Chiral Sulfide Catalysis for Desymmetrizing Enantioselective Chlorination

Article abstract of DOI:10.1002/anie.201811621

An unprecendented chiral sulfide catalyzed desymmetrizing enantioselective chlorination is disclosed. Various aryl-tethered diolefins and diaryl-tethered olefins afforded teralins and tricyclic hexahydrophenalene derivatives, respectively, bearing multiple stereogenic centers in high yields with excellent enantio- and diastereoselectivities. In contrast, the tertiary amine catalyst (DHQD)₂PHAL led to a diastereomeric product. The products could be transformed into a variety of compounds, such as spiro-N-heterocycles.

Full text of DOI:10.1002/anie.201811621

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Accepted Article
Title: Chiral Sulfide Catalysis for Desymmetrizing Enantioselective
Chlorination
Authors: Xiaodan Zhao, Qingxiang Cao, and Jie Luo
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201811621
Angew. Chem. 10.1002/ange.201811621
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10.1002/anie.201811621
Angewandte Chemie International Edition
COMMUNICATION
Chiral Sulfide Catalysis for Desymmetrizing Enantioselective
Chlorination
Qingxiang Cao, Jie Luo, and Xiaodan Zhao*
ion is more prone to form a free carbocation to erode the
enantioselectivity of reaction or decompose. On the basis of our
previous studies on bifunctional chalcogenide-catalyzed
trifluoromethylthiolation,[12] we envisioned that bifunctional
binding strategy might be able to solve the above issues in
electrophilic chlorination of alkenes. This bifunctional binding
might stabilize the chloriranium ion to prevent its decomposition
and the formation of free carbocation to avoid the racemization.
On the other hand, the binding might accelerate the nucleophilic
attack toward the chloriranium ion, especially in an
intramolecular way. The improvement of the rate of reaction
could diminish the possibility that the chlorenium ion is
quenched by nucleophiles.
Abstract: Unprecendented chiral sulfide-catalyzed desymmetrizing
enantioselective chlorination is disclosed. Various aryl-tethered
diolefins and diaryl-tethered olefins afforded teralins or tricyclic
hexahydrophenalene derivatives bearing multiple stereogenic
centers
in
high
yields
with
excellent
enantio-
and
diastereoselectivities. In contrast, tertiary amine catalyst
(DHQD)2PHAL led to a diastereomer product. The products could be
transformed to diverse compounds such as spiro N-heterocycles.
Catalytic halogenation has received considerable attention in
recent years.[1-3] As a very important subdivision in this field,
electrophilic halofunctionalization provides a convenient pathway
to quickly construct chiral halogenated molecules.[2,3] However,
enantioselective electrophilic chlorination, especially with
alkenes, has been far less explored than the corresponding
bromination and iodination[1-8] although chlorine atom is a good
convertible group and widely exists in a huge number of
bioactive compounds and natural products.[9] To date, most
methods for electrophilic chlorination rely on the use of cinchona
alkaloid-based organocatalysts such as (DHQD)2PHAL and
cinchonidine derivatives to deliver enantioselectivity (Scheme
1a).[4-8] But the relatively strong basicity of these organocatalysts
limits the reactivity and scope of substrates. Furthermore, their
specific chiral scaffold cannot satisfy the requirement of chiral
environment in some cases. These features largely hamper the
development of enantioselective chlorination.
(a) Cinchona alkaloid-based organocatalysts for asymmetric chlorination
Nu
HNu
cat.
"Cl+ reagent"

+

Cl
cat:
H
H
H
H
N
H
N
N
O
O
RO
N
N
H
MeO
OMe
N
N
N
(DHQD)2PHAL (Most used)
Cinchonidine derivatives
(b) Chiral sulfide-catalyzed enantioselective chlorination: This work
R
Lewis basic organochalcogen catalysis has emerged as a
powerful tool in enantioselective alkene transformations due to
the particular catalytic properties and readily availability of chiral
organochalcogen catalysts.[10-12] These catalysts have less
basicity and are more compatible with neutral or acidic
conditions in contrast to N-based chiral Lewis base catalysts.
They can properly catch ArS+, Br+ or CF3S+ to form a complex,
and then react with alkenes to generate chiral iranium ions,
followed by nucleophilic attack to give products. It is reasoned
that this unique catalytic fashion might be suitable for
enantioselective chlorination. Nevertheless, no successful
enantioselective example has been demonstrated until now
although Denmark and Yeung groups have made great efforts in
this regard.[11a,f,13] The great potential of this catalysis triggers us
to explore its application in chlorination. Herein, we report our
discovery that a bifunctional chiral sulfide can efficiently catalyze
desymmetrizing chlorination of aryl-tethered diolefins to give
chiral chlorinated tetralins with an all-carbon quaternary
stereocenter (Scheme 1b). Interestingly, tertiary amine catalyst
(DHQD)2PHAL led to a diastereomer product bearing an
opposite absolute configuration at the quaternary center.
R
R
cat.
cat.
R''
Cl
R
Cl
S
Ar
R
S
R
R
(DHQD)2PHAL

R
DCDMH
DCDPH
R
NHBz
R
R
NHBz
NHBz
Scheme 1. Catalytic enantioselective chlorination.
Based on the hypothesis, we would like to pursue an
unprecedented desymmetrizing enantioselective chlorination.
Aryl-tethered diolefin 1a was selected as a model substrate
(Table 1). This class of substrates possess an NHBz group as
H-bonding donor and an aryl group as nucleophile. The
chlorocyclization is particularly attractive since the resulting
tetralins are a class of valuable compounds,[14] and contain a
convertible alkene group and three stereogenic centers including
an all-carbon quaternary center. Due to the excellent catalytic
activity
of
selenide
catalysts
C1
and
C2
in
trifluoromethylthiolation,[12] they were first tested using 1.5
equivalents of NCS as chlorine source. It was found that the
reactions almost did not work with or without TFA (entries 1-3). It
was rationalized that the problem mainly stemmed from the
deactivation of catalysts. This drove us to use chiral sulfide
catalysts, a Lewis base that is harder and more resistant to
oxidation than the corresponding selenide. Gratifyingly, when
sulfide C3 was utilized, the desired product 2a was formed in
39% yield with 53% ee and 8:1 dr (entry 4). Slightly better result
was obtained with catalyst C4 bearing two methoxy groups
(entry 5).
According to the literature,[11a,f,13] organochalcogen-catalyzed
enantioselective electrophilic chlorination of alkenes is quite
difficult. Notably, there are two issues to be more challenging
compared with similar reactions of alkenes involving
bromiranium, arylthiiranium or trifluoromethylthiiranium ion: i)
chlorenium ion is more reactive to be quenched by nucleophiles
before the formation of chloriranium ion; ii) unstable chloriranium
[*] Q. Cao, J. Luo, and Prof. Dr. X. Zhao
Institute of Organic Chemistry & MOE Key Laboratory of Bioinorganic
and Synthetic Chemistry
To further improve the reaction, different chlorine sources
were screened. Highly reactive (PhSO2)2N-Cl and saccharin-Cl
gave products in higher yields with lower selectivity, possibly
because of the strong background reaction of non-catalyzed
chlorination (entries 6 and 7). In contrast, relatively inert DCDMH
improved the enantioseletivity to 73% ee (entry 8). But
School of Chemistry
Sun Yat-Sen University, Guangzhou 510275, China
E-mail: zhaoxd3@mail.sysu.edu.cn
Supporting Information for this article is available on the WWW under
http://XXX (added afterwards)
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10.1002/anie.201811621
Angewandte Chemie International Edition
COMMUNICATION
Chloramine-T gave little product because of the solubility
problem (entry 9). Due to the important role of acid in
electrophilic functionalization,[12] different acids were examined
instead of TFA. To our surprise, enantiomer of 2a was formed
lies at the ortho-position of the phenyl group. The conditions
allowed for efficient chlorination of aliphatic diolefins as well (2o-
2r, 88-95% ee). In these transformations, the catalyst loading
could reduce to 5 mol% when prolonging the reaction time to 24
h. It is noted that the reactions of (Z)-olefin 1q and trisubstituted
olefin 1r worked well to form the corresponding products. The
absolute configuration of products was assigned to 1R, 3R, 4R
based on the X-ray crystallographic study of 2o. The developed
method is effective for aliphatic olefins to undergo twice
cyclizations to construct tricyclic products 3a-3c in good yields
with excellent enantio- and diastereoselectivities using 2.5
.
using Lewis acid TMSOTf or BF3 OEt2 (entries 10 and 11). This
result might be ascribed to which the anion derived from acid
has a big impact on the configuration of intermediate during the
reaction.[12d] This interesting result indicates that the control of
enantioselectivity of reaction can be adjusted by acid. Instead,
when Tf2NH was used, the selectivity improved (entry 12), but
the yield was low. When the amount of chlorinating reagent and
acid was adjusted, product 2a could be yielded in excellent yield,
ee and dr (entry 14). Apparently, no catalyst resulted in no
reaction (entry 15).
equivalents of DCDMH (eq 1). This method provides
a
convenient route for the synthesis of valuable chiral
hexahydrophenalene derivatives.[15]
Table 1: Condition optimization.[a]
R2
R1 R2
R'
R1
Cl
Ph
C4 (10 mol%)
Ph
Ar
+
DCDMH
Cl
Tf2NH
CH2Cl2, -78 oC, 12 h
Ph
cat.
"Cl+ reagent"
+
R1
Ph
acid
NHBz
R1
NHBz
Cl
CH2Cl2, -78 oC, 12 h
R2
R2
Me Ph
Ph
NHBz
1a-1r
2a-2r
Ph
1a
2a
NHBz
R'
H
Me
Ph
F
yield ee
O
O
O
O
2a
2b
2c
2d
2e
2f
87% 94%
87% 92%
81% 93%
O
O
O
Ph
Ph
O
S
Na
S
Me
R'
Cl
S
Cl
N
N
Cl
N Cl
N
N Cl
Me
90% 94%
82% 93%
88% 93%
88% 95%
80% 98%
CH
Me
Ph
S
N
Cl
O
Cl
Br
Me
O
Cl
O
O
NCS
O
NHBz
(PhSO2)2N-Cl
R
Chloramine-T
Saccharin-Cl
DCDMH
NHBz
Cl
2g
2h
CF3
C
Ph
R
2i, 86%, 99% ee
Ph
C1, R = Me
C3, R = Me
C4, R = OMe
R
yield ee
R
C2, R = OMe
Se
S
Cl
2k
p-FC6H4 87% 93%
p-BrC6H4 80% 96%
m-MeC6H4 85% 94%
o-MeC6H4 75% 94%
OMe
OMe
2l
2m
2n (17:1 dr)
S
NHTf
NHTf
Yield [%][b] Ee [%][c] Dr[d]
Entry Cat.
Cl+ reagent
Acid
2o[a]
NHBz
Me
89% 95%
Ph
NHBz
Et
R
C1
C1
C2
C3
C4
NCS
NCS
NCS
NCS
NCS
-
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
<5
<5
<5
39
45
63
35
40
<5
35
32
31
68
91
0
-
-
-
-
-
-
2j, 60%, 93% ee
1
2
3
4
5
Me
Me
Ph
Cl
Cl
Cl
53
57
21
21
73
-
-60
-25
66
74
93
-
8:1
7:1
2:1
2:1
10:1
-
2:1
3:1
8:1
7:1
31:1
-
6
C4 (PhSO2)2N-Cl
Ph
7
C4 Saccharin-Cl
NHBz
NHBz
Me
8
9
C4
DCDMH
C4 Chloramine-T
NHBz
Me
Et
2q, 82%, 90% ee, 15:1 dr[a]
2p, 85%, 91% ee[a]
2r, 83%, 88% ee[a,b]
10
11
12
C4
C4
C4
DCDMH
DCDMH
DCDMH
DCDMH
DCDMH
DCDMH
TMSOTf
BF3 OEt2
Tf2NH
Tf2NH
Tf2NH
Tf2NH
.
Scheme 2. Desymmetrizing enantioselective chlorination of aryl-tethered
diolefins. Reaction conditions: 1 (0.1 mmol), DCDMH (1.0 equiv), Tf2NH (0.5
equiv), C4 (10 mol%), CH2Cl2 (4.0 mL), -78 oC, 12 h. The yields refer to
isolated yields. The ee value was determined by HPLC analysis. Without note,
all the diasteresoselectivities are >20:1. [a] C4 (5 mol%), 24 h. [b] TFA (1.0
equiv) instead of Tf2NH.
13[e] C4
14[e,f] C4
15[e,f]
-
[a] Reaction conditions: 1a (0.05 mmol), Cl+ reagent (1.5 equiv), acid (2.0
equiv), catalyst (10 mol%), CH2Cl2 (2.0 mL), -78 oC, 12 h. [b] NMR yield using
benzyl benzoate as the internal standard. [c] Determined by chiral HPLC
analysis. [d] Determined by NMR. [e] DCDMH (1.0 equiv). [f] Tf2NH (0.5 equiv).
R
Me
With the optimal conditions in hand, the scope of diolefins was
evaluated (Scheme 2). When diolefins tethered by different aryl
groups were utilized, the corresponding products were obtained
in high yields with excellent enantio- and diastereoselectivities
(2a-2h, 92-98% ee, >20:1 dr). To our surprise, electron-deficient
aryl groups such as CF3-substituted aryl group could act as an
efficient nucleophile. In comparison, they are difficult
nucleophiles in electrophilic trifluoromethylthiolation of
alkenes.[12d] This result shows the highly reactive property of
chloriranium ion. Alkyne group well tolerated the conditions,
which offers an opportunity for further transformation (2h, 98%
ee). Bulky 3,5-dimethyl substituted substrate 1i gave the product
with extremely high enantioselectivity. Moreover, it is interesting
to find that electron-rich diolefinic thiophene also efficiently
underwent chlorination to give the desired product with excellent
enantioselectivity (93% ee). Using substrates with different aryl
groups directly connecting to the double bond, the reactions
afforded the desired products in good yields with excellent
diastereoselectivities (2k-2n, 90-96% ee), even if the substituent
R
Cl
Me
Me
C4 (10 mol%)
+
DCDMH
2.5 equiv
(1)
Tf2NH
CH2Cl2, -78 oC, 24 h
NHBz
Me
NHBz
1
3
3a, R = H, 72%, 95% ee
3b, R = Me, 60%, 94% ee
3c, R = Ph, 62%, 95% ee
Cl
Chlorination of gem-diaryl-tethered olefins was also examined
under similar conditions (Scheme 3). The reactions of most
substrates proceeded very efficiently to produce the desired
products in excellent yields and selectivities (up to 99% ee
and >20:1 dr). It is worthy to mention that the enantiomer of 5a
could be obtained using TMSOTf instead of Tf2NH. When C3
was utilized as catalyst, the enantioselectivity improved to 90%.
Additionally, (Z)-alkene 4h worked very well to generate product
5h. By this method, two all-carbon quaternary stereocenters
could be formed simultaneously (5i, 90% ee). This is rare in
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10.1002/anie.201811621
Angewandte Chemie International Edition
COMMUNICATION
enantioselective catalysis and difficult to achieve by other
electrophilic reactions.[1-8] These results reveal the specific
advantages of sulfide-catalyzed electrophilic chlorination.
sulfenylation could promote the aminocyclization of 2a to give
spiro bicyclic molecule 6e. The tethered double bond could be
oxidized to afford carboxylic acid 6f in good yield. It was easily
converted to spiro naphthyl pyrrolidone 6g, a derivative of
important bioactive compounds.[16] In these reactions, the
enantio- and diastereoselectivities remained same except for the
formation of 6e. More transformations of products are placed in
the Supporting Information.
R1 R2
R2
R'
R1
Cl
C4 (10 mol%)
+
DCDMH
Ar
Ar
Tf2NH
CH2Cl2, -78 oC, 12 h
NHBz
4a-4j
NHBz
Ar
5a-5j
Ph
Ph
R1
R1
R1
Cl
yield ee
yield ee
Ph
(DHQD)2PHAL (10 mol%)
5d[b]
5e
5f[c]
p-MeC6H4
5a
>99% 92%
98% 97%
>99% 94%
Ph
Ph
Me
>99% 90%
98% -90%
>99% 94%
Cl
+
DCDPH
(2)
s
5a'[a]
5b
TFE/CH2Cl2/Mesitylene
(3:2:2)
p-BrC6H4
p-CF3OC6H4
1.2 equiv
Ph
NHBz
-60 oC, 12 h
5c
CH2Bn >99% 95% 5g
1a
Ph
m-MeOC6H4 >99% 99%
NHBz
NHBz
Cl
Ph
Ph
2a'
Ph
Cl
Et
82%, 80% ee, 17:1 dr
Ph
Me
Cl
To compare the difference between the developed
chlorination system and tertiary amine catalysis, we also used
commercially available cinchona alkaloid-based organocatalysts
to optimize enantioselective chlorination of 1a. Many conditions
were tried by changing chlorinating reagents, additives, and
solvents, but the cyclized product was formed generally in low
enantioselectivity and poor diastereoselectivity. Interestingly, in
most cases, a diastereomer of 2a as product bearing an
opposite absolute configuration at the quaternary center was
formed. When (DHQD)2PHAL catalyst commonly used for
enantioselective chlorination was utilized, 2a′ was obtained in
mixed solvents with 80% ee (eq 2). The conditions were
effective for the reactions of alkyl diolefins. The similar products
were formed, but in moderate enantioselectivities. These results
indicate the unique character of sulfide catalysis has great
potential to synthesize molecules that cannot be made by other
methods.
NHBz
NHBz
(R1 = H, R2 = Et)
Me
Me
NHBz
5i, 79%, 90% ee
Ph
5h, 94%, 94% ee
5j, >99%, 92% ee
Scheme 3. Desymmetrizing enantioselective chlorination of gem-diaryl-
tethered olefins. Reaction conditions: 4 (0.1 mmol), DCDMH (1.2 equiv), Tf2NH
(0.5 equiv), C4 (10 mol%), CH2Cl2 (4.0 mL), -78 oC, 12 h. The yields refer to
isolated yields. The ee value was determined by HPLC analysis. Without note,
all the diasteresoselectivities are >20:1. [a] C3 (10 mol%) instead of C4,
TMSOTf (1.0 equiv) instead of Tf2NH. [b] With 17:1 dr. [c] With 18:1 dr.
Ph
Ph
Ph
Cl
Cl
(g)
Ph
(a)
Ph
Ph
HOOC
Cl
NBz
6g
Ph
NHBz
NHBn
cat.
O
+
6f
6c
DCDMH
Tf2NH
CH2Cl2, -78 oC, 12 h
78%, 94% ee
95%, 94% ee
96%, 94% ee
(c)
(b)
Ph
(f)
NHBz
cat.:
Ph
1a
2a
NHBz
SPh
Ph
Ph
Ph
Cl
SPh
SPh
SPh
(a)
N
Tf
15%
N
N
N
H
C6
C7
C5
Me
H
H
C8
Bz
Ts
Tf
90%
Ph
Ph
Ph
NHBz
NHBz
NHBz
16%
no ee, 1.5:1 dr
21%
no ee, 1.3:1 dr
2a
94% ee
6b
6a
85% ee, >20:1 dr
no ee, 4:1 dr
78%, 94% ee
72%, 94% ee
(d)
(e)
(b)
Ph
Ph
Ph
Ph
Ph
Cl
Cl
Ph
C4 (10 mol%)
Cl
+
DCDMH
Tf2NH
CH2Cl2, -78 oC, 12 h
2aa
O
Bz
(c)
Ph
O
N
1aa
Bz
NBz
Bn
TolS
80%, 46% ee, 2:1 dr
Ph
6d
97%, 94% ee
Ph
6e
84%, 86% ee
O
Me
S
Me
O
Me
O
O
Cl
F
F
Me
N
H
Scheme 4. Further transformations of products. Reaction conditions: (a)
AgOTf, THF, 75 oC, 36 h. (b) KOtBu, i-Pr2O, 80 oC, 12 h. (c) LiAlH4, Et2O, 0 oC,
4 h. (d) POCl3, PhMe, 120 oC, 24 h. (e) N-TolS-succinimide, PhSePh, CH2Cl2,
-78 oC, 12 h. (f) RuCl3, NaIO4, MeCN/CCl4/H2O, rt, 2 h. (g) CH3COCl, Et2O, rt,
12 h. All the diasteresoselectivities are >20:1.
O
N
S
O
S
N
Tf
NTf
F
F
F
S
S
O
O
F3C
O
F3C
F
Int-I
Me
Me
H
H
O
O
O
O
O
F3C
F3C
S
Cl
S
Cl
O
O
N
N
S
S
+
+
H
O
O
N
O
O
O
product 2a
less stable
To demonstrate the synthetic applications of products, diverse
transformations of 2a were conducted based on the
manipulation of the functional groups. The use of AgOTf and
KOtBu led to the selective elimination of HCl to give different
alkenes 6a and 6b in good yields. The chlorine atom could be
removed by reduction (6c, 95%). When 2a was treated with
POCl3, valuable spiro dihydropyridine derivative 6d was
efficiently formed. Moreover, electrophilic reactions such as
Int-II
Int-II'
Ph
Ph
Scheme 6. Mechanistic insight.
To gain insight into reaction mechanism, control experiments
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10.1002/anie.201811621
Angewandte Chemie International Edition
COMMUNICATION
were carried out (Scheme 5). The H-bonding ability of catalyst
was first investigated. When chiral sulfide was protected by
different groups such as Bz, Ts, and Tf, only C7 with strong H-
bond donor Tf group led to product in high ee and excellent dr
(Scheme 5a). In contrast, C5, C6 and C8 with an improper or no
H-bond donor gave racemic products in low yields with poor dr.
These results indicate that the TfNH group of catalyst is pivotal
for the reactivity and construction of chiral environment of the
transformation. However, when substrate did not contain H-bond
donor, e.g., 1aa with an OBz group, the reaction gave the
product with low ee and poor dr (Scheme 5b). In light of these
results, H-bonding interaction is essential for the success of
reaction. Besides, when the sulfoxide from the corresponding
sulfide catalyst was used as catalyst for chlorination of 1a,
almost no reaction took place under similar conditions, which
reveals that sulfoxide cannot be the catalyst (see the Supporting
Information). Based on these observations and our previous
studies,[12] the mechanism is proposed to go through Int-I
formed by the reaction of catalyst and DCDMH (Scheme 5c). It
interacts with diolefin to generate Int-II with an acid-derived
anion bridge built by H-bond binding. The anion bridge might
guarantee the reactivity of substrate by accelerating the attack of
the phenyl group towards the chloriranium ion and the
stereoselectivity of reaction. As shown on Int-II′, when H-bond
donor does not exist, the bridge cannot be formed, which
possibly leads to the collapse of the chloriranium ion, and then
poor stereoselectivity.
[3]
[4]
a) A. J. Cresswell, S. T.-C. Eey, S. E. Denmark, Angew. Chem. Int. Ed.
2015, 54, 15642; Angew. Chem. 2015, 127, 15866; b) M. G. Martinez,
D. A. Alonso, M. I. Pastor, G. Guillena, A. Baeza, Asian. J. Org. Chem.
2016, 5, 1428.
For asymmetric intramolecular chlorocyclization of alkenes, see: a) K.
Shibatomi, Y. Soga, A. Narayama, I. Fujisawa, S. Iwasa, J. Am. Chem.
Soc. 2012, 134, 9836; b) K. Shibatomi, M. Kotozaki, N, Sasaki, I.
Fujisawa, S. Iwasa, Chem. Eur. J. 2015, 21, 14095; c) K. Shibatomi, K.
Kitahara, N. Sasaki, Y. Kawasaki, I. Fujisawa, S. Iwasa, Nat. Commun.
2017, 8, 15600.
[5]
For asymmetric intramolecular chlorocyclization of alkenes, see: a) D. C.
Whitehead, R. Yousefi, A. Jaganathan, B. Borhan, J. Am. Chem. Soc.
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In summary, we have developed an efficient approach toward
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tethered diolefins and diaryl-tethered olefins by bifunctional
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Acknowledgements
We thank the “One Thousand Youth Talents” Program of China,
the National Natural Science Foundation of China (Grant No.
21772239), and the Natural Science Foundation of Guangdong
Province (Grant No. 2014A030312018) for financial support.
Keywords: enantioselective chlorination · diolefins · sulfide
catalysis · Lewis base catalysis · synthetic methods
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10.1002/anie.201811621
Angewandte Chemie International Edition
COMMUNICATION
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COMMUNICATION
Table of Contents
COMMUNICATION
MeO
5~10 mol%
Qingxiang Cao, Jie Luo, and Xiaodan
Zhao*
R2
R1
R1 R2
S
R1
R'
Cl
R'
Cl
OMe
Ar
NHTf
or
Page No. – Page No.
DCDMH, Tf2NH
R1
R1
up to 90% yield
NHBz
NHBz
R1
NHBz
R2
R2
Chiral
Sulfide
Catalysis
for
Cl
Desymmetrizing
Chlorination
Enantioselective
up to 99% ee, >20:1 dr
Unprecendented chiral sulfide-catalyzed desymmetrizing enantioselective
chlorination is disclosed. Various aryl-tethered diolefins and diaryl-tethered olefins
afforded teralins or tricyclic hexahydrophenalene derivatives bearing multiple
stereogenic centers in high yields with excellent enantio- and diastereoselectivities.
In contrast, tertiary amine catalyst (DHQD)2PHAL led to a diastereomer product. The
products could be transformed to diverse compounds such as spiro N-heterocycles.
This article is protected by copyright. All rights reserved.