One Stone for Three Birds-Rhodium-Catalyzed Highly Diastereoselective Intramolecular [4+2] Cycloaddition of Optically Active Allene-1,3-dienes

Article abstract of DOI:10.1002/cjoc.201900023

RhCl(PPh₃)₃-catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene-dienes afforded cis-fused [3.4.0]-bicyclic products with three chiral centers in good yields with an excellent chemo- and diastereoselectivity. A pair of enantiomers of such products was generated highly selectively from both enantiomers of starting allene-dienes, indicating that the axial chirality dictated the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.

Full text of DOI:10.1002/cjoc.201900023

Accepted Article
Title: One Stone for Three Birds-Rhodium-catalyzed Highly Diastereoselective
Intramolecular [4+2] Cycloaddition of Optically Active Allene-1,3-dienes
Authors: Yulin Han, Anni Qin, and Shengming Ma*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2019, 37, 10.1002/cjoc.201900023.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.201900023.
ISSN 1001-604X • CN 31-1547/O6
mc.manuscriptcentral.com/cjoc
www.cjc.wiley-vch.de

One Stone for Three Birds-Rhodium-catalyzed Highly Diastereoselective
Intramolecular [4+2] Cycloaddition of Optically Active Allene-1,3-dienes
a,b
c
,a,c
Yulin Han, Anni Qin, and Shengming Ma*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai
00032, P. R. China.
2
b
University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
c
Research Center for Molecular Recognition and Synthesis, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P. R. China.
Fax: (+86)21-64167510.
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
3 3
Summary of main observation and conclusion RhCl(PPh ) -catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene-dienes
afforded cis-fused [3.4.0]-bicyclic products with three chiral centers in good yields with an excellent chemo- and diastereoselectivity. A pair of
enantiomers of such products was generated highly selectively from both enantiomers of starting allene-dienes, indicating that the axial chirality dictated
the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.
Background and Originality Content
commercially available aldehydes in 47% to 71% yields with ≥ 92%
ee (Eq. 1, Scheme 2). (S )-1b~1c were obtained in 54%~70% yields
with 93% ee with the aid of
R)-2-(diphenylhydroxymethyl)pyrrolidine ((Eq. 2, Scheme 2).
a
The intramolecular [4+2] cycloaddition between 1,3-dienes
and allene may afford bicycles with three chiral centers in one
≥
(
(
1
step. In 2009, the groups of Toste and Mascareñas independently
Synthesis of (2E,4E)-dienol. (2E,4E)-hexa-2,4-dien-1-ol
2E,4E)-2a was obtained in 58% yield using the reduction of sorbic
demonstrated the gold-catalyzed intramolecular [4+22]
cycloaddition reaction of allene-dienes which have two same R
groups at the "distal" terminal of the allene to give
7
8
9
acid with LiAlH
4
(Eq. 1, Scheme 3). Dien-1-ol compounds 2b , 2c
10
and 2d were synthesized in two steps from α,β-unsaturated
2
3
trans-6,5-fused rings (Scheme 1, a). Wender (Scheme 1, b) and
4
we (Scheme 1, c) reported the rhodium-catalyzed intramolecular
[
4+2] cycloaddition of 1,3-disubstituted allene-dienes to afford
cis-6,5-fused rings. However, the [4+2] cycloadditions of such
substrates with an optically active allene unit afforded the
4
products in low ee albeit with excellent de. Trost et al. had a very
brief study on this topic using substrates of 90% ee (Scheme 1, d),
5
by using the cationic catalyst [(C10
H
8
)Rh(COD)]SbF6, which would
not work for the reaction of substrates containing NTs as the
4
linker. Thus, it is of high interest to develop a general and
efficient cycloaddition of chiral allene-dienes. Herein we present
our new observation on the Rh(I)-catalyzed intramolecular [4+2]
cycloaddition of optically active disubstituted allene-dienes, in
which the internal C=C bond of the allene moiety reacted with the
1
,3-dienes to produce cis-6,5-fused bicyclic products with an
excellent Z/E selectivity for the remaining C=C bond with an
excellent diastereoselectivity and efficiency of chirality transfer
affording the bicyclic products in high ee (Scheme 1, e).
Results and Discussion
1
. Synthesis of starting materials
6
Synthesis of Optically Active Allenes 1. Optically Active
Allenes (R
reaction
a
)-1a~1d were prepared via the CuBr
from propargyl tosylamide
2
-catalyzed EATA
or dimethyl
propargylmalonate, (S)-2-(diphenylhydroxymethyl) pyrrolidine and
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.201900023
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
Scheme
1
Metal-catalyzed intramolecular [4+2] cycloaddition of
Scheme 2 The synthesis of optically active allenes-EATA reaction
allene-dienes.
XH
Ph
Ph
CuBr
2
(20 mol%)
o
XH
+
R CHO
1
+
+
Eq.
1
Previous work
N
dioxane, 130
C
R
1
H
OH
X = NTs, CH(CO
2
Me)
2
(
R
a
)-1
a) Toste and
X
Mascareñas's work
S
R
a
)
-
1a X = NTs, R
1
= n-C H
4
9
(50%,
92% ee
)
97% ee
)
(
(
H
R1 = Bn
cat. L*AuCl
cat. AgSbF6
Ra 1b X =
)-
NTs,
(47%,
= Cy (71%, 99% ee)
R1
(R
a
a
)-1c X = NTs, R
1
X
-
1d X=
1
= C H
97% ee
)
(
R
)
CH(CO
2
Me)
2, R
4
9
(50%,
R1
R1
R2 R2
trans-6,5-fused ring
CuBr
dioxane, 130 o
C
2
(20 mol%)
TsHN
R2
+
R CHO
1
+
+
Ph
Ph
OH
TsHN
Eq. 2
R2
N
H
(
S
a
)-1
b) Wender's work
R
1
=
=
ee
R1
(S
a
)-1b R
Bn (54%, 93%
Cy (70%, 99%
)
)
1
ee
H
(
S
a
)-1c R
R1
cat. [Rh]/L
m
X
X
CH3
H
m =
n =
R1 = H, CH3
0, 1
n
H C
3
a
Scheme 3 Synthesis of allene-dienes (R ,2E,4E)-3 with NTs tether
1
, 2
H
PPh
DIAD
3
TsHN
R2
R2
OH
(2E,4E)-2a-2d
our
work
TsN
c)
previous
+
0 oC to rt
H
R
1
THF,
(
R
a
)-1a-1c
or Sa 1b-1c
CH3
RhCl(PPh3)3 (2 mol%)
toluene, 40 oC, 4.5 h
TsN
R
1
TsN
H
(
)-
(
Ra
,2 ,4 )-
E
3
2
E
CH3
H
1
1
R
a
,2E,4E)-3a R
=
=
n-C H , R = CH3
4
9
(70%,
(44%, 97%
= n-C H7
97% ee
)
(
n-C H9
-
Bn, R2 CH
=
ee
n-C H
4
(R
a
,2E,4E) 3b R
3
)
4
9
cis-6,5-fused ring
6%, 75% ee
Ra
E
,2 ,4
E -3c R
1
= n-C H , R
2
93% ee
9
2% ee
(
)
4
9
3
(59%, )
1
= n
, R2 Ph (39%, 99%
= p-ClC H4 (63%, 98% ee)
=
ee
)
7
(R
(R
a
a
,2E,4E)-3d R
,2E,4E)-3e R
-C
4
H
9
d) Trost's brief touch
on
chirality
trasnfer
1
= Cy, R
2
6
,2E,4E)-3b R1 Bn, R2 CH (56%, 94%
=
=
ee
)
CH3
H
(S
a
a
MeO2C
MeO2C
[(C10H8)Rh(COD)]SbF6
3
-
3h R
1
=
R
2
= CH3
97% ee
S
,2E,4E)
Cy,
(60%, )
(
2-3 mol%)
MeO2C
MeO2C
(
CH2Cl2, r.t., 0.5 h
CH3
H
Synthesis of optically active allene-dienes (R
a
,2E,4E)-3f and
,2E,4E)-3f and
a
(R ,2E,4E)-3g were synthesized by the alkadienylation of sodium
H
R
R
2d
(
R
a
,2E,4E)-3g with malonate tether.
(R
a
R = n-C4H , 87% ee
9
ee
ee
9
8
3%, 87%
9%, 91%
C(CH3)2OBn, 90%
ee
e) This work
salts of (R )-1d with (2E,4E)-2,4-alkadienyl bromides, which were
a
H
H
prepared via the reaction of dienols (2E,4E)-2c and (2E,4E)-2d
with methanesulfonyl chloride and LiBr (Scheme 4).
R2
cat. RhCl(PPh3)3
cat. AgSbF6
X
X
H
R2
EtOH, r.t.
R1
1
Scheme 4 Synthesis of allene-dienes (R
a a
,2E,4E)-3f and (R ,2E,4E)-3g with
R
efficient chirality transfer
generating three chiral centers
with excellent diastereoselectivity
and Z/E selectivity
axially chiral allenes
with high
ee
malonate tether
X = NTs, C
1
= alkyl, Bn, R2 = alkyl, aryl
MeO
2
C
n-C H
4
9
R
MeO
2
C
(
R
a
)-1d, 97% ee
R2
enals: Ethyl (2E,4E)-alkadienoate compounds were obtained by
the Horner–Wadsworth–Emmons reaction of α,β-unsaturated
aldehydes, followed by the reduction with DIBAL-H to afford
MeO C
NaH
2
2
MeO C
THF
0 oC to rt
n-BuLi
2
OH MsCl
LiBr
R2
R
Br
n
-C
4
H
9
THF
o
THF
o
,2E,4E)-3
= Ph (69%, 94% ee)
(65%, 94%
(
2E,4E)-alkadien-1-ol compounds 2b~2d in 71% to 86% yields.
2E,4E)-2c R2 = Ph
2E,4E)-2d R = p-ClC
-
78
C
-78 C to rt
(
R
a
(
(
2
-3f
R
2
Synthesis
of
optically
active
allene-dienes
6
H
4
(R
(R
a
a
,2E,4E)
,2E,4E)-3g R = p-ClC
2
H
ee
)
1
1
6
4
(
R
a
a
/S ,2E,4E)-3a~3e with NTs tether.
1,3-Disubstituted
a
allene-dienes (R ,2E,4E)-3a~3e were prepared via a Mitsunobu
reaction of the corresponding allenes 1a~1c and (2E,4E)-dien-1-ol
compounds 2a~2d in 39-70% yields with 93-99% ee (Scheme 3).
2
.
Rh-catalyzed
highly
diastereoselective
[4+2]
cycloaddition reaction of axially chiral allene-1,3-dienes
When the reaction of optically active 1,3-diene-allene (Ra)-3a
a
(S ,2E,4E)-3b and (S
a
,2E,4E)-3h were obtained in 56% and 60%
o
was conducted with RhCl(PPh
although only one diastereomer (3aR,5S,7aR,Z)-4a was produced
3
)
3
(2 mol%) in toluene at 40 C,
yields with 94% and 97% ee, respectively.
in 76% isolated yield, the enantiopurity of the product was rather
4
disappointing-only 75% ee (entry 1, Table 1). There was a slight
increase in the yield and enantiopurity when running the reaction
at room temperature (entry 2, Table 1). It was observed that the
polar solvents such as 1,4-dioxane, THF, dichloromethane, and
chloroform all failed to increase the yield and enantiopurity and
the reaction was slower (entries 3-6, Table 1). The enantiopurity
was improved to 87% with the addition of 3 mol% AgSbF , albeit
6
the reaction became very sluggish (entry 7, Table 1). To our
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
delight, (3aR,5S,7aR,Z)-4a was produced with 93% ee and 60%
isolated yield when the reaction of (Ra)-3a was conducted with
RhCl(PPh ) (3 mol%) and AgSbF (5 mol%) in toluene (entry 8,
3 3 6
Table 1). Using ethanol as the solvent improved the yield further
up to 87% but the product was only with 76% ee in the absence of
Based on the absolute configuration of the starting material,
the X-ray diffraction study of (3aR,5S,7aR,Z)-4b, and the observed
diastereoselectivity, a mechanism involving cyclometalation for
the rhodium-catalyzed intramolecular [4+2] cycloaddition of
allene-dienes has been proposed in our previous study (Scheme
AgSbF
6
(entry 9, Table 1). We reasoned that the coorination ability
(5 mol%) was then added again to
a
5). R-isomer (R ,2E,4E)-3 exchanged with ligand of the cationic Rh
of EtOH is helping, thus, AgSbF
6
make a cationic Rh catalyst. Indeed, a complete chirality transfer
and excellent yield were obtained, indicating the importance of a
cationic nature of the Rh catalyst (entry 10, Table 1). The
commercial absolute ethanol was also fine with a lower yield
Table
cycloaddition of (R
2
The scope of rhodium-catalyzed a intramolecular [4+2]
a
)-1,3-disubstituted allene-diene
H
H
R2
RhCl(PPh
AgSbF
3 3
)
6
(3 mol%)
(5 mol%)
X
TsN
X
(
entry 11, Table 1). Thus, the standard conditions were defined as
H
EtOH, rt
R2
CH
3
H
H
conducting the reaction with RhCl(PPh
mol%) in anhydrous ethanol.
3 3 6
) (3 mol%) and AgSbF (5
R1
(
R
a
,2E,4E)-3
R1
4
C H
9
4
(
3aR,7aR,E)-5a
Table
1 Rhodium-catalyzed intramolecuar [4+2] cycloaddition of
a
(
R
a
,2E,4E)-3 (ee/%)
t
(h)
4
Entry
(R
a
)-1,3-disubstituted allene-diene (R
a
)-3a
1
2
X/R /R
Isolated Yield/%
ee/%
97
n
1
H
7
NTs/ Bu/CH (3a)
3
x
CH
3
RhCl(PPh
3
)
(
3
y
(
mol%)
6
1
2
3
2
9
9
73 ((3aR,5S,7aR,Z)-4a)
62 ((3aR,5S,7aR,Z)-4b)
75 ((3aR,5S,7aR,Z)-4c)
TsN
AgSbF
6
mol%)
TsN
H
5 CH
(97)
4
Solvent, rt, t
3
3
NTs/Bn/CH
NTs/ Bu/C H (3c)
(3b) (97)
97
H
3
nBu
n
nBu
,2E,4E)-3a
4% ee
3
7
(
R
a
(3aR,5S,7aR,Z)-4a
only one diastereomer
93
(93)
9
b
n
4
NTs/ Bu/Ph (3d) (98)
5
59 ((3aR,5R,7aR,Z)-4d)
79 ((3aR,5R,7aR,Z)-4e)
96
99
(
3aR,5S,7aR,Z)-3a
Entry
x
y
Solvent
t/h
NTs/Cy/p-ClC H (3e)
6
4
Isolated Yield (%)
ee (%)
75
5
6
10
(
98) n
b
1
2
2
2
2
2
2
2
3
3
3
3
-
Toluene
Toluene
Dioxane
THF
4.5
10
58
58
14
15.5
108
8
76
81
37
31
73
67
46
60
87
74
55
C(CO
2
2
Me) / Bu/Ph
23
82 ((3aR,5R,7aR,E)-4f)
94
94
2
-
78
(3f) (94)
c
3
c
-
74
C(CO Me) /
2
2
n
4
-
74
7
6 4
Bu/p-ClC H (3g)
9
80 ((3aR,5R,7aR,E)-4g)
(94)
5
6
-
DCM
77
a
The reaction was conducted with (Ra,2E,4E)-3 (0.5 mmol), RhCl(PPh
mol%), and AgSbF
conducted at 40 C.
)
3 3
(3
-
CHCl
3
70
b
6
(5 mol%) in 5 mL of dry EtOH at rt. The reaction was
c
7
3
5
-
Toluene
Toluene
EtOH
87
o
8
93
9
3.5
3.5
6
76
d
10
5
5
EtOH
94
e
1
1
EtOH
93
a
The reaction was conducted with (R
, and AgSbF in 2 mL of solvent. The reaction was
conducted at 40 C. The recoveries of (R ,2E,4E)-3a of entries 3,
, and 7 were 22%, 20%, and 26%, respectively. (R
a
,2E,4E)-3a (0.2 mmol),
b
RhCl(PPh
3
)
3
6
o
c
a
d
4
a
,2E,4E)-3a
e
with 95% ee. The commercial absolute ethanol was not dried
with 4 Å molecular sieves and used directly.
With the optimal reaction conditions in hand, the scope of the
reaction was investigated. Firstly, we studied the substrates with
2
NTs as the linker. With R being methyl, n-propyl, phenyl, and
Figure 1 The ORTEP representation of (3aR,5S,7aR,Z)-4b.
p-ClC
6 4
H , the reaction afforded the corresponding product
(
3aR,5S,7aR,Z)-4a~4e in moderated to excellent yields with a very
3 3 6
catalyst formed by the reaction of RhCl(PPh ) with AgSbF would
1
high efficiency of axial chirality transfer generating three chiral
centers (entries 1-5, Table 4). The absolute configuration of the
product was established by the X-ray single crystal diffraction
generate Intermediate A and A’. In order to make the R group
pointing away from the 1,3-diene unit, the "inner" C=C bonds in
allene and the s-cis-diene coordinated with the rhodium atom
with the two H atoms in intermediate A and A’ cis orientated. The
1
2
study of (3aR,5S,7aR,Z)-4b (Figure 1).
3aR,5R,7aR,E)-4f and (3aR,5R,7aR,E)-4g were formed when R
was Ph or p-ClC with perfect efficiency of chirality transfer and
Malonate-tether
2
1
(
intermediate A is favored since the steric hindrance between R
6 4
H
and the catalyst in intermediate A’ is much larger. Subsequent
cyclometalation and allylic rearrangement lead to the formation
excellent yields (entries 6 and 7, Table 2).
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
of rhodiabicycloheptene C, in which the three tertiary hydrogen
atoms are cis orientated. Subsequent reductive elimination and
Scheme
5
A
proposed mechanism for the intramolecular [4+2]
cycloaddition of allene-dienes (Ra,2E,4E)-3.
ligand exchange with (R
and regenerate the catalytically active specie A to finish the
a
,2E,4E)-3 would yield (3aR,5S,7aR,Z)-4
L
RhCl( +P Ph
3
)
3
Rh+
L
L
1
3
AgSbF
6
catalytic cycle.
If such a rationale is indeed working, the reaction of
,2E,4E)-3b and (S ,2E,4E)-3h should afford the enantiomeric
=
PPh3
AgCl
L
R2
X
(S
a
a
(
R
a
,2E,4E)-3
products (3aS,5R,7aS,Z)-4b and (3aS,5R,7aS,Z)-4h. Indeed this is
the case, (3aS,5R,7aS,Z)-4b and (3aS,5R,7aS,Z)-4h were formed in
H
H
L
1
R
X
H
R2
R2
H
8
0% yield with 94% ee and 77% yield with 96% ee, respectively
H
R1
H
H
H
H
H
X
H
(Eqs. 1 and 2, Scheme 6). The absolute configuration of
X
R
+
2
(
3aR,5S,7aR,Z)-4
R2
H
Rh+
H
Rh
L
L
H
X
(
3aS,5R,7aS,Z)-4b was established by the X-ray single crystal
R1
R1
H
1
4
H
H
diffraction (Figure 2). In conclusion, the absolute configuration
of the C3a, C5, and C7a in the cycloaddition product are
controlled selectively by the axial chirality of the allene moiety of
the substrate.
A
(3aS,5R,7aS,Z)-4
R1
A'
ligand
exchange
oxidative
addition
(
,2 ,4 )-
Ra E E
3
H
H
H
X
H
H
X
H
Rh+
R2
L
L
H
R1
Rh
H
2
R
R1
H
L
B
D
h3−h1
reductive
elimination
H
H
H
X
H
H
H
Rh
X H
+
R2
L
Rh+
R1
H
2
R
R1
L
C
Scheme
6
Rhodium-catalyzed intramolecuar [4+2] cycloaddition of
(S
a
a
,2E,4E)-3b and (S ,2E,4E)-3h.
H
CH3
RhCl(PPh3)3 (3 mol%)
AgSbF6 (5 mol%)
TsN
TsN
(3a
CH3
H
(Eq. 1)
EtOH, rt, 9 h
H
Bn
Bn
S,5R,7aS,Z)-4b
80% yield, 94%
(
Sa,2E,4E)-3b
ee
9
4% ee
H
CH3
RhCl(PPh3)3 (3 mol%)
AgSbF6 (5 mol%)
TsN
TsN
CH3
H
(Eq. 2)
EtOH, rt, 5 h
H
Cy
Cy
Sa,2E,4E)-3h
7% ee
S,5R,7aS,Z)-4h
77% yield, 96%
ee
(
(3a
9
Figure 2 The ORTEP representation of (3aS,5R,7aS,Z)-4b.
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Conclusions
(50 mL) and washed with an aqueous solution of hydrochloric acid
(
3 M, 50 mL). The organic layer was separated, and the aqueous
3 3 6
We have developed the RhCl(PPh ) /AgSbF -cocatalyzed
layer was extracted with ether (50 mL × 2). The combined organic
layer was washed with 50 mL of brine and dried over anhydrous
intramolecular [4+2] cycloaddition of optically active axially chiral
,3-disubstituted allene-dienes, cis-6,5-fused bicyclic products
1
MgSO
4
. After filtration and evaporation, the residue was purified
)-1a (1.1188 g, 50%)
eluent: petroleum ether/ethyl acetate = 8/1) as a liquid: 97% ee
HPLC conditions: Chiralcel AD-H column, n-hexane/i-PrOH = 98/2,
.5 mL/min, λ = 214 nm, t (major) = 29.02 min, t (minor) = 33.09
min); H NMR (400 MHz, CDCl ) δ 7.77 (d, J = 8.0 Hz, 2 H, Ar-H),
.30 (d, J = 8.4 Hz, 2 H, Ar-H), 5.21-5.13 (m, 1 H, HC=), 5.06-4.98
with three chiral centers could be obtained with an excellent
diastereoselectivity and efficient chirality transfer. In addition, the
absolute configurations in the C3a, C5, and C7a of the products
are controlled by the absolute configuration of the axial allene
chirality. A meachanism involving concerted cyclometalation,
allylic rearrangement, and reductive elimination mechanism
accounts for the observed ennifiency for chirality transfer and
diastereoselectivity. Further studies including the catalyzed
enantioselective [4+2] cycloaddition of racemic allene-dienes
substrates by applying chiral ligand are being conducted in our
laboratory.
by chromatography on silica gel to afford (R
a
(
(
1
R
R
1
3
7
(m, 1 H, HC=), 4.94 (t, J = 5.8 Hz, 1 H, NH), 3.55 (td, J
1
= 6.0 Hz, J
2
=
2
1
.8 Hz, 2 H, NCH
.35-1.25 (m, 4 H, 2 × CH
2
3
), 1.97-1.87 (m, 2 H, CH
2
),
1
3
(
100 MHz, CDCl
3
) δ 203.3, 143.3, 136.9, 129.5, 127.0, 94.3, 87.5,
+
4
1.9, 30.9, 28.0, 22.0, 21.4, 13.7; MS (ESI) m/z: 302 ([M+Na] ), 280
+
([M+H] ); IR (neat) = 3277, 2956, 2926, 2858, 1964, 1598, 1495,
-1
Experimental
1418, 1323, 1185, 1156, 1092, 1071 cm ; HRMS calcd for
C H21NO S (M ): 279.1293, found: 279.1300.
15 2
+
General Information. NMR spectra were taken with an Agilent
00 MR DD2 or Varian 400-MR spectrometer (400 MHz for H
1
4
1
3
(2)
Preparation
of
a
(R )-N-(5-phenyl-2,3-pentadien-1-yl)
6
NMR and 100 MHz for C NMR) in CDCl
taken using TMS ( H, δ = 0), residual CHCl
the internal standards, respectively. Chemical shifts were recorded
in ppm and coupling constants were reported in Hz. Mass and
HRMS spectra were carried out in EI or ESI mode. All reactions
3
. NMR spectra were
(7.26 ppm) in CDCl as
1
toluenesulfonamide (R
a
)-1d (hanyl-10-022)
3
3
TsHN
+
BnCHO
+
Ph
Ph
OH
(S)
10 mmol
CuBr
Dioxane, Ar, 130 oC, 8 h
2
(20 mol%)
TsHN
N
H
Bn
(
R
a
)-1b
1.2 equiv
2.0
equiv
47%, 92% ee
have been carried out in oven-dried Schlenk tubes. RhCl(PPh
3 3
)
(
99%) was purchased from J&k and TCI, AgSbF (99%) was
6
Typical Procedure A: To a flame-dried sealed tube were
added (S)-2-(diphenylhydroxymethyl) pyrrolidine (2.5861 g, 10
mmol), CuBr (0.4516 g, 2.0 mmol, 20 mol%)/(10 mL),
purchased from Alfa Aesar; 4 Å molecular sieves were purchased
from Alfa Aesar and kept in glove box after activation (heated at
4
2
o
o
50 C for 10 h in Muffle furnace, taken out after cooling to 200 C
benzaldehyde (2.5302 g, 20 mmol, 2.0 equiv)/dioxane (10 mL),
and propargyl tosylamide (2.5110 g, 12 mmol, 1.2 equiv)/dioxane
(10 mL) sequentially under argon atmosphere. The tube was then
sealed by screwing the polytetrafluoroethylene plug tightly. The
reaction was complete after being stirred in an oil bath preheated
and then kept in glove box to allow to cool to room temperature).
Petroleum ether (boiling range: 60-90 C) was purchased from
Adamas. Toluene, 1,4-dioxane, and THF were dried over sodium
wire with benzophenone as the indicator and distilled freshly
o
o
before use. CH
2
Cl
2
and CHCl
3
were dried over CaH
2
and distilled
at 130 C for 8 h, which was monitored by TLC. After cooling to
freshly before use. The commercial absolute ethanol (EtOH) was
dried with 4 Å molecular sieves. Other reagents were used as
received without further treatment. All the temperatures are
referred to the oil baths used.
room temperature, the resulting mixture was diluted with ether
(50 mL) and washed with an aqueous solution of hydrochloric acid
(3M, 50 mL). The organic layer was separated, and the aqueous
layer was extracted with ether (50 mL × 2). The combined organic
layer was washed with brine (50 mL) and dried over anhydrous
1
1
. Synthesis of starting materials
.1 Synthesis of optically active 1,3-disubstituated allene
MgSO
. After filtration and evaporation, the residue was purified
4
15
(
(
1) Preparation of (R
R
a
)-N-(2,3-octadien-1-yl) toluenesulfonamide
by chromatography on silica gel to afford (R )-1b (1.4609 g,
a
6
)-1a (hanyl-9-060)
47%) (eluent: petroleum ether/ethyl acetate = 8/1) as a liquid:
92% ee (HPLC conditions: Chiralcel OD-H column,
a
TsHN
+
n-C H CHO
4
9
+
Ph
Ph
CuBr
Dioxane, Ar,130 oC, 12 h
2
(20 mol%)
n-hexane/i-PrOH = 80/20, 1.0 mL/min, λ = 214 nm, t (major) =
R
TsHN
.1 equiv
N
1
H
OH
S)
n-C H
4
9
2
1.48 min, t
7.72 (d, J = 8.0 Hz, 2 H, Ar-H), 7.32-7.18 (m, 5 H, Ar-H), 7.15 (d, J =
.6 Hz, 2 H, Ar-H), 5.41-5.32 (m, 1 H, HC=), 5.06-4.97 (m, 1 H,
HC=), 4.48 (t, J = 5.8 Hz, 1 H, NH), 3.58-3.42 (m, 2 H, NCH ), 3.26
R 3
(minor) = 33.11 min); H NMR (400 MHz, CDCl ) δ
(
(
R
a
)-1a
1
1.2
8 mmol
equiv
50%, 97% ee
7
To a flame-dried three neck flask with a reflux condenser,
S)-2-(diphenylhydroxymethyl) pyrrolidine (2.0703 g, 8 mmol),
CuBr (0.3577 g, 1.6 mmol, 20 mol%), propargyl tosylamide
1.8387 g, 8.8 mmol, 1.1 equiv)/dioxane (10 mL), and pentanal
0.8387 g, 9.6 mmol, 1.2 equiv)/dioxane (20 mL) were
2
(
13
(
dd, J
1
= 6.8 Hz, J
2
= 2.4 Hz, 2 H, CH
) δ 204.2, 143.4, 139.5, 136.9, 129.6, 128.4,
28.38, 127.1, 126.3, 94.0, 88.4, 41.9, 34.9, 21.5; MS (ESI) m/z:
2 3
), 2.41 (s, 3 H, CH ); C NMR
2
(100 MHz, CDCl
3
(
(
1
3
+
+
36 ([M+Na] ), 314 ([M+H] ); IR (neat) = 3278, 3061, 3027, 2920,
sequentially added under argon atmosphere. The reaction was
complete after being stirred in an oil bath preheated at 130 C for
o
2867, 1965, 1598, 1494, 1453, 1424, 1323, 1156, 1093, 1072,
-1
1
031 cm .
1
2 h, which was monitored by TLC. After cooling to room
temperature, the resulting mixture was diluted with diethyl ether
(
3) Preparation
of
(S
a
)-N-(5-phenyl-2,3-pentadien-1-yl)
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
toluenesulfonamide (S
a
)-1b (hanyl-10-007)
TsHN
+
+
Ph
Ph
CuBr
2
(20 mol%)
130
10.5 h
TsHN
TsHN
CyCHO
+
BnCHO
+
Ph
CuBr
Dioxane, Ar, 130 oC, 9 h
2
(20 mol%)
N
o
Dioxane, Ar,
C,
TsHN
H
OH
N
H
(R)
Ph
OH
Cy
70%, 99% ee
(R)
(S
a
)-1c
1.7 equiv
2.0 equiv
1.2 equiv
2.0 equiv
Bn
5 mmol
5
mmol
(S
4%, 93% ee
a
)-1b
5
Following Typical Procedure A, the reaction of
(R)-2-(diphenylhydroxymethyl) pyrrolidine (1.2919 g, 5 mmol),
CuBr (0.2263 g, 1.0 mmol, 20 mol%) /dioxane (6 mL),
cyclohexylformaldehyde (1.1240 g, 10 mmol, 2.0 equiv) /dioxane
(2 mL), and propargyl tosylamide (1.7540 g, 8.4 mmol, 1.7 equiv)
Following Typical Procedure A, the reaction of
R)-2-(diphenylhydroxymethyl) pyrrolidine (1.2941 g, 5 mmol),
CuBr (0.2263 g, 1.0 mmol, 20 mol%), benzaldehyde (1.2050 g, 10
mmol, 2.0 equiv) /dioxane (10 mL), and propargyl tosylamide
(
2
2
o
o
(1.2542 g, 6 mmol, 1.2 equiv) /dioxane (5 mL) at 130 C for 9 h
/dioxane (2 mL) at 130 C for 10.5 h afforded (S
a
)-1c (1.0750 g,
afforded (S )-1b (0.8489 g, 54%) (eluent: petroleum ether/ethyl
acetate = 8/1) as a liquid: 93% ee (HPLC conditions: Chiralcel OD-H
a
70%) (eluent: petroleum ether/ethyl acetate = 10/1) as a liquid:
99% ee (HPLC conditions: Chiralcel AD-H column, n-hexane/i-PrOH
column, n-hexane/i-PrOH = 80/20, 1.0 mL/min, λ = 214 nm,
= 98/2, 1.0 mL/min, λ = 214 nm, t
R
(minor) = 56.16 min, t
58.68 min); H NMR (400 MHz, CDCl ) δ 7.75 (d, J = 8.0 Hz, 2 H,
Ar-H), 7.31 (d, J = 8.0 Hz, 2 H, Ar-H), 5.22-5.17 (m, 1 H, HC=),
5.12-5.04 (m, 1 H, HC=), 4.58 (t, J = 5.2 Hz, 1 H, NH), 3.55 (dd, J
8.8 Hz, J = 5.6 Hz, 2 H, NCH ), 2.43 (s, 3 H, CH ), 1.98-1.85 (m, 1 H,
CH), 1.73-1.57 (m, 5 H, 2 × CH + one proton of CH ), 1.32-0.85 (m,
5 H, 2 × CH + one proton of CH ); C NMR (100 MHz, CDCl ) δ
R
(major) =
1
1
t
R
(minor) = 21.60 min, t
CDCl
.15 (d, J = 7.2 Hz, 2 H, Ar-H), 5.43-5.32 (m, 1 H, HC=), 5.09-4.98
m, 1 H, HC=), 4.44 (t, J = 5.4 Hz, 1 H, NH), 3.57-3.42 (m, 2 H,
NCH ), 3.27 (dd, J = 6.8 Hz, J = 2.0 Hz, 2 H, CH ), 2.41 (s, 3 H,
); C NMR (100 MHz, CDCl ) δ 204.3, 143.4, 139.6, 136.9,
29.6, 128.5, 128.4, 127.1, 126.3, 94.0, 88.4, 41.9, 34.9, 21.5; MS
R
(major) = 31.14 min); H NMR (400 MHz,
) δ 7.72 (d, J = 8.0 Hz, 2 H, Ar-H), 7.35-7.19 (m, 5 H, Ar-H),
3
3
7
(
1
=
2
2
3
2
1
2
2
2
2
1
3
13
CH
1
3
3
2
2
3
202.2, 143.3, 137.0, 129.6, 127.1, 100.5, 88.5, 42.0, 36.8, 32.9,
32.7, 25.9, 25.8, 21.4; MS (EI) m/z (%): 305 (M , 2.65), 155 (100);
+
+
+
(ESI) m/z: 336 ([M+Na] ), 314 ([M+H] ); IR (neat) = 3282, 1966,
1
1
3
599, 1494, 1453, 1418, 1323, 1264, 1184, 1156, 1120, 1092,
IR (neat) = 3290, 2922, 2851, 1958, 1595, 1493, 1451, 1422, 1386,
-
1
+
-1
074, 1031 cm ; HRMS calcd for C18
31.1475, found: 331.1471.
H
23
N
2
O
2
S ([M+NH
4
] ):
1325, 1290, 1228, 1184, 1154, 1090, 1066, 1040, 1019 cm ;
+
HRMS calcd for C17
H23NO
2
S (M ): 305.1449, found: 305.1440.
(
4) Preparation of (R
a
)-N-(4-cyclohexyl-2,3-butadien-1-yl)
(6) Preparation of (R
a
)-Dimethyl 2-(2,3-octadien-1-yl) malonate
6
toluenesulfonamide (R
a
)-1c (hanyl-11-006)
(R )-1d (hanyl-9-167)
a
TsHN
CuBr
2
(20 mol%)
CO
2
Me
MeO
MeO
50%,
2
C
Ph
Ph Dioxane, Ar, 130 oC, 11 h
OH
S)
5mmol
Ph
Ph Dioxane, Ar, 130 oC, 12 h
OH
CuBr2 (20 mol%)
+
+
C
4
H
9
CyCHO
+
C H CHO +
4
9
TsHN
.0 equiv
N
H
MeO
2
C
N
2
C
H
Cy
(R
a
)-1d
97% ee
(
(R
1%, 99% ee
a
)-1c
(
S)
1.9 equiv
1.5 equiv
10 mmol
2
2.0 equiv
7
Following Typical Procedure A, the reaction of
S)-2-(diphenylhydroxymethyl) pyrrolidine (1.2933 g, 5 mmol),
CuBr (0.2265 g, 1.0 mmol, 20 mol%) /dioxane (6 mL),
cyclohexylformaldehyde (1.1170 g, 10.0 mmol, 2.0 equiv)
Following Typical Procedure A, the reaction of
(S)-2-(diphenylhydroxymethyl) pyrrolidine (2.5859 g, 10 mmol),
CuBr (0.4521 g, 2.0 mmol, 20 mol%) /dioxane (10 mL),
(
2
2
pentaldehyde (1.2937 g, 15.0 mmol, 1.5 equiv) /dioxane (10 mL),
/
dioxane (2 mL), and propargyl tosylamide (2.0984 g, 10 mmol,
and dimethyl 2-propargylmalonate (3.1862 g, 18.7 mmol, 1.9
o
16
o
2
.0 equiv) /dioxane (2 mL) at 130 C for 11 h afforded (R
a
)-1c
equiv) /dioxane (10 mL) at 130 C for 12 h afforded (S
a
)-1d
(
1.0850 g, 71%) (eluent: petroleum ether/ethyl acetate = 10/1) as
a liquid: 99% ee (HPLC conditions: Chiralcel AD-H column,
n-hexane/i-PrOH = 98/2, 1.0 mL/min, λ = 214 nm, t (major) =
(minor) = 62.33 min);; H NMR (400 MHz, CDCl ) δ
.76 (d, J = 8.0 Hz, 2 H, Ar-H), 7.30 (d, J = 7.6 Hz, 2 H, Ar-H),
.23-5.16 (m, 1 H, HC=), 5.12-5.04 (m, 1 H, HC=),4.67 (t, J = 4.8 Hz,
(1.2102 g, 50%) (eluent: petroleum ether/ethyl acetate = 30/1) as
a liquid: 97% ee (HPLC conditions: Chiralcel OD-H column,
R
n-hexane/i-PrOH = 100/1, 0.7 mL/min, λ = 214 nm, t
R
(major) =
(minor) = 12.84 min); H NMR (400 MHz, CDCl ) δ
5.20-5.03 (m, 2 H, 2 × HC=), 3.74 (s, 6 H, 2 × CH ), 3.51 (t, J = 7.6
Hz, 1 H, CH), 2.63-2.54 (m, 2 H, CH ), 2.00-1.90 (m, 2 H, CH ),
1.41-1.27 (m, 4 H, 2 × CH ), 0.90 (t, J = 7.0 Hz, 3 H, CH ); C NMR
(100 MHz, CDCl ) δ 203.9, 169.4, 169.3, 92.9, 87.3, 52.5, 51.2,
1
1
5
7
5
1
6.23 min, t
R
3
12.12 min, t
R
3
3
2
2
1
3
H, NH), 3.62-3.50 (m, 2 H, NCH
2
), 2.43 (s, 3 H, CH
3
), 1.98-1.86
),
); C NMR (100
) δ 202.2, 143.3, 137.0, 129.6, 127.1, 100.4, 88.4, 42.0,
2
3
(
m, 1 H, CH), 1.73-1.58 (m, 5 H, 2 × CH
.30-0.90 (m, 5 H, 2 × CH + one proton of CH
MHz, CDCl
6.8, 32.8, 32.7, 25.9, 25.8, 21.4; MS (ESI) m/z: 328 ([M+Na] ); IR
neat) = 3291, 2923, 2851, 1957, 1595, 1493, 1451, 1422, 1386,
2
+ one proton of CH
2
3
1
3
+
1
2
2
31.1, 28.4, 28.0, 22.1, 13.8; MS (EI) m/z (%): 240 (M , 10.25), 79
(100); IR (neat) ν = 2927, 2852, 1732, 1620, 1437, 1341, 1233,
1198, 1153, 1032 cm ; HRMS calcd for C13
3
+
-1
+
3
(
1
H
20
O
4
(M ): 240.1362,
found: 240.1371.
-
1
325, 1290, 1228, 1184, 1154, 1090, 1066, 1040, 1020 cm .
1
.2 Synthesis of axially chiral allene-1,3-dienes
(
5) Preparation of (S
a
)-N-(4-cyclohexyl-2,3-butadien-1-yl)
a
(1) Preparation of (R )-N-(2,3-octadien-1-yl)-N-[(2E,4E)-
toluenesulfonamide (S
a
)-1c (hanyl-11-007)
a
hexadien-1-yl] toluenesulfonamide (R ,2E,4E)-3a. (hanyl-8-083)
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
1
2
14 nm, t
R
(minor) = 18.25 min, t
R
(major) = 19.92 min); H NMR
TsHN
PPh
DIAD (1.2 equiv)
THF, 0 oC (2+ 2 min)
then rt, 17.5 h
3
(1.2 equiv)
CH
3
TsN
(400 MHz, CDCl ) δ 7.68 (d, J = 8.0 Hz, 2 H, ArH), 7.26 (d, J = 6.4
3
+
H C
3
OH
Hz, 4 H, ArH), 7.22-7.14 (m, 3 H, ArH), 6.07-5.87 (m, 2 H, 2 × HC=),
5.67-5.52 (m, 1 H, HC=), 5.35-5.23 (m, 2 H, 2 × HC=), 4.96-4.87 (m,
n-C H
4
9
(
2E,4E)-2a
.1 equiv
n-C H
4
9
(
R
a
)-1a
1
Ra
,2 ,4 )-
E
E
3a
9
7% ee
(
1 H, HC=), 3.88-3.71 (m, 4 H, 2 × NCH
), 3.30 (dd, J
= 7.2 Hz, J
=
);
2
1
2
7
0%, 97% ee
1
.6 Hz, 2 H, CH ), 2.41 (s, 3 H, CH ), 1.71 (d, J = 6.4 Hz, 3 H, CH
C NMR (100 MHz, CDCl ) δ 205.6, 143.1, 139.6, 137.6, 134.6,
3
2
3
3
1
3
To a dry round-bottom flask placed in an ice bath were added
(1.6457 g, 6.24 mmol, 1.2 equiv), (2E,4E)-hexa-2,4-dien-1-ol
a (0.5637 g, 5.72 mmol, 1.1 equiv), (R )-N-(2,3-octadien-1-yl)
toluenesulfonamide (R )-1a (97% ee, 1.4549 g, 5.2 mmol), and 10
mL of THF at 0 C. Diisopropylazodicarboxylate (DIAD) (1.3177 g,
.24 mmol, 1.2 equiv) in 5 mL of THF were added dropwise to the
PPh
2
3
130.35, 130.31, 129.6, 128.37, 128.35, 127.1, 126.3, 124.1, 91.8,
86.9, 48.2, 45.8, 35.1, 21.4, 18.0; MS (ESI) m/z: 416 ([M+Na] ); IR
+
a
a
(neat): ν = 3023, 2916, 2855, 1962, 1658, 1598, 1493, 1443, 1337,
o
-1
+
1154, 1091 cm ; HRMS calcd for C H O NS ([M+H] ): 394.1835,
2
4 28 2
6
found: 394.1837.
o
solution over 2 mins at 0 C with stirring and then rinsed with 5
o
mL of THF. After stirred at 0 C for 2 mins, the resulting mixture
(3) Preparation of (R )-N-(2,3-octadien-1-yl)-N-[(2E,4E)-
a
was allowed to warm up to room temperature naturally and
stirred for 17.5 h at rt as monitored by TLC. The resulting mixture
was concentrated in vacuo and the residue was purified via
octadien-1-yl] toluenesulfonamide (R ,2E,4E)-3c. (hanyl-9-077)
a
PPh3 (1.2 equiv)
DIAD (1.2 equiv)
3
n-C H7
TsHN
OH
TsN
+
chromatography on silica gel to afford (R
a
,2E,4E)-3a (1.3041 g,
0%) (eluent: petroleum ether/ethyl acetate = 30/1) as a liquid:
7% ee (HPLC conditions: Chiralcel OJ-H column, hexane/i-PrOH =
8/2, 0.7 mL/min, λ = 214 nm, t (minor) = 18.98 min, t (major) =
0.36 min); H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 8.0 Hz, 2 H,
= 14.6 Hz, J = 10.6
Hz, 1 H, HC=), 6.01-5.89 (m, 1 H, HC=), 5.71-5.58 (m, 1 H, HC=),
.37-5.28 (m, 1 H, HC=), 5.13-5.04 ( m, 1 H, HC=), 4.87-4.79 (m, 1
H, HC=), 3.85 (d, J = 7.2 Hz, 2 H, NCH ), 3.80 (dd, J = 7.0 Hz, J
.8 Hz, 2 H, NCH ), 2.42 (s, 3 H, CH ), 2.00-1.90 (m, 2 H, CH ), 1.74
d, J = 6.4 Hz, 3 H, CH ), 1.40-1.26 (m, 4 H, 2 × CH ), 0.88 (t, J = 7.0
); C NMR (100 MHz, CDCl ) δ 205.1, 143.0, 137.5,
3
n-C H7
0 oC to 16 h
THF,
rt,
n-C H9
4
7
9
9
2
n-C H9
Ra)-1a
(2E,4E)-2b
.2 equiv
4
(
1
(Ra,2E,4E)-3c
9%, 93% ee
97% ee
5
R
R
1
3
Following Typical Procedure B, the reaction of PPh
mmol, 1.2
3
(0.6334 g,
equiv),
ArH), 7.29 (d, J = 8.0 Hz, 2 H, ArH), 6.06 (dd, J
1
2
2.4
a a
(R )-N-(2,3-octadien-1-yl)toluenesulfonamide (R )-1a (0.5578 g,
2.0 mmol) /THF (5 mL), (2E,4E)-octa-2,4-dien-1-ol 2b (0.3048 g,
2.4 mmol, 1.2 equiv) /THF (3 mL), DIAD (0.5063 g, 2.4 mmol, 1.2
a
equiv) /THF (2 mL) at rt for 16 h afforded (R ,2E,4E)-3c (0.4557 g,
59%) (eluent: petroleum ether/ethyl acetate =20/1) as a liquid:
93% ee (HPLC conditions: Chiralcel OJ-H column, hexane/i-PrOH =
5
2
1
2
=
1
2
3
2
(
3
2
1
3
Hz, 3 H, CH
3
3
1
4
34.5, 130.4, 130.1, 129.5, 127.05, 126.99, 124.2, 92.3, 86.1, 48.2,
6.0, 31.2, 28.2, 22.0, 21.4, 18.0, 13.8; MS (ESI) m/z: 382
100/1, 1.0 mL/min, λ = 214 nm, t
R
(minor) = 8.21 min, t
9.32 min); H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 8.0 Hz, 2 H,
ArH), 7.28 (d, J = 8.4 Hz, 2 H, ArH), 6.06 (dd, J = 15.0 Hz, J = 10.6
Hz, 1 H, HC=), 5.95 (dd, J = 15.2 Hz, J = 10.4 Hz, 1 H, HC=), 5.63
(dt, J = 15.2 Hz, J = 6.8 Hz, 1 H, HC=), 5.34 (dt, J = 15.2 Hz, J
.8 Hz, 1 H, HC=), 5.15-5.05 (m, 1 H, HC=), 4.88-4.80 (m, 1 H, HC=),
R
(major) =
1
3
+
([M+Na] ); IR (neat): ν = 3022, 2957, 2927, 2857, 1962, 1660,
1
2
-
1
1
C
598, 1494, 1441, 1342, 1305, 1156, 1092 cm ; HRMS calcd for
1
2
+
21
H30NO
2
S ([M+H] ): 360.1992, found: 360.1991.
1
2
1
2
=
6
(
[
(
2) Preparation of (R
(2E,4E)-hexadien-1-yl]
hanyl-9-078)
a
)-N-(5-phenyl-2,3-pentadien-1-yl)-N-
3.86 (d, J = 6.8 Hz, 2 H, NCH
2
), 3.81 (dd, J = 2.2 Hz, 2
1
= 7.0 Hz, J
2
toluenesulfonamide (R ,2E,4E)-3b.
a
H, NCH
2
), 2.42 (s, 3 H, CH
3
), 2.04 (q, J = 7.1 Hz, 2 H, CH ), 2.00-1.90
2
(m, 2 H, CH
2
2
), 1.45-1.27 (m, 6 H, 3 × CH ), 0.92-0.85 (m, 6 H, 2 ×
1
3
3 3
CH ); C NMR (100 MHz, CDCl ) δ 205.2, 143.0, 137.6, 135.6,
TsHN
PPh
DIAD (1.2 equiv)
3
(1.2 equiv)
CH
3
OH
TsN
134.6, 129.6, 129.2, 127.1, 124.4, 92.4, 86.1, 48.2, 46.1, 34.6,
+
H C
THF, 0 oC to rt, 20 h
3
31.2, 28.2, 22.3, 22.1, 21.4, 13.8, 13.6; MS (ESI) m/z: 410
Bn
+
R
a
)-1b
(2E,4E)-2a
1.2 equiv
Bn
3b
([M+Na] ); IR (neat): ν = 3021, 2957, 2924, 2864, 1962, 1657,
(
9
2% ee
-1
(
Ra
,2 ,4 )-
4%, 97% ee
E
E
1599, 1450, 1340, 1156, 1094 cm ; HRMS calcd for C H O NS
2
3 34 2
4
+
(
[M+H] ): 388.2305, found: 388.2304.
Typical Procedure B：To a dry round-bottom flask placed in
an ice bath were added PPh (0.5711 g, 2.16 mmol, 1.2 equiv),
)-N-(5-phenyl-2,3-pentadien-1-yl)toluenesulfonamide (R )-1b
92% ee, 0.5890 g, 1.8 mmol)/THF (5 mL),
2E,4E)-hexa-2,4-dien-1-ol 2a (0.2200 g, 2.16 mmol, 1.2
3
(4) Preparation of (R )-N-(2,3-octadien-1-yl)-N-[(2E,4E)-5-phenyl-
a
(
(
(
R
a
a
pentadien-1-yl] toluenesulfonamide (R ,2E,4E)-3d. (hanyl-9-066)
a
TsHN
PPh
DIAD (1.2 equiv)
3
(1.2 equiv)
OH
TsN
+
equiv)/THF (3 mL), and DIAD (0.4456 g, 2.16 mmol, 1.2 equiv)/THF
0
o
rt,
C to 41 h
THF,
o
n-C
H
4
9
(
2 mL) sequentially at 0 C. The resulting mixture was allowed to
(R
9
a
)-1a
)-
E,4E 2c
n-C H9
4
(2
7% ee
1.2 equiv
R
)-
,2E,4E 3d
(
a
warm up to room temperature naturally and stirred for 20 h at rt
as monitored by TLC. Then the resulting mixture was
concentrated in vacuo and purified via chromatography on silica
3
9%, 99% ee
Following Typical Procedure B, the reaction of PPh
mmol, 1.2 equiv), (R )-N-(2,3-octadien-1-yl)
a
toluenesulfonamide (R )-1a (97% ee, 0.5586 g, 2.0 mmol) /THF (5
3
(0.6369 g,
a
gel to afford (R ,2E,4E)-3b (0.3280 g, 44%) (eluent: petroleum
2.4
a
ether/ethyl acetate =20/1) as a liquid: 97% ee (HPLC conditions:
Chiralcel AD-H column, hexane/i-PrOH = 95/5, 1.0 mL/min, λ =
mL), (2E,4E)-5-phenylpenta-2,4-dien-1-ol 2c (0.3834 g, 2.4 mmol,
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
1
.2 equiv) /THF (2 mL), DIAD (0.5006 g, 2.4 mmol, 1.2 equiv) /THF
3 mL) at rt for 41 h afforded (R ,2E,4E)-3d (0.3316 g, 39%)
eluent: petroleum ether/ethyl acetate =30/1) as a liquid: 98% ee
HPLC conditions: Chiralcel AD-H column, supercritical CO
l)/i-PrOH = 85/15, 1.3 mL/min, λ = 214 nm, t (minor) = 19.44 min,
(major) = 20.52 min); H NMR (400 MHz, CDCl ) δ 7.72 (d, J = 8.0
Hz, 2 H, ArH), 7.36 (d, J = 7.6 Hz, 2 H, Ar-H), 7.30 (t, J = 7.6 Hz, 4 H,
Ar-H), 7.22 (t, J = 7.2 Hz, 1 H, ArH), 6.69 (dd, J = 15.4 Hz, J = 10.6
Hz, 1 H, HC=), 6.48 (d, J = 16.0 Hz, 1 H, HC=), 6.26 (dd, J = 15.2 Hz,
= 10.4 Hz, 1 H, HC=), 5.60 (dt, J = 15.2 Hz, J = 6.6 Hz, 1 H, HC=),
.16-5.07 (m, 1 H, HC=), 4.93-4.82 (m, 1 H, HC=), 3.94 (d, J = 6.8
Hz, 2 H, NCH ), 3.84 (dd, J = 6.8 Hz, J = 2.0 Hz, 2 H, NCH ), 2.42
s, 3 H, CH ), 2.03-1.90 (m, 2 H, CH ), 1.40-1.24 (m, 4 H, 2 × CH ),
); C NMR (100 MHz, CDCl ) δ 205.2,
(R
a
,2E,4E)-3f. (hanyl-9-141, hanyl-9-142)
(
(
(
(
a
n-BuLi
1)
(1.16 equiv)
C,
OH
THF, Ar, -78
o
+
15)
min
(
2
2
2) MsCl (1.16 equiv)
THF, -78 oC, 0.5 h
3) LiBr (5.5 equiv)
THF, -78 oC, 2 min
then rt, 3.0 h
(
2E,4E)-2c
.1 equiv
R
1
1
t
R
3
MeO
MeO
2
C
C
THF
2
CO
2
Me
MeO
2
C
0 oC, 3 min
then rt, 9 h
NaH (1.1 equiv)
o
1
2
n-C H
4
9
THF,
0
C, (2 + 30) min
(
R
a
,2E,4E)-3f
69%, 94% ee
1
n-C H9
4
J
2
1
2
(R
9
a
)-1d
7% ee
5
2
1
2
2
Typical Procedure C: To a flame-dried Schlenk tube were
(
3
2
2
added (2E,4E)-5-phenyl-penta-2,4-dien-1-ol 2c (0.3533 g, 2.2
mmol, 1.1 equiv) and anhydrous THF (5 mL) under Ar. The Schlenk
tube was then placed into a dry ice/ethanol bath (-78 C). n-BuLi
1
3
0
1
1
.87 (t, J = 6.8 Hz, 3 H, CH
43.1, 137.5, 136.9, 134.3, 132.9, 129.6, 128.6, 127.7, 127.66,
27.1, 126.3, 92.5, 86.2, 48.3, 46.4, 31.2, 28.2, 22.1, 21.5, 13.8;
3
3
o
(0.93 mL, 2.5 M in hexane, 2.31 mmol, 1.16 equiv) was added
+
+
MS (ESI) m/z: 865 ([2M+Na] ), 444 ([M+Na] ); IR (neat): ν = 3026,
dropwise over 2 minutes and the resulting solution was stirred for
-1
2
924, 2860, 1961, 1598, 1493, 1447, 1338, 1154, 1093 cm ;
1
0
5 minutes at this temperature. MsCl (0.18 mL, d = 1.48 g/mL,
.2664 g, 2.31 mmol, 1.16 equiv) was then added and the
+
32 2
HRMS calcd for C26H O NS ([M+H] ): 422.2148, found: 422.2149.
resulting mixture was stirred for 30 minutes followed by the
addition of LiBr (0.9812 g, 11.0 mmol, 5.5 equiv) at -78 C and
stirred at this temperature for 2 minutes. The resulting mixture
was removed from the dry ice/ethanol bath and then allowed to
warm up to room temperature and stirred at rt for 3 h, and the
solution was used directly in the next step.
(
(
(
(
5)
Preparation
of
o
R
a
)-N-(4-cyclohexyl-2,3-butadien-1-yl)-N-[(2E,4E)-5-
4-chlorophenyl)-pentadien-1-yl]
,2E,4E)-3e. (hanyl-8-179)
toluenesulfonamide
R
a
TsHN
PPh3 (1.2 equiv)
DIAD (1.2 equiv)
Cl
OH
TsN
To a separate flame-dried Schlenk tube was added NaH (60%
dispersion in mineral oil, 0.0884 g, 2.2 mmol, 1.1 equiv). The tube
+
Cl
THF, 0 oC to rt, 23.8 h
Cy
(
9
Ra)-1c
8% ee
(2E,4E)-
1.2 equiv
2
d
Cy
o
was placed into an ice bath (0 C). To the Schlenk tube was added
(Ra,2E,4E)-3e
3%, 98% ee
6
THF (3 mL) followed by the dropwise addition of (R )-dimethyl
a
2
-(2,3-octadien-1-yl) malonate (R )-1d (97% ee, 0.4446 g, 2.0
a
Following Typical Procedure B, the reaction of PPh (0.3902 g,
o
3
mmol) over 2 minutes at 0 C. Then 2 mL of THF were added and
the resulting mixture was then stirred for 30 minutes at this
temperature. The solution containing the (2E,4E)-dienyl bromide
prepared above was then transferred via a syringe to the Schlenk
tube containing the malonate and the resulting mixture was
allowed to warm up to room temperature naturally and stirred
for 9 h as monitored by TLC. A saturated aqueous solution of
NH Cl (5 mL) was added to the resulting mixture to quench the
4
reaction and white solid was precipitated out. Water (5 mL) was
added to dissolve the solid and the resulting mixture was poured
into a separatory funnel and then extracted with Et
The organic layer was combined, washed with brine (20 mL),
dried with anhydrous MgSO , filtered, and concentrated in vacuo.
The residue was purified via flash column chromatography on
silica gel to afford (R ,2E,4E)-3f (0.4888 g, 69%) (eluent:
petroleum ether/ethyl acetate = 30/1) as a liquid: 94% ee (HPLC
conditions: Chiralcel AD-H column, hexane/i-PrOH = 95/5, 1.0
1
a
.44 mmol, 1.2 equiv), (R )-N-(4-cyclohexyl-2,3-butadien-1-yl)
toluenesulfonamide (R
a
)-1c (98% ee, 0.3663 g, 1.2 mmol) /THF (5
mL), (2E,4E)-5-(4-chlorophenyl)-2,4-pentadien-1-ol 2d (0.2831 g,
1
1
(
.44 mmol, 1.2 equiv) /THF (3 mL), DIAD (0.3008 g, 1.44 mmol,
.2 equiv) /THF (2 mL) at rt for 23.8 h afforded (R ,2E,4E)-3e
a
0.3667 g, 63%) (eluent: petroleum ether/ethyl acetate =15/1) as
a liquid: 98% ee (HPLC conditions: Chiralcel AD-H column,
hexane/i-PrOH = 90/10, 0.8 mL/min, λ = 214 nm, t (minor) = 10.86
(major) = 12.03 min); H NMR (400 MHz, CDCl ) δ 7.71 (d, J
8.0 Hz, 2 H, ArH), 7.36-7.24 (m, 6 H, ArH ), 6.66 (dd, J = 15.6 Hz,
= 10.4 Hz, 1 H, HC=), 6.43 (d, J = 16.0 Hz, 1 H, HC=), 6.26 (dd, J
5.2 Hz, J = 10.4 Hz, 1 H, HC=), 5.63 (dt, J = 15.2 Hz, J = 6.6 Hz, 1
= 6.7 Hz, J = 2.8 Hz,
), 3.83 (dd, J = 7.0 Hz, J
), 2.00-1.87 (m, 1 H, CH),
+ CH), 1.32-0.98 (m, 5 H, 2 × CH + CH);
) δ 204.1, 143.2, 137.5, 135.5, 133.9,
R
1
min, t
R
3
=
1
2
O (20 mL × 3).
J
2
1
=
1
2
1
2
4
H, HC=), 5.15-5.07 (m, 1 H, HC=), 4.90 (qd, J
1
2
1
2
1
H, HC=), 3.94 (d, J = 6.8 Hz, 2 H, NCH
.2 Hz, 2 H, NCH ), 2.43 (s, 3 H, CH
.74-1.58 (m, 5 H, 2 × CH
2
1
2
=
a
2
3
2
2
1
3
C NMR (100 MHz, CDCl
3
mL/min, λ = 214 nm, t
R
(major) = 5.32 min, t
H NMR (400 MHz, CDCl ) δ 7.39-7.33 (m, 2 H, ArH), 7.29 (t, J = 7.6
Hz, 2 H, ArH), 7.20 (tt, J = 7.2 Hz, J = 1.5 Hz, 1 H, ArH), 6.72 (dd,
= 15.8 Hz, J = 10.6 Hz, 1 H, HC=), 6.45 (d, J = 15.6 Hz, 1 H, HC=),
6.25 (dd, J = 15.0 Hz, J = 10.6 Hz, 1 H, HC=), 5.63 (dt, J = 15.2 Hz,
= 7.6 Hz, 1 H, HC=), 5.09 (qt, J = 6.7 Hz, J = 2.2 Hz, 1 H, HC=),
.96-4.86 (m, 1 H, HC=), 3.72 (s, 6 H, 2 × CH ), 2.78 (d, J = 8.0 Hz, 2
), 2.61 (dd, J = 7.6 Hz, J = 2.4 Hz, 2 H, CH ), 1.98 (qd, J
.0 Hz, J = 2.8 Hz, 2 H, CH ), 1.44-1.27 (m, 4 H, 2 × CH ), 0.89 (t, J
7.2 Hz, 3 H, CH ); C NMR (100 MHz, CDCl ) δ 205.8, 171.0,
R
(minor) = 5.74 min);
1
4
33.2, 131.5, 129.7, 128.8, 128.6, 128.4, 127.5, 127.2, 98.6, 87.2,
8.3, 46.6, 37.1, 33.0, 32.97, 25.99, 25.91, 25.88, 21.5; MS (ESI)
1
3
3
7
+
35
+
1
2
m/z: 506 ([M( Cl)+Na] ), 504 ([M( Cl)+Na] ); IR (neat): ν = 3029,
J
1
2
2
1
4
923, 2850, 1959, 1596, 1490, 1446, 1405, 1341, 1305, 1156,
-1 35 35 +
1
2
1
090 cm ; HRMS calcd for
82.1915, found: 482.1912.
28 33 2
C H O N ClS ([M( Cl)+H] ):
J
2
1
2
4
3
H, CH
7
=
2
1
2
2
1
=
(
6)
Preparation
of
a
(R )-Dimethyl
2
2
2
2
-(2,3-octadien-1-yl)-2-[(2E,4E)-5- phenylhexadien-1-yl]malonate
13
3
3
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
1
37.1, 134.6, 131.5, 128.54, 128.50, 127.9, 127.4, 126.2, 91.0,
4.5, 58.0, 52.4, 52.36, 35.9, 32.7, 31.3, 28.4, 22.1, 13.8; MS (ESI)
petroleum ether/ethyl acetate =20/1) as a liquid: 94% ee (HPLC
conditions: Chiralcel AS-H column, hexane/i-PrOH = 95/5, 1.0
8
+
+
+
m/z: 787 ([2M+Na] ), 405 ([M+Na] ), 383 ([M+H] ); IR (neat): ν =
mL/min, λ = 214 nm, t
R
(minor) = 31.02 min, t
min); H NMR (400 MHz, CDCl ) δ 7.68 (d, J = 8.4 Hz, 2 H, ArH),
7.32-7.25 (m, 4 H, ArH), 7.23-7.14 (m, 3 H, ArH), 6.07-5.89 (m, 2 H,
× HC=), 5.64-5.53 (m, 1 H, HC=), 5.33-5.24 (m, 2 H, 2 × HC=),
4.95-4.87 (m, 1 H, HC=), 3.88-3.71 (m, 4 H, 2 × NCH ), 3.30 (dd, J
= 7.4 Hz, J = 2.6 Hz, 2 H, CH ), 2.42 (s, 3 H, CH ), 1.71 (d, J = 6.8
Hz, 3 H, CH ); C NMR (100 MHz, CDCl ) δ 205.6, 143.1, 139.7,
37.7, 134.6, 130.4, 129.7, 128.45, 128.42, 127.2, 126.3, 124.2,
91.9, 87.0, 48.3, 45.8, 35.2, 21.5, 18.1; MS (ESI) m/z: 416
R
(major) = 37.67
-
1
1
3
023, 2952, 2860, 1962, 1733, 1594, 1440, 1279, 1190, 1075 cm ;
3
+
HRMS calcd for C24
H
31
O
4
([M+H] ): 383.2217, found: 383.2215.
2
(
7) Preparation of (R
a
)-Dimethyl 2-(2,3-octadien-1-yl)-2-((2E,4E)-
2
1
5
-(4-chlorophenyl)pentadien-1-yl)malonate
(R
a
,2E,4E)-3g.
2
2
3
1
3
(hanyl-9-131, hanyl-9-132)
3
3
1
OH 1) n-BuLi (1.16 equiv)
THF, Ar, -78 oC, (1 15) min
+
Cl
2
) MsCl (1.16 equiv)
THF, -78 oC, 0.5 h
+
2E,4E)-2d
.1 equiv
([M+Na] ); IR (neat): ν = 3665, 3557, 3024, 2914, 2853, 2733,
(
1
3
) LiBr (5.5 equiv)
THF, -78 oC, 5 min
then rt, 0.68 h
Cl
2584, 1963, 1809, 1660, 1599, 1494, 1453, 1340, 1305, 1156,
MeO
MeO
2
C
C
THF
0 oC, 2 min
-1
+
2
CO
2
Me
1092, 1029 cm ; HRMS calcd for C24
H28NO
2
S ([M+H] ): 394.1835,
2
MeO C
then rt 13 h
n
found: 394.1832.
NaH (1.1 equiv)
-C
4
H
9
THF, 0 oC, (1 30) min
+
(R
a
,2E,4E)-3g
ee
(
9) Preparation of (S
(2E,4E)-hexadien-1-yl]
hanyl-9-200)
a
)-N-(4-cyclohexyl-2,3-butadien-1-yl)-N-
n-C H
4
9
65%, 94%
(
R
a
)-1d
[
(
toluenesulfonamide
(S
a
,2E,4E)-3h.
9
7% ee
Following Typical Procedure C, the reaction of
2E,4E)-5-(4-chlorophenyl)-2,4-pentadien-1-ol 2d (0.4321 g, 2.2
mmol, 1.16 equiv), n-BuLi (0.93 mL, 2.5 M in hexane, 2.31 mmol,
.16 equiv), MsCl (0.18 mL, 0.2664 g, 2.31 mmol, 1.16 equiv), LiBr
0.9676 g, 11.0 mmol, 5.5 equiv), NaH (0.0912 g, 2.2 mmol, 1.1
equiv), and (R )-dimethyl 2-(2,3-octadien-1-yl)malonate (R )-1d
97% ee, 0.4803 g, 2.0 mmol) in THF (10 mL) afforded
,2E,4E)-3g (0.5397 g, 65%) (eluent: petroleum ether/ethyl
TsHN
PPh3 (1.05 equiv)
1.05 equiv)
THF, 0 oC to rt, 24 h
CH3
(
OH
DIAD
(
TsN
+
H C
3
Cy
1
(
S
9
1c
(
a)-
9% ee
Cy
(
2E,4E)-2a
(
6
S
E E
a,2 ,4 )-
3h
0%, 97% ee
1.05 equiv
a
a
(
(
3
Following Typical Procedure B, the reaction of PPh (0.5518 g,
R
a
2.1
a
mmol,
1.05
equiv),
a
acetate = 30/1) as an oil: 94% ee (HPLC conditions: Chiralcel AD-H
column, hexane/i-PrOH = 95/5, 0.7 mL/min, λ = 214 nm, t (major)
(minor) = 10.72 min); H NMR (400 MHz, CDCl ) δ
.32-7.23 (m, 4 H, ArH), 6.69 (dd, J = 15.6 Hz, J = 10.4 Hz, 1 H,
= 14.8 Hz, J
= 7.6 Hz, 1 H, CH),
.15-5.05 (m, 1 H, HC=), 4.95-4.85 (m, 1 H, HC=), 3.73 (s, 6 H, 2 ×
), 2.78 (d, J = 7.6 Hz, 2 H, CH ), 2.61 (dd, J = 7.8 Hz, J = 2.2 Hz,
H, CH ), 2.03-1.93 (m, 2 H, CH ), 1.45-1.28 (m, 4 H, 2 × CH ), 0.89
t, J = 7.0 Hz, 3 H, CH ); C NMR (100 MHz, CDCl ) δ 205.8, 171.0,
35.7, 134.3, 132.9, 130.2, 129.2, 128.69, 128.68, 127.3, 91.1,
4.5, 58.0, 52.46, 52.43, 35.9, 32.7, 31.3, 28.5, 22.1, 13.9; MS (ESI)
(S )-N-(4-cyclohexyl-2,3-butadien-1-yl)toluenesulfonamide (S )-1c
R
(99% ee, 0.6420 g, 2.1 mmol, 1.05 equiv) /THF (5 mL),
(2E,4E)-hexa-2,4-dien-1-ol 2a (0.1970 g, 2.0 mmol) /THF (3 mL),
DIAD (0.4366 g, 2.1 mmol, 1.05 equiv) /THF (2 mL) at rt for 24 h
afforded (S ,2E,4E)-3c (0.4463 g, 60%) (eluent: petroleum
ether/ethyl acetate =30/1) as a liquid: 97% ee (HPLC conditions:
1
=
7
9.69 min, t
R
3
1
2
HC=), 6.40 (d, J = 15.6 Hz, 1 H, HC=), 6.23 (dd, J
1
2
=
a
10.4 Hz, 1 H, HC=), 5.65 (dt, J
1
= 15.2 Hz, J
2
5
Chiralcel AD-H column, hexane/i-PrOH = 98/2, 1.0 mL/min, λ =
1
CH
3
2
1
2
214 nm, t (major) = 15.27 min, t (minor) = 16.76 min); H NMR
R
R
2
(
2
2
2
(400 MHz, CDCl ) δ 7.70 (d, J = 8.4 Hz, 2 H, ArH), 7.28 (d, J = 8.0
3
1
3
3
3
Hz, 2 H, ArH), 6.06 (dd, J = 14.8 Hz, J = 10.4 Hz, 1 H, HC=),
1
2
1
8
6.01-5.92 (m, 1 H, HC=), 5.70-5.58 (m, 1 H, HC=), 5.32 (dt, J = 14.8
Hz, J = 6.8 Hz, 1 H, HC=), 5.11-5.06 (m, 1 H, HC=), 4.88 (qd, J =
6.7 Hz, J = 2.8 Hz, 1 H, HC=), 3.86 (d, J = 6.8 Hz, 2 H, NCH ), 3.80
2 2
1 2 2 3
(dd, J = 7.0 Hz, J = 2.2 Hz, 2 H, NCH ), 2.42 (s, 3 H, CH ), 1.99-1.87
1
2
1
3
7
+
35
+
37
+
m/z: 441 ([M( Cl)+Na] ), 439 ([M( Cl)+Na] ), 419 ([M( Cl)+H] ),
3
5
+
4
17 ([M( Cl)+H] ); IR (neat): ν = 3023, 2952, 2859, 1962, 1733,
-
1
35
1
488, 1439, 1278, 1189, 1084 cm ; HRMS calcd for C24
H
30 ClO
4
(m, 1 H, CH of Cy), 1.76-1.58 (m, 8 H, CH + 2 × CH + one proton
3
2
3
5
+
13
([M( Cl)+H] ): 417.1827, found: 417.1825.
of CH ), 1.31-0.96 (m, 5 H, 2 × CH + one proton of CH ); C NMR
2
2
2
(
3
100 MHz, CDCl ) δ 204.0, 143.0, 137.6, 134.5, 130.4, 130.2,
(
[
(
8) Preparation of (S
(2E,4E)-hexadien-1-yl]
hanyl-10-008)
a
)-N-(5-phenyl-2,3-pentadien-1-yl)-N-
129.6, 127.1, 124.3, 98.4, 87.2, 48.2, 46.2, 37.0, 32.9, 26.0, 25.9,
21.5, 18.0; MS (ESI) m/z: 408 ([M+Na] ); IR (neat): ν = 3666, 3553,
3370, 3021, 2923, 2851, 2733, 2659, 2589, 2483, 2364, 2304,
+
toluenesulfonamide (S ,2E,4E)-3b
a
2
247, 1960, 1918, 1811, 1729, 1661, 1598, 1494, 1447, 1344,
TsHN
PPh
3
(1.05 equiv)
CH
3
-1
OH
DIAD (1.05 equiv)
THF, 0 oC to rt, 24 h
TsN
1305, 1261, 1225, 1157, 1119, 1093, 1047, 1019 cm ; HRMS calcd
for C23H32NO S ([M+H] ): 386.2148, found: 386.2143.
2
+
H C
+
3
Bn
(
S
a
)-1b
(2E,4E)-2a
Bn
9
2% ee
S ,2E,4E 3b
)-
ee
(
5
a
3. Rhodium-catalyzed Highly Diastereoselective Intramolecular
4+2] Cycloaddition of Allene-1,3-dienes
1
.05 equiv
6%, 94%
[
Following Typical Procedure B, the reaction of PPh (0.5577 g,
3
2
.1 mmol, 1.05 equiv), (S
a
)-N-(5-phenyl-2,3-pentadien-1-yl)
(1) Preparation of (3aR,5S,7aR,Z)-5-methyl-2-((4-methylphenyl)-
sulfonyl)-4-pentylidene-2,3,3a,4,5,7a-hexahydro-1H-isoindole
(3aR,5S,7aR,Z)-4a. (hanyl-12-162)
toluenesulfonamide (S )-1b (92% ee, 0.6587 g, 2.1 mmol, 1.05
equiv) /THF (5 mL), (2E,4E)-hexa-2,4-dien-1-ol 2a (0.1986 g, 2.0
mmol) /THF (3 mL), DIAD (0.4575 g, 2.1 mmol, 1.05 equiv) /THF (2
a
a
mL) at rt for 24 h afforded (S ,2E,4E)-3g (0.4484 g, 56%) (eluent:
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
4
H, ArH), 7.20 (t, J = 7.2 Hz, 1 H, ArH), 7.10 (d, J = 7.2 Hz, 2 H,
H
H
RhCl(PPh
AgSbF
3
)
3
(3 mol%)
ArH), 5.59 (t, J = 7.6 Hz, 1 H, HC=), 5.43 (dt, J = 10.0 Hz, J = 2.9
Hz, 1 H, HC=), 5.16 (d, J = 10.0 Hz, 1 H, HC=), 3.48 (dd, J
J = 6.4 Hz, 1 H, one proton of NCH ), 3.41-3.21 (m, 5 H, CH of Bn
2 2 2
2 1 2
+ two protons of NCH + CH), 3.14 (dd, J = 10.4 Hz, J = 9.2 Hz, 1
CH
3
1
2
6
(5 mol%)
TsN
TsN
H
CH
1
= 10.0 Hz,
EtOH, Ar, rt, 2 h
3
n-C H
n-C H9
4
9
4
(3aR,5S,7aR,Z)-4a
73%, 97% ee
(
Ra,2E,4E)-3a
ee
H, one proton of NCH ), 2.86-2.76 (m, 1 H, CH), 2.70-2.62 (m, 1 H,
2
9
7%
13
CH), 2.42 (s, 3 H, CH
MHz, CDCl ) δ 143.3, 140.6, 137.2, 133.8, 132.9, 129.5, 128.5,
28.1, 127.5, 127.2, 126.0,125.8, 54.5, 50.5, 39.3, 38.1, 35.3, 33.1,
3 3
), 1.12 (d, J = 7.6 Hz, 3 H, CH ); C NMR (100
3
Typical Procedure I: To a flame-dried Schlenk tube were
added RhCl(PPh (14.2 mg, 0.015 mmol) and AgSbF (8.9 mg,
.025 mmol) inside a glove box. Under argon atmosphere, to the
Schlenk tube was added 3 mL of EtOH outside the glove box. Then
the resulting mixture was stirred at room temperature for 10 min.
1
2
=
1
3
)
3
6
+
+
4.8, 21.5; MS (ESI) m/z: 416 ([M+Na] ), 394 ([M+H] ); IR (neat): ν
0
3078, 3015, 2955, 2908, 2865, 1596, 1490, 1451, 1381, 1337,
-1
292, 1229, 1177, 1153, 1130, 1105, 1086, 1052, 1023 cm ; Anal
Calcd for C24
.26, N 3.26.
2
H27NO S: C 73.25, H 6.92, N 3.56. found: C 73.43, H
a
To the tube were added (R ,2E,4E)-3a (178.6 mg, 0.5 mmol, 97%
7
ee) and EtOH (2 mL) sequentially. After being stirred at room
temperature for 2 h, the reaction was complete as monitored by
TLC. The crude reaction mixture was filtrated through a pad of
silica gel and eluted with diethyl ether (20 mL) and then
concentrated in vacuo to afford the crude product, which was
separated by chromatography on silica gel to afford
3aR,5S,7aR,Z)-4a (131.1 mg, 73%) (eluent: petroleum ether/ethyl
acetate = 30/1) as s liquid: 97% ee (HPLC conditions: Chiralcel
OD-H column, hexane/i-PrOH = 98/2, 1.5 mL/min, λ = 214 nm,
(
(
3) Preparation of (3aR,5S,7aR,Z)-4-phenylethylidene-5-propyl-2-
(4-methylphenyl)sulfonyl)-2,3,3a,4,5,7a-hexahydro-1H-isoindol
e (3aR,5S,7aR,Z)-4c. (hanyl-9-111)
H
n-C H
RhCl(PPh
AgSbF
3
)
3
(3 mol%)
3
7
(
TsN
6
(5 mol%)
TsN
H
EtOH, Ar, rt,
9 h
n-C H7
H
3
n-C H
4
9
n-C
H
4
9
1
t
R
(major) = 8.50 min, t
CDCl
.44-5.34 (m, 2 H, 2 × HC=), 5.12 (d, J = 10.0 Hz, 1 H, HC=), 3.49
dd, J = 10.0 Hz, J = 6.8 Hz, 1 H, one proton of NCH ), 3.36 (t, J =
.4 Hz, 1 H, one proton of NCH ), 3.29 (d, J = 10.0 Hz, 1 H, one
R
(minor) = 11.87 min); H NMR (400 MHz,
(
R
a
,2E,4E)-3c
ee
(3aR,5S,7aR,Z)
-4c
75%, 93%
ee
3
) δ 7.71 (d, J = 8.0 Hz, 2 H, ArH), 7.32 (d, J = 8.0 Hz, 2 H, ArH),
9
3%
5
(
8
1
2
2
Following Typical Procedure I, the reaction of RhCl(PPh
(11.0 mg, 0.012 mmol), AgSbF (6.9 mg, 0.02 mmol), and
(R ,2E,4E)-3c (157.5 mg, 0.4 mmol, 93% ee) in EtOH (4.0 mL)
afforded (3aR,5S,7aR,Z)-4c (118.4 mg, 75%) (eluent: petroleum
ether/ethyl acetate = 30/1) as a liquid: 93% ee (HPLC conditions:
3 3
)
2
6
proton of NCH
proton of NCH
.44 (s, 3 H, CH
2
), 3.21-3.13 (m, 1 H, CH), 3.11-3.04 (m, 1 H, one
), 2.79-2.67 (m, 1 H, CH), 2.64-2.57 (m, 1 H, CH),
), 1.35-1.22 (m, 4 H, 2 ×
), 0.88 (t, J = 6.8 Hz, 3 H, CH
) δ 143.3, 135.6, 133.9, 133.1, 129.4, 129.3,
27.5, 125.8, 54.5, 50.6, 39.2, 38.1, 35.2, 32.1, 26.7, 24.9, 22.2,
1.5, 13.9; MS (EI) m/z (%): 359 (M+, 1.02), 91 (100); IR (neat): ν =
956, 2924, 2894, 2859, 1451, 1335, 1300, 1290, 1232, 1161,
131, 1087, 1052, 1028, 1012 cm ; HRMS calcd for C21
a
2
2
CH
3
), 2.02-1.91 (m, 2 H, CH
2
1
3
2
), 1.07 (d, J = 7.6 Hz, 3 H, CH
3
3
);
C
Chiralcel OD-H column, hexane/i-PrOH = 100/1, 1.0 mL/min, λ =
1
NMR (100 MHz, CDCl
3
214 nm, t
(400 MHz, CDCl
Hz, 2 H, ArH), 5.54-5.48 (m, 1 H, HC=), 5.32 (t, J = 7.4 Hz, 1 H,
HC=), 5.16 (d, J = 10.0 Hz, 1 H, HC=), 3.49 (dd, J = 10.4 Hz, J = 6.8
Hz, 1 H, one proton of NCH ), 3.34 (t, J = 8.8 Hz, 1 H, one proton of
NCH ), 3.24 (dd, J = 10.2 Hz, J = 1.8 Hz, 1 H, one proton of NCH
, 3.21-3.14 (m, 1 H, CH), 3.04 (t, J = 10.0 Hz, 1 H, one proton of
R
(major) = 15.71 min, t
R
(minor) = 19.35 min); H NMR
1
2
2
1
3
) δ 7.70 (d, J = 8.0 Hz, 2 H, ArH), 7.31 (d, J = 8.0
1
2
-
1
H
29NO
2
S
2
+
(
M ): 359.1914, found: 359.1915.
2
1
2
2
)
(
-
2) Preparation of (3aR,5S,7aR,Z)-5-methyl-4-phenylethylidene
2-((4-methylphenyl)sulfonyl)-2,3,3a,4,5,7a-hexahydro-1H-iso-
NCH
2
), 2.68-2.61 (m, 1 H, CH), 2.58-2.50 (m, 1 H, CH), 2.44 (s, 3 H,
), 1.36-1.18 (m, 8 H, 4 × CH ),
); C NMR (100 MHz, CDCl ) δ 143.3,
134.2, 133.6, 131.7, 129.6, 129.4, 127.6, 126.0, 54.5, 50.5, 41.0,
0.8, 39.6, 37.8, 32.1, 26.8, 22.2, 21.5, 20.9, 14.0, 13.9; MS (ESI)
CH
3
), 1.97 (q, J = 6.9 Hz, 2 H, CH
2
2
1
3
indole (3aR,5S,7aR,Z)-4b. (hanyl-9-109)
0.92-0.84 (m, 6 H, 2 × CH
3
3
H
CH3
RhCl(PPh
AgSbF
3
)
3
(3 mol%)
4
TsN
6
(5 mol%)
TsN
H
+
+
+
m/z: 797 ([2M+Na] ), 410 ([M+Na] ), 388 ([M+H] ); IR (neat): ν =
EtOH, Ar, rt, 9 h
CH3
H
3015, 2953, 2923, 2861, 1654, 1597, 1460, 1385, 1333, 1222,
1157, 1120, 1094, 1030 cm ; HRMS calcd for C23
388.2305, found: 388.2305.
-
1
+
Bn
Bn
H
34
O
2
NS([M+H] ):
R
a
,2E,4E 3b
9
R,5S,7aR,Z -4b
3a )
6
(
)-
7% ee
(
2%, 97%
ee
(
4) Preparation of (3aR,5R,7aR,Z)-4-pentylidene-5-phenyl-2-((4-
methylphenyl)sulfonyl)-2,3,3a,4,5,7a-hexahydro-1H-isoindole
3aR,5R,7aR,Z)-4d. (hanyl-9-138)
Following Typical Procedure I, the reaction of RhCl(PPh
13.6 mg, 0.015 mmol), AgSbF (8.7 mg, 0.025 mmol), and
,2E,4E)-3b (196.7 mg, 0.5 mmol, 97% ee) in EtOH (5.0 mL)
3 3
)
(
(
6
(
R
a
afforded (3aR,5S,7aR,Z)-4b (121.6 mg, 62%) (eluent: petroleum
ether/ethyl acetate = 15/1) as a white solid: m.p. 117-120 C
o
(dichloromethane/petroleum ether); 97% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH = 95/5, 1.0 mL/min, λ =
1
2
14 nm, t
R
(major) = 16.45 min, t
R
(minor) = 22.78 min); H NMR
(
400 MHz, CDCl
3
) δ 7.70 (d, J = 8.4 Hz, 2 H, ArH), 7.29 (t, J = 8.4 Hz,
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
H
1 H, CH of Cy), 1.77-1.48 (m, 5 H, 2 × CH + one proton of CH ),
2
2
Ph
RhCl(PPh
AgSbF
EtOH, Ar, 40 oC, 5 h
3
)
3
(3 mol%)
13
1
.34-1.02 (m, 5 H, 2 × CH
2
2
+ one proton of CH ); C NMR (100
TsN
TsN
6
(5 mol%)
H
Ph
MHz, CDCl ) δ 143.3, 142.1, 137.4, 133.1, 131.8, 131.77, 129.5,
3
H
129.1, 129.0, 128.3, 128.2, 127.6, 53.9, 50.0, 45.0, 39.7, 38.2,
3
7
+
n-C H
n-C
4
H9
36.5, 33.8, 33.3, 25.8, 25.7, 21.5; MS (ESI) m/z: 484 ([M( Cl)+H] ),
4
9
35 +
R
a
,2E,4E 3d
)-
(3a
R,5R,7aR,Z -4d
59%, 96%
)
482 ([M( Cl)+H] ); IR (neat): ν = 2921, 2848, 1597, 1487, 1447,
-1
(
ee
9
8% ee
1403, 1344, 1305, 1160, 1090, 1041, 1013 cm ; HRMS calcd for
35 35 +
28 2
C H33 ClNO S ([M( Cl)+H] ): 482.1915, found: 482.1915.
Following Typical Procedure I, the reaction of RhCl(PPh
13.8 mg, 0.015 mmol), AgSbF (8.6 mg, 0.025 mmol), and
,2E,4E)-3d (184.8 mg, 0.5 mmol, 98% ee) in EtOH (5 mL)
afforded (3aR,5R,7aR,Z)-4d (110.0 mg, 59%) (eluent: petroleum
ether/ethyl acetate = 15/1) as a liquid: 96% ee (HPLC conditions:
3 3
)
(
(
6
(
5
6)
Preparation
of
(3aR,5R,7aR,E)-Dimethyl
R
a
-phenyl-4-pentylidene-1,3,3a,4,5,7a-hexahydro-2H-indene-2,2-
dicarboxylate (3aR,5R,7aR,E)-4f. (hanyl-9-147)
H
Chiralcel OD-H column, hexane/i-PrOH = 95/5, 1.0 mL/min, λ =
RhCl(PPh
AgSbF
3
)
3
(3 mol%)
MeO
MeO
2
C
C
MeO
MeO
2
C
C
1
6
(5 mol%)
H
2
(
14 nm, t
400 MHz, CDCl
Hz, 2 H, ArH), 7.24-7.15 (m, 3 H, ArH), 7.13-7.07 (m, 2 H, ArH),
R
(major) = 11.04 min, t
R
(minor) = 13.57 min); H NMR
2
2
EtOH, Ar, rt, 23 h
H
3
) δ 7.56 (d, J = 8.0 Hz, 2 H, ArH), 7.27 (d, J = 8.0
n-C H9
n-C H9
4
4
R
a
,2E,4E)-3f
4% ee
(3aR,5R,7aR,E)
82%,
-4f
94% ee
(
5
=
3
.81 (ddd, J
7.4 Hz, 1 H, HC=), 5.48 (dt, J
.92 (br, 1 H, one proton of NCH
), 3.34-3.25 (m, 1 H, CH), 3.20 (dd, J
= 2.4 Hz, 1 H, one proton of NCH ), 3.07 (dd, J = 9.8 Hz,
= 8.6 Hz, 1 H, one proton of NCH ), 2.83-2.76 (m, 1 H, CH), 2.72
t, J = 10.2 Hz, 1 H, CH), 2.45 (s, 3 H, CH ), 2.08-1.98 (m, 2 H, CH ),
.37-1.22 (m, 4 H, 2 × CH ), 0.88 (t, J = 7.2 Hz, 3 H, CH ); C NMR
100 MHz, CDCl ) δ 143.6, 143.1, 133.7, 133.3, 130.9, 129.7,
1
= 10.2 Hz, J
2
= 4.2 Hz, J
= 10.3 Hz, J
), 3.55 (dd, J
3
= 2.4 Hz, 1 H, HC=), 5.58 (t, J
= 1.9 Hz, 1 H, HC=),
= 10.2 Hz, J = 7.2
9
1
2
Following Typical Procedure I, the reaction of RhCl(PPh3)3
13.8 mg, 0.015 mmol), AgSbF (8.5 mg, 0.025 mmol), and
,2E,4E)-3f (194.4 mg, 0.5 mmol, 94% ee) in EtOH (5.0 mL) at rt
2
1
2
(
(
6
Hz, 1 H, one proton of NCH
0.4 Hz, J
2
1
=
R
a
1
2
2
1
for 23 h (the reaction process is tracked via NMR analysis).
Separation of the crude mixture by chromatography on silica gel
to afford (3aR,5R,7aR,E)-4f (158.7 mg, 82%) (eluent: petroleum
ether/ethyl acetate = 30/1) as a liquid: 94% ee (HPLC conditions:
J
2
2
(
1
(
1
3
(
1
(
3
2
1
3
2
3
3
Chiralcel OD-H column, hexane/i-PrOH = 200/1, 1.0 mL/min, λ =
29.4, 128.5, 128.1, 127.5, 127.0, 126.1, 53.9, 49.6, 45.6, 39.7,
8.0, 32.0, 27.0, 22.2, 21.5, 13.9; MS (ESI) m/z: 444 ([M+Na] ), 422
[M+H] ); IR (neat): ν = 3025, 2954, 2861, 1597, 1483, 1455, 1340,
214, 1159, 1094, 1042 cm ; HRMS calcd for C26H32NO S
1
+
214 nm, t
(400 MHz, CDCl
2 H, ArH), 7.16 (t, J = 7.0 Hz, 1 H, ArH), 5.92 (ddd, J
4.4 Hz, J = 2.4 Hz, 1 H, HC=), 5.75 (d, J = 10.0 Hz, 1 H, HC=), 5.56
t, J = 7.4 Hz, 1 H, HC=), 3.98 (brs, 1 H, one proton of CH ), 3.69 (s,
H, OCH ), 3.63 (s, 3 H, OCH ), 3.24 (dt, J = 12.4 Hz, J = 7.6 Hz, 1
H, one proton of CH ), 2.82-2.74 (m, 1 H, CH), 2.54 (dd, J = 13.6
Hz, J = 8.4 Hz, 1 H, one proton of CH ), 2.30 (dd, J = 13.8 Hz, J
.4 Hz, 1 H, one proton of CH ), 2.15-2.00 (m, 3 H, one proton of
CH + CH ), 1.94 (t, J = 13.0 Hz, 1 H, one proton of CH ), 1.42-1.27
(m, 4 H, 2 × CH ); C NMR (100 MHz,
CDCl ) δ 172.9, 172.2, 144.4, 136.8, 131.0, 129.1, 128.0, 127.9,
27.2, 125.8, 59.5, 52.6, 52.4, 46.1, 40.3, 40.1, 38.9, 37.7, 32.1,
R
(major) = 11.86 min, t
R
(minor) = 19.35 min); H NMR
+
3
) δ 7.33 (d, J = 7.6 Hz, 2 H, ArH), 7.26 (t, J = 7.6 Hz,
2
= 10.0 Hz, J =
-
1
1
2
+
3
[M+H] ): 422.2148, found: 422.2144.
(
2
3
3
3
1
2
(
5) Preparation of (3aR,5R,7aR,Z)-5-(4-chlorophenyl)-4-cyclo-
hexylmethylene-2-((4-methylphenyl)sulfonyl)-2,3,3a,4,5,7a-hexa
2
1
2
2
1
2
=
hydro-1H-isoindole (3aR,5R,7aR,Z)-4e. (hanyl-9-019)
3
2
H
2
2
2
Cl
13
RhCl(PPh
AgSbF
EtOH, Ar, rt, 10 h
3
)
3
(3 mol%)
TsN
2 3
), 0.90 (t, J = 7.2 Hz, 3 H, CH
6
(5 mol%)
TsN
H
3
H
1
2
Cy
Cy
Cl
+
+
6.9, 22.2, 13.9; MS (ESI) m/z: 405 ([M+Na] ), 383 ([M+H] ); IR
(
R
a
,2E,4E)-3e
3aR,5R,7aR,Z)
9%, 99% ee
-4e
(
9
8% ee
(neat): ν = 3021, 2951, 2863, 1733, 1596, 1491, 1442, 1247, 1195,
7
-
1
+
1
162, 1110, 1064 cm ; HRMS calcd for C24
H34NO
4
([M+NH
4
] ):
Following Typical Procedure I, the reaction of RhCl(PPh
14.0 mg, 0.015 mmol), AgSbF (8.6 mg, 0.025 mmol), and
,2E,4E)-3e (247.0 mg, 0.5 mmol, 98% ee) in EtOH (5.0 mL)
3 3
)
400.2482, found: 400.2480.
(
(
6
R
a
(7)
Preparation
of
(3aR,5R,7aR,E)-Dimethyl
afforded (3aR,5R,7aR,Z)-4e (194.1 mg, 79%) (eluent: petroleum
ether/ethyl acetate = 20/1) as a white solid: 99% ee (HPLC
conditions: Chiralcel AD-H column, hexane/i-PrOH = 90/10, 1.0
5-phenyl-4-pentylidene-1,3,3a,4,5,7a-hexahydro-2H-indene-2,2-
dicarboxylate (3aR,5R,7aR,E)-4g. (hanyl-9-134)
H
Cl
RhCl(PPh
AgSbF
)
(3 mol%)
3
3
MeO
MeO
2
C
C
MeO
MeO
2
C
C
mL/min, λ = 214 nm, t
R
(major) = 6.68 min, t
H NMR (400 MHz, CDCl ) δ 7.55 (d, J = 8.4 Hz, 2 H, ArH), 7.29 (d, J
8.0 Hz, 2 H, ArH), 7.13 (d, J = 8.8 Hz, 2 H,ArH), 7.02 (d, J = 8.4 Hz,
H, ArH), 5.80 (ddd, J = 10.2 Hz, J = 4.4 Hz, J = 2.2 Hz, 1 H, HC=),
.54 (d, J = 10.0 Hz, 1 H, HC=), 5.41 (d, J = 9.2 Hz, 1 H, HC=), 3.83
), 3.59 (dd, J = 10.0 Hz, J = 7.2 Hz, 1
), 3.32 (dd, J = 18.4 Hz, J = 8.4 Hz, 1 H,
= 2.8 Hz, 1 H, one proton of NCH ),
.06 (t, J = 9.0 Hz, 1 H, one proton of NCH ), 2.87-2.79 (m, 1 H,
CH), 2.53 (t, J = 10.2 Hz, 1 H, CH), 2.48 (s, 3 H, CH ), 2.25-2.13 (m,
R
(minor) = 7.78 min);
6
(5 mol%)
H
1
2
2
3
EtOH, Ar, rt, 9 h
H
=
2
5
n-C H
n-C
R,5R,7aR,E)-4g
4
H
9
Cl
4
9
(R
a
9
,2E,4E)-3g
4% ee
(3a
80%,
1
2
3
9
4% ee
(brs, 1 H, one proton of NCH
2
1
2
Following Typical Procedure I, the reaction of RhCl(PPh3)3
(13.8 mg, 0.015 mmol), AgSbF6 (8.7 mg, 0.025 mmol), and
H, one proton of NCH
2
1
2
CH), 3.11 (dd, J
1
= 10.0 Hz, J
2
2
(R ,2E,4E)-3g (208.1 mg, 0.5 mmol, 94% ee) in EtOH (5.0 mL) at rt
a
3
2
for 9 h (the reaction process is tracked via NMR analysis) afforded
3
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
(
3aR,5R,7aR,E)-4g (167.4 mg, 80%) (eluent: petroleum ether/ethyl
-indole (3aS,5R,7aS,Z)-4h. (hanyl-10-003)
acetate = 30/1) as a liquid: 94% ee (HPLC conditions: Chiralcel
OD-H column, hexane/i-PrOH = 95/5, 0.7 mL/min, λ = 214 nm,
H
CH3
RhCl(PPh
AgSbF
3 3
)
6
(3 mol%)
(5 mol%)
TsN
TsN
1
CH3
t
R
(major) = 6.50 min, t
CDCl ) δ 7.30-7.20 (m, 4 H, ArH), 5.88 (ddd, J
Hz, J = 2.2 Hz, 1 H, HC=), 5.76 (d, J = 10.4 Hz, 1 H, HC=), 5.54 (t, J =
.4 Hz, 1 H, HC=), 3.94 (brs, 1 H, CH), 3.71 (s, 3 H, OCH ), 3.65 (s, 3
H, OCH ), 3.23 (dt, J = 12.5 Hz, J = 7.5 Hz, 1 H, CH), 2.83-2.74 (m,
H, CH), 2.57 (dd, J = 13.8 Hz, J = 8.2 Hz, 1 H, one proton of
CH ), 2.27 (dd, J = 13.8 Hz, J = 3.8 Hz, 1 H, one proton of CH ),
.10 (qd, J = 7.2 Hz, J = 3.1 Hz, 2 H, CH ), 2.03 (dd, J = 13.6 Hz, J
8.0 Hz, 1 H, one proton of CH ), 1.88 (t, J = 12.8 Hz, 1 H, one
), 1.41-1.24 (m, 4 H, 2 × CH ), 0.90 (t, J = 7.0 Hz, 3 H,
); C NMR (100 MHz, CDCl ) δ 172.9, 172.3, 143.0, 136.6,
R
(minor) = 7.89 min); H NMR (400 MHz,
EtOH, Ar, rt, 5 h
H
H
3
1 2
= 10.0 Hz, J = 4.2
Cy
Cy
3
7
3
Sa
E
E
3h
(3aS,5R,7aS,Z)-4h
ee
(
,2 ,4 )-
97% ee
7
7%, 96%
3
1
2
1
1
2
Following Typical Procedure I, the reaction of RhCl(PPh3)3
13.8 mg, 0.015 mmol), AgSbF (8.7 mg, 0.025 mmol), and
,2E,4E)-3h (193.4 mg, 0.5 mmol, 97% ee) in EtOH (5.0 mL)
2
1
2
2
(
(
6
2
=
1
2
2
1
2
S
a
2
afforded (3aS,5R,7aS,Z)-4h (148.3 mg, 77%) (eluent: petroleum
proton of CH
CH
2
2
o
1
3
ether/ethyl acetate
dichloromethane/ petroleum ether); 96% ee (HPLC conditions:
Chiralcel AS-H column, hexane/i-PrOH = 90/10, 1.0 mL/min, λ =
=
20/1) as
a
solid: m.p. 97-99
C
3
3
(
1
4
31.7, 131.5, 129.6, 128.7, 128.1, 127.4, 59.5, 52.7, 52.6, 45.5,
0.3, 40.1, 38.8, 37.8, 32.1, 27.0, 22.2, 13.9; MS (ESI) m/z: 441
1
3
7
+
35
+
37
+
214 nm, t
(400 MHz, CDCl
Hz, 2 H, ArH), 5.38 (dt, J
= 9.2 Hz, 1 H, HC=), 5.10 (d, J = 10.4 Hz, 1 H, HC=), 3.51 (dd, J
0.4 Hz, J = 6.8 Hz, 1 H, one proton of NCH ), 3.36 (dd, J = 8.8 Hz,
= 7.6 Hz, 1 H, one proton of NCH ), 3.28 (dd, J = 10.2 Hz, J
.0 Hz, 1 H, one proton of NCH ), 3.20-3.12 (m, 1 H, CH), 3.07 (dd,
= 10.8 Hz, J = 8.8 Hz, 1 H, one proton of NCH ), 2.74-2.64 (m, 1
H, CH), 2.63-2.57 (m, 1 H, CH), 2.44 (s, 3 H, CH ), 2.16-2.03 (m, 1
H, CH of Cy), 1.76-1.60 (m, 3 H, CH + one proton of CH ),
.56-1.46 (m, 2 H, CH ), 1.32-0.94 (m, 8 H, CH + 2 × CH + one
R
(major) = 17.51 min, t
) δ 7.71 (d, J = 8.4 Hz, 2 H, ArH), 7.32 (d, J = 8.0
= 10.0 Hz, J = 3.0 Hz, 1 H, HC=), 5.22 (d, J
R
(minor) = 20.67 min); H NMR
([M( Cl)+Na] ), 439 ([M( Cl)+Na] ), 419 ([M( Cl)+H] ), 417
35 +
3
([M( Cl)+H] ); IR (neat): ν = 3018, 2951, 2862, 1733, 1486, 1441,
-
1
1
2
1
C
395, 1248, 1195, 1163, 1102, 1060, 1014 cm ; HRMS calcd for
3
5
35
+
1
=
24
H
33 ClNO
4
([M( Cl)+NH
4
] ): 434.2093, found: 434.2091.
1
2
2
1
J
2
2
1
2
=
(
8) Preparation of (3aS,5R,7aS,Z)-5-methyl-4-(2-phenylethyli-
1
2
dene)-2-((4-methylphenyl)sulfonyl)-2,3,3a,4,5,7a-hexahydro-1H-
isoindole (3aS,5R,7aS,Z)-4b. (hanyl-10-011)
J
1
2
2
3
H
2
2
CH3 RhCl(PPh
AgSbF
3
)
3
(2 mol%)
TsN
6
(3 mol%)
TsN
CH3
1
2
3
2
13
EtOH, Ar, rt, 9 h
H
2 3
proton of CH ); C NMR (100 MHz, CDCl ) δ 143.2, 135.5, 133.8,
H
1
3
33.7, 133.0, 129.6, 129.4, 127.5, 125.7, 54.5, 50.9, 39.2, 38.4,
6.0, 35.1, 33.9, 33.3, 25.86, 25.80, 25.77, 24.9, 21.4; MS (ESI)
Bn
Bn
(
S
a
,2
9
E,4E 3b
)-
4% ee
(
3aS,5
0%, 94%
R,7aS,Z -4b
)
+
+
m/z: 408 ([M+Na] ), 386 ([M+H] ); IR (neat): ν = 2920, 2852, 1746,
ee
8
-1
1
C
458, 1375, 1259, 1162, 1093, 1022 cm ; Anal Calcd for
S: C 71.65, H 8.10, N 3.63. found: C 71.69, H 7.92, N
Following Typical Procedure IV, the reaction of RhCl(PPh
13.8 mg, 0.015 mmol), AgSbF (8.8 mg, 0.025 mmol), and
,2E,4E)-4b (197.4 mg, 0.5 mmol, 94% ee) in EtOH (5.0 mL)
3
)
3
23 2
H31NO
(
(
6
3.37.
S
a
afforded (3aS,5R,7aS,Z)-4b (158.4 mg, 80%) (eluent: petroleum
ether/ethyl acetate = 15/1) as a white solid: m.p. 117-119 C
Supporting Information
o
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
(
dichloromethane/pertrum ether), 94% ee (HPLC conditions:
Chiralcel OD-H column, hexane/i-PrOH = 95/5, 1.0 mL/min, λ =
1
2
14 nm, t
R
(minor) = 22.97 min, t
) δ 7.69 (d, J = 8.4 Hz, 2 H, ArH), 7.28 (t, J = 8.2 Hz, Acknowledgement
H, ArH), 7.19 (t, J = 7.4 Hz, 1 H, ArH), 7.09 (d, J = 7.2 Hz, 2 H,
= 10.0 Hz, J = 3.0
Hz, 1 H, HC=), 5.16 (d, J = 10.0 Hz, 1 H, HC=), 3.48 (dd, J = 10.2 Hz,
= 6.2 Hz, 1 H, one proton of NCH ), 3.41-3.21 (m, 5 H, CH of Bn
two protons of NCH + CH), 3.14 (dd, J = 10.4 Hz, J = 9.2 Hz, 1
), 2.86-2.75 (m, 1 H, CH), 2.70-2.62 (m, 1 H,
R
(major) = 29.65 min); H NMR
(400 MHz, CDCl
3
4
Financial support from National Natural Science Foundation of
China (21690063) is greatly appreciated. We thank Miss Xinyu
Duan in this group for reproducing the results of
ArH), 5.59 (t, J = 7.6 Hz, 1 H, HC=), 5.43 (dt, J
1
2
1
J
+
2
2
2
(3aR,5R,7aR,Z)-4g and (3aS,5R,7aS,Z)-4h presented in this study.
2
1
2
H, one proton of NCH
CH), 2.41 (s, 3 H, CH
MHz, CDCl
2
1
3
3
), 1.12 (d, J = 7.6 Hz, 3 H, CH
3
); C NMR (100 References
3
) δ 143.3, 140.5, 137.2, 133.8, 132.9, 129.5, 128.4,
28.1, 127.5, 127.2, 126.0, 125.8, 54.5, 50.5, 39.2, 38.1, 35.3,
[1] López, F.; Mascareñas, J. L. [4+2] and [4+3] catalytic cycloadditions of
allenes. Chem. Soc. Rev. 2014, 43, 2904.
1
3
+
+
3.0, 24.8, 21.4; MS (ESI) m/z: 416 ([M+Na] ), 394 ([M+H] ); IR
[
2] (a) Mauleón, P.; Zeldin, R. M.; González, A. Z.; Toste, F. D.
Ligand-Controlled Access to [4+2] and [4+3] Cycloadditions in
Gold-Catalyzed Reactions of Allene-Dienes. J. Am. Chem. Soc. 2009, 131,
(neat): ν = 3015, 2954, 2907, 2891, 2865, 1596, 1490, 1451, 1337,
-
1
1
292, 1229, 1177, 1153, 1130, 1105, 1086, 1052, 1023 cm ; Anal
S: C 73.25, H 6.92, N 3.56. found: C 73.27, H
Calcd for C24
.99, N 3.50.
H27NO
2
6348; (b) Alonso, I.; Trillo, B.; López, F.; Montserrat, S.; Ujaque, G.;
6
Castedo, L.; Lledós, A.; Mascareñas, J. L. Gold-Catalyzed [4C+2C]
Cycloadditions of Allenedienes, including an Enantioselective Version
with New Phosphoramidite-Based Catalysts: Mechanistic Aspects of the
(
9) Preparation of (3aS,5R,7aS,Z)-5-methyl-2-((4-methylphenyl)-
sulfonyl)-4-cyclohexylmethylene-2,3,3a,4,5,7a-hexahydro-1H-iso
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Divergence between [4C+3C] and [4C+2C] Pathways. J. Am. Chem. Soc.
009, 131, 13020; (c) González, A. Z.; Toste, F. D. Gold(I)-Catalyzed
Enantioselective [4+2]-Cycloaddition of Allene-dienes. Org. Lett. 2010, 12,
00; (d) Lainhart, B. C.; Alexanian, E. J. Enantioselective Synthesis of
cis-Fused Cyclooctanoids via Rhodium(I)-Catalyzed [4+2+2]
Cycloadditions. Org. Lett. 2015, 17, 1284.
Supplementary crystallographic data have been deposited at the CCDC
1528212.
2
[13] For selected reviews of cycloaddition, see: (a) Lautens, M.; Klute, W.;
Tam, W. Transition Metal-Mediated Cycloaddition Reactions. Chem. Rev.
1996, 96, 49; (b) Carruthers, W.; Cycloaddition Reactions in Organic
Synthesis; Pergamon: Oxford, Oxford, 1990; pp 1-208; For representative
examples of 1,3-dienes with alkenes, see: (c) O’Mahony, D. J. R.;
Belanger, D. B.; Livinghouse, T. On the Counterion Dependence of the
Rhodium(I)-Catalysed [4+2] Cycloaddition - A Remarkable Accelerating
Effect of the Hexafluoroantimonate Anion. Synlett 1998, 443; (d) Sato, Y.;
Oonishi, Y.; Mori, M. Novel Rhodium(I)-Catalyzed Cycloisomerization of
1,3-Diene with Alkene in a Tether: Competitive Reaction with [4+2]
Cycloaddition. Organometallics 2003, 22, 30; (e) O’Mahony, D. J. R.D.;
Belanger B.; Livinghous e, T. Substrate control of stereoselection in the
rhodium(I) catalyzed intramolecular [4+2] cycloaddition reaction. Org.
Biomol. Chem. 2003, 1, 2038; For representative examples of 1,3-dienes
with alkynes, see: (f) Wang, B.; Cao, P.; Zhang, X. An efficient Rh-catalyst
system for the intramolecular [4+2] and [5+2] cycloaddition reactions.
Tetrahedron Lett. 2000, 41, 8041; (g) Motoda, D.; Kinoshita , H.;
Shinokubo, H.; Oshima, K. Phosphane-Free Rhodium Catalyst in an
Anionic Micellar System for [4+2] Annulation of Dienynes. Angew. Chem.
Int. E d. 2004, 43, 1860; (h) Fürstner, A. Stimson, C. C. Two Manifolds for
Metal-Catalyzed Intramolecular Diels–Alder Reactions of Unactivated
Alkynes. Angew. Chem. Int. Ed. 2007, 46, 8845; (i) Kim, S. M.; Park J. H. ;
2
[
3] (a) Wender, P. A.; Jenkins, T. E.; Suzuki, S. Transition Metal-Catalyzed
Intramolecular [4+2] Diene-Allene Cycloadditions: A Convenient Synthesis
of Angularly Substituted Ring Systems with Provision for
Catalyst-Controlled Chemo- and Stereocomplementarity. J. Am. Chem.
Soc. 1995, 117, 1843; (b) Wender, P. A.; Croatt, M. P.; Deschamps, N. M.
Metal-Catalyzed [2+2+1] Cycloadditions of 1,3-Dienes, Allenes, and CO.
Angew. Chem. Int. Ed. 2006, 45, 2459.
[
4] Han, Y.; Ma, S. Rhodium-catalyzed highly diastereoselective
intramolecular [4
+
2] cycloaddition of 1,3-disubstituted
allene-1,3-dienes. Org. Chem. Front. 2018, 5, 2680.
[
5] Trost, B. M.; Fandrick, D. R.; Dinh, D. C. Dynamic Kinetic Asymmetric
Allylic Alkylations of Allenes. J. Am. Chem. Soc. 2005, 127, 14186.
6] Tang, X.; Huang, X.; Cao, T.; Han, Y.; Jiang, X.; Lin, W.; Tang, Y.; Zhang, J.;
[
Yu, Q.; Fu, C.; Ma, S. CuBr
functionalized and naturally occurring allenes. Org. Chem. Front. 2015, 2,
88.
2
-catalyzed enantioselective routes to highly
6
[
7] Gajewski, J. J.; Jurayj, J.; Kimbrough, D. R.; Gande, M. E.; Ganem, B.;
Carpenter, K.. On the Mechanism of Rearrangement of Chorismic Acid
and Related Compounds. J. Am. Chem. Soc. 1987, 109, 1170.
8] Fischer, D. F.; Barakat, S.; Xin, Z.-Q.; Weiss, M. E.; Peters, R. The
Asymmetric Aza-Claisen Rearrangement: Development of Widely
Applicable Pentaphenylferrocenyl Palladacycle Catalysts. Chem. Eur. J.
Chung, Y. K. Au(PPh
reaction of dienynes. Chem. Commun. 2011, 47, 6719.
[14] Crystal data for compound (3aS,5R,7aS,Z)-4b: C24
3 2
)OPOF -catalyzed intramolecular [4+2] cycloaddition
[
H
2
27NO S, MW = 393.52,
monoclinic, space group P 21, final R indices [I > 2σ(I)], R1 = 0.0607, wR2
2
009, 15, 8722.
9] Schultz, E. E.; Lindsay, V. N. G.; Sarpong, R. Expedient Synthesis of Fused
Azepine Derivatives Using Sequential Rhodium(II)-Catalyzed
= 0.1400, R indices (all data) R1 = 0.0661, wR2 = 0.1434, a = 12.3767(19)
o
o
o
[
Å, b = 6.9406(11) Å, c = 13.508(2) Å, α = 90 , β = 114.445(3) , γ = 90 , V =
3
a
1056.4(3) Å , T = 293(2) K, Z = 2, reflections collected/unique 5835 / 3506
Cyclopropanation/1-Aza-Cope Rearrangement of Dienyltriazoles. Angew.
Chem. Int. Ed. 2014, 53, 9904.
10] Oida, S.; Tajima, Y.; Konosu, T.; Nakamura, Y.; Somada, A.; Tanaka, T.;
Habuki, S.; Harasaki, T.; Kamai, Y.; Fukuoka, T.; Ohya, S.; Yasuda, H.
Synthesis and Antifungal Activities of R-102557 and Related
Dioxane-Triazole Derivatives. Chem. Pharm. Bull. 2000, 48, 694.
(Rint = 0.0318), number of observations [> 2σ(I)] 6492, parameters: 255.
Supplementary crystallographic data have been deposited at the CCDC
1528213.
[
[15] Horvath, A.; Benner, J.; Bäeckvall, J.-E. Enantiocontrolled Synthesis of
3-Pyrrolines from α-Amino Allenes. Eur. J. Org. Chem. 2004, 3240.
[16] Ye, J.; Fan, W.; Ma, S. tert-Butyldimethylsilyl-Directed Highly
Enantioselective Approach to Axially Chiral α-Allenols Chem. Eur. J. 2013,
19, 716.
[
11] Wender, P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A.
Transition Metal-Catalyzed [5+2] Cycloadditions of Allenes and
Vinylcyclopropanes:
Chemoselectivity, Relative Stereochemistry, and Chirality Transfer. J. Am.
Chem. Soc. 1999, 121, 5348.
First
Studies
of
Endo-Exo
Selectivity,
(
The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
[
12] Crystal data for compound (3aR,5S,7aR,Z)-4b: C24
monoclinic, space group P 21, final R indices [I > 2σ(I)], R1 = 0.0504, wR2
0.1137, R indices (all data) R1 = 0.0645, wR2 = 0.1218, a = 12.3481(18)
2
H27NO S, MW = 393.52,
=
o
o
o
Å, b = 6.9284(10) Å, c = 13.470(2) Å, α = 90 , β = 114.449(3) , γ = 90 , V =
3
1
049.0(3) Å , T = 293(2) K, Z = 2, reflections collected/unique 6050 / 3719
(
Rint = 0.0292), number of observations [>2σ(I)] 3719, parameters: 255.
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Concise Report
First author et al.
Entry for the Table of Contents
Page No.
One Stone for Three Birds-Rhodium-catalyzed
Highly Diastereoselective Intramolecular [4+2]
H
R2
cat. RhCl(PPh
cat.
AgSbF
6
3 3
)
Cycloaddition
of
Optically
Active
X
X
H
R2
Allene-1,3-dienes
H
R1
chiral allenes
R1
axially
efficient chirality transfer
with
ee
three chiral centers
with excellent
diastereoselectivity
and Z/E
selectivity
high
generating
X = NTs, C
1
2
R
=
Bn,
R =
alkyl,
alkyl, aryl
Rhodium-catalyzed Intramolecular [4+2] Cycloaddition of Optically Active Allene-1,3-dienes.
Yulin Han and Shengming Ma
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.