Allylic substitution for construction of a chiral quaternary carbon possessing an aryl group

Article abstract of DOI:10.1021/jo400248y

Phenylcopper reagents derived from 2:1 PhMgBr/Cu(acac)₂ and 3:1:1 PhMgBr/Cu(acac)₂/ZnI₂ were found to be highly reactive and regioselective in the allylic substitution of γ,γ- disubstituted secondary allylic picolinates designed for construction of a quaternary carbon, whereas the previous 2:1 ArMgBr/CuBr·Me₂S reagent and that with ZnX₂ were unsuccessful. The generality of the ArMgBr/Cu(acac)₂ reagent was examined with enantiomerically enriched allylic picolinates, which furnished quaternary carbons with high efficiency in >92% regioselectivity and >97% chirality transfer. Two cyclohexanes with a quaternary carbon were synthesized by using these reagents.

Full text of DOI:10.1021/jo400248y

Article
pubs.acs.org/joc
Allylic Substitution for Construction of a Chiral Quaternary Carbon
Possessing an Aryl Group
Chao Feng and Yuichi Kobayashi*
Department of Bioengineering, Tokyo Institute of Technology, B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan
S
* Supporting Information
ABSTRACT: Phenylcopper reagents derived from 2:1
PhMgBr/Cu(acac)2 and 3:1:1 PhMgBr/Cu(acac)2/ZnI2 were
found to be highly reactive and regioselective in the allylic
substitution of γ,γ-disubstituted secondary allylic picolinates
designed for construction of a quaternary carbon, whereas the
previous 2:1 ArMgBr/CuBr·Me2S reagent and that with ZnX2
were unsuccessful. The generality of the ArMgBr/Cu(acac)2
reagent was examined with enantiomerically enriched allylic
picolinates, which furnished quaternary carbons with high efficiency in >92% regioselectivity and >97% chirality transfer. Two
cyclohexanes with a quaternary carbon were synthesized by using these reagents.
Scheme 2. Previous and Present Results
INTRODUCTION
■
Exploration of a method for construction of a quaternary
carbon in an enantiomerically enriched form has been an active
area of investigation in connection with synthesis of biologically
important molecules.1 In the past decade, the two types of allylic
substitution shown in Scheme 1 have been studied actively for
Scheme 1. Two Types of Allylic Substitution for
Construction of a Quaternary Carbon
reagents as such are likely reasons for the low efficiency.
Recently, Pd/Ag-catalyzed substitution of allylic acetates with
PhB(OH)2 was applied to allylic acetates of type C (L = OAc),8
but stereochemical outcome and any reason for the moderate
yields were uncertain.9 Because of the importance of this subject
in organic synthesis,2,10 substitution of allylic picolinates was
reinvestigated to find highly efficient reagents derived from
ArMgBr and Cu(acac)2 as presented in this publication.
this purpose.2 Until now, the former substitution using primary
allylic substrates of type A has proceeded with alkyl as well as
alkenyl-, allenyl-, and alkynylcopper reagents, producing olefin B
with high efficiency in terms of enantio- and regioselectivity.3
Substitution with arylcopper reagents was also reported in one
case.3h On the other hand, a group of copper reagents that react
with secondary allylic esters of type C to produce D is limited to
the alkyl group.4 As for aryl reagents, the substitution shown in
Scheme 2 resulted in 82% regioselectivity using the picolinoxy
leaving group.5 However, the regioselectivity is somewhat lower
than that observed in the substitution of the allylic picolinates of
type 4.6,7 Similarly, application of other highly potent leaving
groups such as o-(PPh2)C6H4CO2 and o-(P(O)Ph2)C6H4CO2
originally developed for allylic substitution of type 5 suffers
from low regioselectivity.4b,d Low nucleophilicity of aryl reagents
and increased congestion around secondary substrates and aryl
RESULTS AND DISCUSSION
Preparation. Allylic picolinates shown in Figure 1 were used
for the present investigation (see Tables 1−4 and Scheme 4).
■
Received: February 3, 2013
Published: March 15, 2013
© 2013 American Chemical Society
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exhibited enantioenrichment (i.e., 60−82% ee) as measured by
chiral HPLC analysis, though preparation of similar alcohols
with high ee has been published.4c,e,12 The alcohols were then
converted to picolinates 9−12. The absolute configuration of
alcohol 24 was determined by comparison of the [α]D value with
that reported13 and was consistent with the sense of the CBS
reduction. The same configuration was assigned to the other
alcohols 25−27 by analogy.
Phenylation of Allylic Picolinate 6. Substitution of
picolinate 6 with Ph copper reagents was studied using
30−50 mg of 6 at various temperatures in THF or in other
solvents for 2 h (in most cases) and the product ratios are
presented in Table 1 and Table S1 (Supporting Information).
The procedure developed by us5 for picolinates 4 was examined
first with the reagent derived from PhMgBr and CuBr·Me2S in
a 2:1 ratio in THF to afford a mixture of the expected product
15, regioisomer 16, alcohol 17, and the starting picolinate 6
(entry 1).14 The calculated regioselectivity of 15 over 16 was
76%, which is similar to that obtained for picolinate 1 (82%).
1
No cis isomer was detected by H NMR spectroscopy of the
crude product. In entry 2, 50% more reagent was used at a
higher temperature (−18 °C) to complete the reaction, but
with low product selectivity. The ZnI2-promoted reaction,
developed for allylation of cyclic substrates such as 14,7 raised
the selectivity up to 78% (entry 3). Other ZnX2 (X = Br, Cl,
TsO, PhCO2) resulted in slightly or substantially lower
selectivity (Table S1, Supporting Information) than that in
entry 3. In Et2O, a mixture of 15−17 and diene 18 was pro-
duced, whereas reaction with ZnI2 in CH2Cl2-THF, the mixed
solvent for the allylic substitution with alkynyl copper
reagents,15 showed a moderate product selectivity (62% in
Table S1, Supporting Information). The PhLi-based reagent in
the presence or absence of ZnI2 produced 18 as the major
product (entries 4 and 5).
Figure 1. Substrates examined (Py = 2-pyridyl).
The picolinates 1 and 14 were prepared by the methods
published previously,5,7 while other picolinates 6−8 and 9−13
were synthesized by methods delineated in Scheme 3. Briefly,
Grignard addition to aldehyde 19 produced racemic alcohol 17,
which upon DCC-mediated condensation with PyCO2H
afforded picolinate 6 in 74% yield. Similarly, aldehydes 20
and 22, prepared from geraniol and nerol by oxidation, were
converted to 7 and 8, respectively. For preparation of optically
active picolinates 9−12, Corey−Bakshi−Shibata reduction (CBS
reduction) of the corresponding ketones with (S)-MeCBS11 was
used for our convenience to afford alcohols 24−27, which
Recently, Cu(acac)2-based alkynyl reagents were found to
be highly regioselective in the substitution of cyclic allylic
picolinates.16 By intuition, we envisaged high efficiency with
reagents derived from PhMgBr and Cu(acac)2. In fact, a Ph
reagent derived from PhMgBr and Cu(acac)2 in a 2:1 ratio at
Table 1. Preliminary Investigation of Allylic Substitution of Racemic 6 with Ph Copper Reagents
a
entry
Ph metal (equiv)
PhMgBr (2.0)
copper salt (equiv)
Ph/Cu
additive (equiv)
solvent
temp (°C)
product ratio (%) 15:16:17:18:6
1
CuBr·Me2S (1.0)
CuBr·Me2S (1.5)
CuBr·Me2S (1.5)
CuBr·Me2S (1.5)
CuBr·Me2S (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.5)
2:1
2:1
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
−60
−18
−18
−60
−60
−40
−40
−40
−40
−40
−40
−30
−20
0
53:17:16:0:14
54:45:1:0:0
78:13:3:6:0
0:20:16:64:0
0:14:27:58:0
2
PhMgBr (3.0)
3
PhMgBr (3.2)
2.1:1
2.1:1
2.1:1
2:1
ZnI2 (1.5)
ZnI2 (1.5)
ZnI2 (1.5)
4
PhLi (3.2), MgBr2 (4.0)
PhLi (3.2), MgBr2 (4.0)
PhMgBr (3.0)
5
b
6
>99:0:0:0:0
7
PhMgBr (3.0)
2:1
no reaction
44:41:15:0:0
8
PhMgBr (4.7)
3.1:1
3.1:1
3.1:1
3.1:1
2:1
b
9
PhMgBr (4.7)
ZnI2 (1.5)
ZnBr2 (1.5)
ZnCl2 (1.5)
98:2:0:0:0
b
10
11
12
13
14
PhMgBr (4.7)
97:3:0:0:0
PhMgBr (4.7)
95:5:1:0:0
99:1:0:0:0
95:3:2:0:0
85:13:2:0:0
PhMgBr (3.0)
PhMgBr (3.0)
2:1
PhMgBr (3.0)
2:1
a
Determined by 1H NMR integration ratios of the protons at δ 5.44 (dt, 1 H) and 5.64 (d, 1 H) for 15, 5.26 (d, 1 H) for 16, (5.15 (dm, 1 H) for 17,
b
6.15 (d, 1 H) and 4.87 (s, 2 H) for 18, and 5.80−5.89 (m, 1 H) for 6. Isolated yields of 15: 100% (entry 6), 87% (entry 9), and 90% (entry 10).
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a
phenylcopper reagents producing 15 in the reaction of
picolinate 6 was highly dependent on the copper source,
composition with PhMgBr, and addition of ZnX2. The results
obtained with the Cu(acac)2-based reagents are summarized in
Table 2. First, Cu(acac)2 was found to be a better source of the
Scheme 3. Synthesis of Picolinates 6−8 and 9−13
Table 2. Potential of the Reagents
entry of
result Table 1
Ph/
a
remaining
6 (%)
product selectivity of
b
Cu
ZnI2
15 (%)
1
2
3
4
6
7
8
9
2:1
2:1
3:1
3:1
0
100
0
>99
c
added
44
c
added
0
98
a
Quantity of Cu(acac)2 was 1.5 equiv per picolinate 6, and that of
PhMgBr was 3−3.1 and 4.5−4.7 equiv per 6 for the 2:1 and 3:1 Ph/Cu
b
c
ratios. Based on the products 15−18 and 6. 1.5 equiv per 6.
copper reagent than CuBr·Me2S (result 1). Second, ZnI2 was
found to raise the selectivity of the 3:1 PhMgBr/Cu(acac)2
reagent (result 4 vs result 3), whereas the reaction with the
2:1 reagent was totally prevented by ZnI2 (result 2). From a
practical point of view we recommend the 2:1 PhMgBr/
Cu(acac)2 reagent on the basis of the quantity of PhMgBr. The
procedure using the 2:1 PhMgBr/Cu(acac)2 reagent could
be scaled up to 3.1 g of 6 (10 mmol), which afforded 15 with
99% regioselectivity and 92% yield after purification by
chromatography.
Allylic Substitution with Arylcopper Reagents. The
reagent system used in entry 6 of Table 1 was applied to allylic
substitution summarized in Table 3. The reactions in all entries
Table 3. Allylic Substitution of Racemic 6−8 with ArMgBr/
a
Cu(acac)2
a
Reagents: TPAP, Pr4NRuO4; (S)-MeCBS, (S)-3,3-diphenyl-1-
methylpyrrolidino[1,2-c]-1,3,2-oxazaborole.
−40 °C for 2 h produced 15 exclusively in quantitative yield
(entry 6). This reagent was highly product selective (and thus
regioselective) even at −30 and −20 °C (entries 12 and 13) but
moderately selective at 0 °C (entry 14). In contrast, addition
of ZnI2 prevented the reaction at all (entry 7). Different from
the 2:1 PhMgBr/Cu(acac)2 reagent, a reagent derived from
PhMgBr and Cu(acac)2 in a 3:1 ratio showed almost no
regioselectivity (entry 8), whereas the selectivity was drastically
improved by addition of ZnX2 (X = I, Br, Cl), among which
ZnI2 provided the best selectivity (entries 9−11). In addition,
ZnI2 is less hygroscopic than the other ZnX2 and thus more
practical. An attempted reaction with a 1:1 PhMgBr/Cu(acac)2
reagent even at 0 °C resulted in recovery of picolinate 6 (data
not shown). We also examined reagents derived from
Cu(OAc)2 and Cu(OMe)2. As shown in Table S1 (Supporting
Information), a reagent derived from PhMgBr and Cu(OAc)2
in a 2:1 ratio produced diene 18 as the major product, while
that prepared from Cu(OMe)2 afforded 15 with somewhat low
selectivity of 88%.17 The attempted reaction with 10 mol % of
Cu(acac)2 afforded a mixture of 15/16/17 in a 20:56:24 ratio.
In summary of the preliminary investigation (Table 1 and
Table S1, Supporting Information), product selectivity of the
a
ArMgBr (3 equiv), Cu(acac)2 (1.5 equiv), THF, from −40 to −20 or
b
1
−10 °C, 2 h. Determined by H NMR integration ratios for the
olefinic protons.
completed within 2 h. However, regioselectivity and yields
varied slightly. Thus, the Me substituent at the para and ortho
positions furnished similar regioselectivity and yield (entries 1
and 2), whereas the MeO group at the ortho position slightly
lowered the selectivity and yield (entry 4 vs entries 1−3).
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a
Table 4. Substitution of Chiral Picolinates with Arylcopper Reagents
a
b
Reactions in entry 1 and entries 2−10 were carried out for 3 and 2 h, respectively, at −40 to −10 or to 0 °C. Enantiomeric excess (ee) was
c
d
1
determined by HPLC analysis using DAICEL chiral columns. Determined by H NMR integration ratios for the olefinic protons. CT (chirality
transfer) was calculated by (% ee of product) × 100/(% ee of substrate). Remaining 1 was detected by H NMR and TLC analysis.
e
1
The reaction with the p-FC6H4 reagent proceeded efficiently
as well (entry 5). Substitution of picolinates 7 and 8 was not
affected by the bulkiness of the alkyl groups on the reacting
carbon (γ position), and SN2′ product 34 was obtained se-
lectively (entries 6 and 7). A similar selectivity was observed in
entry 8 to produce 35.
Arylation of Enatiomerically Enriched Allylic Picoli-
nates. The above reagent system consisting of 2:1 ArMgBr/
Cu(acac)2 was applied to enantiomerically enriched picolinates
118 and 9−12 to determine chirality transfer (CT) of the allylic
substitution (Table 4). Substitution of 1 (98% ee) with the Ph
copper reagent for 3 h, however, afforded a mixture of 2 and the
starting picolinate 1 (entry 1 and footnote e), suggesting lower
reactivity of 1 than the substrates examined above. Fortunately,
full conversion was attained by doubling the quantity of the
reagent to produce 2 with 99% CT and >99% regioselectivity
in 86% yield (entry 2). The absolute configuration of 2 was
and regioselectivity in good yields.19 These results indicate
that these picolinates are more susceptible to the reaction
than 1.
Construction of a Quaternary Carbon on the Cyclo-
hexane Ring. The above protocol was applied to picolinates to
create a quaternary carbon on the cyclohexane ring
(Scheme 4). Reaction of 13 with the 2:1 PhMgBr/Cu(acac)2
and 3:1:1 PhMgBr/Cu(acac)2/ZnI2 reagents gave 43 with
82−87% regioselectivity over the regioisomer 44 in good yields.
The next substrate was 14, in which the α carbon is less
congested than that of the other substrates examined in Tables 1,
3, and 4, thus rendering the γ position less accessible than α.
Nevertheless, both of the reagents afforded the desired prod-
uct 45 with >81% regioselectivity over the regioisomer 46.
determined by the specific rotation [[α]25 +2.5 (c 0.16,
D
CHCl3) [lit.5 [α]30D +1.5 (c 0.40, CHCl3)]] and retention time
on chiral HPLC (Supporting Information), establishing anti
SN2′ pathway. On the other hand, the authentic regioisomer 3
was synthesized with 91% regioselectivity along with alcohol 42
(3/2/42 = 67:7:26) using the CuBr·Me2S-based copper reagent
(eq 1), which afforded a 45:55 mixture of 16 and 15 from
substrate 6 (Table 1, entry 2). The different regioselectivity be-
tween 1 and 6 implies that the γ position of 1 is more congested
than 6, rendering the position less accessible. Similarly,
substituted aryl reagents shown in entries 3−6 afforded 36−
39 with high CT in high yields. These results demonstrate high
potency of the ArMgBr/Cu(acac)2 reagents, which would not
be influenced by steric and electronic biases. Next, allylic sub-
stitution of picolinates 9−12 was examined (entries 7−10).
The reactions proceeded with the standard quantity of the
Ph reagent and afforded the anti SN2′ products with high CT
1
Furthermore, the H NMR spectrum of 45 indicates >99%
stereoselectivity, and the trans 1,4-diphenyl stereochemistry is
assigned on the basis of the previous results with alkylcopper
reagents.7
Mechanism. As mentioned in the phenylation of allylic
picolinate 6, no reaction took place with the 1:1 PhMgBr/
Cu(acac)2 reagent. This result is consistent with stoichiometric
consumption of PhMgBr for reduction of Cu(acac)2 to a Cu+
species,20 and thus, 2 and 3 equiv of PhMgBr per Cu(acac)2
should afford species of the formal “Ph−Cu” and “Ph2Cu−”
types, respectively. The former species is sufficiently reactive
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interferes the complexation to form 48b and/or the subsequent
step to afford 49b, thus resulting in not only a decrease in
reactivity but also competition to form 51b, which in turn
gives regioisomer 53b. In practice, however, [ArCu(acac)]−
with the acac ligand are highly reactive to produce 50b,
regioselectively, whereas [ArCuX]− (X = Ar, Br) are less
potent, resulting in low regioselectivity. The recovery of the
regioselectivity by the addition of ZnX2 probably reflects
stronger chelation of the leaving group to ZnX2 to form 48b
(M2+ = Zn2+) than that to MgBr2. However, the remaining
issues to be clarified are (1) a mechanism for [ArCu(acac)]−
to show high reactivity to form 48b/49b and (2) different
levels of the ZnI2-assisted recovery of the regioselectivity
between [Ar2Cu]− derived from CuBr·Me2S and that from
Cu(acac)2.
Scheme 4. Construction of a Quaternary Carbon on the
Cyclohexane Ring
CONCLUSION
■
In conclusion, we have developed the 2:1 ArMgBr/Cu(acac)2
and 3:1:1 ArMgBr/Cu(acac)2/ZnI2 reagents for construc-
tion of a quaternary carbon by allylic substitution, which
proceeds with high stereo-, regio-, and product-selectivity.
We found furthermore that the olefin geometry in allylic
picolinate does not affect CT and regioselectivity but dictates
chirality of the product. This fact would be synthetically
convenient for designing biologically important compounds,
which consist of a chiral quaternary carbon possessing an aryl
group.10b,e,f,22
toward picolinate 6 to produce 15 highly regioselectively
(>99%) (cf. the 1:1 PhMgBr/CuBr·Me2S reagent, however,
generated a 88:12 mixture of 15 and 16, data not shown). The
latter is also reactive but suffers from low regioselectivity. The
selectivity is highly improved by addition of ZnI2 without
substantial reduction of yield. On the other hand, allylic
substitution of the previous picolinates 4 with “Ar−Cu” and
“Ar2Cu−” species derived from CuBr·Me2S and ArMgBr in 1:1
or 1:2 ratios proceeds efficiently as published previously.5
To explain these results, a likely mechanism along the lines of
recent publications8,21 is proposed in Scheme 5, in which the
previous and present picolinates are depicted as 47a (R1 = H)
and 47b (R1 = alkyl), respectively. Electron withdrawal by the
pyridyl group and chelation of the picolinoxy group to M2+
(Mg2+ generated in situ) cooperatively facilitate complexa-
tion of [ArCuX]− to 47a to furnish the π-complex 48a, in
which the Ar group occupies the space opposite the leaving
group (PyCO2), eventually producing the anti SN2′ product
50a through (enyl)Cu species 49a. In contrast, R1 in 47b
EXPERIMENTAL SECTION
■
1
General Remarks. The H NMR (300 or 400 MHz) and 13C
NMR (75 or 100 MHz) spectra were measured in CDCl3 using SiMe4
(δ = 0 ppm) and the centerline of the triplet (δ = 77.1 ppm) as
internal standards, respectively. Signal patterns are indicated as
follows: br s, broad singlet; s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet. Coupling constants (J) are given in hertz (Hz). Chemical
shifts in the 13C NMR spectra accompany minus (for C and CH2) and
plus (for CH and CH3) signs of APT experiments. High-resolution mass
spectroscopy (HRMS) experiments were performed with a double-
focusing mass spectrometer with an ionization mode of positive FAB
or EI as indicated for each compound. The following solvents were
distilled beforehand: THF (from Na/benzophenone), Et2O (from Na/
benzophenone), and CH2Cl2 (from CaH2). After the reactions were
finished, the organic extracts were concentrated by using evaporators,
and the residues were purified by chromatography on silica gel
(spherical silica gel 60 N). Cu(acac)2 was purchased from a commercial
supplier and used without purification, whereas CuBr·Me2S was
prepared as described previously.6b Picolinates 1 (98% ee) and 14
Scheme 5. Plausible Mechanism
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were prepared according to the literature procedures published from our
laboratory.5,7
picolinate 7 (172.1 mg, 80%) as a colorless oil: IR (neat) 1738, 1713,
1245, 1132, 746, 700 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.54−1.82
(m, 3 H), 1.57 (s, 3 H), 1.63 (s, 3 H), 1.79 (d, J = 2 Hz, 3 H), 1.86−
1.98 (m, 1 H), 1.98−2.14 (m, 4 H), 2.66 (t, J = 7 Hz, 2 H), 5.05 (tm,
J = 7 Hz, 1 H), 5.28 (dd, J = 9, 1 Hz, 1 H), 5.86 (dt, J = 9, 6 Hz, 1 H),
7.13−7.20 (m, 3 H), 7.22−7.30 (m, 2 H), 7.44 (ddd, J = 7.5, 5, 1 Hz,
1 H), 7.81 (dt, J = 2, 7.5 Hz, 1 H), 8.10 (dt, J = 7.5, 1 Hz, 1 H),
8.76 (dm, J = 5 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 17.0 (+),
17.8 (+), 25.7 (+), 26.3 (−), 27.1 (−), 34.6 (−), 35.7 (−), 39.6 (−),
73.2 (+), 123.2 (+), 123.9 (+), 125.2 (+), 125.8 (+), 126.6 (+), 128.4
(+), 128.5 (+), 131.8 (−), 136.9 (+), 141.4 (−), 142.2 (−), 148.8 (−),
150.0 (+), 164.7 (−); HRMS (FAB) calcd for C25H31NO2Na
[(M + Na)+] 400.2252, found 400.2253.
Synthesis of Racemic Picolinates 6−8 and 13. 2-Methyl-7-
phenylhept-2-en-4-yl Picolinate (6). To an ice-cold solution of
3-methyl-2-butenal (19) (1.14 g, 13.6 mmol) in THF (60 mL) was
added Ph(CH2)3MgCl (26.5 mL, 0.77 M in THF, 20.4 mmol). The
solution was stirred at rt for 2 h, and saturated NH4Cl and EtOAc were
added with vigorous stirring. The organic layer was separated, and the
aqueous layer was extracted with EtOAc twice. The combined extracts
were dried over MgSO4, washed with brine, and concentrated to afford
a residue, which was purified by chromatography on silica gel with
hexane/EtOAc to furnish alcohol 17 (2.49 g, 90%) as a colorless oil:
IR (neat) 3361, 1453, 748, 699 cm−1; 1H NMR (400 MHz, CDCl3) δ
1.28−1.34 (m, 1 H), 1.42−1.54 (m, 1 H), 1.55−1.74 (m, 2 H), 1.67
(d, J = 1 Hz, 3 H), 1.72 (d, J = 1 Hz, 3 H), 2.63 (t, J = 7 Hz, 2 H), 4.35
(dt, J = 8, 6 Hz, 1 H), 5.15 (dm, J = 9 Hz, 1 H), 7.14−7.21 (m, 3 H),
7.25−7.31 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 18.3 (+), 25.9
(+), 27.4 (−), 36.0 (−), 37.4 (−), 68.6 (+), 125.8 (+), 128.2 (+),
128.4 (+), 128.5 (+), 135.4 (−), 142.5 (−); HRMS (EI) calcd for
C14H20O (M+) 204.1514, found 204.1516.
(Z)-6,10-Dimethyl-1-phenylundeca-5,9-dien-4-ol (23). According
to the oxidation of geraniol, a mixture of nerol (501.6 mg, 3.25 mmol),
TPAP (114.0 mg, 0.324 mmol), NMO (570.0 mg, 4.87 mmol), and
molecular sieves 4A (1.63 g) in CH2Cl2 (20 + 10 mL) was stirred at
1
rt for 1 h to furnish 22 (445.5 mg, 90%) as a colorless oil: H NMR
(400 MHz, CDCl3) δ 1.59 (s, 3 H), 1.68 (d, J = 1 Hz, 3 H), 1.98
(d, J = 1 Hz, 3 H), 2.24 (dt, J = 7, 7.5 Hz, 2 H), 2.59 (t, J = 7.5 Hz,
2 H), 5.10 (tm, J = 7 Hz, 1 H), 5.88 (d, J = 8 Hz, 1 H), 9.90 (d, J =
8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 17.8 (+), 25.1 (+), 25.7
(+), 27.1 (−), 32.7 (−), 122.4 (+), 128.8 (+), 133.8 (−), 163.9 (−), 190.9
(+). The 1H and 13C NMR spectra were consistent with those reported.24
According to the Grignard addition to aldehyde 19, aldehyde 22
(445.5 mg, 2.93 mmol) in THF (25 mL) was subjected to reaction
with Ph(CH2)3MgBr (5.10 mL, 0.80 M in THF, 4.08 mmol) at rt for
1 h to furnish alcohol 23 (737.7 mg, 93%) as a colorless oil: IR (neat)
3364, 1452, 748, 699 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.35 (br s,
1 H), 1.41−1.53 (m, 1 H), 1.55−1.77 (m, 3 H), 1.59 (s, 3 H), 1.68
(s, 3 H), 1.72 (d, J = 1 Hz, 3 H), 2.00−2.17 (m, 4 H), 2.63 (t, J =
7 Hz, 2 H), 4.33 (dt, J = 9, 6 Hz, 1 H), 5.06−5.14 (m, 1 H), 5.18 (d, J
= 9 Hz, 1 H), 7.13−7.20 (m, 3 H), 7.23−7.30 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ 17.7 (+), 23.37 (+), 23.39 (+), 25.7 (+), 26.6
(−), 27.5 (−), 32.4 (−), 36.0 (−), 37.2 (−), 68.0 (+), 124.0 (+), 125.8
(+), 128.3 (+), 128.5 (+), 129.1 (+), 132.5 (−), 138.9 (−), 142.5 (−);
HRMS (FAB) calcd for C19H28ONa [(M + Na)+] 295.2038, found
295.2066.
To an ice-cold suspension of picolinic acid (1.67 g, 13.6 mmol) in
CH2Cl2 (30 mL) were added DMAP (746 mg, 6.11 mmol) and DCC
(3.29 g, 15.9 mmol). The mixture was stirred at 0 °C for 30 min, and
a solution of alcohol 17 (2.49 g, 12.2 mmol) in CH2Cl2 (20 mL) was
added. The resulting mixture was stirred at 0 °C for 2 h, diluted with
Et2O, and filtered through a pad of Celite. The filtrate was
concentrated to give a residue, which was purified by chromatography
on silica gel with hexane/EtOAc to afford picolinate 6 (3.09 g, 82%) as
1
a colorless oil: IR (neat) 1737, 1713, 1245, 1133, 747, 701 cm−1; H
NMR (400 MHz, CDCl3) δ 1.63−1.78 (m, 3 H), 1.73 (d, J = 1 Hz,
3 H), 1.80 (d, J = 1 Hz, 3 H), 1.87−1.98 (m, 1 H), 2.65 (t, J = 7 Hz,
2 H), 5.29 (dm, J = 10 Hz, 1 H), 5.80−5.89 (m, 1 H), 7.14−7.20
(m, 3 H), 7.23−7.30 (m, 2 H), 7.44 (ddd, J = 8, 5, 1 Hz, 1 H),
7.81 (dt, J = 8, 2 Hz, 1 H), 8.10 (dt, J = 8, 1 Hz, 1 H), 8.77 (ddd, J = 5,
2, 1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 18.7 (+), 25.9 (+), 27.2
(−), 34.6 (−), 35.7 (−), 73.3 (+), 123.4 (+), 125.2 (+), 125.8 (+),
126.7 (+), 128.4 (+), 128.5 (+), 136.9 (+), 138.2 (−), 142.2 (−),
148.7 (−), 150.0 (+), 164.7 (−); HRMS (EI) calcd for C20H23NO2
(M+) 309.1729, found 309.1730.
(Z)-6,10-Dimethyl-1-phenylundeca-5,9-dien-4-yl Picolinate (8).
According to the preparation of picolinate 6, alcohol 23 (294.1 mg,
1.08 mmol) was subjected to condensation with picolinic acid
(167.9 mg, 1.36 mmol), DMAP (101.1 mg, 0.828 mmol), and DCC
(297.5 mg, 1.44 mmol) in CH2Cl2 (8 + 2 mL) at rt for 2 h to produce
picolinate 8 (369.3 mg, 91%) as a colorless oil: IR (neat) 1738, 1713,
(E)-6,10-Dimethyl-1-phenylundeca-5,9-dien-4-ol (21). To a sus-
pension of molecular sieves 4A (1.65 g), TPAP (116.0 mg, 0.330 mmol),
and NMO (590.0 mg, 5.04 mmol) in CH2Cl2 (20 mL) was added
a solution of geraniol (501.6 mg, 3.25 mmol) in CH2Cl2 (10 mL). The
mixture was stirred at rt for 1 h and filtered through a pad of Celite. The
filtrate was concentrated to afford a residual oil, which was purified by
chromatography on silica gel (hexane/EtOAc) to furnish 20 (433.9 mg,
1
1245, 1132, 747, 700 cm−1; H NMR (400 MHz, CDCl3) δ 1.58
1
(s, 3 H), 1.62 (s, 3 H), 1.74 (d, J = 1.5 Hz, 3 H), 1.64−1.80 (m, 3 H),
1.86−1.98 (m, 1 H), 2.00−2.20 (m, 3 H), 2.28−2.38 (m, 1 H), 2.65
(t, J = 7 Hz, 2 H), 5.11 (tm, J = 7 Hz, 1 H), 5.31 (dd, J = 10, 1 Hz,
1 H), 5.89 (dt, J = 10, 7 Hz, 1 H), 7.12−7.20 (m, 3 H), 7.22−7.29
(m, 2 H), 7.43 (ddd, J = 8, 5, 1 Hz, 1 H), 7.80 (dt, J = 2, 8 Hz, 1 H),
8.10 (dt, J = 8, 1 Hz, 1 H), 8.76 (ddd, J = 5, 2, 1 Hz, 1 H); 13C NMR
(100 MHz, CDCl3) δ 17.7 (+), 23.4 (+), 25.7 (+), 26.7 (−), 27.3 (−),
32.7 (−), 34.8 (−), 35.8 (−), 72.8 (+), 123.9 (+), 124.0 (+), 125.2
(+), 125.8 (+), 126.6 (+), 128.4 (+), 128.5 (+), 132.0 (−), 136.9 (+),
141.7 (−), 142.1 (−), 148.8 (−), 149.9 (+), 164.6 (−); HRMS (FAB)
calcd for C25H32NO2 [(M + H)+] 378.2433, found 378.2441.
88%) as a colorless oil: H NMR (400 MHz, CDCl3) δ 1.61 (s, 3 H),
1.69 (s, 3 H), 2.15−2.28 (m, 4 H), 2.17 (s, 3 H), 5.04−5.12 (m, 1 H),
5.88 (d, J = 8 Hz, 1 H), 10.00 (d, J = 8 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 17.7 (+), 17.8 (+), 25.7 (+), 25.8 (−), 40.7 (−), 122.7 (+),
1
127.5 (+), 133.0 (−), 163.9 (−), 191.4 (+). The H and 13C NMR
spectra were consistent with those reported.23
According to the Grignard addition to aldehyde 19, aldehyde 20
(433.9 mg, 2.85 mmol) in THF (25 mL) was subjected to reaction with
Ph(CH2)3MgBr (5.00 mL, 0.80 M in THF, 4.00 mmol) at rt for
1 h to produce alcohol 21 (723.7 mg, 93%) as a colorless oil: IR (neat)
3377, 1453, 748, 699 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.36 (br s,
1 H), 1.42−1.54 (m, 1 H), 1.57−1.74 (m, 3 H), 1.59 (s, 3 H), 1.67
(s, 6 H), 2.01 (t, J = 7.5 Hz, 2 H), 2.05−2.14 (m, 2 H), 2.63 (t, J = 7 Hz,
2 H), 4.37 (dt, J = 9, 6 Hz, 1 H), 5.07 (t, J = 7 Hz, 1 H), 5.16 (d, J =
9 Hz, 1 H), 7.14−7.20 (m, 3 H), 7.23−7.30 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ 16.7 (+), 17.8 (+), 25.7 (+), 26.4 (−), 27.3 (−),
36.0 (−), 37.3 (−), 39.6 (−), 68.5 (+), 124.0 (+), 125.8 (+), 128.0 (+),
128.3 (+), 128.5 (+), 131.8 (−), 138.7 (−), 142.5 (−); HRMS (FAB)
calcd for C19H28ONa [(M + Na)+] 295.2038, found 295.2036.
(E)-6,10-Dimethyl-1-phenylundeca-5,9-dien-4-yl Picolinate (7).
According to the preparation of picolinate 6, alcohol 21 (155.8 mg,
0.572 mmol) was subjected to condensation with picolinic acid
(95.9 mg, 0.779 mmol), DMAP (69.6 mg, 0.570 mmol), and DCC
(156.0 mg, 0.756 mmol) in CH2Cl2 (3 + 2 mL) at rt for 2 h to afford
3-Ethylcyclohex-2-enyl Picolinate (13). According to the prepara-
tion of picolinate 6, alcohol 2825 (208.1 mg, 1.65 mmol) was subjected
to condensation with picolinic acid (245.0 mg, 1.99 mmol), DMAP
(202.1 mg, 1.65 mmol), and DCC (450.0 mg, 2.18 mmol) in CH2Cl2
(14 + 2 mL) to give picolinate 13 (318.4 mg, 83%) as a colorless oil:
1
IR (neat) 1736, 1713, 1245, 1133, 911, 748, 709 cm−1; H NMR
(400 MHz, CDCl3) δ 1.03 (t, J = 7.5 Hz, 3 H), 1.65−1.76 (m, 1 H),
1.81−2.11 (m, 7 H), 5.57−5.66 (m, 2 H), 7.45 (dm, J = 7.5 Hz, 1 H),
7.83 (dt, J = 1.5, 7.5 Hz, 1 H), 8.13 (d, J = 7.5 Hz, 1 H), 8.78 (dm, J =
5 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 11.9 (+), 19.5 (−), 28.4
(−), 28.5 (−), 30.4 (−), 70.9 (+), 118.1 (+), 125.2 (+), 126.7 (+),
136.9 (+), 146.7 (−), 148.9 (−), 150.0 (+), 165.1 (−); HRMS (FAB)
calcd for C14H18NO2 (M)+ 232.1338, found 232.1343.
3760
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The Journal of Organic Chemistry
Article
Synthesis of Optically Active Picolinates 9−12. (E)-4,8-
Dimethylnona-3,7-dien-2-one. According to the Grignard addition
to aldehyde 19, aldehyde 20 (466.5 mg, 3.06 mmol) in THF (30 mL)
was subjected to reaction with MeMgBr (4.60 mL, 0.99 M in THF,
4.55 mmol) at rt for 1 h to furnish racemic alcohol rac-24 (467.1 mg,
91%) as a colorless oil.
(R,E)-5,9-Dimethyldeca-4,8-dien-3-ol (25). According to the CBS
reduction to afford alcohol 24, a solution of the above ketone
(77.6 mg, 0.426 mmol) in THF (2 mL) was added to a solution of
(S)-methyloxazaborolidine (0.090 mL, 1.0 M in toluene, 0.090 mmol)
and N,N-diethylaniline borane (0.080 mL, 0.450 mmol) in THF
(4 mL) at −40 °C over 60 min, and the solution was allowed to warm
to −20 °C over 3 h. Cold MeOH (3 mL) was added at −20 °C, and
the solution was stirred at rt for 1 h to furnish alcohol 25 (26.8 mg,
According to the oxidation of geraniol, a mixture of rac-24 (228.2 mg,
1.36 mmol), TPAP (47.2 mg, 0.134 mmol), NMO (318.0 mg,
2.71 mmol), and molecular sieves 4A (677.0 mg) in CH2Cl2 (12 +
2 mL) was stirred at rt for 2 h to furnish the title ketone (188.1 mg,
1
34%) as a colorless oil: IR (neat) 3369, 1454, 1378 cm−1; H NMR
(400 MHz, CDCl3) δ 0.88 (t, J = 8 Hz, 3 H), 1.38−1.54 (m, 2 H),
1.60 (s, 3 H), 1.680 (s, 3 H), 1.683, (s, 3 H), 2.02 (t, J = 8 Hz, 2 H),
2.06−2.16 (m, 2 H), 4.28 (dt, J = 8.5, 7 Hz, 1 H), 5.09 (tm, J = 7 Hz,
1 H), 5.16 (dd, J = 8.5, 1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ
9.8 (+), 16.7 (+), 17.7 (+), 25.7 (+), 26.5 (−), 30.6 (−), 39.7 (−),
70.1 (+), 124.0 (+), 127.9 (+), 131.7 (−), 138.7 (−); HRMS (EI)
1
83%) as a colorless oil: H NMR (400 MHz, CDCl3) δ 1.61 (s, 3 H),
1.69 (s, 3 H), 2.10−2.20 (m, 4 H), 2.13 (d, J = 1 Hz, 3 H), 2.17
(s, 3 H), 5.02−5.12 (m, 1 H), 6.06 (s, 1 H); 13C NMR (100 MHz,
CDCl3) δ 17.7 (+), 19.3 (+), 25.7 (+), 26.2 (−), 31.8 (+), 41.2 (−),
123.1 (+), 123.7 (+), 132.6 (−), 158.3 (−), 198.9 (−). The 1H and 13
C
NMR spectra were identical with those reported.26
1
calcd for C12H22O (M+) 182.1671, found 182.1671. The H and 13C
NMR spectra were identical with those reported.27 The enantio-
meric purity of 60% ee was determined by chiral HPLC analysis:
Chiralcel OD-H, hexane/i-PrOH = 99.8/0.2, 0.700 mL/min, 30 °C,
tR/min =18.8 (R-isomer), 19.6 (S-isomer).
(R,E)-4,8-Dimethylnona-3,7-dien-2-ol (24). To a solution of
(S)-methyl oxazaborolidine (0.030 mL, 1.0 M in toluene, 0.030 mmol)
and N,N-diethylaniline borane (0.036 mL, 0.202 mmol) in THF (1 mL)
at −20 °C was added a solution of the above ketone (30.2 mg,
0.182 mmol) in THF (2 mL) over 5 h. After the addition, the solution
was stirred at −20 °C for further 3 h. Cold MeOH (3 mL) was added
slowly to the solution at −20 °C, and the cooling bath was removed. The
solution was stirred at rt for 1 h and concentrated to afford a residue,
which was purified by chromatography on silica gel (hexane/EtOAc) to
furnish 24 (29.7 mg, 97%) as a colorless oil: [α]24D +23 (c 0.60, CHCl3)
(R,E)-5,9-Dimethyldeca-4,8-dien-3-yl Picolinate (10). According to
the preparation of picolinate 6, alcohol 25 (26.8 mg, 0.147 mmol) was
subjected to condensation with picolinic acid (24.2 mg, 0.197 mmol),
DCC (40.0 mg, 0.194 mmol), and DMAP (17.8 mg, 0.146 mmol) in
CH2Cl2 (1 + 1 mL) at rt for 2 h to give picolinate 10 (36.6 mg, 87%)
as a colorless oil: [α]26 −11 (c 0.31, CHCl3): IR (neat) 1714, 1438,
D
(cf. [α]20 +21.6 (c 0.3, CHCl3) for the R enantiomer of 98% ee);13
1245, 1134, 747, 708 cm−1; 1H NMR (400 MHz, CDCl3) δ 0.94 (t, J =
7 Hz, 3 H), 1.58 (s, 3 H), 1.65 (s, 3 H), 1.66−1.78 (m, 1 H), 1.80
(d, J = 1 Hz, 3 H), 1.84−1.96 (m, 1 H), 2.00−2.16 (m, 4 H), 5.07 (tm,
J = 7 Hz, 1 H), 5.29 (dm, J = 7 Hz, 1 H), 5.76 (dt, J = 9, 7 Hz, 1 H),
7.44 (ddd, J = 7.5, 5, 1 Hz, 1 H), 7.82 (dt, J = 2, 7.5 Hz, 1 H), 8.12
(dt, J = 7.5, 1 Hz, 1 H), 8.77 (ddd, J = 5, 2, 1 Hz, 1 H); 13C NMR
(100 MHz, CDCl3) δ 9.6 (+), 17.0 (+), 17.7 (+), 25.6 (+), 26.3 (−),
28.0 (−), 39.6 (−), 74.6 (+), 123.1 (+), 123.9 (+), 125.1 (+), 126.5
(+), 131.7 (−), 136.8 (+), 141.3 (−), 148.8 (−), 149.9 (+), 164.7 (−);
HRMS (EI) calcd for C18H25NO2 (M+) 287.1885, found 287.1887.
(Z)-4,8-Dimethylnona-3,7-dien-2-one. According to the Grignard
addition to aldehyde 19, aldehyde 22 (520.0 mg, 3.42 mmol) in THF
(25 mL) was subjected to reaction with MeMgBr (5.18 mL, 0.99 M in
THF, 5.13 mmol) at rt for 2 h to produce racemic alcohol rac-26
(492.0 mg, 86%) as a colorless oil.
D
1H NMR (400 MHz, CDCl3) δ 1.23 (d, J = 6 Hz, 3 H), 1.43 (br s, 1 H),
1.60 (s, 3 H), 1.679 (s, 3 H), 1.682, (s, 3 H), 1.99 (t, J = 7 Hz, 2 H),
2.05−2.14 (m, 2 H), 4.57 (dq, J = 8, 6 Hz, 1 H), 5.08 (tm, J = 7 Hz,
1 H), 5.21 (dm, J = 8, 1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 16.5
(+), 17.7 (+), 23.7 (+), 25.7 (+), 26.5 (−), 39.5 (−), 64.8 (+), 124.0 (+),
129.2 (+), 131.7 (−), 137.6 (−); HRMS (EI) calcd for C11H20O
1
(M+) 168.1514, found 168.1514. The H and 13C NMR spectra were
identical with those reported.26 The enantiomeric purity of 82% ee
was determined by chiral HPLC analysis: Chiralcel OD-H, hexane/
i-PrOH = 99.5/0.5, 0.700 mL/min, 30 °C, tR/min =19.7 (R-isomer), 20.7
(S-isomer).
(R,E)-4,8-Dimethylnona-3,7-dien-2-yl Picolinate (9). According to
the preparation of picolinate 6, alcohol 24 (29.7 mg, 0.176 mmol) was
subjected to condensation with picolinic acid (31.2 mg, 0.253 mmol),
DMAP (21.7 mg, 0.178 mmol), and DCC (47.7 mg, 0.231 mmol) in
CH2Cl2 (1 + 1 mL) at rt for 2 h to afford 9 (42.4 mg, 88%) as a
colorless oil: [α]23D −17 (c 0.26, CHCl3); IR (neat) 1738, 1715, 1132,
According to the oxidation of geraniol, a mixture of rac-26 (267.5 mg,
1.59 mmol), TPAP (53.4 mg, 0.152 mmol), NMO (381.0 mg,
3.25 mmol), and molecular sieves 4A (800.1 mg) in CH2Cl2 (12 +
3 mL) was stirred at rt for 3 h to produce the title ketone (204.8 mg,
1
747, 708 cm−1; H NMR (400 MHz, CDCl3) δ 1.46 (d, J = 6 Hz, 3
H), 1.59 (s, 3 H), 1.65 (s, 3 H), 1.78 (d, J = 1 Hz, 3 H), 1.99−2.05
(m, 2 H), 2.06−2.15 (m, 2 H), 5.07 (tm, J = 7 Hz, 1 H), 5.37 (dq, J =
9, 1 Hz, 1 H), 5.95 (dq, J = 9, 6 Hz, 1 H), 7.44 (ddd, J = 8, 4.5, 1 Hz,
1 H), 7.82 (dt, J = 2, 8 Hz, 1 H), 8.12 (dt, J = 8, 1 Hz, 1 H), 8.77 (ddd,
J = 5, 2, 1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 16.8 (+), 17.7
(+), 21.0 (+), 25.7 (+), 26.3 (−), 39.5 (−), 70.0 (+), 123.9 (+), 124.4
(+), 125.1 (+), 126.6 (+), 131.7 (−), 136.9 (+), 140.2 (−), 148.8 (−),
149.9 (+), 164.7 (−); HRMS (EI) calcd for C17H23NO2 (M+)
273.1729, found 273.1733.
(E)-5,9-Dimethyldeca-4,8-dien-3-one. According to the Grignard
addition to aldehyde 19, aldehyde 20 (410.9 mg, 2.70 mmol) in THF
(25 mL) was subjected to reaction with EtMgBr (4.80 mL, 0.80 M
in THF, 3.84 mmol) at rt for 1 h to furnish racemic alcohol rac-25
(463.0 mg, 94%) as a colorless oil.
1
77%) as a colorless oil: H NMR (400 MHz, CDCl3) δ 1.63 (s, 3 H),
1.68 (s, 3 H), 1.87 (d, J = 1 Hz, 3 H), 2.09−2.19 (m, 2 H), 2.15
(s, 3 H), 2.58 (t, J = 7.5 Hz, 2 H), 5.14 (tm, J = 7.5 Hz, 1 H), 6.06 (s,
1 H); 13C NMR (100 MHz, CDCl3) δ 17.6 (+), 25.6 (+), 25.7 (+), 26.8
(−), 31.7 (+), 33.8 (−), 123.8 (+), 124.3 (+), 132.2 (−), 158.9 (−),
1
198.2 (−). The H and 13C NMR spectra were identical with those
reported.26
(R,Z)-4,8-Dimethylnona-3,7-dien-2-ol (26). According to the
CBS reduction to afford alcohol 24, a solution of the above ketone
(109.2 mg, 0.657 mmol) in THF (4 mL) was mixed with a solution of
(S)-methyl oxazaborolidine (0.13 mL, 1.0 M in toluene, 0.13 mmol) and
N,N-diethylaniline borane (0.13 mL, 0.731 mmol) in THF (5 mL) at
−20 °C over 4 h, and the solution was stirred at −20 °C for 3 h. Cold
MeOH (3 mL) was added dropwise at −20 °C, and the solution was
stirred at rt for 1 h to furnish alcohol 26 (82.5 mg, 75%) as a colorless
According to the oxidation of geraniol, a mixture of alcohol rac-25
(212.1 mg, 1.16 mmol), TPAP (41.0 mg, 0.117 mmol), NMO (260.0 mg,
2.22 mmol), and molecular sieves 4A (598.4 mg) in CH2Cl2 (10 + 2 mL)
was stirred at rt for 2 h to produce the title ketone (176.8 mg, 84%) as a
oil: [α]20 +14 (c 0.80, CHCl3); IR (neat) 3340 cm−1; 1H NMR
D
(400 MHz, CDCl3) δ 1.22 (d, J = 6 Hz, 3 H), 1.46 (br s, 1 H), 1.61 (s,
3 H), 1.70 (s, 3 H), 1.72 (d, J = 1 Hz, 3 H), 2.02−2.16 (m, 4 H), 4.53
(dq, J = 9, 6 Hz, 1 H), 5.07−5.15 (m, 1 H), 5.23 (dd, J = 9, 1 Hz, 1 H);
13C NMR (100 MHz, CDCl3) δ 17.7 (+), 23.3 (+), 23.6 (+), 25.7 (+),
26.5 (−), 32.3 (−), 64.3 (+), 124.0 (+), 130.3 (+), 132.5 (−), 137.7
(−). The 1H and 13C NMR spectra were identical with those reported.26
The enantiomeric purity of 66% ee was determined by chiral HPLC
analysis of the corresponding picolinate as described below.
1
colorless oil: IR (neat) 1688, 1621, 1122 cm−1; H NMR (400 MHz,
CDCl3) δ 1.07 (t, J = 7 Hz, 3 H), 1.61 (s, 3 H), 1.69 (s, 3 H), 2.10−2.22
(m, 4 H), 2.14 (s, 3 H), 2.44 (q, J = 7 Hz, 2 H), 5.02−5.12 (m, 1 H),
6.05 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 8.2 (+), 17.7 (+), 19.4 (+),
25.7 (+), 26.2 (−), 37.5 (−), 41.3 (−), 123.0 (+), 123.1 (+), 132.5 (−),
157.9 (−), 201.8 (−); HRMS (EI) calcd for C12H20O (M+) 180.1514,
found 180.1510.
3761
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The Journal of Organic Chemistry
Article
(R,Z)-4,8-Dimethylnona-3,7-dien-2-yl Picolinate (11). According
to the preparation of picolinate 6, alcohol 26 (82.5 mg, 0.490 mmol) was
subjected to condensation with picolinic acid (82.5 mg, 0.670 mmol),
DCC (131.6 mg, 0.638 mmol), and DMAP (56.2 mg, 0.460 mmol) in
CH2Cl2 (2 + 1 mL) at rt for 2 h to afford 11 (114.5 mg, 85%) as a
HPLC analysis: Chiralcel OD-H, hexane/i-PrOH = 99/1, 0.500 mL/min,
30 °C, tR/min =28.1 (R-isomer), 30.5 (S-isomer).
Substitution of Allylic Picolinates. General Procedure for the
Allylation: Synthesis of (E)-(6-Methylhept-4-ene-1,6-diyl)dibenzene
(15). (Table 1, entry 6): To an ice-cold suspension of Cu(acac)2
(38.1 mg, 0.146 mmol) in THF (1 mL) was added a solution of
PhMgBr (0.36 mL, 0.81 M in THF, 0.292 mmol) slowly. The mixture
was stirred at 0 °C for 60 min and cooled to −40 °C before addition of
a solution of picolinate 6 (30.0 mg, 0.0970 mmol) in THF (1 mL).
The resulting mixture was allowed to warm to −20 °C over 2 h and
diluted with hexane and saturated NH4Cl with vigorous stirring. The
layers were separated and the aqueous layer was extracted with hexane
twice. The combined extracts were washed with brine, dried over
MgSO4, and concentrated to give a residue, which was purified by
chromatography on silica gel (hexane/EtOAc) to afford 15 (25.9 mg,
100%).
(Table 1, entry 7): To an ice-cold suspension of Cu(acac)2 (38.3 mg,
0.146 mmol) and ZnI2 (46.8 mg, 0.147 mmol) in THF (1 mL) was
added PhMgBr (0.56 mL, 0.81 M in THF, 0.454 mmol). After being
stirred at 0 °C for 1 h, the mixture was cooled to −40 °C and a solution
of picolinate 6 (29.7 mg, 0.0960 mmol) in THF (1 mL) was added.
The mixture was allowed to warm to −10 °C over 2 h to afford 15
(22.4 mg, 87%) after purification by chromatography.
(Large-scale reaction): A solution of picolinate 6 (3.10 g, 10.02 mmol)
in THF (15 mL) was added to a mixture of Cu(acac)2 (3.93 g,
15.01 mmol) in THF (15 mL) and PhMgBr (32.0 mL, 0.95 M in THF,
30.02 mmol), which had been stirred at 0 °C for 60 min and cooled
to −40 °C before the addition. The mixture was allowed to warm to
−10 °C over 2 h to afford 15 (2.44 g, 92%) after purification by
chromatography on silica gel.
Product 15: colorless oil; IR (neat) 1495, 1454, 975, 763, 746, 698
cm−1; 1H NMR (400 MHz, CDCl3) δ 1.38 (s, 6 H), 1.72 (quint, J = 7
Hz, 2 H), 2.09 (dt, J = 7, 7 Hz, 2 H), 2.62 (t, J = 8 Hz, 2 H), 5.44 (dt,
J = 16, 7 Hz, 1 H), 5.64 (d, J = 16 Hz, 1 H), 7.13−7.21 (m, 4 H),
7.22−7.32 (m, 4 H), 7.32−7.38 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ 29.0 (+), 31.5 (−), 32.2 (−), 35.5 (−), 40.4 (−), 125.70
(+), 125.73 (+), 126.1 (+), 126.2 (+), 128.1 (+), 128.3 (+), 128.5 (+),
140.6 (+), 142.7 (−), 149.4 (−); HRMS (EI) calcd for C20H24 (M+)
264.1878, found 264.1881.
colorless oil: [α]22 −76 (c 0.53, CHCl3); IR (neat) 1713, 1245, 1127,
D
747, 708 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.45 (d, J = 6 Hz, 3 H),
1.60 (s, 3 H), 1.65 (s, 3 H), 1.75 (d, J = 1 Hz, 3 H), 2.00−2.22 (m, 3 H),
2.28−2.39 (m, 1 H), 5.06−5.16 (m, 1 H), 5.39 (d, J = 9.5 Hz, 1 H), 5.95
(dq, J = 9.5, 6 Hz, 1 H), 7.44 (ddd, J = 8, 5, 1 Hz, 1 H), 7.82 (dt, J = 2, 8
Hz, 1 H), 8.12 (dt, J = 8, 1 Hz, 1 H), 8.76 (ddd, J = 5, 2, 1 Hz, 1 H); 13C
NMR (100 MHz, CDCl3) δ 17.6 (+), 21.2 (+), 23.3 (+), 25.7 (+), 26.6
(−), 32.5 (−), 69.6 (+), 123.8 (+), 125.1 (+), 125.2 (+), 126.6 (+), 132.0
(−), 136.8 (+), 140.5 (−), 148.8 (−), 149.9 (+), 164.6 (−); HRMS (EI)
calcd for C17H23NO2 (M+) 273.1729, found 273.1722. The enantiomeric
purity of 66% ee was determined by chiral HPLC analysis: Chiralcel
OD-H, hexane/i-PrOH = 99/1, 0.300 mL/min, 30 °C, tR/min = 46.4
(R-isomer), 53.7 (S-isomer).
(Z)-5,9-Dimethyldeca-4,8-dien-3-one. According to the Grignard
addition to aldehyde 19, aldehyde 22 (440.3 mg, 2.89 mmol) in THF
(25 mL) was subjected to an addition reaction with EtMgBr (5.10 mL,
0.80 M in THF, 4.08 mmol) at rt for 1 h to furnish racemic alcohol
rac-27 (459.8 mg, 87%) as a colorless oil.
According to the oxidation of geraniol, a mixture of rac-27 (206.3 mg,
1.13 mmol), TPAP (36.5 mg, 0.104 mmol), NMO (267.8 mg,
2.29 mmol), and molecular sieves 4A (570.2 mg) in CH2Cl2 (9 + 2 mL)
was stirred at rt for 3 h to give the title ketone (162.6 mg, 80%) as a
1
colorless oil: IR (neat) 1688, 1621, 1125 cm−1; H NMR (300 MHz,
CDCl3) δ 1.06 (t, J = 7 Hz, 3 H), 1.62 (s, 3 H), 1.67 (d, J = 1 Hz, 3 H),
1.87 (d, J = 1 Hz, 3 H), 2.07−2.20 (m, 2 H), 2.42 (q, J = 7 Hz, 2 H),
2.59 (t, J = 7.5 Hz, 2 H), 5.13 (tm, J = 7.5 Hz, 1 H), 6.03 (s, 1 H); 13C
NMR (100 MHz, CDCl3) δ 8.2 (+), 17.7 (+), 25.6 (+), 25.7 (+), 26.9
(−), 33.9 (−), 37.4 (−), 123.7 (+), 123.9 (+), 132.1 (−), 158.5 (−),
201.2 (−); HRMS (EI) calcd for C12H20O (M+) 180.1514, found
180.1519.
(R,Z)-5,9-Dimethyldeca-4,8-dien-3-ol (27). According to the CBS
reduction to afford alcohol 24, a solution of the above ketone
(96.3 mg, 0.534 mmol) in THF (3 mL) was added to a solution of
(S)-methyloxazaborolidine (0.11 mL, 1.0 M in toluene, 0.11 mmol)
and N,N-diethylaniline borane (0.11 mL, 0.619 mmol) in THF (5 mL)
at −20 °C over 2 h, and the solution was stirred at −20 °C for 6 h.
Cold MeOH (3 mL) was added at −20 °C, and the solution was
stirred at rt for 1 h to furnish alcohol 27 (83.9 mg, 88%) as a colorless
oil: [α]22D +3 (c 0.68, CHCl3); IR (neat) 3357, 1448, 1002, 959 cm−1;
1H NMR (300 MHz, CDCl3) δ 0.89 (t, J = 8 Hz, 3 H), 1.34−1.66
(m, 3 H), 1.61 (s, 3 H), 1.69 (s, 3 H), 1.73 (d, J = 1.5 Hz, 3 H), 2.00−
2.20 (m, 4 H), 4.23 (dt, J = 9, 7 Hz, 1 H), 5.06−5.14 (m, 1 H), 5.17
(d, J = 9 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 9.9 (+), 17.7 (+),
23.3 (+), 25.7 (+), 26.6 (−), 30.4 (−), 32.4 (−), 69.5 (+), 124.0 (+),
128.9 (+), 132.4 (−), 138.9 (−); HRMS (EI) calcd for C12H22O (M+)
182.1671, found 182.1672. The enantiomeric purity of 63% ee was
determined by chiral HPLC analysis of the corresponding picolinate as
described below.
(E)-1-Methyl-4-(2-methyl-7-phenylhept-3-en-2-yl)benzene (29).
(Table 3, entry 1): According to the general procedure, a solution
of 6 (30.0 mg, 0.0970 mmol) in THF (1 mL) was added to a mixture
of p-MeC6H4MgBr (0.34 mL, 0.86 M in THF, 0.292 mmol) and
Cu(acac)2 (38.0 mg, 0.146 mmol) in THF (1 mL) at −40 °C, and
the mixture was allowed to warm to −20 °C over 2 h to afford 29 (25.1
mg, 93%) as a colorless oil: IR (neat) 1512, 1454, 975, 817,
1
698 cm−1; H NMR (400 MHz, CDCl3) δ 1.36 (s, 6 H), 1.66−1.76
(m, 2 H), 2.04−2.12 (m, 2 H), 2.31 (s, 3 H), 2.62 (t, J = 8 Hz, 2 H), 5.43
(dt, J = 16, 7 Hz, 1 H), 5.62 (d, J = 16 Hz, 1 H), 7.06−7.13 (m, 2 H),
7.14−7.20 (m, 3 H), 7.21−7.30 (m, 4 H); 13C NMR (100 MHz, CDCl3)
δ 21.0 (+), 29.1 (+), 31.5 (−), 32.3 (−), 35.5 (−), 40.0 (−), 125.7 (+),
125.9 (+), 126.1 (+), 128.3 (+), 128.6 (+), 128.8 (+), 135.2 (−), 140.8
(+), 142.7 (−), 146.5 (−); HRMS (EI) calcd for C21H26 (M+) 278.2035,
found 278.2036.
(R,Z)-5,9-Dimethyldeca-4,8-dien-3-yl Picolinate (12). According to
the preparation of picolinate 6, alcohol 27 (83.9 mg, 0.460 mmol) was
subjected to condensation with picolinic acid (78.8 mg, 0.640 mmol),
DCC (139.1 mg, 0.674 mmol), and DMAP (64.8 mg, 0.530 mmol) in
CH2Cl2 (4 + 1 mL) at rt for 2 h to afford picolinate 12 (112.0 mg,
(E)-1-Methyl-2-(2-methyl-7-phenylhept-3-en-2-yl)benzene (30).
(Table 3, entry 2): According to the general procedure, a solution
of 6 (30.1 mg, 0.0973 mmol) in THF (1 mL) was added to a mixture
of o-MeC6H4MgBr (0.33 mL, 0.87 M in THF, 0.287 mmol) and
Cu(acac)2 (38.1 mg, 0.146 mmol) in THF (1 mL) at −40 °C, and the
mixture was allowed to warm to −20 °C over 2 h to afford 30
(26.0 mg, 96%) as a colorless oil: IR (neat) 1495, 1454, 975, 760, 728,
85%) as a colorless oil: [α]23 −64 (c 0.60, CHCl3); IR (neat) 1714,
D
1245, 1137, 747, 707 cm−1; 1H NMR (400 MHz, CDCl3) δ 0.96 (t, J =
7 Hz, 3 H), 1.61 (s, 3 H), 1.62−1.78 (m, 1 H), 1.65 (s, 3 H), 1.76
(d, J = 1.5 Hz, 3 H), 1.82−1.96 (m, 1 H), 2.00−2.20 (m, 3 H), 2.32−
2.42 (m, 1 H), 5.10−5.18 (m, 1 H), 5.32 (d, J = 10 Hz, 1 H), 5.79 (dt,
J = 10, 7 Hz, 1 H), 7.44 (ddd, J = 8, 5, 1 Hz, 1 H), 7.81 (dt, J = 2, 8 Hz,
1 H), 8.12 (dt, J = 8, 1 Hz, 1 H), 8.76 (ddd, J = 5, 2, 1 Hz, 1 H); 13C
NMR (100 MHz, CDCl3) δ 9.9 (+), 17.6 (+), 23.4 (+), 25.6 (+), 26.6
(−), 28.1 (−), 32.6 (−), 74.2 (+), 123.8 (+), 123.9 (+), 125.1 (+),
126.5 (+), 131.9 (−), 136.8 (+), 141.7 (−), 148.8 (−), 149.9 (+),
164.6 (−). HRMS (EI) calcd for C18H25NO2 (M+) 287.1885, found
287.1887. The enantiomeric purity of 63% ee was determined by chiral
1
698 cm−1; H NMR (400 MHz, CDCl3) δ 1.43 (s, 6 H), 1.63−1.73
(m, 2 H), 2.02−2.10 (m, 2 H), 2.39 (s, 3 H), 2.60 (t, J = 8 Hz, 2 H),
5.32 (dt, J = 16, 7 Hz, 1 H), 5.66 (d, J = 16 Hz, 1 H), 7.10−7.20 (m, 5
H), 7.24−7.30 (m, 3 H), 7.35−7.39 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ 22.7 (+), 29.4 (+), 31.4 (−), 32.3 (−), 35.6 (−), 41.1 (−),
125.67 (+), 125.73 (+), 126.1 (+), 126.2 (+), 126.3 (+), 128.3 (+),
128.5 (+), 132.4 (+), 137.1 (−), 140.5 (+), 142.7 (−), 146.4 (−);
HRMS (EI) calcd for C21H26 (M+) 278.2035, found 278.2037.
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(E)-1-Methoxy-4-(2-methyl-7-phenylhept-3-en-2-yl)benzene (31).
(Table 3, entry 3): According to the general procedure, a solution
of 6 (29.5 mg, 0.0953 mmol) in THF (1 mL) was added to a mixture
of p-MeOC6H4MgBr (0.32 mL, 0.93 M in THF, 0.298 mmol) and
Cu(acac)2 (37.8 mg, 0.144 mmol) in THF (1 mL) at −40 °C, and the
mixture was allowed to warm to −10 °C over 2 h to afford 31
(23.1 mg, 82%) as a colorless oil: IR (neat) 1511, 1250, 1181, 1037,
solution of 7 and 8 (3:2) (37.8 mg, 0.100 mmol) in THF (1 mL)
was added to a mixture of p-FC6H4MgBr (0.33 mL, 0.92 M in THF,
0.304 mmol) and Cu(acac)2 (39.4 mg, 0.151 mmol) in THF (1 mL) at
−40 °C, and the mixture was allowed to warm to −10 °C over 2 h to
afford 35 (28.2 mg, 80%) as a colorless oil: IR (neat) 1603, 1508,
1
1232, 834, 699 cm−1; H NMR (400 MHz, CDCl3) δ 1.34 (s, 3 H),
1.50 (s, 3 H), 1.65 (s, 3 H), 1.60−1.90 (m, 6 H), 2.10 (dt, J = 8, 8 Hz,
2 H), 2.62 (t, J = 8 Hz, 2 H), 5.03−5.10 (m, 1 H), 5.42 (dt, J = 16,
7 Hz, 1 H), 5.61 (dt, J = 16, 1 Hz, 1 H), 6.91−7.00 (m, 2 H), 7.14−
7.21 (m, 3 H), 7.22−7.31 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ
17.6 (+), 23.4 (−), 25.8 (+), 25.9 (+), 31.5 (−), 32.4 (−), 35.5 (−),
41.9 (−), 43.2 (−), 114.7 (d, J = 21 Hz) (+), 124.7 (+), 125.8 (+),
127.4 (+), 128.2 (d, J = 8 Hz) (+), 128.4 (+), 128.5 (+), 131.4 (−),
139.3 (+), 142.6 (−), 144.0 (d, J = 3 Hz) (−), 161.1 (d, J = 242 Hz)
(−); HRMS (FAB) calcd for C25H31F [(M)+] 350.2410, found
350.2410.
1
829, 699 cm−1; H NMR (400 MHz, CDCl3) δ 1.36 (s, 6 H), 1.66−
1.76 (m, 2 H), 2.04−2.12 (m, 2 H), 2.62 (t, J = 8 Hz, 2 H), 3.78
(s, 3 H), 5.41 (dt, J = 16, 7 Hz, 1 H), 5.62 (d, J = 16 Hz, 1 H), 6.83
(dm, J = 9 Hz, 2 H), 7.14−7.20 (m, 3 H), 7.22−7.30 (m, 4 H); 13C
NMR (100 MHz, CDCl3) δ 29.2 (+), 31.5 (−), 32.2 (−), 35.5 (−),
39.8 (−), 55.3 (+), 113.4 (+), 125.7 (+), 125.9 (+), 127.2 (+), 128.3
(+), 128.5 (+), 140.9 (+), 141.6 (−), 142.7 (−), 157.6 (−); HRMS
(EI) calcd for C21H26O (M+) 294.1984, found 294.1986.
(E)-1-Methoxy-2-(2-methyl-7-phenylhept-3-en-2-yl)benzene (32).
(Table 3, entry 4): According to the general procedure, a solution
of 6 (30.4 mg, 0.0983 mmol) in THF (1 mL) was added to a mixture
of o-MeOC6H4MgBr (0.33 mL, 0.89 M in THF, 0.294 mmol) and
Cu(acac)2 (38.0 mg, 0.145 mmol) in THF (1 mL) at −40 °C, and
the mixture was allowed to warm to −20 °C over 2 h to afford 32
(18.8 mg, 65%) as a colorless oil: IR (neat) 1490, 1455, 1241, 1031,
(R,E)-tert-Butyl((5-((4-methoxybenzyl)oxy)-4-methyl-4-phenyl-
pent-2-en-1-yl)oxy)dimethylsilane (2). (Table 4, entry 2): According
to the general procedure, a solution of 1 (98% ee, 30.5 mg, 0.0647
mmol) in THF (1 mL) was added to a mixture of PhMgBr (0.38 mL,
1.00 M in THF, 0.38 mmol) and Cu(acac)2 (50.1 mg, 0.191 mmol) in
THF (1 mL) at −40 °C, and the mixture was allowed to warm to 0 °C
750, 699 cm−1; H NMR (400 MHz, CDCl3) δ 1.44 (s, 6 H), 1.63−
over 2 h to afford 2 (23.6 mg, 86%) as a colorless oil: [α]25 +2.5
1
D
1.74 (m, 2 H), 2.02−2.11 (m, 2 H), 2.61 (t, J = 8 Hz, 2 H), 3.78
(s, 3 H), 5.32 (dt, J = 15.5, 7 Hz, 1 H), 5.78 (dt, J = 15.5, 2 Hz, 1 H),
6.83−6.92 (m, 2 H), 7.12−7.22 (m, 4 H), 7.22−7.30 (m, 3 H); 13C
NMR (100 MHz, CDCl3) δ 27.9 (+), 31.6 (−), 32.3 (−), 35.4 (−),
39.9 (−), 55.1 (+), 111.8 (+), 120.3 (+), 125.2 (+), 125.7 (+), 127.2
(+), 127.3 (+), 128.3 (+), 128.6 (+), 137.2 (−), 140.4 (+), 142.9 (−),
158.3 (−); HRMS (EI) calcd for C21H26O (M+) 294.1984, found
294.1983.
(c 0.16, CHCl3) (cf. [α]30D +1.5 (c 0.40, CHCl3) for the R enantiomer
of 98% ee);5 1H NMR (400 MHz, CDCl3) δ 0.06 (s, 6 H), 0.90
(s, 9 H), 1.43 (s, 3 H), 3.55 (d, J = 9 Hz, 1 H), 3.60 (d, J = 9 Hz, 1 H),
3.80 (s, 3 H), 4.20 (dd, J = 5, 1.5 Hz, 2 H), 4.42 (s, 2 H), 5.55 (dt, J =
16, 5 Hz, 1 H), 5.91 (dt, J = 16, 1.5 Hz, 1 H), 6.84 (d, J = 8 Hz, 2 H),
7.14−7.21 (m, 2 H), 7.24−7.35 (m, 4 H); 13C NMR (100 MHz,
CDCl3) δ −5.0 (+), 18.5 (−), 23.8 (+), 26.1 (+), 44.9 (−), 55.3 (+),
64.3 (−), 73.0 (−), 77.6 (−), 113.7 (+), 126.1 (+), 127.1 (+), 128.07
(+), 128.12 (+), 129.1 (+), 130.7 (−), 136.7 (+), 145.8 (−), 159.1
(−). The 1H NMR and 13C NMR spectra were consistent with
data reported in the literature.5 The enantiomeric purity of 97% ee
was determined by chiral HPLC analysis: Chiralcel OJ-H, hexane/
i-PrOH = 99/1, 0.300 mL/min, 30 °C, tR/min = 24.9 (S-isomer), 33.6
(R-isomer).
(E)-1-Fluoro-4-(2-methyl-7-phenylhept-3-en-2-yl)benzene (33).
(Table 3, entry 5): According to the general procedure, a solution
of 6 (29.8 mg, 0.0963 mmol) in THF (1 mL) was added to a mixture
of p-FC6H4MgBr (0.32 mL, 0.92 M in THF, 0.294 mmol) and
Cu(acac)2 (38.4 mg, 0.147 mmol) in THF (1 mL) at −40 °C, and the
mixture was allowed to warm to −10 °C over 2 h to afford 33
(22.8 mg, 84%) as a colorless oil: IR (neat) 1508, 1230, 1163, 976,
(E)-tert-Butyl((5-((4-methoxybenzyl)oxy)-4-methyl-2-phenylpent-
3-en-1-yl)oxy)dimethylsilane (Regioisomer 3). To an ice-cold
suspension of CuBr·Me2S (19.8 mg, 0.0963 mmol) in THF (1 mL)
was added a solution of PhMgBr (0.25 mL, 0.90 M in THF,
0.225 mmol) slowly. The mixture was stirred at 0 °C for 30 min, and a
solution of picolinate 1 (30.1 mg, 0.0638 mmol) in THF (1 mL) was
added. The mixture was stirred at 0 °C for 2 h and diluted with hexane
and saturated NH4Cl with vigorous stirring. The layers were separated,
and the aqueous layer was extracted with hexane twice. The combined
extracts were washed with brine, dried over MgSO4, and concentrated
to give a residue, which was purified by chromatography on silica
gel (hexane/EtOAc) to afford the regioisomer 3 and 2 in a 91:9 ratio
1
834, 699 cm−1; H NMR (400 MHz, CDCl3) δ 1.36 (s, 6 H), 1.66−
1.77 (m, 2 H), 2.03−2.13 (m, 2 H), 2.62 (t, J = 8 Hz, 2 H), 5.42 (dt,
J = 16, 7 Hz, 1 H), 5.60 (dt, J = 16, 1 Hz, 1 H), 6.91−7.00 (m, 2 H),
7.14−7.21 (m, 3 H), 7.23−7.32 (m, 4 H); 13C NMR (100 MHz,
CDCl3) δ 29.2 (+), 31.5 (−), 32.2 (−), 35.5 (−), 40.0 (−), 114.7 (d,
J = 21 Hz) (+), 125.8 (+), 126.4 (+), 127.7 (d, J = 8 Hz) (+), 128.4
(+), 128.5 (+), 140.4 (+), 142.6 (−), 145.1 (d, J = 3 Hz) (−), 161.1
(d, J = 242 Hz) (−); HRMS (EI) calcd for C20H23F (M+) 282.1784,
found 282.1792.
(E)-(6,10-Dimethylundeca-4,9-diene-1,6-diyl)dibenzene (34).
(Table 3, entry 6): According to the general procedure, a solution
of 7 (38.4 mg, 0.102 mmol) in THF (1 mL) was added to a mixture of
PhMgBr (0.31 mL, 1.02 M in THF, 0.316 mmol) and Cu(acac)2 (39.6 mg,
0.151 mmol) in THF (1 mL) at −40 °C, and the mixture was allowed to
warm to −10 °C over 2 h to afford 34 (32.1 mg, 95%).
(Table 3, entry 7): According to the general procedure, a solution
of 8 (37.1 mg, 0.0983 mmol) in THF (1 mL) was added to a mixture
of PhMgBr (0.29 mL, 1.02 M in THF, 0.296 mmol) and Cu(acac)2
(38.9 mg, 0.149 mmol) in THF (1 mL) at −40 °C, and the mixture
was allowed to warm to −10 °C over 2 h to afford 34 (28.9 mg, 88%).
Product 34: a colorless oil; IR (neat) 1495, 1453, 1445, 698 cm−1;
1H NMR (300 MHz, CDCl3) δ 1.36 (s, 3 H), 1.50 (s, 3 H), 1.65
(s, 3 H), 1.60−1.90 (m, 6 H), 2.10 (dt, J = 8, 8 Hz, 2 H), 2.62 (t, J =
8 Hz, 2 H), 5.02−5.12 (m, 1 H), 5.42 (dt, J = 16, 7 Hz, 1 H), 5.63 (dt,
J = 16, 1 Hz, 1 H), 7.10−7.20 (m, 4 H), 7.20−7.33 (m, 6 H); 13C
NMR (75 MHz, CDCl3) δ 17.8 (+), 23.6 (−), 25.8 (+), 25.9 (+), 31.6
(−), 32.5 (−), 35.6 (−), 41.8 (−), 43.6 (−), 124.8 (+), 125.56 (+),
125.64 (+), 126.6 (+), 127.1 (+), 128.0 (+), 128.2 (+), 128.4 (+),
131.2 (−), 139.3 (+), 142.5 (−), 148.2 (−); HRMS (FAB) calcd for
C25H32Na [(M + Na)+] 355.2402, found 355.2393.
1
(11.3 mg, 42%) as a colorless oil: H NMR (400 MHz, CDCl3) δ
−0.07 (s, 3 H), −0.06 (s, 3 H), 0.82 (s, 9 H), 1.69 (s, 3 H), 3.70−3.82
(m, 3 H), 3.80 (s, 3 H), 3.91 (s, 2 H), 4.37 (s, 2 H), 5.69 (d, J = 7 Hz,
1 H), 6.86 (d, J = 8.5 Hz, 2 H), 7.14−7.35 (m, 7 H); 13C NMR (100
MHz, CDCl3) δ −5.4 (+), 14.5 (+), 18.4 (−), 25.9 (+), 47.1 (+), 55.3
(+), 67.9 (−), 71.0 (−), 75.8 (−), 113.8 (+), 126.3 (+), 128.1 (+),
128.3 (+), 128.5 (+), 129.4 (+), 130.7 (−), 134.1 (−), 142.7 (−),
159.2 (−).
(R,E)-tert-Butyl((5-((4-methoxybenzyl)oxy)-4-methyl-4-(4-
methylphenyl)pent-2-en-1- yl)oxy)dimethylsilane (36). (Table 4,
entry 3): According to the general procedure, a solution of 1 (98% ee,
34.9 mg, 0.0740 mmol) in THF (1 mL) was added to a mixture of
p-MeC6H4MgBr (0.48 mL, 0.93 M in THF, 0.446 mmol) and
Cu(acac)2 (58.4 mg, 0.223 mmol) in THF (1 mL) at −40 °C, and the
mixture was allowed to warm to 0 °C over 2 h to afford 36 (30.2 mg,
93%) as a colorless oil: [α]22 +1.9 (c 0.16, CHCl3); IR (neat) 1513,
D
1
1249, 1098, 836 cm−1; H NMR (400 MHz, CDCl3) δ 0.06 (s, 6 H),
0.90 (s, 9 H), 1.41 (s, 3 H), 2.31 (s, 3 H), 3.52 (d, J = 9 Hz, 1 H), 3.58
(d, J = 9 Hz, 1 H), 3.80 (s, 3 H), 4.19 (dd, J = 5, 1 Hz, 2 H), 4.42
(s, 2 H), 5.54 (dt, J = 16, 5 Hz, 1 H), 5.90 (d, J = 16 Hz, 1 H), 6.84
(d, J = 8 Hz, 2 H), 7.06−7.12 (m, 2 H), 7.15−7.27 (m, 4 H); 13C NMR
(E)-1-(2,6-Dimethyl-11-phenylundeca-2,7-dien-6-yl)-4-fluoroben-
zene (35). (Table 3, entry 8): According to the general procedure, a
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(100 MHz, CDCl3) δ −5.0 (+), 18.5 (−), 21.0 (+), 23.8 (+), 26.1 (+),
44.6 (−), 55.3 (+), 64.4 (−), 73.0 (−), 77.7 (−), 113.7 (+), 126.9 (+),
128.0 (+), 128.8 (+), 129.1 (+), 130.8 (−), 135.6 (−), 136.9 (+),
142.8 (−), 159.1 (−); HRMS (FAB) calcd for C27H39O3Si [(M − H)+]
439.2668, found 439.2669. The enantiomeric purity of 97% ee was
determined by chiral HPLC analysis: Chiralcel OJ-H, hexane/
i-PrOH = 99.8/0.8, 0.300 mL/min, 30 °C, tR/min = 30.5 (S-isomer),
40.1 (R-isomer).
analysis: Chiralcel OJ-H, hexane/i-PrOH = 99/1, 0.300 mL/min, 30 °C,
tR/min = 26.7 (S-isomer), 33.6 (R-isomer).
(R,E)-(4,8-Dimethylnona-2,7-dien-4-yl)benzene (40). (Table 4,
entry 7): According to the general procedure, a solution of 9 (82%
ee, 31.5 mg, 0.115 mmol) in THF (1 mL) was added to a mixture
of PhMgBr (0.34 mL, 1.01 M in THF, 0.343 mmol) and Cu(acac)2
(45.0 mg, 0.172 mmol) in THF (1 mL) at −40 °C, and the mixture
was allowed to warm to −10 °C over 2 h to afford 40 (22.3 mg, 85%)
as a colorless oil: [α]24D +3 (c 0.75, CHCl3); IR (neat) 1445, 973, 762,
699 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.36 (s, 3 H), 1.51 (s, 3 H),
1.62−1.90 (m, 4 H), 1.65 (s, 3 H), 1.72 (dd, J = 6, 1.5 Hz, 3 H), 5.04−
5.12 (m, 1 H), 5.43 (dq, J = 16, 6 Hz, 1 H), 5.65 (dq, J = 16, 1.5 Hz,
1 H), 7.13−7.19 (m, 1 H), 7.24−7.34 (m, 4 H); 13C NMR (100 MHz,
CDCl3) δ 17.6 (+), 18.3 (+), 23.5 (−), 25.6 (+), 25.8 (+), 41.9 (−),
43.6 (−), 122.1 (+), 125.0 (+), 125.6 (+), 126.7 (+), 128.0 (+), 131.3
(−), 140.1 (+), 148.5 (−); HRMS (EI) calcd for C17H24 (M+)
228.1878, found 228.1873. The enantiomeric purity of 81% ee was
determined by chiral HPLC analysis: Chiralcel OJ-H, hexane/
i-PrOH = 99.8/0.2, 0.300 mL/min, 30 °C, tR/min =17.8 (S-isomer),
18.9 (R-isomer).
(R,E)-tert-Butyl((5-((4-methoxybenzyl)oxy)-4-methyl-4-(2-
methylphenyl)pent-2-en-1-yl)oxy)dimethylsilane (37). (Table 4,
entry 4): According to the general procedure, a solution of 1 (98%
ee, 34.8 mg, 0.0738 mmol) in THF (1 mL) was added to a mixture of
o-MeC6H4MgBr (0.52 mL, 0.85 M in THF, 0.442 mmol) and
Cu(acac)2 (58.2 mg, 0.222 mmol) in THF (1 mL) at −40 °C, and
the mixture was allowed to warm to −10 °C over 2 h to afford 37
(30.9 mg, 95%) as a colorless oil: [α]22 −7 (c 0.52, CHCl3); IR
D
(neat) 1613, 1513, 1463, 1250, 1097, 836 cm−1; 1H NMR (400 MHz,
CDCl3) δ 0.04 (s, 6 H), 0.90 (s, 9 H), 1.49 (s, 3 H), 2.31 (s, 3 H), 3.59
(d, J = 9 Hz, 1 H), 3.63 (d, J = 9 Hz, 1 H), 3.80 (s, 3 H), 4.14 (dd, J =
5, 1.5 Hz, 2 H), 4.45 (s, 2 H), 5.38 (dt, J = 16, 6 Hz, 1 H), 5.94 (dt, J =
16, 1.5 Hz, 1 H), 6.85 (dm, J = 9 Hz, 2 H), 7.06−7.16 (m, 3 H), 7.20
(dm, J = 9 Hz, 2 H), 7.34−7.40 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ −5.0 (+), 18.5 (−), 22.9 (+), 24.5 (+), 26.0 (+), 45.7 (−),
55.3 (+), 64.2 (−), 73.0 (−), 77.2 (−), 113.7 (+), 125.6 (+), 126.4
(+), 127.6 (+), 128.0 (+), 129.2 (+), 130.7 (−), 132.4 (+), 136.9 (+),
137.1 (−), 143.3 (−), 159.1 (−); HRMS (FAB) calcd for C27H39O3Si
[(M − H)+] 439.2668, found 439.2669. The enantiomeric purity of
98% ee was determined by chiral HPLC analysis: Chiralcel OJ-H,
hexane/i-PrOH = 99.5/0.5, 0.300 mL/min, 30 °C, tR/min = 35.4
(S-isomer), 40.0 (R-isomer).
(R,E)-(5,9-Dimethyldeca-3,8-dien-5-yl)benzene (41). (Table 4,
entry 8) According to the general procedure, a solution of 10 (60%
ee, 23.3 mg, 0.0811 mmol) in THF (1 mL) was added to a mixture
of PhMgBr (0.24 mL, 1.01 M in THF, 0.242 mmol) and Cu(acac)2
(31.6 mg, 0.121 mmol) in THF (1 mL) at −40 °C, and the mixture
was allowed to warm to −10 °C over 2 h to afford 41 (17.7 mg, 90%)
as a colorless oil: [α]24D +4 (c 0.22, CHCl3); IR (neat) 1445, 977, 763,
1
699 cm−1; H NMR (300 MHz, CDCl3) δ 1.00 (t, J = 7.5 Hz, 3 H),
1.35 (s, 3 H), 1.51 (s, 3 H), 1.62−1.92 (m, 4 H), 1.65 (s, 3 H), 2.02−
2.14 (m, 2 H), 5.02−5.12 (m, 1 H), 5.45 (dt, J = 16, 6 Hz, 1 H), 5.60
(dt, J = 16, 1 Hz, 1 H), 7.10−7.18 (m, 1 H), 7.22−7.34 (m, 4 H); 13C
NMR (100 MHz, CDCl3) δ 14.2 (+), 17.6 (+), 23.5 (−), 25.7 (+),
25.8 (+), 26.0 (−), 41.9 (−), 43.4 (−), 125.0 (+), 125.6 (+), 126.7
(+), 128.0 (+), 129.3 (+), 131.2 (−), 137.8 (+), 148.6 (−); HRMS
(EI) calcd for C18H26 (M+) 242.2035, found 242.2033. The enantio-
meric purity of 59% ee was determined by chiral HPLC analysis:
Chiralcel OJ-H, hexane/i-PrOH = 99.8/0.2, 0.300 mL/min, 30 °C,
tR/min = 21.3 (S-isomer), 22.6 (R-isomer).
(S,E)-(4,8-Dimethylnona-2,7-dien-4-yl)benzene (ent-40). (Table 4,
entry 9): According to the general procedure, a solution of 11
(66% ee, 29.5 mg, 0.108 mmol) in THF (1 mL) was added to a
mixture of PhMgBr (0.33 mL, 1.01 M in THF, 0.333 mmol) and
Cu(acac)2 (42.7 mg, 0.163 mmol) in THF (1 mL) at −40 °C, and the
mixture was allowed to warm to −10 °C over 2 h to afford ent-40
(21.6 mg, 88%) as a colorless oil: [α]23D −2 (c 0.76, CHCl3). The 1H
and 13C NMR spectra were identical with those for 40. The
enantiomeric purity of 66% ee was determined by chiral HPLC
analysis: Chiralcel OJ-H, hexane/i-PrOH = 99.8/0.2, 0.300 mL/min,
30 °C, tR/min = 19.3 (S-isomer), 20.8 (R-isomer).
(R,E)-tert-Butyl((5-((4-methoxybenzyl)oxy)-4-(4-methoxyphenyl)-
4-methylpent-2-en-1-yl)oxy)dimethylsilane (38). (Table 4, entry 5):
According to the general procedure, a solution of 1 (98% ee, 47.2 mg,
0.100 mmol) in THF (1 mL) was added to a mixture of p-MeOC6-
H4MgBr (0.64 mL, 0.93 M in THF, 0.595 mmol) and Cu(acac)2
(78.2 mg, 0.299 mmol) in THF (1 mL) at −40 °C, and the mixture
was allowed to warm to −10 °C over 2 h to afford 38 (43.1 mg, 94%)
as a colorless oil: [α]21 −1 (c 0.79, CHCl3); IR (neat) 1513, 1249,
D
834 cm−1; 1H NMR (400 MHz, CDCl3) δ 0.06 (s, 6 H), 0.90 (s, 9 H),
1.41 (s, 3 H), 3.51 (d, J = 9 Hz, 1 H), 3.56 (d, J = 9 Hz, 1 H), 3.79
(s, 3 H), 3.80 (s, 3 H), 4.19 (dd, J = 5, 2 Hz, 2 H), 4.42 (s, 2 H), 5.53
(dt, J = 16, 5 Hz, 1 H), 5.88 (dt, J = 16, 2 Hz, 1 H), 6.80−6.87 (m, 4
H), 7.15−7.21 (m, 2 H), 7.21−7.27 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ −5.0 (+), 18.5 (−), 23.9 (+), 26.1 (+), 44.3 (−), 55.3 (+),
64.3 (−), 73.0 (−), 77.7 (−), 113.4 (+), 113.7 (+), 127.9 (+), 128.1
(+), 129.1 (+), 130.8 (−), 137.0 (+), 137.9 (−), 157.9 (−), 159.1 (−);
HRMS (FAB) calcd for C27H40O4SiNa [(M + Na)+] 479.2594, found
479.2613. The enantiomeric purity of 97% ee was determined by chiral
HPLC analysis: Chiralcel OJ-H, hexane/i-PrOH = 99/1, 0.500 mL/min,
30 °C, tR/min = 35.6 (S-isomer), 46.3 (R-isomer).
(S,E)-(5,9-Dimethyldeca-3,8-dien-5-yl)benzene (ent-41). (Table 4,
entry 10): According to the general procedure, a solution of 12 (63%
ee, 29.9 mg, 0.104 mmol) in THF (1 mL) was added to a mixture
of PhMgBr (0.31 mL, 1.01 M in THF, 0.313 mmol) and Cu(acac)2
(41.2 mg, 0.157 mmol) in THF (1 mL) at −40 °C, and the mixture
(R,E)-tert-Butyl((4-(4-fluorophenyl)-5-((4-methoxybenzyl)oxy)-4-
methylpent-2-en-1-yl)oxy)dimethylsilane (39). (Table 4, entry 6):
According to the general procedure, a solution of 1 (98% ee, 48.4 mg,
0.103 mmol) in THF (1 mL) was added to a mixture of p-FC6H4MgBr
(0.65 mL, 0.92 M in THF, 0.598 mmol) and Cu(acac)2 (77.9 mg,
0.298 mmol) in THF (1 mL) at −40 °C, and the mixture was allowed
to warm to 0 °C over 2 h to afford 39 (45.6 mg, >99%) as a colorless
was allowed to warm to −10 °C over 2 h to afford ent-41 (20.7 mg,
1
82%) as a colorless oil: [α]23 −3 (c 0.27, CHCl3). The H and 13C
D
NMR spectra were identical with those for 41. The enantiomeric
purity of 62% ee was determined by chiral HPLC analysis: Chiralcel
OJ-H, hexane/i-PrOH = 99.8/0.2, 0.300 mL/min, 30 °C, tR/min =
29.4 (S-isomer), 31.2 (R-isomer).
oil: [α]21 −2.7 (c 0.33, CHCl3); IR (neat) 1510, 1249, 1097, 835,
D
777 cm−1; 1H NMR (400 MHz, CDCl3) δ 0.05 (s, 6 H), 0.90 (s, 9 H),
1.41 (s, 3 H), 3.52 (d, J = 9 Hz, 1 H), 3.55 (d, J = 9 Hz, 1 H), 3.80
(s, 3 H), 4.19 (dd, J = 5, 2 Hz, 2 H), 4.42 (s, 2 H), 5.53 (dt, J = 16, 5 Hz,
1 H), 5.88 (dt, J = 16, 2 Hz, 1 H), 6.84 (d, J = 8.5 Hz, 2 H), 6.91−7.00
(m, 2 H), 7.16 (d, J = 8.5 Hz, 2 H), 7.24−7.31 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ −5.0 (+), 18.5 (−), 24.0 (+), 26.1 (+), 44.5 (−),
55.3 (+), 64.2 (−), 73.0 (−), 77.5 (−), 113.7 (+), 114.7 (d, J = 21
Hz), 128.3 (+), 128.7 (d, J = 8 Hz), 129.1 (+), 130.5 (−), 136.4 (+),
141.4 (d, J = 3 Hz), 159.1 (−), 161.3 (d, J = 243 Hz); HRMS (FAB)
calcd for C26H36FO3Si [(M − H)+] 443.2418, found 443.2406. The
enantiomeric purity of >97% ee was determined by chiral HPLC
1-Ethyl-1-phenyl-2-cyclohexene (43). Phenylation with 2:1
PhMgBr/Cu(acac)2: A solution of 13 (24.6 mg, 0.106 mmol) in
THF (1 mL) was added to a mixture of PhMgBr (0.35 mL, 0.98 M in
THF, 0.343 mmol) and Cu(acac)2 (42.3 mg, 0.162 mmol) in THF
(1 mL) at −40 °C, and the mixture was allowed to warm to −10 °C
over 2 h to afford a mixture of 43 and 44 in a 82:18 ratio (14.4 mg,
73%).
Phenylation with 3:1:1 PhMgBr/Cu(acac)2/ZnI2: To an ice-cold
suspension of Cu(acac)2 (42.5 mg, 0.162 mmol) and ZnI2 (51.0 mg,
0.160 mmol) in THF (1 mL) was added PhMgBr (0.63 mL, 0.77 M in
3764
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The Journal of Organic Chemistry
Article
THF, 0.485 mmol). After being stirred at 0 °C for 1 h, the mixture
was cooled to −40 °C, and a solution of picolinate 13 (25.3 mg,
0.109 mmol) in THF (1 mL) was added. The mixture was allowed to
warm to −10 °C over 2 h to afford a mixture of 43 and 44 in a 87:13
ratio (16.5 mg, 81%).
Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008,
108, 2824−2852. (c) Breit, B.; Schmidt, Y. Chem. Rev. 2008, 108,
2928−2951.
(3) (a) Hornillos, V.; Per
Am. Chem. Soc. 2013, 135, 2140−2143. (b) Magrez, M.; Guen, Y. L.;
Basle, O.; Crev
isy, C.; Mauduit, M. Chem.Eur. J. 2013, 19, 1199−
́
ez, M.; Fananas-Mastral, M.; Feringa, B. L. J.
́
̃
1
Product 43: colorless oil; H NMR (400 MHz, CDCl3) δ 0.73 (t,
́
́
J = 7.5 Hz, 3 H), 1.45−2.08 (m, 8 H), 5.85 (dm, J = 10 Hz, 1 H), 5.90
(dt, J = 10, 3 Hz, 1 H), 7.13−7.23 (m, 2 H), 7.24−7.34 (m, 3 H); 13C
NMR (100 MHz, CDCl3) δ 8.7 (+), 19.0 (−), 25.6 (−), 35.1 (−),
36.7 (−), 43.1 (−), 125.4 (+), 127.3 (+), 127.93 (+), 127.95 (+),
132.9 (+), 148.3 (−). The 1H NMR spectrum was consistent with data
reported in the literature.4b
1,4-Diphenyl-1-vinylcyclohexane (45). Phenylation with 2:1
PhMgBr/Cu(acac)2: A solution of 147 (29.6 mg, 0.0963 mmol) in
THF (1 mL) was added to a mixture of PhMgBr (0.26 mL, 1.14 M in
THF, 0.296 mmol) and Cu(acac)2 (39.0 mg, 0.149 mmol) in THF
(1 mL) at −40 °C, and the mixture was allowed to warm to −10 °C
over 2 h to afford a mixture of 45 and 46 in a 81:19 ratio (19.4 mg,
77%).
Phenylation with 3:1:1 PhMgBr/Cu(acac)2/ZnI2: To an ice-cold
suspension of Cu(acac)2 (38.0 mg, 0.145 mmol) and ZnI2 (46.4 mg,
0.145 mmol) in THF (1 mL) was added PhMgBr (0.49 mL, 0.85 M in
THF, 0.417 mmol). After being stirred at 0 °C for 1 h, the mixture was
cooled to −40 °C and a solution of picolinate 14 (29.5 mg, 0.0960
mmol) in THF (1 mL) was added. The mixture was allowed to warm
to −10 °C over 2 h to afford a mixture of 45 and 46 in a 87:13 ratio
(18.4 mg, 73%).
1203. (c) Fananas-Mastral, M.; Perez, M.; Bos, P. H.; Rudolph, A.;
Harutyunyan, S. R.; Feringa, B. L. Angew. Chem., Int. Ed. 2012, 51,
1922−1925. (d) Jung, B.; Hoveyda, A. H. J. Am. Chem. Soc. 2012, 134,
1490−1493. (e) Gao, F.; Carr, J. L.; Hoveyda, A. H. Angew. Chem., Int.
Ed. 2012, 51, 1−6. (f) Dabrowski, J. A.; Gao, F.; Hoveyda, A. H. J. Am.
Chem. Soc. 2011, 133, 4778−4781. (g) Gao, F.; McGrath, K. P.; Lee,
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(h) Gao, F.; Lee, Y.; Mandai, K.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2010, 49, 8370−8374. (i) Lee, Y.; Li, B.; Hoveyda, A. H. J. Am. Chem.
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Knochel, P. Angew. Chem., Int. Ed. 2005, 44, 4627−4631. (d) Breit, B.;
Demel, P.; Studte, C. Angew. Chem., Int. Ed. 2004, 43, 3786−3789.
(e) Harrington-Frost, N.; Leuser, H.; Calaza, M. I.; Kneisel, F. F.;
Knochel, P. Org. Lett. 2003, 5, 2111−2114. (f) Spino, C.; Beaulieu, C.
Angew. Chem., Int. Ed. 2000, 39, 1930−1932. (g) Ibuka, T.; Tanaka,
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(b) Kiyotsuka, Y.; Acharya, H. P.; Katayama, Y.; Hyodo, T.; Kobayashi,
Y. Org. Lett. 2008, 10, 1719−1722. (c) Kiyotsuka, Y.; Kobayashi, Y. J.
Org. Chem. 2009, 74, 7489−7495.
Product 45: amorphous solid; 1H NMR (400 MHz, CDCl3) δ
1.80−1.96 (m, 6 H), 2.28 (dm, J = 10 Hz, 2 H), 2.50−2.64 (m, 1 H),
5.16 (dd, J = 18, 1 Hz, 1 H), 5.33 (dd, J = 11, 1 Hz, 1 H), 5.88 (dd, J =
18, 11 Hz, 1 H), 7.16−7.26 (m, 4 H), 7.27−7.35 (m, 4 H) 7.39−7.44
(m, 2 H); 13C NMR (100 MHz, CDCl3) δ 30.5 (−), 36.4 (−), 44.0
(−), 44.3 (+), 115.1 (−), 125.9 (+), 126.0 (+), 126.2 (+), 127.0 (+),
128.2 (+), 128.4 (+), 144.6 (+), 147.5 (−), 149.3 (−); HRMS (FAB)
calcd for C20H22 (M+) 262.1722, found 262.1720.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of all compounds prepared. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(7) Our contribution to the former substitution (A → B) using allylic
picolinates: Kaneko, Y.; Kiyotsuka, Y.; Acharya, H. P.; Kobayashi, Y.
Chem. Commun. 2010, 46, 5482−5484.
(8) Ohmiya, H.; Makida, Y.; Li, D.; Tanabe, M.; Sawamura, M. J. Am.
Chem. Soc. 2010, 132, 879−889.
(9) See entries 15 and 16 in Table 2 of ref 8.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ykobayas@bio.titech.ac.jp.
■
Notes
(10) For example, see: (a) Qin, Y.-C.; Stivala, C. E.; Zakarian, A.
Angew. Chem., Int. Ed. 2007, 46, 7466−7469. (b) Zhu, Q.; Lu, Y. Chem.
Commun. 2010, 46, 2235−2237. (c) He, F.; Bo, Y.; Altom, J. D.;
Corey, E. J. J. Am. Chem. Soc. 1999, 121, 6771−6772. (d) Canham, S.
M.; France, D. J.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876−
7877. (e) Bogle, K. M.; Hirst, D. J.; Dixon, D. J. Org. Lett. 2010, 12,
1252−1254. (f) Yang, X.; Zhai, H.; Li, Z. Org. Lett. 2008, 10, 2457−
2460. (g) Esumi, T.; Mori, T.; Zhao, M.; Toyota, M.; Fukuyama, Y.
Org. Lett. 2010, 12, 888−891.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and
Culture, Japan.
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