Dehalogenation of vicinal dihalo compounds by 1,1′-bis(trimethylsilyl)-1: H,1′ H-4,4′-bipyridinylidene for giving alkenes and alkynes in a salt-free manner

Article abstract of DOI:10.1039/c7cc07377a

We report a transition metal-free dehalogenation of vicinal dihalo compounds by 1,1′-bis(trimethylsilyl)-1H,1′H-4,4′-bipyridinylidene (1) under mild conditions, in which trimethylsilyl halide and 4,4′-bipyridine were generated as byproducts. The synthetic protocol for this dehalogenation reaction was effective for a wide scope of dibromo compounds as substrates while keeping the various functional groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal dibromo alkenes also proceeded in a salt-free manner to afford the corresponding alkenes and alkynes.

Full text of DOI:10.1039/c7cc07377a

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DOI: 10.1039/C7CC07377A
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Dehalogenation of Vicinal Dihalo Compounds by 1,1'-
Bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene for Giving Alkenes
and Alkynes in a Salt-free Manner
Received 00th January 20xx,
Accepted 00th January 20xx
Supriya Rej, Suman Pramanik, Hayato Tsurugi* and Kazushi Mashima*
DOI: 10.1039/x0xx00000x
www.rsc.org/
We report transition metal-free dehalogenation of vicinal dehalogenation
of
2,2,3,3-tetrachloro-1,1,1,4,4,4-
dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'- hexafluorobutane to produce 2,3-dichloro-1,1,1,4,4,4-
bipyridinylidene (1) under mild conditions, in which trimethylsilyl hexafluoro-2-butene (Scheme 1a);9a Scaiano and coworkers
halide and 4,4’-bipyridine were generated as byproducts. The demonstrated that 2,2':5',2'':5'',2''':5''',2''''-quinquethiophene
synthetic protocol for this dehalogenation reaction was effective (α-sexithiophene) worked as a photoredox catalyst for the
for a wide scope of dibromo compounds as substrates while dehalogenation of 1,2-dibromo-1,2-diarylethane as well as α-
keeping the various functional groups intact. Furthermore, carbonyl dibromo compounds by tetramethylethylenediamine
reduction of vicinal dichloro alkanes and vicinal dibromo alkenes (TMEDA), giving the corresponding alkenes (Scheme 1b);10b
also proceeded in a salt-free manner to afford the corresponding and Li et al. reported that the Hantzsch ester in the presence
alkenes and alkynes.
of Na2CO3 reduced vicinal dibromo compounds to give the
corresponding alkenes (Scheme 1c).10c
Protection/deprotection sequences comprise
a
key
synthetic protocol in organic chemistry for preparing versatile
organic compounds, such as natural and artificial bioactive
compounds as well as functional organic materials.1 In
contrast to the availability of the protection-deprotection
sequence to carbonyl, amine, and alcoholic groups,1,2 only
halogenation/dehalogenation has been available for alkene
functionalities, although alkenes are often been incorporated
as important interfering intermediates suitable for oxidation,
hydrogenation, olefin metathesis, etc.3,4 Halogenation of
alkenes is easily achieved by adding typical reagents such as
Br2 to alkenes, whereas dehalogenation is much more
complicated and requires the use of metal-based reductants,
such as zinc, iron, copper powders, and metal hydrides, as well
as photo-activated transition metal-mediated reductions.5–8
These reductants, however, result in narrow functional group
compatibility due to their high tendency to further reduce
interfering functionalities.5 Some organic reductants have
been developed for the dehalogenation of vicinal dihalo
compounds:9,10
tetrakis(dimethylamino)ethylene
Carpenter
et
(TDAE)
al.
for
used
the
Mr. S. Rej, Dr. Suman Pramanik, Prof. Dr. H. Tsurugi, Prof. Dr. K. Mashima
Department of Chemistry, Graduate School of Engineering Science
Osaka University, Toyonaka, Osaka (Japan)
Scheme 1. Previous work for metal-free debromination reactions of vicinal dihalo
compounds by (a) TDAE, (b) α-sexithiophene, or (c) Hantzsch ester. (d) This work:
metal- and salt-free dehalogenation reaction of vicinal dihalo compounds by
organosilicon reductant in mild condition.
Tel: +81-6-6850-6248
Fax: +81-6-6850-6249.
E-mail: mashima@chem.es.osaka-u.ac.jp; tsurugi@chem.es.osaka-u.ac.jp
Electronic Supplementary Information (ESI) available: For additional experimental
and spectroscopic data see DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Table 1. Optimization of debromination reactiona
Aside from these pioneering works, the development of a
dehalogenation reaction using organic reducing reagents
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DOI: 10.1039/C7CC07377A
without the formation of salt-wastes has remained
challenging task. We applied organosilicon reducing reagents,
1,1’-bis(trimethylsilyl)-1H,1’H-4,4’–bipyridinylidene ), 1,4-
bis(trimethylsilyl)-1,4-dihydropyrazine 2a), its methylated
a
(
1
(
Entry
Reductant
Solvent
Yield of 5a (%)b
derivatives 2b
cyclohexa-2,5-diene (
,
c
,
3
and 1-methyl-3,6-bis(trimethylsilyl)-
) (Figure 1) to successfully reduce metal
1
2
3
4
5
6
7
8
1
1
1
CD3CN
toluene-d8
C6D6
THF-d8
CD3CN
CD3CN
CD3CN
CD3CN
98 (94)c
67
71
68
66
78
21
0
halides without the formation of salt-waste to afford the
corresponding low-valent catalytically-active metal species.11,12
1
Herein, we report that organosilicon reductant
1 served as a
2a
2b
2c
3
stoichiometric reagent for the salt-free dehalogenation
reaction of vicinal dibromo compounds under mild conditions
while maintain high functional group tolerance to give the
corresponding alkenes, as well as vicinal dichloro alkanes and
vicinal dibromo alkenes to afford the corresponding alkenes
and alkynes (Scheme 1d).
a
Reaction conditions: 4a (0.10 mmol) and reductant (1.0 equiv, 0.10 mmol)
b
stirred in above mentioned solvent at room temperature for 2 h. Yields were
calculated by 1H NMR spectroscopy in the presence of mesitylene as an internal
standard. c Isolated yield is in parenthesis.
With the best reducing reagent
1 and optimized reaction
conditions in hand, we examined the reduction of various
vicinal dibromo compounds, and the results are shown in
Table 2.
Both electron-withdrawing and -donating
substituents at the para-position of the phenyl group of 4a
afforded corresponding olefins 5b and 5c in 92% and 93%
yields, respectively (entries 1 and 2). Compound 4d bearing an
acetoxy group at the para-position of the phenyl group gave
the product 5d in 91% yield, and the acetoxy group remained
intact (entry 3). Similarly, the carboxylic group of erythro-ethyl
2,3-dibromo-3-phenylpropanoate (4e) remained intact during
smooth reduction, giving (E)-ethyl cinnamate [(E)-5e] in 93%
yield (entry 4). Compounds meso-4f and 4g afforded (E)-
stilbene [(E)-5f] in 95% yield and α-methylstyrene (5g) in 90%
yield, respectively (entries 5 and 6). Interestingly, only (E)-
stilbene obtained in 91% yield, even when a dl-1,2-dibromo-
1,2-diphenylethane (dl-4f) was used as a substrate under the
optimized condition.13 Our observation for the selective (E)-
isomer formation from meso- and dl-isomers of 4f suggested
that this debromination might proceed in stepwise manner via
formation of mono-debrominated radical or anionic species
with generation of BrSiMe3 to finally produce the
thermodynamically stable (E)-alkene via sterically favorable
common conformer of the mono-debrominated species,
though we could not find any mono-debrominated adducts by
in situ trapping experiments.5a,d,e,6b,c,7e An advantage of this
Figure 1. Salt-free organosilicon reductants 1, 2a—c, and 3, and their redox potentials
vs ferrocene (Fc).11b,12
We began by searching for the best organosilicon reductant
among 1, 2a—c, and 3 for the debromination reaction of 1,2-
dibromoethylbenzene (4a) in CD3CN at room temperature for
2 h to produce styrene (5a), and the results are summarized in
Table 1. When the reaction was performed using 1, the yield
of 5a reached 98% (entry 1). Notably, the by-products were
trimethylsilyl bromide and 4,4’-bipyridine, both of which were
readily removed during the work-up. We also observed
solvent effects; the yield of 5a decreased to some extent in
toluene-d8, C6D6, and THF-d8 due to the lower solubility of
1 in
those solvents at room temperature (entries 2—4).
Compounds 2a and 2b gave 5a in moderate yields (66% and
78%) (entries 5 and 6). The reaction using 2c produced only a
low yield of 5a (21%), because of the low solubility of 2c in
synthetic protocol using
1 was its applicability to the
CD3CN (entry 7). In contrast, compound
reduce 4a (entry 8). Accordingly, we selected
reducing reagent, which was consistent with the most negative
redox potential of among the organosilicon reductant
3 11b
3
showed no ability to
debromination of aliphatic substrates, in sharp contrast to the
poor yield observed for debromination using metal-based
reducing reagents.6 In fact, vinyl benzoate (5h) was obtained
in 88% yield (entry 7), and cyclohexene (5i) was formed in 86%
yield after a prolonged reaction time (8 h) by reducing 1,2-
1
as the best
1
1—
.
dibromocyclohexane
(
4i
)
(entry 8).
Notably, we also
demonstrated some functional group tolerance, as exemplified
by the production of cholesteryl chloride (5j) (91% yield) and
testosterone propionate (5k) (89% yield) (entries 9 and 10),
with chloride and carbonyls, such as propionate and ketone
moieties, remaining intact.
2 | J. Name., 2012, 00, 1-3
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Table 2. Substrate scope for debromination reactions of vicinal dibromo compoundsa
We found that even under the optimized conditions, 1,2-
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dichloroethylbenzene (6a) was not reDdOucI:e1d0;.10h39o/wC7eCvCe0r,737U7VA
irradiation enhanced the reduction of 6a at room temperature
for 18 h to give 5a in 93% yield (Table 3, entry 1). In fact, the
compound
release of Me3Si groups in the absence of any substrates,
which suggested that the UV light-induced degradation of
1 was gradually decomposed under UV light with a
Entry
1
Substrate 4
Yield of 5 (%)b
92 (5b)
1
accelerated the dechlorination at room temperature. Under
the same irradiation conditions, erythro-2,3-dichloro-3-
phenylpropanoate
diphenylethane (6f) were converted to (E)-ethyl cinnamate
5e) (91% yield) and (E)-stilbene (5f) (87% yield), respectively
(Table 3, entries 1—3). Remarkably, an aliphatic dichloride
(
6e
)
and
meso-1,2-dichloro-1,2-
(
2
93 (5c)
such as 1,2-dichlorocyclohexane
(6i) was also reduced,
producing 5i in 51% yield (Table 3, entry 4).14
3
4
5
91 (5d)
93 (5e)c
95 (5f)c
Table 3. Dechlorination of vicinal dichloro compoundsa
Entry
1
Substrate 6
Yield of 5 (%)
93 (5a)b
2
3
4
91 (5e)c
87 (5f)c
51 (5i)b
6
7
8
90 (5g)
88 (5h)
86 (5i)d,e
a
Reaction conditions: 6 (1.0 equiv, 0.40 mmol) and 1 (1.0 equiv, 0.40 mmol)
stirred in CH3CN at room temperature for 18 h under UV-irradiation. b Yields
were calculated by 1H NMR spectroscopy in the presence of mesitylene as an
internal standard. c Erythro/meso-dibromides were used as starting material and
in products only (E)-isomers were formed as confirmed by 1H NMR spectroscopy.
9
91 (5j)
Finally, we examined debromination of vicinal dibromo
alkenes using reductant
the corresponding alkynes, and the results are shown in Table
4. Smooth reduction of (1,2-dibromovinyl)benzene (7a
proceeded to yield 8a in 85% yield (entry 1). Dibromo alkene
compounds 7b and 7c afforded ethyl phenyl propiolate (8b
1 at room temperature for 8 h to give
)
10
89 (5k)
)
(93% yield) and 1,2-diphenylacetylene (8c) (89% yield) (entries
2 and 3). Aliphatic dibromo alkene 7d required UV irradiation
for 8 h, to give 4-octyne (8d) in 85% yield (entry 4).
a
Reaction conditions: 4 (1.0 equiv, 0.40 mmol) and 1 (1.0 equiv, 0.40 mmol)
b
c
stirred in CH3CN at room temperature for 2 h. Isolated yields are reported.
Erythro/meso-dibromides were used as starting material and in products only
d
(E)-isomers were formed as confirmed by 1H NMR spectroscopy. The reaction
time was 8 h. e Yield was calculated by 1H NMR spectroscopy in the presence of
mesitylene as an internal standard.
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3
Selected examples for the easy transformations of alkenes: (a) M. E.
Jung, U. Karama, and R. Marquez, J. Org. Chem., 1999V,ie6w4A,rt6ic6le3–O6n6lin5e.
Table 4. Debromination of vicinal dibromo alkenesa
DOI: 10.1039/C7CC07377A
(b) W. S. Knowles, Angew. Chem., Int. Ed., 2002, 41, 1998–2007. (c)
R. Noyori, Angew. Chem., Int. Ed., 2002, 41, 2008–2022. (d) K. B.
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Chauvin, Angew. Chem., Int. Ed., 2006, 45, 3741–3747. (f) R. H.
Grubbs, Angew. Chem., Int. Ed., 2006, 45, 3760–3765.
Selected examples for alkene contained steroid functionalizations:
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Földes and L. Kollár, Chem. Rev., 2003, 103, 4095–4129.
Entry
1
Substrate 7
Yield of 8 (%)b
85 (8a)
4
5
Selected examples for metal powder and hydride assisted
debromination reactions: (a) W. M. Schubert, B. S. Rabinovitch, N. R.
Larson, and V. A. Sims, J. Am. Chem. Soc., 1952, 74, 4590−4592. (b)
H. G. Kuivila and L. W. Menapace, J. Org. Chem., 1963, 28
,
2165−2167. (c) N. Vijayashree and A. G. Samuelson, Tetrahedron
Lett., 1992, 33, 559−560. (d) R. Yanada, N. Negoro, K. Yanada, and T.
Fujita, Tetrahedron Lett., 1996, 37, 9313−9316. (e) B. C. Ranu, S. K.
Guchhait, and A. Sarkar, Chem. Commun., 1998, 2113–2114.
Selected examples for photo-activated transition metal compounds
catalyzed debromination reactions: (a) K. Takagi, N. Miyake, E.
Nakamura, Y. Sawaki, N. Koga, and H. Iwamura, J. Org.
Chem., 1988, 53, 1703–1708. (b) I. Willner, T. Tsfania, and Y. Eichen,
J. Org. Chem., 1990, 55, 2656−2662. (c) T. Maji, A. Karmakar, and O.
Reiser, J. Org. Chem., 2011, 76, 736–739.
2
3
4
93 (8b)
89 (8c)
6
7
Selected examples for other related processes for debromination
85 (8d)c,d
reactions: (a) Z. Goren and I. Willner, J. Am. Chem. Soc., 1983, 105
,
7764–7765. (b) I. Willner, Z. Goren, D. Mandler, R. Maidan, and Y.
Degani, J. Photochem., 1985, 28, 215–228. (c) R. Maidan and I.
Willner, J. Am. Chem. Soc., 1986, 108, 1080–1082. (d) T. S. Butcher
and M. R. Detty, J. Org. Chem., 1998, 63, 177–180. (e) B. C. Ranu
and R. Jana, J. Org. Chem., 2005, 70, 8621–8624. (f) A. Schmidt, B.
Snovydovych, and M. Gjikaj, Synthesis 2008, 2798–2804.
a
Reaction conditions: 7 (1.0 equiv, 0.40 mmol) and 1 (1.0 equiv, 0.40 mmol)
b
c
stirred in CH3CN at room temperature for 8 h. Isolated yields are reported.
Yield was calculated by 1H NMR spectroscopy in the presence of mesitylene as an
internal standard. d The reaction was done under UV irradiation.
8
9
(a) M. Wang, L. Wang, P.-H. Li, and J.-C. Yan, Chin. J. Chem., 2004, 22,
We demonstrated that organosilicon compounds
2a—c served as unique salt-free debromination reagents to
reduce vicinal dibromo compounds under mild conditions to
produce the corresponding alkenes. A notable advantage of
1 and
863–866. (b) B. W. Yoo, S. H. Kim, and J. H. Kim, Bull. Korean Chem.
Soc., 2010, 31, 2757–2758. (c) B. W. Yoo, S. H. Kim, and Y. K. Park,
Synth. Commun., 2012, 42, 1632–1636. (d) B. W. Yoo, S. J. Lee, Y. K.
Park, J. Y. Choi, and Y. S. Ahn, Bull. Korean Chem. Soc., 2013, 34
1951–1952.
,
organosilicon reductant
1 is the high compatibility of some
Organo reductant TDAE promoted dehalogenation reaction of poly
haloalkanes: (a) W. Carpenter, J. Org. Chem., 1965, 30, 3082–3084.
(b) A. Haymaker and D. W. Moore, J. Org. Chem., 1966, 31, 789–792.
(c) M. W. Briscoe, R. D. Chambers, S. J. Mullins, T. Nakamura, J. F. S.
Vaughana, and F. G. Drakesmithb, J .Chem. Soc., perkin Trans., 1994,
functional groups, such as chloride and carbonyl groups.
Moreover, vicinal dichloro substrates were also reduced under
UV irradiation conditions to afford the corresponding alkenes
in high yields. This salt-free protocol was applied to the
debromination of vicinal dibromo alkenes, leading to the
formation of the corresponding alkynes. Further application of
these organosilicon compounds to reduce organic compounds
is ongoing in our group.
1
, 3115–3118. (d) R. D. Chambers, S. J. Mullins, T. Nakamura, and A.
J. Roche, J. Fluor. Chem., 1995, 72, 231–233. (e) R. D. Chambers, S.
Nishimura, and G. Sandford, J. Fluor. Chem., 1998, 91, 63–68.
10 Metal-free debromination reactions: (a) W. Li, J. Li, M. Lin, S.
Wacharasindhu, K. Tabei, and T. S. Mansour, J. Org. Chem., 2007, 72
6016–6021. (b) C. D. McTiernan, S. P. Pitre, and J. C. Scaiano, ACS
Catal., 2014, , 4034–4039. (c) W. Chen, H. Tao, W. Huang, G. Wang,
S. Li, X. Cheng, and G. Li, Chem. Eur. J., 2016, 22, 9546–9550.
11 Salt-free reduction by organosilicon reductants: (a) H. Tsurugi, H.
Tanahashi, H. Nishiayama, W. Fegler, T. Saito, A. Sauer, J. Okuda, and
K. Mashima, J. Am. Chem. Soc., 2013, 135, 5986–5989. (b) T. Saito, H.
Nishiyama, H. Tanahashi, K. Kawakita, H. Tsurugi, and K. Mashima, J.
Am. Chem. Soc., 2014, 136, 5161–5170. (c) H. Tsurugi, A. Hayakawa,
,
4
S. R. acknowledges a financial support by Japan International
Cooperation Agency (JICA) for research fellowship (D-1490270). This
work was supported by JSPS KAKENHI Grant Nos. JP26708012
(Grant-in-Aid for Young Scientist (A)) to H. T. and JP15H05808
(Precisely Designed Catalysis with Customized Scaffolding) to K. M.
S. Kando, Y. Sugino, and K. Mashima, Chem. Sci., 2015, 6, 3434–3439.
(d) T. Saito, H. Nishiyama, K. Kawakita, M. Nechayev, B. Kriegel, H.
Tsurugi, J. Arnold, and K. Mashima, Inorg. Chem., 2015, 54, 6004–
6009. (e) T. Yurino, Y. Ueda, Y. Shimizu, S. Tanaka, H. Nishiyama, H.
There are no conflicts to declare.
Tsurugi, K. Sato and K. Mashima, Angew. Chem., Int. Ed., 2015, 54
14437–14441.
12 W. Kaim, J. Am. Chem. Soc., 1983, 105, 707–713.
,
Notes and references
1
P. G. M. Wuts and T. W. Greene, Greene’s Protective Groups on
Organic Synthesis, 4th Edition; John Wiley & Sons: Hoboken, NJ,
2007.
13 See Supporting Information.
14 Note: The reaction between 1,2-difluoro-1,2-diphenylethane and
did not afford any stilbene as C—F bond was unreactive towards
organosilicon reductant
1
2
J. F. W. McOmie, Protective Groups in Organic Chemistry, London
and New York, 1973.
1
.
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DOI: 10.1039/C7CC07377A
TOC used only:
A transition metal free dehalogenation of vicinal dihalo compounds are reported by 1,1'-
bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene in mild and convenient reaction condition. Wide
variety of substrates including vicinal dibromo and vicinal dichloro substrates are applicable and
giving corresponding alkenes in excellent yield. Moreover, the reduction of dibromo alkenes to
form alkynes quantitatively is also achieved by this organosilicon reductant.