Oxidative cyclization of dialdehydes with alcohols and 1,3-dicarbonyl compounds under Rh(III)/Cu(II) conditions

Article abstract of DOI:10.1016/j.tet.2015.10.034

For the preparation of 3-alkoxyphthalides from phthalaldehydes and alcohols, a cyclization reaction in the presence of a rhodium(III) catalyst and copper(II) salt is reported. Cyclization of phthalaldehydes also occurs with 1,3-dicarbonyl compounds under similar conditions to produce 3-substituted phthalides in good yields. An acylrhodium(III) species might be a key intermediate in these cyclization reactions.

Full text of DOI:10.1016/j.tet.2015.10.034

Accepted Manuscript
Oxidative cyclization of dialdehydes with alcohols and 1,3-dicarbonyl compounds
under Rh(III)/Cu(II) conditions
Takanori Matsuda, Kentaro Suzuki, Shinya Abe, Haruki Kirikae, Noboru Okada
PII:
S0040-4020(15)30134-4
10.1016/j.tet.2015.10.034
TET 27206
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 July 2015
Revised Date: 9 October 2015
Accepted Date: 14 October 2015
Please cite this article as: Matsuda T, Suzuki K, Abe S, Kirikae H, Okada N, Oxidative cyclization of
dialdehydes with alcohols and 1,3-dicarbonyl compounds under Rh(III)/Cu(II) conditions, Tetrahedron
(2015), doi: 10.1016/j.tet.2015.10.034.
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Oxidative cyclization of dialdehydes with
alcohols and 1,3-dicarbonyl compounds
under Rh(III)/Cu(II) conditions
Leave this area blank for abstract info.
Takanori Matsuda , Kentaro Suzuki, Shinya Abe, Haruki Kirikae, Noboru Okada
Department of Applied Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601,
Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Oxidative cyclization of dialdehydes with alcohols and 1,3-dicarbonyl compounds
under Rh(III)/Cu(II) conditions
Takanori Matsuda , Kentaro Suzuki, Shinya Abe, Haruki Kirikae, Noboru Okada
Department of Applied Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
For the preparation of 3-alkoxyphthalides from phthalaldehydes and alcohols, a cyclization
reaction in the presence of a rhodium(III) catalyst and copper(II) salt is reported. Cyclization of
phthalaldehydes also occurs with 1,3-dicarbonyl compounds under similar conditions to produce
3-substituted phthalides in good yields. An acylrhodium(III) species might be a key intermediate
in these cyclization reactions.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Phthalaldehydes
Rhodium
C–C bond formation
Cyclization
Phthalides
———
Corresponding author. Tel.: +81 3 5228 8258; fax: +81 3 5261 4631; e-mail: mtd@rs.tus.ac.jp (T. Matsuda)

2
Tetrahedron
1. Introduction
Phthalides (isobenzofuran-1(3H)-ones) are
Table 1
ACCEPTED MANUSCRIPT
Optimization of the reaction conditionsa
a
group of
secondary metabolites that are produced by fungi, liverworts, and
plants.1 Many naturally occurring phthalides possess
pharmacological activities, and some phthalide-containing plants
were used as herbal remedies since ancient times. Given their
importance in synthetic, medicinal, and polymer chemistry, there
are a number of methods available for the preparation of 3-
substituted phthalides.2
Entry
EtOH (2a)
Mol% Rh
Equiv Cu
Yieldb (%)
1
2
3
4
5
1.0 mL (as solvent)
1.0 mL (as solvent)
1.0 mL (as solvent)
1.0 mL (as solvent)
20 equiv 2a
4
4
4
2
4
2
1
3
2
2
83
73
81
68
64
Significant progress has been made in the area of transition-
metal-catalyzed oxidative molecular transformations.3 Recently,
phthalide syntheses by oxidative coupling of benzoic acids with
alkenes,4 of benzimidates with aldehydes,5 of benzoic acids with
aldehydes,6 of mandelic acids with acrylates,7 and between two
aldehydes8 have been reported.9 Herein, we report the cyclization
of phthalaldehydes with alcohols to give 3-alkoxyphthalides after
twofold C–O bond formation in the presence of a rhodium(III)
catalyst and copper(II) salt (Rh(III)/Cu(II) system). 1,3-
Dicarbonyl compounds can also be used as nucleophiles in
cyclization with phthalaldehydes to afford the corresponding 3-
substituted phthalides after consecutive C–O and C–C bond
formation under the Rh(III)/Cu(II) system.10
in MeCN (1.0 mL)
1.0 mL (as solvent)
under N2
6
4
2
76
a
Reaction conditions: 1a (0.100 mmol) reacted with 2a (1.0
mL) in the presence of [Cp*RhCl2]2 and Cu(OAc)2 at 80 °C
under air.
b Isolated yield.
2. Results and discussion
The scope of the cyclization was investigated by coupling 1a
to a variety of alcohols (Table 2). Dialdehyde 1a reacted with
MeOH (2b) and cyclopropylmethanol (2c) to deliver 3-
alkoxyphthalides 3b and 3c in 62 and 64% yield, respectively
(entries 1 and 2). Secondary and tertiary alcohols (2d and 2e)
could also be used (entries 3 and 4). The reaction with 2e under
the optimized conditions was not efficient (46% yield), whereas
the yield was improved to 70% by performing the reaction at 100
°C. We also explored allylic alcohols 2f–h and established that
the reaction yielded the corresponding products 3f–h (entries 5–
7). The reaction of 1a with cinnamyl alcohol (2i, 5 equiv) in
hexane gave product 3i in 63% yield (entry 8). For benzylic
alcohols 2j and 2k the reaction was performed in MeCN and
afforded 3j and 3k, respectively (entries 9 and 10). Several other
phthalaldehyde derivatives were also tested for coupling with 2a.
When phthalaldehyde (1a, 0.100 mmol) was heated in EtOH
(2a, 1.0 mL, 17 mmol) in the presence of [Cp*RhCl2]2 (2 mol%
dimer, 4 mol% Rh; Cp* = pentamethylcyclopentadienyl) as the
catalyst and Cu(OAc)2 (2 equiv) as an oxidant at 80 °C under air,
a cyclization involving twofold C–O bond formation occurred to
afford 3-ethoxyphthalide (3a) in 83% yield (entry 1). Screening
the amounts of rhodium(III) catalyst and copper(II) salt revealed
that 2 mol% of the rhodium(III) dimer catalyst and 2 equiv of the
copper(II) salt were the optimal conditions (entries 1–4). The
reaction could be conducted with alcohol 2a (20 equiv) in MeCN
solvent to afford 3a in 64% yield (entry 5). The reaction
performed under a nitrogen atmosphere led to a slightly
decreased yield of 3a (entry 6).
4,5-Substituted
phthalaldehydes
1b–d
and
2,3-
naphthalenedicarboxaldehyde (1e) underwent cyclization with
EtOH (2a) to furnish products 3l–o (entries 11–14).11

3
Table 2
Cyclization of dialdehydes 1a–e with various alcohols 2a
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Entry
1
Dialdehyde 1
1a (R = H)
Alcohol (2)
MeOH (2b)
Product 3
Yieldb (%)
62c
3b
2
1a
(2c)
3c
64
3
4
1a
1a
i-PrOH (2d)
t-BuOH (2e)
3d
3e
53
46 (70)d
5
6
1a
1a
3f
40 (62)e
(2f)
(2g)
3g
52
7
1a
1a
(2h)
(2i)
3h
3i
38
63
8f
9g
1a
BnOH (2j)
3j
60
59
66
58
65
10g
11
12
13
1a
3,5-(MeO)2C6H3CH2OH (2k)
3k
3l
1b (R = Me)
1c (R = OMe)
1d (R = Cl)
2a
2a
2a
3m
3n
14
(1e)
2a
(3o)
46
a
Reaction conditions: Dialdehyde 1 (0.100 mmol) was reacted at 80 °C in alcohol 2 (1.0 mL) in the presence of [Cp*RhCl2]2 (2.0
µmol, 2 mol% dimer, 4 mol% Rh) and Cu(OAc)2 (0.200 mmol, 2 equiv) under air, unless otherwise noted.
b Isolated yield.
c Obtained as a 20:1 mixture of 3b and 1a. The yield of 3b was determined by 1H NMR.
d The reaction was performed at 100 °C.
e The reaction was performed with [Cp*RhCl2]2 (10 mol% dimer, 20 mol% Rh) at 60 °C.
f Alcohol (5 equiv) was reacted in hexane (1.0 mL).
g Alcohol (5 equiv) was reacted in MeCN (1.0 mL) in the presence of [Cp*RhCl2]2 (5 mol% dimer, 10 mol% Rh).
To better understand the reaction mechanism, several control
experiments were conducted (eqs 1–6). Reaction of 1a and
CD3OD (2b-d4) under the standard conditions afforded 3b-d3.
The protic deuterium atom of CD3OD was not incorporated into
the product (eq 1).
On the other hand, the reaction performed in the presence of a
catalytic amount of the rhodium(III) catalyst without Cu(OAc)2
resulted in the formation of mixture of three 1,3-
dihydroisobenzofuran derivatives, including 3a (eq 3).
a
(1)
(3)
No cyclization was observed when 1a was heated in 2a with
Cu(OAc)2 (2 equiv) in the absence of the rhodium(III) catalyst,
which indicated that the rhodium(III) catalyst was essential for
the formation of 3a (eq 2).
The reaction performed at a lower temperature (60 °C) gave a
mixture of two products, mainly 3a and a small amount of ethyl
2-formylbenzoate (4a), which indicated that 4a was a possible
intermediate en route to 3a (eq 4).
(2)

4
Tetrahedron
(Scheme 2).14 A rhodium hydride species may be responsible for
ACCEPTED MANUSCRIPT
the side reaction.
(4)
It was found that methyl 2-formylbenzoate (4b) was
efficiently converted into 3a as the sole product in the presence
of a catalytic amount of Cu(OAc)2 in 2a (eq 5).
Scheme 2. Formation of 5
We then examined the reactions of substrates that possessed a
ketone moiety. Reaction of 2-acetylbenzaldehyde (6a) in 2
provided 3-ethoxy-3-methylphthalide (7) in 26% yield under the
standard conditions (eq 7). The same product was also obtained
in limited yield from methyl 2-acetylbenzoate (6b).
(5)
However, 3-unsubstituted product 5 was obtained when 4b
was subjected to the reaction with 2a in the presence of the
rhodium(III) catalyst alone (eq 6).
(7)
(6)
We next sought to investigate if other nucleophiles might be
employed in the cyclization of 1 under the Rh(III)/Cu(II) system.
Although the use of phenols, thiols, amines, and carboxylic acids
as the nucleophilic partner failed, dimethyl malonate (8a)
functioned as an efficacious carbon nucleophile and reacted with
1a under similar conditions to give 3-alkylphthalide 9a in
excellent yield after consecutive C–O and C–C bond formation
(Table 3, entry 1). Other dialkyl malonates 8b and 8c also reacted
with 1a to furnish alkylated phthalides 9b and 9c, respectively, in
good yields (entries 2 and 3). In the reaction of 1a with β-keto
esters 8d–f, the corresponding products 9d–f were obtained as
diastereomeric mixtures (entries 4–6). The reaction was
successfully applied to methyl-substituted malonate 8g and β-
keto ester 8h (entries 7 and 8). Although the use of 2-
unsubstituted 1,3-diketones resulted in the formation of complex
mixtures of products or no reaction, 3-methylpentane-2,4-dione
(8i) coupled with 1a to afford 9i in 70% yield (entry 9). The
reaction of substituted phthalaldehydes 1l and 1o with 8a
delivered coupling products 9j and 9k, respectively (entries 10
and 11). We assume that the reaction with 8 would proceed via
path b (Scheme 1), in which the malonate methylene carbon atom
adds to the formyl group of intermediate A.
Based on the results of the aforementioned experiments, two
possible mechanisms accounting for the formation of 3 from 1
and 2 were proposed (Scheme 1). One possibility is that the
reaction proceeds by a Rh–Cu relay catalytic system. The first
step of the reaction would be the formation of acylrhodium(III)
species A that reacts with alcohol 2 to afford 2-formylbenzoate 4
(path a).12 Benzaldehyde failed to undergo the oxidative
esterification with 2a under the standard conditions, therefore the
oxidative esterification of a formyl group of 1a may be assisted
by the other formyl group. Lewis acid (copper)-catalyzed
intramolecular cyclization13 of
4 would give rise to 3-
alkoxyphthalide 3. In an alternative mechanism, catalyzed only
by rhodium(III) (path b), the acylrhodium(III) species A induces
nucleophilic addition of 2 to the formyl group to give six-
membered oxarhodacycle B. Subsequent reductive elimination
produces 3 and a rhodium(I) species, which is oxidized by the
copper(II) salt to regenerate the catalytically active rhodium(III)
species.
Table 3
Reaction of dialdehydes 1 with 1,3-dicarbonyl compounds
8a–ia
Scheme 1. Proposed mechanism.
Entry
1
8
9
Yieldb (%) drc
Formation of phthalide 5 can be accounted for by assuming an
intramolecular Tischenko-type reaction catalyzed by rhodium(III)

5
1
2
3
4
5
6
1a 8a (R1 = R2 = OMe)
1a 8b (R1 = R2 = OEt)
1a 8c (R1 = R2 = Oi-Pr)
9a 85
–
reported in the literature.15 The title compound (14.4 mg, 0.081
ACCEPTED MANUSCRIPT
mmol, 79%) was also obtained from the reaction of 4b (16.8 mg,
0.102 mmol) in EtOH (1.0 mL) in the presence of Cu(OAc)2 (0.9
mg, 0.005 mmol) for 1 h at 80 °C.
9b 79
–
9c 79
–
1a 8d (R1 = cyclopropyl, R2 = OMe) 9d 73
51:49
59:41
51:49
4.2.2. 3-Methoxy-1,3-dihydro-2-benzofuran-1-one
(3b).
1a 8e (R1 = t-Bu, R2 = OEt)
1a 8f (R1 = Ph, R2 = OEt)
9e 70
9f 62
According to GP-1, 1a (13.4 mg, 0.100 mmol) was reacted in
MeOH (2b, 1.0 mL) for 3 h. Purification by preparative TLC on
silica gel (hexane:AcOEt = 3:1) afforded a mixture of 3b and 1a
(20:1 determined by 1H NMR; 10.1 mg and 0.4 mg,
respectively). The estimated yield of 3b was 62%. 1H NMR
(CDCl3, 300 MHz) δ 3.64 (s, 3H), 6.31 (s, 1H), 7.55–7.64 (m,
2H), 7.72 (dt, J = 1.0, 7.4 Hz, 1H), 7.87–7.91 (m, 1H). The
spectral data matched those reported in the literature.16
7
1a 8g (R1 = R2 = OEt)
1a 8h (R1 = Me, R2 = OEt)
1a 8i (R1 = R2 = Me)
9g 72
9h 94
–
8
67:33
4.2.3. 3-(Cyclopropylmethoxy)-1,3-dihydro-2-benzofuran-1-one
(3c). According to GP-1, 1a (13.3 mg, 0.099 mmol) was reacted
in cyclopropylmethanol (2c, 1.0 mL) for 4 h. Purification by
preparative TLC on silica gel (hexane:AcOEt = 2:1) afforded 3c
(12.9 mg, 0.063 mmol, 64%) as a colorless oil. 1H NMR (CDCl3,
300 MHz) δ 0.23–0.26 (m, 2H), 0.54–0.68 (m, 2H), 1.11–1.24
(m, 1H), 3.64–3.76 (m, 2H), 6.44 (s, 1H), 7.56–7.63 (m, 2H),
7.68–7.75 (m, 1H), 7.86–7.91 (m, 1H); 13C NMR (CDCl3, 126
MHz) δ 3.08, 3.43, 10.3, 74.8, 101.9, 123.4, 125.4, 127.2, 130.7,
134.4, 145.0, 168.8; HRMS (ESI) calcd for C12H12NaO3 [M +
Na]+ 227.0679, found 227.0673; IR (ν/cm–1): 1774, 1065, 1011.
9
9i
9j
70
78
–
–
–
10
11
1l
8a
1o 8a
9k 64
a Reaction conditions: Dialdehyde 1 (0.100 mmol) was reacted
with dicarbonyl compound 8 (0.200 mmol) in THF (1.0 mL) at
reflux in the presence of [Cp*RhCl2]2 (2.0 µmol, 2 mol% dimer,
4 mol% Rh) and Cu(OAc)2 (0.150 mmol, 1.5 equiv) under air.
b Isolated yield.
c Determined by 1H NMR.
4.2.4. 3-Isopropoxy-1,3-dihydro-2-benzofuran-1-one
(3d).
According to GP-1, 1a (13.1 mg, 0.098 mmol) was reacted in 2-
propanol (2d, 1.0 mL) for 4 h. Purification by preparative TLC
on silica gel (hexane:AcOEt = 3:1) afforded 3d (10.0 mg, 0.052
3. Conclusion
In summary, an oxidative coupling reaction affording 3-
substituted phthalides has been developed. Phthalaldehydes
coupled with a variety of alcohols in the presence of a
rhodium(III) catalyst and
alkoxyphthalides in yields
rhodium(III)/copper(II) conditions are also effective for the
cyclization of phthalaldehydes with 1,3-dicarbonyl compounds,
which leads to the formation of 3-alkylphthalides in good yields.
1
mmol, 53%) as a white solid. Mp 68 °C; H NMR (CDCl3, 500
MHz) δ 1.34 (d, J = 6.0 Hz, 3H), 1.37 (d, J = 6.0 Hz, 3H), 4.24
(septet, J = 6.3 Hz, 1H), 6.43 (s, 1H), 7.55 (d, J = 7.5 Hz, 1H),
7.58 (t, J = 7.2 Hz, 1H), 7.70 (t, J = 7.3 Hz, 1H), 7.88 (d, J = 7.0
Hz, 1H); 13C NMR (CDCl3, 75.6 MHz) δ 22.1, 23.2, 73.7, 101.4,
123.3, 125.3, 127.2, 130.6, 134.3, 145.5, 168.9; HRMS (ESI)
calcd for C11H12NaO3 [M + Na]+ 215.0679, found 215.0680; IR
(ν/cm–1): 1759, 1065, 903.
a
copper(II) salt to afford 3-
up to 70%. The
4. Experimental section
4.1. General
4.2.5. 3-(tert-Butoxy)-1,3-dihydro-2-benzofuran-1-one
(3e).
According to GP-1, 1a (13.3 mg, 0.099 mmol) was reacted in 2-
methyl-2-propanol (2e, 1.0 mL) at 100 °C for 16 h. Purification
by preparative TLC on silica gel (hexane:AcOEt = 3:1) afforded
All reactions were carried out with standard Schlenk
techniques under an air atmosphere. Column chromatography
was carried out on Wakogel® C-200 (75–150 µm). Preparative
thin-layer chromatography (TLC) was performed on Wakogel®
B-5F. Proton chemical shifts were referenced to residual CHCl3
signal at 7.26 ppm. Carbon chemical shifts were referenced to
CDCl3 at 77.0 ppm. All reagents and solvents were used as
received without further purification.
1
3e (14.4 mg, 0.070 mmol, 70%) as a white solid. Mp 88 °C; H
NMR (CDCl3, 300 MHz) δ 1.45 (s, 9H), 6.55 (s, 1H), 7.46–7.51
(m, 1H), 7.53–7.60 (m, 1H), 7.69 (dt, J = 1.1, 7.4 Hz, 1H), 7.84–
7.89 (m, 1H); 13C NMR (CDCl3, 75.6 MHz) δ 28.6, 77.8, 97.9,
123.2, 125.2, 127.1, 130.4, 134.2, 146.4, 169.1; HRMS (ESI)
calcd for C12H14NaO3 [M + Na]+ 229.0835, found 229.0834; IR
(ν/cm–1): 1759, 1065, 910.
4.2.6. 3-(Crotyloxy)-1,3-dihydro-2-benzofuran-1-one (3f). 1a
(13.3 mg, 0.099 mmol) was reacted in crotyl alcohol (2f, 1.0 mL)
in the presence of [Cp*RhCl2]2 (6.6 mg, 10.7 µmol, 21.5 mol%
Rh) and Cu(OAc)2 (36.7 mg, 0.202 mmol) at 60 °C for 17 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:1) afforded 3f (12.5 mg, 0.061 mmol, 62%) as a colorless oil.
1H NMR (CDCl3, 300 MHz) δ 1.73–1.78 (m, 3H), 4.23–4.42 (m,
2H), 5.59–5.73 (m, 1H), 5.78–5.93 (m, 1H), 6.40 (s, 1H), 7.55–
7.63 (m, 2H), 7.64–7.74 (m, 1H), 7.85–7.91 (m, 1H); 13C NMR
(CDCl3, 75.5 MHz) δ 17.8, 70.6, 101.1, 123.4, 125.4, 125.6,
127.1, 130.7, 132.2, 134.3, 145.1, 168.7; HRMS (ESI) calcd for
C12H12NaO3 [M + Na]+ 227.0679, found 227.0676; IR (ν/cm–1):
1774, 1288, 1065, 926.
4.2. General Procedure for Cyclization of Phthalaldehydes 1
with Alcohols 2 (GP-1).
Schlenk tube was charged with dialdehyde 1 (0.100 mmol),
[Cp*RhCl2]2 (2.0 µmol, 2 mol% dimer, 4 mol% Rh), Cu(OAc)2
(0.200 mmol), and then alcohol 2 (1.0 mL) was added. The
mixture was stirred at 80 °C under air. The reaction mixture was
filtered through a plug of Florisil® washing with hexane–AcOEt,
and the filtrate was concentrated. The residue was purified by
preparative TLC on silica gel to afford the following compounds.
4.2.1. 3-Ethoxy-1,3-dihydro-2-benzofuran-1-one (3a). According
to GP-1, 1a (13.8 mg, 0.103 mmol) was reacted in EtOH (1.0
mL) for 3 h. Purification by preparative TLC on silica gel
(hexane:AcOEt = 3:1) afforded 3a (15.3 mg, 0.086 mmol, 83%)
4.2.7. 3-(Methallyloxy)-1,3-dihydro-2-benzofuran-1-one
(3g).
According to GP-1, 1a (13.2 mg, 0.098 mmol) was reacted in
methallyl alcohol (2g, 1.0 mL) for 4.5 h. Purification by
preparative TLC on silica gel (hexane:AcOEt = 3:1) afforded 3g
(10.5 mg, 0.051 mmol, 52%) as a colorless oil. 1H NMR (CDCl3,
300 MHz) δ 1.83 (s, 3H), 4.22–4.35 (m, 2H), 4.99–5.03 (m, 1H),
1
as a white solid. Mp 69 °C; H NMR (CDCl3, 300 MHz) δ 1.32
(t, J = 7.1 Hz, 3H), 3.86 (dq, J = 9.4, 7.0 Hz, 1H), 3.99 (dq, J =
9.3, 7.1 Hz, 1H), 6.37 (s, 1H), 7.55–7.62 (m, 2H), 7.64–7.74 (m,
1H), 7.85–7.90 (m, 1H). The spectral data matched those

6
Tetrahedron
5.06–5.10 (m, 1H), 6.39 (s, 1H), 7.56–7.64 (m, 2H), 7.71 (dt, J
1H), 3.96 (dq, J = 9.2, 7.1 Hz, 1H), 6.30 (s, 1H), 7.33 (s, 1H),
ACCEPTED MANUSCRIPT
= 1.2, 7.5 Hz, 1H), 7.87–7.92 (m, 1H); 13C NMR (CDCl3, 75.6
MHz) δ 19.5, 73.6, 101.2, 114.2, 123.4, 125.5, 127.2, 130.8,
134.4, 140.3, 145.0, 168.7; HRMS (ESI) calcd for C12H12NaO3
[M + Na]+ 227.0679, found 227.0679; IR (ν/cm–1): 1774, 1134,
926.
7.62 (s, 1H); 13C NMR (CDCl3, 126 MHz) δ 15.1, 20.0, 20.7,
65.6, 102.1, 124.0, 125.0, 125.8, 140.0, 143.2, 144.5, 169.1;
HRMS (ESI) calcd for C12H14NaO3 [M + Na]+ 229.0835, found
229.0831; IR (ν/cm–1): 1759, 1088, 918.
4.2.13. 3-Ethoxy-5,6-dimethoxy-1,3-dihydro-2-benzofuran-1-one
(3m). According to GP-1, 1c (19.4 mg, 0.100 mmol) was reacted
in 2a (1.0 mL) for 5.5 h. Purification by preparative TLC on
silica gel (hexane:AcOEt = 3:1) afforded 3m (13.9 mg, 0.058
4.2.8. 3-[(2-Methylbut-3-en-2-yl)oxy]-1,3-dihydro-2-benzofuran-
1-one (3h). According to GP-1, 1a (13.4 mg, 0.100 mmol) was
reacted in 2-methyl-3-buten-2-ol (2h, 1.0 mL) for 20 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:1) afforded 3h (8.2 mg, 0.038 mmol, 38%) as a white solid. Mp
1
mmol, 58%) as a colorless oil. H NMR (CDCl3, 300 MHz) δ
1.31 (t, J = 7.1 Hz, 3H), 3.77–4.02 (m, 8H), 6.26 (s, 1H), 6.98 (s,
1H), 7.25 (s, 1H); 13C NMR (CDCl3, 126 MHz) δ 15.1, 56.3,
56.4, 65.7, 101.7, 104.6, 105.8, 119.2, 139.4, 151.5, 154.9, 169.0;
HRMS (ESI) calcd for C12H14NaO5 [M + Na]+ 261.0733, found
261.0734; IR (ν/cm–1): 1766, 1350, 1103.
1
50 °C; H NMR (CDCl3, 300 MHz) δ 1.46 (s, 3H), 1.56 (s, 3H),
5.31–5.42 (m, 2H), 6.06 (dd, J = 17.6, 10.6 Hz, 1H), 6.43 (s, 1H),
7.46–7.51 (m, 1H), 7.52–7.60 (m, 1H), 7.68 (dt, J = 1.2, 7.5 Hz,
1H), 7.83–7.88 (m, 1H); 13C NMR (CDCl3, 75.6 MHz) δ 25.4,
28.0, 79.5, 98.4, 116.2, 123.2, 125.2, 127.1, 130.5, 134.2, 142.2,
146.3, 169.0; HRMS (ESI) calcd for C13H14NaO3 [M + Na]+
241.0835, found 241.0839; IR (ν/cm–1): 1759, 1065, 933.
4.2.14. 5,6-Dichloro-3-ethoxy-1,3-dihydro-2-benzofuran-1-one
(3n). According to GP-1, 1d (16.5 mg, 0.081 mmol) was reacted
in 2a (1.0 mL) for 12 h. Purification by preparative TLC on silica
gel (hexane:AcOEt = 3:2) afforded 3n (13.1 mg, 0.053 mmol,
4.2.9. 3-(Cinnamyloxy)-1,3-dihydro-2-benzofuran-1-one (3i). 1a
(13.1 mg, 0.098 mmol) was reacted with cinnamyl alcohol (2i,
62.5 mg, 0.466 mmol) in hexane (1.0 mL) in the presence of
[Cp*RhCl2]2 (1.2 mg, 1.9 µmol, 4.0 mol% Rh) and Cu(OAc)2
(36.3 mg, 0.200 mmol) for 5 h. Purification by preparative TLC
on silica gel (hexane:AcOEt = 3:1) afforded 3i (16.4 mg, 0.062
1
65%) as a white solid. Mp 103–105 °C; H NMR (CDCl3, 300
MHz) δ 1.33 (t, J = 7.0 Hz, 3H), 3.87 (dq, J = 9.2, 7.1 Hz, 1H),
4.01 (dq, J = 9.3, 7.1 Hz, 1H), 6.32 (s, 1H), 7.70 (s, 1H), 7.95 (s,
1H); 13C NMR (CDCl3, 75.5 MHz) δ 15.0, 66.5, 101.4, 125.7,
126.9, 127.1, 135.9, 139.4, 144.0, 166.5; HRMS (ESI) calcd for
C10H8Cl2NaO3 [M + Na]+ 268.9743, found 268.9743; IR (ν/cm–1):
1782, 1342, 933.
1
mmol, 63%) as a colorless oil. H NMR (CDCl3, 300 MHz) δ
4.51 (ddd, J = 12.2, 7.1, 1.3 Hz, 1H), 4.61 (ddd, J = 12.2, 5.9, 1.4
Hz, 1H), 6.36 (ddd, J = 15.8, 7.0, 5.8 Hz, 1H), 6.47 (s, 1H), 6.68–
6.76 (m, 1H), 7.23–7.37 (m, 3H), 7.38–7.44 (m, 2H), 7.57–7.64
(m, 2H), 7.68–7.75 (m, 1H), 7.88–7.93 (m, 1H); 13C NMR
(CDCl3, 126 MHz) δ 70.4, 101.1, 123.5, 123.7, 125.5, 126.7,
127.2, 128.1, 128.6, 130.8, 134.4, 134.7, 136.1, 145.1, 168.6;
HRMS (ESI) calcd for C17H14NaO3 [M + Na]+ 289.0835, found
289.0834; IR (ν/cm–1): 1774, 1065, 926, 748.
4.2.15. 3-Ethoxy-1H,3H-naphtho[2,3-c]furan-1-one
(3o).
According to GP-1, 1e (18.4 mg, 0.100 mmol) was reacted in 2a
(1.0 mL) for 5 h. Purification by preparative TLC on silica gel
(hexane:AcOEt = 5:1) afforded 3o (10.4 mg, 0.046 mmol, 46%)
as a white solid. Mp 178 °C; 1H NMR (CDCl3, 300 MHz) δ 1.36
(t, J = 7.0 Hz, 3H), 3.92 (dq, J = 9.3, 7.1 Hz, 1H), 4.05 (dq, J =
9.2, 7.1 Hz, 1H), 6.53 (s, 1H), 7.58–7.71 (m, 2H), 7.98 (d, J = 7.8
Hz, 1H), 8.00–8.07 (m, 2H), 8.44 (s, 1H); 13C NMR (CDCl3, 75.5
MHz) δ 15.1, 65.8, 102.5, 123.0, 124.3, 126.9, 127.6, 128.7,
129.1, 129.9, 134.0, 136.2, 139.1, 168.8; HRMS (ESI) calcd for
C14H12NaO3 [M + Na]+ 251.0679, found 251.0694; IR (ν/cm–1):
1774, 1088, 933.
4.2.10. 3-(Benzyloxy)-1,3-dihydro-2-benzofuran-1-one (3j). 1a
(13.1 mg, 0.098 mmol) was reacted with benzyl alcohol (2j, 52.0
mg, 0.481 mmol) in MeCN (1.0 mL) in the presence of
[Cp*RhCl2]2 (1.5 mg, 2.4 µmol, 5.0 mol% Rh) and Cu(OAc)2
(36.7 mg, 0.202 mmol) for 4 h. Purification by preparative TLC
on silica gel (hexane:AcOEt = 4:1) afforded 3j (14.0 mg, 0.058
1
4.2.16. 3-(²H )Methoxy-1,3-dihydro-2-benzofuran-1-one (3b-
d3). According to GP-1, 1a (13.4 mg, 0.100 mmol) was reacted in
CD3OD (2b-d4, 1.0 mL) for 3 h at 70 °C. Purification by
preparative TLC on silica gel (hexane:AcOEt = 3:1) afforded a
mmol, 60%) as a colorless oil. H NMR (CDCl3, 500 MHz) δ
4.85 (d, J = 12.0 Hz, 1H), 4.97 (d, J = 11.0 Hz, 1H), 6.43 (s, 1H),
7.32–7.44 (m, 5H), 7.55–7.62 (m, 2H), 7.70 (t, J = 7.5 Hz, 1H),
7.90 (d, J = 7.0 Hz, 1H); 13C NMR (CDCl3, 126 MHz) δ 71.5,
101.0, 123.5, 125.5, 127.2, 128.3, 128.4, 128.6, 130.8, 134.3,
136.1, 145.0, 168.6; HRMS (ESI) calcd for C15H12NaO3 [M +
Na]+ 263.0679, found 263.0681; IR (ν/cm–1): 1774, 1049, 933.
1
mixture of 3b-d3 and 1a (10:1 determined by H NMR; 11.1 mg
and 0.9 mg, respectively). The estimated yield of 3b-d3 was 66%.
1H NMR (CDCl3, 300 MHz) δ 6.30 (s, 1H), 7.55–7.62 (m, 2H),
7.68–7.73 (m, 1H), 7.86–7.90 (m, 1H); 13C NMR (CDCl3, 126
MHz) δ 55.9 (t, J = 21.6 Hz), 103.0, 123.4, 125.4, 127.2, 130.8,
134.4, 144.7, 168.6; HRMS (ESI) calcd for C9H5D3NaO3 [M +
Na]+ 190.0554, found 190.0555; IR (ν/cm–1): 1774, 1065, 926.
4.2.11. 3-[(3,5-Dimethoxybenzyl)oxy]-1,3-dihydro-2-benzofuran-
1-one (3k). 1a (13.2 mg, 0.098 mmol) was reacted with (3,5-
dimethoxyphenyl)methanol (2k, 84.2 mg, 0.501 mmol) in MeCN
(1.0 mL) in the presence of [Cp*RhCl2]2 (3.3 mg, 5.3 µmol, 10.9
mol% Rh) and Cu(OAc)2 (36.3 mg, 0.200 mmol) for 11.5 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:1) afforded 3k (17.4 mg, 0.058 mmol, 59%) as a colorless oil.
1H NMR (CDCl3, 300 MHz) δ 3.80 (s, 6H), 4.77 (d, J = 11.7 Hz,
1H), 4.89 (d, J = 11.7 Hz, 1H), 6.41–6.44 (m, 2H), 6.55–6.58 (m,
2H), 7.55–7.63 (m, 2H), 7.70 (dt, J = 1.1, 7.4 Hz, 1H), 7.87–7.92
(m, 1H); 13C NMR (CDCl3, 75.6 MHz) δ 55.4, 71.4, 100.2,
100.9, 106.1, 123.5, 125.5, 127.1, 130.8, 134.4, 138.3, 144.9,
161.0, 168.7; HRMS (ESI) calcd for C17H16NaO5 [M + Na]+
323.0890, found 323.0888; IR (ν/cm–1): 1774, 1604, 1466, 1157.
4.2.17. 1,3-Dihydro-2-benzofuran-1-one (5). 4b (13.2 mg, 0.191
mmol) was reacted in 2a (2.0 mL) in the presence of [Cp*RhCl2]2
(2.7 mg, 4.4 µmol, 4.6 mol% Rh) for 5.5 h. Purification by
preparative TLC on silica gel (hexane:AcOEt = 5:1) afforded 5
(18.0 mg, 0.134 mmol, 70%).
4.2.18. 3-Ethoxy-3-methyl-1,3-dihydro-2-benzofuran-1-one (7).
According to GP-1, 6a (14.8 mg, 0.100 mmol) was reacted in 2a
(1.0 mL) for 3 h. Purification by preparative TLC on silica gel
(hexane:AcOEt = 3:1) afforded 7 (5.0 mg, 0.026 mmol, 26%) as
a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 1.15 (t, J = 6.9 Hz,
3H), 1.84 (s, 3H), 3.06 (dq, J = 8.8, 7.1 Hz, 1H), 3.41 (dq, J =
8.6, 7.1 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.58 (t, J = 7.4 Hz,
1H), 7.72 (t, J = 7.0 Hz, 1H), 7.88 (d, J = 7.5 Hz, 1H). The
spectral data matched those reported in the literature.17
4.2.12. 3-Ethoxy-5,6-dimethyl-1,3-dihydro-2-benzofuran-1-one
(3l). According to GP-1, 1b (16.4 mg, 0.101 mmol) was reacted
in 2a (1.0 mL) for 2 h. Purification by preparative TLC on silica
gel (hexane:AcOEt = 5:1) afforded 3l (13.8 mg, 0.067 mmol,
66%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 1.31 (t, J =
7.3 Hz, 3H), 2.35 (s, 3H), 2.38 (s, 3H), 3.83 (dq, J = 9.4, 7.2 Hz,
4.3. General Procedure for Cyclization of Phthalaldehydes 1
with 1,3-Dicarbonyl Compounds 8 (GP-2).

7
7.26–7.29 (m, 1H), 7.52–7.59 (m, 1H+2H), 7.59–7.64 (m, 1H),
A Schlenk tube was charged with dialdehyde 1 (0.100 mmol),
[Cp*RhCl2]2 (2.0 µmol, 2 mol% dimer, 4 mol% Rh), Cu(OAc)2
(0.150 mmol), and then THF (1.0 mL) and 1,3-dicarbonyl
compound 8 (0.200 mmol) were added. The mixture was heated
at reflux under air. The reaction mixture was filtered through a
plug of Florisil® washing with hexane–AcOEt, and the filtrate
was concentrated. The residue was purified by preparative TLC
on silica gel to afford the following compounds.
ACCEPTED MANUSCRIPT
7.66 (dt, J = 1.2, 7.4 Hz, 1H), 7.88–7.93 (m, 1H+1H); 13C NMR
(CDCl3, 75.6 MHz) δ 13.9, 14.0, 26.08, 26.14, 45.8, 56.7, 58.3,
62.0, 62.4, 79.5, 79.8, 123.4, 125.88, 125.94, 126.0, 126.1, 129.8,
134.1, 134.3, 147.3, 147.5, 165.9, 166.0, 169.2, 169.4, 206.3,
207.2; HRMS (ESI) calcd for C17H20NaO5 [M + Na]+ 327.1203,
found 327.1201; IR (ν/cm–1): 1774, 1743, 1712, 1288.
4.3.6. 3-(1-Ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-1,3-dihydro-
2-benzofuran-1-one (9f). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8f (38.3 mg, 0.199 mmol) were reacted for 5 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9f (20.2 mg, 0.062 mmol, 62%, 52:48 diastereomer
ratio determined by 1H NMR) as a colorless oil. 1H NMR
(CDCl3, 301 MHz) δ 1.08 (t, J = 7.2 Hz, 3H), 1.24 (t, J = 7.3 Hz,
3H), 4.09 (q, J = 7.1 Hz, 2H), 4.20–4.32 (m, 2H), 4.61 (d, J = 9.3
Hz, 1H), 4.79 (d, J = 7.5 Hz, 1H), 6.33 (d, J = 7.5 Hz, 1H), 6.41
(d, J = 9.3 Hz, 1H), 7.40–7.72 (m, 6H+6H), 7.86–7.94 (m,
1H+1H), 7.97–8.04 (m, 2H+2H); 13C NMR (CDCl3, 75.6 MHz) δ
13.8, 13.9, 57.9, 60.0, 62.1, 62.5, 78.6, 79.2, 123.7, 123.8, 125.7,
125.8, 126.0, 126.3, 128.88, 128.92, 129.0, 129.80, 129.84,
134.2, 134.3, 134.5, 135.4, 135.7, 147.2, 147.3, 165.8,166.0,
169.45, 169.50, 191.5, 191.9; HRMS (ESI) calcd for C19H16NaO5
[M + Na]+ 347.0890, found 347.0889; IR (ν/cm–1): 1774, 1736,
1682, 1288.
4.3.1. 3-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-1,3-dihydro-2-
benzofuran-1-one (9a). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8a (26.4 mg, 0.200 mmol) were reacted for 3 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9a (22.5 mg, 0.085 mmol, 85%) as a colorless oil.
1H NMR (CDCl3, 301 MHz) δ 3.74 (s, 3H), 3.81 (s, 3H), 3.84 (d,
J = 7.5 Hz, 1H), 6.07 (d, J = 7.5 Hz, 1H), 7.51–7.61 (m, 2H),
7.68 (dt, J = 1.2, 7.5 Hz, 1H), 7.89–7.94 (m, 1H). The spectral
data matched those reported in the literature.18
4.3.2. 3-(1,3-Diethoxy-1,3-dioxopropan-2-yl)-1,3-dihydro-2-
benzofuran-1-one (9b). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8b (32.0 mg, 0.200 mmol) were reacted for 3 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9b (23.1 mg, 0.079 mmol, 79%) as a colorless oil.
1H NMR (CDCl3, 301 MHz) δ 1.18 (t, J = 7.1 Hz, 3H), 1.27 (t, J
= 7.0 Hz, 3H), 3.86 (d, J = 6.9 Hz, 1H), 4.17 (dq, J = 2.5, 7.1 Hz,
2H), 4.26 (q, J = 7.1 Hz, 2H), 6.07 (d, J = 6.9 Hz, 1H), 7.53–7.60
(m, 2H), 7.63–7.70 (m, 1H), 7.88–7.93 (m, 1H). The spectral data
matched those reported in the literature.10a
4.3.7. 3-(1,3-Diethoxy-2-methyl-1,3-dioxopropan-2-yl)-1,3-
dihydro-2-benzofuran-1-one (9g). According to GP-2, 1a (13.4
mg, 0.100 mmol) and 8g (34.8 mg, 0.200 mmol) were reacted for
4 h. Purification by preparative TLC on silica gel (hexane:AcOEt
= 3:2) afforded 9g (22.0 mg, 0.072 mmol, 72%) as a colorless oil.
1H NMR (CDCl3, 500 MHz) δ 1.19 (s, 3H), 1.22 (t, J = 6.8 Hz,
3H), 1.30 (t, J = 7.2 Hz, 3H), 4.18–4.26 (m, 2H), 4.29 (q, J = 7.0
Hz, 2H), 6.20 (s, 1H), 7.55 (t, J = 7.5, 1H), 7.59–7.62 (m, 1H),
7.63–7.68 (m, 1H), 7.90 (d, J = 7.0 Hz, 1H); 13C NMR (CDCl3,
126 MHz) δ 13.9, 14.0, 14.7, 57.5, 62.0, 62.3, 81.6, 124.0, 125.7,
127.0, 129.7, 134.2, 146.2, 168.4, 169.1, 169.6; HRMS (ESI)
calcd for C16H18NaO6 [M + Na]+ 329.0996, found 329.0997; IR
(ν/cm–1): 1766, 1736, 1257.
4.3.3. 3-(1,3-Diisopropoxy-1,3-dioxopropan-2-yl)-1,3-dihydro-2-
benzofuran-1-one (9c). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8c (37.6 mg, 0.200 mmol) were reacted for 3 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9c (25.4 mg, 0.079 mmol, 79%) as a colorless oil.
1H NMR (CDCl3, 301 MHz) δ 1.11 (d, J = 6.0 Hz, 3H), 1.16 (d, J
= 6.5 Hz, 3H), 1.22 (d, J = 6.5 Hz, 3H), 1.27 (d, J = 6.5 Hz, 3H),
3.84 (d, J = 7.0 Hz, 1H), 5.00 (septet, J = 6.3 Hz, 1H), 5.10
(septet, J = 6.3 Hz, 1H), 6.04 (d, J = 6.5 Hz, 1H), 7.53–7.58 (m,
1H), 7.59–7.63 (m, 1H), 7.64–7.68 (m, 1H), 7.90 (d, J = 8.0 Hz,
1H); 13C NMR (CDCl3, 75.6 MHz) δ 21.39, 21.42, 21.55, 56.1,
69.99, 70.04, 77.7, 123.3, 125.6, 126.5, 129.8, 134.2, 146.8,
165.3, 165.4, 169.5; HRMS (ESI) calcd for C17H20NaO6 [M +
Na]+ 343.1152, found 343.1155; IR (ν/cm–1): 2985, 1774, 1736.
4.3.8. 3-(1-Ethoxy-2-methyl-1,3-dioxobutan-2-yl)-1,3-dihydro-2-
benzofuran-1-one (9h). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8h (28.7 mg, 0.199 mmol) were reacted for 4 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9h (26.0 mg, 0.094 mmol, 94%, 52:48 diastereomer
ratio determined by 1H NMR) as a white solid. Mp 106–107 °C;
1H NMR (CDCl3, 500 MHz) δ 1.01 (s, 3H), 1.18 (s, 3H), 1.20 (t,
J = 7.0 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H), 2.22 (s, 3H), 2.36 (s,
3H), 4.20 (q, J = 6.1 Hz, 2H), 4.25–4.34 (m, 2H), 6.27 (s,
1H+1H), 7.47–7.59 (m, 2H+2H), 7.61–7.70 (m, 1H+1H), 7.86–
7.92 (m, 1H+1H); 13C NMR (CDCl3, 126 MHz) δ 13.7, 13.8,
13.9, 14.2, 26.4, 26.8, 62.2, 62.5, 63.2, 63.7, 81.5, 81.8, 123.9,
124.4, 125.68, 125.74, 126.6, 127.0, 129.65, 127.00, 134.2,
134.3, 146.2, 146.5, 168.5, 169.3, 169.6, 169.8, 202.0, 203.6;
HRMS (ESI) calcd for C15H16NaO5 [M + Na]+ 299.0890, found
299.0890; IR (ν/cm–1): 1774, 1712, 1250.
4.3.4. 3-(1-Cyclopropyl-3-methoxy-1,3-dioxopropan-2-yl)-1,3-
dihydro-2-benzofuran-1-one (9d). According to GP-2, 1a (13.4
mg, 0.100 mmol) and 8d (28.4 mg, 0.200 mmol) were reacted for
2 h. Purification by preparative TLC on silica gel (hexane:AcOEt
= 3:1) afforded 9d (20.0 mg, 0.073 mmol, 73%, 51:49
1
1
diastereomer ratio determined by H NMR) as a colorless oil. H
NMR (CDCl3, 301 MHz) δ 0.88–1.22 (m, 4H+4H), 2.03–2.16
(m, 1H+1H), 3.76 (s, 3H), 3.85 (s, 3H), 4.05 (d, J = 7.8 Hz, 1H),
4.09 (d, J = 8.1 Hz, 1H), 6.14 (s, 1H), 6.16 (s, 1H), 7.44–7.70 (m,
3H+3H), 7.88–7.94 (m, 1H+1H); 13C NMR (CDCl3, 75.6 MHz) δ
12.5, 12.6, 12.8, 21.3, 21.5, 52.9, 53.1, 62.8, 63.8, 78.0, 78.2,
123.3, 123.7, 125.7, 125.8, 126.08, 126.11, 129.8, 134.3, 147.1,
166.5, 166.6, 169.5, 169.6, 201.4, 202.1; HRMS (ESI) calcd for
C15H14NaO5 [M + Na]+ 297.0733, found 297.0726; IR (ν/cm–1):
1774, 1743, 1704.
4.3.9. 3-(3-Methyl-2,4-dioxopentan-3-yl)-1,3-dihydro-2-
benzofuran-1-one (9i). According to GP-2, 1a (13.4 mg, 0.100
mmol) and 8i (22.8 mg, 0.200 mmol) were reacted for 5 h.
Purification by preparative TLC on silica gel (hexane:AcOEt =
3:2) afforded 9i (17.3 mg, 0.070 mmol, 70%) as a colorless oil.
1H NMR (CDCl3, 301 MHz) δ 1.02 (s, 3H), 2.16 (s, 3H), 2.40 (s,
3H), 6.49 (s, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.4 Hz,
1H), 7.65 (dt, J = 1.4, 7.6 Hz, 1H), 7.90 (d, J = 7.5 Hz, 1H); 13C
NMR (CDCl3, 126 MHz) δ 12.6, 26.8, 27.1, 70.6, 81.8, 123.8,
125.9, 126.6, 129.8, 134.5, 146.5, 169.6, 201.9, 205.4; HRMS
(ESI) calcd for C15H16NaO5 [M + Na]+ 299.0890, found
299.0890; IR (ν/cm–1): 1774, 1712, 1250.
4.3.5. 3-(1-Ethoxy-4,4-dimethyl-1,3-dioxopentan-2-yl)-1,3-
dihydro-2-benzofuran-1-one (9e). According to GP-2, 1a (13.4
mg, 0.100 mmol) and 8e (34.0 mg, 0.197 mmol) were reacted for
2.5 h. Purification by preparative TLC on silica gel
(hexane:AcOEt = 3:1) afforded 9e (21.4 mg, 0.070 mmol, 70%,
1
59:41 diastereomer ratio determined by H NMR) as a colorless
1
oil. H NMR (CDCl3, 500 MHz) δ 1.11 (s, 9H), 1.22 (t, J = 7.2
Hz, 3H), 1.23 (s, 9H), 1.33 (t, J = 7.2 Hz, 3H), 4.13–4.25 (m,
2H), 4.17 (d, J = 9.5 Hz, 1H), 4.19 (d, J = 9.0 Hz, 1H), 4.30 (q, J
= 6.8 Hz, 2H), 6.12 (d, J = 9.0 Hz, 1H), 6.21 (d, J = 9.0 Hz, 1H),

8
Tetrahedron
ACCEPTED MANUSCRIPT
5588. (h) Wendlandt, A. E.; Suess, A. M.; Stahl, S. S. Angew.
4.3.10. 3-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-5,6-dimethyl-
Chem., Int. Ed. 2011, 50, 11062. (i) Liu, Q.; Zhang, H.; Lei, A.
Angew. Chem., Int. Ed. 2011, 50, 10788. (j) Hopkinson, M. N.;
Gee, A. D.; Gouverneur, V. Chem. Eur. J. 2011, 17, 8248. (k)
Newhouse, T.; Baran, P. S. Angew. Chem., Int. Ed. 2011, 50,
3362. (l) Zhou, M.; Crabtree, R. H. Chem. Soc. Rev. 2011, 40,
1875. (m) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc.
Rev. 2011, 40, 5068.
1,3-dihydro-2-benzofuran-1-one (9j). According to GP-2, 1b
(16.2 mg, 0.100 mmol) and 8a (26.4 mg, 0.200 mmol) were
reacted for 9.5 h. Purification by preparative TLC on silica gel
(hexane:AcOEt = 1:1) afforded 9j (22.8 mg, 0.078 mmol, 78%)
as a white solid. Mp 119 °C; 1H NMR (CDCl3, 500 MHz) δ 2.33
(s, 3H), 2.36 (s, 3H), 3.74 (s, 3H), 3.78 (s, 3H), 3.77 (d, J = 7.5
Hz, 1H), 5.96 (d, J = 7.0 Hz, 1H), 7.24 (s, 1H), 7.63 (s, 1H); 13C
NMR (CDCl3, 126 MHz) δ 20.0, 20.8, 52.9, 53.1, 55.9, 77.3,
123.6, 123.9, 126.0, 139.2, 144.55, 144.62, 166.1, 166.2, 169.6;
HRMS (ESI) calcd for C15H16NaO6 [M + Na]+ 315.0839, found
315.0843; IR (ν/cm–1): 1766, 1296, 1203.
4. (a) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J.
Org. Chem. 1998, 63, 5211. (b) Ueura, K.; Satoh, T.; Miura, M.
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14866.
4.3.11. 3-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-1H,3H-
naphtho[2,3-c]furan-1-one (9k). According to GP-2, 1e (18.4
mg, 0.100 mmol) and 8a (26.4 mg, 0.200 mmol) were reacted for
6 h. Purification by preparative TLC on silica gel (hexane:AcOEt
= 3:2) afforded 9k (20.2 mg, 0.064 mmol, 64%) as a white solid.
8. Tan, P. W.; Juwaini, N. A. B.; Seayad, J. Org. Lett. 2013, 15,
5166.
9. For other recently reported catalytic reactions giving phthalides,
see: (a) Phan, D. H. T.; Kim, B.; Dong, V. M. J. Am. Chem. Soc.
2009, 131, 15608. (b) Omura, S.; Fukuyama, T.; Murakami, Y.;
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F.; Cheng, J. J. Org. Chem. 2010, 75, 6043. (f) Luo, F.; Pan, S.;
Pan, C.; Qian, P.; Cheng, J. Adv. Synth. Catal. 2011, 353, 320. (g)
Fei, X.-D.; Ge, Z.-Y.; Tang, T.; Zhu, Y.-M.; Ji, S.-J. J. Org.
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Arcadi, A.; Fabrizi, G.; Goggiamani, A.; Marinelli, F. J. Org.
Chem. 2015, 80, 6986.
1
Mp 167 °C; H NMR (CDCl3, 301 MHz) δ 3.75 (s, 3H), 3.82 (s,
3H), 3.94 (d, J = 7.5 Hz, 1H), 6.22 (dd, J = 7.4, 0.7 Hz, 1H),
7.58–7.70 (m, 2H), 7.92–7.98 (m, 2H), 8.02–8.07 (m, 1H), 8.48
(s, 1H); 13C NMR (CDCl3, 75.6 MHz) δ 53.0, 53.2, 56.2, 77.6,
122.3, 123.6, 127.2, 127.4, 128.6, 129.2, 129.8, 133.4, 136.2,
140.0, 166.2, 166.3, 169.3; HRMS (ESI) calcd for C17H14NaO6
[M + Na]+ 337.0683, found 337.0698; IR (ν/cm–1): 1766, 1743,
1296.
Acknowledgments
10. Recently, an efficient synthesis of 3-substituted phthalides by an
aldol–lactonization process from 2-formylbenzoates and 1,3-
dicarbonyl compounds was reported: (a) Di Mola, A.; Croce, G.;
More, V.; De Caprariis, P.; Filosa, R.; Massa, A. Tetrahedron
2012, 68, 6146. See also, (b) Perillo, M.; Di Mola, A.; Filosa, R.;
Palombi, L.; Massa, A. RSC Adv. 2014, 4, 4239.
This work was partly supported by Japan Society for the
Promotion of Science, Japan (Grant-in-Aid for Scientific
Research (C) No. 25410054) and the Sumitomo Foundation (No.
130325).
11. The use of 2-phenylpropan-2-ol, allyl alcohol, propargyl alcohol,
2-chloroethanol, and 2,2,2-trifluoroethanol resulted in either no
reaction or complex mixtures.
Supplementary Material
12. For transition-metal-catalyzed oxidative esterification of
aldehydes with alcohols, see: (a) Murahashi, S.-I.; Naota, T.; Ito,
K.; Maeda, Y.; Taki, H. J. Org. Chem. 1987, 52, 4319. (b) Yoo,
W.-J.; Li, C.-J. Tetrahedron Lett. 2007, 48, 1033. (c) Wu, X.-F.;
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Lothschütz, C.; Ackermann, M.; Doepp, R.; Anantharaman, S.;
Marchetti, B.; Bertagnolli, H.; Rominger, F. Chem. Eur. J. 2010,
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A. Angew. Chem., Int. Ed. 2012, 51, 5662. (f) Tschaen, B. A;
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Kessar, S. V.; Vohra, R.; Kaur, N. P.; Singh, K. N.; Singh, P. J.
Chem. Soc., Chem. Commun. 1994, 1327.
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Copies of 1H and 13C NMR spectra for all new products.
Supplementary data associated with this article can be found in
the
online
version,
at
http://dx.doi.org/10.1016/j.tet.XXXX.XX.XXX.
References and notes
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