Bis(phenylsulfonyl)methane mediated synthesis of olefins: Via a halogen elimination and double bond migration

Article abstract of DOI:10.1039/c8ob00033f

An effective dehydrochlorination of bis(phenylsulfonyl)alkane to prepare alkene building blocks is developed. The elimination together with double bond migration results in a variety of β,γ-unsaturated bis(phenylsulfonyl)olefins in good yields with only E geometry. The following chemical diversification represents an easy and straightforward access to a series of alkene building blocks.

Full text of DOI:10.1039/c8ob00033f

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Bis(phenylsulfonyl)methane mediated synthesis of olefins via a
halogen elimination and double bond migration
Jing Jianga,c†, Ying Hub,†, Xin Cai a, Liudi Wanga, Yanwei Hua,*, Shaohua Chena, Shilei Zhanga,*, Yinan
Zhangc*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
An effective dehydrochlorination of bis(phenylsulfonyl)alkane to monofluoroalkanes, carboxylic acids, and rearrangement
prepare alkene is developed. The elimination along with double products makes BSM distinguished from other functionalized
bond migration results
a
variety of β,γ-unsaturated methylene synthons.5 In connection with these synthetic
bis(phenylsulfonyl)olefins in good yields with only E geometry. applications, BSM becomes one of the most powerful methide
The following chemical diversification represents a facile and equivalents and has attracted much attention from organic
straightforward access to a series of alkene building blocks.
chemists.6 As part of an ongoing program to discover novel
synthetic methods of chiral building blocks, we used an
organocatalytic method to construct enantioselective mono-
fluoro aldehydes by taking these advantages of BSM.7 In our
recent attempts to further synthesis bis-phenylsulfonyl
functinalized olefins, we found the position of elimination
reaction unprecedentedly took place at the β,γ-position of bis-
phenylsulfonyl methide. Therefore, we herein wish to report a
migrated β,γ-elimination of bis(phenylsulfonyl)-chloroalkane
(Figure 1b).
As the primary moieties that have ability to access most
functional groups, olefins ubiquitously exist in organic compounds
and have the largest scale of production both industrially and
laboratorially. The preparation of olefin is one of the central topics
in organic synthesis and numerous methods have been developed
to rapid construct double bonds in various aspects, such as, Grieco
dehydration, RCM reaction, Tebbe olefination, Wittig reaction.1
Recently, our group has also established
a stereoselective
preparation of enals from consecutive 2-iodoxybenzoic acid (IBX)
oxidation of alcohols and successfully applied to the tandem
synthesis of polyenes.2 However, as the most widespread
strategies, direct eliminations of halogens or pseudohalogens
(selenide, sulfoxide, etc.) are still considered to be the first option
to form double bond. Under a standard E1/E2 basic elimination
condition, the deprotonation position happens at the β-hydrogen of
leaving groups, in which the double bond finally forms between the
carbon bearing a leaving group and the carbon adjacent to (Figure
1a).3 There is no precedent example was found on the β,γ-
elimination.
Figure 1. Bis(phenylsulfonyl)methane mediated elimination to
form β,γ-olefin.
The investigation commenced with the transformation of
BSM to various bis(phenylsulfonyl)-chloroalkane (Scheme 1).
Treatment of primary bromoalkanes with BSM under basic
condition led to the bis-phenylsulfonyl substituted alkanes.
The following chlorination were carried out at the methide
Bis(phenylsulfonyl)methane (BSM) is an highly functionalized
methylene and readily appended to the halogenated
hydrocarbons or α,β-unsaturated Michael alkenes.4 Its
versatile ability that simply converts to alkanes,
carbon
by
N-chlorosuccimide
to
give
desired
bis(phenylsulfonyl)-chloroalkanes
(1) in good yields. The
bis(phenylsulfonyl)-1-chloropentane (1a) was selected as a
model substrate for the optimization of dehydrochlorination
(Table 1). Although our initial purpose of the elimination was
to obtain α,β-bis(phenylsulfonyl)olefin analog 2a’, we quickly
realized that only double bond migrated product 2a with
exclusive E configuration was found. The steric congestion is
probably the main reason that biased the equilibrium toward
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the allylic bis-sulfone 2a 8
Journal Name
.
At the outset of this study, excess outcomes than the unconjugated products (2a, c-e, g-p), which
NaOH in reflux EtOH gave the moderate yield of product 2a could be explained by the more acidity of γ-hydrogen during
,
which was characterized by the NMR and mass spectrometry. the double bond migration to form the conjugate products.
The next evaluation of different bases showed that sodium We were also pleased to find that functional groups such as
ethanolic gave the best yield and strong bases (NaH, KOtBu, hydroxyl (2i), chlorine (2j), esters (2m-n) remained intact
etc.) were detrimental to the reaction (entries 1-5). Among under the basic elimination. No α,β-double bond products
various solvents screened, THF and dioxane were most optimal were detected in all cases. Interestingly, the substrate 1t
(entries 6-9). Further adjustment of the temperature and without
loading amounts of bases indicated five equivalent of NaOEt possibly by an additional nucleophilic substitution of ethoxide,
under heated ether solvents generated the highest yield of but another substrate 1u without -hydrogen gave messy
γ-hydrogen formed a mono-sulfonyl-vinyl product 2t
γ
product 2a (entries 10-14). No α,β-double bond product 2a’ products. Tri- and tetra-substituted alkenes could not be
could be captured even conducting the reaction at the lower obtained under the optimal condition.
Table 2. Scope of dehydrochlorination.a
temperature or reduced loading amount of bases, despite the
vinyl bis(sulfone) with β-aromatic conjugation were obtained
SO2Ph
SO2Ph
NaOEt, THF, 1h
in previous study.9 It is worth to note that hydrogen
substitution instead of elimination directly happened when the
bromo-alkanes and iodo-alkanes were used.
SO2Ph
Cl
PhO2S
R
R
2
1
O
S
O
S
a) K2CO3, DMF, 80 oC;
b) NCS, room temp;
SO2Ph
Cl
PhO2S
R
O
O
Br
R
2a, 73%
2b, 86%
2c, 65%
2d, 67%
BSM
1
Scheme 1. Preparation of bis(phenylsulfonyl)-chloroalkanes 1
Table 1. Optimization of dehydrochlorination.a
2e, 78%
2i, 58%
2f, 64%
2j, 61%
2g, 62%
2k, 57%
2h, 73%
2l, 52%
SO2Ph
SO2Ph
SO2Ph
SO2Ph
SO2Ph
Cl
PhO2S
1a
conditions
2a'
2a
entry
1
base (equiv.)
NaOH (10)
K2CO3 (10)
NaOEt (10)
KOtBu (10)
NaH (10)
solvent
EtOH
EtOH
EtOH
EtOH
THF
temp (oC)
78
yieldb (%)
33
2
78
<5
2m, 58%c
2n, 63%c
2o, 47%c
3
78
40
4
78
32
5
70
25
2p, 51%c,d
2q, 82%
2r, 74%
1u
2s, 81%
6
NaOEt (10)
NaOEt (10)
NaOEt (10)
NaOEt (10)
NaOEt (10)
NaOEt (10)
NaOEt (5)
NaOEt (2)
NaOEt (5)
THF
70
65
7
dioxane
DMF
80
58
8
78
43
1t
2t, 37%
aReaction conditions unless otherwise specified: A mixture of
(1.0 mmol), NaOEt (5.0 mmol) in THF (5.0 mL) was stirred at 70
oC for 1 h. bIsolated yields. cThe reaction was carried out with
1
9
toluene
THF
78
49
10
11
12
13
14
50
53
1
THF
30
30
o
(1.0 mmol), NaOEt (5.0 mmol) in 1,4-dioxane (5.0 mL) at 80 C
for 1 h. d2 h reaction time.
THF
70
73
THF
70
<5
SO2Ph
SO2Ph
Mg
K2CO3, CH3I
93%
dioxane
80
70
(1)
69%
Ph
SO2Ph
Ph
SO2Ph
2b
SO2Ph
4
6
3
5
aReaction conditions unless otherwise specified: A mixture of
1a (1.0 mmol), bases (2.0-10 mmol) in solvent (5.0 mL) was
stirred at indicated temperature for 1 h. bIsolated yields.
SO2Ph
Mg
Selectfluor, KOtBu
F
(2)
Ph
SO2Ph
71%
Ph
SO2Ph
80%
F
2b
After the establishment of the optimal conditions (entry 14,
Table 1), the reaction scope with respect to a series of
bis(phenylsulfonyl)-chloroalkanes was explored (Table 2). To
our delight, the dehydrochlorination proceeded smoothly with
substrates bearing various substituents, affording the E only
products 2a-s in moderate to good yields (47-86%). In this
respect, the conjugate products (2b, 2q-s) had preferential
TsN
Ph
SO2Ph
SO2Ph
O
COOH
(3)
(4)
Ph
Ph
Ph
Ph
64%
2b
7
8
SO2Ph
SO2Ph
Zn/HCl
75%
SO2Ph
2b
Scheme 2. Potential conversion of 2b.
2 | J. Name., 2012, 00, 1-3
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To further demonstrate the utility of this reaction, we
conducted several potential conversions of the product 2b
(Scheme 2). The bis(phenylsulfonyl) methine was alkylated
with iodomethane and fluorinated with selectfluor to generate
Notes and references
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quaternary products
3
and
5,
respectively. Further
desulfonations led the alkene
4
and monofluoro alkene
6,
2
a) X. Chen, Y. Zhang, H. Wan, W. Wang, and S. Zhang, Chem.
Comm. 2016, 52, 3532. b) H. Xie, S. Zhang, H. Li, X. Zhang, S.
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which represented a standard process to deliver longer chain
alkylated and fluorinated products. The bis(phenylsulfonyl)
methine could also be oxidized to carboxylic acid
oxiziridine in good yield, while the incomplete removal of
sulfonyl group produced allyl monosulfone under reductive
7 with
and W. Wang, Nat. Commun., 2011, 2, 211.
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4
M. B. Smith, March's Advanced Organic Chemistry, 7th ed.;
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8
condition. These examples demonstrated the current
elimination method in conjunction with ensuing steps enabled
new opportunities for potential synthesis of the useful building
A. Alexakis, and C. Mazet, Angew. Chem. Int. Ed. 2011, 50
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SO2Ph
5
a) R. Rohlmann, and O. G. Mancheňo, Curr. Org. Chem. 2012,
16, 2160. b) C. Ni, M. Hu, and J. Hu, Chem. Rev. 2015, 115,
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A. Scheidt, Chem. Sci. 2011, 2, 1772. e) M. Ogasawara, M.
PhO2S
SO2Ph
SO2Ph
, favored
PhO2S SO2Ph
E-2a
Cl
H
H
EtO
EtO
SO2Ph
Suzuki, and T. Takahashi, J. Org. Chem. 2012, 77, 5406. f) U.
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1a
2a'
SO2Ph
, disfavored
Z-2a
Scheme 3. Proposed mechanism for the formation of 2a.
The proposed mechanism for the emilination and double
bond migration was described in Scheme 3. The elimination of
6
a) T. Fukuzumi, N. Shibata, M. Sugiura, H. Yasui, S.
Nakamura, and T. Toru, Angew. Chem. Int. Ed. 2006, 45
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β
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converted to product 2a due to the stabilization effect of anion
by the neighbour sulfonyl groups. The direction of double
bond migration exclusively formed the E-product since the
congested hindrance between sulfonyl phenyl group and
carbon chain disfavored the Z-geometry.
Conclusions
In summary, we have developed an unprecedented β,γ
-
7
8
S. Zhang, Y. Zhang, Y. Ji, H. Li, and W. Wang, Chem. Comm.
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elimination process on bis(phenylsulfonyl)alkanes through
double bond migration. The mild reaction conditions were
suitable for a wide range of functionalized substrates with
good yields. Importantly, the
E
configuration only
bis(phenylsulfonyl)olefin products can be further converted to
a broad scope of vinyl building blocks.
9
A. Landa, M. Maestro, C. Masdeu, A. Puente, S. Vera, M.
Oiarbide, and C. Palomo, Chem. Eur. J. 2009, 15, 1562.
Conflicts of interest
The authors declare no competing financial interest.
Acknowledgement
This work was supported by National Natural Science Foundation of
China (S. Zhang, Grant No. 21202112), Suzhou Science and
Technology Project (S. Zhang, Grant No. ZXY201435), Start-up
funding of Jiangsu Specially-Appointed Professor (Y. Zhang), and
PAPD (A Project Funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions).
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