Facile organocatalytic domino oxidation of diols to lactones by in situ-generated TetMe-IBX

Article abstract of DOI:10.1016/j.tet.2014.01.034

The domino oxidation of diols to lactones is an important transformation, and catalytic protocols that allow this conversion smoothly are scarce. Capitalizing on the established reactivity of tetramethyl-IBX (TetMe-IBX) and its in situ generation in the presence of a co-oxidant, such as oxone, we have shown that a variety of diols can be converted to the corresponding lactones in respectable yields by employing the precursor of TetMe-IBX, namely, tetramethyl-o-iodobenzoic acid (TetMe-IA), as a catalyst in 5 mol % in the presence of 2 equiv of oxone.

Full text of DOI:10.1016/j.tet.2014.01.034

Accepted Manuscript
Facile Organocatalytic Domino Oxidation of Diols to Lactones by In Situ-Generated
TetMe-IBX
Samik Jhulki, Saona Seth, Manas Mondal, Jarugu Narasimha Moorthy
PII:
S0040-4020(14)00076-3
10.1016/j.tet.2014.01.034
TET 25208
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 October 2013
Revised Date: 13 January 2014
Accepted Date: 16 January 2014
Please cite this article as: Jhulki S, Seth S, Mondal M, Moorthy JN, Facile Organocatalytic Domino
Oxidation of Diols to Lactones by In Situ-Generated TetMe-IBX, Tetrahedron (2014), doi: 10.1016/
j.tet.2014.01.034.
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ACCEPTED MANUSCRIPT
Facile Organocatalytic Domino Oxidation of Diols to Lactones by In Situ-
Generated TetMe-IBX
Samik Jhulki, Saona Seth, Manas Mondal and Jarugu Narasimha Moorthy*
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, INDIA
ABSTRACT
The domino oxidation of diols to lactones is an important transformation, and catalytic protocols
that allow this conversion smoothly are scarce. Capitalizing on the established reactivity of
tetramethyl-IBX (TetMe-IBX) and its in situ generation in the presence of a co-oxidant such as
oxone, we have shown that a variety of diols can be converted to the corresponding lactones in
respectable yields by employing the precursor of TetMe-IBX, namely, tetramethyl-o-
iodobenzoic acid (TetMe-IA), as a catalyst in 5 mol% in the presence of 2 equiv of oxone.
KEYWORDS: Diols, Lactones, Modified IBX, Catalysis, Oxone, Cascade Reaction
GRAPHIC FOR TOC
Oxone
Oxone
ꢀ 22 examples
ꢀ aliphatic and benzylic
TetMe-IBA
I(III)
TetMe-IA
I(I)
*Corresponding Author.
Tel. +91-512-2597438; fax: +91-512-2597436; e-mail address: moorthy@iitk.ac.in
1

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1. Introduction
Lactones are an important class of functional group compounds that are ubiquitous, and the
lactone moiety constitutes an integral part of the structures of many biologically active natural
products.1 In principle, lactones may be considered as protected diols, which can be easily
generated by treatment with hydride reagents. However, the protection-deprotection protocol of
diols has seldom been employed in the synthesis of natural products due to lack of effective
methodologies that permit conversion of diols to lactones under mild conditions. Thus, there is a
need for facile methodologies that allow conversion of diols to lactones. The literature reveals
that it was Fetizon and co-workers who first showed that lactones can be produced from diols
using Ag2CO3 supported on celite;2 this protocol, however, suffers from the impracticality
associated with the usage of a large excess of silver salt. In the past decade or so, several
improved methods for conversion of diols to lactones have been developed.3 All of these
methods are disadvantageous in terms of one consideration or the other that include harsh
experimental conditions, use of the reagent in more than stoichiometric amounts, application of
toxic metal complexes, etc.3 A notable exception is the methodology reported by Kita and co-
workers, which employs a green iodine reagent, i.e., hypervalent iodine (III), in the presence of
catalytic amounts of KBr.4 Incidentally, this method too suffers from the necessity of the
hypervalent compound being employed in 3 equivalents.
Against the above background, we recently reported the results of a chance observation
involving conversion of diols to lactones in nitromethane at r.t. with the precursor of a
pentavalent iodine, i.e., a biphenyl-based diiodo diacid DIDA (Chart 1),5 employed as a catalyst
in the presence of oxone as a terminal oxidant; it is noteworthy that the application catalytically
of the precursor of a hypervalent iodine compound in the presence of a co-oxidant such as oxone
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is a new and recent dimension in hypervalent iodine-mediated oxidation chemistry, which
obviates isolation of heat- and shock-sensitive IBX.6,7 The diiodo-diacid DIDA was found to be
a respectable reagent for conversion of activated diols to their corresponding lactones
catalytically.5 Presumably, the methoxy substituents attenuate reactivity of the in situ-generated
Bis-IBX such that the conversion of diols to lactones occurs only when the former are activated;
the methodology was found to be unsuccessful for aliphatic diols and led to poor yields or no
reaction at all when the diols were electron-rich and deficient, respectively.5 We were, therefore,
motivated to develop a facile and catalytic protocol for the synthesis of lactones from a domino
oxidation of diols based on an in situ-generated more reactive hypervalent iodine reagent. We
surmised that the precursor of TetMe-IBX, i.e., TetMe-IA, which has been shown recently by
us to be a remarkable catalyst for oxidation of alcohols to their corresponding oxidation
products,7 could be an effective catalyst for the oxidation of diols as well. The rationale for our
conviction were the following: i) the little yet meaningful twisting introduced by steric relay
between consecutive methyl groups has been shown to improve the solubility of IBX, and ii) the
o-methyl group has been demonstrated to increase the rate of alcohol oxidation. Herein, we
report that TetMe-IA does indeed work very nicely as a catalyst for conversion of a variety of
diols to latones. Mechanistically, it is shown that it is the I(V)ꢁI(III)ꢁI(V) cycle that is
involved in the cascade oxidation in the presence of oxone as a co-oxidant.
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Me
O
O
OH
Me
O
Me
OH
O
O
I
O
Me
Me
I
O
O
O
I
O
O
O
Me
Me
O
O
OH
Me
Me
O
Me
Me
I
Me
Me
I
TetMe-IBX
Bis-IBX
COOH
HOOC
COOH
I
O
O
Me
Me
Me
TetMe-IA
DIDA
Scheme 1. The structures of Bis-IBX and TetMe-IBX and their precursor iodo-acids, namely,
DIDA and TetMe-IA, respectively.
2. Results and Discussions
The syntheses of TetMe-IA and TetMe-IBX have previously been reported from our
laboratory.7 To begin with, the reactivity of TetMe-IBX was investigated to test if the latter
indeed works for facile conversion of benzene-1,2-dimethanol into the corresponding lactone.
Buoyed by the observation of the formation of lactone smoothly, catalytic reactivity of the
precursor iodo-acid, i.e., TetMe-IA, was investigated in the presence of added oxone. Thus, the
oxidation of benzene-1,2-dimethanol to its corresponding lactone was examined as a
representative case in a variety of solvents that include nitromethane, THF, ethyl acetate, ethyl
formate, choloroform, dichloromethane, acetone, DMSO, DMF, acetonitrile, H2O, etc. As shown
in Table 1, the reaction initially was found to occur smoothly at r.t. in nitromethane. We
observed that addition of water in nitromethane expedites the reaction, due presumably to higher
solubility of oxone in the aqueous medium, which seemingly facilitates formation rapidly of the
active hypervalent iodine species. From a comprehensive set of screening experiments,
acetonitrile-water (1:1, v/v) was determined to be the best solvent system for domino oxidation
reaction. Further, a catalyst loading of just 5 mol% was found to be sufficient for completion of
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the reactions, cf. Table 1. It is pertinent to note that although the reaction underwent smooth
conversion in water, the choice of water as the solvent─a genuinely green medium─was not
considered due to insolubility of some diols without the added organic solvent. Besides, the
reaction time in water alone was found to be slower requiring approximately 2.5 times longer
duration than that in a mixed solvent system involving equal volumes of acetonitrile and water.
Table 1. Optimization of the Conditions for Oxidation of Benzene-1,2-dimethanol with TetMe-
IA in the Presence of Oxone at Room Temperature.
Entry
Solvent
Catalyst Oxone Time
(mol%) (equiv)
Starting
Material
(%)a
Lactone
(%)a
Dialdehyde
(%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
dry MeNO2
dry DCM
dry THF
10
10
10
10
10
10
10
10
10
10
10
5
5
10
5
5
10
5
2
2
2
2
2
2
2
2
2
2
1
2
1
2
2
2
2
2
2
2
35
36
36
36
36
36
36
36
36
36
36
36
36
36
6.5
15
16
27
36
36
-
96
44
-
-
-
-
-
-
30
-
-
-
-
-
-
-
-
-
-
-
-
25
93
98
42
-
99
98
98
98
37
-
55
99
-
-
-
dry EtOAc
dry HCOOEt
dry CHCl3
dry dioxane
dry DMF
dry DMSO
dry acetone
dry MeNO2
dry MeNO2
dry MeNO2
dry MeCN
MeCN-H2O
H2O
-
48
67
-
-
-
-
60
96
41
-
97
96
94
94
85
6
MeNO2-H2O
MeNO2-H2O
DCM-H2O
CHCl3-H2O
-
8
90
5
5
-
-
a The relative ratios of the products in the reaction mixture were determined by 1H NMR analysis.
With the optimized reaction conditions, the oxidation of a variety of diols to their corresponding
lactones at r.t. was investigated. The results of oxidations are summarized in Table 2.
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Table 2. Catalytic Oxidation of Diols to Lactones Using TetMe-IA/Oxone.a
Products (Yields, %)
Temp
(°C)
Time
(h)
Entry
1
Substrate
Lactone
Lactol
Dialdehyde
30
30
6.5
15
1
2
1l (97)
2l (88)
2
3
30
10
3
3la + 3lb (79)
(1.28:1)b
4
5
6
30
30
30
10
30
7
4d (28)
4l (70) c
4
5
5l (62) c,d
6
6o (88)
6o (30)
7
8
30
30
24
6l (65)
8
7
7la + 7lb (56)e
(1:2.58)b
9
30
30
4
8
9
8l (12)
9l (72)
8d (76)
10
4.5
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11
12
30
45
8
10
11
10o (65)
15
11l (94) f,g
13
45
18
12
13
12l (75)f,g
g,h
14
15
16
60
60
45
24
24
15
13l (55)
14
15
14l (25)g,i
15l (15)j
17
18
30
60
7
16o (96)
16
15
16l (82)
19
30
19
17
17oa +17ob
(98)
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20
60
30
17la + 17lb
(79)
(1:1)b
21
22
45
45
16
18l (96)
19l (98)
18
19
19.5
a
Unless mentioned otherwise, all the reactions were carried out in CH3CN/H2O (1:1) mixture, and the
yields refer to the isolated yields.
b
c
Product mixtures were determined by 1H NMR spectroscopy.
Reaction was carried out in nitromethane as the solvent. Intriguingly, the same reaction in MeCN-H2O
produced a complex mixture of products.
d
e
f
Starting material was recovered in 30% yield.
The remainder corresponds to an intractable polar mixture.
The reaction mixture was heated at 60 °C for two hours to ensure that the lactol was converted to
lactone.
Yield was determined by GC analysis using dodecane as an internal standard with response factors
taken into consideration.
The remainder was found to be a mixture of 5-hydroxypentanoic acid and glutaric acid.
The remainder was found to be a mixture of 6-hydroxyhexanoic acid and adipic acid.
4-Hydroxy-1-phenylbutan-1-one was isolated in 55% yield. The remainder was found to be a complex
mixture of polar material.
g
h
i
j
As can be perused from the results in Table 2, the catalytic protocol is effective for oxidation of a
variety of both aliphatic and benzylic diols to their corresponding lactones. While the yield was
found to be excellent for benzene-1,2-dimethanol (1l, entry 1), substitution as well as changes in
the framework structure led to lesser yields (entries 2-11). The lactonization works well for diols
substituted with electron-donating substituents (entry 2), and reasonably well for substrates with
moderately electron-withdrawing substituents (entries 3-8). It is noteworthy that a highly
electron deficient diol such as (perchloro-1,2-phenylene)dimethanol 6 yielded the corresponding
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lactone 6l in a respectable yield (entry 7), while the same was found to be inert to oxidation by
DIDA/oxone.5 Aliphatic 1,4-diols led to very good yields of lactones (entries 12 and 13). What is
noteworthy is that the diol with a combination of primary and secondary hydroxyl groups, i.e.,
12, (entry 13) yielded predominantly the lactone 12l, which attests to rapid oxidation of the
primary hydroxyl group than the secondary one. The yields of lactones are found to drop with
increasing chain length as revealed by oxidation of 1,5- and 1,6-diol 13 and 14 (entries 14 and
15). The oxidation of 1-phenyl-1,4-butandiol 15 led to the corresponding lactone 15l in a very
poor yield. In this instance, 4-hydroxy-1-phenylbutan-1-one was isolated in 55 % yield (entry
16); clearly, the benzylic oxidation is much faster. The fact that the lactol formation becomes
progressively difficult with increasing chain length is clearly evident from the yields of lactones
derived from butan-1,4-diol 11, pentan-1,5-diol 13 and hexan-1,6-diol 14 (entries 12, 14 and 15).
On the other hand, freezing of bond rotations in butan-1,4-diols improves the yields of domino
oxidation products as is evident from the results of oxidation of conformationally locked cyclic
diols (entries 18, 20, 21 and 22); the butyrolactones were accessed in very good isolated yields.
In these cases, however, a relatively higher temperature (45 °C) was necessary to push the
cyclization followed by oxidation to completion. Clearly, the results in Table 2 vindicate TetMe-
IA as a powerful catalyst for sequential oxidation of the diols of a wider substrate scope to the
corresponding lactones. The results of oxidation of tetrachlorobenzene-1,2-dimethanol 6 (entry
7, Table 2) and several aliphatic diols 11-19 (entries 12-22, Table 2) to their corresponding
lactones establish superior reactivity of TetMe-IA as a catalyst over DIDA.
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3. Mechanistic Considerations
The oxidation of diols to lactones may be readily envisaged to proceed in two steps: the first step
involves oxidation of one of the two hydroxyl functionalities to the corresponding hydroxy-
aldehyde that subsequently undergoes intramolecular nucleophilic attack by the alcohol to
convert to lactol, Scheme 2; the second step constitutes oxidation of the lactol to a lactone. The
isolation of lactol intermediate should constitute a direct proof to the reaction mechanism.
Indeed, the lactol intermediates were readily isolated in at least four instances (entries 6, 11, 17,
19).
Scheme 2. Mechanism of domino oxidation of diols to the corresponding lactones.
To unequivocally establish which of the two hypervalent iodine species, i.e., I(III) and I(V), is
responsible for the observed oxidations under the employed catalytic conditions, a comparative
oxidation study was carried for the case of benzene-1,2-dimethanol 1 as a representative case.
Thus, oxidation of the latter at r.t. was examined by employing 5 mol% of TetMe-IA, TetMe-
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IBA and TetMe-IBX and 2 molar equivalents of oxone. The disappearance of dimethanol as
monitored by TLC analysis was followed in each case. The durations for completion of the
reaction with these reagents in each case were found to be 6.5, 5.0 and 4.0 h, respectively, which
suggest that it is the I(V) species that is responsible for oxidations and that the catalytic cycle
that is involved is I(V)ꢁI(III)ꢁI(V). Further, from an independent experiment, it was firmly
established that the lactone formation is not observed when the reaction is run by employing two
equivalents of I(III) reagent without the added oxone; the I(III) species was generated
independently by reducing the I(V) reagent with a molar equivalent of p-bromobenzyl alcohol.
The unique reactivity of TetMe-IBX for the cascade oxidation is compelling in light of the
reported failure of the oxidation of diols to lactones with parent IBX at r.t. by Corey and co-
workers long ago8 and occurrence of the reaction only at a higher temperature in a combination
of solvents, namely ethyl acetate and DMSO (9:1).9 Indeed, when parent o-iodobenzoic acid was
employed as the catalyst for the oxidation of benzene-1,2-dimethanol 1 under the same
experimental conditions, the reaction was found to be highly sluggish. To establish the fact that
the tetramethylation does indeed play a role, the oxidation of benzene-1,2-dimethanol 1 and
11,12-dihydrodibenzobarrelene-11,12-dimethanol 16─two representative benzylic and aliphatic
diols─was examined with 3-methyl-2-iodobenzoic acid (Me-IA), 3,5-dimethyl-2-iodobenzoic
acid (DiMe-IA) and TetMe-IA in the presence of oxone under identical conditions (Scheme 3).
Although the yields of the lactone product 1l were found to be similar for oxidation of the
benzylic diol 1 with all the three reagents, the duration of reaction was found to be significantly
longer (ca. 15-16 h) for Me-IA as well as DiMe-IA reagent. Further, for the case of aliphatic diol
16, TetMe-IA produced the lactone 16l cleanly at 60 °C after 15 h, while a mixture lactol 16l
and lactone 16o in near equal amounts was obtained after 36 h when Me-IA and DiMe-IA were
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employed as the catalysts in the presence of oxone under identical experimental conditions
(Scheme 3). These results clearly attest to the superior oxidation capability of in situ-generated
TetMe-IBX. The enhanced reactivity and better solubility evidently manifests in short reaction
times when TetMe-IA is employed as the catalyst.
Scheme 3. Results of catalytic oxidation of diols with Me-IA and DiMe-IA in comparison with
TetMe-IA in the presence of oxone under identical experimental conditions.
4. Conclusions
Environmentally-benign catalysts based on hypervalent iodine are appealing for facile
conversion of diols to lactones, although several metal-catalyzed approaches are known.3 We
recently disclosed that the diiodo diacid based on diphenyl, namely DIDA, may accomplish this
domino transformation, but with notable disadvantages that include poor yields in some benzylic
cases and lack of oxidation with aliphatic diols.5 We have shown in the present investigation that
structurally twisted TetMe-IBX, generated in situ, can oxidize a variety of diols to lactones. The
simple experimental conditions involving the use of acetonitrile-water medium and room
temperature for a cascade reaction should constitute a leap forward in the catalytic reactions
based on hypervalent I(V) reagents.
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5. Experimental Section
5.1. General Aspects
Solvents were distilled prior to use and double distilled water was used for the reaction. Dry
solvents used for the screening experiments were obtained following the standard drying
techniques. Reactions were carried out in an open atmosphere without any precaution. Products
of oxidation were isolated by column chromatography using silica gel of of 100−200 ꢀm particle
size. NMR spectra were recorded with JEOL 400 and 500 MHz spectrometers using CDCl3 and
CD3OD as solvents with no internal standards added to them. The values of chemical shifts have
been reported in ppm. In cases where the formation of two regioisomeric oxidation products was
observed as expected, the relative ratio of the regioisomeric products was determined by
integrations of the diagnostic signals in the 1H NMR spectrum of the mixture.
5.2. General Procedure for Catalytic Oxidation of Diols to Lactones Using TetMe-IA via In
situ-Generated TetMe-IBX. In a typical experiment, a round bottom flask containing 4-6 mL of
acetonitrile-water mixture (1:1) was charged with 0.5-1.0 mmol of the diol, 5 mol% of TetMe-
IA, and oxone (2 equiv). The resulting mixture was stirred at r.t. for benzylic diols and at 45 °C
for aliphatic diols. At the end of the reaction, as judged from TLC analysis, little water was
added to dissolve the inorganic salts, and the organic matter was extracted with EtOAc at least
two times. The combined extract was dried over anhydrous Na2SO4, concentrated in vacuo to
obtain the crude product, which was subjected to silica-gel column chromatography using ethyl
acetate/ pet ether to isolate the pure product.
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5.3.
Characterization Data of All Products.
1
5.3.1. Isobenzofuran-1(3H)-one (1l).10 Colorless solid; Rf (25% EtOAc/pet. ether) 0.55; H
NMR (CDCl3, 400 MHz) δ 5.33 (s, 2H), 7.49-7.56 (m, 2H), 7.67-7.71(m, 1H), 7.93 (d, J = 7.8
Hz, 1H).
5.3.2. 5,6-Dimethylisobenzofuran-1(3H)-one (2l).11 Colorless solid; Rf (25% EtOAc/pet.
ether) 0.58;1H NMR (CDCl3, 500 MHz) δ 2.36 (s, 3H), 2.39 (s, 3H), 5.24 (s, 2H), 7.24 (s, 1H),
7.67 (s, 1H).
5.3.3. 5-Bromoisobenzofuran-1(3H)-one (3la).12 Colorless solid; Rf (25% EtOAc/pet. ether)
0.50;1H NMR (CDCl3, 400 MHz) δ 5.30 (s, 2H), 7.67 (s, 1H), 7.68 (d, J = 8.56 Hz, 1H), 7.79 (d,
J = 8.56 Hz, 1H).
5.3.4. 6-Bromoisobenzofuran-1(3H)-one (3lb).13 Colorless solid; Rf (25% EtOAc/pet. ether)
1
0.50; H NMR (CDCl3, 400 MHz) δ 5.29 (s, 2H), 7.39 (d, J = 8.04 Hz, 1H), 7.80 (dd, J1 = 8.04
Hz, J2 = 1.72 Hz, 1H), 7.06 (d, J = 1.72 Hz, 1H).
5.3.5. 5,6-Dichloroisobenzofuran-1(3H)-one (4l).14 Colorless solid; Rf (25% EtOAc/pet.
ether) 0.40; 1H NMR (CDCl3, 500 MHz) δ 5.29 (s, 2H), 7.63 (s, 1H), 8.00 (s, 1H).
5.3.6. 5,6-Dibromoisobenzofuran-1(3H)-one (5l).5 Colorless solid; Rf (25% EtOAc/pet. ether)
0.40; 1H NMR (CDCl3, 500 MHz) δ 5.26 (s, 2H), 7.82 (s, 1H), 8.16 (s, 1H).
5.3.7. 4,5,6,7-Tetrachloro-1,3-dihydroisobenzofuran-1-ol (6o). Colorless solid; Rf (50%
EtOAc/pet. ether) 0.30; IR (KBr) cm-1 3416, 2962, 1382.1H NMR (CD3OD, 500 MHz) δ 5.02 (d,
J = 13.75 Hz, 1H), 5.22 (dd, J1 = 13.75 Hz, J2 = 2.10 Hz, 1H), 6.45 (d, J = 2.10 Hz, 1H). 13C
14

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NMR (CD3OD, 125 MHz) δ 72.6, 102.9, 126.9, 129.0, 133.1, 134.0, 139.8, 140.9. ESI-MS- m/z
[M+Cl]- Calcd for C8H4O2Cl5: 306.8654, found: 306.8651.
5.3.8. 4,5,6,7-Tetrachloroisobenzofuran-1(3H)-one (6l). Colorless solid; Rf (25% EtOAc/pet.
ether) 0.35; IR (KBr) cm-1 1771, 1344, 1270.1H NMR (CDCl3, 400 MHz) δ 5.23 (s, 2H). 13C NMR
(CDCl3, 125 MHz) δ 67.1, 122.9, 126.7, 131.6, 135.4, 138.9, 144.9, 165.7. ESI-MS- m/z [M-H]-
Calcd for C8HO2Cl4: 268.8731, found: 268.8736.
5.3.9. 6-Cyanoisobenzofuran-1(3H)-one (7lb). Colorless solid; Rf (25% EtOAc/pet. ether)
0.45; IR (KBr) cm-1 3055, 2235, 1761, 1485. 1H NMR (CDCl3, 400 MHz) δ 5.39 (s, 2H), 7.83 (s,
1H), 7.84 (d, J = 7.32 Hz, 1H), 8.05 (d, J = 7.32 Hz, 1H). 13C NMR (CDCl3, 125 MHz) δ 69.2,
117.4, 117.6, 126.3, 126.8, 129.5, 132.9, 146.6, 168.9. ESI-MS- m/z [M-H]- Calcd for C9H4O2N:
158.0242, found: 158.0241.
5.3.10. 5-Cyanoisobenzofuran-1(3H)-one (7la). Colorless solid; Rf (25% EtOAc/pet. ether)
0.45; IR (KBr) cm-1 3092, 2236, 1762, 1428. 1H NMR (CDCl3, 400 MHz) δ 5.41 (s, 2H), 7.67 (d,
J = 7.82 Hz, 1H), 7.96 (d, J = 7.82 Hz, 1H), 8.22 (s, 1H). 13C NMR (CDCl3, 125 MHz) δ 69.6,
113.8, 117.3, 123.5, 127.1, 130.0, 137.0, 150.3, 168.6. ESI-MS- m/z [M-H]- Calcd for C9H4O2N:
158.0242, found: 158.0241.
5.3.11. Dibenzo[c,e]oxepin-5(7H)-one (8l).14 Colorless solid; Rf (25% EtOAc/pet. ether) 0.55;
1H NMR (CDCl3, 500 MHz) δ 4.99 (s, 1H), 5.06 (s, 1H), 7.42-7.69 (m, 7H), 7.99 (d, J = 7.95 Hz,
1H).
5.3.12. Biphenyl-2,2'-dicarbaldehyde (8d).15 Colorless solid; Rf (25% EtOAc/pet. ether) 0.30; 1H
NMR (CDCl3, 500 MHz) δ 7.36 (d, J = 7.72 Hz, 1H), 7.60 (t, J = 7.72 Hz, 1H), 7.67 (t, J = 6.6
Hz, 1H), 8.07 (d, J = 6.6 Hz, 1H), 9.84 (s, 1H).
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1
5.3.13. Isochroman-1-one (9l).16 Colorless solid; Rf (25% EtOAc/pet. ether) 0.45; H NMR
(CDCl3, 400 MHz) δ 3.07 (t, J = 5.98 Hz, 2H), 4.54 (t, J = 5.98 Hz, 1H), 7.40 (t, J = 5.4 Hz, 1H),
8.07 (d, J = 7.56 Hz, 1H), 7.54 (t, J = 7.44 Hz, 1H), 8.10 (d, J = 7.80 Hz, 1H).
5.3.14. 1,3,4,5-Tetrahydrobenzo[c]oxepin-1-ol (10o). Colorless gummy solid; Rf (25%
EtOAc/pet. ether) 0.60; IR (KBr) cm-1 3425, 2961, 2855, 1704, 1456.1H NMR (CDCl3, 500 MHz)
δ 2.01 (pent, J = 6.85 Hz, 2H), 2.72 (t, J = 7.55 Hz, 2H), 4.21 (t, J = 6.62, 2H), 4.91 (s, 1H), 6.75
(d, J = 8.25 Hz, 1H), 6.87 (t, J = 7.32 Hz, 1H), 7.08-7.12 (m, 2H), 8.10 (s, 1H). 13C NMR
(CDCl3, 125 MHz) δ 26.3, 28.5, 63.5, 115.3, 120.9, 127.0, 127.5, 130.4, 153.5, 161.2. ESI-MS+
m/z [M-OH]+ Calcd for C10H11O: 147.0810, found: 147.0802.
1
5.3.15. Dihydrofuran-2(3H)-one (11l).17 Colorless liquid; Rf (10% EtOAc/pet. ether) 0.50; H
NMR (CDCl3, 400 MHz) δ 2.22−2.30 (m, 2H), 2.49 (t, J = 8.32 Hz, 2H), 4.35 (t, J = 7.08 Hz,
2H).
5.3.16. 5-Methyldihydrofuran-2(3H)-one (12l).17 Colorless liquid; Rf (10% EtOAc/pet. ether)
1
0.50; H NMR (CDCl3, 500 MHz) δ 1.41 (d, J = 6.4 Hz, 3H), 1.78-1.86 (m, 1H), 2.32-2.39 (m,
1H), 2.50-2.56 (m, 2H), 4.60-4.67 (m, 1H).
5.3.17. Tetrahydro-2H-pyran-2-one (13l).17 Colorless liquid; Rf (10% EtOAc/pet. ether) 0.50;
1H NMR (CDCl3, 500 MHz) δ 1.82-1.93 (m, 4H), 2.55 (t, J = 6.72 Hz, 2H), 4.34 (t, J = 5.58 Hz,
2H).
1
5.3.18. ε-Caprolactone (14l).18 Colorless liquid; Rf (10% EtOAc/pet. ether) 0.50; H NMR
(CDCl3, 500 MHz) δ 1.75-1.85 (m, 6H), 2.61-2.63 (m, 2H), 4.20-4.22 (m, 2H).
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5.3.19. 4-Hydroxy-1-phenylbutan-1-one.19 Colorless solid; Rf (50% EtOAc/pet. ether) 0.40; 1H
NMR (CDCl3, 400 MHz) δ 2.02 (pent, J = 6.4 Hz, 2H), 3.14 (t, J = 6.88 Hz, 2H), 3.75 (t, J =
5.96 Hz, 2H), 7.44-7.48 (m, 2H), 7.55-7.59 (m, 1H), 7.94-7.99 (m, 2H).
5.3.20. 5-Phenyldihydrofuran-2(3H)-one (15l).20 Colorless solid; Rf (25% EtOAc/pet. ether)
1
0.55; H NMR (CDCl3, 400 MHz) δ 2.14-2.16 (m, 1H), 2.64-2.66 (m, 3H), 5.50-5.53 (m, 1H),
7.32-7.52 (m, 5H).
5.3.21. 4,9-benzo-1,3,3a,4,9,9a-hexahydronaphtho[2,3-c]furan-1-ol(16o). Colorless solid; Rf
1
(50% EtOAc/pet. ether) 0.25; IR (KBr) cm-1 3383, 2943, 1457. H NMR (CDCl3, 400 MHz) δ
2.69-2.72 (m, 1H), 2.82-2.88 (m, 1H), 3.54 (dd, J1 = 9.04 Hz, J2 = 1.96 Hz, 1H), 4.02-4.06 (m,
1H), 4.18 (d, J = 3.2 Hz, 1H), 4.41 (d, J = 3.2 Hz, 1H), 4.96 (s, 1H), 7.11-7.16 (m, 4H), 7.23-
13
7.30 (m, 4H). C NMR (CDCl3, 125 MHz) δ 45.0, 46.7, 48.4, 53.7, 69.8, 101.5, 123.9, 124.0,
124.7, 125.3, 126.3, 126.4, 126.5, 140.77, 140.80, 143.4, 143.7. ESI-MS+ m/z [M+Na]+ Calcd for
C18H16O2Na: 287.1048, found: 287.1040.
5.3.22. 4,9-Benzo-3a,4,9,9a-tetrahydronaphtho[2,3-c]furan-1(3H)-one (16l).21 Colorless solid;
Rf (25% EtOAc/pet. ether) 0.40; 1H NMR (CDCl3, 400 MHz) δ 3.04-3.10 (m, 1H), 3.17-3.21 (m,
1H), 3.77-3.81 (m, 1H), 4.29 (d, J = 3.16 Hz), 4.33-4.37 (m, 1H), 4.71 (d, J = 3.44 Hz), 7.14-
7.19 (m, 4H), 7.29-7.37 (m, 4H).
5.3.23. Endo-perhydro-4,7-methanoisobenzofuran-1-one (18l).22 Colorless solid; Rf (25%
1
EtOAc/pet. ether) 0.50; H NMR (CDCl3, 500 MHz) δ 1.44-1.55 (m, 6H), 2.34 (s, 1H), 2.64 (s,
1H), 2.82-2.86 (m, 1H), 2.93-2.97 (m, 1H), 4.20-4.29 (m, 2H).
5.3.24. Exo-perhydro-4,7-epoxyisobenzofuran-1-one (19l) 23
Colorless solid; Rf (25%
.
1
EtOAc/pet. ether) 0.40; H NMR (CDCl3, 500 MHz) δ 1.47-1.60 (m, 2H), 1.73-1.85 (m, 2H),
17

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2.70-2.74 (m, 1H), 2.78-2.80 (d, J = 8.25 Hz, 1H), 4.12 (dd, J1 = 9.45 Hz, J2 = 3.95 Hz, 1H),
4.43 (t, J = 9.2 Hz, 1H), 4.54 (d, J = 4.9 Hz, 1H), 4.88 (d, J = 4.85, 1H).
Acknowledgments. JNM is thankful to the Council of Scientific and Industrial Research (CSIR),
India for financial support. SS and SJ gratefully acknowledge SPM and junior research
fellowships, respectively, from CSIR, India.
Supporting Information Available. 1H and 13C NMR spectral reproductions for the
intermediates, target compound and the products of oxidations.
18

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References
1. (a) Procter, G. in Comprehensive Organic Synthesis; Eds.: Trost, B. M.; Fleming, I.; Ley,
S. V.; Pergamon: Oxford, 1991, 7, 312. (b) Ley, S. V.; Norman, J.; Pinel, C. Tetrahedron
Lett. 1994, 35, 2095. (c) Tanaka, T.; Kouno, I. J. Nat. Prod. 1996, 59, 997. (d) Suzuki, T.;
Ohmori, K.; Suzuki, K. Org. Lett. 2001, 3, 1741. (e) Pal, S. Tetrahedron 2006, 62, 3171.
2. (a) Fétizon, M.; Golfier, M. Acad. Sci. Ser. C 1968, 276, 900. (b) Fétizon, M.; Golfier, M.;
Louis, J-M. Chem. Commun. 1969, 1118. (c) Fétizon, M.; Golfier, M.; Louis, J-M.
Tetrahedron 1975, 31, 171.
3. (a) Beebe, T. R.; Adkins, R.; Baldridge, R.; Hensley, V.; McMillen, D.; Morris, D.; Noe,
R.; Ng, F. W.; Powell, G.; Spielberger, C.; Stolte, M. J. Org. Chem. 1987, 52, 5472. (b)
Lin, Y.; Zhu, X.; Zhou, Y. J. Organomet. Chem. 1992, 429, 269. (c) Aït-Mohand, S.;
Muzart, J. J. Mol. Cat. A 1998, 129, 135. (d) Hirano, M.; Yakabe, S.; Morimoto, T. Synth.
Commun. 1998, 28, 123. (e) Jung, H. M.; Choi, J. H.; Lee, S. O.; Kim, Y. H.; Park, J. H.;
park, J. Organometallics 2002, 21, 5674. (f) Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K.
Org. Lett. 2002, 4, 2361. (g) Hiegel, G. A.; Gilley, C. B. Synth. Commun. 2003, 33, 2003.
(h) Zhu, Q-J.; Dai, W-L.; Fan, K-N. Green Chem. 2010, 12, 205. (i) Coleman, M. G.;
Brown, A. N.; Bolton, B. A.; Guan, H. Adv. Synth. Catal. 2010, 352, 967. (j) Endo, Y.;
Bäckvall, J-E. Chem. −Eur. J. 2011, 17, 12596.
4. Tohma, H.; Maegawa, T.; Takizawa, S.; Kita, Y. Adv. Synth. Catal. 2002, 344, 328.
5. Seth, S.; Jhulki, S.; Moorthy, J. N. Eur. J. Org. Chem. 2013, 2445.
6. (a) Thottumkara, A. P.; Bowsher, M. S.; Vinod, T. K. Org. Lett. 2005, 7, 2933. (b) Schulze,
A.; Giannis, A. Synthesis 2006, 257. (c) Uyanik, M.; Akakura, M.; Ishihara, K. J. Am.
Chem. Soc. 2009, 131, 251.
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7. Moorthy, J. N.; Senapati, K.; Parida, K. N.; Jhulki, S.; Sooraj, K.; Nair, N. N. J. Org.
Chem. 2011, 76, 9593.
8. Corey, E. J.; Palani, A. Tetrahedron Lett. 1995, 36, 3485.
9. Moorthy, J. N.; Singhal, N.; Mal, P. Tetrahedron Lett. 2004, 45, 309.
10. Zhang, Y-H.; Shi, B-F.; Yu, J-Q. Angew. Chem. Int. Ed. 2009, 48, 6097.
11. Padwa, A.; Bullock, W. H.; Norman, B. H.; Perumattam, J. J. Org. Chem. 1991, 56, 4263.
12. Zhang, Y-H.; Shi, B-F.; Yu, J-Q. Angew. Chem. Int. Ed. 2009, 48, 6097.
13. Cheng, P-N.; Chiang, P-T.; Chiu, S-H. Chem. Commun. 2005, 1285.
14. Edwards, D. J.; House, D.; Sheldrake, H. M.; Stone, S. J.; Wallace, T. M. Org. Biomol.
Chem. 2007, 5, 2658.
15. Ide, T.; Takeuchi, D.; Osakada, K. Chem. Commun. 2012, 48, 278.
16. Bonvin, Y.; Callens, E.; Larrosa, I.; Henderson, D. A.; Oldham, J.; Barrett, A. G. M. Org.
Lett. 2005, 7, 4549.
17. Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. Org. Lett. 2002, 4, 2361.
18. Magens, S.; Plietker, B. J. Org. Chem. 2010, 75, 3715.
19. Lokare, K. S.; Odom, A. L. Inorg. Chem. 2008, 47, 11191.
20. Martins, E. O.; Gleason, J. L. Org. Lett. 1999, 1, 1643.
21. Smet, M.; Corens, D.; Dehaen, W. ARKIVOC 2003, 51.
22. Metz, P. Tetrahedron 1989, 45, 7311.
23. Koshiba, T.; Yokoshima, S.; Fukuyama, T. Org. Lett. 2009, 11, 5354.
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SUPPORTING INFORMATION
Facile Organocatalytic Domino Oxidation of Diols to Lactones by In Situ-Generated
TetMe-IBX
Samik Jhulki, Saona Seth, Manas Mondal and Jarugu Narasimha Moorthy*
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, INDIA
moorthy@iitk.ac.in
Table of Contents
1
2
3
4
5
6
7
1H NMR spectrum of isobenzofuran-1(3H)-one in CDCl3.
S-3
S-4
S-5
S-6
S-7
S-8
1H NMR spectrum 5,6-dimethylisobenzofuran-1(3H)-one in CDCl3
1H NMR spectrum of 5-bromoisobenzofuran-1(3H)-one in CDCl3
1H NMR spectrum of 6-bromoisobenzofuran-1(3H)-one in CDCl3
1H NMR spectrum of 5,6-dichloroisobenzofuran-1(3H)-one in CDCl3
1H NMR spectrum of 5,6-dibromoisobenzofuran-1(3H)-one in CDCl3
1H and 13C NMR spectra of 4,5,6,7-tetrachloro-1,3-dihydroisobenzofuran- S-9
1-ol in CD3OD
8
1H and 13C NMR spectra of 4,5,6,7-tetrachloroisobenzofuran-1(3H)-one in S-10
CDCl3
9
1H and 13C NMR spectra of 6-cyanoisobenzofuran-1(3H)-one in CDCl3
1H and 13C NMR spectra of 5-cyanoisobenzofuran-1(3H)-one in CDCl3
1H NMR spectrum dibenzo[c,e]oxepin-5(7H)-one in CDCl3
1H NMR spectrum biphenyl-2,2'-dicarbaldehyde in CDCl3
1H NMR spectrum of isochroman-1-one in CDCl3
S-11
S-12
S-13
S-14
S-15
10
11
12
13
14
1H and 13C NMR spectra of 1,3,4,5-tetrahydrobenzo[c]oxepin-1-ol in S-16
CDCl3
15
16
1H NMR spectrum of dihydrofuran-2(3H)-one in CDCl3
1H NMR spectrum of 5-methyldihydrofuran-2(3H)-one in CDCl3
S-17
S-18
S‐1

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17
18
19
20
21
1H NMR spectrum of tetrahydro-2H-pyran-2-one in CDCl3
1H NMR spectrum of ε-caprolactone in CDCl3
1H NMR spectrum of 4-hydroxy-1-phenylbutan-1-one in CDCl3
1H NMR spectrum of 5-phenyldihydrofuran-2(3H)-one in CDCl3
1H (400 MHz) and 13C NMR (125 MHz) spectra of 4,9-benzo-
1,3,3a,4,9,9a-hexahydronaphtho[2,3-c]furan-1-ol in CDCl3
S-19
S-20
S-21
S-22
S-23
22
23
1H NMR spectrum of 4,9-benzo-3a,4,9,9a-tetrahydronaphtho[2,3-c]furan- S-24
1(3H)-one in CDCl3
1H (500 MHz) and 13C (125 MHz) NMR spectra of a mixture of two S-25
regioisomeric lactols obtained from the oxidation of 5-methoxy-11,12-
dihydrodibenzobarrelene-11,12-dimethanol in CDCl3
24
1H (500 MHz) and 13C (125 MHz) NMR spectra of a mixture of two
regioisomeric lactones obtained from the oxidation of 5-methoxy-11,12-
dihydrodibenzobarrelene-11,12-dimethanol in CDCl3
1H NMR spectrum of Endo-perhydro-4,7-methanoisobenzofuran-1-one
in CDCl3
S-26
25
26
27
S-27
S-28
S-29
1H NMR spectrum of exo-perhydro-4,7-epoxyisobenzofuranone in
CDCl3
References
S‐2

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O
O
FIGURE S1. 1H NMR (400 MHz) spectrum of isobenzofuran-1(3H)-one (1l)1 in CDCl3.
S‐3

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O
Me
Me
O
1
FIGURE S2. H NMR (500 MHz) spectrum 5,6-dimethylisobenzofuran-1(3H)-one (2l)2 in
CDCl3.
S‐4

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O
O
Br
1
FIGURE S3. H NMR (400 MHz) spectrum of 5-bromoisobenzofuran-1(3H)-one (3la)3 in
CDCl3.
S‐5

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O
Br
O
1
FIGURE S4. H NMR (400 MHz) spectrum of 6-bromoisobenzofuran-1(3H)-one (3lb)4 in
CDCl3.
S‐6

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O
Cl
Cl
O
1
FIGURE S5. H NMR (500 MHz) spectrum of 5,6-dichloroisobenzofuran-1(3H)-one (4l)5 in
CDCl3.
S‐7

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O
Br
Br
O
1
FIGURE S6. H NMR (500 MHz) spectrum of 5,6-dibromoisobenzofuran-1(3H)-one (5l)6 in
CDCl3.
S‐8

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Cl
Cl
OH
O
Cl
Cl
Cl
Cl
OH
O
Cl
Cl
1
FIGURE S7. H (500 MHz) and 13C NMR (125 MHz) spectra of 4,5,6,7-tetrachloro-1,3-
dihydroisobenzofuran-1-ol (6o) in CD3OD.
S‐9