A facile synthesis of two series of multifunctional carbon compounds from α,α-dihalo ketones using allylsamarium bromide

Article abstract of DOI:10.1055/s-0029-1216913

The use of allylsamarium bromide to effect two different reactions on the common starting material, a,a-dihalo ketones, is presented. With DMF, α-halo-α-allyl aldehydes were obtained, while α-hydroxy- α-allyl aldehyde acetals were obtained in the presence of NaOMe/MeOH. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216913

PAPER
2749
A Facile Synthesis of Two Series of Multifunctional Carbon Compounds from
a,a-Dihalo Ketones Using Allylsamarium Bromide
Reactionof
a
,
a
-D
i
i
halo K
a
e
tones
w
ith
o
Allylsamari
d
umBromidean Liu, Songlin Zhang,* Jucai Di
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science,
Soochow University, Suzhou 215123, P. R. of China
Fax +86(512)65880352; E-mail: zhangsl@suda.edu.cn
Received 2 March 2009; revised 8 May 2009
O
R1
X
Abstract: The use of allylsamarium bromide to effect two different
reactions on the common starting material, a,a-dihalo ketones, is
presented. With DMF, a-halo-a-allyl aldehydes were obtained,
while a-hydroxy-a-allyl aldehyde acetals were obtained in the pres-
ence of NaOMe/MeOH .
SmBr
R2
R2
1)
, THF, 10 min
R1
2) base
Br
X
O
2
1
R1 = Ph, 4-FC6H4, 4-ClC6H4, 4-MeC6H4, Me(CH2)5
R2 = H, Me
X = Br, Cl
Key words: samarium, aldehydes, acetals, rearrangement, synthe-
sis
Scheme 1
The reactions of allylmetals with carbonyl compounds are
of interest to synthetic chemists. Homoallyl alcohols are
the usual products of these reactions,1 which may be
readily transformed into aldehydes, or can undergo a fac-
ile one-carbon homologation to a-lactones via hydro-
formylation, or be selectively epoxidized to introduce a
third chiral center. Compounds containing a carbon atom
bearing three or four different labile functional groups are
categorized as multifunctional carbon compounds.2–4
These compounds should be of considerable significance
in theoretical and synthetic organic chemistry. But little
attention has been paid to the synthesis of homoallylic al-
cohols containing other attractive functional groups utiliz-
ing these methods via multifunctional carbonyl
compounds. Considering the above reports, the develop-
ment of new and simple synthetic methods for the effi-
cient preparation of multifunctional carbon compounds is
therefore an interesting challenge. We report herein the
reaction of a,a-dihalo ketones with allylsamarium bro-
mide under different conditions to afford two series of
multifunctional carbon compounds, a-halo-a-allyl
aldehydes4 and a-hydroxy-a-allyl aldehyde acetals,
which, to our knowledge, have not been studied so far. It
is worth noting that, in the work presented here, allylsa-
marium(II) bromide reagent, which is well known to have
high reducing ability, can add to a,a-dibromo ketones
without reducing them. It is also different from other or-
ganometallic reagents (such as n-BuLi, PhMgBr, Et2Zn),
which often tend to support metal–halogen exchange re-
action.5
lowed by the addition of a base to give a-halo-a-allyl
aldehydes 2.
First, we investigated the effect of the base on the yield of
product 2a. The results are summarized in Table 1. Initial-
ly, without base, no desired aldehyde could be detected in
the reaction (Table 1, entry 1). Instead of the desired com-
pound, 1,1-dibromo-2-phenylpent-4-en-2-ol (3a) was ob-
tained after the reaction was quenched with water
(Scheme 2).
OH
O
SmBr
Br
Br
1)
, THF, 10 min
Ph
Ph
2) H2O
Br
Br
1a
3a
Scheme 2
Some bases such as K2CO3/MeOH, K2CO3/t-BuOH,
HNEt2, Et3N, pyridine, or NaOH had an effect to the reac-
tion, but yields were generally lower (Table 1, entries 3,
5–9). When DMF, DMSO, or HMPA was used, the yield
of product was very similar (Table 1, entries 10–13). The
effect of these additives can enhance the nucleophilicity
of the alkoxide by coordinating to samarium. After
screening different bases and additives, DMF appeared to
be a good choice and was used in this method. With the
optimized reaction conditions, a variety of a,a-dihalo ke-
tones were prepared and subjected to this reaction. The re-
sults are shown in Table 2.
When R2 = Me (Table 2, entry 7), the reaction gave a low-
er product yield (36%) and when R2 was even larger
(R2 = Ph, Table 2, entries 11, 12), no desired products
were obtained. Instead, a-halo ketones 5k, l were obtained
(Scheme 3), which might have formed by metal–halogen
exchange reaction or reductive reaction.5 When X = Cl
(Table 2, entry 5), the reaction also gave a lower product
As shown in Scheme 1, a,a-dihalo ketones 1 react with al-
lylsamarium bromide in THF at room temperature, fol-
SYNTHESIS 2009, No. 16, pp 2749–2755
x
x.
x
x
.
2
0
0
9
Advanced online publication: 23.07.2009
DOI: 10.1055/s-0029-1216913; Art ID: F05209SS
© Georg Thieme Verlag Stuttgart · New York

2750
X. Liu et al.
PAPER
Table 1 Comparison of the Effect of Bases in the Reaction of a,a-
Dibromo-1-phenylethanone with Allylsamarium Bromidea
yield (34%); the reason probably is that the Br is more re-
active than Cl. However, a,a-dihaloketone bearing a 4-ni-
tro or a 3-nitro group on the aromatic ring (Table 2, entries
8, 9), could not react with allylsamarium bromide. This
might be a result of the oxygen atom of substrate coordi-
nating with the Sm atom of allylsamarium bromide, which
hinders the reaction of allylsamarium bromide with sub-
strate. Meanwhile, no reaction of 2,2-dibromo-1-(2-chlo-
rophenyl)ethanone (1j) was observed under the same
conditions (Table 2, entry 10), probably due to the steric
hindrance in the substrate.
Entry
1
Base
Amount
–
Time (h) Yield (%)b
none
12
24
1
0
0
2
K2CO3
K2CO3
K2CO3
K2CO3
10 mmol
10 mmol
10 mmol
10 mmol
10 mL
10 mL
10 mL
10 mL
10 mL
10 mL
10 mL
10 mmol
c
c
d
3
39
0
4
10
12
2
5
12
34
32
7
e
6
HNEt2
Et3Ne
O
O
SmBr
Ph
1)
, THF, 10 min
7
1
Ph
Ph
Ph
2) DMF
X
Br
8
pyridinee
NaOH
1
X
5k, l
1k, l
9
10
0.25
0.25
0.25
12
16
52
54
52
53
k, X = Br, 67%
l, X = Cl, 65%
10
11
12
13
HMPAe
DMFe
Scheme 3
DMSOe
A possible mechanism is proposed in Scheme 4 according
to literature.6 First, the a,a-dihalo ketone A undergoes al-
lylation leading to the intermediate B. If the reaction was
quenched with water, the product C could be obtained. If
anhydrous DMF was added to the solution of B, the oxy-
gen atom of DMF would coordinate to the Sm atom of B.
This coordination results in the enhanced nucleophilicity
of the oxygen atom. Therefore, the intermediate B under-
goes intramolecular nucleophilic substitution to provide
an a-halo epoxide D, which gets converted into the de-
sired product E. When DMF was added to the solution of
compound C (using 3a, R1 = Ph, R2 = H, X = Br) in THF,
and the reaction mixture was stirred for 10 hours, no reac-
tion occurred. However, initial deprotonation of com-
pound C using 1.5 equivalents of allylsamarium bromide
in THF, followed by the addition of anhydrous DMF, can
also lead to the desired aldehyde E (2a).
f
CaH2
a All reactions were carried out in THF at r.t.
b Isolated yields based on a,a-dibromo ketones.
c MeOH (10 mL) was added to the reaction mixture.
d t-BuOH (10 mL) was added to the reaction mixture.
e Distilled from sodium or CaH2 under N2.
f DMSO (10 mL) was added to the reaction mixture.
Table 2 Reactions of a,a-Dihalo Ketones with Allylsamarium Bro-
mide Followed by Addition of DMF
Entry
1
2
Yield
(%)a
1
2
1a (R1 = Ph, R2 = H, X = Br)
2a
2b
2c
2d
2e
2f
2g
–
54
1b (R1 = 4-MeC6H4, R2 = H, X = Br)
1c (R1 = 4-FC6H4, R2 = H, X = Br)
1d (R1 = 4-ClC6H4, R2 = H, X = Br)
1e (R1 = 4-ClC6H4, R2 = H, X = Cl)
1f (R1 = Me(CH2)5, R2 = H, X = Br)
1g (R1 = Ph, R2 = Me, X = Br)
41
It is interesting that when K2CO3 together with MeOH or
t-BuOH were used in the reaction (Table 1, entries 3 and
5), the yield of 2a depended on the reaction time
(Scheme 5). When the reaction time was one hour, the
yield of the aldehyde 2a was 39% and 1,1-dimethoxy-2-
phenylpent-4-en-2-ol (4a) was also obtained in 5% yield.
If the reaction mixture was stirred for five hours, 2a was
not detected and 4a was obtained in a yield of 56%. Com-
pound 4a is also one of the multifunctional carbon com-
pounds; we therefore investigated the effect of different
bases on the synthesis of 4a (Scheme 6, Table 3).
3
45
4
52
5
34
6
49
7
36
8
1h (R1 = 4-NO2C6H4, R2 = H, X = Br)
1i (R1 = 3-NO2C6H4, R2 = H, X = Br)
1j (R1 = 2-ClC6H4, R2 = H, X = Br)
1k (R1 = Ph, R2 = Ph, X = Br)
n.r.
n.r.
n.r.
0 (67)b
0 (65)c
9
–
10
11
12
–
The yield of the product depends on the strength of the
base. NaOAc, Et3N, and pyridine did not have any effect
on the reaction (Table 3, entries 1, 10, and 11), while the
other bases such as Cs2CO3, NaOH, or CaH2 can promote
this reaction with lower yields (Table 3, entries 4–6).
When NaH or NaOMe was used, the yields were very
similar (Table 3, entries 7–9). After screening different
bases, NaOMe appeared to be the best choice for this re-
action.
–
1l (R1 = Ph, R2 = Ph, X = Cl)
–
a Isolated yields based on a,a-dihalo ketones.
b Yield of 5k.
c Yield of 5l.
Synthesis 2009, No. 16, 2749–2755 © Thieme Stuttgart · New York

PAPER
Reaction of a,a-Dihalo Ketones with Allylsamarium Bromide
2751
R2 Br
O
R2 Br
SmBr
R2
X
DMF
R1
R1 OSmBr
X
R1 OSmBr
Br
X
NMe2
H
A
O
B
H2O
SmBr2
R2 Br
X
O
DMF
X
R2
R1 OH
R1
R1 = Ph, R2 = H, X = Br
X
C
D
SmBr
DMF
R2 Br
R1
X
R2
X
R1 OSmBr
O
B
E
Scheme 4
SmBr
O
Table 3 Comparison of the Effect of Bases in the Reaction of
a,a-Dibromo-1-phenylethanone with Allylsamarium Bromide and
MeOHa,b
1)
Br
HO
Ph
CH(OMe)2
THF, 10 min
Br
CHO
Ph
+
2) K2CO3, MeOH, THF
Ph
Br
Time (h) Yield (%)c
1a
2a
4a
Entry
Base
Time (h)
1
5
39%
0
5%
56%
1
2
NaOAc (10 mmol)
Na2CO3 (10 mmol)
K2CO3 (10 mmol)
Cs2CO3 (10 mmol)
NaOH (10 mmol)
CaH2 (10 mmol)
NaH (10 mmol)
NaOMe (10 mmol)
NaOMe (5 mmol)
pyridine (10 mL)d
Et3N (10 mL)d
24
12
5
0
trace
56
70
34
50
82
83
82
0
Scheme 5
3
O
4
5
HO
R1
CH(OR3)2
SmBr
1)
, THF, r.t.
Br
R1
2) base, R3OH, THF, r.t.
5
12
5
X
R1 = Ph, 4-MeC6H4, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4,
6
4-BrC6H4, 2-naphthyl, Me(CH2)5
R3 = Me, Et
X = Br, Cl
7
5
8
4
Scheme 6
9
4
As shown in Scheme 7, when 2,2-dibromo-1-phenyleth-
anone (1a) was treated with allylsamarium bromide and
NaOMe/MeOH, the yield of product 4a was related to the
reaction time. When the reaction was run for 15 minutes,
4a was obtained in a yield of 5% and 2-bromo-2-phenyl- b MeOH (10 mL) distilled from Mg was added to the reaction mixture.
pent-4-enal (2a) was formed as the main product (39%).
When the reaction mixture was stirred for four hours, 2a
10
11
12
12
0
a All reactions were carried out in THF at r.t.
c Isolated yields based on a,a-dibromo ketones.
d Distilled from sodium or CaH2 under N2.
could not be detected and 4a was obtained in a yield of
83%.
The reaction of 1,1-dibromo-2-phenylpent-4-en-2-ol (3a)
with NaOMe in MeOH at room temperature was also in-
vestigated (Scheme 8). When the reaction time was 15
minutes, the yield of the aldehyde, 2-bromo-2-phenyl-
pent-4-enal (2a), was 34% and 1,1-dimethoxy-2-phenyl-
pent-4-en-2-ol (4a) was obtained simultaneously in a
yield of 6%. When the reaction mixture was stirred for
four hours, 2a was not detected and 4a was obtained in a
yield of 85%.
O
SmBr
THF, 10 min
1)
Br
Br
CHO
HO
Ph
CH(OMe)2
Ph
+
Ph
2) MeONa, MeOH
Br
1a
2a
4a
Time (h)
0.25
4
39%
0
5%
83%
Scheme 7
Synthesis 2009, No. 16, 2749–2755 © Thieme Stuttgart · New York

2752
X. Liu et al.
PAPER
OH
Table 4 Different a-Hydroxy-a-allyl Aldehyde Acetals 4 from a,a-
Dihalo Ketones a
Br
Br
CHO
HO
Ph
CH(OMe)2
NaOMe
Ph
+
MeOH, r.t.
R3
4
Yield (%)b
Ph
Br
Entry
1
3a
2a
4a
1
2
1a R1 = Ph, X = Br
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
4a
4b
4c
4d
4d
4f
82
83
85
84
82
81
83
78
82
56
Time (h)
0.25
4
34%
0
6%
85%
1b R1 = 4-MeC6H4, X = Br
1c R1 = 4-FC6H4, X = Br
1d R1 = 4-ClC6H4, X = Br
1e R1 = 4-ClC6H4, X = Cl
1f R1 = Me(CH2)5, X = Br
1m R1 = 4-BrC6H4, X = Br
1n R1 = 4-MeOC6H4, X = Br
1o R1 = 2-naphthyl, X = Br
1p R1 = Ph, X = Br
3
Scheme 8
4
Under the same reaction condition, 2a was converted into
1,1-dimethoxy-2-phenylpent-4-en-2-ol (4a) in a yield of
88% (Scheme 9).
5
6
7
4m
4n
4o
4p
Br
CHO
HO
Ph
CH(OMe)2
NaOMe
MeOH, r.t.
Ph
8
2a
4a
9
Scheme 9
10
a All reactions were carried out at r.t.
b Isolated yields.
Based on the experimental results, a plausible pathway for
the formation of 4 is illustrated in Scheme 10.6 First, the
a,a-dihalo ketone A undergoes allylation leading to the
product C. The product C undergoes intramolecular nu-
cleophilic substitution providing an a-halo epoxide D,
which gets converted into the a-halo-a-allyl aldehyde E.
The a-halo aldehyde E was converted into the terminal
product G by successive nucleophilic attack of methoxide
anion on the aldehyde E and on the generated a-methoxy-
epoxide F.
Both electron-donating and electron-withdrawing substit-
uents on the aryl unit were tolerated (Table 4, entries 1–4,
7–9); in addition, when X = Cl (Table 4, entry 5), the re-
action gives a similar product yield. The aliphatic sub-
strate (Table 4, entry 6) can also be converted into the
corresponding product in satisfactory yield. When EtOH
was used instead of MeOH (Table 4, entry 10), a consid-
erable decrease in yield took place (56%).
OH
O
In addition, some other organometallic reagents were tried
in the experiment in the hope of obtaining results with a
similar reaction type. We found that when 2,2-dibromo-1-
phenylethanone (1a) was treated with allylzinc bromide
reagent7 or allylindium bromide reagent8 (Allyl3In2Br3)
under the same condition no desired product was detected.
And we also found that the Reformatsky reagent9
(BrZnCH2CO2Et) and Grignard reagent (4-MeC6H4MgBr)
did not react with 2,2-dibromo-1-phenylethanone (1a) in
THF at room temperature.
O
R1
1) AllylSmBr
2) MeOH
NaOMe
Br
R1
Br
X
R1
X
X
A
C
D
X= Br, Cl
X
O
R1
R1
NaOMe
CHO
HO CH(OMe)2
R1
NaOMe
MeOH
OMe
MeOH
In conclusion, the reaction of allylsamarium bromide with
various a,a-dihalo ketones provided a convenient and rap-
id access to two series of trifunctional carbon compounds,
a-halo-a-allyl aldehydes and a-hydroxy-a-allyl aldehyde
acetals, under different reaction conditions. The advan-
tages, such as low reaction temperature, fast reaction rate,
and one-pot operation make this method an attractive and
practical synthesis for multifunctional carbon com-
pounds.
G
F
E
Scheme 10
With these preliminary results in hand, we paid our atten-
tion to a wide scope of a,a-dihalo ketones 1 under the op-
timized reaction condition (Scheme 11). The results are
shown in Table 4.
O
SmBr
THF and Et3N were distilled from sodium benzophenone under N2.
HNEt2 was distilled from Na under N2. DMF, DMSO, and HMPA
were distilled from CaH2 under N2. MeOH was distilled form Mg
under N2. All reactions were conducted under a N2 atmosphere. Me-
tallic samarium and all solvents were purchased from commercial
sources, and used without further purification. Flash column chro-
matography was carried out on Merck silica gel (300–400 mesh). 1H
and 13C NMR spectra were recorded on a Varian Mercury 400 MHz
HO
R1
CH(OR3)2
1)
, THF, r.t.
Br
R1
2) NaOR3, R3OH, THF, r.t.
X
1
4
Scheme 11
Synthesis 2009, No. 16, 2749–2755 © Thieme Stuttgart · New York

PAPER
Reaction of a,a-Dihalo Ketones with Allylsamarium Bromide
2753
spectrometer as solutions in CDCl3. Chemical shifts in H NMR
spectra are reported in parts per million (ppm, d) downfield from the
internal standard Me4Si (TMS). Chemical shifts in 13C NMR spectra
are reported relative to the central line of the CHCl3 signal
(d = 77.50). High-resolution mass spectra were obtained with a
GCT-TOF instrument. The starting material 1f was prepared by
published methods,10 others by bromination of respective ketones.
Other chemicals were purchased from Aldrich or Acros chemical
company and used without further purification.
1H NMR (400 MHz, CDCl3): d = 9.44 (s, 1 H), 7.32–7.17 (m, 4 H),
5.73–5.63 (m, 1 H), 5.10–5.05 (m, 2 H), 3.10 (d, J = 6.8 Hz, 2 H),
2.35 (s, 3 H).
1
13C NMR (100 MHz, CDCl3): d = 190.41, 139.27, 132.77, 132.70,
129.92, 128.43, 120.00, 74.06, 43.22, 21.44.
HRMS (EI+): m/z calcd for C12H1381BrO [M+]: 254.0129; found:
254.0130; m/z calcd for C12H1379BrO [M+]: 252.0150; found:
252.0162.
2-Bromo-2-(4-fluorophenyl)pent-4-enal (2c)
IR (KBr): 3086, 2924, 2831, 2723, 1728, 1643, 1589, 1489, 1427,
1002, 925, 825 cm–1.
a,a-Dibromo Ketones; General Procedure
A solution of ketone (10 mmol) in glacial AcOH (10 mL) was heat-
ed to 50 °C with stirring, and Br2 (22 mmol) in glacial AcOH (5 mL)
was added dropwise. When the decoloration of Br2 had ceased,
NaOAc (7 g) was added in portions. The reaction mixture was
stirred for 15 min after the addition of Br2, and cooled in a refriger-
ator for 2 h, and then poured into cold H2O (100 mL). The crystals
formed were collected by filtration and recrystallized from 95%
MeOH, if necessary.
1H NMR (400 MHz, CDCl3): d = 9.46 (s, 1 H), 7.44–7.06 (m, 4 H),
5.72–5.63 (m, 1 H), 5.13–5.06 (m, 2 H), 3.10 (d, J = 3.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 190.23, 163.14 (1JC,F = 248.2
Hz), 132.36, 131.66, 130.58 (3JC,F = 8.4 Hz), 120.53, 116.26
(2JC,F = 21.7 Hz), 73.11, 43.47.
HRMS (EI+): m/z calcd for C11H1081BrFO [M+]: 257.9879; found:
257.9884; m/z calcd for C11H1079BrFO [M+]: 255.9899; found:
255.9874.
1,1-Dibromo-2- phenylpent-4-en-2-ol (3a)
Allyl bromide(1.2 mmol) and Sm (1.1 mmol) were mixed in anhyd
THF (10 mL) under N2 at r.t. The mixture was stirred for about 1 h
until the Sm powder had disappeared. 2,2-Dibromo-1-phenyleth-
anone (1a; 278 mg, 1 mmol) in THF (3 mL) was added dropwise.
The mixture was stirred for 10 min, then quenched with MeOH (10
mL) to give 3a; yield: 293 mg (92%).
2-Bromo-2-(4-chlorophenyl)pent-4-enal (2d)
IR (KBr): 3078, 2916, 2831, 2729, 1728, 1643, 1589, 1489, 1427,
1095, 1010, 925, 825 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.45 (s, 1 H), 7.37 (m, 4 H), 5.71–
5.61 (m, 1 H), 5.13–5.06 (m, 2 H), 3.09 (d, J = 3.2 Hz, 2 H).
1H NMR (400 MHz, CDCl3): d = 7.46–7.30 (m, 5 H), 5.98 (s, 1 H),
5.56–5.46 (m, 1 H), 5.15–5.05 (m, 2 H), 2.92 (d, J = 6.8 Hz, 2 H),
2.83 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 190.06, 135.48, 134.33, 132.21,
130.06, 129.44, 120.66, 73.06, 43.36.
13C NMR (100 MHz, CDCl3): d = 140.55, 132.39, 128.59, 128.34,
126.58, 120.55, 78.99, 57.68, 43.89.
HRMS (EI+): m/z calcd for C11H1079Br35ClO [M+]: 271.9604; found:
271.9599; m/z calcd for C11H1081Br35ClO [M+]: 273.9583; found:
273.9567.
HRMS (EI+): m/z calcd for C8H779Br81BrO [M+ – C3H5]: 278.8843;
found: 278.8813.
2-Chloro-2-(4-chlorophenyl)pent-4-enal (2e)
IR (KBr): 3093, 2901, 2834, 2715, 1735, 1643, 1597, 1496, 1095,
1010, 925, 825 cm–1.
a-Halo,a-allyl Aldehydes 2; General Procedure
Allyl bromide(1.2 mmol) and Sm (1.1 mmol) were mixed in anhyd
THF (10 mL) under N2 at r.t. The mixture was stirred for about 5
min, and a purple color was formed. The stirring was continued un-
til the Sm powder had disappeared (1 h). Then a solution of the sub-
strate a,a-dihalo ketone was added dropwise and the reaction was
monitored by TLC. The reaction mixture was stirred for 10 min and
then anhyd DMF (10 mL) was added. The mixture was stirred for
another 15 min (when X = Cl, the mixture was stirred for 10 h) and
then poured into cold H2O (10 mL) and 5% HCl (10 mL) was added.
The resulting mixture was extracted with Et2O (4 × 15 mL) and the
combined Et2O layers were dried (MgSO4). The solvent was re-
moved by evaporation under reduced pressure. Purification of the
residue by column chromatography on silica gel [300–400 mesh,
eluent: petroleum ether (bp 60–90 °C)] afforded the product.
1H NMR (400 MHz, CDCl3): d = 9.39 (s, 1 H), 7.38 (m, 4 H), 5.70–
5.61 (m, 1 H), 5.13–5.08 (m, 2 H), 3.01 (d, J = 6.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 191.92, 135.47, 134.09, 131.26,
129.48, 129.08, 120.83, 77.18, 42.91.
HRMS (EI+): m/z calcd for C11H1035Cl2O [M+]: 228.0109; found:
228.0112; m/z calcd for C11H1035Cl37ClO [M+]: 230.0079; found:
230.0141.
2-Allyl-2-bromooctanal (2f)
IR (KBr): 3086, 2931, 2862, 2723, 1728, 1643, 1465, 1381, 995,
925 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.39 (s, 1 H), 5.84–5.74 (m, 1 H),
5.21–5.17 (m, 2 H), 2.77 (t, J = 6.8 Hz, 2 H), 2.01–1.91 (m, 2 H),
1.29–1.45 (m, 8 H), 0.88 (t, J = 6.3 Hz, 3 H).
2-Bromo-2-phenylpent-4-enal (2a)
IR (KBr): 3080, 2901, 2834, 2728, 1732, 1649, 1601, 1488, 1450,
995, 918, 752, 694 cm–1.
13C NMR (100 MHz, CDCl3): d = 193.98, 132.50, 120.29, 73.39,
40.77, 36.72, 31.92, 29.68, 25.61, 22.96, 14.48.
1H NMR (400 MHz, CDCl3): d = 9.47 (s, 1 H), 7.44–7.34 (m, 5 H),
5.74–5.60 (m, 1 H), 5.11–5.05 (m, 2 H), 3.11 (d, J = 9.2 Hz, 2 H).
HRMS (EI+): m/z calcd for C11H1981BrO [M+]: 248.0599; found:
248.0952; m/z calcd for C11H1979BrO [M+]: 248.0619; found:
248.0674.
13C NMR (100 MHz, CDCl3): d = 190.37, 135.63, 132.61, 129.23,
129.29, 128.58, 120.23, 74.06, 43.39.
HRMS (EI+): m/z calcd for C11H1181BrO [M+]: 239.9973; found:
240.0038; m/z calcd for C11H1179BrO [M+]: 237.9993; found:
238.0006.
3-Bromo-3-phenylhex-5-en-2-one (2g)
IR (KBr): 3087, 2923, 2834, 2702, 1729, 1639, 1607, 1514, 1431,
992, 925, 816 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.42–7.29 (m, 5 H), 5.64–5.54 (m,
1 H), 5.03–4.97 (m, 2 H), 3.15–3.01 (m, 2 H), 2.21 (s, 3 H).
2-Bromo-2-p-tolylpent-4-enal (2b)
IR (KBr): 3087, 2923, 2834, 2702, 1729, 1639, 1607, 1514, 1431,
992, 925, 816 cm–1.
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13C NMR (100 MHz, CDCl3): d = 201.48, 137.83, 133.26, 129.08,
128.72, 127.77, 119.61, 75.79, 46.10, 26.32.
HRMS (EI+): m/z calcd for C13H1535ClO2 [M+ – H2O]: 238.0761;
found: 238.0762.
HRMS (EI+): m/z calcd for C12H1379BrO [M+]: 252.0150; found:
252.0138; m/z calcd for C12H1381BrO [M+]: 254.0129; found:
254.0159.
4-(Dimethoxymethyl)dec-1-en-4-ol (4f)
IR (KBr): 3587, 3502, 3078, 2954, 2931, 2862, 1643, 1465, 1080,
979, 918 cm–1.
a-Hydroxy-a-allyl Aldehyde Acetals 4; General Procedure
Allyl bromide (1.2 mmol) and Sm (1.1 mmol) were mixed in anhyd
THF (10 mL) under N2 at r.t. The mixture was stirred for about 10
min, and a purple color was formed. The stirring was continued un-
til the Sm powder had disappeared (1 h). Then a solution of the sub-
strate a,a-dihalo ketone was added dropwise (the reaction was
monitored by TLC). The reaction mixture was stirred for 10 min and
then MeOH (or EtOH) (10 mL) was added followed by NaOMe (or
NaOEt) (5 mmol) in portions. The mixture was stirred for 4 h and
filtered. The solvent was removed by evaporation under reduced
pressure to give the crude product as an oil, which was purified by
column chromatography on silica gel (eluent: PE–EtOAc, 15:1).
1H NMR (400 MHz, CDCl3): d = 5.94–5.84 (m, 1 H), 5.11–5.06 (m,
2 H), 4.12 (s, 1 H), 3.54 (d, J = 1.2 Hz, 6 H), 2.32–2.29 (m, 2 H),
2.05 (s, 1 H), 1.52–1.48 (m, 2 H), 1.38–1.28 (m, 8 H), 0.88 (t,
J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 134.59, 118.23, 110.04, 76.31,
58.61 (d, J = 4.2 Hz), 39.90, 35.21, 32.26, 30.43, 23.23, 23.08,
14.54.
HRMS (EI+): m/z calcd for C13H24O2 [M+ – H2O]: 212.1776; found:
212.1779.
2-(4-Bromophenyl)-1,1-dimethoxypent-4-en-2-ol (4m)
IR (KBr): 3558, 3078, 2937, 2839, 1643, 1604, 1496, 1450, 1188,
1072, 979, 918, 833 cm–1.
1,1-Dimethoxy-2-phenylpent-4-en-2-ol (4a)
IR (KBr): 3556, 3070, 2939, 2839, 1643, 1604, 1496, 1450, 1188,
1149, 1072, 979, 918, 763, 702 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47–7.38 (m, 4 H), 5.65–5.54 (m,
1 H), 5.10–5.02 (m, 2 H), 4.21 (s, 1 H), 3.43 (d, J = 19.2 Hz, 6 H),
2.77–2.61 (m, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.52–7.21 (m, 5 H), 5.68–5.57 (m,
1 H), 5.08–4.98 (m, 2 H), 4.24 (s, 1 H), 3.38 (d, J = 14.8 Hz, 6 H),
2.81–2.65 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 141.54, 133.33, 131.31, 128.81,
121.53, 119.31, 110.61, 77.87, 58.60 (d, J = 13.8 Hz), 41.21.
13C NMR (100 MHz, CDCl3): d = 142.57, 133.90, 128.29, 127.37,
126.88, 118.90, 110.85, 78.11, 58.41 (d, J = 10.1 Hz), 41.30.
HRMS (EI+): m/z calcd for C13H1579BrO2 [M+ – H2O]: 282.0255;
found: 282.0245; m/z calcd for C13H1581BrO2 [M+ – H2O]:
284.0235; found: 284.0235.
HRMS (EI+): m/z calcd for C13H16O2 [M+ – H2O]: 204.1150; found:
204.1156.
1,1-Dimethoxy-2-(4-methoxyphenyl)pent-4-en-2-ol (4n)
IR (KBr): 3556, 3078, 2954, 2839, 1612, 1512, 1465, 1249, 1180,
1080, 979, 918, 833 cm–1.
1,1- Dimethoxy-2-p-tolylpent-4-en-2-ol (4b)
IR (KBr): 3564, 3078, 2931, 2839, 1643, 1512, 1450, 1188, 1149,
1080, 979, 918, 817 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.44–6.86 (m, 4 H), 5.69–5.58 (m,
1 H), 5.10–5.01 (m, 2 H), 4.21 (s, 1 H), 3.80 (s, 3 H), 3.41 (d,
J = 22.4 Hz, 6 H), 2.81–2.61 (m, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.40–7.13 (m, 4 H), 5.68–5.57 (m,
1 H), 5.10–5.00 (m, 2 H), 4.23 (s, 1 H), 3.41 (d, J = 14.8 Hz, 6 H),
2.81–2.62 (m, 3 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 158.83, 134.49, 133.91, 128.02,
118.86, 113.57, 111.04, 77.82, 58.48 (d, J = 23.5 Hz), 55.54, 41.06.
13C NMR (100 MHz, CDCl3): d = 139.51, 136.83, 133.96, 129.02,
126.74, 118.83, 110.94, 77.96, 58.42 (d, J = 15.5 Hz), 41.25, 21.47.
HRMS (EI+): m/z calcd for C14H18O3 [M+ – H2O]: 234.1256; found:
234.1262.
HRMS (EI+): m/z calcd for C14H20O3 [M+]: 236.1412; found:
236.1414.
1,1-Dimethoxy-2-(naphthalen-2-yl)pent-4-en-2-ol (4o)
IR (KBr): 3564, 3062, 2939, 2831, 1643, 1543, 1450, 1072, 972,
910, 748, 694 cm–1.
2-(4-Fluorophenyl)-1,1-dimethoxypent-4-en-2-ol (4c)
IR (KBr): 3564, 3078, 2939, 2839, 1643, 1604, 1512, 1450, 1226,
1188, 1072, 979, 918, 840 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.03–7.42 (m, 7 H), 5.65–5.59 (m,
1 H), 5.12–4.98 (m, 2 H), 4.33 (s, 1 H), 3.39 (d, J = 13.6 Hz, 6 H),
2.94–2.74 (m, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.51–6.99 (m, 4 H), 5.66–5.56 (m,
1 H), 5.10–5.02 (m, 2 H), 4.21 (s, 1 H), 3.43 (d, J = 22.8 Hz, 6 H),
2.79–2.63 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 140.13, 133.78, 133.59, 132.94,
128.82, 127.91, 127.83, 126.31, 126.27, 125.91, 125.20, 119.11,
110.89, 78.34, 58.49 (d, J = 11.1 Hz), 41.29.
13C NMR (100 MHz, CDCl3): d = 162.28 (1JC,F = 243.7 Hz), 138.13
(4JC,F = 3.1 Hz), 133.52, 128.64 (3JC,F = 7.9 Hz), 119.16, 115.00
(2JC,F = 20.9 Hz), 110.86, 77.82, 58.56 (d, J = 18.1 Hz), 41.25.
HRMS (EI+): m/z calcd for C17H18O2 [M+ – H2O]: 254.1307; found:
254.1309.
HRMS (EI+): m/z calcd for C13H15FO2 [M+ – H2O]: 222.1056;
found: 222.1060.
1,1-Diethoxy-2-phenylpent-4-en-2-ol (4p)
IR (KBr): 3587, 3078, 2939, 2839, 1643, 1597, 1496, 1450, 1188,
1149, 1080, 979, 918, 752, 694 cm–1.
2-(4-Chlorophenyl)-1,1-dimethoxypent-4-en-2-ol (4d)
IR (KBr): 3556, 3078, 2939, 2839, 1643, 1597, 1496, 1450, 1188,
1080, 979, 918, 833 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.53–7.22 (m, 5 H), 5.70–5.59 (m,
1 H), 5.10–4.99 (m, 2 H), 4.36 (s, 1 H), 3.79–3.67 (m, 2 H), 3.46–
3.29 (m, 2 H), 2.87–2.68 (m, 3 H), 1.15 (t, J = 6.8 Hz, 6 H).
1H NMR (400 MHz, CDCl3): d = 7.46–7.27 (m, 4 H), 5.63–5.57 (m,
1 H), 5.07–4.99 (m, 2 H), 4.20 (s, 1 H), 3.40 (d, J = 19.6 Hz, 6 H),
2.79–2.65 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 142.55, 134.12, 128.20, 127.29,
127.01, 118.65, 108.38, 77.93, 66.39 (d, J = 5.0 Hz), 40.80, 15.73
(d, J = 12.3 Hz).
13C NMR (100 MHz, CDCl3): d = 141.02, 133.38, 133.29, 128.45,
128.40, 119.32, 110.72, 77.86, 58.61 (d, J = 13.9 Hz), 41.27.
HRMS (EI+): m/z calcd for C15H20O2 [M+ – H2O]: 232.1463; found:
232.1470.
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Reaction of a,a-Dihalo Ketones with Allylsamarium Bromide
2755
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Acknowledgment
We thank the Program for Hi-Tech Research of Jiangsu Science and
Technology Department (BE2008063), Innovation Fund for Small
Technology-based Firms (08C26223201851), Innovator Fund of
Suzhou Government (ZXJ0726), Suzhou LAC Co., LTD, and Suz-
hou Chiral Chemistry Co., LTD (www.suzhoulac.com) for financial
support.
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Synthesis 2009, No. 16, 2749–2755 © Thieme Stuttgart · New York