Selective Long-Distance Isomerization of Terminal Alkenes via Nondissociative Chain Walking

Article abstract of DOI:10.1021/acs.joc.8b01288

Selective long-distance isomerization of terminal alkenes to silyl enol ethers proceeded via nondissociative chain walking using phenanthroline palladium catalysts. Notable features achieved taking advantage of the nondissociative chain walking mechanism

Full text of DOI:10.1021/acs.joc.8b01288

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Article
Selective Long-Distance Isomerization of Terminal
Alkenes via Nondissociative Chain Walking
Yuya Yamasaki, Takaaki Kumagai, Shota Kanno, Fumitoshi Kakiuchi, and Takuya Kochi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01288 • Publication Date (Web): 19 Jul 2018
Downloaded from http://pubs.acs.org on July 19, 2018
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Selective Long-Distance Isomerization of Terminal Alkenes via Nondissociative Chain
Walking
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Yuya Yamasaki, Takaaki Kumagai, Shota Kanno, Fumitoshi Kakiuchi, and Takuya Kochi*
Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi,
Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
kochi@chem.keio.ac.jp
Table of Contents/Abstract Graphic
Abstract
Selective long-distance isomerization of terminal alkenes to silyl enol ethers proceeded via
“nondissociative” chain walking using phenanthroline palladium catalysts. Notable features
achieved taking advantage of the nondissociative chain walking mechanism include high
efficiency obtained regardless of the chain length, high chemoselectivity toward terminal alkenes
over internal ones, and retention of the stereoconfiguration of the stereocenter on the alkyl chain.
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Introduction
Selective alkene isomerization is a powerful method to form desired unsaturated functional
1
groups without using oxidants. While most of the studies on the alkene isomerization have
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focused on those in which double bonds migrates over one carbon, long-distance alkene
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isomerization has also attracted growing attention as increasing efforts have been directed toward
developments of efficient remote functionalization methods.3
In general, there are two extreme types of mechanistic pathways considered for the long-
distance isomerization. One is the “stepwise” isomerization pathway (Figure 1a), in which alkene
exchange processes compete significantly with the isomerization process. In this case, various
intermediate alkenes may be formed during the reaction and have to coordinate to the metal center
again to complete the desired isomerization process. The other is the “nondissociative” chain
walking pathway (Figure 1b),4-7 in which alkene exchange process is much slower than the
isomerization process and substrate alkenes are directly converted to the desired alkenes without
releasing intermediate alkenes from the metal center. The mechanisms of the previously-reported
long-distance isomerization reactions may be unclear and are probably one of the two pathways or
fall between them. For example, Grotjahn and coworkers reported on a long-distance isomerization
of terminal alkenes to alcohols using a bifunctional ruthenium catalyst.2e,f Their examples include
the isomerization over up to 30 carbons, and their results showed that many intermediate alkenes
are formed during the reaction. Mazet and coworkers also reported on isomerization reactions
using palladium phosphine complexes,2g,h and their results on the complete racemization of the
stereocenters in the alkyl chain suggest that alkene exchange occurs rapidly during the
isomerization. Very recently, Kocen, Brookhart, and Daugulis reported on an isomerization
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reaction of terminal alkenes to silyl enol ethers using 2,9-dimethylphenanthroline-palladium
catalyst.2i
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Figure 1. Long-Distance Alkene Isomerizations
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We envisioned that if a long-distance isomerization reaction via the nondissociative chain
walking pathway is established, several distinguished features that are difficult to realize with the
stepwise isomerization pathway would be achieved. However, none of the previously-reported
selective long-distance isomerizations took advantage of the “nondissociative” chain walking
pathway to apply for the isomerization reaction that are otherwise difficult to achieve.8
Herein we report a palladium-catalyzed selective long-distance isomerization of terminal
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alkenes to silyl enol ethers via the nondissociative chain walking pathway (Figure 1d). Several
notable features were achieved taking advantage of the nondissociative chain walking mechanism
such as high efficiency obtained regardless of the chain length, high chemoselectivity toward
terminal alkenes over internal ones, and retention of the stereoconfiguration of the stereocenter on
the alkyl chain.
Results and Discussion
During the investigation of the chain-walking isomerization of 1,n-dienes using a
4
phenanthroline palladium catalyst, we encountered a challenge in settling the position of the
alkene moiety left in the product (Figure 1c). The cycloisomerization reaction is considered to
proceed via the nondissociative chain walking pathway, so we decided to search for a functional
group that can settle the position of the isomerizing alkene right next to it. Initially we attempted
the isomerization of several linear terminal alkenes possessing a functional group at the other
terminus. While methoxycarbonyl and phenyl groups failed to form the desired α,β-unsaturated
systems, alcohol substrates were mostly recovered with only a trace amount of the isomerization
products.10 But the reaction of a substrate possessing an alkoxy group (1a) with 1,10-
phenanthroline palladium catalyst 2a gave an encouraging result that alkenyl ether 3a was obtained
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in 48% yield (eq 1). Long-distance isomerizations of terminal alkenes possessing an alkoxy group
at the other terminus have been achieved and utilized in one-pot cross-coupling reactions by
2
j
2k
Mazet and Marek.
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Then we turned our attention to another class of ethers, silyl ethers, and found that siloxy groups
can settle the position of the isomerizing alkenes effectively next to them. The reaction of TES-
protected 9-decen-1-ol (1b) using 2.5 mol % of 2a and 3 mol % of NaBArf
(Ar = 3,5-(F
f
C)
C
4
3
2
6
3
H )
in 1,2-dichloroethane in the presence of MS 4A at 0 ºC for 3 h under a low-concentration condition
20 mM) provided silyl enol ether 3b in 77% yield (Table 1, entry 1).11 The reaction in
(
dichloromethane proceeded similarly, but the yield was decreased to 71% (E/Z = 27/73). While
the reactions of TBDPS- and TBS-protected alcohols (1c and 1d) gave comparable yields of the
products, the use of TIPS group further improved the yield to 90% (entry 4). The reaction of TIPS-
protected alcohol 1e also proceeds on a 1 g scale or using 0.12 mol % of 2a to give 91 and 92%
yields of 3e (Table 1, entry 5 and eq 2). The number of methylenes between vinyl and siloxy groups
was then examined (Table 1, entries 6-11), and it was found that the length of the methylene chain
had little effect on the yields, and even if the isomerization needs to proceed over 20 carbons, the
reaction was completed in 3 h at 0 ºC to give product 3k in 81% yield (entry 11). Long-distance
isomerizations of terminal alkenes possessing a siloxy group at the other terminus have been
reported,2c,e,j but previous examples required longer reaction times (18-24 h) and/or higher
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temperature (>70 ºC) for shorter substrates (isomerization over up to 8 carbons). The high
efficiency of the long-distance isomerization described here may be attributed to the
nondissociative chain-walking mechanism, where alkene exchange mostly proceeds between silyl
enol ether products and small terminal alkene moieties, and it does not require recoordination of
bulkier intermediate internal alkenes which competes with product recoordination.
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Table 1. Isomerization of ω-Siloxy-α-olefins to Silyl Enol Ethersa
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entry
alkene 1 [SiR
3
]
n
3, isolated yield (%)
3b, 77
E/Z
1
2
1b [SiEt
3
]
8
25/75
15/85
28/72
26/74
26/74
26/74
26/74
26/74
26/74
27/73
23/77
t
1c [Si BuPh
2
]
8
8
3c, 76
t
3
1d [Si BuMe
2
]
3d, 83
i
4
1e [Si Pr
3
]
]
8
3e, 90
5b
6
1e [Si Pr
i
8
3e, 91
3
i
1f [Si Pr
3
]
3
3f, 87
i
7
1g [Si Pr
3
]
4
3g, 89
i
8
1h [Si Pr
3
]
7
3h, 90
i
9
1i [Si Pr
3
]
14
18
20
3i, 86
i
1
0
1
1j [Si Pr
3
]
3j, 84
i
1
1k [Si Pr
3
]
3k, 81
aReaction conditions: 1 (0.5 mmol), 2a (0.0125 mmol), NaBArf
4
2
(0.015 mmol), CH ClCH Cl
2
b
(
25 mL), 0 ºC. Performed using 3.2 mmol (1.0 g) of 1e with 2.5 mol % of 2a and 3 mol % of
NaBArf
in 160 mL of CH
ClCH Cl.
4
2
2
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The long-distance isomerization can also be applied to substrates possessing branches on the
chain. The reaction of TIPS-protected secondary alcohol 1l did not give the corresponding product
1
2
(Table 2, entry 1), but the use of a smaller TES group provided product 3m in 61% yield (entry
1
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). The reaction was also attempted with TES-protected 1-phenyl-6-hepten-2-ol but almost no
isomerization was observed. Substrates possessing a methyl branch were also examined. The
isomerization of 4-methyl-5-hexen-1-ol derivatives 1n and 1o proceeded smoothly to afford 3n
and 3o in excellent yields (entries 3 and 4). In the case of silyl-protected 3-methyl-6-hepten-1-ol
1
p and 1q, the reaction became less efficient probably due to the increased steric congestion around
the alkene moiety, but products 3p and 3q were obtained in 69 and 67% yields, respectively
(entries 5 and 6). The reaction of TES-protected 3-phenyl-5-hexen-1-ol was also examined, but no
formation of the isomerization product was observed.
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Table 2. Selective Isomerization of Branched Siloxy-α-olefinsa
entry
alkene 1
silyl enol ether 3, isolated yield (%) [E/Z]
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i
1
2
1l (R = Pr)
not detected
1m (R = Et)
3m, 61 [15/85]
i
3
4
1n (R = Pr)
3n, 91 [27/73]
3o, 86 [31/69]
1o (R = Et)
5b
6c
1p (R = Pr)
i
3p, 69 [40/60]
3q, 67 [25/75]
1q (R = Et)
aReaction conditions: 1 (1.0 mmol), 2a (0.025 mmol), NaBArf
(0.03 mmol), CH
ClCH Cl (50
4
2
2
mL), 0 ºC, 3 h. Performed using 2 mmol of 1p with 2.5 mol % of 2a and 3 mol % of NaBArf
b
in
4
c
1
00 mL of CH
2
ClCH
2
Cl. Performed using 0.5 mmol of 1q with 2.5 mol % of 2a and 3 mol % of
NaBArf
in 25 mL of CH
ClCH Cl.
4
2
2
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Investigation of the reactions of internal alkenes bearing a siloxy group showed that the
isomerization proceeded but with lower efficiency. Under the same reaction conditions used in
Table 1, the reaction of 1,2-disubstituted alkenes (E)- and (Z)-1r produced product 3b in 58 and
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1% yields, respectively (Scheme 1a and 1b). Conversion of trisubstituted alkene 1s to product 3s
was not efficient at 0 ºC, but the reaction at 40 ºC gave 3s in 79% yield (Scheme 1c). The
isomerization of citronellol derivative 1t also proceeded at 40 ºC to provide 3t in 64% yield
(Scheme 1d).
Scheme 1. Isomerization of Internal Alkenes to Silyl Enol Ethersa
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One of the most striking features of the isomerization via the nondissociative chain walking
pathway is that conversion of terminal alkenes to products are completed without forming
intermediate internal alkenes. Therefore, if coordination of terminal alkenes to catalysts is much
faster than that of internal alkenes, it may be possible to perform chemoselective direct conversion
of terminal alkenes to products in the presence of internal alkenes. This type of reaction is very
difficult to achieve using the stepwise isomerization pathway, which inherently requires efficient
coordination of internal alkenes to catalysts.
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5
6
7
8
9
0
In order to examine the chemoselectivity toward terminal alkenes over internal alkenes,
competition experiments between terminal and internal alkene substrates were performed (Table
3). The reaction of a 1:1 mixture of terminal alkene 1e and 1,2-disubstituted alkene 1r was first
conducted using catalyst 2a (entries 1-3). The reaction was quite selective initially, and terminal
alkene 1e was converted to product 3e in 36% GC yield, while only 2% of product 3b was
generated from internal alkene 1r. The reaction for 30 min gave 3e in 75% yield, but conversion
of 1r to 3b was gradually accelerated to form 3b in 22% yield, as the amount of the remaining 1e
was reduced. Further elongation of the reaction time increased the yield of 3b rather than 3e (entry
3
). Screening of the reaction conditions revealed that the use of tetramethylphenanthroline
palladium catalyst 2b and the increase of the solvent volume was effective for improving the
chemoselectivity (entry 4-6), and the reaction for 30 min gave 3e in 92% yield while generating
only 10 % of 3b (entry 5). The competition experiment was also performed using terminal alkene
1e with trisubstituted alkene 1s (entries 7-9), and in the presence of catalyst 2a, the reaction for 30
min provided 3e in 87% GC yield along with only 7% GC yield of 3s (entry 8).
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Table 3. Chemoselective Isomerization of a Terminal Alkene in the Presence of Internal
Alkenesa
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry catalyst 2 [R’] time (min) GC yield of 3e (%) [E/Z] GC yield of 3b (%) [E/Z]
1
2
2a [H]
5
30
36 [13/87]
75 [17/83]
80 [17/83]
8 [–]c
2 [20/80]
22 [18/82]
41 [18/82]
ndd
2a [H]
3
2a [H]
120
5
4b
5b
6b
2b [Me]
2b [Me]
2b [Me]
30
92 [15/85]
94 [16/84]
10 [16/84]
31 [20/80]
120
aReaction conditions: 1e (50 μmol), 1r (50 μmol), 2 (2.5 μmol), NaBArf
(3 μmol), CH
ClCH Cl
4
2
2
b
c
d
(5 mL), 0 ºC. Performed in 10 mL of CH
2
ClCH
2
Cl. Not determined. Not detected.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry
time (min)
GC yield of 3e (%) [E/Z]
GC yield of 3s (%) [E/Z]
7 [–]b
ndc
7
8
9
5
30
87 [20/80]
90 [24/76]
7 [15/85]
120
31 [20/80]
aReaction conditions: 1e (50 μmol), 1s (50 μmol ), 2 (2.5 μmol), NaBArf
4
(3 μmol),
b
c
CH
2
ClCH Cl (5 mL), 0 ºC. Not determined. Not detected.
2
Finally, the chemoselective isomerization of terminal alkenes over internal alkenes was applied
to substrate 1u, which has both terminal and internal alkene moieties. The reaction of 1u in the
presence of 10 mol % of 2a for 6 h, followed by acid deprotection, provided 60% isolated yield of
ketone 3u, which still possesses the internal alkene moiety without isomerization (Scheme 2).
Scheme 2. Chemoselective Isomerization of a Terminal Alkene Possessing an Internal Alkene
Moiety
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Another feature of the isomerization via the nondissociative chain walking pathway is that
stereoconfiguration of the stereocenter present on the alkyl chain on which metal catalysts migrate
should be maintained after the isomerization. This feature has been previously shown in some
reactions,5d,j,l,13 but has not been demonstrated for simple long-distance isomerization reactions.
When the reaction of (S)-1q (97% ee) in the presence of 2.5 mol % of 2a was performed for 30
min, 38% NMR yield of (S)-3q was obtained with only 2% degradation of the enantiomeric excess
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(Table 4, entry 1). Extension of the reaction time to 60 min improved the yield of (S)-3q to 57%
with maintaining the high enantiomeric excess (95% ee) (entry 2). The observed high level of
retention of the stereochemistry strongly supports that the reaction mostly proceeds via the
nondissociative chain walking pathway. The slight degradation of the enantiomeric excess may be
attributed to dissociation of a small amount of trisubstituted alkene intermediates during the
reaction. When the reaction of (S)-1q was performed in 2 mL of dichloroethane instead of 10 mL,
the yield of (S)-3q was decreased with maintaining the similar level of ee, indicating that the alkene
exchange was somewhat accelerated at high concentration. The reaction at 40 ºC for 30 min gave
(S)-3q in 78% yield but the ee was decreased to 32%, probably because the isomerization was
accelerated significantly, and considerable recoordination/isomerization of the product alkene
started to occur to racemize the stereocenter (entry 4).
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 4. Retention of the Stereoconfiguration at the Stereocenter on the Methylene Chaina
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry time (min) temp (ºC) NMR yield of 3q (%) [E/Z] ee [es] (%, after deprotection)
1
2
30
60
30
30
0
0
38 [21/79]
57 [23/77]
78 [39/61]
27 [26/74]
95 [97]
95 [97]
3
40
0
32 [33]
4b
96 [98]
aReaction conditions: (S)-1q (0.2 mmol), 2a (5 μmol), NaBArf
(6 μmol), MS 4A, CH
ClCH Cl
4
2
2
b
(
10 mL). Performed in 2 mL of CH
2
ClCH Cl (100 mM).
2
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Conclusion
Selective long-distance isomerization of alkenes to silyl enol ethers via the “nondissociative”
chain walking pathway was developed using phenanthroline palladium catalysts. Various terminal
alkenes bearing a siloxy group were efficiently isomerized to silyl enol ethers, and isomerization
of a substrate which requires chain walking over 20 carbons can be conducted at 0 ºC within 3 h
to obtain the corresponding product in high yield. Highly chemoselective isomerization of terminal
alkenes in the presence of internal alkenes and retention of the stereoconfiguration of the
stereocenter on the alkyl chain were also achieved by taking advantage of the nondissociative chain
walking mechanism. Application of the chain-walking isomerization to other reactions such as
cycloisomerization reactions is in progress.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Experimental Section
Unless otherwise noted, all reactions were carried out under nitrogen, and all commercial
reagents were used as received. (3,4,7,8-Me phen)PdMeCl, (phen)PdMeCl, (bpy)PdMeCl and
1,10-Me phen)PdMeCl were prepared by previously-reported methods. NaH was washed three
times with hexane prior to use. Anhydrous DMF and THF were purchased from Kanto Chemical
Co. Inc. and used as received. 1,2-Dichloroethane was distilled from P . Dichloromethane was
purified by passing through a Glass Contour solvent purification system. 3-Methy1-6-hepten-1-ol
4
4
a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
2
2
O
5
was synthesized according to the literature procedure.13 1H, and C{ H} NMR spectra were
recorded on a JEOL ECX-400 or AL-400 spectrometer. Gas chromatography (GC) analyses were
performed using a CBP-10 capillary column (25 m × 0.22 mm, film thickness 0.25 μm). IR spectra
were recorded on a JASCO FT/IR-410 infrared spectrometer. ESI-MS was performed on a JEOL
JMS-T100LCS. HPLC analysis was performed on a HITACHI Elite LaChrom Series HPLC with
a Chiralpak AY-H (0.46 cm x 25 cm) column with UV detection at 254 nm. Flash column
13
1
chromatography was carried out with silica gel 60N (Kanto Chemical Co., Inc.) or AgNO
gel prepared before use.4b,14
3
/silica
Preparation of Alkyl Ether 1a. To a suspension of NaH (808 mg of 60% oil suspension,
washed three times with hexane before use, 20.2 mmol, 2.05 equiv) in DMF (20 mL) was slowly
added 9-decen-1-ol (1.54 g, 9.84 mmol) in DMF (5 mL) at 0 °C. A solution of 1-bromobutane
(1.51 g, 11.0 mmol) in DMF (5 mL) was added dropwise to the flask and the mixture was stirred
30 min. The solution was gradually warmed to room temperature and stirred overnight. After this
period, a saturated aqueous solution of ammonium chloride was introduced to the mixture, which
was then extracted five times with EtOAc. Combined organic portions were washed five times
with water, quickly dried over MgSO , filtered, and concentrated. Column chromatography of the
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crude material on silica gel (hexane:EtOAc = 20:1) afforded of the desired alkyl ether 1a (1.04 g,
5
0% yield) as a colorless oil: IR (neat): 3328 w, 3077 w, 2958 s, 2929 s, 2855 s, 2795 m, 2744 w,
1641 m, 1465 m, 1438 m, 1415 w, 1375 m, 1301 w, 1232 w, 1117 s, 992 m, 910 s, 841 m, 723 w,
-
1 1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
1
5
3
35 w cm ; H NMR (400 MHz, CDCl
3
): δ 0.92 (t, J = 7.6 Hz, 3H), 1.23-1.41 (m, 12H), 1.52-
.59 (m, 4H), 2.04 (q, J = 7.2 Hz, 2H), 3.40 (td, J = 6.8 Hz, 3.6 Hz, 4H), 4.91-5.01 (m, 2H), 5.76-
1
3
.86 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 13.9, 19.4, 26.2, 28.9, 29.1, 29.4 (2×1C), 29.8, 31.9,
+
3.8, 70.6, 71.0, 114.1, 139.2; HRMS (APCI-TOF) m/z: [M+H] Calcd for C14
H
29O 213.2218;
Found 213.2209.
General Procedure A for Preparation of Silyl Ethers 1b-h,l-t. To a solution of the alcohol (1
equiv) in CH Cl (ca. 10 mL per 3 mmol of alcohol) at 0 °C, was added imidazole (1.10 equiv)
2
2
and DMAP (0.05 equiv, if any). Stirring was continued for 5 min, and then the silyl chloride (1.20
equiv). The reaction mixture was gradually warmed to room temperature and stirred for 3 h. After
this period, a saturated aqueous solution of NaHCO
0 min, which extracted with CH Cl three times. Combined organic portions were washed with
brine, quickly dried over MgSO , filtered, and concentrated. Column chromatography of the crude
3
was introduced to the mixture and stirred for
3
2
2
4
material on silica gel (hexane/EtOAc) afforded the desired silyl ethers 1.
Silyl ether 1b. General Procedure A was followed with 803 mg of 9-decen-1-ol and 900 mg of
triethylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc = 20:1) of the crude
material afforded 976 mg of 1b (70% yield) as a colorless oil. The analytical data of 1b are in good
agreement with those reported in literature.15
Silyl ether 1c. General Procedure A was followed with 1.41 g of 9-decen-1-ol and 3.59 g of
tert-butyldiphenylsilyl chloride without using DMAP. Silica gel chromatography (hexane only) of
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
the crude material afforded 2.87 g of 1c (81% yield) as a colorless oil. The analytical data of 1c
are in good agreement with those reported in literature.16
Silyl ether 1d. General Procedure A was followed with 790 mg of 9-decen-1-ol and 929 mg of
tert-butyldimethylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc = 100:1)
of the crude material afforded 1.17 g of 1d (86% yield) as a colorless oil. The analytical data of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
d are in good agreement with those reported in literature.17
Silyl ether 1e. General Procedure A was followed with 783 mg of 9-decen-1-ol and 1.18 g of
triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc = 100:1) of the
crude material afforded 1.25 g of 1e (80% yield) as a colorless oil. IR (neat): 2928 s, 2865 s, 1641
-1 1
w, 1463 w, 1386 w, 1249 w, 1107 m, 1069 w, 994 w, 909 w, 882 m, 790 w, 681 m cm ; H NMR
400 MHz, CDCl ): δ 0.98-1.13 (m, 21H), 1.29-1.39 (m, 10H), 1.50-1.56 (m, 2H), 2.04 (q, J = 8.0
Hz, 2H), 3.67 (t, J = 6.8 Hz, 2H), 4.91-5.02 (m, 2H), 5.76-5.87 (m, 1H); C NMR (100 MHz,
(
3
1
3
CDCl
3
): δ 12.0, 18.0, 25.8, 28.9, 29.1, 29.4, 29.5, 33.0, 33.8, 63.5, 114.1, 139.2; HRMS (APCI-
+
TOF) m/z: [M+H] Calcd for C19
H41OSi 313.2927; Found 313.2928.
Silyl ether 1f. General Procedure A was followed with 856 mg of 4-penten-1-ol and 2.33 g of
triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the crude
material afforded 2.09 g of 1f (87% yield) as a colorless oil. The analytical data of 1f are in good
agreement with those reported in literature.18
Silyl ether 1g. General Procedure A was followed with 1.02 g of 5-hexen-1-ol and 2.26 g of
triisopropylsilyl chloride without using DMAP. Silica gel chromatography (hexane only) of the
crude material afforded 2.26 g of 1g (87% yield) as a colorless oil. The analytical data of 1g are in
good agreement with those reported in literature.19
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Silyl ether 1h. General Procedure A was followed with 1.43 g of 8-nonen-1-ol and 2.32 g of
triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the crude
material afforded 2.50 g of 1h (83% yield) as a colorless oil. IR (neat): 3078 w, 2929 s, 2866 s,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
7
1
2
3
2
728 w, 1642 m, 1464 s, 1383 m, 1247 w, 1108 s, 1070 m, 1013 m, 995 s, 910 s, 883 s, 794 m,
-1 1
18 m, 682 s, 668 s, 657 m, 638 m cm ; H NMR (400 MHz, CDCl
3
): δ 1.03-1.13 (m, 21H), 1.31-
.40 (m, 8H), 1.50-1.57 (m, 2H), 2.04 (q, J = 7.2 Hz, 2H), 3.67 (t, J = 6.4 Hz, 2H), 4.91-5.02 (m,
1
3
H), 5.76-5.86 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 12.0, 18.0, 25.8, 28.9, 29.1, 29.3, 33.0,
+
3.8, 63.5, 114.1, 139.2; HRMS (APCI-TOF) m/z: [M+H] Calcd for C18
H39OSi 299.2770; Found
99.2766.
Silyl ether 1l. General Procedure A was followed with 1.46 g of 1-nonen-5-ol and 2.37 g of
triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the crude
material afforded 184 mg of 1l (6% yield) as a colorless oil. IR (neat): 3079 w, 2943 s, 2867 s,
2724 w, 1825 w, 1642 m, 1367 w, 1288 w, 1247 w, 1216 w, 1130 m, 1086 s, 1059 s, 1013 m, 996
-1 1
m, 910 s, 883 s, 881 w, 720 w, 676 s m ; H NMR (400 MHz, CDCl
3
): δ 0.90 (t, J = 6.8 Hz, 3H),
1
.01-1.12 (m, 21H), 1.26-1.31 (m, 4H), 1.46-1.64 (m, 4H), 2.10 (q, J = 7.2 Hz, 2H), 3.84 (quin, J
1
3
=
5.6 Hz, 1H), 4.92-5.03 (m, 2H), 5.78-5.88 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 12.7, 14.1,
+
1
8.2, 23.0, 27.1, 29.1, 35.7, 36.3, 71.8, 114.1, 139.1; HRMS (APCI-TOF) m/z: [M+H] Calcd for
C
18
H39OSi 299.2770; Found 299.2756.
Silyl ether 1m. General Procedure A was followed with 1.43 g of 1-nonen-5-ol and 2.03 g of
triethylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the crude material
afforded 2.03 g of 1m (79% yield) as a colorless oil. IR (neat): 2957 s, 2876 s, 1642 w, 1459 w,
-1 1
1
414 w, 1378 w, 1238 w, 1134 w, 1057 m, 1011 m, 909 m, 759 s, 743 s, 724 s cm ; H NMR (400
MHz, CDCl
3
): δ 0.60 (q, J = 8.0 Hz, 6H), 0.88-0.91 (m, 3H), 0.96 (t, J = 8.0 Hz, 9H), 1.28-1.32
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(
m, 4H), 1.41-1.55 (m, 4H), 2.01-2.17 (m, 2H), 3.66 (quin, J = 6.0 Hz, 1H), 4.93-5.03 (m, 2H),
1
3
5
.77-5.88 (m, 1H); C NMR (100 MHz, CDCl ): δ 5.1, 7.0, 14.1, 22.9, 27.5, 29.7, 36.3, 36.9, 71.8,
3
+
114.2, 139.0; HRMS (APCI-TOF) m/z: [M+H] Calcd for C15H33OSi 257.2301; Found 257.2293.
0
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8
9
0
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Silyl ether 1n. General Procedure A was followed with 1.72 g of 4-methyl-5-hexen-1-ol and
.49 g of triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc =
00:1) of the crude material afforded 3.69 g of 1n (91% yield) as a colorless oil. IR (neat): 3079
3
1
w, 2958 s, 2943 s, 2894 m, 2867 s, 1640 w, 1464 m, 1383 w, 1247 w, 1107 s, 1070 w, 1014 w,
-1
1
9
95 m, 910 m, 882 m, 785 w, 725 w, 687 m, 682 m, 656 m cm ; H NMR (400 MHz, CDCl
3
): δ
0
.99 (d, J = 6.8 Hz, 3H), 1.03-1.13 (m, 21H), 1.31-1.39 (m, 2H), 1.47-1.61 (m, 2H), 2.13 (sep, J =
13
6.8 Hz, 1H), 3.66 (t, J = 6.8 Hz, 2H), 4.90-4.98 (m, 2H), 5.65-5.74 (m, 1H); C NMR (100 MHz,
): δ 12.0, 18.0, 20.2, 30.7, 32.7, 37.6, 63.5, 112.4, 144.8; HRMS (APCI-TOF) m/z: [M+H]+
CDCl
3
Calcd for C16H35OSi 271.2457; Found 271.2448.
Silyl ether 1o. General Procedure A was followed with 1.72 g of 4-methyl-5-hexen-1-ol and
2
.75 g of triethylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc = 100:1)
of the crude material afforded 2.06 g of 1o (60% yield) as a colorless oil. IR (neat): 3079 w, 2957
-1
s, 2913 s, 2877 s, 1457 m, 1419 w, 1388 w, 1239 w, 1100 s, 1006 m, 911 m, 793 w, 743 s cm ;
1H NMR (400 MHz, CDCl
3
): δ 0.59 (q, J = 8.0 Hz, 6H), 0.94-1.00 (m, 12H), 1.27-1.35 (m, 2H),
1
5
.49-1.57 (m, 2H), 2.12 (sep, J = 6.8 Hz, 1H), 3.59 (t, J = 6.8 Hz, 2H), 4.90-4.98 (m, 2H), 5.64-
13
.73 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 4.4, 6.8, 20.2, 30.6, 32.7, 37.6, 63.0, 112.5, 144.7;
29OSi 229.1988; Found 229.1994.
+
HRMS (APCI-TOF) m/z: [M+H] Calcd for C13
H
Silyl ether 1p. General Procedure A was followed with 1.79 g of 3-methyl-6-hepten-1-ol and
3
.26 g of triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc =
1000:1) of the crude material afforded 638 mg of 1p (16% yield) as a colorless oil. IR (neat): 3699
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w, 3469 w, 3078 w, 2942 s, 2868 s, 2725 w, 1642 w, 1464 s, 1383 w, 1367 w, 1248 w, 1103 s,
-1 1
1
071 m, 1014 m, 995 m, 909 m, 883 s, 803 m, 737 m, 680 s, 658 m cm ; H NMR (400 MHz,
CDCl ): δ 0.89 (d, J = 6.8 Hz, 3H), 0.98-1.13 (m, 21H), 1.18-1.27 (m, 1H), 1.32-1.46 (m, 2H),1.50-
.65 (m, 2H), 1.98-2.14 (m, 2H), 3.66-3.76 (m, 2H), 4.91-5.03 (m, 2H), 5.76-5.86 (m, 1H); C
3
13
1
1
1
1
1
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1
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5
6
0
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8
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0
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8
9
0
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8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
NMR (100 MHz, CDCl
3
): δ 12.0, 18.0, 19.6, 29.1, 31.3, 36.3, 40.0, 61.6, 114.0, 139.3; HRMS
+
(
APCI-TOF) m/z: [M+H] Calcd for C17
H37OSi 285.2614; Found 285.2618.
Silyl ether 1q. General Procedure A was followed with 1.31 g of 3-methyl-6-hepten-1-ol and
1
.81 g of triethylsilyl chloride using DMAP. Silica gel chromatography (hexane only to
hexane:EtOAc = 100:1) of the crude material afforded 2.10 g of 1q (85% yield) as a colorless oil.
IR (neat): 3078 w, 2957 s, 2910 s, 2879 s, 2734 w, 1641 w, 1460 m, 1415 w, 1379 w, 1239 w,
-1
1
1
097 s, 1010 m, 910 m 804 w, 668 w, 637 w cm ; H NMR (400 MHz, CDCl ): δ 0.60 (q, J = 8.0
3
Hz, 6H), 0.89 (d, J = 7.2 Hz, 3H), 0.96 (t, J = 8 Hz, 9H), 1.17-1.26 (m, 1H), 1.31-1.45 (m, 2H),
1.51-1.62 (m, 2H), 1.98-2.14 (m, 2H), 3.58-3.69 (m, 2H), 4.91-5.03 (m, 2H), 5.76-5.86 (m, 1H);
13C NMR (100 MHz, CDCl
): δ 4.4, 6.8, 19.5, 29.1, 31.3, 36.3, 39.9, 61.1, 114.1, 139.2; HRMS
31OSi 243.2144; Found 243.2132.
3
+
(
APCI-TOF) m/z: [M+H] Calcd for C14
H
Silyl ether (E)-1r. General Procedure A was followed with 1.04 g of (E)-5-decen-1-ol and 1.38
g of triethylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc = 150:1) of the
crude material afforded 1.00 g of 1r (56% yield) as a colorless oil. IR (neat): 2957 s, 2935 s, 2876
s, 1700 w, 1653 w, 1457 w, 1414 w, 1386 w, 1240 w, 1103 s, 1007 m, 967 m, 802 w, 740 s, 677
-1 1
s, 668 w cm ; H NMR (400 MHz, CDCl
3
): δ 0.60 (q, 8.0 Hz, 6H), 0.89 (d, 7.2 Hz, 3H), 0.96 (t,
8
5
.0 Hz, 9H), 1.28-1.42 (m, 6H), 1.50-1.57 (m, 2H), 1.97-2.01 (m, 4H), 3.60 (t, J = 6.8 Hz, 2H),
1
3
.34-5.44 (m, 2H); C NMR (100 MHz, CDCl ): δ 4.4, 6.8, 13.9, 22.2, 25.8, 31.8, 32.26, 32.35,
3
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+
3
2.4, 62.8, 130.0, 130.6; HRMS (APCI-TOF) m/z: [M+H] Calcd for C16
H
35OSi 271.2457; Found
2
71.2451.
Silyl ether (Z)-1r. (Z)-5-decen-1-ol was prepared following the procedure reported by Singh et
al.20 General Procedure A was followed with 259 mg of (Z)-5-decen-1-ol and 316 mg of
triethylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the crude material
afforded 320 mg of 1r (72% yield) as a colorless oil. IR (neat): 3005 s, 2955 s, 2934 s, 2876 s,
0
1
2
3
4
5
6
7
8
9
0
1
2
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0
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8
9
0
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8
9
0
1
2
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4
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7
8
9
0
2
733 w, 1654 w, 1458 m, 1414 m, 1381 w, 1238 m, 1178 w, 1102 s, 1014 m, 976 m, 893 w, 853
-1
1
w, 795 m, 776 m, 742 s, 672 w cm ; H NMR (400 MHz, CDCl
3
): δ 0.60 (q, 8.0 Hz, 6H), 0.88-
0
.91 (m, 3H), 0.96 (t, 8.0 Hz, 9H), 1.30-1.34 (m, 4H), 1.36-1.43 (m, 2H), 1.51-1.58 (m, 2H), 2.00-
1
3
2.07 (m, 4H), 3.60 (t, J = 6.6 Hz, 2H), 5.31-5.40 (m, 2H); C NMR (100 MHz, CDCl ): δ 4.4, 6.8,
3
4.0, 22.3, 26.0, 26.93, 26.97, 31.9, 32.5, 62.8, 129.6, 130.1; HRMS (DART-TOF) m/z: [M+H]+
1
Calcd for C16H35OSi 271.2457; Found 271.2459.
Silyl ether 1s. General Procedure A was followed with 2.29 g of 5-methyl-4-hexen-1-ol and
.87 g of triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane:EtOAc =
00:1) of the crude material afforded 4.66 g of 1s (86% yield) as a colorless oil. IR (neat): 2942 s,
893 m, 2867 s, 1464 m, 1381 w, 1249 w, 1104 m, 1067 w, 1013 w, 996 w, 882 m, 796 w, 720 w,
2
1
2
6
1
-1 1
82 m cm ; H NMR (400 MHz, CDCl
3
): δ 0.99-1.13 (m, 21H), 1.53-1.59 (m, 2H), 1.60 (s, 3H),
13
.69 (s, 3H), 2.05 (q, J = 7.2 Hz, 2H), 3.67 (t, J = 6.4Hz, 2H), 5.11-5.15 (m, 1H); C NMR (100
MHz, CDCl
3
): δ 12.0, 17.6, 18.0, 24.3, 25.7, 33.2, 62.9, 124.3, 131.6; HRMS (APCI-TOF) m/z:
35OSi 271.2457; Found 271.2454.
+
[M+H] Calcd for C16
H
Silyl ether 1t. General Procedure A was followed with 4.73 g of 3,7-dimethyl-6-octen-1-ol and
6
.46 g of triisopropylsilyl chloride using DMAP. Silica gel chromatography (hexane only) of the
crude material afforded 4.93 g of 1t (52% yield) as a colorless oil. IR (neat): 2959 s, 2942 s, 2926
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s, 2867 s, 2725 w, 1463 m, 1380 m, 1247 w, 1103 s, 1070 m, 1012 w, 996 w, 918 w, 883 m, 738
-1 1
w, 681 m, 658 m cm ; H NMR (400 MHz, CDCl
3
): δ 0.89 (d, J = 6.8 Hz, 3H), 1.03-1.23 (m,
22H), 1.29-1.40 (m, 2H), 1.55-1.63 (m, 2H), 1.60 (s, 3H), 1.68 (s, 3H), 1.90-2.05 (m, 2H), 3.66-
1
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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3
3
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4
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5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
2
3
.77 (m, 2H), 5.08-5.12 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 12.0, 17.6, 18.0, 19.7, 25.5, 25.7,
+
9.1, 37.2, 40.1, 61.7, 124.9, 131.0; HRMS (APCI-TOF) m/z: [M+H] Calcd for C19
13.2927; Found 313.2929.
H41OSi
General Procedure B for Preparation of Silyl Ethers 1i-k. Alkenyl esters were prepared
21
following the procedure reported by Riepl et al. To a suspension of magnesium (2 equiv) in THF
(ca. 2 mL per 1 mmol of bromoalkane) at rt, was slowly added the bromoalkane (2 equiv). The
reaction mixture was refluxed for 30 min and cooled to rt to form a solution of a Grignard reagent.
In a separate flask, CuI (2 equiv) was suspended in THF (ca. 1 mL per 1 mmol of CuI) and
cooled to -78 °C. A solution of methyllithium (1.0 M in Et O, 2 equiv) was slowly added to the
2
suspension via a syringe. The resulting mixture was stirred at -78 °C for 1 h and allowed to warm
to 0 °C to form an orange suspension, which was then cooled to -78 °C. The aforementioned
solution of Grignard reagent was then slowly added to the mixture via a cannula. The mixture was
stirred at -78 °C for 1 h and then allowed to warm to 0 ºC to form a purple suspension. The mixture
was again cooled to -78 °C, and a solution of methyl 11-iodoundecanoate (1 equiv) in THF (ca. 4
mL per 1 mmol of ester) was added to the mixture via a cannula. The reaction mixture was stirred
at -78 °C for 1 h and then at room temperature for 2 h, and a saturated aqueous solution of NH
and Et O were added to the resulting mixture. The mixture was filtered through a pad of Celite
and the filter cake was washed with Et O. The filtrate was extracted three times with Et O. The
, filtered and concentrated.
4
Cl
2
2
2
combined organic portions were washed with brine, dried over MgSO
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Silica gel column chromatography (hexane:EtOAc = 30:1) of the crude material afforded the
corresponding alkenyl ester that was used without further purification.
To a solution of the alkenyl ester in THF (2 mL per 1 mmol of ester) at 0 °C, was slowly added
a solution of DIBAL-H (1.0 M in toluene, 2.2 equiv), and then allowed to warm to room
temperature. The mixture was stirred for 14 h, and then a 15% aqueous solution of NaOH (0.1 mL
0
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9
0
1
2
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8
9
0
per 1 mmol of ester) was slowly added to the reaction mixture. Et
and water (0.3 mL per 1 mmol of ester) were added to the mixture, which was then warm to room
temperature. The mixture was dried over MgSO and filtered through a pad of Celite. The filter
cake was washed with Et O, and the filtrate was concentrated. Silica gel column chromatography
2
O (0.2 mL per 1 mmol of ester)
4
2
(hexane:EtOAc = 5:1) of the crude material afforded the corresponding alcohol that was used
without further purification.
Preparation of silyl ethers were conducted following General Procedure A using the
aforementioned alcohol. Flash column chromatography was performed using 30% AgNO
gel instead of 100% silica gel (hexane only) to afford the corresponding silyl ethers.
3
/silica
Silyl ether 1i. General Procedure B was followed with 3.27 g of methyl 11-iodoundecanoate.
Silica gel chromatography of the crude material afforded 2.07 g of methyl hexadec-15-enoate
1
0
containing a substantial amount of methyl dodecanoate (ca. 61% yield, ca. 79% purity based on
1
the ratio of the H NMR peak areas) as a colorless oil. 283 mg of this mixture was used for the
reduction and the silyl protection. Column chromatography of the crude material using 30%
AgNO
3
/silica gel afforded 273 mg of silyl ether 1i (50% yield over 2 steps) as a colorless oil. IR
(neat): 3077 w, 2925 s, 2854 s, 2721 w, 1642 w, 1464 m, 1382 w, 1247 w, 1107 s, 1070 m, 1013
-1 1
m, 995 m, 909 m, 883 s, 792 w, 720 w, 680 m, 657 m cm ; H NMR (400 MHz, CDCl ): δ 1.02-
3
1.11 (m, 21H), 1.22-1.39 (m, 22H), 1.50-1.57 (m, 2H), 2.04 (q, J = 6.8 Hz, 2H), 3.66 (t, J = 6.8
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9
13
Hz, 2H), 4.91-5.02 (m, 2H), 5.76-5.87 (m, 1H); C NMR (100 MHz, CDCl
3
): δ 12.0, 18.0, 25.8,
2
8.9, 29.2, 29.5-29.7 (8×1C), 33.0, 33.8, 63.5, 114.1, 139.3; HRMS (APCI-TOF) m/z: [M+H]+
Calcd for C25 53OSi 397.3866; Found 397.3877.
H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Silyl ether 1j. General Procedure B was followed with 2.97 g of methyl 11-iodoundecanoate.
Silica gel chromatography of the crude material afforded 1.56 g of methyl methyl henicos-20-
1
0
enoate containing a substantial amount of methyl dodecanoate (ca. 46% yield, ca. 86% purity
1
based on the ratio of the H NMR peak areas) as a white solid. 319 mg of this mixture was used
for the reduction and the silyl protection. Column chromatography of the crude material using 30%
AgNO
3
/silica gel afforded 363 mg of silyl ether 1j (43% yield over 2 steps) as a colorless oil. IR
(neat): 3077 w, 2924 s, 2854 s, 2721 w, 1823 w, 1642 w, 1464 s, 1382 w, 1367 w, 1248 w, 1107
-1
1
s, 1070 m, 1014 m, 995 m, 909 m, 883 s, 791 w, 721 w, 681 s, 658 m, 640 m cm ; H NMR (400
MHz, CDCl ): δ 0.99-1.15 (m, 21H), 1.21-1.39 (m, 30H), 1.50-1.57 (m, 2H), 2.04 (q, J = 7.2 Hz,
2H), 3.66 (t, J = 6.8 Hz, 2H), 4.91-5.02 (m, 2H), 5.76-5.87 (m, 1H); C NMR (100 MHz, CDCl
3
13
3
):
δ 12.0, 18.0, 25.8, 29.0, 29.2, 29.5-29.7 (12×1C), 33.1, 33.8, 63.5, 114.1, 139.3; HRMS (APCI-
+
TOF) m/z: [M+H] Calcd for C29
H
61OSi 453.4492; Found 453.4487.
Silyl ether 1k. General Procedure B was followed with 1.68 g of methyl 11-iodoundecanoate.
Silica gel chromatography of the crude material afforded 1.50 g of methyl tricos-22-enoate
10
containing a substantial amount of methyl dodecanoate (ca. 62% yield, ca. 75% purity calculated
by NMR peak area) as a white solid. 346 mg of this mixture was used for the reduction and the
silyl protection. Column chromatography of the crude material using 30% AgNO
afforded 127 mg of silyl ether 1k (22% yield over 2 steps) as a colorless oil. IR (neat): 3077 w,
925 s, 2854 s, 2726 w, 1821 w, 1641 w, 1465 s, 1384 w, 1366 w, 1301 w, 1247 w, 1107 s, 1070
3
/silica gel
2
-1 1
m, 1012 w, 994 m, 909 m, 882 m, 791 w, 719 w, 681m, 658 m cm ; H NMR (400 MHz, CDCl ):
3
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6
δ 1.01-1.13 (m, 21H), 1.21-1.39 (m, 34H), 1.50-1.56 (m, 2H), 2.04 (q, J = 7.2 Hz, 2H), 3.66 (t, J
1
3
=
6.8 Hz, 2H), 4.91-5.02 (m, 2H), 5.76-5.87 (m, 1H); C NMR (100 MHz, CDCl ): δ 12.0, 18.0,
3
25.8, 29.0, 29.2, 29.5-29.7 (14×1C), 33.1, 33.8, 63.5, 114.1, 139.3; HRMS (APCI-TOF) m/z:
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
[
M+H] Calcd for C31
H65OSi 481.4805; Found 481.4793.
Preparation of Terminal Alkene Possessing an Internal Alkene Moiety 1u. 6-(4-
Methoxyphenylmethoxy)-1-hexanal22 and (E)-3-penten-1-ol23 were prepared following the
procedures reported in literature.
-(4-Methoxyphenylmethoxy)-4-triethylsiloxy-1-nonene. The Grignard reaction24 and the
9
TES-protection of the alcohol25 were carried out by procedures similar to those reported in
literature. To a solution of 6-(4-methoxyphenylmethoxy)-1-hexanal (4.82 g, 20.4 mmol) in Et
2
O
(
100 mL) was added allyl magnesium bromide (1.0 M in Et O, 50 mL) at -78 ºC. The reaction
2
mixture was stirred at room temperature for 1.5 h. A saturated solution of ammonium chloride was
added to the mixture at 0 ºC The organic layer was separated and the aqueous layer was extracted
three times with Et
2
O. The combined organic portions were dried over Na
2
SO and the volatile
4
materials were removed in vacuo to afford 9-(4-methoxyphenylmethoxy)-1-nonen-4-ol, which
was used in the next step without further purification.
To a solution of 9-(4-methoxyphenylmethoxy)-1-nonen-4-ol in CH
imidazole (4.50 g, 66.1 mmol) and TESCl (5.50 mL, 32.8 mmol) at 0 ºC, and the reaction mixture
was stirred at room temperature for 2.5 h. A saturated aqueous solution of NaHCO was added to
the resulting mixture, which was then extracted with EtOAc. The combined organic portions were
washed with brine, dried over Na SO , filtered, and concentrated. Silica gel column
2
Cl
2
(100 mL) were added
3
2
4
chromatography (hexane:EtOAc = 20:1 to 10:1) of the crude material afforded 2.67 g of 9-(4-
methoxyphenylmethoxy)-4-triethylsiloxy-1-nonene (6.79 mmol, 33% yield over 2 steps) as a
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
colorless oil: IR (neat): 3074 w, 2938 s, 2913 s, 2876 s, 1640 w, 1613 m, 1586 w, 1515 s, 1461 m,
-
1 1
1
415 w, 1362 w, 1302 w, 1248 s, 1173 w, 1097 s, 1042 m, 1005 m, 911 w, 833 w, 742 m cm ; H
NMR (400 MHz, CDCl ): δ 0.59 (q, J = 8.0 Hz, 6H), 0.95 (t, J = 8.0 Hz, 9H), 1.24-1.49 (m, 6H),
.56-1.63 (m, 2H), 2.20 (t, J = 6.0 Hz, 2H), 3.43 (t, J = 6.8 Hz, 2H), 3.68 (quin, J = 6.0 Hz, 1H),
.80 (s, 3H), 4.43 (s, 2H), 5.01 (s, 1H), 5.04 (d, J = 7.2 Hz, 1H), 5.75-5.86 (m, 1H), 6.88 (d, J =
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
9
3
1
3
.2 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H); C NMR (100 MHz, CDCl ): δ 5.0, 6.9, 25.2, 26.3, 29.8,
3
6.8, 42.0, 55.2, 70.1, 71.9, 72.5, 113.7, 116.6, 129.2, 130.8, 135.3, 159.1; HRMS (APCI-TOF)
+
m/z: [M+H] Calcd for C23
H
41
3
O Si 393.2825; Found 393.2817.
1
4
9
-Iodo-4-triethylsiloxy-1-nonene. The PMB-deprotection with DDQ and the conversion to
2
6
the alkyl iodide were carried out by procedures similar to those reported in literature. To a
solution of 9-(4-methoxyphenylmethoxy)-4-triethylsiloxy-1-nonene (7.06 g, 18.0 mmol) in 110
mL (10:1, v/v) of CH
mmol), and the reaction mixture was stirred at room temperature for 30 min. A saturated aqueous
solution of NaHCO was added to the mixture. Insoluble materials were filtered off, and the filtrate
was extracted with CH Cl . The organic layer was washed with brine, dried over Na SO , filtered,
and concentrated. Column chromatography of the crude material on silica gel (hexane:EtOAc =
:1, then again with benzene:EtOAc = 8:1 to 3:1) afforded 3.00 g of 6-triethylsiloxy-8-nonen-1-ol
11.0 mmol, 61% yield).
To a solution of 6-triethylsiloxy-8-nonen-1-ol (3.00 g, 11.0 mmol) in benzene (75 mL)
were added imidazole (1.36 g, 20.0 mmol), PPh (4.30 g, 16.4 mmol) and I (4.20 g, 16.5 mmol).
The reaction mixture was stirred at room temperature for 30 min. A saturated aqueous solution of
Na SO was added to the mixture, which was then diluted with ether. The organic layer was
2
Cl
2
/pH 7 buffer (NaH
2
PO
4
/Na
2
HPO
4
) at 0 ºC was added DDQ (5.00 g, 22.0
3
2
2
2
4
5
(
3
2
2
3
separated and washed with water and then with brine. The resulting solution was dried over
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