Selenium and tellurium chalcogenides as mild and efficient reducing agents for α-halo ketones

Article abstract of DOI:10.1055/s-1998-2130

Bis(triphenylstannyl) selenide (2) and bis(tert-butyldimethylsilyl) telluride (3) are two new reagents which in the presence of fluoride ion and under mild conditions, effectively promote the dehalogenation of α-halo ketones.

Full text of DOI:10.1055/s-1998-2130

August 1998
SYNTHESIS
1137
Selenium and Tellurium Chalcogenides as Mild and Efficient Reducing Agents for
α-Halo Ketones
Erwin K. V. Schultz, David N. Harpp*
Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6
Fax +1(514)3983797; E-mail: harpp@omc.lan.mcgill.ca.
Received 26 June 1997; revised 30 October 1997
Abstract: Bis(triphenylstannyl) selenide (2) and bis(tert-
butyldimethylsilyl) telluride (3) are two new reagents which in the
presence of fluoride ion and under mild conditions, effectively
promote the dehalogenation of α-halo ketones.
We wish to report that when 2 and 3 are combined with
potassium fluoride dihydrate, various α-halo ketones are
reductively reduced in isolated yields of ca. 75% under
very mild conditions (Table).
Key words: selenium, tellurium, chalcogenides, reductive dehalo-
genation, α-halo ketones
The reactions were carried out for 24 hours at room tem-
perature to allow them to go to completion as TLC analy-
sis over shorter reaction times indicated persistent starting
material. All reactions except entry 8, were completed af-
ter 24 hours; this was confirmed by the subsequent NMR
analysis of the crude sample. The lower yield obtained for
entry 6 can be explained by difficulties that occurred dur-
ing the purification process; it had to be twice submitted
to chromatography to provide a pure product. Another
point of interest concerns the reaction times which can be
dramatically decreased by refluxing. This is an important
observation since it allows for sensitive substrates to un-
dergo dehalogenation at room temperature whereas rela-
tively uncomplicated substrates can be reduced in ca. 2
hours. A final but significant observation nonetheless, in-
volves the selective reduction of the α-bromo group with-
out affecting the nitro functionality (entry 9).
The reductive dehalogenation of α-halocarbonyl com-
pounds is an extensively researched area of organic chem-
istry. A wide variety of reagents have been employed to
1
carry out this reaction; the choice of reducing agent is
usually dependent on what other functional groups are
present in the molecule. Several reagents exist that will
reduce only the halogen of α-halo ketones, leaving the
2
3
carbonyl group intact. Among them are LDA, aqueous
4
5
TiCl , iodide ion, various inorganic phosphorus com-
pounds, tellurium reagents, thiols and selenols, metal
halides, cyanoborohydrides, molybdenum and palladi-
um catalysts, sodium dithionite, nickel boride, and
3
6
7
8
9
10
1
1
12
13
1
4
various metal carbonyls.
Recently, our laboratory reported that bis(triphenylstan-
nyl) telluride (1) in the presence of fluoride ion, reductive-
ly reduces various α-halogenated ketones under mild con-
Both reagents allow for effective reductive dehalogena-
tion, but selenide 2 is the reagent of choice. It has no sig-
nificant odor and is not water sensitive making it easy to
handle. In addition, 2 can be stored in the refrigerator over
long periods of time without any trace of decomposition;
this is not the case for tellurium reagent 3. On the other
1
5
ditions. Even though the latter is an excellent reducing
agent, it is foul-smelling and stains all glassware it comes
in contact with. In order to further explore and widen the
use of these types of reagents, we believed it important to
investigate two related molecules: bis(triphenylstannyl)
selenide (2) and bis(tert-butyldimethylsilyl) telluride (3).
These compounds belong to the general class of the fol-
lowing structure: R M-X-MR ; M = Si, Sn, Pb; X = O, S,
15
hand bis(triphenylstannyl) telluride (1), is a more stable
tellurium reagent also refrigerator stable but, as with tel-
lurium reagent 3, stains all glassware it touches.
3
3
Se, Te.
The choice of solvent has a strong influence on the reac-
tion. A variety of solvents, e.g. THF, chloroform, or ace-
tonitrile can be used, however, the reaction is faster in the
more polar acetonitrile.18
Compound 2 was prepared according to a modified litera-
ture procedure by Einstein and co-workers and com-
In an attempt to further explore the utility of the bis(triph-
enylstannyl) selenide (2), related substrates other than
α-halo ketones were submitted to identical reaction con-
ditions; those tried were lactone 4, dioxolane 5 and a poly-
functional compound 6.
1
6
pound 3 according to the method by Detty and co-
1
7
workers as shown.
In the case of substrates 4 and 6, no reduced product could
be isolated. Instead a coupling reaction occurred which
led to the formation of diselenide 7 (54%)19 and selenide

1
138
Papers
Table. Dehalogenation of α-Halo Ketonesa
SYNTHESIS
b
c
Entry
α-Halo Ketone
Time (h)
Product
Yield 2
%)
Yield 3
(%)
(
d
1
2
3
4
5
6
PhCOCH Br
24
2e
PhCOCH3
(94) 65
(92)d
(89)d
(84)d
75
72
2
PhCOCH Br
PhCOCH3
2
PhCOCH Cl
24
2e
PhCOCH3
75
2
PhCOCH Cl
PhCOCH3
2
PhCOC(CH ) Br
24
24
PhCOCH(CH3)2
81
65
3
2
PhCOCH(CH )Br
PhCOCH CH3
48
3
2
7
8
24
48
81
71
72
82
9
24
89
79
a
Unless otherwise specified, all reactions were carried out at r.t. in MeCN with the halo ketone/telluride 2 or selenide 3/KF · 2 H O 1:1:3 (mole
2
ratio).
b
c
Isolated yields obtained with the selenide reagent 2.
Isolated yields obtained with the telluride reagent 3.
d 1
e
H NMR yields.
Refluxing solvent.
2
0
8
(
(59%). In the case of dioxolane 5, no reaction occurred In earlier work in our laboratory mechanisms were sug-
followed by NMR) and most of the starting material was gested,18 which involved an enolate species. We have
still present even after 96 hours.
been able to confirm the intermediacy of an enolate by
trapping it with benzaldehyde. This trapping was carried
out on several of the substrates shown in the Table. Hence,
enolate 11 resulting from substrate 10 was trapped as the
β-hydroxy ketone 12 whereas enolate 14 resulting from
substrate 13 was trapped as the enone 15.
When substrate 4 was reacted with reagents 1 and 3, a com-
plex mixture was obtained that seemed to be composed of
unreacted starting material, some reduced product, an alk-
ene that could have resulted from the elimination of HBr
and other unidentified compounds. Substrate 5 displayed
no reactivity in the presence of reagents 1 and 3. On the
other hand, an efficient reduction of substrate 6 was ob-
served when treated with either 1 or 3; compound 9 was
formed in isolated yields of 74% and 91% respectively.
The formation of the enolate could involve the following
2
2
steps with fluoride ion as the initiator. Destannylation
–
would release Ph SnSe which would displace halide.
3

August 1998
SYNTHESIS
1139
flask was rinsed twice with MeCN or Et O (10 mL). The solution was
2
then concentrated and the resulting solid purified by column chroma-
tography (dry-pack, hexanes/EtOAc 60:40) yielding 7 as a pair of di-
astereomers: 0.12 g (54%).
1
H NMR (200 MHz, CDCl ): δ = 1.69 (s, 3H), 1.73 (s, 3H), 2.46 (m,
3
4
H), 4.31 (m, 4H).
C NMR (200 MHz, CDCl ): δ = 25.1 (s), 25.2 (s), 37.6 (s), 37.7 (s),
1
3
3
4
4.4 (s), 44.7 (s), 65.1 (s), 65.2 (s), 177.2 (s), 177.4 (s).
7
7
Se NMR (300 MHz, CDCl , internal reference Me Se): δ = 536.2
3
2
(
s), 537.8 (s).
+
EI-MS: m/z (%) = 358 (14, [M ]), 100 (100).
Dehalogenation of Ethyl [2-(2-Chloroacetamido)thiazol-4-yl]ace-
tate (6):
A mixture of ethyl [2-(2-chloroacetamido)thiazol-4-yl]acetate (0.40 g,
Further fluorodestannylation delivers elemental selenium
and the reduced product.
1.5 mmol), bis(triphenylstannyl) selenide (2) (1.17 g, 1.5 mmol) and
KF•2 H O (0.43 g, 4.6 mmol) in MeCN (40 mL) was stirred at r.t. for
2
Bis(triphenylstannyl) Selenide (2):
48 h under N . The mixture was filtered using Celite, and the reaction
2
To a solution of selenium powder (2.21 g, 28.0 mmol) in EtOH
flask was rinsed twice with MeCN or Et O (10 mL). The solution was
2
(
6
60 mL) and water (15 mL) was slowly added NaBH4 (2.49 g,
6.0 mmol). The solution was refluxed for 4 h and then allowed to
return to r.t. A solution of Ph SnCl (21.57 g, 56.0 mmol) in benzene
then concentrated and the resulting solid purified by column chroma-
tography (dry-pack, hexanes/EtOAc 50:50) to yield 8: 0.24 g (59%).
1
H NMR (200 MHz, CDCl ): δ = 1.25 (t, 3H, J = 7.2 Hz), 3.59 (s, 2H),
3
3
(
70 mL) was added dropwise via an addition funnel. The resulting
3.69 (s, 2H), 4.15 (q, 2H, J = 7.2 Hz), 6.80 (s, 1H).
13
mixture was stirred at r.t. for 3 h. The mixture was subsequently fil-
tered over Celite and the aqueous layer removed. The remaining or-
ganic layer was concentrated and the resulting solid was purified by
C NMR (200 MHz, CDCl ): δ = 14.1 (s), 25.3 (s), 36.8 (s), 61.2 (s),
3
111.4 (s), 143.1 (s), 157.7 (s), 168.3 (s), 170.4 (s).
7
7
Se NMR (300 MHz, CDCl , internal reference Me Se): δ = 274.3.
3
2
+
+
recrystallization (CHCl /EtOH) to yield 2: 15.7 g (72%); mp 141–
MS-FAB : m/z (%) = 535 (43, [M + 1 ] ), 307 (40), 228 (22).
3
1
6
1
42°C (lit. mp 148°C).
1
H NMR (200 MHz, CDCl ): δ = 7.39–7.18 (m, 30H).
Trapping of Enolate 11:
3
1
3
C NMR (200 MHz, CDCl ): δ = 128.5 (s), 129.3 (s), 129.4 (s), 136.5
A mixture of 2-bromo-4'-methoxyacetophenone (0.235 g, 1.03 mmol),
bis(triphenylstannyl) selenide (2) (0.80 g, 1.03 mmol), KF (0.18 g,
3.10 mmol) and benzaldehyde (3.4 ml, 33.4 mmol) in anhyd MeCN
3
(
s), 138.6 (s).
+
MS (NBA-FAB ) = 778.0
(
25 mL) was stirred at r.t. for 48 h under N . The mixture was filtered
2
Bis(tert-butyldimethylsilyl) Telluride (3):
using Celite, and the resulting filter cake washed with Et O. The so-
2
A 50-mL three-necked, round-bottomed flask was flamed and cooled
lution was concentrated and to the resulting crude residue was added
under N . The flask was charged with 1 M Super Hydride in THF
Et O (30 mL) and water (5 mL). The organic layer was removed and
2
2
(29 mL, 29.0 mmol). The flask was cooled in an ice bath and telluri-
the remaining aqueous layer was reextracted with Et O. The organic
2
um powder (1.78 g, 14.0 mmol) was added. The mixture was warmed
to r.t. and stirred for 2 h. The mixture was cooled to ice-bath temper-
ature and tert-butylchlorodimethylsilane (4.87 g, 32.0 mmol) was
added in one portion. The resulting mixture was stirred for 2 h at r.t.
The low boiling volatiles were removed by distillation directly from
the reaction vessel. The product 3 was isolated (1.78 g, 36%) as a gray
solid after initial distillation from the mixture as an oil; bp 105°C/4.5
layers were combined and dried with (MgSO ) and finally concentrat-
4
ed. The resulting crude residue was left in the fume hood for several
hours to get rid of the excess benzaldehyde and then purified by col-
umn chromatography (dry-pack, benzene/EtOAc 92:8) to yield com-
pound 12: 0.18 g (67%).
1
H NMR (200 MHz, CDCl ): δ = 3.30 (m, 2H, AB-X system), 3.85
3
(s, 4H, OH + OCH ), 5.31 (t, 1H, J = 6.0 Hz), 6.92 (d, 2H, J = 9.0 Hz),
3
1
7
Torr (lit. bp 90–95°C/5.5 Torr).
7.39 (m, 5H), 7.92 (d, 2H, J = 9.0 Hz).
1
13
H NMR (200 MHz, CDCl ): δ = 0.53 (s, 12H), 0.97 (s, 18H).
C NMR (200 MHz, CDCl ): δ = 46.8 (s), 55.4 (s), 70.1 (s), 113.7
3
3
(s), 125.7 (s), 127.5 (s), 128.2 (s), 128.4 (s), 129.5 (s), 130.4 (s), 143.0
Dehalogenation of 2-Bromo-4'-nitroacetophenone (Entry 9);
Typical Procedure:
(s), 163.8 (s), 198.6 (s).
A mixture of 2-bromo-4'-nitroacetophenone (0.32 g, 1.3 mmol),
Trapping of Enolate 14:
bis(triphenylstannyl) selenide (2) (1.01 g, 1.3 mmol) and KF•2 H O
A mixture of 2-bromo-4'-nitroacetophenone (0.25 g, 1.02 mmol),
bis(triphenylstannyl) selenide (2) (0.80 g, 1.03 mmol), KF (0.18 g,
3.10 mmol) and benzaldehyde (3.4 mL, 33.4 mmol) in anhyd MeCN
2
(0.37 g, 3.9 mmol) in MeCN (30 mL) was stirred at r.t. for 24 h under
N . The mixture was filtered using Celite, and the reaction flask
2
rinsed twice with MeCN or Et O (10 mL). The solution was then con-
was stirred at r.t. for 24 h under N . The mixture was filtered using
2
2
centrated and the resulting solid purified by column chromatography
Celite, and the resulting filter cake washed with Et O. The solution
2
(
dry-pack, benzene) to yield 4'-nitroacetophenone: 0.19 g (89%).
was concentrated and to the resulting crude residue was added Et O
(30 mL) and water (5 mL). The organic layer was removed and the
2
1
H NMR (200 MHz, CDCl ): δ = 2.66 (s, 3H), 8.09 (d, 2H, J =
3
8
.6 Hz), 8.29 (d, 2H, J = 8.0 Hz).
remaining aqueous layer was reextracted with Et O. The organic lay-
2
1
3
C NMR (200 MHz, CDCl ): δ = 26.9 (s), 123.8 (s), 129.3 (s), 141.3
ers were combined and dried (MgSO ) and finally concentrated. The
3
4
(
s), 150.1 (s), 196.3 (s).
resulting crude residue was left in the fume hood for several hours (to
get rid of the excess benzaldehyde) and then purified by column chro-
+
EI-MS: m/z (%) = 165 (24, [M ]), 150 (100), 120 (8).
matography (dry-pack, benzene) to yield compound 15: 0.15 g (56%).
1
Dehalogenation of (±)-α-Bromo-α-methyl-γ-butyrolactone (4):
A mixture of (±)-α-bromo-α-methyl-γ-butyrolactone (0.154 mL,
H NMR (200 MHz, CDCl ): δ = 7.48 (m, 4H), 7.66 (m, 2H), 7.85 (m,
3
1H), 8.14 (d, 2H, J = 9.0 Hz), 8.36 (d, 2H, J = 9.0 Hz).
13
1
.3 mmol), bis(triphenylstannyl) selenide (2) (1.02 g, 1.3 mmol) and
C NMR (200 MHz, CDCl ): δ = 121.2 (s), 123.9 (s), 128.7 (s), 129.1
3
KF•2 H O (0.36 g, 3.9 mmol) in MeCN (30 mL) was stirred at r.t. for
(s), 129.4 (s), 131.2 (s), 134.2 (s), 143.0 (s), 146.8 (s), 150.0 (s), 189.0 (s).
MS (NBA-FAB ) = 254
2
+
2
4 h under N . The mixture was filtered using Celite, and the reaction
2

1
140
Papers
SYNTHESIS
Dehalogenation of Ethyl [2-(2-Chloroacetamido)thiazol-4-yl]ace-
tate (6) with Reagent 3: Typical Procedure:
A mixture of ethyl [2-(2-chloroacetamido)thiazol-4-yl]acetate (0.26 g,
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2596.
1
1
.00 mmol), bis(tert-butyldimethylsilyl) telluride (3) (0.54 g,
.52 mmol) and KF•2 H O (0.38 g, 4.00 mmol) in MeCN (30 mL)
2
was stirred at r.t. for 48 h under N . The mixture was filtered using
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2
Celite, and the reaction flask was rinsed twice with Et O. The solution
2
was then concentrated and the resulting solid purified by column chro-
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matography (dry-pack, hexanes/EtOAc 40:60) to yield 9: 0.21 g (91%).
1
H NMR (200 MHz, CDCl ): δ = 1.19 (t, 3H, J = 7.2 Hz), 2.19 (s, 3H),
3
3
.66 (s, 2H), 4.15 (q, 2H, J = 7.2 Hz), 6.77 (s, 1H), 10.55 (b, 1H, N-H).
Molander, G. A.; Hahn, G. J. Org. Chem. 1986, 51, 1135.
Fuji, K.; Node, M.; Kawabata, T.; Fujimoto, M. J. Chem. Soc.,
Perkin Trans. I 1987, 1043.
E. K. V. Schultz gratefully acknowledges the Government of the Prov-
ince of Quebec for an F.C.A.R. Fellowship; we thank the National
Sciences and Engineering Council of Canada for financial support of
this work.
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1
153.
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(
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(
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4
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1
13
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(Attached Proton Test) and an isotopic distribution report.
21
(20) Compound 8 is a selenide which is confirmed by MS (expected:
+
1
13
77
2
3, 1385.
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