Chemoselective epoxidation of electron deficient enones with iodosylbenzene

Article abstract of DOI:10.1055/s-2004-832814

The epoxidation of electron deficient olefins is demonstrated with PhIO and an assortment of enones.

Full text of DOI:10.1055/s-2004-832814

LETTER
2403
Chemoselective Epoxidation of Electron Deficient Enones with Iodosylbenzene
Chemoselective
Ep
oxidationo
v
f
Electron
D
i
eficien
n
t
E
nones M. McQuaid, Thomas R. R. Pettus*
Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, CA 93106-9510, USA
Fax 805-893-5690; E-mail: pettus@chem.ucsb
Received 13 May 2004
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Abstract: The epoxidation of electron deficient olefins is demon-
strated with PhIO and an assortment of enones.
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*
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*
Key words: enone epoxidation, iodosylbenzene, enones
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Scheme 2
Iodosylbenzene (PhIO) is widely used as an oxygen
source.1 It is made by treatment of PhI(OAc)2 with sodium
hydroxide.2 Iodosylbenzene is a polymeric substance with
the characteristic [T] shape common for I(III) compounds
(Figure 1).3 While resembling most hypervalent com-
pounds in regard to thermal instability,4 the polymeric and
insoluble nature of iodosylbenzene decreases its reactivity
as an oxidant.
In the same report, the conversion of ketenes to polyesters
is proposed to proceed through a similar process by epoxi-
dation of a ketene intermediate (Scheme 2).9 This sug-
gests that PhIO might epoxidize other electron deficient
alkenes.
To determine the scope of this reaction, a series of enones
were examined in combination with iodosylbenzene
(Table 1, entries 1–10). CDCl3 was used as the solvent,
which thereby enabled the reactions to be followed by
1H NMR. The bromo-enone 19 and PhIO prove unreactive
under these conditions (entry 1). Similarly, the diesters
2–4 are recovered unchanged along with PhIO (entry
2–4). It is interesting to note, however, that the cyclo-
hexenone 5,10 which is presumed to form a similarly sta-
bilized anion, undergoes reaction with iodosylbenzene to
furnish the epoxide 611 in 90% yield (entry 5). The cyclo-
hexenone 7, which proves difficult to handle and store be-
cause of its propensity towards enolization,12 affords the
corresponding epoxide 8 in a 45% yield along with the
trione 17 (entry 6).13 The a-sulfonated cyclohexenone 914
affords the epoxide 1015 in a 91% yield (entry 7). To our
surprise, the nitrile cyclohexenone derivative 11,16 ap-
pears to lead to the decomposition of iodosylbenzene.
However, addition of 4.1 equivalents of PhIO produces
the epoxide 1217 in a respectable 75% yield (entry 8). The
Meldrums acid derivative 1318 undergoes epoxidation
very rapidly (<2 h) to afford the epoxide 1419 in >95%
yield (entry 9).
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Figure 1
During a recent synthesis of epoxysorbicillinol,5 we found
that the most electron deficient enone contained within 15
undergoes chemoselective and diastereoselective epoxi-
dation with PhIO (0.1 M in CH3NO2) to afford 16 in a
92% yield (Table 1, entry 10). Presumably, the oxygen
atom of PhIO serves as a nucleophile in this transforma-
tion. This reactivity, commonly observed with ROO– sys-
tems, has rarely been observed with I(III) reagents.6
Although predicted by theoretical calculations,7 careful
scrutiny of the literature reveals only one example, where
unmodified iodosylbenzene has been reported to effect an
epoxidation of an electron deficient olefin (Scheme 1).8
NC
NC
CN
O
On the basis of this series of compounds, we speculate
that a correlation exists between reactivity of substrates
with PhIO and the stability of the anticipated anionic
intermediate. Highly electron deficient enones, where the
resulting anion should be fairly stable with the PKa of
conjugate acid <14.2, appear to smoothly undergo this
epoxidation procedure. The only substrate that does not fit
this reasoning is compound 4. However, we presume
compound 4 is less reactive than compound 5 because of
extended conjugation with the phenyl ring system.
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NC
CN
CN
CN
Scheme 1
SYNLETT 2004, No. 13, pp 2403–2405
0
3
.1
1
.2
0
0
4
Advanced online publication: 08.09.2004
DOI: 10.1055/s-2004-832814; Art ID: S04504ST
© Georg Thieme Verlag Stuttgart · New York

2404
K. M. McQuaid, T. R. R. Pettus
LETTER
Table 1 Epoxidation of Electron Deficient Enonesa
O
O
O
EWG
EWG
R1
EWG
O
PhIO
R1
R1
CHCl3
R2
R2
R3
O
R2
R3
R3
IPh
Entry
1
Enone
Cond.
Approx. PKa of conj. acid
18
Product
None
Yield (%)
1.1 equiv
0
1
2
3
4
5
7
2
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
1.1 equiv
4.1 equiv
1.1 equiv
16.4
16.4
14.2
14.2
13.3
12.5
10.2
7.3
None
None
None
0
3
0
0
4
5
90
45
91
75
>95
6
6b
8
7
10
12
9
8c
11
9
14
13
10
1.1 equiv
13.3
92
15
16
a Conditions: 0.1 M in CDCl3, 1.1 equiv of PhIO added in one portion at r.t. In most cases, complete reaction required from 2–18 h. b In addition
to the epoxides 6, the known b-diketone 17 is also formed in small amounts.14 c More than 1.1 equiv is required for complete epoxidation.
Synlett 2004, No. 13, 2403–2405 © Thieme Stuttgart · New York

LETTER
Chemoselective Epoxidation of Electron Deficient Enones
2405
General Procedure: Compounds 2, 3 were purchased from Aldrich
and used without purification. All other starting compounds 1, 4, 5,
7, 9, 11, 13, and 15 were prepared according to known literature
procedures. Epoxides 6, 10 and 16 are known compounds. Key
spectroscopic data for 8, 12 and 14 are provided. The starting mate-
rial (0.1 mmol) was dissolved in CDCl3 (1 mL) and placed in a seal-
able NMR tube. PhIO was added and the reaction vessel was
intermittently vortex stirred. After 12 h, 1 equiv of DMF was added
as a standard and a 1H NMR spectrum was obtained. The yields of
epoxides were based on comparison with the standard. However,
compounds 6, 8, 10, 12, and 14 were also isolated by chromato-
graphy in comparable yields in larger scale reactions conducted in
chloroform. Volatility makes isolation of the epoxides 6 and 8
problematic and their isolated yields are lower.
(8) Moriarty, R. M.; Gupta, S. C.; Hu, H.; Berenschot, D. R.;
White, K. B. J. Am. Chem. Soc. 1981, 103, 686.
(9) Kowalski, C. J.; Webber, A. E.; Fields, K. W. J. Org. Chem.
1982, 47, 5088.
(10) Liotta, D.; Barnum, C.; Puleo, R.; Zima, G.; Bayer, C.;
Kezar, H. S. J. Org. Chem. 1981, 46, 2920.
(11) Christoffers, J. J. Org. Chem. 1999, 64, 7668.
(12) Reich, H. J.; Renga, J. M. Org. Synth. 1980, 59, 58.
(13) Compound 8: 1H NMR (400 MHz, CDCl3): d = 3.60 (m, 1
H), 2.59 (m, 1 H), 2.35 (m, 1 H), 2.26 (s, 3 H), 2.16 (m, 1 H),
1.86 (m, 1 H), 1.76 (m, 1 H). We believe that byproduct 17
arises upon bifurcation of the mechanism as shown below
(Scheme 3).
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I
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H
Acknowledgment
I
I
O
Ph
O
Ph
O
Ph
17
Research Grants from the National Science Foundation (Career-
0135031) and NIH (GM-64831) are greatly appreciated. K.M.M., a
UCSB undergraduate student, acknowledges funding provide by
the College of Creative Studies (CCS) and a gift by the DeWolfe
family to the organic program at UCSB.
Scheme 3
(14) Ghera, E.; Hassner, A.; Ostercamp, D. J. Org. Chem. 1995,
60, 5135.
(15) De la Pradilla, R. F.; Castro, S.; Manzano, P.; Martin-Ortega,
M.; Priego, J.; Viso, A.; Rodriguez, A.; Fonseca, I. J. Org.
Chem. 1998, 103, 686.
(16) Fleming, F. F.; Shook, B. C. Org. Synth. 2002, 78, 254.
(17) Compound 12: 1H NMR (400 MHz, CDCl3): d = 1.73–1.79
(m, 1 H), 1.88–1.97 (m, 1 H), 2.05–2.14 (m, 1 H), 2.19–2.27
(m, 1 H), 2.34–2.40 (m, 1 H), 2.61–2.68 (m, 1 H), 4.04–4.06
(m, 1 H). 13C NMR (400 MHz, CDCl3): d = 16.7, 22.6, 35.8,
51.6, 63.1, 114.1, 196.8.
References
(1) (a) Silva, A. R.; Freire, C.; de Castro, B. New. J. Chem. 2004,
253. (b) Varvoglis, A. Hypervalent Iodine in Organic
Synthesis; Academic Press: San Diego, 1996.
(2) Saltzman, H.; Sharefkin, J. G. Org. Synth. 1963, 43, 60.
(3) Macikenas, D.; Skrzpezak-Jankun, E.; Protasiewicz, J. D.
Angew. Chem. Int. Ed. 2000, 39, 2007.
(4) It is reported to explode at 210 °C. We, however, find that 3
g of PhIO can explode upon drying over toluene (110 °C, 0.1
torr), reducing a drying pistol to dust.
(5) Pettus, L. H.; van de Water, R. W.; Pettus, T. R. R. Org. Lett.
2001, 3, 905.
(6) Ochiai, M.; Nakanishi, A.; Suefuji, T. Org. Lett. 2000, 2,
2923.
(7) Barea, G.; Maseras, F.; Lledos, A. New. J. Chem. 2003, 27,
811.
(18) Ziegler, F. E.; Guenther, T.; Nelson, R. V. Synth. Commun.
1980, 10, 661.
(19) (a) Tsuno, T.; Sugiyama, K.; Ago, H. Heterocycles 1994, 38,
2631. (b) Compound 14: IR (CH2Cl2): 3061, 3007, 2935,
1797, 1769, 1408, 1382, 1334, 1275, 1265, 1257, 1223,
1200, 1169, 1128, 1109, 1043, 1022, 985, 916, 908 cm–1. 1H
NMR (400 MHz, CDCl3): d = 1.60 (d, 1 H, J = 5.3 Hz), 1.84
(s, 3 H) 1.85 (s, 3 H), 3.76 (q, 1 H, J = 5.3 Hz). 13C NMR
(400 MHz, CDCl3): d = 12.8, 27.8, 28.2, 55.6, 64.7, 105.9,
161.9, 163.7. ES-MS: found [M + Na]+ 209.0420.
Synlett 2004, No. 13, 2403–2405 © Thieme Stuttgart · New York