Palladium(II)-catalyzed isomerization-Claisen rearrangement of 2-alkoxy diallyl ethers

Article abstract of DOI:10.1016/j.tet.2004.06.150

Diallyl ethers bearing an enol ether react in the presence of PdCl ₂ as catalyst to give α-allyl α-alkoxy ketones by selective isomerization via formal 1,2-H migration at the more substituted allyl group, followed by Claisen rearrangement. This

Full text of DOI:10.1016/j.tet.2004.06.150

Tetrahedron 60 (2004) 9735–9744
Palladium(II)-catalyzed isomerization-Claisen rearrangement of
2-alkoxy diallyl ethers
*
Cristina Nevado and Antonio M. Echavarren
´ ´
Institute of Chemical Research of Catalonia (ICIQ), E-43007 Tarragona and Departamento de Quımica Organica,
´
Universidad Autonoma de Madrid, Cantoblanco, E-28049 Madrid, Spain
Received 30 April 2004; revised 8 June 2004; accepted 12 June 2004
Available online 27 August 2004
Abstract—Diallyl ethers bearing an enol ether react in the presence of PdCl2 as catalyst to give a-allyl a-alkoxy ketones by selective
isomerization via formal 1,2-H migration at the more substituted allyl group, followed by Claisen rearrangement. This rearrangement is also
promoted by AuCl3 and IrCl3, although the yields are lower with these catalysts.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Cyclization of 1,6-dienes 1 proceeds readily in the presence
Pd(II) complexes1–5 to give cyclopentane derivatives 2a,
along with products of double bond migration 2b–c
(Scheme 1). In particular, cationic allyl palladium com-
plexes have been shown to be effective catalysts for these
cyclizations.2,4a,b,5b,c Complexes of Rh(I),1,6 Ru(II)7 and
Scheme 2.
other transition metals5c also catalyze the cycloisomeriza-
tion of dienes.
of substrates of type 3 to give g,d-unsaturated ketones 5. To
a more limited extend, Au(III) and Ir(III) also catalyze this
rearrangement.
2. Results and discussion
Scheme 1.
We first examined the reaction of 6 and 7, readily available
by addition of 2-tetrahydropyranyl-lithium to benzaldehyde
or 2-naphtaldehyde followed by alkylation of the secondary
alcohol with allyl bromide and NaH in DMF. Reaction of 6
with [Pd(MeCN)2Cl2] in toluene at 110 8C affords a-allyl
ketone 8 in moderate yield (Table 1, entry 1). The reaction
does not proceed satisfactorily with this catalyst in other
solvents such as THF, CH2Cl2, or 1,2-dichloroethane.
Decomposition was observed in the presence of a cationic
complex formed in situ from Pd(MeCN)2Cl2 and AgBF4
(Table 1, entry 2), while no reaction takes place with Pd(II)
complexes bearing PPh3 or AsPh3 as ligands (Table 1,
entries 3–5). Similarly, a Pd(0) catalyst is ineffective
(Table 1, entry 6). The best results are obtained by simply
using PdCl2 in refluxing toluene (Table 1, entries 7 and 8).
Lower conversions were realized in polar chlorinated
solvents (Table 1, entries 9 and 10). The reaction also
proceeds with AuCl3 (Table 1, entry 11) and IrCl3 (Table 1,
As part of a broader study on the cyclization of 1,6-enynes
catalyzed by electrophilic transition-metal halides or
complexes,8,9 we had examined the cyclization of enynes
bearing enol ethers by using Pd(II) or Au(III) as catalysts.10
This type of enynes undergo methoxycyclization in
methanol as solvent to form carbo- and heterocycles with
an acetal functional group.10 We decided to assay substrates
of type 3 in which an electron-rich enol ether could react as
a nucleophile in an intramolecular reaction with a (h2-
alkene)palladium complex 4 to form 6-membered rings
(Scheme 2). However, we have observed that PdCl2
catalyzes the selective isomerization-Claisen rearrangement
Keywords: Claisen rearrangement; Palladium; Isomerization; Enol ethers.
* Corresponding author. Tel.: C3491-977920218; fax: C3491-
977920225; e-mail: aechavarren@iciq.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.150

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C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
Table 1. Isomerization-Claisen rearrangement of substrates 6–7
Entry
Substrate
Catalyst (mol%)
Reaction conditions
Product (yield)
1
2
3
4
5
6
7
8
6
6
6
6
6
6
6
7
6
6
6
6
7
6
6
6
6
6
6
[Pd(MeCN)2Cl2] (10)
[Pd(MeCN)2Cl2] (10)CAgBF4 (10)
[Pd(PPh3)2Cl2] (10)
[Pd(PPh3)2Cl2] (10)CAgBF4 (10)
[Pd(AsPh3)2Cl2] (10)
[Pd2(dba)3$dba] (10)
PdCl2 (10)
PdCl2 (10)
PdCl2 (10)
PdCl2 (10)
AuCl3 (5)
AuCl3 (5)
IrCl3 (10)
PtCl2 (5)
FeCl3 (5)
RhCl3 (5)
[Rh(PPh3)3Cl] (5)
[Rh(OAc)2]2 (5)
[Rh(COD)2-m-Cl2] (5)
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 17 h
Toluene, 110 8C, 12 h
CH2Cl2, 40 8C, 17 h
1,2-Dichloroethane 83 8C, 17 h
Toluene, 80 8C, 4 h
CH3NO2, 80 8C, 14 h
Toluene, 110 8C, 12 h
Toluene, 110 8C, 17 h
Toluene, 0 8C, 1 h
Toluene, 80 8C, 20 h
Toluene, 80 8C, 20 h
Toluene, 80 8C, 20 h
Toluene, 80 8C, 20 h
8 (50%)
—
a
n.r.b
a
—
n.r.b
n.r.b
8 (84%)
9 (93%)
8 (10%)
8 (10%)
8 (57%)
9
10
11
12
13
14
15
16
17
18
19
a
—
9 (70%)
n.r.b
a
—
n.r.b
n.r.b
n.r.b
n.r.b
a
Decomposition of 6 was observed.
Starting material was recovered.
b
entry 13), although the yields were lower and the reactions
were not as clean as those catalyzed by PdCl2. On the other
hand, PtCl2 or FeCl3 gave no positive results (Table 1,
entries 14 and 15). RhCl3 and other rhodium complexes also
failed to promote the rearrangement of 6 (Table 1, entries
16–19).
Claisen rearrangement.11 Although we cannot exclude a
thermal [3,3] sigmatropic process for this second step, the
known rate-acceleration of this reaction in the presence of
Pd(II)12,13 strongly suggest that PdCl2 catalyzes this Claisen
rearrangement.
Enyne 26, in which a 2-butynyl group has replaced the allyl
substituent, reacts with AuCl3 in toluene to give a mixture of
allene 27 and tricycle 2814 (Scheme 4). In this case, no
reaction was observed with PdCl2. Allene 27 results from a
1,2-H migration similar to that shown in Scheme 3 to form
enol ether 29, followed by a Claisen rearrangement.
Acyclic derivatives 10 and 12 undergo rearrangement to
give ketones 11 and 13, respectively (Table 2, entries 1 and
2). Similarly, 2,3-dihydrofuranyl derivative 14 provides 15
in good yield (Table 2, entry 3). However, under identical
conditions, substrate 16 gives a 1:1 mixture of 17a and 17b
(Table 2, entry 4). The formation of 17b by double-bond
migration of 17a is somewhat puzzling, since no alkene
isomerizations were detected in similar compounds 8, 9, 11,
or 13 under these reaction conditions.
A more functionalized substrate was prepared from TIPS-
protected D-glucal (30)15,16 (Scheme 5). Reaction of 30 with
the 6 equiv. of t-Buli gives the 2-lithiated species,15,16
which reacted with benzaldehyde to give 31 in 29% yield,
along with recovered 30. Under these conditions, 31 was
isolated as a 6.5:1 mixture of epimers at the new
stereocenter.17 Allylation of the secondary alcohol of 31
furnished 32 (87%), whose reaction with PdCl2 under the
standard conditions was somewhat sluggish, although
finally proceeded with a higher amount of catalyst to
provide 33 in 78% yield as a 5.4:1 mixture of C-1 epimers.
The configuration of the major epimer 33 was assigned on
the basis of a NOESY experiment. In this case, in addition to
the expected rearrangement, elimination of the C-4 silyloxy
substituent has taken place.
Substrates 18 and 20 (4:1 E/Z mixture) rearrange with
moderate to good stereoselectivities to give 19 and 21,
respectively (Table 2, entries 5 and 6). Importantly, the
reactions proceed with clean allylic inversion. Similarly,
prenyl derivative 22 suffers allylic inversion to give
exclusively 23, albeit in modest yield (Table 2, entry 7).
A substrate with an alkyl substituent a to the allylic oxygen
failed to react under the standard conditions (Table 2,
entry 8).
These results are consistent with the mechanism shown in
Scheme 3. Accordingly, Pd(II) is probably involved in the
selective, formal 1,2-H migration of 3 to give vinyl allyl
ether intermediate 25, which subsequently undergoes a
The elimination of the substituent at C-4 indicates that,
instead of a formal 1,2-H migration, the reaction is initiated

C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
Table 2. Palladium-catalyzed isomerization-Claisen rearrangement of substrates 6–7a
9737
Entry
Substrate
Product
Isomeric ratio
Yield (%)
76
1
—
10
11
2
3
—
—
80
88
12
14
13
15
4
1:1
70
16
17a
C
17b
5
6
2.5:1
88
80
18 (4:1 E/Z)
19
6:1
20 RZ2-Napth(4:1 E/Z)
21 RZ2-Napth
7b
—
—
46
—
22
24
23
8
n.r.c
a
Reactions carried out with PdCl2 (10 mol%) in toluene at 110 8C for 12 h.
20 mol% PdCl2.
Starting material was recovered.
b
c
by formation of a (h3-allyl)palladium complex 34
(Scheme 6), followed by a regioselective proton elimin-
ation18 to give diene 35 (or its Z diastereomer),19 which
subsequently undergoes Claisen rearrangement.
3. Conclusion
Diallyl ethers bearing an enol ether 3 undergo selective
isomerization by formal 1,2-H migration at the more

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C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
proceeds by initial formal 1,2-H migration at the least
substituted allyl (Scheme 7).20,21
This palladium-catalyzed transformation allows for the
synthesis of functionalized ketones 5 via intermediates 3,
which are easily assembled by the addition of the a-lithium
derivatives of enol ethers to aldehydes, followed by
allylation of the resulting secondary alcohols (Scheme 8).
Scheme 3.
4. Experimental
4.1. General
All reactions were carried out under Ar in dry freshly
distilled solvents under anhydrous conditions. THF was
˚
dried by using 4 A molecular sieves. Toluene and DMF
were distilled from sodium/benzophenone and CaH2
˚
respectively and were kept with 4 A. Aldehydes were
distilled from NaHCO3 under Ar or reduced pressure
depending on the boiling points.
Thin layer chromatography was carried out using TLC-
aluminium sheets with 0.2 mm of silica gel (Merk GF234).
Chromatography purifications were carried out using flash
Scheme 4.
Scheme 5.
substituted allyl in the presence of Pd(II), followed by
Claisen rearrangement to give a-allyl a-alkoxy ketones 5.
This rearrangement is also promoted by AuCl3 and IrCl3,
although the yields are lower with these catalysts. This
reaction is regiocomplementary to that recently described
by Nelson et al. using cationic Ir(I) complexes, which
grade silica gel (SDS Chromatogel 60 ACC, 40–60 mm)
with distilled solvents.
NMR spectra were recorded at 23 8C on a Bruker AC-300
and Bruker AMX-500 apparatus. Mass spectra (FAB, EI)
were recorded on a HP1100MSD spectrometer. Elemental
Scheme 6.

C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
9739
7.59 (dd, JZ8.5, 1.6 Hz, 1H), 7.86–7.91 (m, 3H), 7.95 (d,
JZ0.8 Hz, 1H). 13C NMR (CDCl3, 75 MHz, DEPT) d 20.66
(CH2), 22.98 (CH2), 67.24 (CH2), 75.27 (CH), 99.00 (CH),
125.44 (CH), 125.99 (CH), 126.47 (CH), 126.64 (CH),
128.31 (CH), 128.51 (CH), 128.79 (CH), 133.69 (C), 133.92
(C), 139.44 (C), 155.08 (C). EI-HRMS Calcd for C16H16O2:
240.1150. Found: 240.1147.
4.2.3. 2-Ethoxy-1-phenylprop-2-en-1-ol. Yield: 27%. Pale
yellow solid; mp 48–50 8C. H NMR (CDCl3, 300 MHz) d
1
1.32 (t, JZ7.3 Hz, 3H), 2.58 (d, JZ5.3 Hz, 1H), 3.82 (q,
JZ7.3 Hz, 2H), 4.13 (d, JZ2.4 Hz, 1H), 4.23 (d, JZ
2.4 Hz, 1H), 5.16 (d, JZ5.3 Hz, 1H), 7.50–7.31 (m, 5H).
13C NMR (CDCl3, JZ75 MHz) d 14.92, 63.89, 75.52,
83.32, 127.20, 128.33, 128.86, 142.67, 163.31. EI-HRMS
Calcd for C11H13O2 (MCK1): 177.0920. Found: 177.0921.
Scheme 7.
4.2.4. 2-Ethoxy-1-(furan-2-yl)prop-2-en-1-ol. Yield: 53%.
1
Colorless oil. H NMR (CDCl3, 300 MHz) d 1.33 (t, JZ
7.1 Hz, 3H), 2.83 (d, JZ6.1 Hz, 1H), 3.85 (q, JZ7.1 Hz,
2H), 4.15 (d, JZ2.6 Hz, 1H), 4.29 (d, JZ2.6 Hz, 1H), 5.15
(d, JZ6.1 Hz, 1H), 6.33 (dt, JZ3.2, 0.8 Hz, 1H), 6.36 (dd,
JZ3.2, 1.8 Hz, 1H), 7.40 (dd, JZ1.8, 0.8 Hz, 1H). 13C
NMR (CDCl3, JZ75 MHz, DEPT) d 14.89 (CH3), 64.02
(CH2), 69.64 (CH), 83.55 (CH2), 107.72 (CH), 110.90 (CH),
142.78 (CH), 154.94 (C), 161.12 (C). Anal. Calcd for
C9H12O2: C, 64.27; H, 7.19. Found: C, 64.06; H, 7.19.
Scheme 8.
analyses were performed on a LECO CHNS 932 micro-
analyzer. Melting points were determined using a
Gallenkamp melting point apparatus.
4.2.5. (4,5-Dihydrofuran-2-yl)(phenyl)methanol. Yield:
60%. Yellow oil. 1H NMR (CDCl3, 300 MHz) d 2.65 (d, JZ
4.4 Hz, 1H), 2.64 (tdd, JZ9.3, 2.3, 1.6 Hz, 2H), 4.37 (t, JZ
9.3 Hz, 2H), 4.78 (td, JZ2.4, 0.8 Hz, 1H), 5.25 (brs, 1H),
7.38–7.27 (m, 3H), 7.43 (dd, JZ7.9, 1.4 Hz, 2H). 13C NMR
(CDCl3, JZ75 MHz) d 29.78, 70.22, 70.53, 96.89, 126.56,
127.93, 128.26, 140.56, 158.88. Anal. Calcd for C11H12O2:
C, 74.98; H, 6.86. EI-HRMS Calcd for C11H12O2: 176.0837.
Found: 176.0833.
4.2. General procedure for the preparation of benzylic
alcohols
A solution containing 1.2 equiv. of the corresponding enol
ether in dried THF (volume of THF necessary to make the
concentration of enol ether 2 M) was cooled at K78 8C and
1 equiv. of t-BuLi was added dropwise. The mixture was
warmed up to K5 8C and then stirred at that temperature for
5 h. The solution was then cooled at K78 8C and 1 equiv. of
the aldehyde was slowly added. The mixture was warmed
up to room temperature overnight and then quenched with
4 mL of a saturated NH4Cl solution. The mixture was
extracted with 3!20 mL of Et2O and the combined organic
layers were dried over MgSO4. Solvent was removed under
reduced pressure and the residue was purified by silica gel
chromatography (15:1 hexane/EtOAc mixture containing
5% Et3N was used as eluent). Reactions were carried out in
a 30–50 mmol scale.
4.2.6. (4,5-Dihydrofuran-2-yl)(4-methoxyphenyl)metha-
nol. Yield: 83%. Colorless oil. 1H NMR (CDCl3, 300 MHz)
d 2.68 (tdd, JZ9.3, 2.8, 1.6 Hz, 2H), 3.84 (s, 3H), 4.44 (t,
JZ9.3 Hz, 2H), 4.83 (td, JZ2.8, 1.2 Hz, 1H), 5.25 (brs,
1H), 6.93 (d, JZ8.9 Hz, 2H), 7.39 (d, JZ8.9 Hz, 2H) (OH
signal was not observed). 13C NMR (CDCl3, JZ75 MHz,
DEPT) d 31.23 (CH3), 56.69 (CH3), 70.61 (CH), 71.28
(CH2), 98.11 (CH), 115.18 (CH), 129.34 (CH), 134.25 (C),
160.55 (C), 160.80 (C). EI-HRMS Calcd for C12H14O3:
206.0943. Found: 206.0945. Anal. Calcd for C12H14O3: C,
69.88; H, 6.84. Found: C, 69.58; H, 6.77.
4.2.1. (5,6-Dihydro-4H-pyran-2-yl)(phenyl)methanol.22
Yield: 66%. Yellow oil. H NMR (CDCl3, 300 MHz) d
1.75–1.83 (m, 2H), 2.01–2.07 (m, 2H), 2.58 (d, JZ5.3 Hz,
1H), 3.97–4.00 (m, 2H), 4.77 (t, JZ3.6 Hz, 1H), 5.02 (d,
JZ4.8 Hz, 1H), 7.24–7.44 (m, 5H). 13C NMR (CDCl3, JZ
75 MHz) d 20.64, 22.94, 67.17, 75.12, 98.79, 127.22,
128.25, 128.86, 141.94, 154.99.
1
4.2.7. (2S,3R,4S)-3,4-Dihydro-2-(triisopropylsilyloxy-
methyl)-2H-pyran-3,4-bistriisopropilsilyloxy-6-phenyl-
methanol (31). Yield: 29%, 6.5:1 mixture of epimers at the
carbinol center. Colorless oil. 1H NMR (CDCl3, 300 MHz) d
1.06–1.09 (m, 63H), 2.57 (d, JZ4.4 Hz, 1H), 3.83 (dd, JZ
11.3, 4.0 Hz, 1H), 4.01–4.08 (m, 3H), 4.31–4.36 (m, 1H),
4.89–4.91 (m, 1H), 5.15 (d, JZ4.0 Hz, 1H), 7.30–7.38 (m,
3H), 7.47 (dd, JZ8.1, 2.0 Hz, 2H). 13C NMR (CDCl3, JZ
75 MHz, DEPT) d 12.62 (CH), 12.95 (CH), 13.07 (CH),
18.69 (CH3), 18.73 (CH3), 18.77 (CH3), 62.33 (CH2), 66.60
(CH), 70.62 (CH), 74.56 (CH), 81.94 (CH), 97.80 (CH),
127.84 (CH), 128.38 (CH), 128.74 (CH), 141.25 (C), 153.87
4.2.2. (5,6-Dihydro-4H-pyran-2-yl)(naphthalen-2-
yl)methanol. Yield: 75%. Pale yellow solid; mp 61–
1
63 8C. H NMR (CDCl3, 300 MHz) d 1.82–1.90 (m, 2H),
2.10–2.14 (m, 2H), 2.75 (bs, 1H), 4.06 (t, JZ8.9 Hz, 2H),
4.88 (t, JZ3.6 Hz, 1H), 5.26 (s, 1H), 7.55–7.49 (m, 2H),

9740
C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
1
(C). MALDI-HRMS (dithranol-NaI matrix) Calcd for
C40H76O3NaSi3: 743.4898. Found: 743.4903.
62%. Colorless oil. H NMR (CDCl3, 300 MHz) d 1.33 (t,
JZ7.1 Hz, 3H), 3.89–3.80 (m, 2H), 4.17–4.04 (m, 2H), 4.21
(d, JZ2.2 Hz, 1H), 4.43 (d, JZ2.2 Hz, 1H), 4.85 (s, 1H),
5.24 (dc, JZ11.3, 1.7 Hz, 1H), 5.35 (dc, JZ17.4, 1.7 Hz,
1H), 5.98 (ddt, JZ17.4, 11.3, 5.7 Hz, 1H), 6.36–6.40 (m,
2H), 7.42 (dd, JZ1.6, 1.0 Hz, 1H). 13C NMR (CDCl3,
75 MHz, DEPT) d 14.91 (CH3), 63.85 (CH2), 70.55 (CH2),
75.49 (CH), 84.11 (CH2), 108.87 (CH), 110.77 (CH), 118.01
(CH2), 135.07 (CH), 142.90 (CH), 153.56 (C), 159.83 (C).
EI-HMRS Calcd for C12H16O3: 208.1099. Found: 208.1094.
4.3. General procedure for the alkylation of benzylic
alcohols.
A solution containing 1.2 equiv. of NaH (60% in mineral
oil) in dried DMF (volume of DMF necessary to make the
concentration of NaH 1.0 M) was cooled at 0 8C. A 1 equiv.
solution of the corresponding benzylic alcohol in DMF
(volume of DMF necessary to make the concentration of the
alcohol 1.0 M) was added dropwise. The mixture was
warmed up to room temperature and stirred for 20 min and
1 equiv. of the alkylating agent was added. The reaction was
stirred at room temperature for 4 h and then quenched with a
water-ice mixture and diluted with Et2O. The organic layer
is washed several times with water and then dried over
MgSO4. Solvent was removed under reduced pressure and
the residue was purified by silica gel chromatography (100:1
hexane/EtOAc containing 5% Et3N was used as eluent). All
reactions were carried out in a 5–15 mmol scale.
4.3.5. 5-[(Allyloxy)(phenyl)methyl]-2,3-dihydrofuran
(14). Yield: 81%. Colorless oil. 1H NMR (CDCl3,
300 MHz) d 2.62 (dddd, JZ9.3, 9.3, 2.6, 1.4 Hz, 2H),
4.01 (ddd, JZ5.7, 1.6, 1.2 Hz, 2H), 4.36 (td, JZ9.3, 2.8 Hz,
2H), 4.82 (td, JZ2.4, 0.8 Hz, 1H), 4.92 (bs, 1H), 5.18 (dq,
JZ10.1, 1.2 Hz, 1H), 5.27 (dq, JZ17.0, 1.6 Hz, 1H), 5.93
(ddt, JZ17.0, 10.1, 5.7 Hz, 1H), 7.43–7.25 (m, 5H). 13C
NMR (75 MHz, CDCl3, DEPT) d 30.39 (CH2), 70.52 (CH2),
71.19 (CH2), 77.13 (CH), 98.74 (CH), 118.04 (CH2), 127.94
(CH), 128.64 (CH), 128.95 (CH), 135.17 (CH), 139.63 (C),
158.20 (C). EI-HMRS Calcd for C14H16O2: 216.1150.
Found: 216.1143.
4.3.1. 6-[(Allyloxy)(phenyl)methyl]-3,4-dihydro-2H-
pyran (6). Yield: 88%. Colorless oil. H NMR (CDCl3,
1
300 MHz) d 1.76–1.82 (m, 2H), 2.02–2.08 (m, 2H), 3.90–
4.09 (m, 4H), 4.66 (s, 1H), 4.86 (t, JZ3.6 Hz, 1H), 5.17 (dc,
JZ10.5, 1.2 Hz, 1H), 5.27 (dc, JZ17.4, 2.0 Hz, 1H), 5.94
(ddt, JZ17.4, 10.5, 5.7 Hz, 1H), 7.23–7.42 (m, 5H). 13C
NMR (CDCl3, 75 MHz) d 135.61, 140.50, 135.48, 128.73,
128.7, 127.75, 117.66, 99.70, 81.68, 70.33, 67.04, 22.98,
22.78. EI-HMRS Calcd for C15H18O2: 230.1307. Found:
230.1300. Anal. Calcd for C15H18O2: C, 78.23; H, 7.88.
Found: C, 78.03, H, 8.14.
4.3.6. 5-[(Allyloxy)(4-methoxyphenyl)methyl]-2,3-di-
hydrofuran (16). Yield: 83%. Colorless oil. 1H NMR
(CDCl3, 300 MHz) d 2.63–2.70 (m, 2H), 3.85 (s, 3H), 4.03
(d, JZ5.7 Hz, 2H), 4.41 (td, JZ3.6, 9.7 Hz, 2H), 4.87 (td,
JZ2.4, 0.8 Hz, 1H), 4.91 (d, JZ0.8 Hz, 1H), 5.22 (dq, JZ
10.1, 1.6 Hz, 1H), 5.31 (dq, JZ7.0, 1.6 Hz, 1H), 5.97 (ddt,
JZ10.1, 7.0, 5.7 Hz, 1H), 6.93 (dd, JZ8.5, 2.0 Hz, 2H),
7.38 (dd, JZ8.5, 2.0 Hz, 2H). 13C NMR (CDCl3, 75 MHz,
DEPT) d 30.37 (CH2), 55.89 (CH3), 70.33 (CH2), 71.17
(CH2), 76.80 (CH), 98.33 (CH), 114.34 (CH), 117.88 (CH2),
129.23 (CH), 131.77 (C), 135.28 (CH), 158.49 (C), 160.02
(C). EI-HMRS Calcd for C15H18O3: 246.1256. Found:
246.1255.
4.3.2. 6-[(Allyloxy)(naphthalen-2-yl]methyl)-3,4-di-
hydro-2H-pyran (7). Yield: 74%). Colorless oil. H NMR
1
(CDCl3, 300 MHz) d 1.86 (q, JZ6.0 Hz, 2H), 2.14 (td, JZ
6.0, 3.8 Hz, 2H), 4.01–4.12 (m, 2H), 4.14–4.23 (m, 2H),
4.93 (s, 1H), 5.02 (t, JZ3.4 Hz, 1H), 5.28 (dq, JZ10.1,
1.4 Hz, 1H), 5.39 (dq, JZ17.0, 1.6 Hz, 1H), 6.00–6.14 (m,
1H), 7.49–7.56 (m, 2H), 7.63 (ddd, JZ8.5, 1.6, 1.2 Hz, 1H),
7.88–7.93 (m, 3H), 7.96 (bs, 1H). 13C NMR (CDCl3,
75 MHz, DEPT) d 20.82 (CH3), 23.00 (CH3), 67.09 (CH2),
70.40 (CH2), 81.85 (CH), 99.79 (CH), 117.76 (CH2), 125.84
(CH), 126.40 (CH), 126.55 (CH), 126.73 (CH), 128.30
(CH), 128.45 (CH), 128.77 (CH), 133.77 (C), 133.91 (C),
135.50 (CH), 138.04 (C), 153.70 (C). EI-HMRS Calcd for
C19H20O2: 280.1463. Found: 280.1469.
4.3.7. 5-[(But-2-enyloxy)(phenyl)methyl]-2,3-dihydro-
furan (18). Yield: 38%. Colorless oil. 4:1 E/Z. H NMR
1
(CDCl3, 300 MHz) d 1.62 (dt, JZ5.1, 0.8 Hz, 3H, Z
isomer), 1.75 (dc, JZ4.7, 1.1 Hz, 3H, E isomer), 2.62–
2.70 (m, 2H, E and Z isomers), 3.97–4.14 (m, 2H, E and Z
isomers), 4.34–4.48 (m, 2H, E and Z isomers), 4.85 (td, JZ
2.6, 1.0 Hz, 1H, E and Z isomers), 4.96 (d, JZ1 Hz, 1H, E
and Z isomers), 5.60–5.74 (m, 2H, E and Z isomers), 7.30–
7.48 (m, 5H, E and Z isomers). 13C NMR (CDCl3, 75 MHz)
d (only signals for the major E isomer) 13.85, 18.44, 30.38,
64.86, 70.24, 71.13, 76.91, 77.09, 98.59, 98.69, 127.40,
127.97, 128.03, 128.54, 128.57, 128.82, 128.89, 130.48,
139.81, 158.39. EI-HMRS Calcd for C15H17O2 (MCK1):
229.1229. Found: 229.1223. Anal. Calcd for C15H18O2: C,
78.23; H, 7.88. Found: C, 78.25, H, 7.83.
4.3.3. 1-[1-(Allyloxy)-2-ethoxyallyl]benzene (10). Yield:
73%. Colorless oil. H NMR (CDCl3, 300 MHz) d 1.29 (t,
1
JZ6.9 Hz, 3H), 3.78 (tdd, JZ9.7, 7.0, 2.4 Hz, 2H), 4.10
(cdt, JZ12.9, 5.7, 1.6 Hz, 2H), 4.14 (d, JZ2.0 Hz, 1H),
4.38 (d, JZ2.0 Hz, 1H), 4.79 (s, 1H), 5.25 (dc, JZ10.5,
1.2 Hz, 1H), 5.36 (dc, JZ17.4, 1.6 Hz, 1H), 6.01 (ddt, JZ
17.4, 10.5, 5.7 Hz, 1H), 7.50–7.29 (m, 5H). 13C NMR
(CDCl3, 75 MHz, DEPT) d 14.92 (CH3), 63.72 (CH2), 70.47
(CH2), 81.93 (CH), 83.33 (CH2), 117.64 (CH2), 127.78
(CH), 128.26 (CH), 128.73 (CH), 135.42 (CH), 140.75 (C),
162.17 (C). EI-HMRS Calcd for C14H18O2: 218.1307.
Found: 218.1303.
4.3.8. 6-[(But-2-enyloxy)(naphthalen-2-yl)methyl]-3,4-
dihydro-2H-pyran (20). Yield: 69%. Yellow oil. 4:1 E/Z.
1H NMR (CDCl3, 300 MHz) d 1.63 (dt, JZ5.1, 0.9 Hz, 3H,
Z isomer), 1.74 (dq, JZ3.8, 0.9 Hz, 3H, E isomer), 1.81 (m,
2H, E and Z isomers), 2.09 (m, 2H, E and Z isomers), 4.19–
3.93 (m, 4H, E and Z isomers), 4.87 (s, 1H, E and Z
isomers), 4.95 (t, JZ3.6 Hz, 1H, E and Z isomers), 5.80–
5.63 (m, 2H, E and Z isomers), 7.59–7.44 (m, 2H, E and Z
isomers), 7.57 (dd, JZ8.7, 1.8 Hz, 1H, E and Z isomers),
4.3.4. 2-[1-(Allyloxy)-2-ethoxyallyl]furan (12). Yield:

C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
9741
7.91–7.82 (m, 4H, E and Z isomers). 13C NMR (CDCl3,
75 MHz, DEPT) d (only signals for the major E isomer)
13.99 (CH3, Z isomer), 18.57 (CH3, E isomer), 20.85 (CH2),
23.03 (CH2), 64.82 (CH2, Z isomer), 67.13 (CH2, E isomer)
70.17 (CH2, E isomer), 81.62 (CH, E isomer), 81.79 (CH, Z
isomer), 99.82 (CH, E isomer), 99.95 (CH, Z isomer),
125.92 (CH), 126.38 (CH), 126.54 (CH), 126.76 (CH),
127.72 (CH), 128.28 (CH), 128.31 (CH), 128.45 (CH),
128.64 (CH, Z isomer), 128.77 (CH, E isomer), 130.29 (CH,
Z isomer), 133.75 (C, E isomer), 133.91 (C, E isomer),
138.15 (C, E isomer), 153.80 (C, E isomer). EI-HMRS
Calcd for C20H22O2: 294.1620. Found: 294.1621.
128.59 (CH), 135.48 (CH), 140.39 (C), 152.27 (C).
MALDI-HRMS (dithranol-NaI matrix) Calcd for C43H80-
O5NaSi3: 783.5211. Found: 783.5209.
4.4. General procedure for the isomerization-Claisen
rearrangement
A mixture of the di-allylic ether (1 equiv.) and PdCl2
(0.1 equiv.) was dissolved in dried toluene (volume of
toluene necessary to make the concentration of the substrate
0.05 M). The solution was refluxed for 14 h and then filtered
through a short path of Celite. The solvent was removed
under reduced pressure and the residue was purified by silica
gel chromatography (100:1 hexane/EtOAc containing 5%
Et3N as eluent) to yield the corresponding ketones.
Reactions were carried out in a 0.3–0.8 mmol scale.
4.3.9. 6-[(3-Methylbut-2-enyloxy)(phenyl)methyl]-3,4-
dihydro-2H-pyran (22). Yield: 59%. Colorless oil. 1H
NMR (CDCl3, 300 MHz) d 1.65 (d, JZ1.2 Hz, 3H), 1.79 (d,
JZ1.2 Hz, 3H), 1.82–1.88 (m, 2H), 2.13–2.08 (m, 2H),
3.96–4.12 (m, 4H), 4.70 (s, 1H), 4.90 (t, JZ3.6 Hz, 1H),
5.45 (tq, JZ16.9, 1.2 Hz, 1H), 7.28–7.40 (m, 3H), 7.45–
7.48 (m, 2H). 13C NMR (CDCl3, 75 MHz, DEPT) d 18.72
(CH3), 20.77 (CH2), 22.99 (CH2), 26.46 (CH3), 65.96
(CH2), 67.02 (CH2), 81.56 (CH), 99.58 (CH), 121.97 (CH),
127.82 (CH), 128.07 (CH), 128.69 (CH), 137.40 (C), 140.77
(C), 153.83 (C). EI-HMRS Calcd for C17H21O2 (MCK1):
257.1540. Found: 257.1538.
4.4.1. (2-Allyltetrahydro-2H-pyran-2-yl)(phenyl)metha-
none (8). Yield: 84%. Colorless oil. 1H NMR (CDCl3,
300 MHz) d 1.38–1.63 (m, 4H), 1.68–1.74 (m, 1H), 2.35–
2.44 (m, 1H), 2.56–2.70 (m, 2H), 3.29–3.38 (m, 1H), 3.78–
3.85 (m, 1H), 4.98 (ddd, JZ17.2, 2.0, 1.4 Hz, 1H), 5.05
(ddt, JZ10.1, 2.0, 1.0 Hz, 1H), 5.71 (ddt, JZ17.2, 10.1,
7.4 Hz, 1H), 7.42 (m, 2H), 7.54 (tt, JZ7.3, 1.6 Hz, 1H), 8.30
(dt, JZ7.3, 1.6 Hz, 2H). 13C NMR (CDCl3, 75 MHz,
DEPT) d 20.26 (CH2), 25.85 (CH2), 32.07 (CH2), 45.37
(CH2), 66.37 (CH2), 86.22 (C), 119.33 (CH2), 128.93 (CH),
130.38 (CH), 132.57 (CH), 133.42 (CH), 136.34 (C), 203.97
(C). FAB-HRMS Calcd for C15H19O2 (MCC1): 231.1385.
Found: 231.1378.
4.3.10. 2-[1-(Allyloxy)-2-methylpropyl]-tetrahydro-2H-
pyran (24). Yield: 72%. Colorless oil. H NMR (CDCl3,
1
300 MHz) d 0.82 (d, JZ6.5 Hz, 3H), 0.95 (d, JZ6.5 Hz,
3H), 1.74–2.06 (m, 5H), 3.08 (d, JZ8.1 Hz, 1H), 3.79
(dddd, JZ14.9, 6.5, 1.6, 1.2 Hz, 1H), 3.90–4.10 (m, 3H),
4.65 (t, JZ4.0 Hz, 1H), 5.11 (m, 1H), 5.23 (ddd, JZ17.4,
3.7, 1.6 Hz, 1H), 5.88 (dddd, JZ17.4, 10.5, 6.5, 5.2 Hz,
1H). 13C NMR (CDCl3, 75 MHz, DEPT) d 19.83 (CH3),
19.88 (CH3), 20.80 (CH2), 23.20 (CH2), 31.06 (CH), 66.70
(CH2), 70.08 (CH2), 86.59 (CH), 100.45 (CH), 117.04
(CH2); 136.05 (CH), 152.13 (C). EI-HMRS Calcd for
C12H20O2: 196.1463. Found: 196.1455.
4.4.2. (2-Allyltetrahydro-2H-pyran-2-yl)(naphthalen-2-
yl)methanone (9). Yield: 93%. Colorless oil. 1H NMR
(CDCl3, 300 MHz) d 1.46–1.81 (m, 5H), 2.49–2.55 (m, 1H),
2.74–2.78 (m, 2H), 3.43 (td, JZ11.7, 2.4 Hz, 1H), 3.90 (dq,
JZ11.7, 2.0 Hz, 1H), 5.01 (c, JZ1.6 Hz, 1H), 5.06–5.13
(m, 1H), 5.80 (ddt, JZ17.4, 10.1, 7.3 Hz, 1H), 7.55–7.66
(m, 2H), 7.91 (dd, JZ8.5, 2.0 Hz, 2H), 8.03 (d, JZ8.9 Hz,
1H), 8.31 (dd, JZ8.9, 1.6 Hz, 1H), 9.06 (d, JZ1.6 Hz, 1H).
13C NMR (CDCl3, 75 MHz) d 20.89, 25.89, 32.18, 45.71,
66.49, 86.46, 119.37, 126.21, 127.07, 128.24, 128.53,
129.03, 130.64, 132.13, 132.59, 133.24, 133.54, 136.05,
203.73. EI-HRMS Calcd for C19H20O2: 280.1463. Found:
280.1468. Anal. Calcd for C19H20O2: C, 81.40; H, 7.19.
Found: C, 81.21; H, 7.34.
4.3.11. 6-[(But-2-ynyloxy)(phenyl)methyl]-3,4-dihydro-
2H-pyran (26). Yield: 63%. White vitreous solid. 1H
NMR (CDCl3, 300 MHz) d 1.75–1.79 (m, 2H), 1.84 (t, JZ
2.4 Hz, 3H), 2.04–2.09 (m, 2H), 3.91–4.03 (m, 2H), 4.10
(dc, JZ15.4, 2.4 Hz, 1H), 4.17 (dc, JZ15.4, 2.4 Hz, 1H),
4.89 (s, 1H), 4.91 (t, JZ3.8 Hz, 1H), 7.24–7.36 (m, 3H),
7.40–7.44 (m, 2H). 13C NMR (CDCl3, 75 MHz) d 140.78,
140.42, 128.73, 128.56, 128.12, 113.59, 74.07, 69.99, 64.87,
25.63, 22.95, 21.95, 16.15, 13.05. EI-HMRS Calcd for
C16H18O2: 242.1301. Found: 242.1296.
4.4.3. 2-Ethoxy-2-methyl-1-phenylpent-4-en-1-one (11).
Yield: 76%. Colorless oil. H NMR (CDCl3, 300 MHz) d
1
1.11 (t, JZ6.9 Hz, 3H), 2.47 (s, 3H), 2.60 (dd, JZ14.2,
6.9 Hz, 1H), 2.75 (dd, JZ14.2, 6.9 Hz, 1H), 3.32–3.42 (m,
2H), 5.02 (dd, JZ3.2, 1.2 Hz, 1H), 5.07–5.12 (m, 1H),
5.69–5.83 (m, 1H), 7.43 (m, 2H), 7.54 (tt, JZ7.3, 1.2 Hz,
1H), 8.30 (m, 2H). 13C NMR (CDCl3, 75 MHz, DEPT) d
16.06, 22.67, 42.61, 60.71, 85.39, 119.28, 128.87, 130.74,
133.30, 133.44, 135.81, 204.11. EI-HRMS Calcd for
C14H19O2 (MCC1): 219.1385. Found: 219.1394. Anal.
Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 77.31; H,
8.24.
4.3.12. (2S,3R,4S)-6-[(Allyloxy)(phenyl)methyl]-3,4-bis-
(triisopropylsilyloxy)-3,4-dihydro-2-(triisopropylsilyl-
oxymethyl)-2H-pyran (32). Yield: 87%. Colorless oil. This
product was purified by flash chromatography with hexane
1
containing 5% Et3N. H NMR (CDCl3, 300 MHz) d 0.98–
1.08 (m, 63H), 3.86 (d, JZ6.1 Hz, 2H), 3.70–4.27 (m, 5H),
4.72 (s, 1H), 5.15–5.20 (m, 2H), 5.30 (ddt, JZ17.4, 3.4,
1.7 Hz, 1H), 5.95 (dddd, JZ17.4, 10.5, 5.9, 5.1 Hz, 1H),
7.21–7.29 (m, 3H), 7.43 (dd, JZ7.7, 1.8 Hz, 2H). 13C NMR
(CDCl3, 75 MHz, DEPT) d 12.63 (CH), 13.02 (2!CH),
18.68 (CH3), 18.79 (CH3), 18.85 (CH3), 62.71 (CH2), 66.65
(CH), 70.53 (CH), 70.58 (CH2), 81.24 (CH), 81.80 (CH),
97.86 (CH), 117.34 (CH2), 127.64 (CH), 128.14 (CH),
4.4.4. 2-Ethoxy-1-(furan-2-yl)-2-methylpent-4-en-1-one
(13). Yield: 80%. Colorless oil. 1H NMR (CDCl3,
300 MHz) d 1.20 (t, JZ6.9 Hz, 3H), 1.47 (s, 3H), 2.58
(dddd, JZ14.4, 6.7, 1.4, 1.2 Hz, 1H), 2.72 (dddd, JZ14.4,

9742
C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
6.7, 1.4, 1.2 Hz, 1H), 3.47 (dc, JZ8.7, 6.9 Hz, 1H), 3.38 (dc,
JZ8.7, 6.9 Hz, 1H), 5.06–5.15 (m, 2H), 5.77 (dddd, JZ
17.0, 10.5, 7.9, 6.9 Hz, 1H), 6.57 (dd, JZ3.6, 1.6 Hz, 1H),
7.64 (dd, JZ3.6, 0.8 Hz, 1H), 7.66 (dd, JZ1.6, 0.8 Hz, 1H).
13C NMR (CDCl3, JZ75 MHz) d 16.09, 21.97, 42.65,
60.49, 84.21, 112.45, 119.27, 121.07, 133.07, 147.24,
150.94, 192.92. Anal. Calcd for C12H16O3: C, 69.21; H,
7.44. Found: C, 69.05; H, 7.64.
isomer), 69.91 (CH2, major isomer), 95.13 (C, major
isomer), 95.48 (C, minor isomer), 116.48 (CH2, minor
isomer), 116.87 (CH2, major isomer), 128.69 (CH, both
isomers), 130.65 (CH, major isomer), 130.87 (CH, minor
isomer), 132.90 (CH, major isomer), 132.99 (CH, minor
isomer), 136.58 (C, minor isomer), 137.07 (C, major
isomer), 139.20 (CH, minor isomer), 139.56 (CH, major
isomer), 203.75 (C, minor isomer), 205.06 (C, major
isomer). EI-HRMS Calcd for C15H19O2 (MCC1):
231.1385. Found: 231.1386. Anal. Calcd for C15H18O2: C,
78.23; H, 7.88. Found: C, 78.23; H, 7.79.
4.4.5. (2-Allyltetrahydrofuran-2-yl)(phenyl)methanone
(15). Yield: 88%. Colorless oil. 1H NMR (CDCl3,
300 MHz) d 1.81–2.01 (m, 3H), 2.56–2.69 (m, 2H), 2.80
(dddd, JZ13.8, 6.6, 1.6, 0.8 Hz, 1H), 3.77–3.85 (m, 1H),
3.99–4.06 (m, 1H), 5.04–5.10 (m, 1H, overlapped), 5.12
(ddt, JZ7.7, 2.0, 0.8 Hz, 1H), 5.80 (dddd, JZ17.0, 10.1,
7.7, 6.6 Hz, 1H), 7.46 (m, 2H), 7.56 (tt, JZ7.3, 1.2 Hz, 1H),
8.19 (dd, JZ8.1, 1.2 Hz, 2H). 13C NMR (CDCl3, 75 MHz,
DEPT) d 26.02 (CH2), 34.44 (CH2), 43.95 (CH2), 69.58
(CH2), 92.62 (C), 119.36 (CH2), 128.73 (CH), 130.68 (CH),
133.11 (CH), 133.22 (CH), 136.34 (C), 204.11 (C). EI-
HRMS Calcd for C14H17O2 (MCC1): 217.1229. Found:
217.1238. Anal. Calcd for C14H16O2: C, 77.75; H, 7.46.
Found: C, 78.16; H, 7.42.
4.4.8. [2-(But-3-en-2-yl)-tetrahydro-2H-pyran-2-
yl](naphthalen-2-yl)methanone (21). Yield: 80%. Color-
1
less oil. 6:1 mixture of diastereomers. H NMR (CDCl3,
300 MHz) d 0.91 (d, JZ7.1 Hz, 3H, minor isomer), 1.27 (d,
JZ6.9 Hz, 3H, major isomer), 1.45–1.81 (m, 5H, both
isomers), 2.37–2.52 (m, 1H, major isomer), 2.40–2.48 (m,
1H, minor isomer), 2.92–3.07 (m, 1H, both isomers), 3.39–
3.49 (m, 1H, both isomers), 3.91–4.00 (m, 1H, both
isomers), 4.79 (ddd, JZ17.2, 1.8, 1.2 Hz, 1H, major
isomer), 4.96 (ddd, JZ10.3, 1.8, 0.8 Hz, 1H, major isomer),
5.16 (ddd, JZ17.2, 1.8, 1.6 Hz, 1H, minor isomer), 5.23
(ddd, JZ10.5, 1.6, 1.4 Hz, 1H, minor isomer), 5.67 (ddd,
JZ17.2, 10.3, 8.5 Hz, 1H, major isomer), 6.26 (ddd, JZ
17.2, 10.5, 6.3 Hz, 1H, minor isomer), 7.40–7.54 (m, 4H,
minor isomer), 7.55–7.67 (m, 4H, major isomer), 7.91 (d,
JZ8.7 Hz, 1H, major isomer), 8.03 (d, JZ8.9 Hz, 1H,
minor isomer), 8.32 (dd, JZ8.9, 1.8 Hz, 1H, major isomer),
8.38 (dd, JZ8.7, 1.8 Hz, 1H, minor isomer), 9.06 (d, JZ
1.8 Hz, 1H, major isomer), 9.13 (d, JZ1.8 Hz, 1H, minor
isomer). 13C NMR (CDCl3, 75 MHz) d 14.07 (minor
isomer), 15.03 (major isomer), 20.74 (major isomer),
24.33 (minor isomer), 25.40 (minor isomer), 26.05 (major
isomer), 26.84 (minor isomer), 27.13 (major isomer), 45.09
(minor isomer), 46.89 (major isomer), 65.52 (minor
isomer), 66.74 (major isomer), 88.84 (minor isomer),
88.92 (major isomer), 116.67 (major isomer), 116.05
(minor isomer), 126.44 (minor isomer), 126.48 (major
isomer), 126.99 (major isomer), 127.06 (minor isomer),
128.09 (minor isomer), 128.21 (major isomer), 128.46
(major isomer), 128.54 (minor isomer), 128.95 (major
isomer), 129.04 (minor isomer), 130.66 (both isomers),
132.21 (major isomer), 132.26 (minor isomer), 133.27
(major isomer), 133.65 (minor isomer), 134.17 (major
isomer), 135.97 (major isomer), 136.03 (minor isomer),
138.93 (major isomer), 139.46 (minor, isomer), 203.65
(minor isomer), 203.79 (major isomer) (one 13C signal of
the minor diastereomer is missing due to overlapping).
FAB-HMRS Calcd for C20H21O2 (MCK1): 293.1542.
Found: 293.1554.
4.4.6. (2-Allyltetrahydrofuran-2-yl)(4-methoxyphenyl)-
methanone (17a) and [tetrahydro-2-[(E)-prop-1-enyl]-
furan-2-yl](4-methoxyphenyl)methanone (17b). Yield:
70%. Colorless oil. The regioisomers are obtained as a 1:1
1
inseparable mixture. H NMR (CDCl3, 300 MHz) d 1.71
(dd, JZ3.2, 1.6 Hz, 3H), 1.77–1.99 (m, 6H), 2.59–2.75 (m,
4H), 3.77–3.87 (m, 2H), 3.88 (s, 3H), 3.89 (s, 3H), 3.97–
4.07 (m, 2H), 5.02–5.04 (m, 1H), 5.07–5.11 (m, 1H), 5.72–
5.87 (m, 3H), 6.91 (dd, JZ8.9, 2.0 Hz, 2H), 6.94 (dd, JZ
8.9, 2.0 Hz, 2H), 8.19 (dd, JZ8.9, 2.0 Hz, 2H), 8.26 (dd,
JZ8.9, 2.0 Hz, 2H). 13C NMR (CDCl3, 75 MHz, DEPT) d
18.52 (CH3), 25.55 (CH2), 25.92 (CH2), 34.32 (CH2), 36.06
(CH2), 44.13 (CH2), 55.99 (2!CH3), 69.35 (CH2), 69.44
(CH2), 92.51 (C), 92.73 (C), 113.75 (CH), 113.90 (CH),
119.13 (CH), 126.86 (CH), 128.57 (C), 129.00 (C), 133.27
(CH), 133.37 (CH), 133.52 (CH), 133.63 (CH), 163.67 (2!
C), 199.90 (C), 202.16 (C). EI-HRMS Calcd for C15H18O3:
246.1256. Found: 246.1252. Anal. Calcd for C15H18O3: C,
73.15; H, 7.37. Found: C, 73.58; H, 7.51.
4.4.7. [2-(But-3-en-2-yl)-tetrahydrofuran-2-yl](phenyl)-
methanone (19). Yield: 88%. Colorless oil. 2.5:1 mixture
1
of diastereomers. H NMR (CDCl3, 300 MHz) d 0.91 (d,
JZ6.9 Hz, 3H, minor isomer), 1.10 (d, JZ6.9 Hz, 3H,
major isomer), 1.59–1.87 (m, 2H major isomer, 3H minor
isomer), 1.99 (ddd, JZ12.7, 8.1, 8.1 Hz, 1H, major isomer),
2.43 (ddd, JZ12.7, 8.1, 5.7 Hz, 1H, major isomer), 2.60–
2.51 (m, 1H, minor isomer), 2.86–2.99 (m, 1H, both
isomers), 3.69–3.79 (m, 2H, major isomer), 3.88–3.91 (m,
2H, minor isomer), 4.93–5.13 (m, 2H, both isomers), 5.67
(ddd, JZ17.2, 10.3, 8.7 Hz, 1H, major isomer), 6.02 (ddd,
JZ18.4, 10.7, 6.9 Hz, 1H, minor isomer), 7.38–7.44 (m,
3H, major isomer), 7.8–7.54 (m, 3H, minor isomer), 8.18 (d,
JZ7.1, 1.6 Hz, 2H, major isomer), 8.20 (dt, JZ7.1, 1.6 Hz,
2H, minor isomer). 13C NMR (CDCl3, 75 MHz, DEPT) d
14.86 (CH3, minor isomer), 15.82 (CH3, major isomer),
26.28 (CH2, major and minor isomer), 30.56 (CH2, minor
isomer), 32.40 (CH2, major isomer), 44.07 (CH, minor
isomer), 45.84 (CH, major isomer), 69.88 (CH2, minor
4.4.9. [Tetrahydro-2-(2-methylbut-3-en-2-yl)-2H-pyran-
2-yl](phenyl)methanone (23). Yield: 46%. Colorless oil.
1H NMR (CDCl3, 300 MHz) d 0.88–0.23 (m, 1H), 1.08 (s,
3H), 1.10 (s, 3H), 1.16–1.50 (m, 3H), 1.60–1.75 (m, 1H),
2.40–2.47 (m, 1H), 3.35 (td, JZ12.1, 2.7 Hz, 1H), 3.78–
3.84 (m, 1H), 4.92–4.99 (m, 2H), 6.12 (dd, JZ17.4,
11.3 Hz, 1H), 7.40 (m, 2H), 7.50 (tt, JZ7.3, 1.4 Hz, 1H),
8.28 (dd, JZ8.1, 1.4 Hz, 2H). 13C NMR (CDCl3, JZ
75 MHz) d 21.51 (2!C), 23.10, 24.72, 25.78, 30.06, 66.68,
91.46, 112.70, 128.69, 131.18, 132.96, 145.76, 198.18 (one

C. Nevado, A. M. Echavarren / Tetrahedron 60 (2004) 9735–9744
9743
13C signal is missed due to overlapping). FAB-HRMS Calcd
2. Radetich, B.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120,
8007–8008.
for C17H21O2 (MCK1): 257.1542. Found: 257.1549.
3. (a) Heumann, A.; Moukhliss, M. Synlett 1998, 1211–1212.
(b) Heumann, A.; Moukhliss, M. Synlett 1999, 268.
4. (a) Widenhoefer, R. A.; Perch, N. S. Org. Lett. 1999, 1,
1103–1105. (b) Kisanga, P.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2000, 122, 10017–10126. (c) Kisanga, P.; Goj, L. A.;
Widenhoefer, R. A. J. Org. Chem. 2001, 66, 635–637. (d) Goj,
L. A.; Widenhoefer, R. A. J. Am. Chem. Soc. 2001, 123,
11133–11147. (e) Widenhoefer, R. A. Acc. Chem. Res. 2002,
35, 905–913.
4.4.10. [2-(Buta-2,3-dien-2-yl)-tetrahydro-2H-pyran-2-
yl](phenyl)methanone (27). Yield: 34%. Colorless oil. H
1
NMR (CDCl3, 300 MHz) d 1.52–1.69 (m, 4H), 1.74 (t, JZ
3.1 Hz, 3H), 1.78–1.83 (m, 1H), 2.31–2.40 (m, 1H), 3.46–
3.53 (m, 1H), 3.79–3.83 (m, 1H), 4.84 (m, 2H), 7.44 (dd,
JZ8.7, 8.5 Hz, 2H), 7.55 (t, JZ8.5 Hz, 1H), 8.22 (d, JZ
8.7 Hz, 2H). 13C NMR (CDCl3, 75 MHz, DEPT) d 14.30
(CH3), 20.27 (CH2), 25.09 (CH2), 31.13 (CH2), 64.98
(CH2), 77.28 (CH2), 84.97 (C), 101.04 (C), 128.01 (CH),
129.87 (CH), 132.51 (CH), 133.67 (C), 200.77 (C), 206.60
(C). EI-HRMS Calcd for C16H18O2: 242.1307. Found:
242.1287.
5. (a) Bray, K. L.; Fairlamb, I. J. S.; Lloyd-Jones, G. C. Chem.
Commun. 2001, 187–188. (b) Bray, K. L.; Charmant,
J. P. H.; Fairlamb, I. J. S.; Lloyd-Jones, G. C. Chem. Eur. J.
2001, 7, 4205–4215. (c) Lloyd-Jones, G. C. Org. Biomol.
Chem. 2003, 1, 215–236.
4.4.11. Tricycle 28. Yield: 40%. White solid: mp 58–59 8C.
1H NMR (300 MHz, CDCl3) d 7.45–7.41 (m, 2H), 7.39–
7.28 (m, 3H), 6.14 (d, JZ5.7 Hz, 1H), 5.13 (d, JZ5.7 Hz,
1H), 4.56 (s, 1H), 3.31 (ddd, JZ10.9, 4.4, 2.4 Hz, 1H), 2.27
(ddd, JZ12.4, 10.9, 2.4 Hz, 1H), 1.82–1.74 (m, 2H), 1.45–
1.26 (m, 2H), 1.19 (s, 3H), 1.18–1.10 (m, 1H); 13C NMR
(75 MHz, CDCl3, DEPT) d 140.41 (C), 140.40 (CH), 128.73
(CH), 128.56 (CH), 128.12 (CH), 113.59 (CH), 74.07 (CH),
69.99 (C), 64.87 (CH2), 25.63 (CH), 22.95 (CH2), 21.95 (C),
16.14 (CH2), 13.05 (CH3). Anal. Calcd for C16H18O2: C,
79.31; H, 7.49. Found: C, 79.06; H, 7.36.
6. Bright, A.; Malone, J. F.; Nicholson, J. K.; Powel, J.; Shaw,
B. L. J. Chem. Soc., Chem. Commun. 1971, 712–713.
7. (a) Yamamoto, Y.; Ohkoshi, N.; Kameda, M.; Itoh, K. J. Org.
Chem. 1999, 64, 2178–2179. (b) Yamamoto, Y.; Nakagai, Y.;
Ohkoshi, N.; Itoh, K. J. Am. Chem. Soc. 2001, 123,
6372–6380.
´ ´
8. (a) Fernandez-Rivas, C.; Mendez, M.; Echavarren, A. M.
´
J. Am. Chem. Soc. 2000, 122, 1221–1222. (b) Mendez, M.;
Mun˜oz, M. P.; Echavarren, A. M. J. Am. Chem. Soc. 2000,
´
122, 11549–11550. (c) Mendez, M.; Mun˜oz, M. P.; Nevado,
´
C.; Cardenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc.
´
´
2001, 123, 10511–10520. (d) Fernandez-Rivas, C.; Mendez,
M.; Nieto-Oberhuber, C.; Echavarren, A. M. J. Org. Chem.
2002, 67, 5197–5201. (e) Nevado, C.; Charruault, L.;
4.4.12. [(2R,5S,6R)-2-Allyl-5,6-dihydro-5-triisopropyl-
silyloxy-6-(triisopropylsilylxoymethyl)-2H-pyran-2-
yl](phenyl)methanone (33). Yield: 78%. Pale yellow oil.
This product was purified by flash chromatography with
hexane containing 5% Et3N as eluent. Mixture of epimers at
C-2: 5.4:1. Only major isomer is described. Configuration of
the new quaternary center was stablished by NOESY
´
Michelet, V.; Nieto-Oberhuber, C.; Mun˜oz, M. P.; Mendez,
ˆ
M.; Rager, M.-N.; Genet, J. P.; Echavarren, A. M. Eur. J. Org.
Chem. 2003, 706–713. (f) Nieto-Oberhuber, C.; Mun˜oz,
´
M. P.; Bun˜uel, E.; Nevado, C.; Cardenas, D. J.; Echavarren,
A. M. Angew. Chem., Int. Ed. 2004, 43, 2402–2406.
9. Nevado, C.; Echavarren, A. M. Chem. Soc. Rev. 2004, 33, in
press.
1
experiments. H NMR (CDCl3, 300 MHz) d 1.03–1.15 (m,
42H), 2.78 (ddt, JZ14.4, 6.7, 1.4 Hz, 1H), 2.95 (ddt, JZ
14.4, 7.9, 1.2 Hz, 1H), 3.78–3.90 (m, 2H), 4.04 (dd, JZ9.7,
1.8 Hz, 1H), 4.39 (dt, JZ7.7, 1.8 Hz, 1H), 5.04–5.13 (m,
2H), 5.81–6.05 (m, 3H), 7.35–7.57 (m, 3H), 8.12 (dd, JZ
8.5, 1.4 Hz, 2H). 13C NMR (CDCl3, JZ75 MHz) d 12.51,
13.37, 18.56, 18.78, 41.29, 64.13, 64.55, 76.71, 86.14,
118.90, 128.31, 128.61, 130.84, 131.12, 131.21, 132.74,
133.52, 201.79. MALDI-HRMS (dithranol-NaI matrix)
Calcd for C34H58O4NaSi2: 609.3771. Found: 609.3766.
´
10. Nevado, C.; Cardenas, D. J.; Echavarren, A. M. Chem. Eur. J.
2003, 9, 2627–2635.
11. Recent review: Martın Castro, A. M. Chem. Rev. 2004, 104,
2939–3002.
´
12. (a) van der Baan, J. L.; Bickelhaupt, F. Tetrahedron Lett. 1986,
27, 6267–6270. (b) Mikami, K.; Takahashi, K.; Nakai, T.
Tetrahedron Lett. 1987, 28, 5879–5882. (c) Sugiura, M.;
Yanagisawa, M.; Nakai, T. Synlett 1995, 447–448. (d) Sugiura,
M.; Nakai, T. Chem. Lett. 1995, 697–698.
13. (a) Overman, L. E. Angew. Chem., Int. Ed. 1984, 23, 579–586.
(b) Lutz, R. P. Chem. Rev. 1984, 84, 206–247.
Acknowledgements
14. (a) Tricycle 28 is the product of an intramolecular cyclopro-
panation catalyzed by Au(III). Nevado, C.; Ferrer, C.;
Echavasren, A. M. Org. Lett. 2004, 6, 010486573. (b) Related
structures have been published in Pt(II)-catalyzed transform-
ations. See: Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem.
Soc. 2001, 123, 11863–11869.
The present work was supported by the MCyT (Project
PB97-0002-C2), the ICIQ Foundation, and the CAM
(predoctoral fellowship to C. N.) We also thank Johnson
Matthey PLC for a generous loan of transition metal salts.
15. (a) Friesen, R. W.; Loo, R. W.; Sturino, C. F. Can. J. Chem.
1994, 72, 1262–1272. (b) Friesen, R. W.; Loo, R. W.
J. Organomet. Chem. 1991, 56, 4821–4823. (c) Friesen,
R. W.; Sturino, C. F.; Daljeet, A. K.; Kolaczewska, A. J. Org.
Chem. 1991, 56, 1944–1947. (d) Friesen, R. W.; Daljeet,
A. K. Tetrahedron Lett. 1990, 31, 6133–6136. (e) Lellouche,
J.-P.; Koeller, S. J. Org. Chem. 2001, 66, 693–696.
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17. The stereoselectivity in the formation of alcohols like 31 from
a-lithiated silyl protected glucal has not been studied in detail.
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19. Silylation of a 2-formyl derivative of 4-deoxyglucal under
kinetic conditions with TBSOTf and Et3N proceeded with 3:1
´ ´
E:Z stereoselectivity: Alvarez, E.; Dıaz, M. T.; Perez, R.;
´
Ravelo, J. L.; Regueiro, A.; Vera, J. A.; Zurita, D.; Martın, J. D.
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ˆ
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