Catalytic addition-elimination reactions towards butenolides

Article abstract of DOI:10.1080/10426500801901053

A wide range of selenium-containing reagents are known to undergo addition - elimination reactions under different reaction conditions. We report on selenium electrophiles, which are regenerated under the reaction conditions employed, and therefore only catalytic amounts of these reagents are necessary.

Full text of DOI:10.1080/10426500801901053

This article was downloaded by: [University of California Santa Cruz]
On: 28 March 2013, At: 10:39
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Catalytic Addition-Elimination
Reactions Towards Butenolides
Danielle M. Browne a , Osamu Niyomura a & Thomas
Wirth a
a School of Chemistry, Cardiff University, Cardiff,
United Kingdom
Version of record first published: 29 Oct 2008.
To cite this article: Danielle M. Browne , Osamu Niyomura & Thomas Wirth (2008):
Catalytic Addition-Elimination Reactions Towards Butenolides, Phosphorus, Sulfur, and
Silicon and the Related Elements, 183:4, 1026-1035
To link to this article: http://dx.doi.org/10.1080/10426500801901053
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages

whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 183:1026–1035, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801901053
Catalytic Addition-Elimination Reactions Towards
Butenolides
Danielle M. Browne, Osamu Niyomura,
and Thomas Wirth
School of Chemistry, Cardiff University, Cardiff, United Kingdom
A wide range of selenium-containing reagents are known to undergo addition –
elimination reactions under different reaction conditions. We report on selenium
electrophiles, which are regenerated under the reaction conditions employed, and
therefore only catalytic amounts of these reagents are necessary.
Keywords Butenolides; diselenides; selenium electrophiles; stereoselective synthesis
INTRODUCTION
For several decades now, selenium reagents have attracted growing
interest for their application in organic synthesis.1,2 Selenium dioxide
is a well known and traditionally used oxidizing agent for alkenes, ke-
tones and other substrates, but it was not until 1977 that Umbreit and
Sharpless found that only catalytic amounts of selenium dioxide could
be used to functionalize alkenes.3 Phenylseleninic acid (Ph-SeO2H) has
been used as a catalyst for the epoxidation of alkenes and Baeyer-
Villiger oxidations. In addition, polystyrene bound arylseleninic acid
can be used in catalytic amounts in the oxidation of alkenes, ketones
and aromatic systems, which have avoided the contamination of re-
action products. It was found that the catalyst is stable to the reac-
tion conditions and can be recycled with no apparent loss of activity.4
Knochel and coworkers reported the use of organoselenium reagents
containing perfluoroalkyl substituents in flourous solvents in similar
transformations.5 The butylselenide pre-catalyst 1 is oxidized to the
corresponding selenenic acid under the reaction conditions while the
fluorous biphasic catalysis allowed efficient separation of the catalyst
We are thankful for the high-resolution mass spectrometric data obtained from the
EPSRC National Mass Spectrometry Service Centre, Swansea, UK. We thank EPSRC
for support.
Address correspondence to Thomas Wirth, School of Chemistry, Cardiff University,
Cardiff CF10 3AT, United Kingdom. E-mail: wirth@cf.ac.uk
1026

Catalytic Addition-Elimination Reactions Towards Butenolides
1027
from the reaction mixture. The catalyst could be recycled more than ten
times without either decrease in yields or increase in reaction times. A
typical epoxidation is shown below.
Selenenylation-deselenenylation sequences provide double bond
transpositioned allylic alcohols and ethers from alkenes. The sequence
involves two steps: Selenenylation with PhSeX (X = Cl, OR, NR2) fol-
lowed by oxidation with O3, NaIO4, or peroxides (H2O2, t-BuOOH,
mCPBA) where stoichiometric amounts of PhSeX and large excess of
oxidant are normally required. It was found by Torii et al. that this
could be achieved in a single step by electrochemical generation of sele-
nium electrophiles from catalytic amounts of diphenyl diselenide.6 This
was achieved without the formation of phenylseleninic acid and selen-
amide and in the absence of peroxides. Electrochemically generated
phenylselenenyl electrophiles react regioselectively with alkenes pro-
ducing the selenide, followed by electrochemical oxidation to provide the
corresponding selenoxide, which instantly undergoes syn-elimination to
give the desired product.
The selenenylation reagent is regenerated in situ and the transfor-
mation is enhanced by the addition of metal salts such as magnesium
sulfate. This is increasing the yields of the corresponding products by
preventing the reaction to phenylselenenic acid and phenylseleninic
acid both by disproportionation and electro-oxidation.
Further developments by Wirth et al. showed that the electrochem-
ical oxyselenenylation-deselenenylation conversion of alkenes into al-
lylic compounds can be successfully achieved with catalytic amounts
of diphenyl diselenide (10 mol%) or other enantiomerically pure di-
selenides using acceptor substituted alkenes such as 2 as substrates.7
Tetraethylammonium bromide was employed in the reaction to act as
both, a redox catalyst and an electrolyte. The reaction is initiated by the

1028
D. M. Brown et al.
anodic oxidation of bromide to bromine, which reacts with the diselenide
to form the corresponding arylselenenyl bromide. After addition to the
alkene and formation of the selenide, a second equivalent of bromine
forms an unstable tetravalent selenium derivative, which acts as a good
leaving group thus generating the elimination product 3. Compound 3
has been obtained with up to 66% ee with 10 mol% of diselenide 4 in
place of diphenyl diselenide in this reaction.
The reaction sequence developed by Tomoada et al. employs nitrogen-
containing enantiomerically pure selenium reagents as catalysts in the
presence of copper(II) nitrate for the conversion of alkenes into the
allylic compounds.8 After screening a range of oxidizing agents, it was
found that sodium persulfate was best for the catalytic reaction. Higher
˚
conversions were observed using 3A molecular sieves, showing that
the removal of water is essential for the reaction to proceed. Still the
reaction is sluggish and turnover numbers are low.
This prompted work by Tiecco et al. to convert α,β-unsaturated es-
ters, amides, and nitriles into α-alkoxy or α-hydroxy derivatives.9 They
developed a multistep one-pot synthesis using excess ammonium per-
sulfate and using only catalytic amounts of diphenyl diselenide. They
have shown that the intermediate alkylphenyl selenides reacts with the
persulfates regioselectively towards the elimination products 5, which
were obtained in good yields (23–90%) in just a few hours. An electron-
withdrawing group in the allylic position is essential for the success
of the reaction as simple unsubstituted alkenes gave rise to product
mixtures.
Tiecco et al. also carried out intermolecular versions of this cat-
alytic oxidation to produce butenolides, which are obtained from the
reaction of the easily available β,γ -unsaturated acids with catalytic
amounts of diphenyl diselenide and an excess of ammonium persulfate

Catalytic Addition-Elimination Reactions Towards Butenolides
1029
in acetonitrile.10 The carboxy group is found to act as both an internal
nucleophile and as an electron withdrawing group in the γ position and
again produces good yields in relatively short reaction times. It was also
observed in some cases that better yields were obtained with the cat-
alytic reaction compared to using stoichiometric amounts of diphenyl
diselenide.
Tiecco and coworkers has taken this one step further and utilizes
the previous reaction conditions to convert alkenols to the correspond-
ing 2,5-dihydrofurans.11 Excellent yields were obtained (90–96%) with
traces of a side product. The cyclization - elimination process gives rise
to two stereoisomeric of the 2,5-dihydrofurans in good yields, where
the selectivity reflects the steric demands in the approach of the elec-
trophile to the π-bond. Erythro-unsaturated alcohols yield trans-2,5-
dihydrofurans whereas the threo-unsaturated alcohols gave the cis-
products. The observed stereoselecitvities of the process imply that
only the major isomer of the intermediate undergoes elimination to
afford the corresponding 2,5-dihydrofurans. When ammonium persul-
fate was reacted with the major isomer of the intermediate the de-
sired product was quantitatively transformed, where as the minor
isomer gave unidentified products, showing the cis relationship ren-
ders the approach of the persulfate anion to the selenium atom more
difficult.
Tomoda et al. reported the first catalytic asymmetric conversion of
trans-β-methyl styrene into optically active allylic ethers using diaryl
diselenides with a chiral pyrrolidine moiety in the ortho-position.12
Yields of 24% and enantioselectivities of up to 32% ee were observed
using previous literature methods and with copper(II) nitrate. The mod-
erate asymmetric induction is believed to be due the strong interaction
between the electrophilic selenium atom and the tertiary nitrogen of
the chiral pyrrolidine moiety.
The highest diastereoselectivities (96% de) of asymmetric methoxy-
selenenylation of alkenes together with excellent chemical yields (99%)
were achieved using ferrocenyl selenium triflates.13 Diselenide 6 is the
precursor for the electrophile and when applied to a range of alkenes
all resulted in high yields (96–99%) and moderate to high diastereose-
lectivities (15–96%). It was observed that sterically large groups in the
alkene are necessary to achieve high facial selectivity.
In 1998, Wirth and coworkers used peroxydisulfates for the
generation of the nitrogen containing selenium electrophile for
the catalytic oxyselenenylation-elimination reaction with trans-β
methylstyrene.14 It is known that metal ions can accelerate the
decomposition of peroxo disulfates and varying the metal salts was
found to have a strong influence on the stereoselectivity with nickel

1030
D. M. Brown et al.
nitrate being the most effective salt with ee’s of up to 71% and when
diselenide 7 was used enantioselectivities of up to 75% was observed.
These are the highest enantioselecitivities obtained for the catalytic
oxyselenenylation-elimination reaction so far obtained, but a major
drawback was again the low turnover number.
RESULTS AND DISCUSSION
In recent work on the cyclization of alkenoic acids 8 into the corre-
sponding butenolides 9, we found that acetonitrile, 5 mol% diphenyl
diselenide as a catalyst and bis(trifluoroacetoxy)iodobenzene as the
oxidant were the optimum conditions for this reaction procedure.15
Lower catalytic loading resulted in the rearranged products 10 be-
cause the hypervalent iodine reagent then directly reacts with the
substrate.
Full conversion to the products was observed only with diphenyl
diselenide. Diphenyl disulfide showed less reactivity, and diphenyl
ditelluride reacted even slower, as well. This lower reactivity is then
reflected in the increased amount of rearranged product 10, which
results from the direct reaction of alkene 8 with the hypervalent
iodine oxidant. If performed in acetonitrile, the capture of the inter-
mediate phenonium ion by acetonitrile and subsequent hydrolysis
led to the formation of the by-product 10. A range of other dichalco-
gen catalysts was also tested and the results are summarized in
Table I.
From the results in Table I, it can be clearly seen that diselenides are
the better catalysts, where diphenyl diselenide having superior yields to

Catalytic Addition-Elimination Reactions Towards Butenolides
1031
TABLE I Different Dichalcogen Catalysts for the
Addition / Elimination Sequence
Catalyst
13 : 14 (Ratio)
Yield (%)
(PhSe)2
(MeSe)2
(PhS)2
(MeS)2
(PhTe)2
100:0
100:0
70
56
—
—
—
25:75a
25:75a
28:72a
aDetermined by NMR.
dimethyl diselenide. The other results indicate that the other catalysts
are not as active as the diselenides and give mainly the rearranged
product that correlate with the results of using lower catalytic loadings
with diphenyl diselenide or no catalyst at all.
For the investigation of trisubstituted alkenes in such cyclization
reactions, (E)-4-phenylpent-3-enoic acid 11 was synthesized. The cy-
clization resulted in a mixture of products and compounds 13 and 14
were observed.
After the initial selenolactonization to 12, the elimination to
13 occurred similar to disubstituted alkene substrates. 4-Oxo-3-
phenylpentanoic acid 14 was found as a by-product, but without the
diselenide catalyst, 14 was the only product being formed. The reaction
of bis(trifluoroacetoxy)iodobenzene with 11 leads, after cyclization, to
a phenyl migration via phenonium ion 15 and reaction with trifluo-
roacetate or water and subsequent ring-opening of the ketal results in
the formation of 14. Compound 12 was also synthesized independently
to investigate its further oxidation. The elimination product 13 (86%
yield) was the only product observed and no rearranged product 14
was detected. The rearrangement to 14 therefore occurs only via the
direct reaction of 11 with bis(trifluoroacetoxy)iodobenzene.

1032
D. M. Brown et al.
EXPERIMENTAL
General
1H and 13C NMR experiments were carried out on a Bruker 400-DPX
spectrometer. IR measurements were taken using a Perkin-Elmer 1600
FTIR spectrometer as a liquid film. Low-resolution mass spectrometry
was carried out using a Varian Saturn 2 GC-MS. Flash chromatography
was completed using Fisher Silica Gel (35–70 mesh). Preparative thin
layer chromatography was carried out using Merck silica gel 60 F254
on glass plates. All solvents used were dried and purified by standard
methods. Reactions requiring the exclusion of air were carried out under
an atmosphere of argon in oven-dried glassware.
5-Phenylfuran-2(5H)-one (9)16
Colorless oil, (24 mg, 70%); 1H NMR (400 MHz, CDCl3): δ = 7.53 (1H,
dd,J 5.5, 1.6 Hz, H-4), 7.40–7.35 (3H, m, H-7,9), 7.30–7.25 (2H, m, H-8),
6.23 (1H, dd, J 5.5, 2.0 Hz, H-5), 6.01 (1H, dd, J 2.0, 1.6 Hz, H-3) ppm;
13C NMR (63 MHz, CDCl3): δ = 173.1 (C-2), 155.9 (C-4), 134.3 (C-6),
129.4 (C-9), 129.2 (2C, C-8), 126.5 (2C, C-7), 120.1 (C-3), 84.4 (C-5) ppm.
N-(5-Oxo-3-phenyltetrahydrofuran-2-yl)ethanamide (10)
Colorless oil, (29 mg, 28%); IR (film): νmax = 3299, 1782, 1678, 1541,
1372, 1260, 1166, 943, 826, 732, 698 cm–1; 1H NMR (400 MHz, CDCl3):
δ = 7.12–7. 38 (5H, m, H-1,2,3), 6.15 (1H, dd, J 7.7, 1.4 Hz, H-8), 3.55
(1H, q, J 9.1 Hz, H-5), 3.00 (1H, dd, J 8.8, 17.6 Hz, H-6a), 2.70 (1H,
dd, J 10.7, 17.6 Hz, H-6b), 1.95 (3H, s, H-10) ppm; 13C NMR (63 MHz,
CDCl3): δ = 174.3 (C-7), 171.4 (C-9), 136.9 (C-4), 129.3 (2C, C-2), 128.2
(C-1), 127.1 (2C, C-3), 86.1 (C-8), 46.9 (C-5), 37.2 (C-6), 23.2 (C-10)

Catalytic Addition-Elimination Reactions Towards Butenolides
1033
ppm; MS: m/z(%): 160 (M+100), 178 (58), 201 (70), 220 (18); HRMS
C12H14NO3: found 220.0979, calcd. 220.0974.
(E)-4-Phenylpent-3-enoic acid (11)17
2-Phenylpropanal (10 mmol, 1.34 g) and malonic acid (10 mmol, 1.04
g) was mixed thoroughly with chromatography grade silica (200 mesh,
1 g) and the resulting powder in a microwave tube was subjected to mi-
crowave irradiation (300 W, 50◦C, 10 min). The reaction mixture was al-
lowed to cool to room temperature and extracted with dichloromethane
(30 mL). The solvent was removed under reduced pressure the com-
pound was purified by flash chromatography eluting with petroleum
ether:ethyl acetate:acetic acid (90:8:2).18
White solid (689 mg, 41%); m.p. = 56–58◦C; IR (film): νmax = 3583,
–1
3055, 2360, 2341, 1699, 1444, 1392, 1287, 939, 818, 748, 696, 666 cm
;
1H NMR (400 MHz, CDCl3): δ = 7.41–7.45 (2H, m, H-7,11), 7.32–7.37
(2H, m, H-8, 10), 7.26–7.29 (1H, m, H-9), 5.96 (1H, td, J 7.0, 1.4 Hz,
H-3), 3.34 (2H, d, J 7.2 Hz, H-2), 2.13 (3H, s, H-5) ppm; 13C NMR (63
MHz, CDCl3): δ = 178.2 (C-1), 142.9 (C-6), 138.7 (C-4), 128.8 (C-8, 10),
128.3 (C-9), 125.8 (C-7, 11), 118.4 (C-3), 34.2 (C-2), 16.3 (C-5) ppm;
MS: m/z(%): 176 (M+44), 131 (100), 91 (38); HRMS C11H12O2: found
176.0830, calcd. 176.0837.
Dihydro-5-methyl-5-phenyl-4-(phenylselenyl)furan-2(3H)-one
(12)
To a solution of diselenide (0.6 mmol) in acetonitrile (10 mL)
(E)-4-phenylbut-3-enoic acid (1.2 mmol) was added, followed by
bis(trifluoroacetoxy)iodobenzene (0.6 mmol) and the mixture stirred

1034
D. M. Brown et al.
under argon at room temperature until TLC showed no remaining start-
ing material. The solvent was then evaporated under reduced pressure
and the residue was purified immediately by flash column chromatog-
raphy eluting with ethyl acetate : light petroleum (2:8) to yield the
addition products.
IR (film): νmax = 3016, 2918, 2860, 1608, 1472, 1375, 1037, 835, 687
1
cm–1; H NMR (400 MHz, CDCl3): δ = 7.37–7.43 (4H, m, H-Ar), 7.15–
7.30 (6H, m, H-Ar), 3.95 (1H, t, J 7.5 Hz, H-3), 2.85 (1H, dd, J 18.0, 7.8
Hz, H-2a), 2.70 (1H, dd, J 18.0, 7.3 Hz, H-2b) ppm; 13C NMR (63 MHz,
CDCl3): δ = 174.2 (C-1), 143.2 (C-5), 134.9 (2C, C-10), 129.5 (2C, C-11),
128.7 (2C, C-7), 128.5 (C-12), 128.1 (C-8), 127.7 (C-9) 124.3 (2C, C-6),
89.0 (C-4), 48.2 (C-3), 37.8 (C-2), 25.7 (C-13) ppm; MS: m/z(%): 332 (M+,
8), 314 (20), 234 (10), 184 (26), 159 (56), 131 (100), 103 (35), 91 (9), 77
(70); HRMS C17H16O2Se: found 332.0314, calcd. 332.0316.
General Procedure for the Catalytic Reaction
To a solution of diphenyl diselenide (5 mol%, 3.4 mg, 0.01 mmol) in
acetonitrile (3 mL) was added the β,γ -unsaturated acid (0.22 mmol),
followed by bis(trifluoroacetoxy)iodobenzene (100 mg, 0.23 mmol) and
the mixture stirred under argon at room temperature until TLC showed
no remaining starting material. The solvent was then evaporated under
reduced pressure and the residue was purified immediately by flash
column chromatography eluting with ethyl acetate : light petroleum
(2:8) to yield the cyclization products.
5-Methyl-5-phenylfuran-2(5H)-one (13)19
1H NMR (400 MHz, CDCl3): δ = 7.57 (1H, d, J 5.5 Hz, H-3), 7.20-7.40
(5H, m, H-6,7,8), 5.98 (1H, d, J 5.5 Hz, H-2), 1.78 (3H, s, H-11) ppm;
13C NMR (63 MHz, CDCl3): δ = 172.4 (C-1), 160.4 (C-3), 139.3 (C-5),
128.9 (2C, C-7), 128.4 (C-8), 124.8 (2C, C-6), 119.4 (C-2), 88.9 (C-4), 26.4
(C-11) ppm.
4-Oxo-3-phenylpentanoic acid (14)20
1H NMR (400 MHz, CDCl3): δ = 7.20–7.40 (5H, m, H-7,8,9), 4.10 (1H,
dd, J 9.8, 4.7 Hz, H-3), 3.20 (1H, dd, J 17.4, 9.9 Hz, H-2a), 2.50 (1H,

Catalytic Addition-Elimination Reactions Towards Butenolides
1035
dd, J 17.4, 4.7 Hz, H-2b), 2.05 (3H, s, H-5) ppm; 13C NMR (63 MHz,
CDCl3): δ = 206.8 (C-4), 177.8 (C-1), 142.9 (C-6), 128.9 (2C, C-7), 127.9
(2C, C-8), 127.3 (C-9), 54.6 (C-3), 36.7 (C-5), 28.8 (C-2) ppm.
REFERENCES
[1] T. G. Back, Ed., Organoselenium Chemistry (Oxford University Press, Oxford, 1999).
[2] T. Wirth, Ed., Top. Curr. Chem. (Springer, Berlin, 2000), Vol. 208.
[3] M. A. Umbreit and K. B. Sharpless, J. Am. Chem. Soc., 99, 5526 (1977).
[4] R. T. Taylor and L. A. Flood, J. Org. Chem., 48, 5160 (1983).
[5] B. Betzemeier, F. Lhermitte, and P. Knochel, Synlett, 489 (1999).
[6] S. Torii, K. Uneyama, M. Ono, and T. Bannou, J. Am. Chem. Soc., 103, 4606 (1981).
[7] O. Niyomura, M. Cox, and T. Wirth, Synlett, 251 (2006).
[8] M. Iwaoka and S. Tomoda, J. Chem. Soc., Chem Commun., 1165 (1992).
[9] M. Tiecco, L. Testaferri, M. Tingoli, L. Bagnoli, and C. Santi, J. Chem. Soc., Chem.
Commun., 637 (1993).
[10] M. Tiecco, L. Testaferri, M. Tingoli, L. Bagnoli, and C. Santi, Synlett, 798 (1993).
[11] M. Tiecco, L. Testaferri, and C. Santi, Eur. J. Org. Chem., 797 (1999).
[12] K. Fujita, M. Iwaoka, and S. Tomoda, Chem. Lett., 923 (1994).
[13] S. Fukuzawa, K. Takahashi, H. Kato, and H. Yamazaki, J. Org. Chem., 62, 7711
(1997).
[14] T. Wirth, S. Ha¨uptli, and M. Leuenberger, Tetrahedron: Asymmetry, 9, 547 (1998).
[15] D. M. Browne, O. Niyomura, and T. Wirth, Org. Lett., 9, 3169 (2007).
[16] M. Renard and L. A. Ghosez, Tetrahedron, 57, 2597 (2001).
[17] M. C. Kloetzel, J. Am. Chem. Soc., 62, 1708 (1940).
[18] S. H. M. Kumar, S. B. V. Reddy, J. E. Reddy, and J. S. Yadav, Tetrahedron Lett., 40,
2401 (1999).
[19] Y.-Z. Chen, L.-Z. Wu, M.-L. Peng, D. Zhang, L.-P. Zhang, and C.-H. Tung, Tetrahe-
dron, 62, 10688 (2006).
[20] D. J. Fairfax, D. J. Austin, S. L. Xu, and A. Padwa, J. Chem. Soc., Perkin Trans. 1,
2837 (1992).