Selenium-catalyzed regioselective cyclization of unsaturated carboxylic acids using hypervalent iodine oxidants

Article abstract of DOI:10.1021/ol202800k

A new and convenient selenium-catalyzed regioselective cyclization of γ, δ-unsaturated carboxylic acids to the corresponding 3, 6-dihydro-2Hpyran- 2-ones is described. The cyclization products have been obtained in good to excellent yields using diphenyl diselenide as a catalyst and [bis(trifluoroacetoxy)iodo]benzene as a stoichiometric oxidant 2011 American Chemical Society.

Full text of DOI:10.1021/ol202800k

ORGANIC
LETTERS
2011
Vol. 13, No. 24
6504–6507
Selenium-Catalyzed Regioselective
Cyclization of Unsaturated Carboxylic
Acids Using Hypervalent Iodine Oxidants
Fateh V. Singh and Thomas Wirth*
School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, U.K.
wirth@cf.ac.uk
Received October 18, 2011
ABSTRACT
A new and convenient selenium-catalyzed regioselective cyclization of γ,δ-unsaturated carboxylic acids to the corresponding 3,6-dihydro-2H-
pyran-2-ones is described. The cyclization products have been obtained in good to excellent yields using diphenyl diselenide as a catalyst and
[bis(trifluoroacetoxy)iodo]benzene as a stoichiometric oxidant.
In the past few decades, organoselenium chemistry has
been developed into an important tool in synthetic organic
chemistry. Several organoselenium reagents have been
employed in various useful synthetic transformations such
as selenenylations, selenocyclizations, selenoxide elimi-
nations, and 2,3-sigmatropic rearrangements.1 Recently,
organoselenium reagents have been used catalytically in
various synthetic transformations such as oxidation of
alcohols,2 olefins,3 and carbonyl compounds;4 elimination
reactions of diols;5 DielsꢀAlder reactions;6 and Baylisꢀ
Hillman7 and radical chain reactions.8 Recently, we have
reported the selenium-catalyzed synthesis of butenolides9
and isocoumarins10 by cyclization of β,γ-butenoic acids
and stilbene carboxylic acids, respectively. The cyclization
of γ,δ-unsaturated pentenoic acids with selenium reagents
as catalysts is still unexplored. Our target was to achieve
the synthesis of 2H-pyran-2-ones by cyclization of γ,δ-
unsaturated pentenoic acids using selenium reagents as
a catalyst. The 2H-pyran-2-one scaffolds are known for
various biological properties, and this structural motif
is found in several natural products.11 In addition, the
(1) (a) Organoselenium Chemistry; Wirth, T., Ed.; Wiley-VCH:
Weinheim, 2011. (b) Santi, C.; Santoro, S.; Battistelli, B. Curr. Org. Chem.
2010, 14, 2442. (c) Freudendahl, D. M.; Shahzad, S. A.; Wirth, T. Eur. J.
Org. Chem. 2009, 1649–1664. (d) Freudendahl, D. M.; Santoro, S.;
Shahzad, S. A.; Santi, C.; Wirth, T. Angew. Chem. 2009, 121, 8559–8562.
Angew. Chem., Int. Ed. 2009, 48, 8409–8411. (e) Browne, D. M.; Wirth,
T. Curr. Org. Chem. 2006, 10, 1893–1903. (f) Wirth, T. Angew. Chem.
2000, 112, 3890–3900. Angew. Chem., Int. Ed. 2000, 39, 3740–3751.
(g) Wirth, T. Tetrahedron 1999, 55, 1–28.
(2) (a) Onami, T.; Ikeda, M.; Woodard, S. S. Bull. Chem. Soc. Jpn.
1996, 69, 3601–3605. (b) Ehara, H.; Noguchi, M.; Sayama, S.; Onami, T.
J. Chem. Soc., Perkin Trans. 1 2000, 1429–1431. (c) van der Toorn, J. C.;
Kemperman, G.; Sheldon, R. A.; Arends, I. W. C. E. J. Org. Chem. 2009,
74, 3085–3089. (d) Singh, P.; Singh, A. K. Eur. J. Inorg. Chem. 2010,
4187–4195.
(3) (a) Betzemeier, B.; Lhermitte, F.; Knochel, P. Synlett 1999, 489–
491. (b) Goodman, M. A.; Detty, M. R. Synlett 2006, 1100–1104. (c)
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Santoro, S.; Santi, C.; Sabatini, M.; Testaferri, L.; Tiecco, M. Adv.
Synth. Catal. 2008, 350, 2881–2884. (f) Brodsky, B. H.; Du Bois, J. J.
Am. Chem. Soc. 2005, 127, 15391–15393. (g) Carrera, I.; Brovetto, M. C.;
Seoane, G. A. Tetrahedron Lett. 2006, 47, 7849–7852.
(5) Crich, D.; Neelamkavil, S.; Sartillo-Piscil, F. Org. Lett. 2000, 2,
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(6) Lenardao, E. J.; Mendes, S. R.; Ferreira, P. C.; Perin, G.; Silveira,
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Silveira, C. C. Tetrahedron Lett. 2009, 50, 5215–5217.
(8) (a) Clive, D. L. J.; Pham, M. P.; Subedi, R. J. Am. Chem. Soc.
2007, 129, 2713–2717. (b) Crich, D.; Sannigrahi, M. Tetrahedron 2002,
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(9) (a) Browne, D. M.; Niyomura, O.; Wirth, T. Org. Lett. 2007, 9,
3169–3171. (b) Browne, D. M.; Niyomura, O.; Wirth, T. Phosphorus
Sulfur 2008, 183, 1026–1035.
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Org. Chem. 2001, 66, 2429–2433. (b) Miyake, Y.; Nishibayashi, Y.;
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r
10.1021/ol202800k
Published on Web 11/15/2011
2011 American Chemical Society

2H-pyran-2-onesystem canbeusedasasyntheticprecursor
in DielsꢀAlder reactions and other ring transformations.
Herein, we report a convenient way to cyclize a series of
γ,δ-unsaturated pentenoic acids 1 to the corresponding
3,6-dihydro-2H-pyran-2-ones 2 using diphenyl diselenide
as a catalyst. The synthesis of 3,6-dihydro-2H-pyran-2-
ones 2 has been reported via a cationic, palladium-cata-
lyzed [2 þ 2] cycloadditionꢀallylic rearrangement se-
quence of ketene with R,β-unsaturated aldehydes and
ketones.12
The synthesis of the required γ,δ-unsaturated pentenoic
acids 1 was achieved by Wittig reactions of benzophenones
with the ylide generated from (3-carboxypropyl)(triphenyl)-
phosphonium bromide in THF using n-butyllithium as
base.13 The reaction products 1aꢀg were isolated in good
yields. Due to the small difference in substituents, the
NMR spectra of compounds 1bꢀg are confirming an
almost equal mixture of E and Z isomers. The synthesis
of (E)-5-phenylpent-4-enoic acid 1h was achieved by a
palladium-catalyzed Heck reaction of iodobenzene and
4-pentenoic acid in 52% yield.
the cyclic product 2a was obtained in 32% yield with more
reactive cyclic FIBA.14
Table 1. Different Hypervalent Iodine Compounds in the Cy-
clization of 1a
reaction
2a yield
entry
oxidant
PhI(OAc)2
time (min)
(%)
1
30
30
23
2
PhI(OCOCF3)2
PhI(OCOCF3)2
C6F5I(OCOCF3)2
IBA a
IBX b
FIBA c
80
3d
4
30
85
30
73
5
180
180
30
traces
ꢀ
6
7
32
a IBA: 1-Hydroxy-1,2-benziodoxol-3-(1H)-one. b IBX: 1-Hydroxy-
1,2-benziodoxol-3-(1H)-one 1-oxide. c FIBA: 5,6,7,8-Tetrafluoro-1-hy-
droxy-1,2-benziodoxol-3-(1H)-one 1-oxide. d Additional use of ultraso-
nic bath.
In addition, different polar and nonpolar solvents
were used for the cyclization of 1a using [bis(trifluoro-
acetoxy)iodo]benzene (Table 2). The cyclization reaction
proceeded well in polar and aprotic solvents such as
acetonitrileand dichloromethane (Table 2, entries 1 and 7).
The reaction was not working properly in polar and protic
solvents suchas diethyl ether, tetrahydrofuran, and metha-
nol which might be explained by their ability to coordinate
to the phenylselenenyl cation (Table 2, entries 2, 4, and 6).
The cyclized product 2a was observed in 15% yield in the
nonpolar and aprotic solvent toluene.
Initially, optimal reaction conditions and reagents for
the diphenyl diselenide catalyzed cyclization were estab-
lished using 5,5-diphenylpent-4-enoic acid 1a as a model
substrate. The cyclization reactions were performed with
1ainacetonitrile using10mol % of diphenyldiselenide asa
catalyst and 1 equiv of a hypervalent iodine reagant as an
oxidant at room temperature. The isolated product was
characterized as the six-membered, cyclized compound
6,6-diphenyl-3,6-dihydro-2H-pyran-2-one 2a as shown in
Scheme 1.
Scheme 1. Catalytic Cyclization of 1a Using Different Hyper-
valent Iodine Reagents
Table 2. Different Solvents for the Cyclization of 1a Using
[Bis(trifluoroacetoxy)iodo]benzene
reaction
2a yield
entry
solvent
time (min)
(%)
1
2
3
4
5
6
7
MeCN
THF
30
180
180
180
180
180
30
85
15
63
42
15
24
83
In order to find the best reaction conditions, we per-
formed the same reaction by using different cyclic and
acyclic hypervalent iodine reagents (Table 1). The cyc-
lized product 2a was obtained in 80% yield with [bis-
(trifluoroacetoxy)iodo]benzene (Table 1, entry 2) while
the yield was lower (23%) using the less reactive (diace-
toxyiodo)benzene. When the reaction was carried out in an
ultrasonic bath, the reaction was complete in 30 min and
the cyclized product 2a was isolated in 85% yield (Table 1,
entry 3). The fully fluorinated and more soluble reagent
[bis(trifluoroacetoxy)iodo]pentafluorobenzene was also
used, but 2a was obtained in only 73% yield. The cyclic
hypervalent iodine IBA as well as the iodine(V) reagent
IBX did not activate the diselenide sufficiently, although
DMSO
Et2O
toluene
MeOH
CH2Cl2
Finally, to optimize the amount of diphenyl diselenide
we also attempted the reaction shown in Table 2, entry 1
with 8 and 5 mol % of diphenyl diselenide, and the cyclized
product was obtained in reduced yields of 80% and 58%,
respectively. No reaction was observed in the absence of
diphenyl diselenide. Optimal conditions for the cyclization
of 1ato 2awere foundtoconsist of 1 equiv of [bis(trifluoro-
acetoxy)iodo]benzene with 10 mol % diphenyl diselenide
(12) Hattori, T.; Suzuki, Y.; Ito, Y.; Hotta, D.; Miyano, S. Tetra-
hedron 2002, 58, 5215–5223.
(13) Nicolai, S.; Erard, S.; Gonzalez, D. F.; Waser, J. Org. Lett. 2010,
12, 384–387.
(14) Richardson, R. D.; Zayed, J. M.; Altermann, S.; Smith, D.;
Wirth, T. Angew. Chem. 2007, 119, 6649–6652. Angew. Chem., Int. Ed.
2007, 46, 6529–6532.
Org. Lett., Vol. 13, No. 24, 2011
6505

in acetonitrile irradiated with ultrasound for 30 min. A
series of γ,δ-unsaturated pentenoic acids 1bꢀh were suc-
cessfully cyclized to yield the products 2bꢀh in 51ꢀ87%
yield as shown in Scheme 2. Unsymmetrically substituted
acids 1bꢀ1e and 1g were prepared and used as mixtures of
E- and Z-isomers (ratio ∼1:1).
Scheme 3. Catalytic Cyclization of Trisubstituted γ,δ-Unsatu-
rated Pentenoic Acids 3 to Lactones 4
Scheme 2. Catalytic Cyclization of γ,δ-Unsaturated Pentenoic
Acids 1 to 3,6-Dihydro-2H-pyran-2-ones 2
bromide, and elongation using carbon dioxide in three
steps (see Supporting Information). The cyclization of
compound 3a was performed under the identical reaction
conditions (ultrasound, 30 min) as described above for 1,
and the cyclized product 4a was isolated in 57% yield.
However, when the same substrate 3a was treated with the
reagent combination without ultrasound, the cyclized
product 4a was isolated in a slightly higher yield (68%).
Subsequently, the cyclization of various acids 3bꢀd to
lactones 4 was performed in good yields. The reaction
tolerated aryl substituents with differing electron demands
as shown in Table 4. Interestingly, the presence of the
methyl substituent at position C-5 in compounds 3 did not
effect the course of the reaction and five-membered cycli-
zation products were not observed.
The cyclization reactions were working smoothly with
substrates 1 having halogen bearing aromatic substituents,
and the products were isolated in good to excellent yields
(Table 3, entries 2ꢀ5). In the cyclization of 5-phenyl-5-p-
tolylpent-4-enoic acid 1g the reaction product 2g was
obtained in 55% yield. However, in contrast to products
2aꢀ2h, the reaction product 2g was not stable above room
temperature. Surprisingly, the catalytic cyclization of (E)-
5-phenylpent-4-enoic acid 1h was relatively slow and full
conversion was not achieved even after 5 h of reaction
time/sonication (Table 3, entry 8). The cyclized product 1h
was obtained in only 51% yield. Interestingly, the six-
membered selenocyclization product 8h as a reaction
intermediate was also isolated in 15% yield which supports
the mechanistic proposal (Scheme 5). The cyclization of
4-pentenoic acid 1idid not proceedat all under the reaction
conditions, and the cyclized product was detected only in
traces. This result clearly indicates that aryl substituents in
1 are necessary to achieve successful cyclizations to 2. All
reaction products were fully characterized.
Table 4. Cyclization of (E)-5-Arylhex-4-enoic Acids 3
entry
3
4 yield (%)
1
2
3
4
3a: R1 = R2 = H
68
71
74
81
3b: R1 = F, R2 = H
3c: R1 = H, R2 = F
3d: R1 = H, R2 = Et
Scheme 4. Catalytic Cyclization of 6,6-Diarylhex-5-enoic Acids
5 to 6-(Diarylmethylene)tetrahydro-2H-pyran-2-ones 6
Table 3. Cyclization of γ,δ-Unsaturated Pentenoic Acids 1
entry
1
2 yield (%)
1
2
3
4
5
6
7
8
9
1a: R1 = R2 = Ph
85
87
79
68
73
81
55a
51b
ꢀ
1b: R1 = Ph, R2 = 4-Br-C6H4
1c: R1 = Ph, R2 = 4-Cl-C6H4
1d: R1 = Ph, R2 = 4-F-C6H4
1e: R1 = Ph, R2 = 3-Cl-C6H4
1f: R1 = R2 = 4-Cl-C6H4
1g: R1 = Ph, R2 = 4-Me-C6H4
1h: R1 = H, R2 = Ph
Additionally, this approach was extended to elongated
acids 5 which were synthesized by a similar route to com-
pounds 1.13 The cyclization of these acids 5 was per-
formed under identical reaction conditions. The spec-
troscopical analysis of isolated products revealed that no
seven-membered lactones have been obtained but that an
exo-cyclization led to six-membered lactones 6 with an exo
double bond in good yields (Scheme 4). Cyclizations of
corresponding γ,δ-unsaturated alcohols at different tem-
peratures and reaction conditions lead only to decomposi-
tion products.
1i: R1 = R2 = H
a Reaction was carried out in dichloromethane. b In addition to 2h,
the selenolactone intermediate was isolated in 15% yield.
We then investigated the cyclization of of trisubstituted
γ,δ-unsaturated pentenoic acids 3 under similar reaction
conditions (Scheme 3). The synthesis of acids 3was achieved
by the addition of arylmagnesium bromide reagents to
cyclopropyl methyl ketone, ring opening/elimination by
6506
Org. Lett., Vol. 13, No. 24, 2011

have already proven by NMR experiments.9a Phenylsele-
nenyl trifluoroacetate 7 reacts with the γ,δ-unsaturated
pentenoic acid 1 to yield a selenolactone 8. The selenide
functionality of lactone 8 is then activated for elimination
by[bis(trifluoroacetoxy)iodo]benzenevia intermediate9 to
finally yield the 3,6-dihydro-2H-pyran-2-ones 2 as reaction
products. The selenium electrophile 7 is regenerated by this
process leading to the catalytic cycle (Scheme 5).
Scheme 5. Proposed Mechanism for the Catalytic Cyclization of
γ,δ-Unsaturated Pentenoic Acids 1
In summary, we have established a new approach for the
facile synthesis of different six-membered lactones from
γ,δ-unsaturated carboxylic acids using catalytic amounts
of diphenyl diselenide. Our method to synthesize these
scaffolds is very simple, economical, and metal-free. Re-
search studies about the wider scope of this approach are
currently in progress.
Acknowledgment. Financial support by the EU, FP7
IIF Marie Curie grant and the School of Chemistry,
Cardiff University, is gratefully acknowledged. We thank
the EPSRC National Mass Spectrometry Service Centre,
Swansea, for mass spectrometric data.
On the basis of our previous research efforts9a and
further evidenced by the isolation of a selenolactone as a
reaction intermediate during the catalytic cyclization of
(E)-5-phenylpent-4-enoic acid 1h, we propose a catalytic
cycle as shown in Scheme 5. The reaction is initiated by the
formation of phenylselenenyl trifluoroacetate 7 which we
Supporting Information Available. Experimental pro-
cedures and spectral data for compounds 1ꢀ6 and 8h.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Org. Lett., Vol. 13, No. 24, 2011
6507