Reaction of Dess-Martin periodinane with 2-(alkylselenyl)pyridines. Dehydration of primary alcohols under extraordinarily mild conditions

Article abstract of DOI:10.1016/j.tetlet.2010.02.002

Dess-Martin periodinane oxidizes very rapidly 2-pyridylseleno derivatives RR′CHCH₂SePy in CHCl₃ or CH₂Cl₂ and more chemoselectively than mCPBA. Tetravalent selenanes, RR′CHCH₂Se(OAc)₂Py, se

Full text of DOI:10.1016/j.tetlet.2010.02.002

Tetrahedron Letters 51 (2010) 1863–1866
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Tetrahedron Letters
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Reaction of Dess–Martin periodinane with 2-(alkylselenyl)pyridines.
Dehydration of primary alcohols under extraordinarily mild conditions
*
Thanos Andreou, Jordi Burés, Jaume Vilarrasa
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Av. Diagonal 647, 08028 Barcelona, Catalonia, Spain
a r t i c l e i n f o
a b s t r a c t
Dess–Martin periodinane oxidizes very rapidly 2-pyridylseleno derivatives RR0CHCH2SePy in CHCl3 or
CH2Cl2 and more chemoselectively than mCPBA. Tetravalent selenanes, RR0CHCH2Se(OAc)2Py, seem to
be formed. Treatment of these intermediates with aqueous NaHCO3 gives rise to irreversible hydrolysis
and elimination to terminal alkenes. As the OH/SePy exchange can be performed in minutes, the overall
process is an exceptionally efficient procedure for the dehydration of primary alcohols.
Ó 2010 Elsevier Ltd. All rights reserved.
Article history:
Received 11 January 2010
Revised 28 January 2010
Accepted 1 February 2010
Available online 4 February 2010
Keywords:
Pyridylselenanes
Terminal double bonds
In connection with a total synthesis of amphidinolide K,1 the
oxidation of the OH group of fragment C11–C22 (1a, Scheme 1)
was required. Under standard Swern conditions2 2a was obtained.
However, to our initial surprise, the treatment of 1a with Dess–
Martin periodinane (DMP)3 gave almost quantitatively a Se deriv-
ative (1b, the characterization of which will be explained below),
which was not identical to the selenoxide (1c) we obtained as a
major compound, among by-products, from 1a and 3-chloroper-
oxybenzoic acid (mCPBA). A second equivalent of DMP was neces-
sary to form the aldehyde at C11 (conversion of 1b to 2b); 2a and
DMP also gave 2b, which could not be isolated but it gave an elim-
ination product (2d) during the workup.
close to the Se atom and the proton signals of the pyridine ring
underwent downfield shifts, with broadening of some peaks. We
supposed that an unstable species such as selenane 3b had been
formed.8 Attempts to purify or isolate it from the reaction mixture
accelerated its decomposition.
On the other hand, from 3a and mCPBA, 3c was obtained as the
major compound, most NMR signals of which could be easily as-
signed from the final reaction mixture.9 Intermediate 3c gave 3d
on treatment with aq NaHCO3. All these facts, which we hypothe-
sized to occur as shown in Scheme 2, ran in parallel to those men-
tioned for 1a.
The equimolar reaction of the 2-pyridylseleno group (2-pyrid-
ylselenenyl, SePy) with DMP can be viewed as a simple redox pro-
cess (IV + SeII?IIII + SeIV). However,
a
search of the literature
SePy
O
O
indicated that there is no precedent for the use of hypervalent io-
dine reagents for the oxidation of RSeAr or RSeHet.4 There are, of
course, many important studies on the preparation of SeAr deriva-
tives,5 their oxidation with peroxyacids or peroxides, and their syn-
eliminations.6
From the TBS-monoprotected derivative of hexane-1,6-diol (3)
and PySeSePy in toluene or CH2Cl2, we prepared quickly and quan-
titatively, at rt, 2-pyridylselenide 3a by the addition of a solution of
PMe3 in toluene.7 When the reaction of 3a with DMP (Scheme 2)
was monitored by 1H NMR spectroscopy in CDCl3, upfield and
downfield shifts were noted for the acetoxy groups but neither
Ac2O nor AcOH was formed, as confirmed by the addition of small
amounts into independent NMR tubes. The triplet of the CH2 group
DMP
DMP
Swern
DMP
X
N
O
SePy
TBDPS
Se
2a
O
X
O
O
11
HO
SePy
O
O
TBDPS
HO
O
O
2b (X = ?)
workup
TBDPS
TBDPS
1a
22
1b, X = ?
O
mCPBA
O
O
1c, X = O
TBDPS
2d
* Corresponding author. Tel.: +34 934021258; fax: +34 933397878.
E-mail address: jvilarrasa@ub.edu (J. Vilarrasa).
Scheme 1. Oxidations of 1a.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.002

1864
T. Andreou et al. / Tetrahedron Letters 51 (2010) 1863–1866
TBSO
OH
toluene, rt
AcO
Se
AcO
I
O
3
O
N
O
+
+
..
PySeSePy
PMe3
O
OTBS
OTBS
:
rt
rt
I
AcO
:
OAc
3b
OAc
AcO
Se
N
H
O
OH
O
O
O
OTBS
Cl
3a
N
3c
rt
Se
O
Cl
1.92
21.6
workup
TBSO
7.39
7.90
7.96
175.6
135.5
138.3
138.3
8.13
8.00
7.26
7.52
7.43
6.97
120.8
O
126.2
124.2
126.3
125.2
119.6
O
2.43
5.2
156.1
3.43
31.4
2.74
35.8
163.7
155.7
8.63
8.67
8.42
149.9
149.5
N
N
149.6
+
"PySeOH"
N
Se
AcO
Se
Se
3d
O
δSe 254
δSe 675
δSe 834
Scheme 2. Conversion, at rt, of 3a–d. Relevant 1H, 13C and 77Se NMR chemical shifts in CDCl3 of model compounds.
To confirm or discard the initial formation of selenanes, we pre-
mCPBA was slower than with DMP, under identical conditions.
However, when mCPBA was previously purified (removing 3-chlo-
robenzoic acid), the reaction was completed as quickly as with
DMP (ca. 30 min in CDCl3). Thus, both the reagents are similarly
useful for the oxidation of SePy. Nevertheless, a key point was to
examine whether these oxidants are compatible or not with other
sensitive groups, especially with double bonds prone to epoxida-
tion.15 When we treated a mixture of 0.10 mmol of 4a and
0.10 mmol of cyclohexene with 0.10 mmol of pure mCPBA in a
NMR tube in CDCl3, at rt for a few minutes, 40% of 4a was oxidized
to 4b while 50% of cyclohexene was converted to its epoxide.16
Therefore, mCPBA does not distinguish between a cis-disubstituted
double bond and the SePy group. In the cases of 1a and 5a we
noted partial epoxidations of the double bonds with mCPBA. In
sharp contrast, DMP reacts very selectively with the SePy group.
Not all the solvents were appropriate. At 0.1–0.2 M concentra-
tions, with 3a and 1.2 equiv of DMP, the reaction was completed
in CHCl3 in around 30 min and in CH2Cl2 within 50 min; in 9:1
CH2Cl2–toluene the reaction was slower, but still efficient. On the
other hand, the oxidation process did not progress in THF, in
CH3CN, or in 1:1 CH2Cl2–pyridine, as if coordinating solvents inter-
acted with the iodine atom of DMP, disturbing the approach of the
SePy group.
Treatment of 3b with aqueous NaHCO3 or Na2CO3, or with
methanolic NEt3, at rt, quickly gave the elimination product (3d).
Most likely, 3b is hydrolyzed to 3c, which undergoes the known
spontaneous syn-elimination to give 3d, as indicated in Scheme 2.
With the optimum conditions in hand, we investigated sub-
strates 4a–8a. Table 1 shows the results for SePy derivatives arising
from primary alcohols, prepared by means of a simple reaction
with PySeSePy and PMe3 (which gives O@PMe3 and PySeH as co-
products). In practice, 1.10 equiv of DMP was enough for a full con-
version, but 1.20 equiv was added if the commercial sample had a
purity <97% when checked by 1H NMR. Without isolation, they
were shaken with a slightly alkaline aqueous solution, as men-
tioned above. The organic layer contained only the alkene or unsat-
urated compound.
pared PySeMe, which could simplify the NMR analysis of the reac-
tion mixtures. Furthermore, its PySe(OAc)2Me and PySe(O)Me
derivatives were expected to be more stable (at least, a b-elimina-
tion is not possible). The 77Se NMR peak of PySeMe (254 ppm
downfield to Me2Se)10 was shifted to 675 ppm when DMP was
added, whereas it was shifted to 834 ppm with mCPBA (Scheme
2, bottom). The corresponding 1H/13C/gCOSY/HSQC/HMBC NMR
spectra were also different (see also Scheme 2). Everything pointed
out that, in the reactions of SePy derivatives with DMP, k4 selen-
anes were the first noticeable intermediates.11 Therefore, in
Scheme 1, we believe that X means two magnetically equivalent
AcO groups.
The trend of Se(IV) to be linked by single bonds to its ligands
(rather than by double bonds) is paradigmatic and understandable
for all elements down within each group of the periodic table.
There seems that the two-electron transfer between I(V) and Se(II)
eventually gives rise to the transfer of two AcO groups.
In this context, we carried out additional experiments to exam-
ine whether (1) the oxidation of SePy by DMP was more rapid or
not than that of alcohols, (2) oxidizing agents other than peroxides
and DMP could carry out the same transformation, (3) the SePy
group is more suitable than SeAr groups, and (4) DMP has advan-
tages or not in relation to peroxides.
With regard to question 1, we treated an equimolar mixture of
alcohol 3 and its SePy derivative 3a with 0.8 equiv of DMP. Only 3a
reacted to give 3b, while the alcohol was recovered unchanged (see
also the conversion of 1a to 1b).
Regarding question 2, standard oxidizing reagents such as 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) and ammonium ceriu-
m(IV) nitrate (CAN), in moist or anhydrous CH2Cl2 or CH3CN, did
not affect the SePy group. IBX, a DMP precursor, did not react at
all in CH2Cl2 (where it is insoluble) or in CH3CN; even by heating
3a and IBX (2.0 equiv) in Me2SO-d6 for 5 h at 50 °C, the conversion
was very low (only a trace of 3d was detected by TLC).12 The Swern
reagent (Me2SO, ClCOCOCl), under standard conditions,2 did not re-
act with 3a either.
Concerning question 3, in competition experiments between
PhCH2CH2CH2SePy (see 4a, in Table 1) and its SePh analogue
This very mild procedure can be applied to molecules contain-
ing C–C double bonds (entries 2 and 5), without precautions. As ex-
pected, the procedure was compatible with common protecting
groups (see entries 3 and 5, as well as 1b). Double bond isomeriza-
tion was not observed in the case of entries 4 and 5.
(PhCH2CH2CH2SePh) with a defect of DMP, only 4a was oxidized.
5
Its o-nitro derivative, PhCH2CH2CH2SeC6H4(o-NO2),
hardly re-
acted.13 Thus, DMP reacts very selectively with SePy.
As far as question 4 is concerned, the reaction of SePy groups
with H2O2 is not recommendable in general, since secondary reac-
tions may occur.14 Moreover, the reaction of 4a with commercial
In summary, after the conversion of primary alcohols to SePy
derivatives with PySeSePy/PMe3 in 90–98% yields, oxidation with
DMP affords k4 selenanes. With a basic workup, they are hydro-

T. Andreou et al. / Tetrahedron Letters 51 (2010) 1863–1866
1865
Table 1
From primary alcohols to alkenes or unsaturated compounds
(PySe)2
workup
rt
DMP
PMe3
R
R
R
R
SePy
OH
SePy
toluene or
CH2Cl2–tol
rt, 10 min
CH2Cl2
rt
R'
R'
4–8
R'
AcO OAc
R'
4d–8d
4a–8a
30–60 min
4b–8b
step Aa
step Bb
step C step D
Entry
1
SePy derivative
Ph
SePy
Yield, % step A
93
Alkene or unsaturated compd
Yield, % B–D
Ph
95
90
4a
4d
SePy
(CH )
2
3
98
95
2 7
5d
(CH2)7
OPMB
5a
OPMB
SePy
99
6a
6d
SePy
4
5
93
98
95c
O
7d
O
7a
SePy
PMBO
PMBO
TBDPS
O
O
O
O
95d
TBDPS
8d
8a
a Alcohols 4–8 (1.0 mmol) in toluene or CH2Cl2 (ca. 5 mL), a commercially available toluene solution of Me3P (1.0 M, 1.2 mL), and a solution of PySeSePy in toluene or CH2Cl2
(1.1 mmol in 2.0 mL) were mixed at 0 °C or at rt. Stirring the mixture under Ar for 10 min, washing with water, and filtering through a small pad of silica gel, gave 4a–8a.
b DMP (1.1–1.2 equiv) was added to the SePy derivative (0.20 mmol of 4a–8a) in CH2Cl2 (1–2 mL). After stirring for 30–60 min at rt (or 1–2 h if the reaction was carried out in
9:1 CH2Cl2–toluene), TLC indicated that the substrate had been consumed. A vigorous stirring of the final solutions with aq NaHCO3 for 10–60 min or shaking them strongly
for a few minutes with aq Na2CO3 left pure organic solutions of 4d–8d.
c
Conversion percentage as observed by 1H NMR (the product is too volatile to be isolated operating at 0.1–1.0 mmol scales).
2.0 equiv of DMP was used (step B) in this case.
d
3. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–4156.
4. Very recent reviews of hypervalent iodine reagents: (a) Uyanik, M.; Ishihara, K.
lyzed and converted spontaneously in situ to olefins in 90–99%
yields. The full process can be carried out at rt within 1 h (for the
Chem. Commun. 2009, 2086–2099; (b) Dohi, T.; Kita, Y. Chem. Commun. 2009,
most simple cases) or 2 h. DMP can be considered an alternative
to mCPBA (and to peroxides in general) that can be used in the
presence of double bonds prone to epoxidation. Thus, a new appli-
cation of DMP (not shared by DDQ, CAN or IBX) has been disclosed:
it oxidizes SePy groups in the presence of alcohols and double
bonds.
The overall process seems an academic exercise on red-ox reac-
tions involving trivalent and pentavalent P, divalent and tetrava-
lent Se, and pentavalent and trivalent iodine (three elements in a
diagonal that is parallel to that of the borderline metals or semi-
metallic elements). In practice, we have discovered by accident
the mildest procedure for the dehydration of primary alcohols re-
ported to date, to the best of our knowledge.
2073–2085; (c) Ladziata, U.; Zhdankin, V. V. Synlett 2007, 527–537; (d) Barton,
D. H. R.; Crich, D. Tetrahedron 1985, 41, 4359–4364; for the use of PhI(OAc)2 as
an acetoxylation reagent, see: (e) Iglesias-Arteaga, M. A.; Arcos-Ramos, R. O.
Tetrahedron Lett. 2006, 47, 8029–8031; (f) Prakash, O.; Kaur, H.; Sharma, V.;
Bhardwaj, V.; Pundeer, R. Tetrahedron Lett. 2004, 45, 9065–9067, and references
therein; for the oxidation of functional groups other than alcohols, see: (g)
Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem. Soc. 2004, 126,
5192–5201 (IBX, N and S compounds), and references therein; (h) Nicolaou, K.
C.; Sugita, K.; Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124, 2221–2232
(dienes to vinyl epoxides).
5. o-Nitrophenylselenoxides: (a) Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975,
40, 947–949; (b) Grieco, P.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41,
1485–1486; (c) Reich, H. J.; Wollowitz, S.; Trend, J. E.; Chow, F.; Wendelborn, D.
F. J. Org. Chem. 1978, 43, 1697–1705; (d) Sayama, S.; Onami, T. Tetrahedron Lett.
2000, 41, 5557–5560, and references therein. As known, o-NO2C6H4SeCN and
Bu3P are the standard reagents for the conversion of primary alcohols to
terminal olefins (the Grieco–Sharpless olefination reaction).
6. Reviews of arylselenoxide eliminations: (a) Uemura, S. Phosphorus, Sulfur,
Silicon 2005, 180, 721–728; (b) Back, T. G. Organoselenium Chemistry; Oxford
Univ. Press: Oxford, 1999; for the use of SePy derivatives, see: (c) Toshimitsu,
A.; Owada, H.; Terao, K.; Uemura, S.; Okana, M. J. Org. Chem. 1984, 49, 3796–
3800; (d) Toshimitsu, A.; Hayashi, G.; Terao, K.; Uemura, S. J. Chem. Soc., Perkin
Trans 1 1988, 2113–2117. and references therein.
7. For a review of the scope of PySeSePy see: (a) Toshimitsu, A.; Esteban, J.;
Vilarrasa, J. e-EROS (Encyclopedia of Reagents for Organic Synthesis), RD454;
Wiley, 2007; for other uses of PySeSePy/PMe3, see: (b) Martín, M.; Martínez, G.;
Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 2004, 45, 5559–5561; (c) Esteban, J.;
Costa, A. M.; Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 2004, 45, 5563–5567; (d)
Burés, J.; Martín, M.; Urpí, F.; Vilarrasa, J. J. Org. Chem. 2009, 74, 2203–2206; for
the preparation and characterisation of PySe(CH2)nCOOR, see: (e) Bhalla, A.;
Nagpal, Y.; Kumar, R.; Mehta, S. K.; Bhasin, K. K.; Bari, S. S. J. Organomet. Chem.
2009, 694, 179–189.
Acknowledgments
This work was partially funded by the Government of Spain
(Madrid) via Grants SAF02-02728 and CTQ2006-15393. T.A. re-
ceived a doctorate studentship (IGSoC program) from the General-
itat de Catalunya (Barcelona, 2003–2006) and later a studentship
via Fundació Bosch Gimpera–UB for one year. Experiments of Laia
Esteban, when she was a DEA student in our Department, deserve
to be mentioned. Thanks are due to Francisco Cárdenas, UB NMR
Service, for registering the 77Se NMR spectra.
8. The involvement of a N-acetylpyridinium acetate of the selenoxide (instead of
3b) was ruled out on the basis of the NMR spectra, as the well-known
References and notes
downfield shifts expected for all pyridine protons and b and
c
carbons as well
1. (a) Mas, G.; Gonzalez, L.; Vilarrasa, J. Tetrahedron Lett. 2003, 44, 8805–8809; (b)
Andreou, T.; Costa, A. M.; Esteban, L.; Gonzalez, L.; Mas, G.; Vilarrasa, J. Org. Lett.
2005, 7, 4083–4086.
as upfield shifts of the
observed.
a carbons, if a N-acylation had taken place, were not
9. The protons of the CH2 group linked to Se of 3a (a triplet at d 3.17) were split
2. Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978, 43, 2480–2482.
and appeared at 3.23 ppm (ddd) and 3.10 ppm (ddd), indicating that a new

1866
T. Andreou et al. / Tetrahedron Letters 51 (2010) 1863–1866
stereocenter (Se) had been created (see 3c). The carbon signal of that CH2 was
14. (a) In fact, Toshimitsu et al. (Ref. 6c) already reported that ozone was
preferable to H2O2. In our hands, oxidation of 4a with H2O2 was slow (even
with a large excess and gentle stirring of the biphasic system); when after 2–3
h, aq NaHCO3 was added to the reaction mixture, 4c partially returned to 4a.
Related redox reactions, which look like disproportionations, were described
with SePh groups, see: Clark, R. D.; Heathcock, C. H. J. Org. Chem. 1976, 41,
1396–1403, and references therein (selenenic acid PhSeOH, formed partially by
elimination from RCH2CH2Se(O)Ph, was oxidised to seleninic acid PhSeO2H
while the selenoxide was reduced to RCH2CH2SePh); (b) it is also known that
ArSeO2H (and their precursors ArSeSeAr/ArSeX) catalyse Baeyer–Villiger and
epoxidation reactions of H2O2: Ten Brink, G.-J.; Fernandes, B. C. M.; Van Vliet,
M. C. A.; Arends, I. W. C. E.; Sheldon, R. A., J. Org. Chem. 2001, 66, 2429–2433,
and references therein; oxidations of SeAr groups with H2O2 have been clearly
counter-indicated in some instances: (c) Blay, G.; Cardona, L.; Collado, A. M.;
García, B.; Morcillo, V.; Pedro, J. R. J. Org. Chem. 2004, 69, 7294–7302
(significant epoxidation of the double bond of an unsaturated o-NO2C6H4Se
derivative); (d) Lu, L.; Zhang, W.; Carter, R. G. J. Am. Chem. Soc. 2008, 130, 7253–
7255, and references therein (the o-NO2C6H4Se oxidation with peroxides
proved problematic in complex molecules with sensitive groups).
shifted from 25.8 to 50.4 ppm, while C2 and C3 of the pyridine ring were
shifted from 155.7 and 125.4 ppm to 160.9 and 122.1 ppm, respectively.
10. Nakanishi, W.; Matsumoto, S.; Ikeda, Y.; Sugawara, T.; Kawada, Y.; Iwamura, H.
Chem. Lett. 1981, 1353–1356.
11. (a) There are few reported diarylselenium bis(carboxylates), cf.: Todo, H.;
Miyagawa, N.; Yokoyama, M. Chem. Lett. 1992, 1677–1678, and references
therein. The 77Se chemical shifts of PhSeMe (202 ppm), PhSe(OAc)2Me
(658 ppm) and PhSe(@O)Me (832 ppm) are parallel to those obtained by us
in the pyridine series (shown in Scheme 2). We also confirmed this pattern for
other SePy derivatives not included here for the sake of simplification; e.g.,
PySeCH2CH2Ph
(347 ppm),
PySe(OAc)2CH2CH2Ph
(709 ppm)
and
PySe(@O)CH2CH2Ph (853 ppm); for very recent, representative examples of
tetrasubstituted Se compounds (k4 selenanes) of type R2Se(OR)2, see: (b) Back,
T. G.; Kuzma, D.; Parvez, M. J. Org. Chem. 2005, 70, 9230–9236; (c) Back, T. G.;
Moussa, Z.; Parvez, M. Angew. Chem., Int. Ed. 2004, 43, 1268–1270.
12. For more soluble IBX derivatives (‘modified IBX’), see: (a) Moorthy, J. N.;
Singhal, N.; Senapati, K. Tetrahedron Lett. 2008, 49, 80–84, and references
therein; (b) Richardson, R. D.; Zayed, J. M.; Altermann, S.; Smith, D.; Wirth, T.
Angew. Chem., Int. Ed. 2007, 46, 6529–6532. Although they have not been
examined by us, the most active might behave as DMP.
13. As the deactivating electronic effect of the Py and 2-nitrophenyl groups on the
Se oxidation should be similar, the reactivity differences may be attributed to
the steric effect of the NO2 group (which may hinder the approach required for
the electronic transfer) and to the cooperation of the lone pair of the pyridine
nitrogen atom in the chelation of the pentavalent iodine. This last statement is
confirmed by the fact that SePy is oxidized more rapidly than SePh.
15. For an over-oxidation in situ of the resulting elimination product (from a bis-o-
NO2C6H4Se derivative) by the mCPBA excess, see: Blay, G.; Cardona, M. L.;
García, B.; Pedro, J. R. J. Org. Chem. 1991, 56, 6172–6175.
16. As it could be expected, an excess of mCPBA (0.22 mmol) added to a mixture of
4a (0.10 mmol) and cyclohexene (0.10 mmol) in CDCl3, gave quantitatively,
after the workup, both 4d and cyclohexene epoxide.