Reaction of selenium and tellurium halides with propargyl alcohols. the regio- and stereoselectivity of addition to the triple bond

Article abstract of DOI:10.1002/poc.1729

A convenient method to incorporate selenium into an organic molecule is reported. Various aspects of the reaction of SeCl₂ with propargyl alcohols, i.e., identity of reacting functionality, regiospecificity, and stereospecificity, differ from e

Full text of DOI:10.1002/poc.1729

Research Article
Received: 14 February 2010,
Revised: 25 March 2010,
Accepted: 6 April 2010,
Published online in Wiley Online Library: 16 June 2010
(wileyonlinelibrary.com) DOI 10.1002/poc.1729
Reaction of selenium and tellurium halides
with propargyl alcohols. The regio- and
stereoselectivity of addition to the triple bondy
a
a
a
a
*
Samuel Braverman , Marina Cherkinsky , Ranjan Jana , Yuliya Kalendar
and Milon Sprechera
A convenient method to incorporate selenium into an organic molecule is reported. Various aspects of the reaction of
SeCl2 with propargyl alcohols, i.e., identity of reacting functionality, regiospecificity, and stereospecificity, differ from
expectations based on known reactions of these alcohols with SCl2. Selenium dihalides undergo smooth 1,2-addition
to the triple bond of various propargylic alcohols resulting in the formation of the corresponding functionalized
divinyl selenides in high yields and with complete regio- and stereospecificity. Of special mechanistic interest is the
syn-addition and anti-Markovnikov orientation observed in all cases. Copyright ß 2010 John Wiley & Sons, Ltd.
Keywords: alkynes; divinyl selenides; electrophilic addition; regioselectivity; selenium dichloride; stereoselectivity
INTRODUCTION
EXPERIMENTAL
Materials and methods
The field of sigmatropic rearrangements of allylic and propargylic
esters of sulfur acids at various oxidation states has proven to be
a rich source of synthetically valuable and mechanistically
intriguing reactions, often yielding novel and surprising
products.[1–4] Some of the best and most productive examples
are the reactions of propargylic alcohols with sulfur dichloride
and sulfur monochloride. The former results in the formation of
the appropriate sulfoxylates 1 followed by tandem double
[2,3]sigmatropic rearrangement and cyclization of the generated
diallenyl sulfone 2 via a diradical intermediate to thiophene
dioxide derivatives 3 (Scheme 1).[5] This reaction was used by
us as a model for the cycloaromatization of various p and
heteroatom bridged diallenes.[6–9] More recently, this cyclization
has also been used as a model for the design of a new class
of DNA cleaving molecules, which could mimic the
anti-tumor activity of the naturally occurring enediynes.[10,11]
This activity is attributed to a cyclized diradical intermediate.
The reactions of propargylic alcohols with sulfur monochloride
result in the formation of dialkoxy disulfide esters.[12] The latter
undergo facile multiple sigmatropic rearrangements and cycliza-
tion to yield novel products related to the naturally occurring
zwiebelanes.[13]
Due to the distinct characteristic features of the organosele-
nium compounds in organic synthesis[14] as well as in biological
systems[15] on the one hand, and our past work on the reaction
of electrophilic sulfur reagents such as SCl2 and S2Cl2 with
hydroxyalkynes, on the other, we decided to examine the
reactivity of the corresponding selenium halides with such
substrates. We were surprised to discover that the various aspects
of the reaction of SeCl2 with propargyl alcohols, i.e., chemo-
selectivity, regiospecificity and stereospecificity, differ from
expectations based on known reactions of these alcohols
with SCl2. Here we present the complete results of the conti-
nuing investigation, partly reported in a preliminary communi-
cation.[16]
The THF solution of selenium dichloride was prepared by the
known procedure[17] and used immediately. All solvents and
reagents were obtained from Aldrich or Fluka and used without
further purification with the following exception: THF was
distilled from sodium benzophenone dianion just before use and
chloroform was distilled from P2O5. All reactions were carried out
under dry argon atmosphere using oven-dried glassware.
Reagents and solvents were handled by using standard
syringe–septum cap techniques. Column chromatography was
performed with Merck silica gel 60 (230–400 mesh), and TLC was
run on precoated Merck silica gel plates 60 F254. Preparative thin
layer chromatography was carried out in glass sheets precoated
with Merck silica gel 60 F254 (0.5 mm). All new compounds have
satisfactory analytical and spectroscopic data.
Melting points were obtained on a Thomas Hoover melting
point apparatus and are uncorrected. IR spectra were recorded on
a Bruker Tensor 27 FTIR instrument. H NMR and 13C NMR were
recorded on Bruker AC-200, DPX-300 or DMX-600 spectrometers
in either CDCl3 or other deuterated solvents, using TMS as an
internal standard. Chemical shifts are reported in d units, and
coupling constants in Hertz. COSY and NOSY experiments have
been carried out in order to assign 1H and 13C spectra and
confirmed the structures of new compounds. Mass spectra were
1
*
Correspondence to: S. Braverman, Department of Chemistry, Bar-Ilan Univer-
sity, Ramat-Gan 52900, Israel.
E-mail: bravers@mail.biu.ac.il
a
S. Braverman, M. Cherkinsky, R. Jana, Y. Kalendar, M. Sprecher
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
y
This article is published in Journal of Physical Organic Chemistry as a special
issue on Twelfth European Symposium on Organic Reactivity, edited by Amnon
¸
Stanger, Zvi Rappoport, and Marie-Francoise Ruasse.
J. Phys. Org. Chem. 2010, 23 1114–1120
Copyright ß 2010 John Wiley & Sons, Ltd.

REACTION OF SELENIUM AND TELLURIUM HALIDES WITH PROPARGYL ALCOHOLS
O
(175 MHz, CDCl3), d (ppm): 36.1 (C-2), 60.2 (C-1), 122.1 (CH ¼ ,
1
2JC,Se ¼ 22.5 Hz), 129.2 (C ¼ , JC,Se ¼ 109.7 Hz). HRMS Calcd. for
S
OH
O
SCl2,
pyridine
-70 oC
O
O
C8H12Cl2O820Se 289.9380, found 289.9385.
4-chloro-3-(2-hydroxypropan-2-yl)-5,5-dimethyl-5H-1,2-oxasel
enole 2-oxide (6)
CHCl3
reflux
S
O
O
O
1
O
O
White solid, mp 175–177 8C; yield 15%. IR (neat): 2981, 1653,
O
S
S
S
1360, 1170, 1035, 852, 676 cmꢁ1 1H NMR (700 MHz, CDCl3), d
.
75 o
C
(ppm): 1.51 (3H, s), 1.62 (3H, s), 1.68 (3H, s), 1.75 (3H, s), 5.20 (1H,
br). 13H NMR (175 MHz, CDCl3), d (ppm): 28.1 (CH3-C-5), 28.5
(CH3-C-OH), 29.3 (CH3-C-OH), 30.4 (CH3-C-5), 72.5 (C-OH), 98.8
H
2
3
2
1
(C-5, JC,Se ¼ 13.2 Hz), 141.8 (C-4), 152.7 (C-3, JC,Se ¼ 119.2 Hz).
Scheme 1. Reaction of propargyl alcohols with SCl2. Tandem sigma-
tropic rearrangements and cyclizations of dipropargylic sulfoxylates
HRMS Calcd. for C8H14ClO380Se (MHþ) 272.9797, found 272.9793.
obtained on Auto flex Tof/Tof Bruker (Germany) MALDI (matrix
assisted laser desorbtion ionization) instrument with graphite
matrix. High-resolution mass spectra were obtained on a
VG-Fison Autospec instrument.
General procedure for the preparation of divinyl selenides
4j-l from selenium dibromide and propargyl alcohols
The CHCl3 solution of selenium dibromide (2 mmol) prepared
from metallic selenium (0,158 g, 2 mmol) and molecular bromine
(0.1 mL, 2 mmol)[18] was added dropwise to a solution of the
corresponding propargyl alcohol (4 mmol) in dry CHCl3 (5 ml) at
0 8C under nitrogen atmosphere. Then the reaction mixture was
stirred at room temperature for 0.75–1.5 h. After the completion
of the reaction (TLC), the reaction mixture was diluted with
dichloromethane (20 ml) and washed with water (5 ml) and brine
(2 ꢀ 5 ml). The organic layer was dried over MgSO4. After the
evaporation of the solvent, the crude product was purified by
column chromatography on silica gel (hexane-EtOAc, 4:1).
Analytical and spectroscopic data for representative com-
pounds:
(3Z,30Z)-3,30-selenobis(4-bromo-2-methylbut-3-en-2-ol) (4k)
Colorless solid, yield 85%, mp 96 8C; 1H NMR (300 MHz, CDCl3),
d (ppm): 1.62 (s, 12H), 2.71 (s, broad, 2H), 6.43 (s, 2H). 13C NMR
(75 MHz): d 28.5 (CH3), 75.1 (C), 103.2 (CH ¼ ), 144.3 (C). HRMS
Calcd. for C10H16Br2O2Se 405.8682, found 405.8675.
(3Z,30Z)-3,30-selenobis(4-bromo-2-phenylbut-3-en-2-ol) (4l)
Colorless solid, yield 73%, was obtained as an inseparable
mixture of two diastereomers in the ratio 1: 1 (according 1H NMR
spectrum). IR (neat): 3454 (br), 3059, 2983, 1708, 1493, 1446, 1357,
1207, 1134, 1068, 910, 765, 700 cmꢁ1. 1H NMR (300 MHz, CDCl3), d
(ppm) (for both diastereomers): 1.939 & 1.944 (6H each, s), 6.66 &
6.666 (2H each, s), 3.24 & 3.27 (2H each, br), 7.29–7.48 (m). 13C
General procedure for the preparation of divinyl selenides
(and diselenides) from selenium dichloride and
propargyl alcohols
The THF solution of selenium dichloride (1 mmol) prepared by the
known procedure[17] was added dropwise to a solution of the
corresponding propargyl alcohol (2 mmol) in dry THF (2 ml) at
0 8C. Then the reaction mixture was stirred at room temperature
for 0.5–2 h. After the completion of the reaction (TLC), the
reaction mixture was extracted with ethyl acetate (20 ml) and
washed with water (5 ml) and brine (2 ꢀ 5 ml). The organic layer
was dried over MgSO4. After the evaporation of the solvent, the
crude product was purified by column chromatography on silica
gel with hexanes-EtOAc, 4:1 as eluent. Whenever possible,
by-product diselenides were chromatographically separated
from their selenide counterpart, collecting the fractions with
larger Rf values.
Analytical and spectroscopic data for representative com-
pounds:
(2Z,20Z)-2,20-selenobis(3-chloroprop-2-en-1-ol) (4a): Viscous
liquid, IR (neat) 3453 (broad), 2972, 1571, 1368, 1169, 1129,
980 cmꢁ1; 1H NMR (600 MHz, CDCl3): d 3.62 (bs, 2H, OH), 4.46 (d,
4H, J ¼ 1.1 Hz), 6.55 (t, 2H, J ¼ 1.1 Hz); 13C NMR (150 MHz): d 60.9
2
1
(CH2), 122.2 (CH, JC,Se ¼ 22.6 Hz), 132.8 (C, JC,Se ¼ 112.6 Hz);
HRMS: m/z calcd for C6H8Cl2O728Se: 259.9074; found: 259. 9058.
(2Z,20Z)-2,20-selenobis(3-chlorobut-2-en-1-ol) (4b): Solid, m.p.
NMR (75 MHz) d (ppm): 28.13 & 28.25 (CH3), 78.46 & 78.49 (CCH3),
—
106.43 & 106.51 (CH ), 124.93 (C-ipso), 125.73 & 125.77 (CH),
—
—
127.82 (CH), 128.39 & 128. 43 (CH), 143.14 & 144.99 (C ). HRMS
—
56–58 8C; IR (KBr) 3324 (broad), 2976, 1606, 1455, 1015 cmꢁ1
;
Calcd. for C20H20Br2O2Se 529.8995, found 529.8963.
3-Z-4-trichlorotelluro-3-chloro-2-methylbut-3-en-2-ol (9a).
1H NMR (600 MHz, CDCl3): d 2.40 (t, 6H, J ¼ 0.9 Hz), 3.67 (bs, 2H),
4.41 (q, 4H, J ¼ 0.9 Hz); 13C NMR (150 MHz): d 26.6 (CH3), 63.5
White crystals, mp 81–83 8C (from Et2O), yield 49%. H NMR
1
1
2
(CH ), 126.5 ( CCH , JC,Se ¼ 112.3 Hz), 134.0 ( CCl, JC,Se
¼
(300 MHz, CDCl3), d (ppm): 1.57 (6H, s), 1.85 (1H, br), 7.75 (1H, s). 1H
NMR (75 MHz, CDCl3), d (ppm): 28.6 (CH3), 95.3 (C-2), 131.7 (C-4,
1JC,Te ¼ 281.5 Hz), 161.2 (C-3). MS MALDI (Graphite) m/z 353.14
([M-H]ꢁ, 2643).
—
—
—
—
2
2
15.9 Hz); HRMS: m/z calcd for C8H12Cl2O820Se: 289.9380; found:
289.9358.
(3Z,30Z)-3,30-diselanediylbis(4-chloro-2-methylbut-3-en-2-ol (8a):
Yellowish solid, yield 6%, m. p. 88–89 8C; 1H NMR (600 MHz,
CDCl3): d 1.64 (s, 12H), 2.70 (bs, 2H), 6.17 (s, 2H); 13C NMR
(150 MHz): d 28.22 (CH3), 74.9 (C), 113.0 (CH), 139.5 (C ¼ ,
1JC,Se ¼ 132.4 Hz); HRMS: m/z calcd for C10H1376Cl2O278Se2: (Mþ),
397.8814; found: 397.8816; Anal. Calcd C, 30.25; H, 4.06; found C,
30.29; H, 3.88.
(3Z,5Z)-3,5-bis(chloromethylene)-2,2,6,6-tetramethyl-1,4-oxasel
enane (10)
The CHCl3 solution of selenium dichloride (5.1 mmol), prepared
from elemental Se (0.4 g) and SO2Cl2 (0.41 ml) in dry CHCl3 (6 ml)
at rt and stirring for 4 h, was added dropwise to a solution of the
corresponding propargyl alcohol (0.5 ml, 5.1 mmol) in dry CHCl3
(10 ml) at 0 8C. Then the reaction mixture was stirred at room
temperature for 2 h. After the completion of the reaction (TLC),
the reaction mixture was evaporated and the crude product
was purified by column chromatography on silica gel with
hexanes-EtOAc, 7:1 as eluent.
(3Z,30Z)-3,30-selenobis(4-chlorobut-3-en-1-ol) (5)
Colorless oil, yield 52.6%. IR (neat): 3437 (broad), 3066, 2961,
.
2915, 1722, 1605, 1416, 1293, 1037, 952, 779 cmꢁ1 1H NMR
(700 MHz, CDCl3), d (ppm): 2.05 (2H, br), 2.76 (4H, td, J ¼ 6.4,
0.9 Hz), 3.83 (4H, t, J ¼ 6.4 Hz), 6.5 (2H, t, J ¼ 0.9 Hz). 13H NMR
J. Phys. Org. Chem. 2010, 23 1114–1120
Copyright ß 2010 John Wiley & Sons, Ltd.
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S. BRAVERMAN ET AL.
R1
R2
Light-yellow solid, m. p. 49–59 8C; yield 28%. IR (neat): 3058,
3007, 2935, 1578, 1449, 1365, 1302, 1218, 1168, 1130, 1017, 985,
2 R3
1
735 cmꢁ1. H NMR (700 MHz, CDCl3), d (ppm): 1.64 (12H, s), 6.31
(2H, s). 13C NMR (75 MHz) d (ppm): 28. 4 (CH3), 76.6 (C-2 & C-6),
OH
2
—
111.2 (CH , J
¼ 39.0 Hz), 140.5 (C-3, 1JC,Se ¼ 97.5 Hz)). MS (CI/
—
C-Se
CH4): m/z 300 ([M-H]þ, 100%), 265 (M-Cl, 31%), 229 (M-2Cl, 26%),
207 (31%), 185 (29%). HRMS Calcd. for C10H3147Cl2O78Se 301.9536,
found 301.99530.
SeCl2 , THF, rt
[Se + SO2Cl2]
or SeBr2, CHCl3, rt
[Se + Br2]
(Z)-3-chloro-2-((1,2-dibromo-1-chloro-3-hydroxyprop-2-
yl)selenanyl)prop-2-en-1-ol (11)
Colorless solid, yield 53%, was obtained as an inseparable
mixture of two diastereomers in the ratio 2.3:1. IR (neat): 3425,
3070, 2926, 1658, 1592, 1444, 1129, 1059, 779, 522 cmꢁ1. Major
diastereomer: 1H NMR (300 MHz, CDCl3), d (ppm): 7.04 (1H, t,
X
X
Se
R3
R3
R1
R1
R2
—
J ¼ 1.4 Hz, CH ), 6.31 (1H, s, CHClBr), ABq system: 4.75 & 4.37 (1 H
—
R2
—
OH
each, dd, J ¼ 14, 1.4 Hz, CH C ), ABq system: 4.12 & 3.96 (1 H
—
OH
2
each, J ¼ 12.5 Hz, CH2CBr), 3.90 (2H, br). 13C NMR (75MHz) d
4
—
(ppm): 62.0 (CH C ), 63.5 (CHBrCl), 67.3 (CH CBr), 76.4 (CBr),
—
2
2
1
X = Cl, Br
—
—
129.6 (CH ), 131.3 (C ). Minor diastereomer: H NMR (300 MHz,
—
—
Scheme 2. Synthesis of functionalized divinyl selenides by electrophilic
addition of selenium dihalides to propargylic alcohols
CDCl3), d (ppm): 7.02 (1H, t, J ¼ 1.4 Hz, CH ¼ ), 6.32 (1H, s, CHClBr),
—
ABq system: 4.71 & 4.38 (1 H each, dd, J ¼ 14, 1.4 Hz, CH C ), ABq
—
system: 4.10 and 3.99 (1 H each, J ¼ 12.5 Hz, CH2CBr), 3.90 (2H, br).
2
13
—
—
C NMR (75 MHz) d (ppm): 62.0 (CH C ), 63.9 (CHBrCl), 69.1
and Table 1, compounds 4a–4i.[16] Similarly, 2-bromovinyl
selenides 4 (X ¼ Br) are prepared by the reaction of in situ
prepared selenium dibromide, readily obtained from elemental
selenium and bromine in chloroform (Table 1, compounds 4j–4l).
Although a number of methods have been developed for the
synthesis of vinyl selenides,[19,20] the synthesis of divinyl selenides
is much less investigated.[21–27] Furthermore, although the
addition of electrophilic selenium species to olefinic systems
has been the subject of many studies,[28–30] the additions to
acetylenic systems have received much less attention.[18,19,31–36]
Electrophilic addition of phenylselenenyl chloride to internal
double bonds of acyclic allylic alcohols usually resulted in the
formation of a mixture of regioisomers.[37] Allylic alcohols with
terminal double bonds react with phenylselenenyl chloride under
2
—
—
(CH CBr), 77.5 (CBr), 129.7 (CH ), 131.2 (C ). HRMS Calcd. for
—
—
2
C6H789Br81Br35Cl2O820Se 421.7413, found 421.7421.
(3Z,30Z)-3,30-selenodibromide(bis(4-chloro-2-methylbut-3-en-2-o-
methylbut-3-en-2-ol)) (13)
Viscous oil, yield 38%. IR (neat): 3414, 2983, 2935, 1689, 1604,
1463, 1368, 1238, 1178, 981, 940, 869, 793 cmꢁ1 1H NMR
.
(300 MHz, CDCl3), d (ppm): 1.52 (12 H, s), 1.94 (2H, br) 6.82 (2H, s).
13
—
C NMR (150 MHz) d (ppm): 28.1 (CH ), 74.8 (C-2), 118.1 (CH ),
—
3
139.4 (C-3). HRMS Calcd. for C10H15BrCl2O78Se 395.8798; found
395.8831.
(S,4Z,11Z)-4,11-bis(chloromethylene)-1,8-dioxa-5,12-disele
naspiro[6.6]tridecane (15)
Viscous oil, yield 36%. IR (neat): 1643, 1413, 1267, 1192, 1082,
1027, 967, 800, 756 cmꢁ1. 1H NMR (700 MHz, CDCl3), d (ppm): 2.67
—
(2H, dddd, J ¼ 16.0, 11.5, 4.0, 2.0 Hz, CH C ) and 3.17 (2H, dddd,
—
2
0
0
—
J ¼ 16.0, 4.0, 2.0, 1.0 Hz, CH C ), 3.01 & 3.03 (2H each, AA XX
—
system, JAX ¼ 13.5 Hz, CH2Se), 3.77 (2H, dtd, J ¼ 13.0, 4.0, 0.5 Hz,
CH2O), 3.96 (2H, ddd, J ¼ 13.0, 11.5, 2.0 Hz, CH2O), 6.53 (2H, dd,
2
Table 1. Preparation of divinyl selenides by electrophilic
addition of selenium dihalides to propargyl alcohols
J ¼ 2.0, 1.0 Hz, CH ). 13C NMR (175 MHz) d (ppm): 33.9 (C-6 &
—
—
Compound
R1
R2
R3
X
Yield (%)a
1
C-13, JC,Se ¼ 68.8 Hz), 35.8 (C-3 & C-10), 60.4 (C-2 & C-9), 105.2
1
—
—
(C-7), 118.6 (CH
,
2JC,Se ¼ 36.3 Hz), 130.0 (C-4 & C-11, JC,Se
¼
103.6 Hz). HRMS Calcd. for C11H3147Cl2O78Se2 407.8658; found
407.8624.
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
H
H
H
Me
Et
Ph
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
87
91
89
86
82
83
77b
63
72b
90
85
73
H
H
Me
Me
Me
Ph
Cy
H
Me
Et
Ph
H
RESULTS AND DISCUSSION
Reaction of propargyl alcohols with selenium dihalides.
Regio- and stereospecific synthesis of functionalized
divinyl selenides
4j
4k
4l
H
Me
Ph
H
H
H
Me
Me
In sharp contrast to the above-mentioned findings with sulfur
halides, we have found that in situ prepared selenium dichloride,
readily obtained from elemental selenium and sulfuryl
chloride,[17] in all cases with one exception (vide infra) undergoes
smooth 1,2-addition to the triple bond of various propargylic
alcohols resulting in the formation of functionalized divinyl
selenides 4 (X ¼Cl) in high yields and with complete regio- and
stereospecificity (the latter varying with substrate) (Scheme 2)
a Yields are given for isolated products after column chroma-
tography, except for compounds 4g and 4i.
b In these cases, we were unable to separate selenides 4g and
4i from the corresponding diselenides 8d and 8e, by column
chromatography; yields refer to the mixture of two products.
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J. Phys. Org. Chem. 2010, 23 1114–1120

REACTION OF SELENIUM AND TELLURIUM HALIDES WITH PROPARGYL ALCOHOLS
kinetic conditions to provide anti-Markovnikov adducts and
OH
R1
OH
R1
R2
R3
Cl
R1
R3
Cl
under thermodynamic conditions to produce Markovnikov
R2
SeCl2
R1
R3
R2
OH
adducts.[37] Treatment of unsymmetrical nonterminal alkynes
with in situ generated phenylselenenyl fluoride afforded a 1: 1
mixture of the two regiomers.[35] It was also reported that the
addition of electrophilic selenium reagents to alkynes produced
preferably the corresponding E-adducts.[32,34]
Se
Cl
SeCl
A
OH
OH
R1
R2
R3
R2
OH
R1
Se
R2
In contrast to the above, and of special mechanistic interest, is
our finding of syn-addition and anti-Markovnikov orientation in
the addition of the selenium halides to the triple bond of
propargyl alcohols.[16] The structures of these products have
been assigned on the basis of their NMR spectra. The Se-C
R3
R3
Cl Cl
4
Scheme 4. Mechanism of electrophilic addition of SeCl2 to the triple
bond of propargylic alcohols
coupling constants (measured from the 77Se satellites in the 13
C
NMR spectra) were of special diagnostic value in determining the
regiochemistry of the obtained divinyl selenides. The stereo-
chemistry of the newly generated double bond was assigned as Z
by NOESY experiments.
*
three-membered ring, permitting p –s (C–O) overlap. Nucleo-
philic attack of chloride ion in an Cl-addition–Se-elimination
sequence is directed preferentially to the distal end of the
p-bond because of the stabilization of the ‘intermediate
It would seem that the observed regiospecific syn-addition of
selenium dichloride to the triple bond of propargylic alcohols
involves a directing effect by the hydroxyl group, since the acetate
and tosylate esters of propargyl alcohols do not react even after a
prolonged period of time, and alkynes such as phenyl acetylene
and propargyl bromide react very sluggishly and lead to a mixture
of possible isomers. When the reaction was run in the presence of
triethylamine, the electrophilicity of the selenium was neutralized
and neither 1,2-adducts nor seleninate ester were detected.
To confirm the directing effect by the hydroxyl group and to
investigate the effect of the distance of the OH from the triple
bond on the observed regio- and stereospecificity we performed
the reaction of SeCl2 with homopropargyl alcohol. In this case,
substantial loss of stereo- and regioselectivity occurred. All
possible isomers were observed in the NMR spectra of the
crude reaction mixture and Z-anti-Markovnikov product 5 was
chromatographically isolated as a major component (Scheme 3).
The reaction of selenium dihalogenides with the triple bond of
propargyl alcohols rather than the other groups is in keeping with
the Hard–Soft paradigm. Selenirenium ions have been postulated
as principal intermediates in addition reactions of selenium-
containing electrophiles to acetylenes.[35,38–40] Recently, the
selenirenium ions, which were produced by the reaction of the
electrophilic selenium reagents with acetylenes at ꢁ40 to ꢁ80 8C
were detected by 77Se NMR spectroscopy. The structures
of 1-phenyl-2,3-di-tert-butyl-, 1-phenyl-2,3-diadamantyl-, and
1-methyl-2,3-di-tert butylselenirenium salts have been deter-
mined by single-crystal X-ray diffraction.[41]
*
carbanion’ by overlap with said s (C–O) orbital.
An interesting observation was made upon the reaction of
SeCl2 with 2,5-dimethyl-3-hexyne-2,5-diol. In this case, the
reaction proceeded slowly and produced, instead of divinyl
selenide, the seleninate ester 6 presumably via 7 (Scheme 5).
Steric hindrance of the four methyl groups precluded addition to
the triple bond.
The cyclic intermediate 7 is presumed to react with a second
molecule of SeCl2 followed by hydrolysis during aqueous
work-up to give the observed product 6. The presence of the
—
seleninate moiety Se( O)O is based on its NMR spectral data
—
which reveal four non-equivalent methyl groups, as well as on IR
data. 2,5-Dimethyl-3-hexyne-2,5-diol reacts with sulfur dichloride
under the same reaction conditions in a similar manner.[42]
Similar saturated g-selentines have been prepared recently by
Back,[43] by a procedure involving the [2,3]sigmatropic rearrange-
ment of allylic selenoxide.[44,45] They were found to have
significant biological activity related to oxidative stress.[46]
In some cases, synthesis of divinyl selenides 4 was accom-
panied by the formation of the corresponding divinyl diselenides
8 as minor products (Scheme 6). Diselenides 8a, 8b, and 8c were
separated from their selenide counterpart by column chroma-
tography. However, we were unable to isolate diselenides 8d and
8e upon chromatography and their contents were determined by
1H NMR analysis of crude reaction mixture. Diselenide formation
can be explained by the formation of selenium monochloride
Se2Cl2 via disproportionation of selenium dichloride.[47]
Thus, although no reaction of the hydroxyl group with
selenium dichloride to yield selenoxylate esters (R-O-Se-O-R)
could be detected (with one exception, vide infra), the hydroxyl
group still plays an important role, responsible for the surprising
regio- and stereochemical results. These may be rationalized by
the postulate that the stable conformation of A (Scheme 4) is one
in which C–O bond is perpendicular to the plane of the
Reactions of propargyl alcohols with chalcogen tetrahalides
It was found that SeCl4 also adds readily to propargyl alcohols in a
completely regio- and stereospecific manner yielding the
corresponding divinyl selenium dichlorides as unstable inter-
mediates. The latter undergo either transposition of chlorine to
Cl
Cl
Cl
Cl
SeCl2
THF, rt
Se
Se
Cl
Cl
Se
+
+
OH
OH
OH
HO
OH
OH
OH
Z-5 major isomer
Scheme 3. Reaction of homopropargyl alcohol with SeCl2
J. Phys. Org. Chem. 2010, 23 1114–1120
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S. BRAVERMAN ET AL.
THF
0oC to rt
HO
HO
H2O
HO
Cl
Cl
Cl
SeCl2
HO
O
HO
OH
Se
Se
Cl
Se
ClSe
Cl Se
O
O
O
O
7
6
Scheme 5. Formation of cyclic seleninate ester 6
3SeCl2
Se2Cl2 + SeCl4
Cl
protonated olefinic carbon. The stereochemistry of the newly
generated double bond was assigned as by NOESY
Z
Cl
Se2Cl2/THF
0 oC to rt
R1
Se Se
R1
OH
experiments, which showed a strong interaction of the respective
vinylic hydrogen with the methyl hydrogen atoms. Reaction of
TeCl4 with 1-phenyl-2-propyn-1-ol in dry CH2Cl2 at ꢁ15 8C
produces an oil from which anti-adduct with anti-Markovnikov
R2
R1
R2
OH
R2
OH
8a-e
orientation 9b[48] was isolated as
a major product by
8a, R1=R2=Me, 6 %; 8b, R1=Me, R2=Et, 10 %; 8c, R1=H, R2=Ph, 12%;
8d, R1=Me, R2=Ph, 8d/4g 30:70; 8e, R1 _ R2=Cy, 8e/4i 7:93
recrystalization from dry Et2O.
Scheme 6. Formation of divinyl diselenides.
Reactivity of functionalized divinyl selenides
In contrast to the findings presented above, electrophilic addition
of benzeneselenenyl chloride to internal double bonds of acyclic
allylic alcohols usually resulted in the formation of a mixture of
regioisomers.[37] In an attempt to explore the allylic alcohol
functionality of the newly prepared selenides we have reacted
selenium dichloride with one equivalent of a,a-dimethyl
propargyl alcohol instead of two equivalents (refer to
Scheme 2). However, instead of the formation of 1,4-diselenane
derivatives, as possible SeCl2 adduct to the original divinyl
selenide, the 1,4-oxaselenane 10 shown in Scheme 8 was
obtained. Formation of the latter via a simple intramolecular
dehydration of the divinyl selenide diallylic diol is unlikely in view
of the stability of the latter under acidic conditions. The
alternative mechanism is being investigated.
Interestingly, the reaction has shown a surprising sensitivity to
the substitution of the allylic function. For example, using the
unsubstituted propargyl alcohol afforded the corresponding
1,4-oxaselenane as a minor product. The major product appears
to be formed via a subsequent intermolecular reaction of the
appropriate divinyl selenide with SeCl2.
Bromination of divinyl selenide also showed a surprising
sensitivity to the substitution of the allylic function. Thus,
using the unsubstituted propargyl alcohol, the products 11 and
12 of bromine addition to the double bond were obtained
(Scheme 9). Bromination of divinyl selenide, derived from
a,a-dimethylpropargyl alcohol, with one equivalent of Br2
afforded selenium dibromide 13 (Scheme 10), whereas two
equivalents of Br2 produced a complex mixture of products,
including bromination of double bond, formation of selenium
dibromide and cyclization.
the double bond, or hydrolysis to the corresponding divinyl
selenoxides. In these reactions also syn-addition and anti-
Markovnikov orientation are observed. The full description of
these results will be published elsewhere.
Finally, the reaction of TeCl4 with propargyl alcohols was found
to differ sharply from that of SeCl4. The corresponding vinyl
tellurium trichlorides 9 are obtained as a mixture of regio- and
stereoisomers (Scheme 7). Unlike selenium halogenide additions,
the reaction shows a surprising sensitivity to substitution on the
propargylic moiety. Thus, 2-methylbut-3-yn-2-ol upon reaction in
dry chloroform at room temperature affords as a major product
(> 90% according to 1H NMR spectrum of the crude reaction
mixture) the syn-adduct with Markovnikov orientation (9a)
(Scheme 7). The latter was isolated from the crude reaction
mixture by recrystalization from Et2O. The structure of this
product has been assigned on the basis of its NMR spectra. The
Te-C coupling constants (measured from the 125Te satellites in the
13C NMR spectra) were of special diagnostic value in determining
the regiochemistry of the obtained vinyl tellurotrichlorides. The
carbon atoms directly attached to tellurium were easily identified
since 1JC,Te >> 2JT,Se. Thus, for compound 9a, the one-bond
1
coupling constant, JC,Te ¼ 281.5 Hz, was observed for the
H
TeCl 3
Me
Me
TeCl4
H3C
H3C
Cl
CHCl3, rt
OH
OH
Ph
9a
O
TeCl4
-15 oC
CH2Cl2
H
Ph
OH
H
Se
OH
H
TeCl3
- H2O
SeCl2
SeCl2
CHCl3, rt
Cl
Cl
Se
Cl
H
10
HO
OH
OH
OH
OH
Cl
Se
Cl
Cl
Cl
H
9b
Cl
Se Cl
Scheme 7. Reaction of propargyl alcohols with TeCl4
Scheme 8. Synthesis of 1,4-oxaselenanes
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J. Phys. Org. Chem. 2010, 23 1114–1120

REACTION OF SELENIUM AND TELLURIUM HALIDES WITH PROPARGYL ALCOHOLS
Cl
Cl
Br
CONCLUSION
Br2 (1 equiv),
CHCl3, rt
Se
Br
In summary, we have shown that various aspects of the reaction
of SeCl2 with propargyl alcohols, i.e., identity of reacting
functionality, regiospecificity and stereospecificity, differ from
expectations based on known reactions of these alcohols with
SCl2. Selenium dihalides undergo smooth 1,2-addition to the
triple bond of various propargylic alcohols under mild reaction
conditions resulting in the formation of the corresponding
functionalized divinyl selenides in high yields and with complete
regio- and stereospecificity. The syn-addition and anti-
Markovnikov orientation observed in all cases are of special
mechanistic interest. This is a convenient method to incorporate
selenium into an organic molecule, and novel highly functiona-
lized divinyl selenides of synthetic and biological interests are
accessible by this simple procedure.
Cl
Cl
53 %
HO
OH
Se
11
Br2 (2 equiv),
CHCl3, rt
Cl
Cl
HO
OH
Se
Br
Br
17 %
Br
HO
Br
OH
12
Cl
Cl
Cl
Cl
Br
Br
Br2 (1 equiv), CHCl3, rt
38 %
Se
OH
Se
OH
OH
OH
13
Scheme 9. Bromination of functionalized divinyl selenides
Acknowledgements
OH
O
This work has been supported by a grant from the Israel Science
Foundation (Grant No.919-05).
n
SeCl2, THF, rt
Cl
nOH
n = 0, 1
Cl
SeCl
16
Cl
O
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Cl
H
O
Se
Se
H
Se
nO
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