Novel lactonization with phenonium ion participation induced by hypervalent iodine reagents

Article abstract of DOI:10.1021/ol034616f

(Matrix presented) A novel lactonization of 4-aryl-4-pentenoic acids is described using aryl-λ³-iodanes as reagents for this transformation. The hypervalent iodine species acts as a hypernucleofuge, generating intermediate phenonium ions, which react to aryl-migrated lactones.

Full text of DOI:10.1021/ol034616f

ORGANIC
LETTERS
2
003
Vol. 5, No. 12
157-2159
Novel Lactonization with Phenonium Ion
Participation Induced by Hypervalent
Iodine Reagents
2
†
‡
†
†
Amanda C. Boye, Dominik Meyer, Crystal K. Ingison, Andrew N. French, and
Thomas Wirth*
,§
Chemistry Department, Albion College, Albion, Michigan 49224, Department of
Chemistry, UniVersity of Basel, 4056 Basel, Switzerland, and Department of
Chemistry, Cardiff UniVersity, P.O. Box 912, Cardiff CF10 3TB, UK
wirth@cf.ac.uk
Received April 10, 2003
ABSTRACT
3
A novel lactonization of 4-aryl-4-pentenoic acids is described using aryl-λ -iodanes as reagents for this transformation. The hypervalent iodine
species acts as a hypernucleofuge, generating intermediate phenonium ions, which react to aryl-migrated lactones.
4
The participation of aryl groups in reactions involving
carbocations was proposed by Cram some time ago.
unsaturated systems have been carried out. We investigated
the cyclization of the unsaturated carboxylic acid 1 using
(diacetoxyiodo)benzene as the hypervalent iodine reagent.
The formation of lactone 3 was anticipated after replacement
of the hypervalent iodine moiety (a super-leaving group)5
in intermediate 2 with the acetate nucleophile. However, the
formation of product 5 was observed. The formation of 5
can be rationalized by a participation of the phenyl moiety,
which results in the formation of a phenonium ion intermedi-
ate 4. An interesting solvent effect, similar to those already
1
Different interpretations led to controversial discussions, and
2
many reports on phenonium ions have been published. The
presence of phenonium ions in reactions has now been shown
by different experimental, spectroscopic, and computational
2
b,c
methods. Despite the variety of studies in phenonium ion
chemistry, the ion has not been widely applied to synthetic
chemistry. In this paper, we report such an application in a
novel cyclization of aryl-substituted unsaturated carboxylic
acids induced by hypervalent iodine compounds.
6
7
described by Koser and Moriarty, was noted in this reaction.
When the reaction is performed at higher dilution, the yields
of 5 are quite low. In a minimum amount of solvent, the
reaction favors the formation of product 5 (87% yield).
Hypervalent iodine compounds are well-known for their
3
mild oxidative properties. These compounds can also be
used as electrophilic reagents, and various cyclizations of
†
Albion College.
University of Basel.
Cardiff University.
(3) (a) Varvoglis, A. HyperValent Iodine in Organic Synthesis; Academic
Press: Oxford, 1997. (b) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271. (c)
Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523. (d) Wirth, T.,
Ed. Top. Curr. Chem. 2003, 224.
‡
§
(1) (a) Cram, D. J. J. Am. Chem. Soc. 1949, 71, 3863. (b) Cram, D. J.;
Davis, R. J. Am. Chem. Soc. 1949, 71, 3871. (c) Cram, D. J. J. Am. Chem.
Soc. 1949, 71, 3875. (d) Cram, D. J. J. Am. Chem. Soc. 1964, 86, 3767. (e)
Brown, H. C.; Morgan, K. J.; Chloupek, F. J. J. Am. Chem. Soc. 1965, 87,
(4) Shah, M.; Taschner, M. J.; Koser, G. F.; Rach, N. L. Tetrahedron
Lett. 1986, 27, 4557.
(5) (a) Stang, P. J.; Hanack, M.; Subramanian, L. R. Synthesis 1982, 85.
(b) Ochiai, M. In Chemistry of HyperValent Compounds; Wiley-VCH:
Akiba, K., Ed.; New York, 1999, 359.
(6) Rebrovic, L.; Koser, G. F. J. Org. Chem. 1984, 49, 2462.
(7) Prakash, O.; Pahuja, S.; Goyal, S.; Sawhney, S. N.; Moriarty, R. M.
Synlett 1990, 337.
2
137.
2) (a) Vogel, P. In Carbocation Chemistry; Elsevier: Amsterdam, 1985;
Chapter 7. (b) Olah, G. A.; Porter, R. D. J. Am. Chem. Soc. 1970, 92, 7627.
c) Del Rio, E.; Men e´ ndez, M. I.; L o´ pez, R.; Sordo, T. L. J. Phys. Chem.
A 2000, 104, 5568.
(
(
1
0.1021/ol034616f CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/10/2003

Table 1. Reaction of 1 with Various Hypervalent Iodine Reagents
entry
reagent
product (low concentration, ∼0.04 M)
product (high concentration, ∼4 M)
1
2
3
4
PhI(OAc)2
PhI(OH)OTs
PhI(OCOCF3)2
IBXa
5 (20%)
6 (35%)
complex mixture
no reaction
5 (87%)
6 (52%)
6 (86%)
no reaction
a
IBX: 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide.
8
Compound 5 was identified by its spectroscopic data as well
tuted 4-aryl-4-pentenoic acids of type 7 in the lactonization
reaction. The reaction with 1 proceeded very quickly at room
temperature, but the reactions with para-substituted aryl
alkenoic acids 7 were found to be more sluggish and starting
material usually was recovered. Additionally, both unrear-
ranged compounds 8 and rearranged compounds 9 were
found as reaction products. 4-Aryl-4-pentenoic acids 7 have
as by acidic hydrolysis, which resulted in the formation of
the known carboxylic acid 6. We have also investigated
other hypervalent iodine reagents in the lactonization of 1.
9
The results are summarized in Table 1.
Scheme 1. Rearrangement Induced by Hypervalent Iodine
Reagents
Scheme 2. Electronically Different Substrates 7 for
Cyclization and Rearrangement
1
1
been synthesized by Suzuki reactions of 4-bromo-4-
1
2
pentenoic acid ethyl ester and the appropriate para-
substituted phenylboronic acids with subsequent cleavage of
the ethyl esters. The methyl-substituted carboxylic acid 7a
(
9
R ) Me) gave only 10% yield of the rearranged product
a, together with 9% yield of product 8a (R ) Me, R′ )
1
3
3
Only aryl-λ -iodanes can be used as efficient reagents for
OH, no rearrangement), and 59% of the carboxylic acid 7a
was recovered after the reaction. It was expected that
electron-donating substituents should stabilize the phenonium
a lactonization reaction of 1, whereas IBX,1 an aryl-λ -
iodane (entry 4), is too weak an electrophile to promote the
reaction. In the case of [hydroxy(tosyloxy)iodo]benzene
0
5
(
Koser reagent, entry 2) and [bis(trifluoroacetoxy)iodo]-
(11) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Littke,
A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020.
benzene (entry 3), the lactonization with subsequent aryl
migration is followed by direct hydrolysis of the ketal and
the 4-oxocarboxylic acid 6 is the only product isolated in
these reactions.
(12) Gilchrist, T. L.; Kemmitt, P. D.; Germain, A. L. Tetrahedron 1997,
53, 4447.
(
13) Representative procedure: A slurry of 7a (19.9 mg, 0.105 mmol),
(
(
diacetoxyiodo)benzene (52.5 mg, 0.163 mmol) and methylene chloride
0.05 mL) was stirred for 2 h at room temperature before adding a small
After the encouraging results obtained with (diacetoxy-
iodo)benzene as a reagent, we investigated different substi-
amount of water. After extraction with methylene chloride (three times),
the combined organic phases were dried over magnesium sulfate and
concentrated in vacuo. Silica gel chromatography (1:4 ethyl acetate/pentane)
yielded 2.2 mg (9%) of 8a and 2.4 mg (10%) of 9a as oils. 5-Hydroxy-
methyl-5-(4-methyl-phenyl)-furan-2-one (8a). 1H NMR (CDCl3, 400
MHz): δ 2.28 (s, 3H, ArCH3), 2.29-2.74 (m, 4H, CH2CH2), 3.65 (d, 1H,
J ) 14 Hz, HOCH2), 3.75 (d, 1H, J ) 14 Hz, HOCH2), 7.13-7.20 (m, 4H,
(
8) Spectroscopic data of acetic acid 2-benzyl-5-oxo-tetrahydrofuran-2-
1
yl ester 5. H NMR (CDCl3, 400 MHz): δ 1.99 (s, 3H, COOCH3), 2.09-
2
1
.75 (m, 4H, CH2CH2), 3.18 (d, 1H, J ) 14 Hz, PhCH2), 3.28 (d, 1H, J )
13
-1
4 Hz, PhCH2), 7.19-7.28 (m, 5H, ArH). C NMR (CDCl3, 100 MHz):
ArH). IR (CHCl3): ν 3524, 3018, 2242, 2253, 1725 cm . 5-Acetoxy-5-
1
δ 21.7, 28.6, 30.1, 44.4, 109.3, 127.4, 128.5, 130.7, 133.2, 169.3, 175.3.
(4-methyl-phenyl)-dihydrofuran-2-one (9a). H NMR (CDCl3, 400
-1
IR (CHCl3): ν 3684, 3028, 2400, 1794, 1751 cm . MS: m/z (rel intensity)
MHz): δ 2.00 (s, 3H, COOCH3), 2.11-2.72 (m, 4H, CH2CH2), 2.28 (s, 3
+
2
52 (65, [M + NH4 ]), 209 (42), 192 (100), 77 (5). HRMS: (C13H14O4 +
H, ArCH3), 3.14 (d, 1H, J ) 14 Hz, ArCH2), 3.22 (d, 1H, J ) 14 Hz,
+
13
NH4 ) calcd, 252.1236; found, 252.1234.
9) Betancourt de Perez, R. M.; Fuentes, L. M.; Larson, G. L.; Barnes,
C. L.; Heeg, M. J. J. Org. Chem. 1986, 51, 2039.
10) Wirth, T. Angew. Chem., Int. Ed. 2001, 40, 2812.
ArCH2), 7.06-7.12 (m, 4H, ArH). C NMR (CDCl3, 100 MHz): δ 21.5,
(
22.2, 29.1, 30.5, 44.4, 110.0, 129.6, 130.5, 131.0, 138.1, 169.5, 175.8. MS:
+
m/z (rel intensity) 266 (80, [M + NH4 ]), 224 (5), 223 (35), 206 (100),
+
(
188 (9). HRMS: (C14H16O4 + NH4 ) calcd, 266.1392; found, 266.1389.
2158
Org. Lett., Vol. 5, No. 12, 2003

ion intermediates. Recently, several publications on intra-
molecular cyclizations have appeared and only stabilized
phenonium ion intermediates were successfully employed
Scheme 3. Stepwise Rearrangement by Iodolactonization and
Subsequent Oxidation
14
in these cyclizations. Reaction of the 4-methoxy-substituted
derivative 7b (R ) OMe) with (diacetoxyiodo)benzene
resulted in a 38% yield of rearranged product 9b15 together
with 5% of an unrearranged product 8b, which has either
lost the acetoxy group during the workup or the intermediate
phenonium ion has been trapped by water (R′ ) OH). Also,
reactions with carboxylic acids 7 bearing electron-withdraw-
3
ing substituents (7c, R ) Cl; 7d, R ) CF ) have been carried
out, but only small amounts of rearranged and unrearranged
products (20-30%) have been detected by NMR along with
unreacted starting material (35-40%). The effect of the para-
substitution on the overall reaction is quite remarkable. While
it was expected that the presence of electron-donating groups
would facilitate the rearrangement process in these reactions,
this was not the case. The presence of any substituent slowed,
dramatically, the overall reaction, and mixtures of rearranged
and unrearranged products were obtained for all substrates.
Interestingly, these reactions represent the first examples of
electron-deficient aryl groups (7c,d) participating in a
phenonium ion rearrangement.
6% yield, but only to an enantiomeric excess of 4%.17 To
further prove the existence of an unstable hypervalent
5
intermediate of type 2 in the reaction pathway, we synthe-
18
sized iodolactone 11 by treatment of 1 with ICl. We
examined various methods for oxidizing 11 to the corre-
sponding hypervalent intermediate 12. While a ligand
exchange reaction with (diacetoxyiodo)benzene was unsuc-
cessful, oxidation with sodium perborate in glacial acetic
19
acid led to the formation of the rearranged compound 5,
which proves that the hypervalent iodine species 12 is a
precursor for the phenonium ion intermediate.
The chiral hypervalent iodine reagent 1016 in the cycliza-
tion of 1 described above led to the rearranged lactone 5 in
In summary, we have presented a novel lactonization and
subsequent rearrangement with phenonium ion participation.
For the first time, phenonium ion intermediates have been
generated using the feature of hypervalent iodine substituents
being hypernucleofuges in organic synthesis.
(
14) (a) Nagumo, S.; Furukawa, T.; Ono, M.; Akita, H. Tetrahedron Lett.
997, 38, 2849. (b) Nagumo, S.; Hisano, T.; Kakimoto, Y.; Kawahara, N.;
Ono, M.; Furukawa, T.; Takeda, S.; Akita, H. Tetrahedron Lett. 1998, 40,
109. (c) Nagumo, S.; Ishii, Y.; Kakimoto, Y.; Kawahara, N. Tetrahedron
1
8
Lett. 2002, 43, 5333. (d) Nagumo, S.; Ono, M.; Kakimoto, Y.; Furukawa,
T.; Hisano, T.; Mizukami, M.; Kawahara, N.; Akita, H. J. Org. Chem. 2002,
Acknowledgment. We thank the National Science Foun-
dation (INT- 9976636) for funding (A.C.B. and C.K.I.) and
the EPSRC National Mass Spectromety Service Centre,
Swansea, for mass spectrometric data.
6
7, 6618.
15) Procedure as described in ref 13: 7b (20.1 mg, 0.0975 mmol) and
diacetoxyiodo)benzene (47.7 mg, 0.148 mmol) gave 1.1 mg (5%) of 8b
(
(
and 9.7 mg (38%) of 9b. 5-Hydroxymethyl-5-(4-methoxy-phenyl)-
1
dihydro-furan-2-one (8b). H NMR (CDCl3, 400 MHz): δ 2.29-2.74 (m,
4
H, CH2CH2), 3.59-3.79 (q, 2 H, OHCH2), 3.75 (s, 3H, ArOCH3), 6.84
OL034616F
(
d, 2H, J ) 8 Hz, ArH), 7.24 (d, 2H, J ) 8 Hz, ArH). 5-Acetoxy-5-(4-
1
methoxy-phenyl)-dihydro-furan-2-one (9b). H NMR (CDCl3, 400
MHz): δ 2.09 (s, 3H, COOCH3), 2.19-2.80 (m, 4H, CH2CH2), 3.22 (d,
1
(16) Hirt, U. H.; Schuster, M. F. H.; French, A. N.; Wiest, O. G.; Wirth,
T. Eur. J. Org. Chem. 2001, 1569.
(17) Separation of the enantiomers: Daicel OD-H, hexane/2-propanol
9:1, t(minor) ) 33.0 min, t(major) ) 38.4 min.
(18) Haas, J.; Piguel, S.; Wirth, T. Org. Lett. 2002, 4, 297.
(19) McKillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299.
H, J ) 14.2 Hz, ArCH2), 3.28 (d, 1H, J ) 14.2 Hz, ArCH2), 3.82 (s, 3H,
13
ArOCH3), 6.94 (d, 2H, J ) 8 Hz, ArH), 7.22 (d, 2H, J ) 8 Hz, ArH).
C
NMR (CDCl3, 100 MHz): δ 22.2, 29.1, 30.4, 43.9, 55.6, 109.9, 114.3,
1
1
25.5, 132.2, 159.0, 169.6, 175.8. IR (CHCl3): ν 3019, 2399, 1797, 1743,
-
1
514, 1220 cm
.
Org. Lett., Vol. 5, No. 12, 2003
2159