Studies on electrophilic interaction of 2,3-allenols with electrophilic halogen reagents: Selective synthesis of 2,5-dihydrofurans, 3-halo-3-alkenals, or 2-halo-2-alkenyl ketones

Article abstract of DOI:10.1002/adsc.200800088

The reaction of primary 2,3-allenols with iodine (I₂) afforded 2,5-dihydrofurans while that of readily available 1-aryl or 1-methyl substituted 2,3-allenols with bromine (Br₂), N-bromosuccinimide (NBS), I ₂ or N-iodosuccin

Full text of DOI:10.1002/adsc.200800088

FULL PAPERS
DOI: 10.1002/adsc.200800088
Studies on Electrophilic Interaction of 2,3-Allenols with
Electrophilic Halogen Reagents: Selective Synthesis of
2,5-Dihydrofurans, 3-Halo-3-alkenals, or 2-Halo-2-alkenyl
Ketones
Jing Li,a Chunling Fu,a Guofei Chen,a Guobi Chai,a and Shengming Maa,b,*
a
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027,
Zhejiang, Peopleꢀs Republic of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, 354 Fenglin Lu, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-21-6416-7510; e-mail: masm@mail.sioc.ac.cn
Received: February 11, 2008; Published online: May 19, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The reaction of primary 2,3-allenols with lectivity and yields via a sequential electrophilic in-
iodine (I2) afforded 2,5-dihydrofurans while that of teraction of X+ with the allene moiety, 1,2-aryl or
readily available 1-aryl or 1-methyl substituted 2,3- 1,2-proton shift, and H+ elimination process.
allenols with bromine (Br2), N-bromosuccinimide
(NBS), I2 or N-iodosuccinimide (NIS) formed the
not easily available but synthetically useful 3-halo-3- Keywords: alcohols; aldehydes; allenes; electrophilic
alkenals and 2-halo-2-alkenyl ketones with good se- addition; halogens; ketones
Introduction
reaction afforded a regioisomeric mixture of 2-iodoal-
lylic ethers.[8] In our laboratory we have obsevered
Elecotrophilic additions of alkenes and alkynes with that the reaction of “X+” with functionalized allenes
“X+” have provided many useful methodologies for afforded cyclic alkenyl halides[9] or the halohydroxyla-
the efficient synthesis of halides.[1] The electrophilic tion products.[10] In 1993, Friesen et al. reported that
addition of allenes with “X+” is also quite attractive the reaction of 2,3-allenols with I2 in Et2O afforded
since 2-haloallylic halides or alcohols are usually 3,4-diiodo-2-alken-1-ol with a stereoselectivity of 7:1
formed.[2] The electrophilic addition of alkyl-substitut- to 9:1 (Z/E).[11] In a primary communication we have
ed allenes afforded terminal- or center-attack prod- reported that the sequential electrophilic addition re-
ucts, depending on the structures of the allenes and action with “X+” and 1,2-migration of 2,3-allenols af-
electrophiles:[3] Chlorination of propadiene afforded a forded 3-halo-3-enals.[12] In this paper, we report our
mixture of 2,3-dichloro-1-propene and propargylic detailed study in this area.
chloride[4] while that of 3-methyl-1,2-butadiene afford-
ed a mixture of regioisomeric 2,3-dichloro-3-methyl-1-
butene and 1,2-dichloro-3-methyl-2-butene.[5] The Results and Discussion
manganese-mediated chlorination of monosubstituted
allenes afforded a mixture of 2,3-dichloro-1-alkenes Preparation of the Starting Materials 2a–i
and 1,2-dichloro-2-alkenes.[6] Bromination of phenyl-
1,2-propadiene in MeOH at 08C also led to a regioi- Primary 2,3-allenols 2a–i used in this study were pre-
someric mixture of 2-bromoallylic methyl ethers, how- pared by reduction of the related 2,3-allenates 1a–i
ever, in a non-polar solvent such as CS2, CH2Cl2, or with DIBAL-H (Table 1).[13]
CCl4 only 2,3-dibromo-1-phenyl-1-propene was
formed.[7] Iodination of dialkyl-substituted allenes
formed 1,2-diiodo-2-alkenes in CHCl3 or CH2Cl2
whereas in the presence of Hg(OAc)2 in MeOH the
G
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Studies on Electrophilic Interaction of 2,3-Allenols with Electrophilic Halogen Reagents
FULL PAPERS
Table 1. Synthesis of primary 2,3-allenols 2a–i.
Scheme 1.
Entry R1
R2
Time [h] Yield [%] of 2a–i
1
2
3
4
5
6
7
8
9
n-C7H15 H (1a)
n-C6H13 CH3 (1b)
n-C7H15 CH3 (1c)
n-C6H13 n-C3H7 (1d) 6.2
n-C7H15 n-C3H7 (1e) 6.7
5.3
2.5
3.8
23 (2a)
36 (2b)
57 (2c)
70 (2d)
53 (2e)
32 (2f)
33 (2g)
38 (2h)
40 (2i)
Electrophilic Cyclization of Primary 2,3-Allenols 2
with I2
Our initial study began with the reaction of 2-propyl-
deca-2,3-dien-1-ol 2d with 2.5 equiv. of I2 in CH3CN/
H2O=15/1 at room temperature.[12] Instead of the
diiodination product,[11] 2,5-dihydrofuran 6d was
formed in 60% yield. Then, we studied the scope of
this cyclization reaction with some of the typical re-
sults being summarized in Table 3. It can be conclud-
CH3
Bn (1f)
3.5
4.8
3.3
3.5
n-C3H7 Bn (1g)
n-C4H9 Bn (1h)
n-C6H13 Bn (1i)
Preparation of Secondary 2,3-Allenols 5a–q
Table 3. Electrophilic cyclization of primary 2,3-allenols 2
with I2.[a]
Secondary 2,3-allenols 5a–q were prepared from the
reaction of the corresponding propargylic bromides
with aldehydes in the presence of NaI and SnCl2
(Table 2).[14]
Table 2. Synthesis of secondary 2,3-allenols 5a–q.
Entry R1
R2
Time [h] Isolated Yield
[%] of 6
1
2
3
4
5
6
7
8
9
n-C7H15 H (2a)
n-C6H13 CH3 (2b)
n-C7H15 CH3 (2c)
n-C6H13 n-C3H7 (2d) 22
n-C7H15 n-C3H7 (2e) 22
1.3
20
16
65 (6a)
60 (6b)
72 (6c)
60 (6d)
63 (6e)
67 (6f)
73 (6g)
75 (6h)
82 (6i)
Entry R1
R2
Time [h] Yield [%]
CH3
n-C3H7
n-C4H9
Bn (2f)
Bn (2g)
Bn (2h)
1.7
10
2.5
1.7
1
2
n-C4H9 Ph 12
n-C4H9 m,p-OCH2OC6H3 15
40 (5a)
45 (5b)
45 (5c)
57 (5d)
44 (5e)
66 (5f)
51 (5g)
62 (5h)
41 (5i)
3
4
n-C4H9 p-MeOC6H4
n-C4H9 p-MeC6H4
10
12
n-C6H13 Bn (2i)
5
n-C2H5 m,p-OCH2OC6H3 16
[a]
The reaction was carried out using 0.4–0.5 mmol of 2,3-
allenols.
6
7
n-C2H5 p-MeOC6H4
n-C2H5 p-MeC6H4
12
11
8
9
allyl
allyl
allyl
m,p-OCH2OC6H3 12
p-MeOC6H4
p-MeC6H4
11
17
17
20
11
17
20
20
10
ed that differently substituted primary 2,3-allenols
2a–i can be used to prepare the 2,4-disubstituted-3-iodo-
2,5-dihydrofurans 6a–i in moderate to good yields.
The carbon-iodine bond in 6d may undergo a cou-
pling reaction with 1-hexyne or phenylboronic acid to
afford 3-hexynyl- or phenyl-substituted 2,5-dihydro-
furan 7a or 8a, respectively, in excellent yields
(Scheme 2).
10
11
12
13
14
15
16
17
56 (5j)
62 (5k)
58 (5l)
46 (5m)
66 (5n)
49 (5o)
52 (5p)
46 (5q)
n-C4H9 a-Naphthyl
n-C4H9 m-BrC6H4
n-C4H9 p-ClC6H4
n-C4H9 p-NO2C6H4
n-C4H9 o,p-Cl2C6H3
n-C4H9 o-ClC6H4
n-C4H9 CH3
Preparation of Tertiary 2,3-Allenol 5r
Reaction of Secondary 2,3-Allenols with X2
The tertiary 2,3-allenol 5r was prepared from the re- However, when we tried to extend this reaction to 1-
action of the corresponding propargylic bromide with aryl-substituted 2,3-allenols, the expected 2-aryl-2,5-
acetophenone in the presence of In in THF/H2O=1/1 dihydrofuran 9 was not formed. The reaction of 1-
(Scheme 1).[15]
phenyl-2-butyl-2,3-butadienol 5a with Br2 in aqueous
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FULL PAPERS
Scheme 2.
Table 4. Reaction of secondary 2,3-allenols 5 with X2 (or NBS).
Entry R1
R2
X+ [equiv] Temp. [8C] Time [min] Yield [%] of 10 or 11 10/12 or 11/13[a]
1
2
3
4
5
6
7
8
n-C4H9 Ph (5a)
n-C4H9 m,p-OCH2OC6H3 (5b) Br2 (2)
NBS (1.2)
Br2 (2)
0
r.t.
0
r.t.
r.t.
r.t.
r.t.
r.t.
0
0
0
0
0
r.t.
r.t.
0
0
0
0
0
0
r.t.
0
30
50
30
60
90
30
30
30
60
140
25
25
30
30
25
30
40
30
30
35
30
40
30
30
50
100
50
30
25
55
60
30
50
30
30
80 (10a)
78 (10b)
93 (10b)
80 (11b)
71 (10c)
88 (10c)
77 (11c)
89 (11c)
87 (10d)
90 (10d)
68 (11d)
78 (10e)
84 (10e)
69 (11e)
87 (11e)
80 (10f)
88 (10f)
83 (11f)
86 (10g)
64 (10g)
55 (11g)
79 (11g)
68 (10h)
88 (10h)
complicated
57 (10i)
ꢀ95:5
98:2
99:1
>99:1
ꢀ99:1
99:1
>99:1
>99:1
97:3
I2 (2)
n-C4H9 p-MeOC6H4 (5c)
Br2 (2)
NBS (1.2)
I2 (2)
NIS (2)
Br2 (1.2)
NBS (1.2)
I2 (2)
9
n-C4H9 p-MeC6H4 (5d)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
97:3
97:3
C2H5
m,p-OCH2OC6H3 (5e) Br2 (1.2)
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
97:3
NBS (1.2)
I2 (2)
NIS (2)
Br2 (1.2)
NBS (1.2)
I2 (2)
Br2 (1.2)
NBS (1.2)
I2 (2)
C2H5
C2H5
p-MeOC6H4 (5f)
p-MeC6H4 (5g)
97:3
97:3
96:4
NIS (1.2)
allyl
allyl
m,p-OCH2OC6H3 (5h) Br2 (1.2)
>99:1
>99:1
-
>99:1
>99:1
-
ꢀ98:2
ꢀ97:3
ꢀ97:3
90:10
93:7
NBS (1.2)
I2 (1.2)
Br2 (1.2)
NBS (1.2)
I2 (1.2)
0
r.t.
0
p-MeOC6H4 (5i)
0
62 (10i)
complicated
37 (11i)
50 (10j)
71 (10j)
73 (10k)
76 (10k)
49 (10l/12l)
45 (10l/12l)
r.t.
À20
0
0
0
0
r.t.
0
I2 (1.2)
allyl
p-MeC6H4 (5j)
Br2 (1.2)
NBS (1.2)
Br2 (2)
NBS (1.2)
Br2 (1.2)
NBS (1.2)
n-C4H9 a-naphthyl (5k)
n-C4H9 m-BrC6H4 (5l)
80:20
80:20
[a]
1
The ratios of 10/12 or 11/13 determined by the H NMR analysis.
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FULL PAPERS
CH3CN (CH3CN:H2O=15:1) afforded 3-bromo-2-(n-
Then the reaction was extended to the tertiary 2,3-
butyl)-2-phenyl-3-butenal 10a in 77% yield.[12] By allenol, i.e., 2-phenyl-3-ethylpenta-3,4-dien-2-ol 5r af-
screening the most commonly used solvents and the fording 4-bromo-4-enone 12r in 83% yield
ratio of MeCN/H2O, it was found that a mixed solvent (Scheme 4).
of MeCN/H2O (15:1) is still the best reaction solvent.
Subsequently, the reaction of secondary 2,3-allenols
with X2 (or NXS) was performed under these condi-
tions (Table 4). It can be concluded that 2,3-allenols
with differently substituted phenyl groups at the 1-po-
sition may be used to prepare 3-halo-3-enals in good
yields. By introducing the allyl group to the 2-position
of 2,3-allenols, halogenation of the allylic C C double
bond was not observed, indicating a much higher re-
activity of the allene functionality. For the synthesis
Scheme 4.
À
of bromides, both Br2 and NBS may be applied, how-
A rationale for this transformation is shown
ever, the yields with NBS are usually higher than (Scheme 5). The interaction of ꢂꢂX+’ꢀ with the internal
those with Br2, probably due to the higher reactivity C=C bond of the allene moiety would form inter-
of Br2 towards the remaining C=C bond (compare en-
tries 2/3, 5/6, 12/13, 16/17, 23/24 and 30/31, Table 4).
The corresponding reaction with I2 can also occur
smoothly to afford 3-iodo-3-enals 11 in good to high
yields (entries 4, 7, 11, 14, 18 and 21, Table 4). The
structures of the products were determined unambig-
uously by the X-ray diffraction study of 11b.[12] Again
for the same reason the yields with NIS are higher
than those with I2 (compare entries 7/8, 14/15, 21/22).
The reaction of 5h and 5i with I2 at room temperature
afforded a complicated mixture (entries 25 and 28,
Table 4), while the reaction of 5i with I2 at À208C af-
forded 11i in 37% yield (entry 29, Table 4). In some
cases, a maximum of 5% of b,g-enone products 12 or
Scheme 5.
13 were also formed (entries 1, 9–11, 19–22, 29–31,
Table 4). The ratio of 10/12 or 11/13 depends on the
electronic effect of the substituent of the aryl group
at the 1-position: with a more electron-donating mediate 14, which would undergo a 1,2-shift of the Ar
group, the ratio of 10/12 or 11/13 is higher. group to open the three-membered ring forming the
However, the substrates with a naphthyl or an aryl cationic homoallylic alcohol intermediate 15. Upon
group bearing an electron- withdrawing group afford- releasing of H+ the reaction would form the final 3-
ed a mixture of aldehydes 10/12 and ketones 11/13 halo-3-enals 10 (or 11). If a 1,2-H transfer occurred,
with relatively poor selectivity (entries 32–35, the reaction would form the ketone product 12 (or
Table 4). Again, it should be noted that the reactions 13) via the intermediacy of 16.
of 5k–l with “I+” are quite complicated, failing to
afford the expected iodides.
When the 1-aryl group was replaced with an alkyl Conclusions
group, i.e., a methyl group, a 2-halo-2-alkenyl ketone,
i.e., 13q, was formed as the major product In summary, it was observed that the reaction of pri-
(Scheme 3).
mary 2,3-allenols with I2 afforded 3-iodo-2,5-dihydro-
furans. Under the similar reaction conditions, the re-
action of 1-aryl-2,3-allenols afforded 3-halo-3-enals
highly selectively when an electron-donating substitu-
ent is connected to the aryl group at the 1-position.
However, with a relatively electron-withdrawing aryl
group or a naphthyl group at the 1-position, a 1,2-H
transfer was observed as the minor pathway as well;
With an alkyl group group at the 1-position, the 1,2-H
shift was observed as the major pathway to afford the
2-halo-2-alkenyl ketones as the major products. Due
Scheme 3.
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Jing Li et al.
FULL PAPERS
tion and column chromatography on silica gel (petroleum
to the easy availability of the starting compounds 5
and the not readily available nature as well as the
synthetic potential of 3-halo-3-enals or 2-halo-2-al-
kenyl ketones, this method will be very useful in or-
ganic synthesis.[12] Further studies are being carried
out in our laboratory.
ether/ethyl acetate=10:1) afforded 5a[16] as an oil; yield:
1
0.66 g (40%); H NMR (400 MHz, CDCl3): d=7.40–7.26 (m,
5H), 5.10 (s, 1H), 5.04–4.96 (m, 2H), 2.21 (bs, 1H), 1.90–
1.73 (m, 2H), 1.42–1.32 (m, 2H), 1.32–1.22 (m, 2H), 0.84 (t,
J=7.2 Hz, 3H).
Cyclization of Primary 2,3-Allenols with I2; General
Procedure
Experimental Section
A solution of 2 (0.5 mmol) and iodine (1.25 mmol) in 4 mL
of MeCN/H2O (15:1) was stirred at room temperature.
When the reaction was complete as monitored by TLC, the
mixture was then quenched with 6 mL of water, which was
followed by the addition of a saturated aqueous solution of
Na2S2O3. This mixture was extracted with diethyl ether (3”
25 mL), washed with an aqueous solution of NaCl, and
dried over Na2SO4. Concentration and column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate=40:1) af-
forded 6.
General Methods
All the reactions were carried out in the open air unless oth-
1
erwise indicated. H and 13C NMR spectra were recorded on
a Bruker AM-300 spectrometer or Bruker AM-400 spec-
trometer. IR spectra were recorded on a Bruker Vector 22
spectrometer. Mass spectra were recorded on a HP 5989 A
spectrometer. Flash-column chromatography was carried
out on silica gel H (10–40 m). Petroleum ether with a boiling
point range from 60 to 908C was used. For the data of com-
pounds reported in the previous communication,[12] see the
related supporting information attached to this publication.
2-Heptyl-3-iodo-2,5-dihydrofuran (6a): The reaction of
85.7 mg (0.5 mmol) of 2a and 319.5 mg (1.25 mmol) of I2 in
4 mL of MeCN and 0.27 mL of H2O at rt for 80 min afford-
1
ed 6a as an oil; yield: 97.5 mg (65%); H NMR (400 MHz,
CDCl3): d=6.21 (d, J=1.6 Hz, 1H), 4.72–4.64 (m, 1H),
4.60–4.50 (m, 2H), 1.80–1.71 (m, 1H), 1.56–1.44 (m, 1H),
1.40–1.21 (m, 10H), 0.87 (t, J=6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=134.8, 92.1, 89.8, 76.2, 33.8, 31.8,
29.5, 29.2, 24.1, 22.6, 14.1. IR (neat): n=1612, 1464, 1345,
1237, 1068, 1008 cmÀ1; MS (70 ev, EI): m/z (%)=294 (M+,
2.73), 195 (100); HR-MS: m/z=294.0479, calcd. for
C11H19IO (M+): 294.0481.
Primary 2,3-Allenols
Compounds 2a–i were prepared according to the known
procedure from 2,3-allenoate 1a–i.[13]
2-Propyldeca-2,3-dien-1-ol (2d); Typical Procedure:
DIBAL-H (51.9 mL, 1.0 mol/L solution in toluene,
59.1 mmol) was added dropwise to a solution of 5.88 g
(24.7 mmol) of 1d in 35 mL of anhydrous toluene at À788C.
After 6.2 h at À788C the reaction was complete as moni-
tored by TLC. The mixture was then quenched with 25 mL
of methanol and washed with 300 mL of aqueous HCl solu-
tion (5%). The organic layer was separated and the aqueous
layer was extracted with ether. The combined organic layer
was dried over Na2SO4, filtered, and evaporated. The resi-
due was purified by column chromatography on silica gel
(eluent: petroleum ether/ethyl acetate=5:1) to give 2d as
Coupling Reactions of 3-Iododihydrofuran 6d
Sonogashira Coupling of 6d with 1-Hexyne to Afford
2-Hexyl-3-hexynyl-4-propyl-2,5-dihydrofuran (7a)
1
an oil; yield: 3.39 g (70%); H NMR (300 MHz, CDCl3): d=
5.39–5.30 (m, 1H), 4.07–3.93 (m, 2H), 2.05–1.91 (m, 4H),
1.53–1.21 (m, 11H), 0.93 (t, J=7.5 Hz, 3H), 0.88 (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=198.7, 105.4,
95.7, 63.0, 31.7, 31.4, 29.3, 28.8, 22.6, 20.9, 14.0, 13.8; IR
(neat): n=3316, 1964, 1465, 1378, 1156, 1092, 1017 cmÀ1; MS
(70 eV, EI): m/z (%)=196 (M+, 0.13), 165 (M+ÀCH2OH,
1.79), 71 (100); elemental analysis: calcd for C13H24O (%): C
79.53, H 12.32; found: C 79.51, H 12.36.
A
mixture of 82.0 mg (0.25 mmol) of 6d, 26.9 mg
Synthesis of Secondary 2,3-Allenols
(0.325 mmol) of 1-hexyne, 24.7 mg (0.325 mmol) of Et2NH,
4.0 mg (10 mol%) of CuI, and 8.5 mg (5 mol%) of PdCl2
Compounds 5a–q were prepared according to the known
procedure[14]
(PPh3)2 in 2 mL of CH3CN was stirred at 308C under N2 for
17 h (monitored by TLC, petroleum ether/ethyl acetate=
40:1). Water (6 mL) was added and the reaction mixture
was extracted with ether. The combined extract was washed
with saturated brine. After drying over Na2SO4, filtration,
and evaporation, the residue was purified by column chro-
matography on silica gel (petroleum ether/ethyl acetate=
100:1) to afford 7a as an oil; yield: 67.3 mg (96%); H NMR
(400 MHz, CDCl3): d=4.74–4.68 (m, 1H), 4.59–4.50 (m,
2H), 2.36 (t, J=6.8, 2H), 2.25–2.20 (m, 2H), 1.75–1.67 (m,
2-Butyl-1-phenylbuta-2,3-dien-1-ol (5a); Typical Proce-
dure:
A solution of 1.43 g (8.2 mmol) of 3a, 2.21 g
(11.5 mmol) of SnCl2, and 1.73 g (11.4 mmol) of NaI in
40 mL of DMF was stirred for 1 h at room temperature.
Then a solution of 1.16 mL (11.4 mmol) of aldehyde 4a in
40 mL of DMF was added dropwise at 08C. After 12 h at
08C as monitored by TLC, the mixture was quenched with
15 mL of water, extracted with diethyl ether, washed with
saturated NaCl, and dried over anhydrous Na2SO4. Evapora-
1
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Studies on Electrophilic Interaction of 2,3-Allenols with Electrophilic Halogen Reagents
FULL PAPERS
1H), 1.56–1.20 (m, 15H), 0.94–0.85 (m, 9H); 13C NMR
(100 MHz, CDCl3): d=143.9, 119.1, 96.1, 87.7, 76.5, 73.3,
34.9, 31.8, 30.9, 29.4, 28.8, 24.6, 22.6, 21.8, 21.0, 19.2, 14.1,
13.9, 13.5; IR (neat): n=2221, 1653, 1464, 1432, 1379, 1258,
1061 cmÀ1; MS (70 eV, EI): m/z (%)=276 (M+, 10.67), 191
(100); HR-MS: m/z=276.2443; calcd. for C19H32O:
276.2453.
chromatography on silica gel (petroleum ether/ethyl ace-
tate=100:1) afforded a mixture of 10a[12] and 12a; yield:
Suzuki Coupling of 6d with Phenylboronic Acid to
Afford 2-Hexyl-3-phenyl-4-propyl-2,5-dihydrofuran
(8a)
1
91.2 mg (80%) (10a:12aꢀ95:5, determined by H NMR).
1
The following data are discernible for 12a: H NMR: d=
5.78 (d, J=2.2 Hz, 1H), 5.63 (d, J=2.2 Hz, 1H).
3-Bromo-2-butyl-2-(1-naphthyl)-3-butenal (10k)
The reaction of 100.2 mg (0.4 mmol) of 5k and 1.6 mL (0.5m
in MeCN, 0.8 mmol) of Br2 in 2.4 mL of MeCN and 0.27 mL
of H2O at 08C for 30 min afforded a mixture of 10k and 12k
(90:10); yield: 108.1 mg (73%).
10k: oil, 1H NMR (300 MHz, CDCl3): d=9.86 (s, 1H),
8.15–8.09 (m, 1H), 7.95–7.83 (m, 2H), 7.55–7.41 (m, 4H),
6.26 (s, 1H), 6.04–5.95 (m, 1H), 2.55–2.41 (m, 1H), 2.35–
2.20 (m, 1H), 1.50–1.23 (m, 3H), 0.89 (t, J=6.9 Hz, 4H);
13C NMR (75 MHz, CDCl3): d=197.1, 134.5, 134.1, 133.3,
131.5, 129.5, 129.3, 126.5, 126.1, 125.7, 125.0, 124.9, 122.4,
64.9, 33.0, 27.1, 23.0, 13.9; IR (KBr): n=3050, 2957, 2714,
1731, 1599, 1510, 1466, 1397, 1343, 1095, 1025 cmÀ1; MS
(70 eV, EI): m/z (%)=332 [M+ (81Br), 0.22], 330 [M+ (79Br),
0.23], 303 [M+ (81Br)ÀCHO, 5.24], 301 [M+ (79Br)ÀCHO,
4.93], 165 (100); HR-MS (EI): m/z=330.0626, calcd. for
C18H1979BrO: 330.0619.
The mixture of 82.5 mg (0.25 mmol) of 6d, 62.0 mg
(0.5 mmol) of phenylboronic acid, 15.5 mg (5 mol%) of
Pd(PPh3)4, 0.1 mL of CH3OH, and 0.3 mL (2M in H2O) of
G
Na2CO3 in 2 mL of toluene was refluxed under N2 for 10 h
as monitored by TLC (petroleum ether/ethyl acetate=40:1).
Water (6 mL) was added and the reaction mixture was ex-
tracted with ether. The combined extract was washed with
saturated NaCl. After drying over Na2SO4, filtration, and
evaporation, the residue was purified by column chromatog-
raphy on silica gel to afford 8a as an oil; yield: 64.2 mg
1
(92%); H NMR (400 MHz, CDCl3): d=7.29 (t, J=7.2 Hz,
1
The following data are discernible for 12k: H NMR: d=
2H), 7.22–7.19 (m, 1H), 7.12 (d, J=8.0 Hz, 2H), 5.20–5.14
(m, 1H), 4.72 (dd, J1 =12.4, J2 =5.6 Hz, 1H), 4.64 (dd, J1 =
12.4, J2 =2.8 Hz, 1H), 2.20–2.09 (m, 2H), 1.49–1.14 (m,
12H), 0.83 (t, J=7.2 Hz, 3H), 0.77 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=135.05, 134.95, 134.8,
128.3, 128.2, 126.9, 88.8, 77.6, 34.6, 31.8, 29.3, 27.9, 24.7, 22.5,
21.5, 14.1, 14.0; IR (neat): n=1719, 1597, 1490, 1464, 1378,
1065 cmÀ1; MS (70 eV, EI): m/z (%)=272 (M+, 9.67), 271
(M+ÀH, 36.37), 187 (100); HR-MS: m/z=272.2144, calcd.
for C19H28O: 272.2135.
5.82 (d, J=2.2 Hz, 1H), 5.62 (d, J=2.2 Hz, 1H).
The reaction of 75.5 mg (0.3 mmol) of 5k and 64.2 mg
(0.36 mmol) of NBS in 4 mL of MeCN and 0.27 mL of H2O
at 08C for 50 min afforded a mixture of 10k and 12k (93:7);
yield: 75.8 mg (76%).
Reduction of Crude 3-Bromo-2-butyl-1-(1-naphthyl)-
3-buten-1-one (12k) with NaBH4; Synthesis of 3-
Bromo-2-butyl-1-(1-naphthyl)-3-buten-1-ol (18k)
Reaction of Secondary 2,3-Allenols (5) with X2 (or
NXS)
3-Bromo-2-butyl-2-phenyl-3-butenal (10a); Typical
Procedure
A solution of 38.3 mg of crude 12k obtained from chromato-
graphic separation and 3.5 mg (0.092 mmol) of NaBH4 in
3 mL of THF was stirred at room temperature for 26 h
(monitored by TLC, petroleum ether/ethyl acetate=5:1).
The mixture was then quenched with 2 mL of water fol-
lowed by extraction with diethyl ether (3”10 mL), washed
with saturated brine, and dried over anhydrous Na2SO4.
Evaporation and column chromatography on silica gel (pe-
troleum ether/ethyl acetate=20:1) afforded 18k as an oil;
To a solution of 82.4 mg (0.41 mmol) of 5a in 2.4 mL of
MeCN and 0.27 mL of H2O was added with stirring 1.6 mL
(0.5M in MeCN, 0.8 mmol) of Br2 at 08C for 30 min. After
complete consumption of the allenol as monitored by TLC,
the mixture was quenched with 6 mL of water followed by
the addition of a saturated aqueous solution of Na2S2O3, ex-
tracted with diethyl ether (25 mL”3), washed with NaCl,
and dried over anhydrous Na2SO4. Evaporation and column
Adv. Synth. Catal. 2008, 350, 1376 – 1382
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1381

Jing Li et al.
FULL PAPERS
1
yield: 26.5 mg (90%); H NMR (300 MHz, CDCl3): d=8.29 References
(d, J=8.1 Hz, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.82 (d, J=
8.1 Hz, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.56–7.43 (m, 3H),
5.91 (s, 1H), 5.75 (s, 1H), 5.36 (d, J=9.3 Hz, 1H), 2.86–2.74
(m, 1H), 2.28 (d, J=1.8 Hz, 1H), 1.49–1.32 (m, 1H), 1.23–
0.84 (m, 4H), 0.82–0.73 (m, 1H), 0.70 (t, J=6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=137.3, 136.7, 133.9, 131.5,
128.9, 128.6, 126.1, 125.6, 125.3, 123.8, 120.8, 77.4, 72.7, 57.3,
29.0, 28.9, 22.1, 13.8; IR (KBr): n=3446, 3048, 2955, 2858,
1625, 1597, 1511, 1465, 1394, 1378, 1260, 1225, 1166,
1046 cmÀ1; MS (70 eV, EI): m/z (%)=334 [M+ (81Br), 0.13],
332 [M+ (79Br), 0.12], 317 [M+ (81Br)ÀOH, 1.25], 315 [M+
(79Br)ÀOH, 1.15], 157 (100); elemental analysis: calcd. for
C18H21BrO (%): C 64.87, H 6.35; found: C 64.83, H 6.37.
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one (12r)
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The reaction of 56.4 mg (0.30 mmol) of 5r and 0.72 mL
(0.5M in MeCN, 0.36 mmol) of Br2 in 3.3 mL of MeCN and
0.27 mL of H2O at 08C for 30 min afforded 12r as an oil:
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1
yield: 66.2 mg (83%); H NMR (300 MHz, CDCl3): d=7.41–
7.27 (m, 5H), 6.07 (d, J=2.4 Hz, 1H), 5.94 (d, J=2.4 Hz,
1H), 2.29 (q, J=7.2 Hz, 1H), 2.29 (q, J=7.2 Hz, 1H), 2.10
(s, 3H), 0.91 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=205.0, 138.2, 135.2, 128.6, 128.4, 127.5, 122.4,
68.9, 27.3, 27.2, 9.3; IR (KBr): n=2975, 2880, 1713, 1617,
1495, 1438, 1078 cmÀ1; MS (70 eV, EI): m/z (%)=268 [M+
(81Br), 0.05], 266 [M+ (79Br), 0.05], 239 [M+ (81Br)ÀC2H5,
79
2.39], 237 [M+ ( Br) C2H5, 2.38], 129 (100); HR-MS: m/z=
À
291.0174, calcd. for C13H1581BrONa (M+ +Na): 291.0184,
289.0192, calcd for C13H1579BrONa (M+ +Na): 289.0204.
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Acknowledgements
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We gratefully acknowledge the National Natural Science
Foundation of China (No. 20572093), Zhejiang Provincial
Natural Science Foundation of China (Y 404262), and
Cheung Kong Scholar Program for financial support. We
thank Mr. Zhichao Ma in our group for reproducing the re-
sults presented in entries 4 and 5 of Table 3.
[16] S. Ma, W. Gao, J. Org. Chem. 2002, 67, 6104-6112.
1382
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ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 1376 – 1382