Unprecedented direct oxygen atom transfer from hypervalent oxido-λ3-iodanes to α,β-unsaturated carbonyl compounds: Synthesis of α,β-epoxy carbonyl compounds

Article abstract of DOI:10.1021/ol006129v

Tetra-n-butylammonium oxido-λ³-iodane, prepared from 1-hydroxy-1,2-benziodoxol-3(1H)-one by reaction with tetra-n-butylammonium fluoride, directly undergoes oxygen atom transfer to γ,β-unsaturated carbonyl compounds, yielding epoxides.

Full text of DOI:10.1021/ol006129v

ORGANIC
LETTERS
2
000
Vol. 2, No. 19
923-2926
Unprecedented Direct Oxygen Atom
Transfer from Hypervalent
Oxido-λ -iodanes to r,â-Unsaturated
Carbonyl Compounds: Synthesis of
2
3
r,â-Epoxy Carbonyl Compounds
Masahito Ochiai,* Akinobu Nakanishi, and Takashi Suefuji
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima,
1-78 Shomachi, Tokushima 770-8505, Japan
mochiai@ph2.tokushima-u.ac.jp
Received May 30, 2000
ABSTRACT
3
Tetra-n-butylammonium oxido-λ -iodane, prepared from 1-hydroxy-1,2-benziodoxol-3(1H)-one by reaction with tetra-n-butylammonium fluoride,
directly undergoes oxygen atom transfer to r,â-unsaturated carbonyl compounds, yielding epoxides.
3
5
3
4
Hypervalent λ - and λ -organoiodanes are mild, selective,
â-ketoacetals and â-alkoxyesters are obtained under acidic
conditions. All of these oxidations are believed to involve
the electrophilic attack of the hypervalent iodine(III) on
enolate anions or enols generated in situ from the R,â-
unsaturated ketones via Michael addition, followed by
reductive elimination of iodobenzene. There have been no
and environmentally friendly oxidizing reagents in organic
1
3
synthesis. λ -Aryliodanes with oxygen ligands such as
iodosylbenzene, (diacetoxyiodo)benzene, and [hydroxy(tos-
yloxy)iodo]benzene oxidize R,â-unsaturated carbonyl com-
pounds and afford a variety of rearranged and unrearranged
products, depending on the reaction conditions and the
structure of substrates: for instance, oxidation of chalcones
with iodosylbenzene or its derivatives affords R-hydroxy-
3
preceding examples that involve nucleophilic attack of λ -
organoiodanes on R,â-unsaturated carbonyl compounds. We
report herein the oxidation of R,â-unsaturated carbonyl
compounds to the corresponding epoxides using a new λ -
iodane, tetra-n-butylammonium oxido-λ -iodane 2 (Scheme
). The reaction probably involves a nucleophilic attack of
the oxyanion of 2 attached to the hypervalent iodine(III) on
5
2
3
â-alkoxyacetals under basic conditions, while rearranged
3
(
1) For reviews of organoiodanes, see: (a) Koser, G. F. The Chemistry
of Functional Groups, Supplement D; Wiley: New York, 1983; Chapter
8. (b) Ochiai, M.; Nagao, Y. J. Synth. Org. Chem., Jpn. 1986, 44, 660. (c)
1
1
Moriarty, R. M.; Prakash, O. Acc. Chem. Res. 1986, 19, 244. (d) Merkushev,
E. B. Russ. Chem. ReV. 1987, 56, 826. (e) Ochiai, M. ReV. Heteroat. Chem.
the electron-deficient olefins.
1
989, 2, 92. (f) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990,
3
65. (g) Stang, P. J. Angew. Chem., Int. Ed. Engl. 1992, 31, 274. (h) Kita,
(2) (a) Moriarty, R. M.; Prakash, O.; Freeman, W. A. J. Chem. Soc.,
Chem. Commun. 1984, 927. (b) Tamura, Y.; Yakura, T.; Terashi, H.; Haruta,
J.; Kita, Y. Chem. Pharm. Bull. 1987, 35, 570.
(3) Moriarty, R. M.; Khosrowshahi, J. S.; Prakash, O. Tetrahedron Lett.
1985, 26, 2961.
(4) Singh, O. V.; Garg, C. P.; Kapoor, R. P. Synthesis 1990, 1025.
(5) Oxidation of tetracyanoethylene with iodosylbenzene affords tetra-
cyanoethylene oxide. This reaction probably involves a nucleophilic attack
of the oxygen atom of iodosylbenzene to the electron-deficient olefin. See:
Moriarty, R. M.; Gupta, S. C.; Hu, H.; Berenschot, D. R.; White, K. B. J.
Am. Chem. Soc. 1981, 103, 686.
Y.; Tohma, H.; Yakura, T. Trends Org. Chem. 1992, 3, 113. (i) Varvoglis,
A. The Organic Chemistry of Polycoordinated Iodine; VHC Publishers:
New York, 1992. (j) Koser, G. F. The Chemistry of Functional Groups,
Supplement D2; Wiley: New York, 1995; Chapter 21. (k) Kitamura, T. J.
Synth. Org. Chem., Jpn. 1995, 53, 893. (l) Stang, P. J.; Zhdankin, V. V.
Chem. ReV. 1996, 96, 1123. (m) Muraki, T.; Togo, H.; Yokoyama, M. ReV.
Heteroat. Chem. 1997, 17, 213. (n) Zhdankin, V. V.; Stang, P. J. Chemistry
of HyperValent Compounds; Wiley: New York, 1999; Chapter 11. (o)
Ochiai, M. Chemistry of HyperValent Compounds; Wiley: New York, 1999;
Chapter 12.
1
0.1021/ol006129v CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/30/2000

Iodane 2 is stable to atmospheric moisture and easily soluble
in common organic solvents.
Scheme 1
Attempted oxygen atom transfers to electron-deficient
conjugated enones were carried out without isolation of the
3
tetra-n-butylammonium oxido-λ -iodane 2: thus, exposure
of (E)-1,2-dibenzoylethylene (3a) to the crude oxidoiodane
2
(1.2 equiv), prepared as described above and dissolved in
a variety of solvents, at room temperature under nitrogen
resulted in oxygen atom transfer and afforded the epoxide 4
as a mixture of stereoisomers (Table 1). In less polar solvents
Table 1. Oxygen Atom Transfer from Oxidoiodane 2 to
Unsaturated Diketone 3aa
Epoxidation of olefins with iodosylarenes or their deriva-
tives generally requires transition metal catalysts coordinated
to porphyrins, which has been studied in detail as a model
1i,6
of cytochrome P-450 oxidation. In most cases, iodosyl-
arenes act as efficient oxygen donors toward the coordinated
metals to generate the reactive metal-oxo species. Direct
3
entry
3a
solvent
time (h)
4a (% yieldb)
ratioc
oxygen atom transfer from λ -organoiodanes to simple or
activated olefins yielding the corresponding epoxides has
been shown to be a difficult process.1i Attempts to use
iodosylbenzene as the synthetic equivalent of the hydrop-
eroxide anion in the epoxidation of conjugated enones have
1
2
3
4
5
6
7
8
9
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(Z)-3a
benzene
CH2Cl2
THF
MeCN
DMF
DMSO
HMPA
DMIe
5
5
2
5
1
5
1
1
20
1
58
64
83
77
85
82
73
83
0
70:30d
75:25d
89:11
74:26
81:19
78:22
94:6
84:16
d
83:17
87:13d
5
been reported; however, the reaction of R,â-unsaturated
-
ketones with (diacetoxyiodo)benzene/HO afforded R-dike-
tones instead of R,â-epoxy ketones.7
Synthesis of the oxygen transfer agent, tetra-n-butylam-
MeOH
3
monium oxido-λ -iodane 2, is very simple: when a THF
DMFf
1
1
0
1
12
42
3
78
solution of tetra-n-butylammonium fluoride (1 M, 0.4 mL,
DMFg
14
3
0
1
.4 mmol) was added to a stirred suspension of 1-hydroxy-
,2-benziodoxol-3(1H)-one (1) (106 mg, 0.4 mmol) in
DMF
83:17
a
The reaction was carried out using 1.2 equiv of tetra-n-butylammonium
oxido-λ3-iodane 2 at room temperature under nitrogen. b Isolated yields.
dichloromethane (5 mL) at room temperature under nitrogen,
the reaction mixture immediately turned to a colorless clear
solution. After stirring the solution for 30 min, evaporation
c
d
Ratio of trans-4a:cis-4a. A large amount of 3a was recovered as a mixture
of stereoisomers. e DMI: 1,3-dimethyl-2-imidazolidinone. NaH was used
f
g
5
as a base instead of n-Bu4NF. Oxido-λ -iodane 6 was used instead of
oxido-λ -iodane 2.
3
of solvents gave oxidoiodane 2 as a solid of high purity (by
1
2 2
H NMR). Recrystallization from AcOEt/CH Cl /hexane
8
,9
gave iodane 2 (162 mg, 80%) as colorless crystals. The
facile formation of salt 2 is probably due to the high acidity
such as dichloromethane and benzene, the oxygen transfer
reaction is slow and epoxide 4 was obtained in moderate
yields (50-60%) (Table 1, entries 1 and 2). No epoxidation
was observed when the reaction was carried out in the protic
solvent methanol. Increased solvation to the oxygen atom
of the apical OH group of o-iodosylbenzoic acid 1 with pK
a
9
c
)
7.25. The bicyclic structure of 2 was confirmed by the
carbonyl absorption band (1616 cm ) in its IR spectrum.
-1
9a,10
(
6) (a) Groves, J. T.; Nemo, T. E.; Myers, R. S. J. Am. Chem. Soc. 1979,
01, 1032. (b) Meunier, B. Chem. ReV. 1992, 92, 1411.
7) Reaction of (diacetoxyiodo)benzene with hydroxide anion produces
iodosylbenzene. See: Saltzman, H.; Sharefkin, J. G. Org. Synth. 1963, 43,
0.
3
of oxido-λ -iodane 2 via hydrogen bonding results in
1
(
decreased nucleophilicity of iodane 2, and therefore unsatur-
ated diketone 3a was recovered as a mixture of stereoisomers.
Dipolar aprotic solvents including DMF, DMSO, MeCN,
DMI, HMPA, and THF gave good yields (73-85%) of trans
epoxide 4a with more than 80% stereoselectivity (Table 1,
entries 3-8).
Z)-Isomer 3a also afforded an 83:17 mixture of trans-
and cis-4a in the reaction with oxidoiodane 2 in DMF (Table
, entry 12). Facile base-catalyzed isomerization of diketone
6
(
8) Tetra-n-butylammonium 1-oxido-1,2-benziodoxol-3(1H)-one (2):
-
1 1
mp 128-129 °C; IR (KBr) 2961, 1616, 1592, 1348, 752, 668 cm ; H
NMR (CDCl3) δ 8.11 (dd, J ) 7.5, 1.3 Hz, 1H), 7.95 (d, J ) 7.8 Hz, 1H),
7
.64 (ddd, J ) 7.8, 7.6, 1.3 Hz, 1H), 7.47 (dd, J ) 7.6, 7.5 Hz, 1H), 3.26
(
m, 8H), 1.63 (quint, J ) 7.4 Hz, 8H), 1.44 (sext, J ) 7.4 Hz, 8H), 0.99 (t,
13
J ) 7.4 Hz, 12H); C NMR (CDCl3) δ 169.0, 134.0, 132.0, 130.4, 128.5,
(
1
24.7, 121.1, 58.7, 23.9, 19.7, 13.6; FAB MS m/z negative 263 [(M -
+
+
n-Bu4N) ], positive 242 (n-Bu4N) . Anal. Calcd for C23H40INO3: C, 54.65;
H, 7.98; N, 2.77. Found: C, 54.26; H, 7.95; N, 2.75.
1
(9) For syntheses of sodium, calcium, and ammonium 2-iodosylbenzoates,
which show low solubility toward common organic solvents, see: (a) Baker,
G. P.; Mann, F. G.; Sheppard, N.; Tetlow, A. J. J. Chem. Soc. 1965, 3721.
3a under these conditions seems to be responsible for
(
b) Siebert, H.; Handrich, M. Z. Anorg. Allg. Chem. 1976, 426, 173. (c)
Moss, R. A.; Alwis, K. W.; Bizzigotti, G. O. J. Am. Chem. Soc. 1983, 105,
81. (d) Moss, R. A.; Wilk, B.; Krogh-Jespersen, K.; Blair, J. T.; Westbrook,
J. D. J. Am. Chem. Soc. 1989, 111, 250.
(10) For X-ray structure analysis of sodium 2-iodosylbenzoates, see:
Katritzky, A. R.; Savage, G. P.; Palenik, G. J.; Qian, K.; Zhang, Z. J. Chem.
Soc., Perkin Trans. 2 1990, 1657.
6
2924
Org. Lett., Vol. 2, No. 19, 2000

Table 2. Epoxidation of R,â-Unsaturated Carbonyl Compounds 3 with Oxidoiodane 2 at 50 °C
a
The reaction was carried out under nitrogen. b Isolated yields. c 3b (39%) was recovered unchanged. d 3c (20%) was recovered unchanged. e 3d (37%)
was recovered unchanged.
11
extensive stereoconvergence in the epoxidation; in fact, the
diketones (E)- and (Z)-3a rapidly isomerize to the equilibrium
mixture (E:Z ) 70-76:24-30) even under less basic
conditions using tetra-n-butylammonium acetate (DMF/rt/3
h).
2-cyclohexenone 3b returned a large amount of the olefin
and afforded R,â-epoxy ketone 4b in only 9% yield.
Sterically less hindered 3e and highly electron deficient
olefins 3f-h afforded a reasonable yield of epoxides 4e-h.
Exclusive retention of stereochemistry of olefins was ob-
served in the epoxidation of 3c,d, in which no isomerization
of olefins takes place under these conditions.
The epoxidation of R,â-unsaturated carbonyl compounds
probably involves Michael-type addition of oxidoiodane 2
and produces enolate anion 7 (Scheme 2). The leaving ability
3
15
of the λ -iodanyl group of 7 is high, and therefore,
intramolecular cyclization of 7 with reductive elimination
of o-iodobenzoate anion 8 gives the epoxide with retention
of stereochemistry.
3
Sodium oxido-λ -iodane 5, an effective catalyst for the
hydrolysis of esters and phosphates in aqueous micellar
cetyltrimethylammonium chloride solutions at pH 8,
9c,12
also
cause epoxidation of (E)-3a in DMF at room temperature,
Scheme 2
albeit in low yield (Table 1, entry 10). On the other hand,
5
13
reactivity of tetra-n-butylammonium oxido-λ -iodane 6 for
the oxygen atom transfer appears to be low and a large
amount of the unsaturated diketone 3a was recovered (Table
1, entry 11). This is probably due to the decreased nucleo-
philicity of the anionic oxygen atom of 6 directly bonded to
the more electronegative pentavalent iodine.12
Table 2 summarizes the results of the epoxidation of
electron-deficient olefins at 50 °C. Nucleophilicity of oxi-
doiodane 2 seems to be moderate,14 because the reaction of
(
11) The recovered diketone 3a in this epoxidation always consists of a
mixture of (E)- and (Z)-isomers.
12) Moss, R. A.; Alwis, K. W.; Shin, J. J. Am. Chem. Soc. 1984, 106,
651.
13) Frigerio, M.; Santagostino, M.; Sputore, S.; Palmisano, G. J. Org.
(
2
(
Chem. 1995, 60, 7272.
Org. Lett., Vol. 2, No. 19, 2000
2925

Acknowledgment. We wish to acknowledge financial
support by a Grant-in-Aid for Scientific Research on Priority
Areas (A) “The Chemistry of Inter-element Linkage” (No.
09239102) from the Ministry of Education, Science, Sports
and Culture, Japan.
OL006129V
3
(
14) The oxido anion of λ -iodane 2 exhibits a modest R-effect. (a) Moss,
R. A.; Swarup, S.; Ganguli, S. J. Chem. Soc., Chem. Commun. 1987, 860.
b) Colthurst, M. J.; Kanagasooriam, A. J.; Wong, M. S.; Contini, C.;
Williams, A. Can. J. Chem. 1998, 76, 678.
3
(
(15) The λ -phenyliodanyl group shows a very high leaving group ability
and is called a hyperleaving group. See ref 1o.
2926
Org. Lett., Vol. 2, No. 19, 2000