Iodobenzene-catalysed iodolactonisation using sodium perborate monohydrate as oxidant

Article abstract of DOI:10.1016/j.tetlet.2007.09.078

A convenient approach has been developed for iodolactonisation using iodobenzene as catalyst. The active reagent was generated in situ with tetra-n-butylammonium iodide (TBAI) and hypervalent iodine reagent, diacetoxyiodobenzene (PIDA). PIDA, in turn, was generated in situ using a catalytic amount of iodobenzene with sodium perborate monohydrate as the stoichiometric oxidant. A variety of olefinic acids including δ-pentenoic acids, δ-pentynoic acids and δ-hexynoic acid gave high yields of lactones using this methodology.

Full text of DOI:10.1016/j.tetlet.2007.09.078

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Tetrahedron Letters 48 (2007) 8220–8222
Iodobenzene-catalysed iodolactonisation using sodium
perborate monohydrate as oxidant
Hongjun Liu and Choon-Hong Tan*
Department of Chemistry, 3 Science Drive 3, National University of Singapore, Singapore 117543, Singapore
Received 30 July 2007; revised 3 September 2007; accepted 12 September 2007
Available online 18 September 2007
Abstract—A convenient approach has been developed for iodolactonisation using iodobenzene as catalyst. The active reagent was
generated in situ with tetra-n-butylammonium iodide (TBAI) and hypervalent iodine reagent, diacetoxyiodobenzene (PIDA). PIDA,
in turn, was generated in situ using a catalytic amount of iodobenzene with sodium perborate monohydrate as the stoichiometric
oxidant. A variety of olefinic acids including d-pentenoic acids, d-pentynoic acids and d-hexynoic acid gave high yields of lactones
using this methodology.
Ó 2007 Elsevier Ltd. All rights reserved.
Besides being mild oxidants, there are many impressive
reactions, including C–C and C–X bond formations,
that can be performed using hypervalent iodine
reagents.1 It is now possible to promote certain trans-
formations using catalytic amounts of iodine reagents,
in combination with stoichiometric oxidants.2 It was
demonstrated by Kita and Ochiai that m-chloroper-
benzoic acid (mCPBA) was an effective oxidant for the
in situ re-generation of the active hypervalent iodine(III)
reagent.3,4 It was also reported that peracetic acid,
sodium perborate, NaIO4 and CrO3 were unsuitable as
the stoichiometric oxidants.3b Recently, N-bromosuccin-
imide (NBS) was used with a catalytic amount of
o-substituted amidyl iodobenzene for the bromination
of alkenes.5
a convenient approach which would also provide a plat-
form for the development of a catalytic version. We
found that hypervalent diacetyloxyiodate(I), under mild
conditions, can promote iodolactonisation (Scheme 1).
This reagent can be prepared from a mixture of diacet-
oxyiodobenzene (PIDA) and tetra-n-butylammonium
iodide (TBAI) in a 1:1 molar ratio. The iodolactoni-
sation reaction of pent-4-enoic acid 1a and 2,2-dimethyl-
pent-4-enoic acid 1b proceeded smoothly at room
temperature with diacetyloxyiodate(I). Excellent yields
of 84% and 98% were obtained, respectively, after 1 h.
In the absence of TBAI, the reaction did not progress,
even with heating.
When a 1:1 mixture of PIDA and TBAI was observed
using 1H NMR experiments, a new peak (s, d
1.91 ppm) appeared and gradually replaced the Ac
group (s, d 1.99 ppm) of PIDA (see Supplementary
data). An equal amount of iodobenzene was also
detected downfield. This new singlet was not assigned
to acetyl hypoiodite (IOAc) as it is known to have a
The chemistry of hypervalent iodine(I) reagents is rela-
tively less explored. Diacetyloxyiodate(I) has been
shown to promote oxidative phenolic coupling6 and
the iodoacetoxylation and azidoiodination of alkenes.7
Polymer-bound diazidoiodate(I) was developed as a safe
alternative to IN3. The reagent was not deactivated after
extensive washing of the resin with solvent. Formation
of the ionic diacetyloxyiodate(I) was proposed as an
intermediate during the preparation of this reagent.8
O
R
R
R
R
CO2H
I(OAc)2
O
1.1 equiv.
Halolactonisation is widely used to construct lactones
from olefinic carboxylic acids.9 We were keen to develop
n-Bu4NI 1.1 equiv.; CH2Cl2, rt
I
R=H, 1a
R=H, 2a; Yield: 84%
R=Me, 1b
R=Me, 2b; Yield: 98%
*
Scheme 1. Iodolactonisation actived by hypervalent diacetyloxy-
Corresponding author. Tel.: +65 65162845; fax: +65 67791691;
iodate(I).
e-mail: chmtanch@nus.edu.sg
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.078

H. Liu, C.-H. Tan / Tetrahedron Letters 48 (2007) 8220–8222
8221
chemical shift of 2.19 ppm.10 The generation of mole-
CO2H
1b
PhI(OAc)2
TBAI
cular iodine was also excluded as a possibility after a
simple starch test was conducted. The iodo group on
lactones 2a–b is derived from TBAI. A catalytic version
of this reaction is, thus, possible if we could regenerate
PIDA in situ.
OAc
n-Bu4N I
OAc
NaBO3
+
AcOH
O
PhI
O
n-Bu4NAcO
AcOH
+
I
+
2b
To investigate the catalytic version, we reduced the
amount of PIDA and added a stoichiometric amount
of a co-oxidant. With 10 mol % of PIDA, several oxi-
dants including mCPBA were used as the oxidant (Table
1, entries 1–3) for the iodolactonisation of 2,2-dimethyl-
pent-4-enoic acid 1b. A moderate yield of 16% was
obtained when mCPBA was used (entry 1). It was an
unsuitable oxidant as it may also oxidise the olefin.
Several side-products were observed. Sodium perborate
in acetic acid was shown to oxidise iodobenzene to
PIDA.11 We found that sodium perborate monohydrate
(NaBO3ÆH2O) was the ideal oxidant for the iodolacton-
isation, giving the product cleanly. With an increased
amount of acetic acid (3 equiv), the yield was improved
to 64% (entry 3).
Scheme 2. Proposed catalytic cycle.
Table 2. Iodolactonisation of d-pentenoic acids
O
R1
R1
CO2H
I
R2
R2
O
5 mol%
R3
I
n-Bu4NI 1.1 equiv.,
NaBO3 H2O 2 equiv.,
AcOH 5 equiv.,
R3
2a, 2c-g
1a, 1c-g
CH2Cl2, 40 ºC
Entry
1
R1
R2
R3
Time (h)
2
Yielda (%)
1
2
3
4
5
6
1a
H
H
H
H
H
H
H
H
H
H
H
Me
Et
22
12
10
13
11
19
2a
2c
2d
2e
2f
80
1c
1d
1e
1f
Bn
Et
Me
H
97 (dr 2:1)
81 (dr 3:2)
84 (dr 2:1)b
87 (dr 5:1)c
83 (dr 5:1)
The reaction worked well even when the catalyst, PIDA
was replaced with iodobenzene (entry 4). Increasing the
amount of acetic acid to 5 equiv, only 5 mol % of iodo-
benzene was required to obtain a yield of 83% (entry 6).
The catalyst amount could be reduced to 1 mol % but
the yield became unacceptable. When no catalyst (PhI)
was used, only a trace amount of the product was
observed. Increasing the amount of TBAI did not affect
the reaction at all. Other solvents such as THF, CH3CN,
ClCH2CH2Cl were also useful for this reaction but the
best result was obtained with CH2Cl2. This reaction also
worked when TBAI was replaced with NaI (entry 9).
Based on these results, we proposed a plausible catalytic
cycle (Scheme 2).
1g
H
2g
a Isolated yield.
b 3 equiv oxidant used.
c 5 equiv oxidant used.
observed and lactones 2a and 2c–g were obtained in
excellent isolated yields. The 5-exo-trig ring-closing
reaction was preferred and the other possible regio-
isomer from a 6-endo-trig closure was not observed.
No exocyclic olefin due to elimination was observed in
any of the reactions. For the a-substituted acids, a
mixture of two diastereoisomers was obtained. NOE
experiments showed that syn lactones were the major
isomers (Table 2, entries 2–4). Similarly, 2f and 2g were
obtained in 5:1 ratio in favour of the syn lactone.
A series of d-pentenoic acids were subjected to the opti-
mised conditions for iodolactonisation using 5 mol % of
iodobenzene (Table 2). Complete conversions were
Table 1. Iodobenzene catalysed iodolactonisation
This protocol was also used to prepare iodoenol lac-
tones 4a–d from d-pentynoic acids 3a–c and d-hexynoic
acid 3d (Table 3). Haloenol lactones were previously
synthesised as potential inhibitors of serine proteases
and glutathione S-transferases.12 The 5-exo-dig reaction
was favoured and is also highly diastereoselective; only
the E olefins 4a–c were formed. While complete conver-
sions were observed, the instability of these iodoenol
lactones led to lower than expected yields.
O
CO2H
catalyst, oxidant, AcOH
O
n-Bu4NI 1.1 equiv.
CH2Cl2, 40 ºC
I
1b
2b
Entry Oxidant (equiv) Catalyst
(equiv)
AcOH Time Yielda
(equiv) (h)
(%)
1
2
3
4
5
6
7
8
9c
mCPBA (1.5)b
PIDA (0.1)
1
1
3
3
5
5
5
5
5
1
21
12
10
10
10
10
10
23
16
46
64
68
81
83
28
Trace
56
NaBO3ÆH2O (5) PIDA (0.1)
NaBO3ÆH2O (5) PIDA (0.1)
NaBO3ÆH2O (5) PhI (0.1)
NaBO3ÆH2O (2) PhI (0.1)
NaBO3ÆH2O (2) PhI (0.05)
NaBO3ÆH2O (2) PhI (0.01)
When (E)-hex-3-enoic acid 5 was subjected to the same
conditions, the 5-endo-trig lactone was obtained
(Scheme 3). The iodo group was eliminated under the
reaction conditions to provide a,b-unsaturated lactone
6 in an excellent yield (Scheme 3).
NaBO3ÆH2O (2)
NaBO3ÆH2O (7) PhI (0.1)
0
a Isolated yield.
In conclusion, we have developed a new approach to
iodolactonisation using iodobenzene as catalyst. The
active reagent was identified as diacetyloxyiodate(I)
b Unpurified mCPBA, rt.
c NaI (5 equiv) instead of TBAI; DMF as solvent.

8222
H. Liu, C.-H. Tan / Tetrahedron Letters 48 (2007) 8220–8222
Table 3. Iodolactonisation of various alkynes
References and notes
O
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I
R1
R1
CO2H
O
10 mol%
R2
R2
nBu4NI 1.1 equiv.,
NaBO3 H2O 5 equiv.,
AcOH 7 equiv.,
I
3a-d
4a-d
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4d
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57
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Et
Bn
H
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I
O
5 mol%
nBu4NI 1.1 equiv.,
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5
´
´
´
´
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CH2Cl2, 40 ºC, 38 h
Scheme 3. Iodolactonisation followed by elimination of iodo group.
and was generated in situ with hypervalent iodine
reagent, PIDA. PIDA, in turn, was generated in situ
using a catalytic amount of iodobenzene and sodium
perborate as the stoichiometric oxidant. A variety of
olefinic acids gave high yields of lactones using this
methodology. This study should provide a platform
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Acknowledgements
This work was supported by grants (R-143-000-222-112)
and a scholarship (to L.H.J.) from the National Univer-
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Experimental procedures, characterisation and spectro-
scopic data (PDF). Supplementary data associated with
this article can be found, in the online version, at
doi:10.1016/j.tetlet.2007.09.078.