Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

Article abstract of DOI:10.3762/bjoc.13.92

Alkynyl selenides were synthesized by a straightforward one-pot and three-step methodology, without the need of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K₃PO₄-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted acetylenes.

Full text of DOI:10.3762/bjoc.13.92

Transition-metal-free one-pot synthesis of alkynyl selenides
from terminal alkynes under aerobic
and sustainable conditions
Adrián A. Heredia and Alicia B. Peñéñory*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 910–918.
INFIQC, Facultad de Ciencias Químicas, Universidad Nacional de
Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina
doi:10.3762/bjoc.13.92
Received: 16 December 2016
Accepted: 19 April 2017
Published: 16 May 2017
Email:
Alicia B. Peñéñory* - penenory@fcq.unc.edu.ar
* Corresponding author
Associate Editor: B. Stoltz
Keywords:
© 2017 Heredia and Peñéñory; licensee Beilstein-Institut.
License and terms: see end of document.
alkynyl selenide; electrophilic cyclization; nucleophilic substitution;
potassium selenocyanate; terminal alkynes
Abstract
Alkynyl selenides were synthesized by a straightforward one-pot and three-step methodology, without the need of diselenides as
starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of
dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction be-
tween KSeCN and alkyl halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding
alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted
benzofuran and indole derivatives starting from convenient 2-substituted acetylenes.
Introduction
Alkynyl selenides, as many other selenium compounds, have plications of alkynyl selenides are electrophilic addition reac-
potential anti-oxidant activities, and may play a role in certain tions, many of them modulated by transition-metal catalysts
diseases such as cancer, heart diseases, inflammatory processes, [11]. Some examples are: hydroboration which results in a
arthritis, and skin damage caused by exposure to UV radiation vinylborane selenide used in Pd-catalyzed Suzuki cross-cou-
[1-3]. However, all these properties belong to organoselenides pling reactions [12], the addition to tributyltin hydride in the
due to their ability to engage in enzymatic processes [4,5] and presence of Pd and Cu catalysts to afford (E)-α-selenylstan-
alkynyl selenides have demonstrated only limited biological nanes for the synthesis of trisubstituted alkenes [13] and
properties [6,7]. On the other hand, these compounds are widely hydrozirconation with further replacement of Zr atom by hydro-
applied in organic chemistry due to the presence of an alkynyl gen or halogen [14] or their use in the preparation of α-seleno-
group [8,9] and an organoselenium moiety [10] in one mole- α,β-unsaturated ketones [15]. Besides, hydrogen halide-addi-
cule both comprising versatile building blocks or intermediates tion reactions to alkynyl selenides in the absence of transition
in organic synthesis. Some of the most outstanding synthetic ap- metals [16] and the addition of p-toluenesulfonic acid [17] are
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Beilstein J. Org. Chem. 2017, 13, 910–918.
applied to obtain vinyl organometallic compounds and key sele- presence of only t-BuOK, the corresponding alkynyl selenide 5
noester intermediates. Finally, electrophilic cyclizations [18,19] was obtained together with dialkyl selenides R2Se and R2Se2.
of systems bearing a selenide alkynyl group allow the synthesis In view of the important synthetic application of alkynyl
of seleno-functionalized heterocycles [20,21]. Recently, the use selenides, we envisioned the possibility of obtaining alkynyl an-
of alkynyl selenides as substrates for Pd-catalyzed Suzuki, alogues based on our methodology developed for the synthesis
Negishi, Kumada and Sonogashira cross-coupling reactions has of vinyl selenides.
been reported with good yields [22].
We herein report the optimized reaction conditions for the one-
Due to the synthetic relevance of alkynyl selenides several pot and three-step synthesis of alkynyl selenides 5 using
methodologies for their synthesis have been developed. Among KSeCN as selenium source in PEG 200 as the solvent under an
them are reactions between lithium or sodium acetylides and oxygen atmosphere. The reaction does not require diselenides
electrophilic selenium reactants [23]. The use of hypervalent or selenyl halides as starting electrophilic reagents, thus
iodine(III) species [24] or alkynyl bromides with RSeLi [25] as offering important advantages over the methods currently re-
nucleophilic selenium species or the reaction of alkynyl bro- ported in the literature (Scheme 1, B).
mides under Cu catalysis [26-29], from terminal alkynes in the
Results and Discussion
presence of bases and Cu [30-33], Fe [34,35] or In [36] cataly-
sis, or with t-BuOK without of transition metal [37] have been Optimization of conditions
reported. In general, these methodologies require selenyl During a base screening for the synthesis of alkyl styryl
halides or diselenides as starting materials, which limit their ap- selenides (1) [38], we observed that the addition of K3PO4 to
plication. Furthermore, in most cases these procedures involve RSeCN, obtained in situ by reaction of RX with KSeCN,
the use of reducing agents, such as elemental Mg or Zn, transi- afforded exclusively the corresponding R2Se2. Based on this
tion-metal catalysis, inert atmosphere, controlled temperatures, result we started seeking the best conditions to afford alkynyl
and long reaction times.
selenide 5a using styryl bromide (4a), 2 and n-octyl bromide
(3a). Thus, we applied the optimized conditions for the synthe-
Recently, we have reported the synthesis of vinyl selenides 1 by sis of 1 (Scheme 1, A), replacing the reducing agent by t-BuOK
a three-step one-pot procedure using KSeCN (2), alkyl (3) and in the third step. When 1.5 equiv of t-BuOK with regard to 4a
styryl halides (4) with good yields (Scheme 1, A) [38]. This were employed in the reaction, alkyne 5a was obtained in 24%,
reaction proceeds through an initial nucleophilic substitution while the use of 2.0 and 3.0 equiv increased the yield to 61%
reaction between the alkyl halide and KSeCN to afford the cor- and 53%, respectively (Scheme 2). Using more than two equiv
responding alkyl selenocyanate (RSeCN). The treatment of the of base resulted in a lower yield of alkyne 5a and the formation
latter with K3PO4 generates the alkyl selenolate anion (RSe−) of styryl selenide 1a could be detected.
which reacts with another RSeCN molecule to give the corre-
sponding diselenide R2Se2. Reduction of the latter diselenide by
treatment with NaBH4 affords an alkyl selenolate anion, which
reacts with styryl halide to give the desired styryl selenide 1.
During optimization of the reaction conditions to 1 and in the
Scheme 2: Effect of t-BuOK on the formation of n-octyl alkynyl
selenide 5a.
Afterward we performed some control experiments. Thus, the
reaction of styryl bromide (4a) with 1 equiv of t-BuOK afforded
64% yield of phenylacetylene (6a), while the elimination reac-
tion was quantitative with 2 equiv of the base. These results
suggested that 6a is a key intermediate in the reaction. Further-
more, the fact that in the presence of 1 equiv of base the elimi-
nation product was obtained in approximately 50% yield
implies that the deprotonation of 6a is faster than the elimina-
Scheme 1: One-pot synthesis of vinyl and alkynyl selenides.
tion from 4a.
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Beilstein J. Org. Chem. 2017, 13, 910–918.
Since 6a is an intermediate compound of the reaction, we opti- were found with DMF and PEG 200, we chose PEG 200 as the
mized the reaction conditions using terminal alkyne 6a as the solvent for subsequent reactions, which is a non-toxic and inex-
substrate instead of styryl bromide (4a), following a three-step pensive biodegradable material also used as a sustainable and
one-pot procedure (see Scheme 2). First, we explored the reac- alternative solvent due to its reusability [39].
tivity of KSeCN (2), n-octyl bromide (3a) and acetylene 6a in
DMF as solvent under different atmospheric conditions Table 2 summarizes the results for the screening and concentra-
(Table 1, entries 1–3). Conducting the reaction under an inert tion of the base used. Formation of 5a increases as the volume
atmosphere, compound 5a was obtained with a yield of 38%. A of solvent increases from 1 mL to 3 mL, with yields of 61%,
slightly higher performance was observed when the reaction 71% and 84%, respectively (Table 2, entries 1–3); no consider-
was carried out under an air atmosphere (41%) and a remark- able change (80%) was observed in 4 mL of PEG 200 (Table 2,
ably improved yield of 71% was obtained under an oxygen at- entry 4). To understand this trend, the reaction between 6a and
mosphere with continuous bubbling. These results show that the Ph2Se2 was performed, in which the concentration of reactants
presence of oxygen in the reaction medium contributes to the was twelve times higher than that under standard conditions,
formation of the expected product.
Scheme 3, observing the formation of phenyl (2-phenyl-
ethynyl)selane [24] and the addition product 1-phenyl-2-
(phenylselanyl)vinylselanylbenzene [40] (27% and 73% yields
of relative area by GC, respectively). This result shows that
under the conditions used, the Ph2Se2 addition reaction to the
triple bond competes with Se-alkynylation. This side reaction is
less efficient when the concentration decreases, favoring the
reaction of interest when the amount of solvent increases.
Table 1: Solvent screening for the one-pot synthesis of selenide 5a.a
Table 2: Concentration effects and base screening for the one-pot
synthesis of selenide 5a.a
entry
solvent
yield % 5ab
1
DMF
71
38
41
47
9
2c
3d
4
DMF
DMF
MeCN
NMP
5
6
DMSO
dioxane
toluene
ethanol
isopropanol
water
10
<5
18
43
65
nd
63
71
7
entry
base
PEG 200 (mL)
yield % 5ab
8
9
1
t-BuOK
t-BuOK
t-BuOK
t-BuOK
KOH
1
2
3
4
3
3
3
3
3
3
61
10
11
12
13
2
71
3
84
PEG 300
PEG 200
4
80
5
37
aThe reaction was performed by using: 0.25 mmol of 6a, 1.35 equiv of
2, 3a and K3PO4 and 1.1 equiv of t-BuOK in 2 mL of solvent under O2
atmosphere, unless otherwise indicated. bQuantified by GC with
internal standard. nd: not detected. cUnder N2. dOpen to air.
6
NaOMe
CuI/Et3N
t-BuOK
t-BuOK
t-BuOK
55
7c
8d
9d,f
10f,h
31
93 (78)e
(56)e,g
26i
aThe reaction was performed by using: 0.25 mmol of 6a, 1.35 equiv of
2, 3a and K3PO4 and 1.1 equiv of t-BuOK in PEG 200 as solvent under
O2 atmosphere, unless otherwise indicated. bQuantified by GC with
internal standard. cCuI (10 mol %), 1.1 equiv of Et3N at 100 °C for 24 h
under N2 atmosphere. d0.25 mmol of 6a, 1.0 equiv of 2, 3a and
K3PO4, and 2.0 equiv of t-BuOK; 6a and t-BuOK were added in the
last step. eIsolated yield. fWithout addition of K3PO4. gTogether with
R2Se and R2Se2 (35% with a ratio of 1:6). hn-Octyl selenocyanate,
prepared by reaction of 3a (0.25 mmol) and 2 (0.25 mmol) in 1 mL of
PEG 200, was dropped to a solution of alkynyl anion, obtained by
reaction of 6a (0.25 mmol) and t-BuOK (0.25 mmol) in 2 mL of PEG
200 under N2 atmosphere, and heated at 100 °C for 2 h. iTogether with
a mixture of R2Se and R2Se2 (74% with a ratio of 1:3).
Next, we performed a screening of solvents under oxygen atmo-
sphere (Table 1). Best yields were obtained with DMF,
isopropanol or polyethylene glycol (PEG) as the solvents
(Table 1, entries 1, 10, 12 and 13), whereas only moderate
yields below 50% were obtained when the reaction was con-
ducted in acetonitrile or ethanol (Table 1, entries 4 and 9). Poor
yields below 20% were observed by using N-methylpyrroli-
done (NMP), dimethyl sulfoxide (DMSO), dioxane or toluene
(Table 1, entries 5–8). Finally, product 5a was not detectable at
all when performing the reaction in water. As similar yields
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Beilstein J. Org. Chem. 2017, 13, 910–918.
reaction between the selenium atom-centered radical and the
alkenyl moiety.
Table 3: One-pot synthesis of alkynyl selenides 5.a
Scheme 3: Effect of reactants concentration on alkynyl selenide for-
mation.
Subsequently, a set of bases able to deprotonate the alkyne in
the last step was tested. By using KOH or NaOMe, 5a was
generated in 37% and 55% yield, respectively (Table 2 entries 5
and 6). The CuI/Et3N system, a commonly used combination to
activate alkynes in Sonogashira reactions, was also tested,
giving 31% yield of 5a (Table 2, entry 7). However, t-BuOK
afforded the best results and therefore selected for the subse-
quent reactions. Next, the ratio of reactants was further investi-
gated in order to obtain the best possible product yield. Thus, by
using 6a/2/3a/K3PO4/t-BuOK at a 1:1:1:1:2 ratio, respectively,
and by adding 6a with t-BuOK in the last step, the yield of
selenide 5a was 93% quantified by GC and 78% isolated yield
(Table 2, entry 8). As a control experiment, the reaction was
repeated under optimized conditions but without the addition of
K3PO4 (Table 2, entry 9). As previously observed [38], the
reaction occurred with the formation of di-n-octyl selenide and
di-n-octyl diselenide as byproducts, decreasing the yield of 5a
to 56% and hampering its isolation. Similar results were ob-
tained when adding n-octyl selenocyanate to a solution of
alkynyl anion under N2 atmosphere followed by heating at
100 °C for 2 h (Table 2, entry 10).
entry R–X
yield % 5b
1
2
3
4
n-OctBr
78
67
77
79
5a
5a
5b
5c
n-OctOTs
MeI
n-BuBr
5
41
5d
6
7
8
9
c-HexCH2Br
c-HexBr
56
nd
nd
nd
5e
5f
t-BuBr
5g
PhCH2Br
5h
aThe reaction was performed by using: 0.25 mmol of 6a, 1.0 equiv of
2, 3 and K3PO4 and 2.0 equiv of t-BuOK, in 3 mL PEG 200 as solvent
under an O2 atmosphere; 6a and t-BuOK were added in the last step.
bIsolated yield, nd: not detected.
With the optimized reaction conditions at hand, we explored the
scope and limitation of this methodology (Scheme 1B) for the
synthesis of alkyl alkynyl selenides 5 from various substituted The reaction with (bromomethyl)cyclohexane afforded 5e in
terminal arylacetylenes 6, synthesized according to known pro- 56% yield (Table 3, entry 6). The difference in reactivity rela-
cedures [41,42], and different alkyl halides 3.
tive to 5a is probably due to steric hindrance caused by the
cyclohexyl ring to the alkynyl anion attack. The basic reaction
Table 3 comprises the results obtained from the reaction of conditions were responsible for promoting elimination reac-
phenylacetylene (6a) with different alkyl halides 3. The reac- tions (E2) when secondary and tertiary alkyl halides were used,
tion of primary alkyl bromides afforded the corresponding preventing formation of 5f and 5g products, and this is a limita-
alkynyl selenide 5 in moderate to good yields. It is worth men- tion of the procedure reported herein (Table 3, entries 7 and 8).
tioning, that replacing n-octyl bromide by the corresponding By employing a benzylic halide such as benzyl bromide, the ex-
tosylated compound, the yield of 5a decreased from 78% to pected product 5h (Table 3, entry 9) was not detected. Again,
67% (Table 3, entries 1 and 2). A comparable reactivity was the basic environment and moderate acidity of the methylene
found for the reactions with methyl iodide and n-butyl bromide, protons in benzyl selenocyanate (7h) or dibenzyl diselenide
affording 5b and 5c in 77% and 79% yields, respectively (8h) may afford intermediates prone to decomposition, directly
(Table 3, entries 3 and 4). However, with 6-bromohex-1-ene the affecting formation of 5h.
yield of compound 5d dropped to 41% (Table 3, entry 5) and
2-methyltetrahydro-2H-selenopyran was detected by GC–MS. Furthermore, the electronic and steric effects offered by differ-
This indicates a possible competitive intramolecular addition ent substituents on the aryl moieties attached to the acetylenic
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Beilstein J. Org. Chem. 2017, 13, 910–918.
group were also studied (Table 4). Thus, the p-methyl-substi- to 52%. This is ascribed to a lower acidity of the acetylenic
tuted derivative 6b afforded the selenide 5i in comparable proton in 6c in relation to the unsubstituted alkyne 6a (Table 4,
yields as with the unsubstituted alkyne 6a (Table 4, entries 1 entry 3). For phenylethynyl derivatives substituted in para or
and 2). The presence of a strong electron donor such as a me- ortho position by halides, the yields of the corresponding prod-
thoxy group (compound 6c), decreased the yield of product 5j ucts 5k and 5l were 64% and 61%, respectively (Table 4,
Table 4: One-pot synthesis of alkynyl selenide 5.a
entry
1
R, 6
product 5
yield %b
78
Ph
6a
5a
2
3
4
81
52
64
6b
6c
6d
5i
5j
5k
5
61
6e
5l
6
7
nd
53
6f
5m
5n
6g
8
nd
6h
5o
5p
5q
9c
<5d
51
6i
6j
10c
aThe reaction was performed by using: 0.25 mmol of 6, 1.0 equiv of 2, 3a and K3PO4 and 2.0 equiv of t-BuOK, in 3 mL of PEG 200 as solvent under
an O2 atmosphere; 6 and t-BuOK were added in the last step. bIsolated yield, nd: not detected. c3.0 equiv of t-BuOK and stirring at 100 °C for 6 h
were used in the last step. dThe main product was 1-ethyl-2-(octylselanyl)-1H-indole (9) in 62% isolated yield.
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Beilstein J. Org. Chem. 2017, 13, 910–918.
entries 4 and 5). The ortho-substituent showed no remarkable
steric hindrance since the reactive center was located relatively
far from this group.
On the other hand, in the presence of a strong electron-with-
drawing substituent such as a nitro group, the corresponding
product 5m was not detected (Table 4, entry 6). This result indi-
cates that although the acidity of acetylenic proton in 6f is
higher than that for the unsubstituted one 6a, the resulting anion
is highly stabilized by this group, thus reducing its nucleophilic
character and being unreactive against di(n-octyl) diselenide
(8a). Alkyne 6g, having a styryl group afforded compound 5n
in 53% yield (as a mixture of E and Z isomers in a 5:1 ratio, re-
spectively; Table 4, entry 7) and the aliphatic terminal
alkyne 6h failed to react under the selected conditions (Table 4,
entry 8).
Scheme 4: Synthesis of N-ethyl-2-(n-octylselanyl)-1H-indole (9) and
3-iodo-2-(n-octylselanyl)benzofuran (10).
In order to apply the present methodology to the one-pot syn-
thesis of heterocycles derived from indole and benzofuran, con-
venient ortho-substituted phenylacetylenes were also tested. To
our delight, the o-diethylamino-substituted derivative 6i much less unpleasant odor than the aliphatic diselenides
afforded N-ethyl-2-(n-octylselanyl)-1H-indole (9) in 62% iso- (R2Se2). Thus the global 79% yield of 5c obtained by our
lated yield (Scheme 4). The primary selenyl-substituted prod- method, involves the generation of R2Se2 over two steps fol-
uct 5p was only detected in traces by GC–MS suggesting that lowed by reaction with phenylacetylene. The other methods re-
this product cyclized in the reaction medium to afford indole 9 ported comparable or smaller isolated yields of 5c (Table 5).
(Table 4, entry 9). On the other hand, when o-MeO-substituted
phenylacetylene 6j was employed the corresponding selenyl- Proposed mechanism
substituted product 5q was isolated in 51% yield (Table 4, entry In order to assess the mechanism of the three-step one-pot syn-
10). The subsequent electrophilic addition of I2 to selenide 5q thesis of 5, the reaction between the commercial reagents 6a
afforded 3-iodo-2-(n-octylselanyl)benzofuran (10) in excellent and 0.5 equiv of diphenyl diselenide (as analogue to the dialkyl
yield (93% isolated yield, Scheme 4).
diselenides 8 proposed as intermediates) was carried out in the
presence of 1 equiv t-BuOK at 100 °C for 1 h under air
Finally, we compared our method with syntheses reported in the atmosphere. As a result, phenyl(2-phenylethynyl)selane [34]
literature that mainly rely on commercially available selenium was isolated in 64% yield. Repeating the reaction under oxygen
compounds such as n-Bu2Se2, Me2Se2 or Ph2Se2. Our proce- the conversion to the alkynyl selenide increased to 90%
dure does not require transition-metal catalysts, it uses PEG 200 (Scheme 5A). After work-up a positive test with I2/starch indi-
as solvent within shorter or comparable reaction times and it has cator of the aqueous layer confirmed the presence of H2O2 [43]
the advantage of in situ generating R2Se2 from commercially resulting from the superoxide radical anion (O2·−) generated
available and cheaper salts, that are easier to handle and have a during reaction under oxygen atmosphere. It is also possible
Table 5: Comparison of the present method with other reported procedures for the synthesis of 5c from 6a and n-Bu2Se2.
entry
conditions
yield % 5ca
reference
1
NpsFe3O4 (10 mol %), K2CO3, DMF, 80 °C, 14 h
NpsCuO (10 mol %), K2CO3, DMSO, 80 °C, 14 h
InCl3 (10 mol %), Cs2CO3, DMSO, 80 °C, 12 h
CuI (1 equiv), HMPA, N2, rt, 2 h
51
79
64
70
60
79
[34]
2
[32]
3
[36]
4b
5b
6c
[26]
BuSeLi, THF, N2, 0 °C, 1 h
[25]
K3PO4, t-BuOK, PEG 200, O2, 100 °C, 3 h 10 min
this work
aIsolated yield. bThe reaction was performed by using 1-bromo-2-phenylacetylene as starting material. cThe reaction was performed by using KSeCN
(1.0 equiv) and n-BuBr (1.0 equiv) for the in situ generation of n-Bu2Se2.
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Beilstein J. Org. Chem. 2017, 13, 910–918.
fact, that the reaction occurs under air atmosphere, the presence
of oxygen promotes the oxidation of anion 11 to 8 [45], contin-
uing the cycle until complete consumption of 11.
Due to the aerobic conditions and the presence of oxidative
species such as O2·−, O22− or H2O2, the oxidative retro-alkyl-
ation is favored [46-49]. Therefore, we can explain the forma-
tion of indole 9 by oxidation of 5p, generated in situ as de-
scribed above, to afford the iminium intermediate 12. Hydroly-
sis of the latter liberates the secondary amine 13 (Scheme 7).
This intermediate was detected by GC–MS in traces. Finally,
the presence of base in excess and the correct arrangement and
electronic properties of both the amine and alkynyl groups
promote a spontaneous cyclization reaction to form indole 9 in
good yields [50].
Scheme 5: Control reactions and mechanistic study.
that the superoxide radical anion oxidizes the alkyl selenide
anion (11) to the corresponding alkyl selenide radical and the
formed O22− affords H2O2 after work-up. On the other hand,
when the same reaction was performed under a nitrogen atmo-
sphere and after one hour quenched with MeI, alkynyl selenide
was formed in 47% yield together with methyl(phenyl)selane in
50% yield, determined as relative areas by GC. The latter result
confirms that under inert gas atmosphere the phenyl selenide
anion remains unoxidized and can be trapped by methylation.
Furthermore, under the current reaction conditions no reduction
of Se–Se bonds by the used base t-BuOK as proposed in the lit-
erature takes place (Scheme 5B) [44].
Scheme 7: Proposed mechanism for the formation of indole 9.
Conclusion
We have developed a novel one-pot procedure for the synthesis
To account for the results obtained we propose the following of alkyl alkynyl selenides in moderate to good yields. The reac-
mechanism for the formation of alkynyl selenides (5) tion does not require selenolate anions as starting materials and
(Scheme 6). In the first step a nucleophilic substitution reaction proceeds through the in situ formation of diselenides from com-
between the alkyl halide 3 with KSeCN (2) yields alkyl seleno- mercially available potassium selenocyanate. Furthermore, the
cyanate 7, which, after addition of K3PO4, quantitatively reaction readily takes place in PEG 200, a sustainable solvent,
affords dialkyl diselenide 8 [38]. Subsequently, the arylacet- in short reaction times and under an oxygen atmosphere. The
ylene 6 and t-BuOK are added with concomitant generation of method is also applicable to the synthesis of functionalized
the corresponding arylacetylene anion. The anion of 6, once heterocycles in good to excellent yields.
formed, attacks the diselenide intermediate 8, leading to the ex-
pected product 5 and an alkyl selenolate anion (11). Given the
Supporting Information
Supporting Information File 1
Experimental details, characterization data and copies of
1H, 13C and 77Se NMR spectra for products 5a–e, 5i–l, 5n,
5q, 9 and 10.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-92-S1.pdf]
Acknowledgements
This work was supported partly by Consejo Nacional de
Investigaciones Científicas y Técnicas (CONICET) and Fondo
de Ciencia y Tecnología (FONCYT), Argentina. A. A. H. grate-
Scheme 6: Proposed mechanism for the formation of selenides 5.
fully acknowledges the receipt of a fellowship from CONICET.
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Beilstein J. Org. Chem. 2017, 13, 910–918.
28.Sharma, A.; Schwab, R. S.; Braga, A. L.; Barcellos, T.; Paixão, M. W.
Tetrahedron Lett. 2008, 49, 5172–5174.
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