Studies on ZnBr2-mediated synthesis of axially chiral aryl-substituted allenes from terminal alkynes, aromatic aldehydes and (S)-α,α-diphenylprolinol

Article abstract of DOI:10.1016/j.tet.2013.07.021

The studies on the ZnBr₂-mediated synthesis of axially chiral aryl-substituted allenes from terminal alkynes, aromatic aldehydes, and commercially available chiral amine (S)-α,α-diphenylprolinol were conducted. Axially chiral aryl-substituted a

Full text of DOI:10.1016/j.tet.2013.07.021

Tetrahedron 69 (2013) 8959e8963
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Studies on ZnBr2-mediated synthesis of axially chiral
aryl-substituted allenes from terminal alkynes, aromatic
aldehydes and (S)-a,a-diphenylprolinol
a
b
b
a,b,
*
€
Juntao Ye , Ruizhi Lu , Wu Fan , Shengming Ma
a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
Shanghai 200032, PR China
b Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University,
3663 North Zhongshan Lu, Shanghai 200062, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The studies on the ZnBr2-mediated synthesis of axially chiral aryl-substituted allenes from terminal
alkynes, aromatic aldehydes, and commercially available chiral amine (S)-a,a-diphenylprolinol were
conducted. Axially chiral aryl-substituted allenes can be obtained in moderate yields with up to 96% ee.
Received 16 April 2013
Received in revised form 28 June 2013
Accepted 8 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 12 July 2013
Keywords:
Allene
Axially chiral
Asymmetric synthesis
a,a-Diphenylprolinol
Zinc bromide
1. Introduction
1H NMR analysis (a, Scheme 1). To expand the scope as well as dem-
onstrate the practicability of this ‘chiral amine’ approach, we recently
Allenes have become a very important class of basic organic
compounds in organic synthesis, pharmaceutical chemistry, and
materials science.1 However, efficient methods for the synthesis of
opticallyactive allenes, especially thosewithan axial chirality, are still
highly desirable.2e4 Recently, we have developed two convenient
approaches for the synthesis of axially chiral 1,3-disubstituted allenes
from terminal alkynes and aldehydes utilizing the ‘chiral ligand’
approach4a or ‘chiral amine’ approach4b,c based on our previously
reported ZnI2-promoted one-pot synthesis of 1,3-disubstituted
allenes from terminal alkynes, aldehydes and morphine.5 While the
developed a highly enantioselective synthesis of axially chiral
allenolsfromTBS-protectedpropargylicalcoholsandaldehydesinthe
presence of (S)- -diphenylprolinol 3 or its enantiomer, inwhich the
a-
a,a
‘chiral amine’ approach utilizing (S)-a,a-diphenylprolinol 3 repre-
sents a highly efficient protocol for the synthesis of axially chiral
1,3-disubstituted allenes from terminal alkynes and aldehydes, our
preliminary study revealed that the substrate scope is quite limited.
For example, the reaction of aromatic aldehydes such as benzalde-
hyde 2b afforded the corresponding product (R)-4bb inverylow yield
with moderate ee whereas the reaction of unprotected propargyl al-
cohol 1c only afforded trace amount of the product as determined by
* Corresponding author. Tel./fax: þ86 21 6260 9305; e-mail address: masm@
Scheme 1. Synthesis of axially chiral allenes using (S)-a,a-diphenylprolinol 3.
sioc.ac.cn (S. Ma).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.021

8960
J. Ye et al. / Tetrahedron 69 (2013) 8959e8963
TBS group is not only acting as a protecting group, but also as a steric-
dictating group.4b Again, aliphatic aldehydes proved to be the more
compatible with this procedure as the reactions of aromatic alde-
hydes provided very low yields of the corresponding aryl-substituted
allenes (b, Scheme 1).4b
reaction, 1.5 equiv of terminal alkyne and 2.0 equiv of aromatic
aldehydes in the presence of 1.0 equiv of (S)- -diphenylprolinol
3 and ZnBr2 were defined as the standard conditions for substrates
a,a
scope evaluation (entry 3, Table 2).
Table 2
Optimization of the reaction conditionsa
2. Results and discussion
Surprisingly, we noticed that Periasamy et al. reported a similar
procedure for the synthesis of axially chiral 1,3-disubstituted
allenes from both aliphatic and aromatic aldehydes in the pres-
ence of (S)-
that stirring the solution of ZnBr2, (S)-a,a-diphenylprolinol 3, and
a,a
-diphenylprolinol 3.6 In their paper, they claimed
Entry
Ratio of 1d/2b/(S)-3
(R)-4db
Yieldb (%)
eec (%)
terminal alkynes in toluene for 10 min at 120 ꢀC followed by the
addition of aldehydes at room temperature and then gradually
heated to 120 ꢀC from room temperature are very important for the
high yields and ees for aryl-substituted allenes. However, we have
not been able to reproduce their results in terms of yield and ee, for
example, in the reaction of 1-decyne 1d with benzaldehyde 2b,
even after examining with several different well-known sources of
ZnBr2 with different purity (entry 1 vs entries 2e5, Table S1 in
Supplementary data). Furthermore, we also noticed that the re-
action time had an obvious influence on both the yield and enan-
tiomeric excess of the aryl-substituted allene product (R)-4db
(Table 1): when the reaction time was prolonged from 4 h to 16 h,
the yield of (R)-4db improved from less than 7e33% whereas the ee
of (R)-4db dropped from 96% to 84%, indicating that the axially
chiral aryl-substituted allene product (R)-4db underwent in situ
racemization under this set of reaction conditions.7 Herein we wish
to disclose our own observation on this ZnBr2-mediated reaction.
1
2
3
4
5
6
1.3:1:1
1.5:1:1
1.5:2:1
1.5:2.2:1
1.2:2:1
1.7:2:1
43
47
42
33
39
44
91
91
94
96
94
94
a
The reactions were carried out by adding ZnBr2 (1.0 mmol), (S)-3 (1.0 mmol), 1-
decyne 1d (1.2e1.7 mmol)/toluene (2 mL), and benzaldehyde 2b (1e2.2 mmol)/
toluene (1 mL) sequentially under Ar atmosphere at rt, heating for 2.5 h at 90 ꢀC
followed by 6 h at 120 ꢀC.
b
Isolated yield of (R)-4db.
Determined by chiral HPLC analysis.
c
The optimized reaction conditions are applicable to a reasonably
range of electron-poor and -rich aromatic aldehydes (Table 3):
halogen-substituted aromatic aldehydes with a Br, Cl or F atom at
meta- or para-position are well tolerated, affording the corre-
sponding axially chiral aryl-substituted allenes in moderate yields
and up to 96% ee (entries 2e6, Table 3). Aromatic aldehydes con-
taining a CH3, CF3 or MeO group can also be smoothly transformed
into the desired products, furnishing the axially chiral allenes in
practical yields and with 92e95% ee (entries 7e10, Table 3). In
addition to normal alkyl-substituted terminal alkynes 1b and 1d,
cycloalkyl-substituted terminal alkyne 1e may also be employed to
yield (R)-4eb in 44% yield with 95% ee (entry 12, Table 3). It should
be noted that aliphatic aldehyde 2m is also compatible with the
Table 1
The influence of reaction time on the reaction of 1-decyne 1d, benzaldehyde 2b, and
(S)-a,a
-diphenylprolinol 3a
Entry
t (h)
(R)-4db
Yieldb (%)
eec (%)
Table 3
Synthesis of axially chiral allenes from 1-alkynes 1, aldehydes 2 and (S)-3a
1
2
4
6
7d
13
25
32
33
96
94
94
91
84
3
8
10
16
4e
5
a
The reactions were carried out with ZnBr2 (0.7 mmol), (S)-3 (1.0 mmol), 1-
decyne 1d (1.1 mmol), benzaldehyde 2b (1 mmol), and toluene (3 mL).
Entry
R1
R2
(R)-4
b
Isolated yield of (R)-4db.
Determined by chiral HPLC analysis.
c
Yieldb (%)
eec (%)
d
Contaminated with unreacted 1d, the molar ratio of (R)-4db to 1d is 1:3.17 as
1
2
3
4
5
6
7
8
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C8H17 (1d)
n-C10H21 (1b)
c-C6H11 (1e)
CH2OBn (1f)
Ph (2b)
42 (R-4db)
30 (R-4dd)
36 (R-4de)
48 (R-4df)
39 (R-4dg)
47 (R-4dh)
32 (R-4di)
44 (R-4dj)
31 (R-4dk)
49 (R-4dl)
46 (R-4bb)
44 (R-4eb)
58 (R-4fm)
94
96
95
91
90
92
94
92
95
94
93
95
98
determined by 1H NMR.
p-BrC6H4 (2d)
m-BrC6H4 (2e)
p-ClC6H4 (2f)
m-ClC6H4 (2g)
p-FC6H4 (2h)
p-CH3C6H4 (2i)
m-CH3C6H4 (2j)
p-CF3C6H4 (2k)
m-MeOC6H4 (2l)
Ph (2b)
e
Heated for 30 min at 120 ꢀC before adding benzaldehyde 2b.
After extensive optimization of the reaction conditions, we
eventually found that when the reaction mixture of 1.3 equiv of
1-decyne 1d, 1.0 equiv of benzaldehyde 2b, (S)-a,a-diphenylproli-
9
nol 3, and ZnBr2 was heated for 2.5 h at 90 ꢀC followed by 6 h at
120 ꢀC, the yield of (R)-4db could be improved to 43% and the ee
could be maintained at 91% (entry 1, Table 2). The ratio of 1-decyne
1d to benzaldehyde 2b was also found to be crucial for the yield as
well as the ee of (R)-4db. Increasing the amount of 1-decyne 1d was
beneficial for the yield of the reaction (entry 1 vs 2, 5 vs 6, Table 2)
whereas increasing the amount of benzaldehyde 2b improved the
enantioselectivity but diminished the yield of (R)-4db (entries 2e4,
Table 2). In view of both the yield and enantioselectivity of the
10
11
12
13
Ph (2b)
c-C6H11 (2m)
a
The reactions were carried out by adding ZnBr2 (1.0 mmol), (S)-3 (1.0 mmol), 1-
alkynes 1 (1.5 mmol)/toluene (2 mL), and aldehyde 2 (2.0 mmol)/toluene (1 mL)
sequentially under Ar atmosphere at rt, heating for 2.5 h at 90 ꢀC followed by 6 h at
120 ꢀC.
b
Isolated yield of (R)-4.
Determined by chiral HPLC analysis.
c

J. Ye et al. / Tetrahedron 69 (2013) 8959e8963
8961
current procedure, affording (R)-4fm in 58% yield with slightly
higher ee than those of aromatic aldehydes (entry 13, Table 3).
(%): 228.2 (Mþ, 1.00), 157 (MþꢁC5H11, 1.79), 130.1 (100); IR (neat):
n
¼2924, 2854, 1950, 1599, 1496, 1459, 1261, 1072, 1028 cmꢁ1; HRMS
calcd for C17H24 [Mþ]: 228.1878, found: 228.1881.
3. Conclusion
The following compounds were prepared according to the above
typical procedure. The corresponding racemic compounds were
prepared according to our early report.5
We have studied the ZnBr2-mediated synthesis of axially chiral
aryl-substituted allenes from terminal alkynes, aromatic aldehydes,
and commercially available chiral amine (S)-
a
,
a
-diphenylprolinol 3
4.2.2. (R)-1-(4-Bromophenyl)undeca-1,2-diene (R-4dd). The re-
action of ZnBr2 (229.3 mg, 1.0 mmol, 98% from Alfa), 1d (214.1 mg,
1.5 mmol, 98%), 2d (377.9 mg, 2.0 mmol, 98%), (S)-3 (258.3 mg,
1.0 mmol, 98%), and toluene (3 mL) afforded (R)-4dd6 (91.0 mg,
30%) (eluant: petroleum ether) as a colorless liquid: 96% ee
(HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH¼400:1,
in detail. Due to the easy reproducibility of the current procedure,
ready availability of the starting materials, as well as the potentials
of the axially chiral allenes products,1,8 this protocol will be of in-
terest for the synthetic community. Further studies in this area are
ongoing in our laboratory.
0.5 mL/min,
l¼214 nm, tR (minor)¼7.2 min, tR (major)¼8.2 min);
4. Experimental section
4.1. General remarks
[
a
]
19 ꢁ198.1 (c 1.03, CHCl3) (reported value for 90% ee: [
a
]
25 ꢁ139.2
D
D
(c 0.50, CHCl3)); 1H NMR (400 MHz, CDCl3)
d
¼7.40 (d, J¼8.4 Hz, 2H,
AreH), 7.14 (d, J¼8.0 Hz, 2H, AreH), 6.06 (dt, J1¼6.4 Hz, J2¼3.0 Hz,
1H, one proton from CH]C]CH), 5.56 (q, J¼6.5 Hz, 1H, one proton
from CH]C]CH), 2.12 (qd, J1¼7.1 Hz, J2¼2.7 Hz, 2H, CH2),1.52e1.40
(m, 2H, CH2), 1.40e1.12 (m, 10H, CH2ꢂ5), 0.87 (t, J¼6.8 Hz, 3H, CH3);
NMR spectra were recorded with a Bruker AM-300 or AM-400
instrument. Chemical shifts are reported in relative to TMS [1H:
d
¼0.00 ppm (TMS)], solvent residual peaks [13C:
d
¼77.0 ppm
13C NMR (100 MHz, CDCl3)
d
¼205.2, 134.2, 131.6, 128.1, 120.1, 95.6,
(CDCl3)] or internal standard [19F:
d
¼0.00 ppm (CFCl3)]. IR spectra
93.7, 31.8, 29.4, 29.3, 29.2, 29.1, 28.6, 22.7, 14.1; MS (EI) m/z (%): 308
were measured with a Bruker Tensor 27 instrument. MS analyses
were performed with a Agilent Technologies 5975C instrument.
HRMS analyses were performed with a Waters GCT Premier in-
strument. Specific optical rotations were measured with OA PolAAr
3005 instrument. HPLC analyses were performed with Waters 2489
detector and Waters 515 pump. All reactions were carried out in
oven-dried Schlenk tubes. ZnBr2 was purchased from Acros (98%),
Alfa Aesar (98% or 99.9%) or Sinopharm, China (98%) and kept in
glovebox; 1-dodecyne 1b (97%) and 1-decyne 1d (98%) were pur-
(Mþ(81Br), 1.95), 306 (Mþ(79Br), 1.68), 129 (100); IR (neat):
n
¼2924,
2853, 1950, 1488, 1465, 1386, 1070, 1010 cmꢁ1; HRMS calcd for
C17H2379Br [Mþ]: 306.0983, found: 306.0985.
4.2.3. (R)-1-(3-Bromophenyl)undeca-1,2-diene (R-4de). The re-
action of ZnBr2 (229.8 mg, 1.0 mmol, 98% from Alfa), 1d (211.1 mg,
1.5 mmol, 98%), 2e (370.1 mg, 2.0 mmol), (S)-3 (258.2 mg, 1.0 mmol,
98%), and toluene (3 mL) afforded (R)-4de (109.5 mg, 36%) (eluant:
petroleum ether) as a colorless liquid: 95% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼100/0, 0.5 mL/min,
chased from Alfa Aesar; (S)-a,a-diphenylprolinol 3 (98%) was pur-
chased from Shanghai Darui Finechemicals. Liquid aldehydes were
distilled right before use. Toluene was dried over sodium wire with
benzophenone as indicator and distilled freshly before use. Other
reagents were used as received from commercial sources. All the
temperatures are referred to the oil baths used. The petroleum
ether (30e60 ꢀC) for chromatography was distilled before use.
l
¼214 nm, tR (major)¼13.0 min, tR (minor)¼15.0 min); [
a
]
20 ꢁ192.9
D
(c 1.01, CHCl3); 1H NMR (400 MHz, CDCl3)
d
¼7.43 (s, 1H, AreH), 7.29
(dt, J1¼7.6 Hz, J2¼1.5 Hz, 1H, AreH), 7.21e7.12 (m, 2H, AreH), 6.04
(dt, J1¼6.4 Hz, J2¼3.1 Hz, 1H, one proton from CH]C]CH), 5.60
(q, J¼6.7 Hz, 1H, one proton from CH]C]CH), 2.12 (qd, J1¼7.1 Hz,
J2¼3.0 Hz, 2H, CH2), 1.53e1.40 (m, 2H, CH2), 1.40e1.15 (m, 10H,
CH2ꢂ5), 0.87 (t, J¼6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
4.2. Preparation of (R)-4dbe(R)-4fb (Table 3)
d
¼205.4, 137.5, 129.9, 129.4, 129.3, 125.1, 122.7, 95.7, 93.5, 31.8, 29.4,
29.3, 29.2, 29.0, 28.6, 22.7,14.1; MS (EI) m/z (%): 308 (Mþ(81Br),1.17),
4.2.1. (R)-1-Phenylundeca-1,2-diene (R-4db). Typical procedure: To
an oven-dried Schlenk tube was added ZnBr2 (229.9 mg, 1.0 mmol,
98% from Alfa) inside a glovebox, the Schlenk tube was then taken
out of the glovebox and heated the ZnBr2 until melting under
vacuum with a heating gun. (S)-3 (258.4 mg, 1.0 mmol, 98%), 1d
(212.1 mg, 1.5 mmol, 98%)/toluene (2 mL), and 2b (212.0 mg,
2.0 mmol)/toluene (1 mL) were then added sequentially under ar-
gon atmosphere. The Schlenk tube was then equipped with a con-
denser and placed in a pre-heated oil bath at 90 ꢀC with stirring for
2.5 h. The reaction mixture was then heated to 120 ꢀC in about
10 min and further stirred for 6 h at 120 ꢀC. After cooling to room
temperature, the crude reaction mixture was filtered through
a short pad of silica gel and eluented with ether (20 mL). After
evaporation, the residue was purified by chromatography on silica
gel to afford (R)-4db6 (95.8 mg, 42%) (eluant: petroleum ether) as
a colorless liquid: 94% ee (HPLC conditions: Chiralcel OD-H column,
306 (Mþ(79Br),1.25),129 (100); IR (neat):
n
¼2955, 2924, 2853,1950,
1590, 1566, 1475, 1069 cmꢁ1; HRMS calcd for C17H2379Br [Mþ]:
306.0983, found: 306.0984.
4.2.4. (R)-1-(4-Chlorophenyl)undeca-1,2-diene (R-4df). The re-
action of ZnBr2 (229.1 mg, 1.0 mmol, 98% from Alfa), 1d (212.2 mg,
1.5 mmol, 98%), 2f (287.7 mg, 2.0 mmol, 98%), (S)-3 (258.4 mg,
1.0 mmol, 98%), and toluene (3 mL) afforded (R)-4df6 (125.1 mg,
48%) (eluant: petroleum ether) as a colorless liquid: 91% ee (HPLC
conditions: Chiralcel OD-H column, hexane/i-PrOH¼100:0, 0.7 mL/
19
min,
l
¼254 nm, tR (minor)¼10.9 min, tR (major)¼14.6 min); [
a
]
D
25
ꢁ204.1 (c 1.04, CHCl3) (reported value for 90% ee: [
a]
ꢁ167.8 (c
D
0.50, CHCl3)); 1H NMR (300 MHz, CDCl3)
d
¼7.30e7.13 (m, 4H,
AreH), 6.07 (dt, J1¼6.3 Hz, J2¼3.1 Hz, 1H, one proton from CH]C]
CH), 5.56 (q, J¼6.6 Hz, 1H, one proton from CH]C]CH), 2.11 (qd,
J1¼7.1 Hz, J2¼2.8 Hz, 2H, CH2), 1.53e1.13 (m, 12H, CH2ꢂ6), 0.87 (t,
hexane/i-PrOH¼100:0, 0.7 mL/min,
l
¼214 nm, tR (major)¼8.8 min,
J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
¼205.2, 133.7, 132.1,
d
20
tR (minor)¼9.6 min); [
a
]
ꢁ227.5 (c 0.99, CHCl3) (reported value
128.6, 127.7, 95.5, 93.7, 31.9, 29.4, 29.3, 29.2, 29.1, 28.6, 22.7, 14.1; MS
D
for 98% ee: [
a
]
25 ꢁ225.1 (c 0.50, CHCl3)); 1H NMR (300 MHz, CDCl3)
(EI) m/z (%): 264 (Mþ(37Cl), 1.47), 262 (Mþ(35Cl), 4.07), 129 (100); IR
D
d
¼7.34e7.24 (m, 4H, AreH), 7.24e7.12 (m, 1H, AreH), 6.11 (dt,
(neat):
n
¼2854, 1951, 1491, 1092, 1014 cmꢁ1; HRMS calcd for
J1¼6.0 Hz, J2¼3.0 Hz, 1H, one proton from CH]C]CH), 5.55 (q,
J¼6.7 Hz, 1H, one proton from CH]C]CH), 2.12 (qd, J1¼7.1 Hz,
J2¼2.9 Hz, 2H, CH2), 1.55e1.14 (m, 12H, CH2ꢂ6), 0.87 (t, J¼6.5 Hz,
C17H2335Cl [Mþ]: 262.1488, found: 262.1484.
4.2.5. (R)-1-(3-Chlorophenyl)undeca-1,2-diene (R-4dg). The re-
action of ZnBr2 (230.3 mg, 1.0 mmol, 98% from Alfa), 1d (212.4 mg,
1.5 mmol, 98%), 2g (288.1 mg, 2.0 mmol), (S)-3 (258.7 mg, 1.0 mmol,
3H, CH3); 13C NMR (75 MHz, CDCl3)
d
¼205.1, 135.2, 128.5, 126.6,
95.1, 94.5, 31.9, 29.4, 29.3, 29.20, 29.17, 28.8, 22.7, 14.1; MS (EI) m/z

8962
J. Ye et al. / Tetrahedron 69 (2013) 8959e8963
98%), and toluene (3 mL) afforded (R)-4dg (102.5 mg, 39%) (eluant:
petroleum ether) as a colorless liquid: 90% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼400:1, 0.7 mL/min,
(qd, J1¼7.0 Hz, J2¼2.9 Hz, 2H, CH2),1.53e1.16 (m,12H, CH2ꢂ6), 0.87 (t,
J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
¼205.1, 138.1, 135.0,
d
128.4, 127.4, 127.2, 123.7, 95.0, 94.5, 31.9, 29.4, 29.3, 29.20, 29.15, 28.8,
l¼214 nm, tR (major)¼3.9 min, tR (minor)¼4.4 min); [
a]
20 ꢁ220.3 (c
22.7, 21.4, 14.1; MS (EI) m/z (%): 242 (Mþ, 1.03), 91 (100); IR (neat):
D
1.06, CHCl3); 1H NMR (400 MHz, CDCl3)
d
¼7.26 (s, 1H, AreH),
n
¼2955, 2924, 2854, 1949, 1606, 1587, 1488, 1464, 1378 cmꢁ1; HRMS
7.22e7.15 (m, 1H, AreH), 7.15e7.09 (m, 2H, AreH), 6.04 (dt,
J1¼6.4 Hz, J2¼3.0 Hz, 1H, one proton from CH]C]CH), 5.58 (q,
J¼6.7 Hz, 1H, one proton from CH]C]CH), 2.11 (qd, J1¼7.0 Hz,
J2¼2.9 Hz, 2H, CH2), 1.53e1.40 (m, 2H, CH2), 1.40e1.14 (m, 10H,
CH2ꢂ5), 0.87 (t, J¼6.4 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
calcd for C18H26 [Mþ]: 242.2035, found: 242.2034.
4.2.9. (R)-1-(4-Trifluoromethylphenyl)undeca-1,2-diene
(R-4dk).
The reaction of ZnBr2 (228.7 mg, 1.0 mmol, 98% from Alfa), 1d
(211.9 mg, 1.5 mmol, 98%), 2k (348.3 mg, 2.0 mmol), (S)-3 (258.4 mg,
1.0 mmol, 98%), and toluene (3 mL) afforded (R)-4dk6 (90.6 mg, 31%)
(eluant: petroleum ether) as a colorless liquid: 95% ee (HPLC con-
ditions: Chiralcel OD-H column, hexane/i-PrOH¼100:0, 0.5 mL/min,
d
¼205.4, 137.2, 134.5, 129.6, 126.5, 126.4, 124.7, 95.6, 93.7, 31.9, 29.4,
29.3, 29.2, 29.1, 28.6, 22.7, 14.1; MS (EI) m/z (%):264 (Mþ(37Cl), 0.66),
262 (Mþ(35Cl), 2.07), 129 (100); IR (neat):
n¼2925, 2854, 1950, 1594,
1571, 1477, 1077 cmꢁ1; HRMS calcd for C17H2335Cl [Mþ]: 262.1488,
found: 262.1486.
l
¼254 nm, tR (minor)¼10.4 min, tR (major)¼11.3 min); [
a
]
20 ꢁ151.7
D
25
(c 1.06, CHCl3) (reported value for 82% ee: [
CHCl3)); H NMR (300 MHz, CDCl3)
a]
ꢁ142.5 (c 0.55,
D
1
d¼7.53 (d, J¼8.1 Hz, 2H, AreH),
4.2.6. (R)-1-(4-Fluorophenyl)undeca-1,2-diene (R-4dh). The re-
action of ZnBr2 (229.9 mg, 1.0 mmol, 98% from Alfa), 1d (211.7 mg,
1.5 mmol, 98%), 2h (249.1 mg, 2.0 mmol), (S)-3 (259.3 mg,1.0 mmol,
98%), and toluene (3 mL) afforded (R)-4dh6 (116.7 mg, 47%) (eluant:
petroleum ether) as a colorless liquid: 92% ee (HPLC conditions:
Chiralcel OJ-H column, hexane/i-PrOH¼100:0, 0.6 mL/min,
7.37 (d, J¼8.4 Hz, 2H, AreH), 6.14 (dt, J1¼6.3 Hz, J2¼3.1 Hz, 1H, one
proton from CH]C]CH), 5.62 (q, J¼6.7 Hz, 1H, one proton from
CH]C]CH), 2.14 (qd, J1¼7.1 Hz, J2¼3.0 Hz, 2H, CH2), 1.54e1.15 (m,
12H, CH2ꢂ6), 0.87 (t, J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d
¼206.1, 139.1 (d, J¼1.5 Hz), 128.4 (q, J¼32.2 Hz), 126.6, 125.4 (q,
J¼3.9 Hz), 124.3 (q, J¼270.0 Hz), 95.7, 93.8, 31.8, 29.4, 29.3, 29.2, 29.1,
l
¼214 nm, tR (major)¼8.2 min, tR (minor)¼9.4 min); [
a
]
23 ꢁ180.8 (c
28.5, 22.7, 14.1; 19F NMR (282 MHz, CDCl3)
d
¼ꢁ63.0; MS (EI) m/z (%):
D
25
1.00, CHCl3) (reported value for 90% ee: [
a
]
ꢁ146.5 (c 0.50,
296 (Mþ, 1.15), 129 (100); IR (neat):
n
¼2927, 2856, 1950, 1616, 1467,
D
CHCl3)); 1H NMR (300 MHz, CDCl3)
d¼7.27e7.17 (m, 2H, AreH), 6.97
1324, 1164, 1124, 1066, 1017 cmꢁ1; HRMS calcd for C18H23F3 [Mþ]:
296.1752, found: 296.1756.
(t, J¼8.7 Hz, 2H, AreH), 6.08 (dt, J1¼6.3 Hz, J2¼3.0 Hz, 1H, one
proton from CH]C]CH), 5.55 (q, J¼6.7 Hz, 1H, one proton from
CH]C]CH), 2.11 (qd, J1¼7.0 Hz, J2¼2.9 Hz, 2H, CH2), 1.53e1.13 (m,
12H, CH2ꢂ6), 0.87 (t, J¼6.3 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
4.2.10. (R)-1-(3-Methoxyphenyl)undeca-1,2-diene (R-4dl). The re-
action of ZnBr2 (230.9 mg, 1.0 mmol, 98% from Alfa), 1d (212.0 mg,
1.5 mmol, 98%), 2l (272.2 mg, 2.0 mmol), (S)-3 (258.3 mg, 1.0 mmol,
98%), and toluene (3 mL) afforded (R)-4dl6 (126.6 mg, 49%) (eluant:
petroleum ether) as a colorless liquid: 94% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼100:1, 0.6 mL/min,
d
¼204.9 (d, J¼1.7 Hz),161.7 (d, J¼243.2 Hz),131.1 (d, J¼3.2 Hz),127.9
(d, J¼8.6 Hz), 115.4 (d, J¼21.8 Hz), 95.3, 93.6, 31.9, 29.4, 29.3, 29.2,
29.1, 28.8, 22.7, 14.1; 19F NMR (282 MHz, CDCl3)
d¼ꢁ116.4; MS (EI)
m/z (%): 246 (Mþ, 3.44), 175 (MþꢁC5H11, 3.77), 148 (100); IR (neat):
n
¼2926, 2855, 1950, 1599, 1509, 1230, 1156 cmꢁ1; HRMS calcd for
l
¼214 nm, tR (major)¼6.4 min, tR (minor)¼7.3 min); [
a
]
19 ꢁ209.1 (c
D
25
C17H23F [Mþ]: 246.1784, found: 246.1787.
1.00, CHCl3) (reported value for 94% ee: [
a
]
ꢁ193.5 (c 0.33,
D
CHCl3)); 1H NMR (400 MHz, CDCl3)
d¼7.21 (t, J¼7.8 Hz, 1H, AreH),
4.2.7. (R)-1-(4-Methylphenyl)undeca-1,2-diene (R-4di). The re-
action of ZnBr2 (229.5 mg, 1.0 mmol, 98% from Alfa), 1d (212.1 mg,
1.5 mmol, 98%), 2i (240.1 mg, 2.0 mmol), (S)-3 (258.3 mg, 1.0 mmol,
98%), and toluene (3 mL) afforded (R)-4di6 (78.6 mg, 32%) (eluant:
petroleum ether) as a colorless liquid: 94% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼100:0, 0.7 mL/min,
6.91e6.83 (m, 2H, AreH), 6.74 (dd, J1¼8.0 Hz, J2¼2.4 Hz, 1H, AreH),
6.09 (dt, J1¼6.4 Hz, J2¼3.0 Hz, 1H, one proton from CH]C]CH),
5.56 (q, J¼6.7 Hz, 1H, one proton from CH]C]CH), 3.80 (s, 3H,
OCH3), 2.12 (qd, J1¼7.1 Hz, J2¼2.8 Hz, 2H, CH2), 1.53e1.16 (m, 12H,
CH2ꢂ6), 0.87 (t, J¼6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼205.2, 159.8, 136.6, 129.4, 119.2, 112.3, 111.7, 95.2, 94.5, 55.1, 31.8,
l
¼254 nm, tR (major)¼9.8 min, tR (minor)¼11.3 min); [
a
]
15 ꢁ221.9 (c
29.4, 29.3, 29.19, 29.15, 28.7, 22.7, 14.1; MS (EI) m/z (%): 258 (Mþ,
D
1.03, CHCl3) (reported value for 90% ee: [
a]
D
25 ꢁ151.5 (c 0.51, CHCl3));
3.83), 160 (100); IR (neat):
n
¼2925, 2854, 1950, 1598, 1490, 1466,
1H NMR (300 MHz, CDCl3)
d¼7.18 (d, J¼7.8 Hz, 2H, AreH), 7.10 (d,
1155, 1087, 1047 cmꢁ1; HRMS calcd for C18H26O [Mþ]: 258.1984,
found: 258.1985.
J¼7.8 Hz, 2H, AreH), 6.09 (dt, J1¼6.3 Hz, J2¼2.9 Hz, 1H, one proton
from CH]C]CH), 5.54 (q, J¼6.5 Hz, 1H, one proton from CH]C]
CH), 2.32 (s, 3H, CH3), 2.11 (qd, J1¼6.9 Hz, J2¼2.5 Hz, 2H, CH2),
1.53e1.16 (m, 12H, CH2ꢂ6), 0.87 (t, J¼6.3 Hz, 3H, CH3); 13C NMR
4.2.11. (R)-1-Phenyltrideca-1,2-diene (R-4bb). The reaction of ZnBr2
(229.3 mg, 1.0 mmol, 98% from Alfa), 1b (257.3 mg, 1.5 mmol, 98%),
2b (212.5 mg, 2.0 mmol), (S)-3 (259.4 mg, 1.0 mmol, 98%), and
toluene (3 mL) afforded (R)-4bb4c (117.9 mg, 46%) (eluant: petro-
leum ether) as a colorless liquid: 93% ee (HPLC conditions: Chiralcel
(75 MHz, CDCl3)
d¼204.8, 136.2, 132.1, 129.2, 126.4, 95.0, 94.3, 31.9,
29.4, 29.3, 29.20, 29.17, 28.8, 22.7, 21.1, 14.1; MS (EI) m/z (%): 242 (Mþ,
1.26), 129 (100); IR (neat):
n
¼2955, 2924, 2854, 1949, 1513,
1465 cmꢁ1; HRMS calcd for C18H26 [Mþ]: 242.2035, found: 242.2037.
OD-H column, hexane/i-PrOH¼100:0, 1.0 mL/min,
l
¼214 nm, tR
(major)¼6.2 min, tR (minor)¼6.8 min); [
a
]
26 ꢁ183.5 (c 0.94, CHCl3)
D
20
4.2.8. (R)-1-(3-Methylphenyl)undeca-1,2-diene (R-4dj). The re-
action of ZnBr2 (230.1 mg, 1.0 mmol, 98% from Alfa), 1d (211.7 mg,
1.5 mmol, 98%), 2j (240.9 mg, 2.0 mmol), (S)-3 (258.6 mg, 1.0 mmol,
98%), and toluene (3 mL) afforded (R)-4dj6 (105.6 mg, 44%) (eluant:
petroleum ether) as a colorless liquid: 92% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼100:0, 0.7 mL/min,
(reported value for 95% ee: [
(300 MHz, CDCl3)
a]
ꢁ181.6 (c 1.05, CHCl3)); 1H NMR
D
d
¼7.34e7.26 (m, 4H, AreH), 7.22e7.13 (m, 1H,
AreH), 6.12 (dt, J1¼6.6 Hz, J2¼3.1 Hz, 1H, one proton from CH]C]
CH), 5.56 (q, J¼6.7 Hz, 1H, one proton from CH]C]CH), 2.12 (qd,
J1¼7.1 Hz, J2¼3.0 Hz, 2H, CH2), 1.54e1.15 (m, 16H, CH2ꢂ8), 0.88 (t,
J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
¼205.1, 135.1, 128.5,
d
l
¼254 nm, tR (major)¼10.3 min, tR (minor)¼11.8 min); [
a
]
20 ꢁ194.9
126.5, 95.1, 94.5, 31.9, 29.64, 29.60, 29.4, 29.3, 29.19, 29.17, 28.8,
22.7, 14.1.
D
25
(c 1.02, CHCl3) (reported value for 90% ee: [
a]
ꢁ125.3 (c 0.50,
D
CHCl3)); 1H NMR (300 MHz, CDCl3)
d¼7.23e7.14 (m, 1H, AreH),
7.14e7.05 (m, 2H, AreH), 6.99 (d, J¼7.2 Hz, 1H, AreH), 6.08 (dt,
J1¼6.3 Hz, J2¼3.0 Hz, 1H, one proton from CH]C]CH), 5.54 (q,
J¼6.6 Hz, 1H, one proton from CH]C]CH), 2.33 (s, 3H, CH3), 2.12
4.2.12. (R)-3-Cyclohexyl-1-phenyl-1,2-propadiene (R-4eb). The re-
action of ZnBr2 (229.3 mg, 1.0 mmol, 98% from Alfa), 1e (165.8 mg,
1.5 mmol, 98%), 2b (212.6 mg, 2.0 mmol), (S)-3 (259.5 mg, 1.0 mmol,

J. Ye et al. / Tetrahedron 69 (2013) 8959e8963
8963
98%), and toluene (3 mL) afforded (R)-4eb4c (87.8 mg, 44%) (eluant:
Supplementary data
petroleum ether) as a colorless liquid: 95% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH¼100:0, 1.0 mL/min,
1H, 13C NMR and HPLC spectra of all products. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.07.021.
l
¼214 nm, tR (major)¼7.4 min, tR (minor)¼8.3 min); [
a
]
25 ꢁ326.3 (c
D
24
1.02, CHCl3) (reported value for 99% ee: [
a]
ꢁ335.2 (c 1.01,
D
CHCl3)); 1H NMR (300 MHz, CDCl3)
d
¼7.34e7.22 (m, 4H, AreH),
7.22e7.12 (m, 1H, AreH), 6.15 (dd, J1¼6.3 Hz, J2¼3.0 Hz, 1H, one
proton from CH]C]CH), 5.56 (t, J¼6.2 Hz, 1H, one proton from
CH]C]CH), 2.21e2.04 (m, 1H, CH from cyclohexyl), 1.92e1.55 (m,
5H, protons from cyclohexyl), 1.39e1.07 (m, 5H, protons from
References and notes
1. For most recent reviews on the chemistry of allenes, see: (a) Ma, S. Chem. Rev.
2005, 105, 2829; (b) Ma, S. Aldrichimica Acta 2007, 40, 91; (c) Brasholz, M.; Re-
issig, H.-U.; Zimmer, R. Acc. Chem. Res. 2009, 42, 45; (d) Ma, S. Acc. Chem. Res.
2009, 42, 1679; (e) Alcaide, B.; Almendros, P.; Campo, T. M. d Chem.dEur. J. 2010,
16, 5836; (f) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A.
Chem. Rev. 2011, 111, 1954; (g) Inagaki, F.; Kitagaki, S.; Mukai, C. Synlett 2011, 594;
cyclohexyl); 13C NMR (75 MHz, CDCl3)
126.4, 101.0, 95.4, 37.6, 33.2, 33.1, 26.1, 26.0.
d¼204.1, 135.2, 128.5, 126.6,
ꢀ
~
(h) Lopez, F.; Mascarenas, J. L. Chem.dEur. J. 2011, 17, 418; (i) Yu, S.; Ma, S. Angew.
4.2.13. (R)-((4-Cyclohexylbuta-2,3-dienyloxy)methyl)benzene
(R-4fm). The reaction of ZnBr2 (230.3 mg, 1.0 mmol, 98% from Alfa),
1f (219.6 mg, 1.5 mmol, 98%), 2m (223.9 mg, 2.0 mmol), (S)-3
(258.7 mg, 1.0 mmol, 98%), and toluene (3 mL) afforded (R)-4fm4c
(139.8 mg, 58%) (eluant: petroleum ether/ethyl ether¼400:1) as
a colorless liquid: 98% ee (HPLC conditions: Chiralcel OD-H column,
Chem., Int. Ed. 2012, 51, 3074.
2. For reviews on the synthesis of allenes, see: (a) Sydnes, L. K. Chem. Rev. 2003,
103, 1133; (b) Krause, N.; Hoffmann-Roder, A. Tetrahedron 2004, 60, 11671; (c)
€
Brummond, K. M.; DeForrest, J. E. Synthesis 2007, 795; (d) Ogasawara, M. Tet-
rahedron: Asymmetry 2009, 20, 259; (e) Yu, S.; Ma, S. Chem. Commun. 2011, 5384.
3. For selected most recent examples, see: (a) Vyas, D. J.; Hazra, C. K.; Oestreich, M.
Org. Lett. 2011, 13, 4462; (b) Ohmiya, H.; Yokobori, U.; Makida, Y.; Sawamura, M.
Org. Lett. 2011, 13, 6312; (c) Uehling, M. R.; Marionni, S. T.; Lalic, G. Org. Lett. 2012,
14, 362; (d) Yang, M.; Yokokawa, N.; Ohmiya, H.; Sawamura, M. Org. Lett. 2012,
14, 816; (e) Li, Z.; Boyarskikh, V.; Hansen, J. H.; Autschbach, J.; Musaev, D. G.;
Davies, H. M. L. J. Am. Chem. Soc. 2012, 134, 15497; (f) Li, H.; Muller, D.; Guenee, L.;
Alexakis, A. Org. Lett. 2012, 14, 5880.
4. (a) Ye, J.; Li, S.; Chen, B.; Fan, W.; Kuang, J.; Liu, J.; Liu, Y.; Miao, B.; Wan, B.; Wang,
Y.; Xie, X.; Yu, Q.; Yuan, W.; Ma, S. Org. Lett. 2012, 14, 1346; (b) Ye, J.; Fan, W.; Ma,
S. Chem.dEur. J. 2013, 19, 716; (c) For CuBr/ZnBr2− co-mediated reactions, see:Lu,
R.; Ye, J.; Cao, T.; Chen, B.; Fan, W.; Lin, W.; Liu, J.; Luo, H.; Miao, B.; Ni, S.; Tang,
X.; Wang, N.; Wang, Y.; Xie, X.; Yu, Q.; Yuan, W.; Zhang, W.; Zhu, C.; Ma, S. Org.
Lett. 2013, 15, 2254.
hexane/i-PrOH¼100:1, 1.0 mL/min,
l
¼214 nm, tR (major)¼5.3 min,
tR (minor)¼5.7 min); [
a]
27 ꢁ83.2 (c 1.02, CHCl3) (reported value for
D
21
ꢁ82.9 (c 0.6, CHCl3)); 1H NMR (300 MHz, CDCl3)
€
ꢀ ꢀ
98% ee: [a]
D
d
¼7.39e7.23 (m, 5H, AreH), 5.34e5.15 (m, 2H, CH]C]CH), 4.54 (s,
2H, OCH2Ar), 4.04 (dd, J1¼6.8, J2¼2.3 Hz, 2H, C]C]CCH2O),
2.10e1.92 (m, 1H, CH from cyclohexyl), 1.86e1.54 (m, 5H, protons
from cyclohexyl), 1.39e1.00 (m, 5H, protons from cyclohexyl); 13C
€
NMR (75 MHz, CDCl3)
71.6, 68.8, 37.0, 33.04, 33.00, 26.1, 25.9.
d
¼203.9, 138.3, 128.3, 127.8, 127.5, 97.9, 89.3,
5. Kuang, J.; Ma, S. J. Am. Chem. Soc. 2010, 132, 1786.
6. Periasamy, M.; Sanjeevakumar, N.; Dalai, M.; Gurubrahamam, R.; Reddy, P. O.
Org. Lett. 2012, 14, 2932. In fact, we also observed that the calibrated specific
optical rotations of the same allenes with similar ee from the current study and
the reported data by Periasamy et al. in this report are also very different (see
Table S2 in Supplementary data), we don’t understand why.
Acknowledgements
7. For selected studies on racemization of allenes upon heating, see: (a) Dykstra, C.
E. J. Am. Chem. Soc. 1977, 99, 2060; (b) Seeger, R.; Krishnan, R.; Pople, J. A.;
Schleyer, P. R. J. Am. Chem. Soc. 1977, 99, 7103.
8. For selected most recent examples on the application of axially chiral allenes,
see: (a) Cai, F.; Pu, X.; Qi, X.; Lynch, V.; Radha, A.; Ready, J. M. J. Am. Chem. Soc.
2011, 133, 18066; (b) Butler, K. L.; Tragni, M.; Widenhoefer, R. A. Angew. Chem.,
Int. Ed. 2012, 51, 5175; (c) Zeng, R.; Fu, C.; Ma, S. J. Am. Chem. Soc. 2012, 134, 9597;
(d) Adams, C. S.; Boralsky, L. A.; Guzei, I. A.; Schomaker, J. M. J. Am. Chem. Soc.
2012, 134, 10807.
Financial support from the National Natural Science Foundation
of China (21232006) and the National Basic Research Program of
China (2011CB808700) is greatly appreciated. We thank Mr. Can
Zhu and Mr. Rong Zeng in our group for reproducing the results
reported by Periasamy et al. in entry 1, Table S1 and Mr. Xin Huang
for reproducing the results presented in entries 2, 4, and 10 of
Table 3.