Hypervalent iodine-induced multi-component reactions: Novel thiocyano- and isothiocyano-phenylselenenylating reaction of alkenes

Article abstract of DOI:10.1002/(SICI)1099-0690(200005)2000:10<1865::AID-EJOC1865>3.0.CO;2-I

A simple and efficient thiocyano- or isothiocyano-phenylselenenylation of alkenes has been developed. The reactions occur when alkenes are treated with [bis(acetoxy)iodo]benzene, trimethylsilyl isothiocyanate or potassium thiocyanate and diphenyl diseleni

Full text of DOI:10.1002/(SICI)1099-0690(200005)2000:10<1865::AID-EJOC1865>3.0.CO;2-I

FULL PAPER
Hypervalent Iodine-Induced Multi-Component Reactions: Novel Thiocyano-
and Isothiocyano-phenylselenenylating Reaction of Alkenes
Roberto Margarita,[a,b] Chiara Mercanti,[a] Luca Parlanti,[a,b] and Giovanni Piancatelli*[a]
Keywords: Alkenes / Iodine / Selenium / Sulfur / Isothiocyanates / Thiocyanates
A simple and efficient thiocyano- or isothiocyano-phenylse-
lenenylation of alkenes has been developed. The reactions
whereas both more-substituted alkenes and styrenes gave
exclusively 1,2-phenylseleno-isothiocyanates. The overall
occur when alkenes are treated with [bis(acetoxy)iodo]ben- transformation represents the addition of PhSeSCN to the ol-
zene, trimethylsilyl isothiocyanate or potassium thiocyanate
efinic double bonds, in situ generated by the above re-
and diphenyl diselenide. Mono- and disubstituted alkenes agents combination.
led to the formation of 1,2-phenylseleno-thiocyanates,
Introduction
In recent years, the combination of hypervalent iod-
ine(III) reagents with trimethylsilyl derivatives of inorganic
anions has been exploited to develop new synthetic
methods in organic chemistry.[1,2] An investigation of the
mechanism showed the formation of new hypervalent re-
agents, such as [bis(cyano)iodo]benzene which is formed
from the reaction of (PhIO)n with trimethylsilyl cyanide and
can be isolated as a crystalline solid which is stable at room
temperature under nitrogen for several weeks. Other deriv-
atives, usually prepared in situ, have been demonstrated to
undergo interesting reactions by a simple, efficient and en-
vironmentally less-hazardous methodology.[3,4] As part of
our interest in the chemistry of iodine(III) reagents, we re-
cently described the reactivity of [bis(acetoxy)iodo]benzene
(BAIB) with trimethylsilyl isothiocyanate (TMSNCS), as an
ideal combination of reagents for a facile synthesis of 1,2-
dithiocyanates from alkenes.[5,6] Since the manipulation of
the thiocyanate group gives an easy access to various sulfur
functional groups[7] and sulfur-containing heterocycles,[8]
the direct thiocyanation of alkenes is a valuable transforma-
tion.[9] Thiocyanate derivatives have also been demonstrated
to possess a good fungicidal activity.[10]
We thought that the in situ formation of the pseudohal-
ogen species thiocyanogen could be usefully employed in
multicomponent reactions, in order to achieve different
functional group formation at the same time. In the last few
years, our research group has been involved in organoselen-
ium compound synthesis.[12] Since selenium compounds
have been known to be versatile reagents in organic chem-
istry, owing to their flexible and easily manipulated nature,
we wanted to apply the developed technology in this field.
As reported, the selenenyl halides are important reagents as
selenium electrophiles; they are usually prepared by treating
diselenides with a stoichiometric amount of halogen, and
these reactions are described to be either instantaneous or
very fast.[13]
Now we describe an original multicomponent reaction,
promoted by the hypervalent iodine(III), which, in com-
bination with TMSNCS or potassium thiocyanate and di-
phenyl diselenide, was able to perform a novel thiocyano-
or isothiocyano-phenylselenenylating reaction of alkenes.
The overall transformation represents the addition of
PhSeSCN to the olefinic double bonds, in mild experi-
mental conditions, which must be considered an interesting
outcome, since it results in a desymmetrization of the struc-
tures. Previous reports have described the generation in situ
of this intermediate and its reaction with alkenes to give the
addition products. Phenylselenenyl thiocyanate, described
to be unstable and impossible to isolate, is produced when
phenylselenenyl chloride is allowed to react with either pot-
assium thiocyanate[14] or mercury(II) thiocyanate.[15]
The experimental evidence allowed us to propose a pos-
sible reaction pathway for the dithiocyanation reaction.
Treatment of BAIB with TMSNCS gave rise to a ligand
exchange around the hypervalent iodine(III) atom, thermo-
dynamically favored by the siliconϪoxygen bond forma-
tion, to give the unstable [bis(thiocyanato)iodo]benzene A
[Equation (1)].[6] The decomposition of this species led to
the formation of thiocyanogen which then performs the anti
electrophilic addition to the olefins giving the desired 1,2
dithiocyanato derivatives.[11]
[a]
`
Dipartimento di Chimica, Universita ‘‘La Sapienza’’, Piazzale
Aldo Moro 5, Box no. 34-Roma 62, 00185 Roma, Italy
Fax: (internat.) ϩ 039-06/490631
Results and Discussion
E-mail: piancatelli@axrma.uniroma1.it
Centro CNR di Studio per la Chimica delle Sostanze Organiche
[b]
The approach to functional group diversity could be eas-
`
Naturali, Universita ‘‘La Sapienza’’,
Piazzale Aldo Moro 5, Box no. 34-Roma 62, 00185 Roma, Italy ily obtained by adding the simple diphenyldiselenide to the
Eur. J. Org. Chem. 2000, 1865Ϫ1870 1865
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0510Ϫ1865 $ 17.50ϩ.50/0

R. Margarita, C. Mercanti, L. Parlanti, G. Piancatelli
FULL PAPER
Scheme 1. Synthesis of phenylselenyl thiocyanates
Scheme 3. Synthesis of phenylselenyl isothiocyanates
method.[15] This result proved that the addition reaction
proceeded in a stereospecific manner, providing only the
trans diastereoisomer, and in agreement with previous re-
ports of the addition of PhSeSCN to olefinic double
bonds.[15]
Electron-poor olefins, such as acrylates, were recovered
unchanged from the reaction medium, while electron-rich
ones, such as dihydropyran, were very reactive, providing a
mixture of compounds, useless from the synthetic point of
view. Interestingly, more substituted systems furnished the
isomeric 1,2-phenylseleno-isothiocyanates as the unique re-
action product (Scheme 3). Both trisubstituted olefins and
styrene derivatives reacted in this fashion and the corres-
ponding anti adducts were obtained in high yields. The ad-
dition showed high chemoselectivity, being able to differen-
tiate the two olefinic double bonds on terpene derivatives,
such as 3d and 3e, and to selectively functionalize the
C6ϪC7 double bond (Table 2).
thiocyanating system. In fact, by treatment of 0.6 equiv. of
the latter with 1.5 equiv. of BAIB and 3 equiv. of TMSNCS
or potassium thiocyanate, either in acetonitrile or dichloro-
methane, terminal and disubstituted olefins 1 could be
transformed at room temperature into anti 1,2-phenylse-
leno-thiocyanato derivatives 2 in good yields and short re-
action times (Scheme 1). Table 1 collects the results of this
particular transformation on simple model substrates.
Table 1. Synthesis of phenylselenyl thiocyanates 2a؊c
Substrate
Product
R
RЈ
Yield (%)
1a
1b
1c
2a
2b
2c
nC6H13
Cyclohexyl
-(CH2)4-
H
H
80
75
65
Structural assignments of the compounds 2 were based
1
on IR, H and 13C NMR spectra. 1,2-Phenylseleno-thiocy-
Table 2. Synthesis of phenylselenyl isothiocyanates 4a؊e
anate compounds showed spectral data in agreement with
the structures: 2a: IR: 2140 cmϪ1 (sharp, SCN); 13C NMR:
δ ϭ 110.0 (SCN); 2b: IR: 2135 cmϪ1 (sharp, SCN); 13C
NMR: δ ϭ 112.0 (SCN); 2c: IR: 2135 cmϪ1 (sharp, SCN);
13C NMR: δ ϭ 112.0 (SCN).
Substrate Product R
RЈ RЈЈ Yield (%)
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
H
Ph H 54
Ph Me 82
Me 75
H
-(CH2)4-
-(CH2)2C(Me)ϭCH(CHO)
Me Me 91
-(CH2)2C(Me)ϭCH(CH2OAc) Me Me 88
All the reactions proceeded regioselectively, as shown by
the GC-MS analysis of the crude reaction mixtures. The
Scheme 2. Oxidative elimination of phenylselenium group from 2a
In the case of all the examined alkenes, a single re- structure and the regiochemistry of the 1,2-phenylseleno-
gioisomer was obtained, as shown by the GC-MS analysis isothiocyanato derivatives were fully confirmed by means
of the crude reaction mixtures. The regioselectivity of the of the spectroscopic data. Compound 4a: IR: 2042 cmϪ1
formed compounds was assigned on the basis of chemical (broad, -NCS); the 13C NMR confirmed the presence of the
and spectroscopic evidence. In fact, when a compound such isothiocyanate group (δ ϭ 134.5, br. s, -NCS), while the
as 2a, formed by the thiocyano-phenylselenenylation of oct- 13C-DEPT 135 NMR experiments allowed us to establish
1-ene (1a), was oxidized to the corresponding selenoxide, a the regiochemistry of the reaction product, showing that
spontaneous syn-elimination took place to afford 1-hexyle- the phenylselenium group is linked to a CH2 group (δ ϭ
thenyl thiocyanate (2d), clearly demonstrating that the 36.3) and showing a coupling with 77Se (d, JCϪSe
ϭ
phenylselenium group in the compound 2a was linked to 74 Hz).[15,16] Compound 4b: IR: 2085 cmϪ1 (broad, -NCS);
the terminal carbon atom (Scheme 2). Usually, the 1H 13C NMR: δ ϭ 134.4 (br. s, -NCS); 13C-DEPT 135 NMR:
NMR spectroscopic data were in agreement with the above- δ ϭ 44.0 (CH2ϪSePh, d, JCϪSe ϭ 76 Hz). Compound 4c:
described Markovnikov orientation. In cyclic alkenes such IR: 2085 cmϪ1 (broad, -NCS); 13C NMR: δ ϭ 131.7 (br.
1
as 2c, the H NMR analysis does not give any information s, -NCS), 13C-DEPT 135 NMR: δ ϭ 54.6 (CHϪSePh, d,
about the stereochemistry since the protons attached to the JCϪSe ϭ 70 Hz). In cyclic alkenes, the formation of a single
carbon atoms bearing the phenylseleno and thiocyanate diastereoisomer was observed, with a trans-relationship of
groups appear as a complex multiplet between δ ϭ the two functional groups, as previously described.[15]
3.06Ϫ3.34. However, the addition of PhSeSCN to an ol-
This substrate dependent reactivity needed further in-
efinic double bond is a two-step process and the first step vestigations to elucidate the reaction pathway. Diphenyl dis-
is the formation of a seleniranium cation. In the second elenide has been reported to be oxidised by several spe-
step, the anionic part of the reagent is fixed trans stereospe- cies,[17] so we had to demonstrate which oxidation BAIB
cifically.[13,15] Moreover, 2c showed identical spectroscopic was performing. Chemical evidence showed that simple ol-
data with an authentic sample prepared by a known efins are inert to direct treatment with BAIB and (PhSe)2
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Eur. J. Org. Chem. 2000, 1865Ϫ1870

Hypervalent Iodine-Induced Multi-Component Reactions
FULL PAPER
Both 1,2-phenylseleno-thiocyanate and 1,2-phenylseleno-
isothiocyanate derivatives may be considered as useful in-
termediates. For example, the oxidative removal of the
phenylselenium group of substrate 2a with sodium period-
ate led to 1-hexylethenyl thiocyanate (2d) (Scheme 2). The
same reaction with 4e gave the allylic ether 7; reductive
elimination with tributyltin hydride[21] restores the double
bonds giving back 3e, thus showing a particular example of
reversibility (Scheme 6).
Scheme 4. Mechanism of phenylseleno-thiocyanation of olefins
for short reaction times, and led to a mixture of acetoxy-
phenylseleno adducts after several hours, showing a reactiv-
ity typical of PhSeOAc.[18] We were able to elucidate that
this process, although occurring, is not responsible for the
oxidation since it is relatively slow. 13C NMR spectroscopy
of the phenylseleno-thiocyanation reaction mixture (PhSe-
SePh, BAIB and TMSNCS in CD3CN with TMS as in-
ternal standard) initially shows a peak at δ ϭ 107.5, as-
signed to thiocyanogen, besides those of the reagent and
iodobenzene, demonstrating that the formation of the thio-
cyanating system is a very fast process.[6] Subsequently, a
new signal is formed at δ ϭ 111.9 which was assigned to
PhSeSCN, and this species is responsible for the anti adduct
formation as shown by the final addition of an olefin
(Scheme 4). The nature of the nucleophilic attack to the se-
leniranium intermediate by the nitrogen or the sulfur atom
has already been demonstrated to be dependent on the
‘‘hardness’’ of these atoms and of the carbon center under-
going the reaction.[19]
The addition products 4d and 4e (Table 2) seemed par-
ticularly interesting since they contain a carbon-nitrogen
bond on a quaternary center. Since this kind of adduct is
derived from an ionic reaction which proceeds with com-
plete Markovnikov regioselectivity, we considered the pos-
sibility of obtaining an anti-Markovnikov regioisomeric
analogue using the radical process with BAIB, NaN3 and
(PhSe)2,[20] so that we could obtain a CϪN bond on a ter-
tiary center. Performing the reaction on (E)-1-acetoxy-3,7-
dimethylocta-2,6-diene (3e) gave the expected product 5 in
70% yield; (E)-3,7-dimethylocta-2,6-dienal (3d), which has
a Michael acceptor in the structure, gave the azido-phenyl-
selenenylation product 6 in 75% yield as a diastereoisomeric
mixture after the intramolecular 5-exo cyclization of the ini-
tially formed carbon radical (Scheme 5). These two meth-
odologies are therefore complementary and offer a protocol
for the selective functionalization of terpene derivatives
with CϪSe and CϪN functional groups.
Scheme 6. Reductive and oxidative elimination of phenylselenium
group from 4e
On the other hand, the isothiocyanate group may be use-
fully employed in the synthesis of unsymmetrical thio-
ureas.[22] These functional groups are emerging as funda-
mental structural units in tailored receptors that are capable
of binding anions exclusively through hydrogen bonding.
For this reason, we explored the reactivity of our quatern-
ary isothiocyanates with a simple amine, namely benzylam-
ine. The reaction with 4c proceeded cleanly without solvent
and led in almost quantitative yield to the corresponding
mixed thiourea 8. This result prompted us to investigate
the possibility of building single structures with multiple
thiourea units. In this sense, we were able to design and
prepare a branched derivative 9 based on a tris(ethyleneam-
ino)amine substructural unit (Scheme 7). The physical
properties of this compound are currently under investi-
gation.
Scheme 7. Synthesis of N,NЈ-disubstituted thioureas
Furthermore thiourea-functionalized amino acids have
also been demonstrated to be competitive inhibitors of the
nitrite synthesis and to be able to decrease the NADPH
oxidizing activity of the enzyme and to alter the heme-iron
spin state.[23]
Conclusion
The unprecedented hypervalent iodine-promoted multic-
omponent reaction represents a new and mild method for
preparing regio- and stereoselectively desymmetrized com-
Scheme 5. Reagent and conditions: a. BAIB, (PhSe)2, NaN3,
CH2Cl2, r.t., 12 h; b. BAIB, KSCN or TMSNCS, (PhSe)2, CH3CN
or CH2Cl2, r.t., 2 h
Eur. J. Org. Chem. 2000, 1865Ϫ1870
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R. Margarita, C. Mercanti, L. Parlanti, G. Piancatelli
FULL PAPER
oil in 80% yield. 1H NMR (CDCl3): δ ϭ 0.79Ϫ0.93 (m, 3 H),
1.10Ϫ1.90 (m, 9 H), 1.91Ϫ2.10 (m, 1 H), 3.20 (m, 2 H, CH2SePh),
3.35 (m, 1 H, CHSCN), 7.21Ϫ7.43 (m, 3 H), 7.51Ϫ7.65 (m, 2 H).
pounds from alkenes. This method should gain significant
synthetic importance, since it shows the same reactivity as
the PhSeCl/Hg(SCN)2 reagent combination,[15] but without
sharing some of its undesirable effects, such as high toxicity
and waste disposal problems. Furthermore, the previously
known procedure affords 1,2-phenylseleno-isothiocyanates
selectively, while the new reaction sequence leads to the
formation of either 1,2-phenylseleno-thiocyanates or 1,2-
phenylseleno-isothiocyanates, depending on the nature of
the alkenes, in good to excellent yields. These compounds
are useful intermediates for many synthetic applications,
due to the variety of reactions in which the above functional
groups can be subsequently involved.[24] Naturally occur-
ring and synthetic thiocyanate and isothiocyanates are
widespread compounds showing interesting biological ac-
tivities.[25]
Ϫ
13C NMR (CDCl3): δ ϭ 14.0, 22.5, 26.6, 28.5, 31.4, 33.5, 33.9,
51.1, 111.0 (SCN), 127.9, 128.7, 129.3, 133.5. Ϫ IR (CHCl3): ν˜ ϭ
2140 (sharp), 2960, 3075 cmϪ1. Ϫ C15H21NSSe (326.36): calcd. C
55.20, H 6.49; found C 55.32, H 6.38.
1-Cyclohexyl-2-phenylselenylethyl Thiocyanate (2b): Following the
general procedure, freshly distilled vinylcyclohexane (1b) was added
to give 1-cyclohexyl-2-phenylselenylethyl thiocyanate (2b) as a col-
1
orless viscous oil in 75% yield. H NMR (CDCl3): δ ϭ 0.80Ϫ2.11
(m, 11 H), 3.25Ϫ3.41 (m, 3 H, CH2SePh and CHSCN), 7.22Ϫ7.38
(m, 3 H), 7.50Ϫ7.72 (m, 2 H). Ϫ 13C NMR (CDCl3): δ ϭ 25.6,
25.7, 25.8, 26.0, 28.0, 30.8, 40.6, 57.8, 111.9 (SCN), 127.7, 128.7,
129.2, 133.3. Ϫ IR (CHCl3): ν˜ ϭ 2135 (sharp), 2935, 3070 cmϪ1
.
Ϫ C15H19NSSe (324.34): calcd. C 55.55, H 5.90; found C 55.65,
H 5.85.
trans-2-Phenylselenylcyclohexyl Thiocyanate (2c): Following the
general procedure, freshly distilled cyclohexene (1c) was added to
give trans 2-phenylselenylcyclohexyl thiocyanate (2c) as a colorless
Experimental Section
General: Unless noted otherwise, all starting materials were ob-
tained from commercial suppliers and were used without further
purification. If purification was required, it was performed accord-
ing to the method reported in Purification of Laboratory Chemicals
D. D. Perrin, L. F. Armarego, Pergamon Press, 1980. 1H NMR
spectra were recorded on a Varian GEMINI 200 (200 MHz) or a
Bruker VRX 400 (400 MHz) spectrometers as solutions in CDCl3,
unless otherwise indicated. Chemical shifts are expressed in parts
per million (ppm, δ) downfield from tetramethylsilane (TMS) and
are referenced to CDCl3 (7.24 ppm) as internal standard. Splitting
patterns are designed as s, singlet; d, doublet; t, triplet; q, quadru-
plet; m, multiplet; b, broad. Coupling constants are given in Hz.
13C NMR spectra were recorded on a Varian GEMINI 200
(50 MHz) or a Bruker VRX 400 (100 MHz) spectrometers as solu-
tions in CDCl3, unless otherwise indicated. Chemical shifts are ex-
pressed in parts per million (ppm, δ) downfield from tetramethylsil-
ane (TMS) and are referenced to the center line of CDCl3
(77.0 ppm) as internal standard. IR spectra were recorded in
CHCl3 solution, using a Shimadzu IR 470 spectrometer and are
reported in wavenumbers (cmϪ1). Mass spectra were obtained on
a Hewlett-Packard HPLC-MS coupling mass spectrometer and on
a Hewlett-Packard 5971A GC-MS selective detector. GC spectra
were obtained on a Hewlett-Packard 5880-HP 5880A apparatus.
Routine monitoring of reaction was performed using Merck Kiesel-
gel 0.25 mm 60 F254 silica gel, TLC plates. Flash chromatography
was performed with Merck Kieselgel 60 (230Ϫ400 mesh).
1
viscous oil in 65% yield. H NMR (CDCl3): δ ϭ 1.20Ϫ1.90 (m, 6
H), 2.14Ϫ2.32 (m, 1 H), 2.35Ϫ2.50 (m, 1 H), 3.06Ϫ3.34 (m, 2 H,
CHSePh and CHSCN), 7.20Ϫ7.40 (m, 3 H), 7.50Ϫ7.65 (m, 2 H).
Ϫ
13C NMR (CDCl3): δ ϭ 14.0, 22.5, 26.6, 28.6, 31.4, 33.5, 33.9,
51.1, 111.0 (SCN), 127.9, 128.8, 129.3, 133.5. Ϫ IR (CHCl3): ν˜ ϭ
2135 (sharp), 2860, 3025 cmϪ1. Ϫ C13H15NSSe (296.29): calcd. C
52.70, H 5.10; found C 52.60, H 5.23.
1-Phenyl-2-phenylselenylethyl Isothiocyanate (4a): Following the
general procedure, freshly distilled styrene (3a) was added to give
1-phenyl-2-phenylselenylethyl isothiocyanate (4a) as a colorless vis-
cous oil in 55% yield. 1H NMR (CDCl3): δ ϭ 3.29 (d, J ϭ 6.96 Hz,
2 H, CH2SePh), 4.84 (t, J ϭ 6.96 Hz, 1 H, CHNCS), 7.21Ϫ7.45
(m, 8 H), 7.45Ϫ7.65 (m, 2 H). Ϫ 13C NMR (CDCl3): δ ϭ 36.3
(JCϪSe ϭ 74 Hz), 61.7, 126.1, 127.9, 128.7, 129.0, 129.4, 133.8,
134.5 (NCS), 138.1. Ϫ IR (CHCl3): ν˜ ϭ 2042 (broad), 2855, 2960,
3075 cmϪ1. Ϫ C15H13NSSe (318.29): calcd. C 56.60, H 4.12; found
C 56.45, H 4.24.
1-Methyl-1-phenyl-2-phenylselenylethyl Isothiocyanate (4b): Follow-
ing the general procedure, freshly distilled 2-phenylpropene (3b)
was added to give 1-methyl-1-phenyl-2-phenylselenylethyl isothio-
cyanate (4b) as a colorless viscous oil in 82% yield. 1H NMR
(CDCl3): δ ϭ 1.87 (s, 3 H), 3.40 (d, J ϭ 12.66 Hz, 1 H, CHSePh),
3.48 (d, J ϭ 12.66 Hz, 1 H, CHSePh), 7.11Ϫ7.68 (m, 10 H). Ϫ 13C
NMR (CDCl3): δ ϭ 29.6, 44.0 (JCϪSe ϭ 76 Hz), 67.6, 124.9, 127.5,
128.2, 128.7, 129.2, 130.1, 133.6, 134.4 (NCS), 141.8. Ϫ IR
(CHCl3): ν˜ ϭ 2085 (broad), 2940, 3070 cmϪ1. Ϫ C16H15NSSe
(332.32): calcd. C 57.83, H 4.55; found C 57.72, H 4.64.
Phenylseleno-thiocyanation of Olefins. General Procedure: To a mix-
ture of BAIB (1.5 mmol), KSCN or TMSNCS (3 mmol) and
(PhSe)2 (1 mmol) in CH3CN or CH2Cl2 (5 mL) was added 1 mmol
of olefin. The solution was stirred at room temperature for 2 h
before an aqueous solution of Na2S2O3 (1 mL) and AcOEt (5 mL)
were added. The solution was then transferred into a separating
funnel and the two phases separated. The water layer was extracted
with AcOEt (3 ϫ 5 mL) and the combined organic extracts were
washed with saturated NaHCO3 and brine. After drying over
Na2SO4 or MgSO4, the solvent was removed under reduced pres-
sure. The crude material was purified by silica gel flash chromato-
graphy (hexane/AcOEt, 95:5) to afford the desired compounds.
(1R*,2R*)-1-Methyl-2-phenylselenylcyclohexyl Isothiocyanate (4c):
Following the general procedure, freshly distilled 1-methylcyclohex-
ene (3c) was added to give (1R*,2R*)-1-methyl-2-phenylselenylcy-
clohexyl isothiocyanate (4c) as a colorless viscous oil in 75% yield.
1H NMR (CDCl3): δ ϭ 1.51 (s, 3 H), 1.41Ϫ2.01 (m, 6 H),
2.10Ϫ2.30 (m, 2 H), 3.37 (dd, J1 ϭ 4 Hz, J2 ϭ 7.2 Hz, 1 H,
CHSePh), 7.20Ϫ7.35 (m, 3 H), 7.55Ϫ7.69 (m, 2 H). Ϫ 13C NMR
(CDCl3): δ ϭ 22.0, 23.8, 26.1, 30.8, 38.1, 54.6 (JCϪSe ϭ 70 Hz),
65.3, 127.9, 129.2, 129.7, 131.7 (NCS), 134.8. Ϫ IR (CHCl3): ν˜ ϭ
2085 (broad), 2865, 3010 cmϪ1. Ϫ C14H17NSSe (310.32): calcd. C
54.19, H 5.52; found C 54.30, H 5.62.
1-Hexyl-2-phenylselenylethyl Thiocyanate (2a): Following the gen-
eral procedure, freshly distilled oct-1-ene (1a) was added to give 1-
hexyl-2-phenylselenylethyl thiocyanate (2a) as a colorless viscous
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Eur. J. Org. Chem. 2000, 1865Ϫ1870

Hypervalent Iodine-Induced Multi-Component Reactions
FULL PAPER
(E)-5-Heptenyl-1,1,5-trimethyl-7-oxo-2-phenylselenyl Isothiocyanate (E)-1-Acetoxy-6-azido-3,7-dimethyl-7-phenylselenyloct-2-ene
(4d): Following the general procedure, freshly prepared (E)-3,7-di-
methylocta-2,6-dienal (3d) was added to give (E)-5-heptenyl-1,1,5-
(5):
Following the general procedure, freshly distilled (E)-1-acetoxy-3,7-
dimethylocta-2,6-diene (3e) was added to give (E)-1-acetoxy-6-az-
trimethyl-7-oxo-2-phenylselenyl isothiocyanate (4d) as a colorless ido-3,7-dimethyl-7-phenylselenyloct-2-ene (5) as a colorless viscous
1
viscous oil in 91% yield. 1H NMR (CDCl3): δ ϭ 1.52 (s, 3 H), 1.55
oil in 70% yield. H NMR (CDCl3): δ ϭ 1.28 (s, 3 H), 1.37 (s, 3
(s, 3 H), 2.10Ϫ2.85 (m, 7 H), 3.00 (dd, J1 ϭ 12.5 Hz, J2 ϭ 5 Hz, 1 H), 1.69 (s, 3 H), 2.01 (s, 3 H), 2.06Ϫ2.29 (m, 4 H), 3.17 (dd, J1 ϭ
H, CHSePh), 5.84 (dd, J1 ϭ 8 Hz, J2 ϭ 1 Hz, 1 H), 9.99 (d, J ϭ 9.48 Hz, J2 ϭ 1.56 Hz, CHN3, 1 H), 4.56 (d, J ϭ 7.04 Hz, 2 H),
7.8 Hz, 1 H), 7.22Ϫ7.30 (m, 3 H), 7.50Ϫ7.71 (m, 2 H). Ϫ 13C NMR
5.38 (t, J ϭ 7.06 Hz, 1 H), 7.26Ϫ7.36 (m, 3 H), 7.57Ϫ7.62 (m, 2
(CDCl3): δ ϭ 17.5, 26.4, 29.1, 29.5, 39.8, 57.8, 65.8, 128.0, 129.4, H). Ϫ 13C NMR (CDCl3): δ ϭ 16.0, 20.7, 25.4, 27.6, 28.6, 36.9,
130.0, 134.2, 138.2, 162.2, 191.1. Ϫ IR (CHCl3):ν˜ ϭ 3015, 2068 50.8, 61.0,71.7, 119.9, 127.4, 128.9, 138.4, 140.6, 171.1. Ϫ IR
(broad), 1670 cmϪ1. Ϫ C17H21NOSSe (336.38): calcd. C 55.73, H (CHCl3): ν˜ ϭ 3000, 2900, 2085, 2080, 1730 cmϪ1. Ϫ GC-MS: m/
5.78; found C 55.62, H 5.82.
z ϭ 367 (M ؉ Ϫ N2). Ϫ C18H25N3O2Se (394.38): calcd. C 54.82, H
6.39; found C 54.75, H 6.50.
(E)-7-Acetoxy-5-heptenyl-1,1,5-trimethyl-2-phenylselenyl Isothiocy-
anate (4e): Following the general procedure, freshly distilled (E)-1-
acetoxy-3,7-dimethylocta-2,6-diene (3e) was added to give (E)-7-
acetoxy-5-heptenyl-1,1,5-trimethyl-2-phenylselenyl isothiocyanate
(4e) as a colorless viscous oil in 88% yield. 1H NMR (CDCl3): δ ϭ
1.49 (s, 3 H), 1.52 (s, 3 H), 1.72 (s, 3 H), 2.00Ϫ2.65 (m, 7 H), 3.00
(dd, J1 ϭ 11.2 Hz, J2 ϭ 2.2 Hz, 1 H, CHSePh), 4.58 (d, J ϭ 6 Hz,
2 H), 5.33 (t, J ϭ 6 Hz, 1 H), 7.26Ϫ7.38 (m, 3 H), 7.50Ϫ7.68 (m,
2 H). Ϫ 13C NMR (CDCl3): δ ϭ 16.8, 21.6, 27.1, 29.5, 30.1, 38.5,
58.3, 61.9, 66.5, 120.4, 128.1, 129.8, 131.1, 134.4, 141.1, 171.4. Ϫ
IR (CHCl3): ν˜ ϭ 1726, 2072 (broad), 2865, 2990 cmϪ1. Ϫ
C19H25NO2SSe (410.43): calcd. C 55.60, H 6.14; found C 55.71,
H 6.22.
Oxidative Elimination of Phenylselenium Group. General Procedure:
To a mixture of NaHCO3 (1.5 mmol) and NaIO4 (2.5 mmol) in
methanol/water (9 mL, 6:1) was added 1 mmol of alkylphenylselen-
ide. The solution was stirred at room temperature until disappear-
ance of the starting material, then an aqueous solution of NH4Cl
(2 mL) and AcOEt (10 mL) was added. The solution was then
transferred into a separating funnel and the two phases separated.
The water layer was extracted with AcOEt (4 ϫ 5 mL) and the
combined organic extracts were washed with saturated NaHCO3
and brine. After drying over Na2SO4, the solvent was removed un-
der reduced pressure. The crude material was purified by silica gel
flash chromatography (hexane/AcOEt, 95:5) to afford the desired
compounds.
Azido-phenylselenenylation of Olefins. General Procedure: To a mix-
ture of BAIB (1.5 mmol), (PhSe)2 (0.6 mmol) and NaN3 (3 mmol)
in CH2Cl2 (5 mL) was added 1 mmol of olefin. The solution was
stirred at room temperature for 12 h before an aqueous solution of
Na2S2O3 (1 mL) and AcOEt (5 mL) was added. The solution was
then transferred into a separating funnel and the two phases separ-
ated. The water layer was extracted with AcOEt (3 ϫ 5 mL) and
the combined organic extracts were washed with saturated
NaHCO3 and brine. After drying over Na2SO4 or MgSO4, the solv-
ent was removed under reduced pressure. The crude material was
purified by silica gel flash chromatography (hexane/AcOEt, 80:20)
to afford the desired compound.
1-Hexylethenyl Thiocyanate (2d): Following the general procedure,
1-hexyl-2-phenylselenylethyl thiocyanate (2a) was added to give 1-
hexylethenyl thiocyanate (2d) as a colorless viscous oil in 52% yield.
1H NMR (CDCl3): δ ϭ 0.90 (t, J ϭ 6.3 Hz, 3 H), 1.20Ϫ1.41 (m, 6
H), 1.48Ϫ1.68 (m, 2 H), 2.39 (t, J ϭ 7.5 Hz, 2 H), 5.43 (d, J ϭ
1.6 Hz, 1 H), 5.47 (d, J ϭ 1.4 Hz, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ
13.9, 22.4, 27.5, 28.2, 31.3, 36.3, 109.8 (SCN), 117.5, 135.5. Ϫ IR
(CHCl3): ν˜ ϭ 2145 (sharp), 2860, 3030 cmϪ1. Ϫ C9H15NS (169.28):
calcd. C 63.86, H 8.93; found C 63.78, H 8.85.
(E,E)-1-Acetoxy-7-methoxy-3,7-dimethylocta-2,5-diene (7): Follow-
ing the general procedure, (E)-7-acetoxy-5-heptenyl-1,1,5-trime-
thyl-2-phenylselenyl isothiocyanate (4e) was added to give (E,E)-
1-acetoxy-7-methoxy-3,7-dimethylocta-2,5-diene (7) as a colorless
viscous oil in 30% yield. 1H NMR (CDCl3): δ ϭ 1.25 (s, 6 H), 1.68
(s, 3 H), 2.04 (s, 3 H), 2.76 (d, J ϭ 6.8 Hz, 2 H), 3.14 (s, 3 H), 4.58
(d, J ϭ 7 Hz, 2 H), 5.30Ϫ5.44 (m, 1 H), 5.48Ϫ5.52 (m,2 H). Ϫ 13C
NMR (CDCl3): δ ϭ 16.5, 21.0, 25.8, 42.4, 50.3, 61.3, 74.7, 119.1,
127.1, 137.7, 140.9, 171.1. Ϫ IR (CHCl3): ν˜ ϭ 1726 (CϭO), 3030
cmϪ1. Ϫ C13H22O2 (210.32): calcd. C 74.24, H 10.54; found C
74.30, H 10.62.
2-(3-Azido-1,2,2-trimethylcyclopentyl)-2-phenylselenylethanal (6):
Following the general procedure, freshly distilled (E)-3,7-dimethyl-
octa-2,6-dienal (3d) was added to give 2-(3-azido-1,2,2-trimethylcy-
clopentyl)-2-phenylselenenylethanal (6) as a colorless viscous oil in
75% yield and as a mixture of diasteroisomers. (1° isomer) 1H
NMR (CDCl3): δ ϭ 0.88 (s, 3 H), 0.92 (s, 3 H), 1.17 (s, 3 H),
1.68Ϫ2.20 (m, 4 H), 3.59 (d, J ϭ 7.26 Hz, 1 H), 3.73 (dd, J1
ϭ
9.00 Hz, J2 ϭ 8.92 Hz, 1 H), 7.25Ϫ7.34 (m, 3 H), 7.47Ϫ7.52 (m, 2
H), 9.51 (d, J ϭ 7.24 Hz, 1 H). Ϫ APT (CDCl3): (odd) δ ϭ 17.5,
20.1, 21.4, 64.7, 70.4, 128.8, 129.5, 135.3, 135.4, 192.3; (even) δ ϭ
25.2, 36.9, 47.5, 48.0, 127.3. Ϫ (2° isomer) 1H NMR (CDCl3): δ ϭ
0.96 (s, 3 H), 0.97 (s, 3 H), 1.22 (s, 3 H), 1.70Ϫ2.25 (m, 4 H), 3.49
(d, J ϭ 7.28 Hz, 1 H), 3.69 (dd, J1 ϭ 8.26 Hz, J2 ϭ 8.06 Hz, 1 H),
7.23Ϫ7.31 (m, 3 H), 7.42Ϫ7.50 (m, 2 H), 9.50 (d, J ϭ 7.24 Hz, 1
N,NЈ-Disubstituted Thioureas. General Procedure: To a solution of
amine (1 mmol) dissolved in the minimal amount of CH2Cl2 was
added 1 equiv. of isothiocyanate derivative. The solution was stirred
at room temperature until disappearance of the starting material.
The solvent was then removed under reduced pressure. The crude
material was purified by silica gel flash chromatography (hexane/
AcOEt, 80:20) to afford the desired compounds.
1
H). Ϫ (3° isomer) H NMR (CDCl3): δ ϭ 1.09 (s, 3 H), 1.21 (s, 3
H), 1.28 (s, 3 H), 1.70Ϫ2.22 (m, 4 H), 3.49 (d, J ϭ 6.62 Hz, 1 H),
3.59 (dd, J1 ϭ 8.22 Hz, J2 ϭ 9.16 Hz, 1 H), 7.25Ϫ7.31 (m, 3 H),
1
7.45Ϫ7.62 (m, 2 H), 9.42 (d, J ϭ 6.68 Hz, 1 H). Ϫ (4° isomer) H
N-Benzyl-NЈ-1-[(1R*,2R*)-1-methyl-2-phenylselenylcyclohexyl]-
thiourea (8): Following the general procedure, 1-methyl-2-phenylse-
lenylcyclohexyl isothiocyanate (4c) was added to benzylamine to
give N-benzyl-NЈ-1-[(1R*,2R*)-1-methyl-2-phenylselenylcyclohex-
NMR (CDCl3): δ ϭ 1.09 (s, 3 H), 1.21 (s, 3 H), 1.28 (s, 3 H),
1.65Ϫ2.25 (m, 4 H), 3.49 (d, J ϭ 6.76 Hz, 1 H), 3.71 (dd, J1
ϭ
8.80 Hz, J2 ϭ 9.16 Hz, 1 H), 7.23Ϫ7.30 (m, 3 H), 7.42Ϫ7.45 (m, 2
H), 9.46 (d, J ϭ 6.18 Hz, 1 H). Ϫ IR (CHCl3): ν˜ ϭ 3000, 2900, yl]thiourea (8) as a colorless viscous oil in 95% yield. 1H NMR
2085, 1728 cmϪ1. Ϫ GC-MS: m/z ϭ 323 (M ؉ Ϫ N2). Ϫ
C16H21N3OSe (350.32): calcd. C 54.86, H 6.04; found C 54.90, H
6.09.
(CDCl3): δ ϭ 1.2Ϫ2.2 (m, 11 H), 3.95 (dd, J1 ϭ 8.1 Hz, J2 ϭ
6.0 Hz, 1 H), 4.24 (d, J ϭ 5.6 Hz, 2 H), 4.70 (t, J ϭ 5.6 Hz, 1 H)
4.84 (s, 1 H), 7.20Ϫ7.30 (m, 8 H), 7.55Ϫ7.69 (m, 2 H). Ϫ 13C NMR
Eur. J. Org. Chem. 2000, 1865Ϫ1870
1869

R. Margarita, C. Mercanti, L. Parlanti, G. Piancatelli
FULL PAPER
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1870
Eur. J. Org. Chem. 2000, 1865Ϫ1870