α-Regioselective construction of gem-bisprenyl structures via zinc-mediated prenylation of esters in THF

Article abstract of DOI:10.1016/j.tet.2013.07.008

The in situ generated prenylzinc reagent from the reaction of zinc with prenyl bromide has been shown to undergo a new type of α-regioselective addition reaction with a wide range of esters that affords gem-bisprenyl structures. The reaction proceeds under mild conditions to provide α,α′-adducts with complete α-regioselectivity. A mechanism with the consideration of the steric factors is proposed to account for the regioselective results.

Full text of DOI:10.1016/j.tet.2013.07.008

Tetrahedron 69 (2013) 7970e7974
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journal homepage: www.elsevier.com/locate/tet
a-Regioselective construction of gem-bisprenyl structures via
zinc-mediated prenylation of esters in THF
*
Li-Ming Zhao , Li-Jing Wan, Shu-Qing Zhang, Rui Sun, Feng-Yan Ma
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal
University, Xuzhou 221116, Jiangsu, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The in situ generated prenylzinc reagent from the reaction of zinc with prenyl bromide has been shown
Received 26 April 2013
Received in revised form 20 June 2013
Accepted 3 July 2013
to undergo a new type of
bisprenyl structures. The reaction proceeds under mild conditions to provide
-regioselectivity. A mechanism with the consideration of the steric factors is proposed to account for the
regioselective results.
a
-regioselective addition reaction with a wide range of esters that affords gem-
a,a
0-adducts with complete
a
Available online 8 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Prenylation
Esters
Regioselectivity
Steric repulsion
1. Introduction
on the synthesis of biologically important molecules via
a-pre-
nylation, we became interested in exploring the -regioselective
a
The prenyl unit occurs widely in a variety of natural products
and biologically important molecules.1 Natural products possessing
a gem-bisprenyl fragment are very common in nature.2 Further-
more, the gem-bisprenyl fragment is also an important building
block and versatile synthon, frequently employed for the synthesis
of polycyclic polyprenylated acylphloroglucinols (PPAPs)3 and cy-
clohexane derivatives.4 As a result, a reliable method for the con-
struction of such a structure is therefore potentially valuable in
organic and medicinal chemistry. In principle, the introduction of
highly relevant gem-bisprenyl fragments can be easily achieved by
metal-mediated bisprenylation reaction of carboxylates using
prenyl halide as the prenyl source. Unfortunately, to the best of our
knowledge, no report has been made on the direct bisprenylation of
esters using prenylic metal reagents. One reason is that carboxylic
esters are generally considered poor electrophiles in such a re-
action. Another is that there is considerable difficulty in controlling
prenylation of the relatively little explored carboxylic esters to
broaden the scope of the reaction. We describe here a straightfor-
ward and practical zinc-mediated method for the prenylation of
esters with high
a-regioselectivity using commercially available
prenyl bromide to afford bisprenyl alkyl carbinols in good to ex-
cellent yields. Although zinc as a mediator has proved to be very
effective for the allylation of carboxylic acid derivatives,8 zinc as
a mediator used in prenylmetal-ester a-regioselective reaction has
not been demonstrated so far. As a related reaction, Ishino’s group
reported the zinc-promoted gem-bisallylation of acid chlorides
with substituted allyl chlorides, such as crotyl chloride and cin-
namyl chloride in the presence of chlorotrimethylsilane to afford
a mixture of
a and g products. However, when using the prenyl
chloride as the allyl source, the reaction gave only a monoallylation
product, phenyl prenyl ketone, as a
g
product.9
the
Recently our group reported the direct prenylation reaction of
aldehydes and ketones in a highly -regioselective manner for the
preparation of
-prenylated alcohols.6 More recently, we described
a
-regioselectivity of the prenylation.5
2. Results and discussion
a
Conditions for the zinc-mediated approach to gem-bispreny-
lated products were explored by the reaction of methyl 4-
chlorobenzoate 1a with prenyl bromide (Table 1). To our delight,
the utilization of same reaction conditions previously applied in the
prenylation of aldehydes and ketones led to the desired gem-bis-
a
a direct synthesis of linear homoallylic amines via a highly
a-
regioselective prenylation of imines.7 With these successful reports
prenylated product with perfect
with prenylzinc bromide in hexamethylphosphoramide (HMPA) at
a
-regioselectivity.6 Treating 1a
* Corresponding author. Tel.: þ86 516 83403165; fax: þ86 516 83536977; e-mail
address: lmzhao@jsnu.edu.cn (L.-M. Zhao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.008

L.-M. Zhao et al. / Tetrahedron 69 (2013) 7970e7974
7971
Table 1
Optimization of reaction conditionsa
Cl
O
Cl
Br
O
+
Zn/solvent/T
HO
Cl
O
3a
1a
2a
Entry
Solvent
T (ꢀC)
t (h)
2ab (%)
3ab (%)
1
2
3
4
5
6
HMPA
DMPU
130
120
100
Reflux
Reflux
50
12
14
14
15
20
20
76
75
73
79
84
d
d
d
THF/DMPUc
THF
7
13
Trace
d
THF
THF
a
Reactions were performed with ester (1.0 mmol), prenyl bromide (2.4 mmol), and zinc (3.0 mmol).
Isolated yields.
The ratio is 1.5/1.
b
c
Table 2
130 ꢀC for 12 h afforded the desired product 2a in 76% yield (entry
1). To replace the carcinogenic HMPA by a less toxic solvent, we
then examined the effect of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)
pyrimidinone (DMPU) on the bisprenylation, which is usually used
as safe substitute for the carcinogenic HMPA,10 and were pleased to
Reaction of prenyl bromide with various esters
O
R
Zn
THF/reflux
R'
+
Br
R
O
HO
observe that the alternative solvent did not affect the a-regiose-
2
1
lective prenylation (entry 2). When the solvent was switched to the
cosolvent of THF/DMPU, the reaction still proceeded efficiently to
afford the desired product 2a in 73% yield with only a small amount
of the intermediate ketone 3a (entry 3). This positive result, in
which the reaction could be performed under much milder con-
ditions, prompted us to optimize the reaction conditions further. At
this point, we wondered whether THF could be used as the solvent
without any additive despite the fact that THF as the sole solvent
Entry
Substrate
Product
Yielda (%)
1
2
3
4
5
6
7
8
Methyl benzoate 1b
Ethyl benzoate 1c
Isopropyl benzoate 1d
2b
2b
2b
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
53
56
54
77
85
86
85
80
88
55
52
61
56
86
71
61
Methyl 2-fluorobenzoate 1e
Methyl 3-fluorobenzoate 1f
Methyl 4-fluorobenzoate 1g
Methyl 2,4-dichlorobenzoate 1h
Methyl 3,4-dichlorobenzoate 1i
Methyl 4-bromobenzoate 1j
Methyl 3-methyl benzoate 1k
Methyl 4-methyl benzoate 1l
Methyl furan-2-carboxylate 1m
Methyl cyclohexanecarboxylate 1n
Methyl 2-(2,4,5-trifluorophenyl)acetate 1o
Methyl 2-(naphthalen-2-yl)acetate 1p
Methyl 3-phenylpropanoate 1q
has been proven to disfavor the
carbonyl compounds.6,11 Gratifyingly, the result revealed that THF
alone was also an effective solvent for this -regioselective bis-
a-regioselective prenylation of
9
10
11
12
13
14
15
16
a
prenylation (entry 4), thus making this reaction quite practical and
attractive for the synthetic community. A longer reaction time was
necessary to achieve good conversion of ketone 3a (entry 5). Dis-
appointingly, decreasing the reaction temperature to 50 ꢀC led to
complete recovery of the starting material (entry 6).
a
Isolated yields.
With optimized reaction conditions in hand, we next in-
vestigated the scope of the double prenylation of esters, and the
results are shown in Table 2. Some esters of benzoic acid, including
methyl benzoate 1b, ethyl benzoate 1c, and isopropyl benzoate 1d,
were investigated first. The results indicated that the alkoxy group
of the esters had no obvious influence on the reaction as the same
product 2b was all obtained in similar yield (entries 1e3). Sub-
sequently, methyl benzoate bearing different substituents in the
phenyl ring was surveyed. The results showed that both electron-
withdrawing and electron-donating groups on the phenyl ring,
such as fluoride (entries 4e6), chloride (entries 7 and 8), bromide
(entry 9), and methyl groups (entries 10 and 11), were all com-
patible with this reaction and gave moderate to good yields of the
achieved, and no
reaction.
g-prenylated products were found during the
Polar aprotic solvents, such as HMPA and DMPU are known to
play a key role in the -prenylation of carbonyls and imines. When
there is no polar aprotic solvent present, the -regioselectivity is
very poor.6,7 In contrast, the
-adduct was obtained exclusively in
the absence of HMPA or DMPU in the -bisprenylation of esters,
illustrating that a polar aprotic solvent did not play an important
role in the reaction. This leads us to propose a new mechanism that
is different from the previously reported [3,5]-sigmatropic rear-
a
a
a
a
desired
a
-bisprenylation products 2eel. The phenyl group of the
rangement mechanism in the a-prenylation of carbonyls and im-
benzoate can be further replaced with a furyl ring, and the desired
product 2m can be obtained in moderate yield (entry 12). More-
over, the aliphatic carboxylic ester 1n can also be applied to the
method (entry 13). Notably, other substituted carboxylic esters,
such as methyl 2-(2,4,5-trifluorophenyl)acetate 1o (entry 14),
methyl 2-(naphthalen-2-yl)acetate 1p (entry 15), and methyl 3-
phenylpropanoate 1q (entry 16) could be tolerated in the process,
and the corresponding
moderate to good yields under the same condition. A noteworthy
observation was that, in all entries, perfect -regioselectivity was
ines,6,7 as shown in Scheme 1. The first step involves the in situ
formation of the prenylzinc reagent, which interconverts between
primary prenylzinc species I and tertiary prenylzinc species II.12
Consequently, two possible pathways forming the transition state
A (TS-A) and transition state B (TS-B) should be considered.13 Of the
two possible transition states A and B, TS-A would be more favor-
able because of the absence of steric interactions between the
alkoxyl group and hydrogen atom of the terminal olefin. Con-
versely, the presence of bulkier substituent in which the hydrogen
atom is replaced by a methyl group leads to the increase of steric
a,a
0-adducts 2oeq could be obtained in
a

7972
L.-M. Zhao et al. / Tetrahedron 69 (2013) 7970e7974
repulsion in TS-B shown in the graphic, and so the formation of 4 is
prevented. The TS-A thus formed would undergo the elimination of
group compatibility in comparison with organolithium and
Grignard reagents. These facts imply that there might be weak
complexation of ester carbonyl group with prenylzinc bromide.
Consequently, TS-B is unstable compared with TS-A due to the
overpowering steric repulsion of the methyl group of the terminal
olefin with alkyloxy group of ester in TS-B.
To demonstrate the proposed mechanism, we performed the
following experiment. First, ketone 3a was synthesized and then
treated with prenylzinc bromide at reflux in THF for 14 h
alkyloxy zinc bromide to deliver the ketone 3 as an
a product,
which is subsequently attacked by the prenyl species. For this to be
the case with the intermediate 3, the reaction with prenyl species
might produce two isomers:
state C (TS-C) and transition state D (TS-D), respectively. However,
the reaction cleanly produced the -adduct 2 as single isomer. The
a-adduct and g-adduct via transition
a
above rationale of the different steric repulsion between TS-A and
TS-B can also be used to account for the regioselectivity in the
(Scheme 2). During the reaction course, only
a-adduct was ob-
addition of ketone 3 with prenyl species. The exclusive
a-adduct 2
served. The formation of -adduct was not observed by TLC and
g
rather than -addition of ketone 3 can be rationalized by the
g
GCeMS. This result showed that the proposed mechanism seemed
minimization of steric repulsion between the hydrogen atom of the
terminal olefin and the substituents on the carbonyl group of the
substrate in TS-C, in a manner analogous to the TS-A. In the case of
TS-D, the steric interaction between the terminal substituents of
the olefin and the groups attached to the carbonyl group is highly
unfavorable; therefore, the addition proceeds exclusively via TS-C,
to be a reasonable assumption.
O
HO
Br
Zn/THF/reflux
which results in the exclusive formation of a,a
0-adduct 2.
Cl
Cl
3a
2a
Scheme 2. Reaction of ketone 3a and prenylzinc bromide.
To confirm the role of steric bulk around carbonyls, we next
performed a reaction by using hindered ketone benzophenone as
the substrate under the aforementioned conditions (Scheme 3). The
reaction afforded a-adduct 5 exclusively in 60% yield and no g-
adduct was observed by TLC and GCeMS. The result clearly dem-
onstrates the contribution of steric repulsion in determining the
regioselectivity of prenylation. This behavior is also similar to that
observed in earlier work by Miginiac and Barbot,15 thus confirming
the validity of the proposed mechanism.
O
HO
Br
Zn/THF/reflux
5
Scheme 3. Reaction of benzophenone and prenylzinc bromide.
3. Conclusion
In conclusion, this study introduces a highly efficient procedure
for the construction of gem-bisprenyl building blocks by using an in
situ generated prenylzinc reagent under mild conditions, enabling
quick access to gem-bisprenyl structures found in a wide variety of
natural products. The reaction is very convenient due to the use of
commercially available and cheap reagents, such as prenyl bromide,
zinc, and THF, and the procedure is simple. More importantly, the a-
regioselectivity could be achieved in the absence of a polar aprotic
solvent, thus making this protocol all the more attractive. With
these advantages, we believe that this reaction will become a useful
and practical method to synthesize the natural products and nat-
ural product analogues with a gem-bisprenyl fragment.
Scheme 1. Proposed reaction mechanism.
Although the proposed reaction mechanism in Scheme 1 differs
from the previously reported mechanisms of the allylation of al-
dehyde,14 at least the following facts support such a mechanism.
First, it should be noted that the argument of TS-B being disfavored
by steric reasons is chemically reasonable due to the poor elec-
trophilicity and steric hindrance of ester despite the fact that such
a transition state is possible in the case of the allylation of aldehyde.
On the other hand, organozinc reagents show moderate reactivity
toward many organic electrophiles and have higher functional
4. Experimental section
4.1. General procedure for the synthesis of a,a
0-adduct 2
Prenyl bromide (2.4 mmol) was added into a suspension of ac-
tivated zinc powder (3.0 mmol) in dry THF (15 ml); the reaction
mixture was stirred for 1 h at room temperature. Filtered the so-
lution through an Schlenk filter and kept under N2 for the following
reaction. A solution of ester 1 (1.0 mmol) in dry THF (3 ml) was

L.-M. Zhao et al. / Tetrahedron 69 (2013) 7970e7974
7973
added the solution of prenylzinc bromide prepared above. The
mixture was heated to reflux under N2 atmosphere for 20 h. The
residue was purified by flash column chromatography (petroleum
2H), 2.51e2.41 (m, 4H), 2.29 (s, 3H), 1.99 (s, 1H), 1.59 (s, 6H), 1.50 (s,
6H). 13C NMR (100 MHz, CDCl3)
: 145.6, 136.4, 134.6, 126.7, 126.0,
125.2, 121.5, 117.9, 75.6, 39.6, 25.0, 20.6, 17.0. HRMS (ESI): m/z calcd
for C18H26ONa [MþNa]þ: 281.1881; Found: 281.1881.
d
ether/ethyl acetate, 20/1, v/v) to afford the
a,a
0-adduct 2.
4.1.1. Characterization of 2a. Pale yellow oil. 1H NMR (400 MHz,
4.1.10. Characterization of 2l. Colorless oil. 1H NMR (400 MHz,
CDCl3) : 7.34 (d, J¼8.4 Hz, 2H), 7.28 (d, J¼8.4 Hz, 2H), 4.97 (t,
J¼8.0 Hz, 2H), 2.55e2.48 (m, 4H), 2.09 (s, 1H), 1.66 (s, 6H), 1.56 (s,
6H). 13C NMR (100 MHz, CDCl3)
: 145.2, 136.2, 132.1, 128.0, 127.1,
d
CDCl3)
J¼6.4 Hz, 2H), 2.54e2.51 (m, 4H), 2.34 (s, 3H), 2.05 (s, 1H), 1.66 (s,
6H), 1.58 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 143.7, 135.7, 135.6,
d
: 7.30 (d, J¼7.6 Hz, 2H), 7.13 (d, J¼7.6 Hz, 2H), 5.02 (t,
d
d
118.4, 76.4, 40.7, 26.0, 18.1. HRMS (ESI): m/z calcd for C17H23OClNa
128.6, 125.4, 118.9, 76.5, 40.6, 26.0, 21.0, 18.0. HRMS (ESI): m/z calcd
[MþNa]þ: 301.1335; Found: 301.1358.
for C18H26ONa [MþNa]þ: 281.1881; Found: 281.1888.
4.1.2. Characterization of 2b. Colorless oil. 1H NMR (400 MHz,
4.1.11. Characterization of 2m. Yellow oil. 1H NMR (400 MHz, CDCl3)
CDCl3)
1H), 5.0 (t, J¼4.0 Hz, 2H), 2.60e2.50 (m, 4H), 2.09 (s, 1H), 1.65 (s,
6H), 1.57 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 146.7, 135.7, 127.9,
126.3, 125.5, 118.9, 76.6, 40.7, 26.0, 18.0. HRMS (ESI): m/z calcd for
C17H24ONa [MþNa]þ: 267.1725; Found: 267.1725.
d
: 7.41 (d, J¼8.0 Hz, 2H), 7.32 (t, J¼7.2 Hz, 2H), 7.25e7.20 (m,
d
: 7.34 (s,1H), 6.30 (s,1H), 6.17 (s,1H), 5.05 (s, 2H), 2.55e2.53 (m, 4H),
2.22 (s, 1H), 1.69 (s, 6H), 1.59 (s, 6H). 13C NMR (100 MHz, CDCl3)
d:
d
158.8,141.3,135.8,118.4,110.1,105.5, 74.2, 38.3, 26.0,18.0. HRMS(ESI):
m/z calcd for C15H22O2Na [MþNa]þ: 257.1517; Found: 257.1527.
4.1.12. Characterization of 2n. Colorless oil. 1H NMR (400 MHz,
4.1.3. Characterization of 2e. Colorless oil. 1H NMR (400 MHz,
CDCl3)
d: 5.22 (t, J¼7.2 Hz, 2H), 2.20e2.09 (m, 4H), 1.80e1.74 (m,
CDCl3)
d
: 7.51 (t, J¼8.0 Hz, 1H), 7.25e7.19 (m, 1H), 7.11 (t, J¼7.6 Hz,
4H),1.74 (s, 6H),1.62 (s, 6H),1.41 (s,1H),1.25e0.85 (m, 7H). 13C NMR
1H), 6.98 (dd, J¼12.0, 8.4 Hz, 1H), 4.98 (t, J¼7.2 Hz, 2H), 2.75e2.59
(100 MHz, CDCl3) d: 134.6, 119.6, 76.6, 45.5, 35.0, 27.1, 26.9, 26.7,
(m, 4H), 2.24 (s, 1H), 1.64 (s, 6H), 1.59 (s, 6H). 13C NMR (100 MHz,
26.2, 18.0. HRMS (ESI): m/z calcd for C17H30ONa [MþNa]þ:
CDCl3)
d
: 159.2 (J¼244.0 Hz), 135.8, 133.2 (J¼12.0 Hz), 128.7
273.2194; Found: 273.2207.
(J¼5.0 Hz), 128.4 (J¼8.0 Hz), 123.7 (J¼3.0 Hz), 118.8, 115.7
(J¼24.0 Hz), 75.8 (J¼6.0 Hz), 39.1 (J¼4.0 Hz), 26.0, 18.0. HRMS (ESI):
m/z calcd for C17H23OFNa [MþNa]þ: 285.1631; Found: 285.1640.
4.1.13. Characterization of 2o. Colorless oil. 1H NMR (400 MHz,
CDCl3)
2H), 2.74 (s, 2H), 2.20e2.01 (m, 4H), 1.75 (s, 6H), 1.63 (s, 1H), 1.58 (s,
6H). 13C NMR (100 MHz, CDCl3)
: 135.7, 129.5, 126.0, 120.4
d
: 7.22e7.15 (m, 1H), 6.91e6.84 (m, 1H), 5.21 (t, J¼7.2 Hz,
4.1.4. Characterization of 2f. Colorless oil. 1H NMR (400 MHz,
d
CDCl3)
4.99 (t, J¼5.6 Hz, 2H), 2.58e2.47 (m, 4H), 2.12 (s, 1H), 1.66 (s, 6H),
1.57 (s, 6H). 13C NMR (100 MHz, CDCl3)
(J¼6.0 Hz), 136.2, 129.3 (J¼8.0 Hz), 121.1, 118.4, 113.0 (J¼44.0 Hz),
76.4, 40.7, 26.0, 18.0. HRMS (ESI): m/z calcd for C17H23OFNa
[MþNa]þ: 285.1631; Found: 285.1642.
d
: 7.30e7.25 (m, 1H), 7.16e7.13 (m, 2H), 6.93e6.89 (m, 1H),
(J¼5.0 Hz), 120.2 (J¼7.2 Hz), 118.7, 105.0 (J¼19.7 Hz), 104.6
(J¼21.1 Hz), 75.2, 37.6, 37.0, 26.1, 18.0. HRMS (ESI): m/z calcd for
C18H23OF3Na [MþNa]þ: 335.1599; Found: 335.1599.
d: 162.9 (J¼243.0 Hz), 149.7
4.1.14. Characterization of 2p. Colorless oil. 1H NMR (400 MHz,
CDCl3)
1H), 7.51e7.41 (m, 4H), 5.28 (s, 2H), 3.27 (s, 2H), 2.30e2.16 (m, 4H),
1.75 (s, 6H), 1.56 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 134.8, 134.2,
d: 8.18 (d, J¼8.0 Hz, 1H), 7.83 (d, J¼8.0 Hz, 1H), 7.76e7.74 (m,
4.1.5. Characterization of 2g. Colorless oil. 1H NMR (400 MHz,
d
CDCl3)
2.52 (s, 4H), 2.09 (s,1H),1.66 (s, 6H),1.55 (s, 6H). 13C NMR (100 MHz,
CDCl3)
d
: 7.38e7.34 (m, 2H), 7.02e6.97 (m, 2H), 4.99 (t, J¼6.8 Hz, 2H),
134.0, 133.5, 129.2, 128.6, 127.2, 125.6, 125.4, 125.2, 125.1, 119.5, 76.1,
41.2, 38.0, 26.2, 18.1. HRMS (ESI): m/z calcd for C22H28ONa
[MþNa]þ: 331.2038; Found: 331.2036.
d: 161.5 (J¼243.0 Hz), 142.2 (J¼12.0 Hz), 136.1, 127.2
(J¼8.0 Hz),118.6,114.6 (J¼20.0 Hz), 76.4, 40.8, 26.0,18.0. HRMS (ESI):
m/z calcd for C17H23OFNa [MþNa]þ: 285.1631; Found: 285.1640.
4.1.15. Characterization of 2q. Colorless oil. 1H NMR (400 MHz,
CDCl3)
2H), 2.70e2.65 (m, 2H), 2.24 (d, J¼7.6 Hz, 4H), 1.78e1.73 (m, 2H),
1.76 (s, 6H), 1.66 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 142.9, 135.1,
d: 7.30e7.25 (m, 2H), 7.20e7.16 (m, 3H), 5.23 (t, J¼7.6 Hz,
4.1.6. Characterization of 2h. Colorless oil. 1H NMR (400 MHz,
CDCl3)
4.91 (t, J¼6.8 Hz, 2H), 3.02e2.63 (m, 4H), 2.32 (s, 1H), 1.64 (s, 6H),
1.61 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 141.8, 136.1, 132.9, 131.2,
d: 7.63 (d, J¼8.0 Hz, 1H), 7.34 (s, 1H), 7.22 (d, J¼8.0 Hz, 1H),
d
128.4, 125.7, 119.1, 75.0, 41.2, 37.8, 30.1, 26.2, 18.1. HRMS (ESI): m/z
calcd for C19H28ONa [MþNa]þ: 295.2038; Found: 295.2032.
d
130.7, 130.4, 126.7, 118.5, 77.1, 37.7, 25.9, 18.1. HRMS (ESI): m/z calcd
for C17H22OCl2Na [MþNa]þ: 335.0945; Found: 335.0945.
Acknowledgements
4.1.7. Characterization of 2i. Colorless oil. 1H NMR (400 MHz, CDCl3)
We are thankful for the financial support from the Natural Sci-
ence Foundation of Jiangsu Province (BK2012576), Major Program of
Natural Science Foundation (12KJA150005) and Priority Academic
Program Development of Jiangsu Higher Education Institutions.
d
: 7.51 (d, J¼2.0 Hz, 1H), 7.37 (d, J¼8.4 Hz, 1H), 7.22 (dd, J¼8.4 Hz,
J¼2.0 Hz, 1H), 4.97 (t, J¼6.8 Hz, 2H), 2.56e2.44 (m, 4H), 2.12 (s, 1H),
1.67 (s, 6H), 1.56 (s, 6H). 13C NMR (100 MHz, CDCl3)
: 147.2, 136.6,
d
132.1,130.2,129.8,128.0,125.1,118.0, 76.2, 40.6, 26.0,18.1. HRMS (ESI):
m/z calcd for C17H22OCl2Na [MþNa]þ: 335.0945; Found: 335.0923.
Supplementary data
4.1.8. Characterization of 2j. Colorless oil. 1H NMR (400 MHz,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.008.
CDCl3)
J¼6.8 Hz, 2H), 2.56e2.46 (m, 4H), 2.09 (s, 1H), 1.66 (s, 6H), 1.56 (s,
6H). 13C NMR (100 MHz, CDCl3)
: 145.7, 136.2, 130.9, 127.5, 120.3,
d
: 7.43 (d, J¼8.8 Hz, 2H), 7.28 (d, J¼8.4 Hz, 2H), 4.97 (t,
d
References and notes
118.4, 76.5, 40.6, 26.0, 18.1. HRMS (ESI): m/z calcd for C17H23OBrNa
[MþNa]þ: 345.0830; Found: 345.0830.
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