IR (neat): n˜ =3363,
3060, 2881, 2341, 1965, 1645, 1596, 1488, 1446, 1418, 1219, 1184, 1001,
999, 918, 827 cmꢀ1; HRMS: m/z (%): calcd for C10H17O4: 201.1127,
found: 201.1130 (100) [M +ꢀMe], 185 (60), 157 (90).
4-(2-Hydroxy-3-phenyl-4-pentenyl)-2,2-dimethyl-1,3-dioxan-5-ol (15b): a
mixture in a ratio of 2:2:2:1, an isomer corresponding to 2= : 1H NMR
7
(400 MHz, C6D6, 258C, TMS) d=1.42 (s, 3H), 1.50 (s, 3H), 1.66 (ddd,
3J(H,H)=14.4, 10.5, 5.6 Hz, 1H), 1.77 (brs, 1H), 1.94 (brs, 1H), 2.13
(ddd, 3J(H,H)=14.4, 7.6, 2.2 Hz, 1H), 3.21 (t, 3J(H,H)=8.1 Hz, 1H),
3.54–3.70 (brs, 2H), 4.05 (brs, 1H), 4.17 (q, 3J(H,H)=5.8 Hz, 1H), 4.50
900, 748, 705, 633 cmꢀ1
; HRMS (EI): m/z (%): calcd for C27H30O4
3
3
(dt, J(H,H)=7.6, 5.8 Hz, 1H), 5.05 (dd, J(H,H)=10.2, 1.7 Hz, 1H), 5.08
(dd, 3J(H,H)=17.1, 1.7 Hz, 1H), 5.95 (ddd, 3J(H,H)=17.1, 10.2, 1.7 Hz,
1H), 7.07–7.47 (m, 5H); 13C NMR (100 MHz, C6D6, 258C, TMS): d=
25.73, 28.46, 34.43, 58.28, 61.84, 71.92, 75.25, 78.41, 107.43, 116.65, 126.98,
418.2144, found: 418.2149 (56) [M +], 400 (19), 380 (25), 359 (19), 358
(69), 341 (100).
(2R,3S)-6-Phenyl-1-triphenylmethoxy-7-octene-2,3,5-triol (13b):
a mix-
ture in a ratio of 3:2:1:1, an isomer corresponding to 3= : 1H NMR
128.86, 128.95, 138.94, 141.19; an isomer corresponding to 2= : 1H NMR
7
7
(300 MHz, CDCl3, 258C, TMS): d=1.45 (m, 1H), 2.18 (m, 1H), 2.35
(400 MHz, C6D6, 258C, TMS): d=1.39 (s, 3H), 1.43 (s, 3H), 1.71 (ddd,
3J(H,H)=14.2, 10.2, 5.9 Hz, 1H), 1.83 (ddd, 3J(H,H)=14.4, 7.6, 2.4 Hz,
1H), 1.94 (brs, 1H), 2.04 (brs, 1H), 3.19 (dd, 3J(H,H)=8.6, 7.3 Hz, 1H),
3.52–3.67 (brs, 2H), 3.98 (brs, 1H), 4.19 (q, 3J(H,H)=5.9 Hz, 1H), 4.48
3
(brs, 1H), 2.66 (d, J(H,H)=4.7 Hz, 1H), 2.68 (d, 3J(H,H)=7.7 Hz, 1H),
3.13 (m, 1H), 3.11 (d, 3J(H,H)=4.7 Hz, 1H), 3.12 (d, 3J(H,H)=4.7 Hz,
3
1H), 3.63 (quint, J(H,H)=4.7 Hz, 1H), 3.92 (m, 1H), 4.15 (m, 1H), 5.19
(d, 3J(H,H)=17.9 Hz, 1H), 5.20 (d, 3J(H,H)=10.2 Hz, 1H), 6.06 (ddd,
3J(H,H)=17.9, 10.2, 9.1 Hz, 1H), 7.12–7.45 (m, 20H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=35.91, 57.62, 64.39, 72.63, 73.27,
74.34, 86.93, 117.86, 126.90, 127.66, 128.34, 137.52, 140.71, 143.42; an
3
3
(dt, J(H,H)=7.6, 5.9 Hz, 1H), 5.09 (dd, J(H,H)=17.0, 1.7 Hz, 1H), 5.13
(dd, 3J(H,H)=10.2, 1.7 Hz, 1H), 6.10 (ddd, 3J(H,H)=17.0, 10.2, 8.6 Hz,
1H), 7.08–7.47 (m, 5H); 13C NMR (100 MHz, C6D6, 258C, TMS): d=
25.79, 28.44, 34.44, 58.01, 61.76, 71.92, 75.29, 78.44, 107.43, 117.56, 126.85,
isomer corresponding to 2= : 1H NMR (300 MHz, CDCl3, 258C, TMS):
128.43, 128.84, 138.40, 141.82; an isomer corresponding to 2= : 1H NMR
7
7
d=1.53 (m, 1H), 1.82 (dm, 3J(H,H)=10.7 Hz, 1H), 2.70 (brs, 1H), 2.94
(d, 3J(H,H)=6.1 Hz, 1H), 3.16–3.32 (m, 3H), 3.40 (dd, 3J(H,H)=9.6,
3.9 Hz, 1H), 3.11 (d, 3J(H,H)=4.7 Hz, 1H), 3.12 (d, 3J(H,H)=4.7 Hz,
1H), 3.68 (m, 1H), 3.94 (m, 1H), 4.18 (m, 1H), 5.08 (d, 3J(H,H)=
11.5 Hz, 1H), 5.09 (d, 3J(H,H)=16.6 Hz, 1H), 5.94 (ddd, 3J(H,H)=17.2,
11.5, 9.1 Hz, 1H), 7.12–7.44 (m, 20H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=36.32, 57.34, 64.85, 72.88, 73.23, 74.29, 87.01, 116.91,
126.59, 127.74, 128.54, 137.84, 140.33, 143.39; an isomer corresponding to
(300 MHz, C6D6, 258C, TMS): d=1.15 (s, 3H), 1.24 (s, 3H), 1.36 (brs,
1H), 1.42 (ddd, 3J(H,H)=13.7, 4.1, 2.5 Hz, 1H), 1.68 (m, 1H), 2.85 (s,
1H), 3.20–3.36 (m, 2H), 3.32 (t, 3J(H,H)=5.8 Hz, 1H), 3.87 (q,
3
3J(H,H)=6.0 Hz, 1H), 3.97 (m, 1H), 4.12 (dt, J(H,H)=8.0, 6.0 Hz, 1H),
5.04 (dd, 3J(H,H)=10.2, 1.1 Hz, 1H), 5.09 (dd, 3J(H,H)=17.0, 1.1 Hz,
1H), 6.11 (ddd, 3J(H,H)=17.0, 10.2, 8.5 Hz, 1H), 7.05–7.28 (m, 5H);
13C NMR (100 MHz, C6D6, 258C, TMS): d=25.41, 27.98, 33.72, 57.19,
61.47, 73.83, 76.64, 78.20, 108.15, 116.23, 126.68, 128.33, 129.15, 139.37,
1= : 1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.38 (dt, 3J(H,H)=14.8,
1
141.33; an isomer corresponding to = : 1H NMR (300 MHz, C6D6, 258C,
7
7
9.4 Hz, 1H), 1.53 (d, 3J(H,H)=14.8 Hz, 1H), 2.66 (d, 3J(H,H)=4.1 Hz,
1H), 2.86 (brs, 1H), 3.21 (t, 3J(H,H)=9.4 Hz, 1H), 3.22 (d, 3J(H,H)=
5.5 Hz, 2H), 3.50 (d, 3J(H,H)=3.0 Hz, 1H), 3.60 (dq, 3J(H,H)=4.1,
5.5 Hz, 1H), 3.86 (m, 1H), 4.04 (t, 3J(H,H)=9.4 Hz, 1H), 5.17 (dd,
3J(H,H)=16.8, 1.7 Hz, 1H), 5.21 (dd, 3J(H,H)=10.2, 1.7 Hz, 1H), 6.11
(ddd, 3J(H,H)=16.8, 10.2, 9.4 Hz, 1H), 7.12–7.44 (m, 20H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d= 35.91, 57.75, 64.37, 72.65, 73.27,
74.32, 86.93, 117.11, 126.91, 127.67, 128.34, 137.52, 140.71, 143.42; an
TMS): d=1.14 (s, 3H), 1.25 (s, 3H), 1.58–1.78 (m, 3H), 3.03 (s, 1H), 3.25
(dd, 3J(H,H)=6.6, 5.5 Hz, 1H), 3.79 (q, 3J(H,H)=6.0 Hz, 1H), 4.03 (m,
1H), 5.10 (dd, 3J(H,H)=17.0, 1.1 Hz, 1H), 5.12 (dd, 3J(H,H)=10.4,
1.1 Hz, 1H), 6.33 (ddd, 3J(H,H)=17.0, 10.4, 8.2 Hz, 1H); 13C NMR
(100 MHz, C6D6, 258C, TMS): d=34.17, 57.14, 61.41, 73.92, 76.72, 78.20,
116.70, 128.59, 128.74, 138.81, 142.21; IR (neat): n˜ =3418, 2984, 2934,
2876, 1637, 1601, 1495, 1454, 1371, 1246, 1219, 1165, 1059, 1003, 920, 845,
762, 704 cmꢀ1; HRMS: m/z (%): calcd for C16H21O4: 277.1440, found:
277.1433 (18) [M +ꢀMe], 292 (1), 278 (3), 203 (8), 185 (9), 175 (8), 157
(100).
isomer corresponding to 1= : 1H NMR (300 MHz, CDCl3, 258C, TMS):
7
d=1.39 (dt, 3J(H,H)=15.3, 8.8 Hz, 1H), 1.93 (d, 3J(H,H)=15.3 Hz, 1H),
2.46 (brs, 1H), 2.70 (d, 3J(H,H)=4.4 Hz, 1H), 3.23 (t, 3J(H,H)=8.8 Hz,
1H), 3.30 (d, 3J(H,H)=5.2 Hz, 2H), 3.55 (d, 3J(H,H)=2.5 Hz, 1H), 3.66
(dq, 3J(H,H)=4.4, 5.5 Hz, 1H), 3.92 (m, 1H), 4.04 (t, 3J(H,H)=9.4 Hz,
1H), 5.10 (d, 3J(H,H)=16.8 Hz, 1H), 5.11 (d, 3J(H,H)=11.7 Hz, 1H),
5.96 (ddd, 3J(H,H)=16.8, 11.7, 8.8 Hz, 1H), 7.12–7.44 (m, 20H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=35.91, 57.60, 64.44, 72.80,
73.37, 74.65, 86.95, 117.86, 126.93, 127.69, 128.37, 137.71, 140.05, 143.44;
IR (neat): n˜ =3412, 3059, 3032, 2928, 2876, 2247, 1734, 1597, 1491, 1448,
General Procedure for the self-allylation of w-formyl allyl ether 21: Com-
pound 21 (1.0 mmol) and diethylzinc (2.4 mmol, 1.0m hexane) were
added successively via syringe at 08C under N2 to a solution of Pd(OAc)2
(22.6 mg, 0.1 mmol) and nBu3P (80.9 mg, 0.4 mmol) in dry toluene
(0.5 mL). The mixture was allowed to warm to ambient temperature and
stirred for 3 h. The mixture was diluted with AcOEt and then washed
with 0.2m HCl, sat. NaHCO3, and brine, and the organic phase was dried
(MgSO4) and concentrated in vacuo to give an oil, which was purified by
column chromatography on silica gel (AcOEt/hexane 1:10) to give 22a in
95% yield or 22b in 85% yield.
1421, 1223, 1184, 1076, 991, 949, 910, 849, 764, 733, 706, 648, 633 cmꢀ1
;
HRMS (EI): m/z (%): calcd for C27H29O4: 417.2070, found: 417.2039 (7)
[M +ꢀPh], 376 (5), 359 (4), 299 (14), 260 (39), 259 (100), 258 (50).
1-(o-Hydroxyphenyl)-3-buten-1-ol (22a): 1H NMR (400 MHz, CDCl3,
4-(2-Hydroxy-4-pentenyl)-2,2-dimethyl-1,3-dioxan-5-ol (15a): a mixture
in a ratio of 1:1, isomer 1: 1H NMR (300 MHz, CDCl3, 258C, TMS): d=
258C, TMS): d=2.61 (t, 3J(H,H)=6.9 Hz, 2H), 2.99 (brs, 2H), 4.65 (d,
3
3J(H,H)=12.1 Hz,
3J(H,H)=6.9 Hz,
1 1 H), 4.97 (t,
H), 4.73 (d, 3J(H,H)=12.1 Hz,
1.38 (s, 3H), 1.46 (s, 3H), 1.65 (ddd, J(H,H)=14.3, 9.6, 5.0 Hz, 1H), 1.81
1
H), 5.16 (d, 3J(H,H)=10.2 Hz, 1H), 5.18 (d,
(ddd, 3J(H,H)=14.3, 8.5, 2.8 Hz, 1H), 2.16–2.39 (m, 3H), 3.57–3.72 (m,
2H), 3.88 (brs, 1H), 4.23 (dt, 3J(H,H)=6.3, 5.2 Hz, 1H), 4.45 (ddd,
3J(H,H)=8.5, 6.3, 5.0 Hz, 1H), 5.15 (d, 3J(H,H)=15.7 Hz, 1H), 5.16 (d,
3J(H,H)=10.7 Hz, 1H), 5.81 (dddd, 3J(H,H)=15.7, 10.7, 8.0, 6.6 Hz,
1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=25.42, 28.09, 35.46,
42.51, 61.58, 68.12, 74.29, 77.79, 107.72, 118.41, 134.13; isomer 2:
1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.38 (s, 3H), 1.49 (s, 3H),
1.66–1.71 (m, 2H), 1.95 (brs, 1H), 2.25–2.32 (m, 2H), 3.14 (brs, 1H),
3.64 (dd, 3J(H,H)=5.6, 5.2 Hz, 2H), 3.89 (quint, 3J(H,H)=6.0 Hz, 1H),
4.21 (dt, 3J(H,H)=6.3, 5.6 Hz, 1H), 4.38 (dt, 3J(H,H)=6.9, 6.3 Hz, 1H),
5.11 (d, 3J(H,H)=10.4 Hz, 1H), 5.12 (d, 3J(H,H)=17.3 Hz, 1H), 5.83
(ddt, 3J(H,H)=17.3, 10.4, 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=25.4, 28.0, 35.1, 41.7, 61.5, 70.6, 76.6, 77.9, 108.6, 117.6,
134.4; IR (neat): n˜ =3408, 2986, 2936, 1641, 1456, 1371, 1218, 1167, 1043,
3J(H,H)=17.0 Hz, 1H), 5.87 (ddt, J(H,H)=17.0, 10.2, 6.9 Hz, 1H), 7.24–
7.46 (m, 4H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=41.9, 63.5,
70.4, 118.2, 126.5, 127.8, 128.3, 129.6, 134.6, 137.9, 141.6; IR (neat): n˜ =
3333, 3071, 2916, 1643, 1450, 1319, 1211, 1003, 918, 871, 764 cmꢀ1; HRMS
(EI): m/z (%): calcd for C11H14O2: 178.0994, found: 178.0936 (3) [M +],
177 (11), 160 (100).
3
Tridec-12-ene-1,10-diol (22b): 1H NMR (400 MHz, CDCl3, 258C, TMS):
d=1.23–1.68 (m, 16H), 1.69–1.98 (brs, 2H), 2.15 (ddd, 3J(H,H)=13.7,
3
7.4, 6.8 Hz, 1H), 2.30 (dt, J(H,H)=13.7, 5.9 Hz, 1H), 3.55 (m, 1H), 3.64
(t, 3J(H,H)=6.6 Hz, 2H), 5.12 (dd, 3J(H,H)=15.8, 1.4 Hz, 1H), 5.13
(dqm, 3J(H,H)=11.4, 1.4 Hz, 1H), 5.83 (dddd, 3J(H,H)=15.8, 11.4, 6.8,
5,9 Hz, 1H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=25.6, 25.7,
29.2, 29.4, 29.5, 29.6, 32.8, 36.8, 41.9, 62.9, 70.6, 117.9, 134.8; IR(neat): n˜ =
6640
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 6629 – 6642

Allylation of Aldehydes
FULL PAPER
3333, 3078, 2924, 2855, 2361, 1712, 1643, 1458, 1365, 1265, 1057, 910,
725 cmꢀ1; HRMS (EI): m/z (%): calcd for C13H26O2: 214.1933, found:
214.1858 (20) [M +], 213 (100), 196 (9), 184 (6).
(100 MHz, CDCl3, 258C, TMS): d=20.9, 23.6, 24.4, 26.1, 29.6, 31.0, 32.3,
41.3, 63.0, 80.4, 84.0, 86.3, 126.7, 127.6, 128.2, 128.5, 144.2, 149.0; IR
(neat): n˜ =3031, 2939, 2869, 1751, 1489, 1450, 1373, 1204, 1087, 903, 849,
764, 702 cmꢀ1; HRMS (EI): m/z (%): calcd for C31H34O4: 470.2457:
found: 470.2455 (9) [M +], 409 (19), 408 (57), 394 (27), 393 (100).
Structure determination
Conversion of 2b to a cyclic acetal, trans-2,2-dimethyl(4-(4-hydroxybu-
tyl))-5-methyl-1,3-dioxacyclohexane (16): i) A solution of 2b (59 mg,
0.37 mmol, anti/syn 5:1) in dichloromethane (13 mL) was cooled to
ꢀ788C, and ozone was bubbled through until a blue color appeared (ca.
5 min). The excess of ozone was removed by a flow of O2. The mixture
was allowed to warmto 0 8C. To this solution was added a solution of
NaBH4 (238.2 mg, 6.3 mmol) in MeOH/H2O (4 mL, 1:1) and then the
mixture was stirred at ambient temperature for 12 h. The mixture was di-
luted with AcOEt and washed with 2m HCl and sat. NaHCO3. The or-
ganic phase was dried (MgSO4) and the solvent was removed in vacuo to
give an oil.
(4R,5S,6R,7R,8R)-4-Allyl-5,6,7-tris(benzyloxy)-8-(benzyloxymethyl)-2,2-
dimethyl-1,3-dioxaoctane (19): p-TsOH (6.5 mg, 0.034 mmol) at ambient
temperature under N2 was added to
a solution of 9a (80.9 mg,
0.34 mmol) in 2,2-dimethoxypropane (5 mL). The mixture was stirred at
reflux for 3 h, diluted with AcOEt, washed with sat. NaHCO3 and brine,
dried (MgSO4), and concentrated in vacuo to give an oil, which was puri-
fied by column chromatography on silica gel (AcOEt/hexane 1:10) to
give 19 (155 mg, 73%). 1H NMR (400 MHz, C6D6, 278C, TMS): d=1.25
(s, 3H), 1.26 (s, 3H), 2.45 (ddd, 3J(H,H)=15.1, 7.3, 3.9 Hz, 1H), 2.79
(ddd, 3J(H,H)=15.1, 10.0, 7.3 Hz, 1H), 3.51 (dd, 3J(H,H)=10.0, 1.1 Hz,
1H), 3.83 (dd, 3J(H,H)=10.0, 3.9 Hz, 1H), 3.91 (dd, 3J(H,H)=10.0,
7.8 Hz, 1H), 4.02 (t, 3J(H,H)=7.8 Hz, 1H), 4.10 (dt, 3J(H,H)=10.0,
3.9 Hz, 1H), 4.21 (dd, 3J(H,H)=7.8, 1.1 Hz, 1H), 4.26 (dd, 3J(H,H)=7.8,
3.9 Hz, 1H), 4.28–4.41 (m, 3H), 4.56 (d, 3J(H,H)=11.0 Hz, 1H), 4.68 (d,
3J(H,H)=11.4 Hz, 1H), 4.80 (d, 3J(H,H)=11.0 Hz, 1H), 4.92 (d,
3J(H,H)=12.0 Hz, 1H), 5.09 (d, 3J(H,H)=11.4 Hz, 1H), 5.12 (d,
3J(H,H)=10.0 Hz, 1H), 5.19 (d, 3J(H,H)=17.3 Hz, 1H), 6.02 (ddt,
3J(H,H)=17.1, 10.0, 7.3 Hz, 1H), 7.04–7.35 (m, 20H); 13C NMR
(100 MHz, C6D6, 258C, TMS): d=24.5, 26.3, 35.1, 71.2, 71.9, 72.0, 73.3,
74.2, 74.5, 74.7, 74.8, 77.5, 80.9, 81.4, 100.4, 116.0, 127.1, 127.2, 127.3,
127.4, 127.5, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 136.6, 138.9, 139.1,
139.2, 139.4, 139.5; IR (neat): n˜ =3063, 3030, 2990, 2864, 2360, 1641,
ii) A solution of the oil and p-TsOH (8 mg, 0.04 mmol) in 2,2-dimethoxy-
propane (5 mL) was stirred at ambient room temperature for 3 h. The
mixture was diluted with AcOEt (50 mL) and washed with sat. NaHCO3
and brine. The organic phase was dried (MgSO4) and concentrated in
vacuo to give an oil, which was purified by column chromatography on
silica gel (AcOEt/hexane 1:7) to give 16 (trans/cis 8:1; 22 mg, in 30%
overall yield). 1H NMR (400 MHz, CDCl3, 258C, TMS): d=0.74 (d,
3J(H,H)=6.8 Hz, 1H), 1.05 (d, 3J(H,H)=7.1 Hz, 1H, cis), 1.38 (s, 3H),
1.39 (s, 3H, cis), 1.42 (s, 3H), 1.43 (s, 3H, cis), 1.34–1.71 (m, 7H), 3.44
(ddd, 3J(H,H)=10.2, 7.9, 2.4 Hz, 1H), 3.48 (t, 3J(H,H)=11.7 Hz, 1H),
3.57 (dd, 3J(H,H)=11.7, 1.7 Hz, 1H, cis), 3.65 (t, 3J(H,H)=6.4 Hz, 2H),
3.66 (dd, 3J(H,H)=11.7, 5.2 Hz, 1H), 3.92 (ddd, 3J(H,H)=7.9, 4.9,
2.7 Hz, 1H, cis), 4.08 (dd, 3J(H,H)=11.7, 2.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3, 258C, TMS, trans-16): d=12.7, 19.2, 21.2, 29.7, 32.6,
32.7, 34.0, 62.8, 66.1, 74.9, 98.1; cis-16: d=10.6, 19.1, 21.7, 30.9, 31.8, 32.7,
33.9, 62.7, 66.9, 71.4, 98.1; IR (neat): n˜ =3410, 2939, 2862, 1651, 1458,
1380, 1265, 1203, 1111, 1065, 910, 864, 802, 756 cmꢀ1; HRMS (EI): m/z
(%): calcd for C11H22O3: 202.1569: found: 202.1563 (0.1) [M +], 188 (12),
187 (100), 173 (1).
1497, 1454, 1381, 1327, 1207, 1074, 1028, 999, 912, 827, 734, 698 cmꢀ1
;
HRMS (EI): m/z (%): calcd for C40H46O6: 622.3294, found: 622.3290 (8)
[M +], 581 (10), 564 (10), 552 (5), 532 (39), 531 (100).
5,6,7-Tris(benzyloxy)-4-benzyloxymethyl-2,2-dimethyl-8-(1-phenylallyl)-
1,3-dioxaoctane: 1H NMR (400 MHz, CDCl3, 258C, TMS): d=0.68 (s,
3H), 1.08 (s, 3H), 3.44 (dd, 3J(H,H)=10.4, 2.0 Hz, 1H), 3.58 (t, 3J
(H,H)=9.9 Hz, 1H), 3.72 (dd, 3J(H,H)=10.4, 2.9 Hz, 1H), 3.83 (dd,
3J(H,H)=8.8, 1.2 Hz, 1H), 3.90 (d, 3J(H,H)=7.1 Hz, 1H), 3.99 (dd,
3J(H,H)=7.1, 1.2 Hz, 1H), 4.27 (d, 3J(H,H)=9.9 Hz, 1H), 4.28 (d,
3J(H,H)=11.2 Hz, 1H), 4.35 (d, 3J(H,H)=12.2, 1H), 4.40–4.49 (m, 3H),
4.43 (d, 3J(H,H)=8.8 Hz, 1H), 4.55 (d, 3J(H,H)=12.2 Hz, 1H), 4.58 (d,
3J(H,H)=12.2 Hz, 1H), 4.70 (d, 3J(H,H)=11.2 Hz, 1H), 4.84 (dd, 3J
(H,H)=17.1, 1.7 Hz, 1H), 4.93 (dd, 3J(H,H)=9.9, 1.7 Hz, 1H), 5.93 (dt,
3J(H,H)=17.1, 9.9 Hz, 1H), 7.11–7.34 (m, 25H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=23.7, 26.4, 53.3, 71.1, 71.2, 72.0, 72.3, 73.3, 76.0,
77.3, 78.3, 100.4, 116.7, 126.0, 127.3, 127.4, 127.7, 127.8, 127.9, 128.0,
128.1, 128.2, 128.3, 128.4, 128.7, 129.0, 138.3, 138.4, 138.5, 138.6, 138.8,
143.0; IR (neat): n˜ =3032, 2862, 2360, 1497, 1458, 1380, 1211, 1072, 918,
864, 810, 740, 702 cmꢀ1; HRMS (EI): m/z (%): calcd for C46H50O6:
698.3607, found: 698.3558 (15) [M +], 699 (100).
trans-2,2-Dimethyl-4-(3-hydroxypropyl)-5-phenyl-1,3-dioxacyclohexane
(17): This compound was obtained in 15% overall yield by using the pro-
cedure to obtain 16; 1H NMR (400 MHz, CDCl3, 258C, TMS): d=1.23–
1.65 (m, 4H), 1.48 (s, 3H), 1.61 (s, 3H), 2.29 (brs, 1H), 2.80 (dt,
3J(H,H)=5.3, 11.5 Hz, 1H), 3.57 (tm, 3J(H,H)=5.5 Hz, 1H), 3.84 (dd,
3J(H,H)=5.3, 11.5 Hz, 1H), 3.97 (t, 3J(H,H)=11.5 Hz, 1H), 4.08 (ddd,
3J(H,H)=11.5, 8.6, 2.4 Hz, 1H), 7.16–7.35 (m, 5H); IR (neat): n˜ =3437,
3030, 2995, 2941, 2873, 1949, 1454, 1383, 1267, 1201, 1055, 922, 723 cmꢀ1
;
HRMS (EI): m/z (%): calcd for C15H22O3: 250.1569, found: 250.1605 (4)
[M +], 235 (43), 191 (10), 175 (100).
(4S’,4aR’,8aR’)-Hexahydro-4-(4-triphenylmethoxybutyl)-4H-benzo[d]-
[1,3]dioxin-2-one (18): i) A solution of 2g (35 mg, 0.18 mmol) in dichloro-
methane (12 mL) was cooled to ꢀ788C, and ozone was bubbled through
until a blue color appeared (ca. 5 min.). The excess of ozone was re-
moved by a flow of O2. The mixture was allowed warm to 08C. To this
solution was added a solution of NaBH4 (114 mg, 3.0 mmol) in MeOH/
H2O (2 mL, 1:1) at 08C and the resultant mixture was stirred at ambient
temperature for 12 h. The mixture was diluted with AcOEt and washed
2m HCl and sat. NaHCO3. The organic phase was dried (MgSO4) and the
solvent was removed in vacuo to give an oil.
(4S,5R,6R,7R,8R)-4-Allyl-5,6,7-tris(benzyloxy)-8-(benzyloxymethyl)-1,3-
dioxaoctan-2-one (20): THF (5 mL) via a syringe was added to a N2
purged two-necked round bottomflask containing (6 S)-11 (140 mg,
0.24 mmol) and 1,1’-carbonyldiimidazole (60 mg, 0.36 mmol). The mix-
ture was stirred at roomtemperature for 12 h and then refluxed for 24 h.
The reaction mixture was diluted with ethyl acetate (30 mL), washed
with sat. NaCl (20 mL). The organic phase was dried (MgSO4) and con-
centrated in vacuo, and the residue was subjected to column chromatog-
raphy on silica gel (hexane/ethyl acetate 4:1) to give a semicarbamate
(81 mg, 50%) at the C2-OH (Rf =0.15, hexane/AcOEt 2:1). Into a N2
purged two-necked round bottomflask containing the carbamate
(0.12 mmol) and NaH (50% dispersion in mineral oil; 10 mg, 0.2 mmol),
dry dioxane (3 mL) was introduced via a syringe and the reaction mixture
was stirred at 808C for 6 h. The reaction mixture was diluted Et2O
(20 mL) and washed with sat. NH4Cl (10 mL), and sat. NaCl (10 mL).
The organic phase was dried (MgSO4) and concentrated in vacuo, and
the residue was purified by column chromatography on silica gel
(AcOEt/hexane 1:8) to give a cyclic carbonate 20 (85 mg, 58%; Rf =0.60,
hexane/AcOEt 2:1). 1H NMR (400 MHz, CDCl3, 258C, TMS) d=2.45
(brdt, 3J(H,H)=14.2, 7.0 Hz, 1H), 2.61 (brdt, 3J(H,H)=14.2, 7.0 Hz,
1H), 3.76 (dd, 3J(H,H)=4.3, 11.3 Hz, 1H), 3.83 (brd, 3J(H,H)=11.3 Hz,
ii) To a solution of the oil in dichloromethane (2 mL) were added trie-
thylamine (59 mg, 0.59 mmol) and triphenylmethyl chloride (53 mg,
0.19 mmol), and the mixture was stirred at ambient room temperature
for 3 h. After dilution with AcOEt (50 mL), the mixture was washed with
sat. NaHCO3 and brine, dried (MgSO4), and concentrated in vacuo to
give an oil. iii)
A solution of the oil and 1,1’-carbonyl-diimidazole
(221 mg, 1.36 mmol) in dry THF (2 mL) was stirred at ambient tempera-
ture for 48 h. The solvent was removed in vacuo and the residue was di-
rectly subjected to column chromatography on silica gel (AcOEt/hexane
gradient 1:4!1:1) to give 18 (40 mg, 47% overall yield). 1H NMR
3
(400 MHz, CDCl3, 278C, TMS): d=0.94 (dq, J(H,H)=3.7, 11.9 Hz, 1H),
1.21–1.89 (m, 13H), 2.14 (brdd, 3J(H,H)=10.8, 4.4 Hz, 1H), 3.08 (t,
3J(H,H)=10.8, 4.2 Hz, 2H), 3.98 (dt, 3J(H,H)=4.4, 11.0 Hz, 1H), 4.12
(ddd, 3J(H,H)=2.7, 7.1, 10.2 Hz, 1H), 7.10–7.45 (m, 15H); 13C NMR
Chem. Eur. J. 2005, 11, 6629 – 6642
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Y. Tamaru et al.
1H), 3.90 (d, 3J(H,H)=9.5 Hz, 1H), 4.05 (d, 3J(H,H)=9.5 Hz, 1H), 4.33
and aldehydes: k) J. Montgomery, M. Song, Org. Lett. 2002, 4, 4009–
4011. Reductive coupling of alkynes and imines: l) S. J. Pater, T. F.
Jamison, Angew. Chem. 2004, 116, 4031–4034; Angew. Chem. Int.
Ed. 2004, 43, 3941–3944; m) S. J. Pater, T. F. Jamison, Angew. Chem.
2003, 115, 1402–1405; Angew. Chem. Int. Ed. 2003, 42, 1364–1367;
reductive coupling of dienes and aldehydes: n) M. Kimura, K.
Kojima, T. Inoue, Y. Tamaru, Synthesis 2004, 3089–3091; o) M.
Kimura, A. Ezoe, S. Tanaka, Y. Tamaru, Angew. Chem. 2001, 113,
3712–3714; Angew. Chem. Int. Ed. 2001, 40, 3600–3602; p) K. Shi-
bata, M. Kimura, K. Kojima, S. Tanaka, Y. Tamaru, J. Organomet.
Chem. 2001, 624, 348–353; q) K. Shibata, M. Kimura, M. Shimizu,
Y. Tamaru, Org. Lett. 2001, 3, 2181–2183; r) M. Kimura, K. Shibata,
Y. Koudahashi, Y. Tamaru, Tetrahedron Lett. 2000, 41, 6789–6793;
s) M. Kimura, S. Matsuo, K. Shibata, Y. Tamaru, Angew. Chem.
1999, 111, 3586–3589; Angew. Chem. Int. Ed. 1999, 38, 3386–3388;
t) M. Kimura, H. Fujimatsu, A. Ezoe, K. Shibata, M. Shimizu, S.
Matsumoto, Y. Tamaru, Angew. Chem. 1999, 111, 410–413; Angew.
Chem. Int. Ed. 1999, 38, 397–400; u) M. Kimura, A. Ezoe, K. Shiba-
ta, Y. Tamaru, J. Am. Chem. Soc. 1998, 120, 4033–4034; reductive
coupling of alkynes, dienes, and aldehydes: v) M. Kimura, A. Ezoe,
M. Mori, Y. Tamaru, J. Am. Chem. Soc. 2005, 127, 201–209. Reduc-
tive coupling of dienes and imines: w) M. Kimura, A. Miyachi, K.
Kojima, S. Tanaka, Y. Tamaru, J. Am. Chem. Soc. 2004, 126, 14360–
14361.
3
3
(d, J(H,H)=10.0 Hz, 1H), 4.40–4.54 (m, 4H), 4.57 (t, J(H,H)=12.0 Hz,
2H), 4.69 (brd, 3J(H,H)=12.0 Hz, 2H), 5.00 (d, 3J(H,H)=10.0 Hz, 1H),
5.07 (d, 3J(H,H)=16.0 Hz, 1H), 5.13 (t, 3J(H,H)=7.0 Hz, 1H), 5.28
3
3
(brdd, J(H,H)=4.3, 10.0 Hz, 1H), 5.70 (ddt, J(H,H)=10.0, 16.0, 7.0 Hz,
1H), 7.14–7.34 (m, 20H); 13C NMR (400 MHz, CDCl3 258C, TMS): d=
36.1, 69.0, 72.3, 73.0, 73.1, 73.2, 74.8, 75.0, 75.7, 118.1, 126.8, 127.1, 127.2,
127.3, 127.4, 127.5, 127.9, 128.1, 128.2, 128.3, 133.1, 137.8, 138.0, 138.6,
154.3; IR (neat): n˜ =1744 (s), 1258 (s), 1096 (s), 733 cmꢀ1 (s); HRMS
(EI): m/z (%): calcd for C38H40O7: 608.2774, found: 608.2768 (100) [M +].
Acknowledgements
We thank Mrs. Minoru Tazoe and Yasukazu Shiino for their technical
help and Mr. Ohhama, NMR Facility, for his splendid technical assis-
tance. Financial support by the Ministry of Education, Culture, Sports,
Science and Technology, Japanese Government (Grant-in-Aid for Scien-
tific Research (B) and Grant-in-Aid for Scientific Research on Priority
Areas), is gratefully acknowledged.
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Received: April 21, 2005
Published online: August 30, 2005
6642
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Chem. Eur. J. 2005, 11, 6629 – 6642