Regioselective Markovnikov hydrochalcogenation of terminal alkynes with indium(III) benzenechalcogenolates

Article abstract of DOI:10.1055/s-2008-1072725

Indium(III) benzenechalcogenolates (chalcogen = sulfur and selenium) promote the rigorous Markovnikov hydrochalcogenation of terminal alkynes. The generality and limitations of the reaction with aminoalkynes leading to allylic amines bearing vinylic chalc

Full text of DOI:10.1055/s-2008-1072725

LETTER
1165
Regioselective Markovnikov Hydrochalcogenation of Terminal Alkynes with
Indium(III) Benzenechalcogenolates
Regioselective
M
l
arkovn
o
ikov Hydroc
v
halcogenatio
i
n of Te
s
r
minal AlkynesPeppe,* Liérson Borges de Castro, Melina de Azevedo Mello, Olga Soares do Rego Barros
Departamento de Química, Universidade Federal de Santa Maria-UFSM, Campus UFSM, Santa Maria, RS – 97105-900, Brazil
Fax +55(55)32208031; E-mail: peppe@quimica.ufsm.br
Received 18 June 2007
InX
+
PhE-EPh
XIn(EPh)2
Abstract: Indium(III) benzenechalcogenolates (chalcogen = sulfur
and selenium) promote the rigorous Markovnikov hydrochalcoge-
nation of terminal alkynes. The generality and limitations of the re-
action with aminoalkynes leading to allylic amines bearing vinylic
chalcogenide substituents are discussed.
X = Br, I; E = S, Se, Te
Equation 1
IIn(SePh)2 and IIn(SPh)2 promote the ring-opening reac-
tion of epoxides to the corresponding b-hydroxy chalco-
genides with rigorous regioselectivity;4 the nucleophile
incorporation at the less-hindered carbon atom was ob-
served for alkyl-substituted epoxides, and at the benzylic
carbon atom for aryl derivatives. Further, IIn(EPh)2
(E = S, Se) were used to prepare unsymmetrical chalco-
genides, REPh (R = alkyl and acyl) from the correspond-
ing organyl halides.5 Coupling with vinylic bromides was
achieved under Pd(0) catalysis,6 and Michael additions to
enones were observed with the IIn(SPh)2 compound.4b
Key words: indium(III) benzenechalcogenolates, aminoalkynes,
hydrochalcogenation, regioselective Markovnikov addition.
The addition of the chalcogenol constituents, REH (E = S,
Se) across a triple bond of an alkyne is the simplest con-
ceivable route to a vinyl chalcogenide. But, the rigorous
regio- and stereoselective production of one of the three
possible isomers from a terminal alkyne 1 (Scheme 1) is
still a challenge. The direct reaction between a chalco-
genol, REH (E = S, Se) and an alkyne follows a free-rad-
ical pathway and leads to a mixture of the anti-
Markovnikov adducts 3 and 4.1 Bases with alkaline-metal
counterions were shown to mediate hydrochalcogena-
tions; the products depend on the nature of the alkyne; ar-
omatic derivatives produce the anti-Markovnikov adducts
3 and 4 with predominancy of isomer 4 while aliphatic de-
rivatives give rise to mixtures of isomers 2 and 4.2
OH
O
R3
R4
R1
R2
CH2Cl2
EPh
R4
R1
R2
R3
( E = S, Se; R1, R2, R3, R4 = alkyl and aryl)
CH2Cl2
R-Y
Ar
R-EPh
(E = Se; Y = Cl, Br, I, R = alkyl,
benzyl, allyl, etc.)
IIn(EPh)2
Only using transition-metal catalysts, rigorous regioselec-
tive protocols leading to the Markovnikov adduct 2 were
disclosed.3
Pd(PPh3)4
Br
O
EPh
Ar
(E = S, Se)
EPh
O
R1
R1
RE
R1
R1
[RE-H]
R
R1
R
R1
+
+
E = S
ER
RE
Scheme 2
2
3
4
1
R, R1 = alkyl or aryl; E = S, Se
The indium(III) chalcogenolates were also successfully
employed to solve the problem of the Markovnikov addi-
tion leading to adducts 2. We have demonstrated that
BrIn(SePh)2 promotes the hydroselenation of alkynes
with remarkable stereoselectivity towards adducts 2.7 The
reaction does not occur in anhydrous solvents, but it pro-
ceeds satisfactorily in aqueous ethanol (Scheme 3). It
seems that the reaction involves an anionic complex of in-
dium, H[L2(PhSe)InOH] formed by hydrolysis of
BrIn(SePh)2.
Scheme 1
Recent work introduced the indium(III) chalcogenolates,
obtained from the oxidative insertion of indium monoha-
lides into the chalcogen–chalcogen bonds of diphenyl
dichalcogenide (Equation 1), as useful reagents to pro-
duce new carbon–chalcogen bonds.
The phenylchalcogenolate species bonded to the indi-
um(III) center is a mild nucleophile, and as such reacts in
nonaqueous media with a variety of electrophiles to pro-
duce organic chemicals of interest (Scheme 2). Both,
Accordingly, both compounds IIn(EPh)2 (E = Se, Te) pro-
duced high yields of the Markovnikov adducts 2 from re-
actions with propargylic alcohols,8 even in anhydrous
solvents according to a mechanism involving as the key
SYNLETT 2008, No. 8, pp 1165–1170
Advanced online publication: 16.04.2008
x
x.
x
x.
2
0
0
8
DOI: 10.1055/s-2008-1072725; Art ID: S04607ST
© Georg Thieme Verlag Stuttgart · New York

1166
C. Peppe et al.
LETTER
R
and the indium(III) halide compound inhibited the reac-
tion.
L2InSePh +
H2O
R
PhSe
Indium(III) benzeneselenolate, In(SePh)3 is an alterna-
tive, halide-free, and easy accessible compound contain-
ing In–Se bonds. It is readily prepared by heating the
metal and diphenyl diselenide in high boiling aromatic
solvents, such as toluene or xylenes.10 We attempted to
generate this compound, under Barbier conditions, from
indium metal and diphenyl diselenide in aqueous ethanol
(entry 5), dichloromethane (entry 6), and 1,2-dichloro-
ethane (entry 7) solutions containing the aminoalkyne 5e.
To our satisfaction, product 6¢e was observed, although in
low yields (entries 5 and 6) or contaminated with the vi-
nylic diselenide 7¢e (entry 7). The experiments corre-
sponding to entries 8 and 9 [in DCE–i-PrOH (20:1)] were
conducted aiming to eliminate the production of 7¢e; both
succeeded, especially the experiment conducted with pre-
viously prepared In(SePh)3 (entry 9), in which product 6¢e
was obtained with the satisfactory yield of 89% after 2
hours of continuous reflux.
R
H [L2(PhSe)InOH]
active species in
ionic addition
L2InOH
+
PhSeH
(hydroselenation)
Scheme 3
step the coordination of the alcohol, through its hydroxyl
site to the indium center of the complex.
Due to the great importance of allylamines as synthetic in-
termediates as well as their presence in the structures of
natural products and pharmaceuticals, we set out to inves-
tigate the ability of indium(III) chalcogenolates to pro-
mote hydrochalcogenation of aminoalkynes. The
preparation of allylamines bearing vinylic chalcogenide
substituents is very much desired, because both, vinylic
sulfides or selenides undergo cross-coupling reaction with
Grignard reagents catalyzed by nickel(II) salts.9
Established the optimized reaction conditions, we set out
to investigate the generality and the limitations of the hy-
drochalcogenation reactions of aminoalkynes 5,11 promot-
ed by the In(EPh)3 (E = S, Se) compounds. The results are
in Table 2.12 We first notice that there are no significant
differences between the performance of the sulfur or the
selenium reagents. On the other hand, the reactivity de-
pendence on the substitution pattern in substrates 5 is
striking. Terminal propargylic amines (entries 1–14) af-
ford the Markovnikov vinylic chalcogenide. The reaction
between the indium(III)-benzenethiolate with ami-
noalkyne 5b was the only exception to this trend and N-
We were disappointed verifying that in our first attempt to
hydroselenate the propargyl tertiary amine, 4-(prop-2-
ynyl)morpholine (5e) with IIn(SePh)2, no product 6¢e was
obtained either in aqueous ethanol or CH2Cl2 solutions
(Table 1, entries 1 and 2); small amount of 6¢e was ob-
tained using the analogous indium complex BrIn(SePh)2
in CH2Cl2 (entry 3), but no sign of 6¢e was detected in eth-
anol (entry 4). We have not investigated properly the rea-
sons for this failure; we assumed that production of an
ammonium halide salt derived from the propargyl amine
Table 1 Hydroselenation of 5e under Various Reaction Conditions
N
O
N
O
N
O
[In(III)-SePh]
solvent
+
SePh
6'e
PhSe
SePh
7'e
5e
[In(III)SePh]
IIn(SePh)2
Solvent
CH2Cl2
Conditions
40 °C, 24 h
78 °C, 24 h
40 °C, 24 h
78 °C, 12 h
78 °C, 18 h
40 °C, 12 h
83 °C, 12 h
83 °C, 6 h
83 °C, 2 h
Yields of 6¢e:7¢e (%)a
1
2
3
4
5
6
7
8
9
0:0
0:0
IIn(SePh)2
EtOH (95%)
CH2Cl2
BrIn(SePh)2
BrIn(SePh)2
10:0
0:0
EtOH (95%)
EtOH(95%)
CH2Cl2
b
In(SePh)3
25:0
55:0
75:7
87:0c
89:0c
b
In(SePh)3
b
In(SePh)3
DCE
b
In(SePh)3
DCE–i-PrOH (20:1)
DCE–i-PrOH (20:1)
d
In(SePh)3
a Estimated by 1H NMR spectroscopy.
b Under Barbier conditions, with In(SePh)3 prepared in situ from indium metal and (PhSe)2.
c Isolated yield of analytically pure product.
d In(SePh)3 previously prepared.
Synlett 2008, No. 8, 1165–1170 © Thieme Stuttgart · New York

LETTER
Regioselective Markovnikov Hydrochalcogenation of Terminal Alkynes
1167
[2,2-bis(phenylthio)propyl]-4-methylbenzenesulfon-
plete inhibition of reaction with the aminoalkyne 5h con-
amide was obtained as a secondary product. No sign of taining a quaternary propargylic carbon atom.
products were obtained from aminoalkynes 5 containing
After examining the scope of the protocol leading to the
Markovnikov adducts 6, we searched for the origin of the
diselenated byproduct 7¢e, detected during the optimiza-
tion experiments (Table 1). We assumed that compound
7¢e was derived from an indium acetylide, which have
been proposed in the reaction of indium(III) salts with
alkynes in the presence of amines as proton acceptors.15
The experiments described in Scheme 4 support this prop-
osition, the indium acetylide was captured by two differ-
internal triple bonds (entries 21 and 22). Nonpropargylic
aminoalkynes (entries 17–20) either did not react with the
indium chalcogenolates (entries 17 and 18) or produced
smaller yields compared to the propargylic derivatives
(entries 19 and 20).13 The degree of substitution at the pro-
pargylic carbon atom in substrates 5 (R1, R2) dramatically
affects reactivity; the higher the degree of substitution at
this site, the smaller were the yields obtained (entries 1–
12 vs. 13 and 14); and it is important to notice the com-
Table 2 Investigations of the Generality and Limitations of the Hydrochalcogenation Reactions of Aminoalkynes 5 Promoted by the In(EPh)3
(E = S, Se) Compounds
R1 R2
n
NR3R4
In(EPh)3
NR3R4
R
R
n
R2
DCE–i-PrOH (20:1)
83 °C, 6 h
R1
EPh
5
6, E = S; 6', E = Se
Entry
1
Product
6ab
6¢ab
6b
R
R1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
R2
R3
R4
H
H
H
H
H
H
Et
Et
n
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
3
3
1
1
Yield (%)a
H
H
H
62
65
67c
75
62
46
72
57
90
89
76
74
20
17
0
2
H
H
H
3
H
H
Ts
4
6¢b
6cb
6¢cb
6d
H
H
Ts
5
H
H
Me
6
H
H
Me
7
H
H
Et
8
6¢d
6e
H
H
Et
9
H
H
-(CH2)2O(CH2)2-
-(CH2)2O(CH2)2-
-(CH2)5-
10
11
12
13
14
15
16
17
18
19
20
21
22
6¢e
6f
H
H
H
H
6¢f
H
H
-(CH2)5-
6g
H
n-C5H11
-(CH2)2O(CH2)2-
-(CH2)2O(CH2)2-
-(CH2)4-
6¢g
6h
H
n-C5H11
H
Me
Me
H
6¢h
6i
H
-(CH2)4-
0
H
-(CH2)2O(CH2)2-
-(CH2)2O(CH2)2-
-(CH2)2O(CH2)2-
-(CH2)2O(CH2)2-
Et
0
6¢i
H
H
0
6jd
6¢jd
6k
H
H
36
38
0
H
H
n-Bu
n-Bu
H
Et
Et
6¢k
H
Et
0
a Isolated yield of analytically pure product.
b Reaction at 45 °C.
c Plus 27% of N-[2,2-bis(phenylthio)propyl]-4-methylbenzenesulfonamide.
d Yield after 24 h.
Synlett 2008, No. 8, 1165–1170 © Thieme Stuttgart · New York

1168
C. Peppe et al.
LETTER
N
O
SePh
6'e, 24%
N
O
N
O
D
In(SePh)3 + PhSeSePh
DCE, 83 °C, 6 h
In(SePh)3
+
DCE–D2O (20:1)
83 °C, 6 h
83%
D
SePh
80% deuteration
5e
N
O
PhSe
SePh
7'e, 53%
Scheme 4
Scheme 5
C8H17
120% Et3N
C7H15
+
In(EPh)3
C8H17
DCE
83 °C, 6 h
EPh
PhE
1
2
8
E = S, 8, 56%; E = Se, 2', 30%; 8', 29%
ent electrophiles; deuterated water gave 83% of the failure of phenylacetylene to react under an oxygen-free
dideuterated vinylselenide 6¢e (80% of deuteration),16 and atmosphere was also observed before, when we deter-
diphenyldiselenide reacted with the indium acetylide, in mined a diselenation reaction of its triple bond promoted
anhydrous 1,2-dichloroethane, to produce the E-diselena- by benzeneseleno radical obtained by exposing benzene-
ted byproduct 7¢e in 53% of yield together with the vinylic selenol to molecular oxygen.7
selenide 6¢e.17
Although the mechanism of this reaction is still uncertain,
To gain a deeper insight into the reactivity of the indi- there are a number of experimental facts supporting a pre-
um(III) chalcogenolates, we have examined their reac- liminary picture. The pathway seems to involve an indium
tions with n-decyne and phenylacetylene in acetylide intermediate, captured by two different electro-
dichloroethane under a dry nitrogen atmosphere. Both, the philes (D2O and PhSeSePh) and suggested by the need of
sulfur and selenium compounds fail to react, even after triethyl amine acting as a base to promote the reaction
prolonged heating. However, upon addition of triethyl- with n-decyne. We also notice that indium-mixed com-
amine (1.2 mol equiv), the hydrochalcogenation of n-de- plexes containing halide and chalcogenolate ligands
cyne was observed (Scheme 5), producing initially and [XIn(EPh)2; X = Br, I, E = S, Se] are ineffective, probably
accordingly to our previous studies,7 the Markovnikov ad- due to precipitation of an ammonium cation during gener-
ducts 2 that undergo isomerization to the internal vinylic ation of the indium acetylide. Finally, we propose a coor-
chalcogenides 8, isolated as a mixture of isomers.18 The dination of the aminoalkyne through its nitrogen basic
In(EPh)4
NR3R4
NHR3R4
R2
NR3R4
R2
2
+
2 In(EPh)3
R2
(PhE)2In
R1
R1
R1
(I)
R2
R2
NR3R4
R1
R1
NR3R4
NR3R4
H
(PhE)2In
In(EPh)3
+
+
R2
R1
EPh
EPh
6
PhE-EPh
R2
R1
PhE
NR3R4
EPh
7
Scheme 6
Synlett 2008, No. 8, 1165–1170 © Thieme Stuttgart · New York

LETTER
Regioselective Markovnikov Hydrochalcogenation of Terminal Alkynes
1169
(6) Ranu, B. C.; Chattopadhyay, K.; Banerjee, S. J. Org. Chem.
2006, 71, 423.
center to the indium(III) chalcogenolate responsible for
transferring the chalcogenolate nucleophile, as strongly
suggested by the low yields obtained with aminoalkynes
containing tertiary propargylic carbon atoms and by the
ineffective reaction with the quaternary aminoalkyne 5h.
(7) Peppe, C.; Lang, E. S.; Ledesma, G. N.; de Castro, L. B.;
Barros, O. S. D.; Mello, P. D. Synlett 2005, 3091.
(8) For hydroselenation, see: (a) Barros, O. S. D.; Lang, E. S.;
de Oliveira, C. A. F.; Peppe, C.; Zeni, G. Tetrahedron Lett.
2002, 43, 7921. For hydrotelluration, see: (b) Barros, O. S.
D.; Lang, E. S.; Peppe, C.; Zeni, G. Synlett 2003, 1725.
(9) (a) Gerard, J.; Hevesi, L. Tetrahedron 2001, 57, 9109.
(b) Okamura, H.; Miura, M.; Takei, H. Tetrahedron Lett.
1979, 20, 43. (c) Okamura, H.; Miura, M.; Kosugi, K.;
Takei, H. Tetrahedron Lett. 1980, 21, 87.
Scheme 6 illustrates how we envisage this reaction, giv-
ing a preliminary pathway which is in agreement with the
experimental details discussed above, although the struc-
ture of the key intermediate, anion (I), was not estab-
lished.
(10) Annan, T. A.; Kumar, R.; Mabrouk, H. E.; Tuck, D. G.;
For this to end, we note that we have introduced new spe-
cies of indium(III) chalcogenolates, In(EPh)3 (E = S, Se),
capable of the Markovnikov hydrochalcogenation of ter-
minal alkynes. The addition is fairly broad in scope and
generally works well especially with terminal propargyl
amines. The products, allylic amines bearing vinylic chal-
cogenide substituents, seem to be valuable synthetic inter-
mediates for further elaborations.
Chadha, R. K. Polyhedron 1989, 8, 865.
(11) (a) Aminoalkynes 5a,d–f were prepared from propargyl
bromide and the corresponding amine, 5h was prepared from
3-chloro-3-metyl-1-butyne according to: Hennion, G. F.;
Nelson, K. W. J. Am. Chem. Soc. 1957, 79, 2142.
(b) Compounds 5g,i,j were prepared from the corresponding
propargyl p-toluenosulfonate and dialkylamines according
to: Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.;
Elsevier: New York, 1988. (c) Compound 5b was prepared
from propargylamine 5a according to: Lo, M. M.-C.;
Neumann, C. S.; Nagayama, S.; Perlstein, E. O.; Schreiber,
S. L. J. Am. Chem. Soc. 2004, 126, 16077. (d) Compound
5c was obtained commercially from Aldrich.
Acknowledgment
C.P. is grateful to CNPq for financial support. CAPES (to L.B.D.)
and CNPq (to M.D.M. and O.S.D.B.) are acknowledged for the
award of scholarships.
(12) General Procedure for the Markovnikov
Hydrochalcogenation of the Aminoalkynes
A Schlenk tube equipped with a reflux condenser, under N2
atmosphere, was charged with DCE (2 mL), i-PrOH (0.1
mL), aminoalkyne 5 (1 mmol), and In(EPh)3 (1 mmol). The
mixture was heated, under reflux, for 6 h. At the end of this
period, the reaction was quenched with H2O (10 mL), the
organics extracted with CH2Cl2 (2 × 15 mL). The extract
was dried (Na2SO4) and evaporated to dryness under
vacuum. The oily residue was purified by column
chromatography (SiO2, hexanes–EtOAc) to produce the
adducts 6 and 6¢ as heavy oils and in yields given in Table 2.
Spectroscopic Data for Compounds 6
References and Notes
(1) For radical addition of thiols into alkynes, see: (a) Mitsudo,
T.; Kondo, T. Chem. Rev. 2000, 100, 3205 and references
therein. For selenols: (b) Comasseto, J. V.; Ferreira, J. T. B.
J. Organomet. Chem. 1981, 216, 287.
(2) For cesium thiolates, see: (a) Kondoh, A.; Takami, K.;
Yorimitsu, H.; Oshima, K. J. Org. Chem. 2005, 70, 6468.
For sodium thiolates, see: (b) Truce, W. E.; Tichenor, G. J.
W. J. Org. Chem. 1972, 37, 2391. (c) Truce, W. E.; Simms,
J. A.; Boudakian, M. M. J. Am. Chem. Soc. 1956, 78, 695.
(d) Truce, W. E.; Simms, J. A. J. Am. Chem. Soc. 1956, 78,
2756. For lithium selenolates, see: (e) Zeni, G.; Stracke, M.
P.; Nogueira, C. W.; Braga, A. L.; Menezes, P. H.; Stefani,
H. A. Org. Lett. 2004, 6, 1135.
(3) For hydroselenation catalyzed by Pd and Pt compounds,
see: (a) Ananikov, V. P.; Malyshev, D. A.; Beletskaya, I. P.;
Aleksandrov, G. G.; Eremenko, I. L. J. Organomet. Chem.
2003, 679, 162. (b) Kamiya, I.; Nishinaka, E.; Ogawa, A. J.
Org. Chem. 2005, 70, 696. For hydrothiolation catalyzed by
nickel(II) compounds, see: (c) Ananikov, V. P.; Malyshev,
D. A.; Beletskaya, I. P.; Aleksandrov, G. G.; Eremenko, I. L.
Adv. Synth. Catal. 2005, 347, 1993. (d) Ananikov, V. P.;
Orlov, N. V.; Beletskaya, I. P. Organometallics 2006, 25,
1970. For hydrothiolation catalyzed by Pd compounds, see:
(e) Ogawa, A.; Ikeda, A.; Kimura, K.; Hirao, T. J. Am.
Chem. Soc. 1999, 121, 5108; and references therein.
(f) Ananikov, V. P.; Orlov, N. V.; Beletskaya, I. P.;
Khrustalev, V. N.; Antipin, M. Y.; Timofeeva, T. V. J. Am.
Chem. Soc. 2007, 129, 7252. For hydrothiolation catalyzed
by a rhodium compound, see: (g) Cao, C.; Fraser, L. R.;
Love, J. A. J. Am. Chem. Soc. 2005, 127, 17614.
2-(Phenylthio)prop-2-en-1-amine (6a):19 1H NMR (CDCl3):
d = 7.54–7.17 (m, 5 H), 5.31 (t, J = 1.2 Hz, 1 H), 4.98 (s, 1
H), 3.28 (s, 2 H), 1.82 (s, 2 H). 13C NMR (CDCl3):
d = 136.96, 132.51, 129.08, 128.60, 127.65, 113.59, 46.87.
2-(Phenylseleno)prop-2-en-1-amine (6¢a): 1H NMR
(CDCl3): d = 7.43 (m, 2 H), 7.18 (m, 3 H), 5.61 (s, 1 H), 5.19
(s, 1 H), 3.30 (s, 2 H), 1.70 (s, 2 H). 13C NMR (CDCl3):
d = 144.50, 133.89, 128.98, 128.15, 127.47, 116.45, 48.37.
4-Methyl-N-(2-(phenylthio)allyl)benzenesulfonamide (6b):
1H NMR (CDCl3): d = 7.62 (m, 2 H), 7.19 (m, 7 H), 5.35 (s,
1 H), 5.03 (s, 1 H), 3.56 (s, 2 H), 2.31 (s, 3 H). Fast
decomposition in CDCl3 solution prevented the recording of
a satisfactory 13C NMR spectrum.
N-[2,2-Bis(phenylthio)propyl]-4-methylbenzenesulfon-
amide (secondary product): 1H NMR (CDCl3): d = 7.71 (m,
2 H), 7.45 (m, 4 H), 7.37 (m, 2 H), 7.30 (m, 6 H), 5.13 (t,
J = 6.0 Hz, 1 H), 2.98 (d, J = 6.0 Hz, 2 H), 2.36 (s, 3 H), 1.19
(s, 3 H). 13C NMR (CDCl3): d = 143.45, 136.91, 136.50,
129.85, 129.68, 129.60, 128.80, 127.04, 61.41, 50.58, 25.64,
21.47.
4-Methyl-N-[2-(phenylseleno)allyl]benzenesulfonamide
(6¢b): 1H NMR (CDCl3): d = 7.61 (m, 2 H), 7.32 (m, 2 H),
7.18 (m, 5 H), 5.67 (s, 1 H), 5.25 (s, 1 H), 3.60 (s, 2 H), 2.32
(s, 3 H). 13C NMR (CDCl3): d = 143.32, 136.78, 136.71,
133.85, 129.50, 129.27, 127.86, 127.62, 127.02, 120.61,
48.69, 21.39.
(4) For b-hydroxyselenides, see: (a) Barros, O. S. D.;
de Carvalho, A. B.; Lang, E. S.; Peppe, C. Lett. Org. Chem.
2004, 1, 43. For b-hydroxysulfides, see: (b) Ranu, B. C.;
Mandal, T. Can. J. Chem. 2006, 84, 762.
N-Methyl-2 (phenylthio)prop-2-en-1-amine (6c): 1H NMR
(CDCl3): d = 7.38–7.18 (m, 5 H), 5.26 (s, 1 H), 4.96 (s, 1 H),
(5) Ranu, B. C.; Mandal, T. J. Org. Chem. 2004, 69, 5793.
Synlett 2008, No. 8, 1165–1170 © Thieme Stuttgart · New York

1170
C. Peppe et al.
LETTER
(13) We have searched for the reasons leading to this failure.
3.23 (s, 2 H), 2.29 (s, 3 H), 1.64 (s, 1 H). 13C NMR (CDCl3):
d = 143.72, 132.88, 132.60, 129.06, 127.73, 114.68, 55.84,
34.92.
From the reaction involving homopropargylamine 5i and
In(SePh)3, we have isolated after 24 h of continuous reflux
1,2-bis(phenylseleno)ethane (PhSeCH2CH2SePh) in 62% of
yield based on 5i. 1H NMR (CDCl3): d = 7.35 (m, 4 H), 7.17
(m, 6 H), 3.05 (s, 4 H). 13C NMR (CDCl3): d = 133.04,
131.45, 129.14, 127.21, 27.16.14 Bis(phenylseleno)ethane
was similarly prepared by heating In(SePh)3, Et3N in DCE in
40% of yield. These facts strongly suggest parallel reactions
between aminoalkynes 5i and 5j with DCE to form
quaternary ammonium derivatives that inhibit or reduce the
efficiency of the hydrochalcogenation reactions.
(14) Gulliver, D. J.; Hope, E. G.; Levason, W. J. Chem. Soc.,
Perkin Trans. 2 1984, 429.
(15) (a) Sakai, N.; Kanada, R.; Hirasawa, M.; Konakahara, T.
Tetrahedron 2005, 61, 9298. (b) Sakai, N.; Hirasawa, M.;
Konakahara, T. Tetrahedron Lett. 2003, 44, 4171.
(16) 4-[3,3-Dideuterio-2-(phenylseleno)allyl]morpholine was
prepared, in 83% of yield, according to the general method
described above using D2O as the deuterium source: 1H
NMR (CDCl3): d = 7.52 (m, 2 H), 7.23 (m, 3 H), 5.51 (s, 0.2
H), 4.80 (s, 0.2 H), 3.64 (m, 4 H), 3.14 (s, 2 H), 2.38 (m, 4 H).
(17) (E)-4[2,3-Bis(phenylseleno)allyl]morpholine (7¢e) was
prepared in 53% of yield together with 6¢e (24%) from
aminoalkyne 5e (1 mmol), In(SePh)3 (1 mmol), and diphenyl
diselenide (2 mmol) in anhyd DCE (4 mL) using the general
procedure described in ref. 12.
N-Methyl-2 (phenylseleno)prop-2-en-1-amine (6¢c) 1H
NMR (CDCl3): d = 7.47 (m, 2 H), 7.22 (m, 3 H), 5.60 (s, 1
H), 5.14 (s, 1 H), 3.29 (s, 2 H), 2.29 (s, 3 H), 1.83 (s, 1 H).
13C NMR (CDCl3): d = 141.59, 134.62, 129.20, 128.35,
127.81, 117.71, 57.40, 34.92.
N,N-Diethyl-2 (phenylthio)prop-2-en-1-amine (6d):20 1
H
NMR (CDCl3): d = 7.43–7.20 (m, 5 H), 5.26 (s, 1 H), 4.73
(s, 1 H), 3.14 (s, 2 H), 2.50 (q, J = 7.1 Hz, 4 H), 0.95 (t,
J = 7.1 Hz, 6 H). 13C NMR (CDCl3): d = 145.24, 133.81,
133.05, 129.03, 127.86, 112.44, 58.33, 46.61, 11.54.
N,N-Diethyl-2 (phenylseleno)prop-2-en-1-amine (6¢d): 1H
NMR (CDCl3): d = 7.53 (m, 2 H), 7.23 (m, 3 H), 5.55 (s, 1
H), 4.79 (s, 1 H), 3.24 (s, 2 H), 2.50 (q, J = 7.1 Hz, 4 H), 0,97
(t, J = 7.1 Hz, 6 H). 13C NMR (CDCl3): d = 144.57, 135.85,
131.49, 129.11, 127.89, 113.83, 59.91, 46.45, 11.60.
4-[2-(Phenylthio)allyl]morpholine (6e): 1H NMR (CDCl3):
d = 7.39 (m, 2 H), 7.25 (m, 3 H), 5.20 (s, 1 H), 4.72 (s, 1 H),
3.65 (m, 4 H), 3.04 (s, 2 H), 2.37 (m, 4 H). 13C NMR
(CDCl3): d = 143.36, 134.15, 132.48, 129.06, 128.13,
112.84, 66.89, 63.86, 53.14.
4-[2-(Phenylseleno)allyl]morpholine (6¢e): 1H NMR
(CDCl3): d = 7.52 (m, 2 H), 7.23 (m, 3 H), 5.51 (s, 1 H), 4.80
(s, 1 H), 3.64 (m, 4 H), 3.14 (s, 2 H), 2.38 (m, 4 H). 13C NMR
(CDCl3): d = 142.42, 136.03, 129.11, 128.40, 128.07,
114.44, 66.93, 65.30, 53.13.
Spectroscopic Data for 7¢e
1-[2-(Phenylthio)allyl)]piperidine (6f): 1H NMR (CDCl3):
d = 7.39 (m, 2 H), 7.24 (m, 3 H), 5.23 (s, 1 H), 4.74 (s, 1 H),
1H NMR (CDCl3): d = 7.48 (m, 2 H), 7.33 (m, 2 H), 7.22 (m,
3 H), 7.18 (m, 3 H), 6.67 (s, 1 H), 3.67 (m, 4 H), 3.22 (s, 2
H), 2.42 (m, 4 H). 13C NMR (CDCl3): d = 134.33, 133.04,
131.55, 129.53, 129.28, 129.21, 129.08, 127.84, 126.95,
123.81, 66.80, 63.26, 52.97; 2D-NOE: no effect involving
the singlet at d = 6.67 ppm as required by the E-stereo-
isomer.
3.02 (s, 2 H), 2.33 (m, 4 H), 1.53 (m, 4 H), 1.36 (m, 2 H). 13
C
NMR (CDCl3): d = 143.77, 133.96, 132.88, 129.06, 127.99,
112.90, 64.10, 54.18, 25.77, 24.25.
1-[2-(Phenylseleno)allyl)]piperidine (6¢f): 1H NMR
(CDCl3): d = 7.53 (m, 2 H), 7.23 (m, 3 H), 5.51 (s, 1 H), 4.80
(s, 1 H), 3.11 (s, 2 H), 2.34 (m, 4 H), 1.53 (m, 4 H), 1.37 (m,
2 H). 13C NMR (CDCl3): d = 143.23, 135.96, 129.11,
128.87, 127.96, 114.10, 65.54, 54.20, 25.83, 24.27.
4-[2-(Phenylthio)oct-1-en-3-yl]morpholine (6g): 1H NMR
(CDCl3): d = 7.40 (m, 2 H), 7.25 (m, 3 H), 5.00 (s, 1 H), 4.46
(s, 1 H), 3.65 (t, J = 4.6 Hz, 4 H), 2.80 (dd, J = 7.8, 6.1 Hz,
1 H), 2.49 (m, 4 H), 1.62 (m, 2 H), 1.24 (m, 6 H), 0.82 (t,
J = 6.5 Hz, 3 H). 13C NMR (CDCl3): d = 147.61, 136.62,
129.18, 128.58, 128.14, 113.58, 72.22, 67.18, 50.85, 31.85,
29.67, 26.32, 22.52, 14.01.
(18) Spectroscopic Data for the Products of
Hydrochalcogenation of n-Decyne with Indium(III)
Benzenechalcogenolates
2-Phenylselenodec-1-ene (2¢):7 1H NMR (CDCl3): d = 7.48
(m, 2 H), 7.22 (m, 3 H), 5.43 (s, 1 H), 5.04 (s, 1 H), 2.21 (t,
J = 7.3 Hz, 2 H), 1.47 (quint, J = 7.3 Hz, 2 H), 1.20 (br s, 10
H), 0.82 (t, J = 6.8 Hz, 3 H). 13C NMR (CDCl3): d = 143.5,
134.67, 129.13, 129.04, 127.65, 116.07, 38.32, 31.83, 29.32,
29.19, 28.81, 28.67, 22.64, 14.09.
(Z)- + (E)-2-Phenylselenodec-2-ene (8¢; isolated as an
unassigned 3:2 mixture of isomers): 1H NMR (CDCl3):
d = 7.38 (m, 2 H), 7.16 (m, 3 H), 5.89 (t, J = 7.3 Hz, 0.4 H),
5.71 (t, J = 7.1 Hz, 0.6 H), 2.18 (q, J = 7.1 Hz, 1.2 H), 2.03
(q, J = 7.3 Hz, 0.8 H), 1.92 (s, 3 H), 1.32 (quint, J = 7.3 Hz,
2 H), 1.21 (m, 8 H), 0.81 (t, J = 7.3 Hz, 1.2 H), 0.80 (t,
J = 7.3 Hz, 1.8 H).
(Z)- + (E)-2-Phenylthiodec-2-ene (8, isolated as an
unassigned 1:1 mixture of isomers): 1H NMR (CDCl3):
d = 7.34 (m, 5 H), 5.95 (tq, J = 7.3 Hz, 1.2 Hz, 0.5 H), 5.89
(tq, J = 7.3 Hz, 1.2 Hz, 0.5 H), 2.38 (q, J = 7.2 Hz, 1 H), 2.19
(q, J = 7.3 Hz, 1 H), 1.97 (d, J = 1.2 Hz, 1.5 H), 1.94 (d,
J = 1.2 Hz, 1.5 H), 1.47 (m, 2 H), 1.35 (m, 8 H), 0.95 (m, 3
H).
4-[2-(Phenylseleno)oct-1-en-3-yl]morpholine (6¢g): 1H
NMR (CDCl3): d = 7.51 (m, 2 H), 7.25 (m, 3 H), 5.41 (s, 1
H), 4.68 (s, 1 H), 3.65 (t, J = 4.5 Hz, 4 H), 2.79 (dd, J = 8.2,
5.6 Hz, 1 H), 2.50 (m, 4 H), 1.56 (m, 2 H), 1.23 (m, 6 H), 0.82
(t, J = 6.2 Hz, 3 H). 13C NMR (CDCl3): d = 147.62, 135.18,
132.07, 129.17, 128.41, 110.38, 71.49, 67.15, 50.85, 31.79,
29.87, 26.03, 22.50, 13.99.
4-[4-(Phenylthio)pent-4-enyl]morpholine (6j): 1H NMR
(CDCl3): d = 7.37–7.20 (m, 5 H), 5.09 (s, 1 H), 4.83 (s, 1 H),
3.63 (m, 4 H), 2.36 (m, 4 H), 2.23 (m, 4 H), 1.67 (quint,
J = 7.9 Hz, 2 H). 13C NMR (CDCl3): d = 145.26, 133.07,
129.09, 128.54, 127.77, 113.29, 66.71, 57.86, 53.49, 34.10,
24.92.
4-[4-(Phenylseleno)pent-4-enyl]morpholine (6¢j): 1H NMR
(CDCl3): d = 7.45 (m, 2 H), 7.23 (m, 3 H), 5.43 (s, 1 H), 5.08
(s, 1 H), 3.64 (m, 4 H), 2.37 (m, 4 H), 2.28 (t, J = 7.5 Hz, 2
H), 2.23 (t, J = 7.5 Hz, 2 H), 1,67 (quint, J = 7.5 Hz, 2 H).
13C NMR (CDCl3): d = 142.29, 134.54, 129.20, 128.65,
127.79, 117.19, 66.36, 57.64, 53.27, 35.76, 24.83.
(19) Kuniyasu, H.; Ogawa, A.; Sato, K.-I.; Ryu, I.; Kambe, N.;
Sonoda, N. J. Am. Chem. Soc. 1992, 114, 5902.
(20) Kawakita, M.; Yokota, K.; Akamatsu, H.; Irisawa, S.;
Morikawa, O.; Konishi, H.; Kobayashi, K. J. Org. Chem.
1997, 62, 8015.
Synlett 2008, No. 8, 1165–1170 © Thieme Stuttgart · New York

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