TBuO 2H/Cu(acac) 2-Mediated Intramolecular Oxidative Lactonization of o -Allyl Arylaldehydes: Synthesis of 1-Oxoisochromans

Article abstract of DOI:10.1055/s-0040-1706469

A concise route for the ^tBuO ₂H/Cu(acac) ₂-mediated synthesis of 1-oxoisochromans is described. This includes: (i) oxidation of oxygenated o -allyl arylaldehydes and (ii) sequential intramolecular lactonization of the resulting olefin-containing benzoic acids. A plausible mechanism is proposed and discussed.

Full text of DOI:10.1055/s-0040-1706469

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 52, A–K
paper
A
en
M.-Y. Chang et al.
Paper
Synthesis
tBuO2H/Cu(acac)2-Mediated Intramolecular Oxidative Lactoni-
zation of o-Allyl Arylaldehydes: Synthesis of 1-Oxoisochromans
Meng-Yang Chang*a,b
Kai-Xiang Laia
Kuan-Ting Chena
0
0
0
0
-
0
0
0
2
-
1
9
8
3
-
8
5
7
0
R
R
R
R
tBuO2H, Cu(acac)2
solvents
OCHO
OH
OAc
Ar
Ar
Ar
Ar
O
+
O
+
O
a Department of Medicinal and Applied Chemistry,
Kaohsiung Medical University, 100 Shin-Chuan 1st
Rd., Kaohsiung 80708, Taiwan
b Department of Medical Research, Kaohsiung Medical
University Hospital, 100 Tzyou 1st Rd., Kaohsiung
80708, Taiwan
O
O
O
O
(for HCO2H)
23 examples
(for H2O)
62–86% yields
(for AcOH)
3 C–O bond formations
mychang@kmu.edu.tw
MDeMeepanaigClr-otmYmraryeencnshgptaCoonhnfgadM@ninkgegmdiAcuiu.netdahluoa.rtnwd Applied Chemistry, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd., Kaohsiung 80708, Taiwan
Received: 14.07.2020
Accepted after revision: 14.08.2020
Published online: 29.09.2020
creased in recent reports, as shown in Scheme 1. These ele-
gant synthetic routes have exhibited some advantages, in-
cluding one-pot facile operation, high site-specific selectivi-
ty, and optimal reaction conditions. For the involvement of
monooxygenase, Gotor et al. demonstrated the regioselec-
tive Baeyer–Villiger lactonization of 1-indanone.16a Fujita et
al. investigated the PhI(OAc)2-mediated oxidation of 2-vinyl
benzoate followed by intramolecular annulation of in situ
formed iodonium ion.16b Yeung et al. explored the possibili-
ty of NBS-mediated method as an efficient benzannulation
of ortho-vinylbenzoic acid.16c By the addition of
Pd(OAc)2/ZnF2, Baudoin et al. developed an intermolecular
cross-coupling of trioxygenated propene and 2-bromoben-
zonitrile.16d By the use of E. coli/ADH-A, Gotor-Fernández et
al. described the ketoreductase-mediated chemoenzymatic
cyclization of 2-(2-oxopropyl)benzonitrile.16e Yu et al. re-
ported the Pd(OAc)2 mediated ortho-C–H alkylation of ben-
zoic acid and epoxide.16f Sharpless dihydroxylation of o-all-
ylbenzamide with OsO4 has been studied by Salvadori and
co-workers.16g Despite the above-mentioned synthetic
DOI: 10.1055/s-0040-1706469; Art ID: ss-2020-f0381-op
Abstract A concise route for the tBuO2H/Cu(acac)2-mediated synthe-
sis of 1-oxoisochromans is described. This includes: (i) oxidation of oxy-
genated o-allyl arylaldehydes and (ii) sequential intramolecular lacton-
ization of the resulting olefin-containing benzoic acids. A plausible
mechanism is proposed and discussed.
Key words tBuO2H, Cu(acac)2, 1-oxoisochromans, intramolecular oxi-
dative annulation, o-allyl arylaldehydes
tBuO2H (tert-butyl hydroperoxide, TBHP) associated
with metal complexes can serve as a useful reagent in the
contraction of diversified building blocks or functional
group transformations via different bond formations or
cleavage. For example, Sharpless epoxidation shows the
tBuO2H/Ti(OiPr)4-mediated conversion from allylic alcohols
to 2,3-epoxyalcohols.1 Also, the combination of
tBuO2H/VO(acac)2 has been utilized for allylic epoxidation.2
Recently, by the involvement of other transition metals,
tBuO2H/Cu(acac)2 (this work)
monooxygenase
t
OsO4
various BuO2H-mediated reactions have been well devel-
(Gotor, ref. 16a)
(Salvadori, ref. 16g)
oped, including Cu(II),3 Ru(II),4 Pd(II),5 Fe(III),6 Co(II),7
Rh(II),8 Au(III),9 and Bi(III).10 By the use of co-oxidants (e.g.,
I2,11 NIS,12 and CAN13), however, other tBuO2H-mediated re-
actions have been investigated. Among these combinations,
tBuO2H/copper salts have been a major focus for different
oxidative reactions.3 To date, there are no reports on the
synthesis of substituted 1-oxoisochromans by the combina-
tion of tBuO2H/Cu(II).
1-Oxoisochroman (3,4-dihydrocoumarin) having a ben-
zofused -lactone bicyclic skeleton is an important unit in a
wide variety of natural products,14 bioactive molecules,15
and functionalized building blocks.16 Hence, development
of new methodologies to provide access to these diversified
1-oxoisochromans and their derivatives has steadily in-
Ar
O
Ar
Ar
R'
NEt2
O
O
O
R'
R'
R'
Ar
Ar
Ar
O
OH
OMe
O
O
O
Pd(OAc)2
(Yu, ref. 16f)
PhI(OAc)2
1-oxoisochromans
(Fujita, ref. 16b)
R'
R'
H
OTMS
OMe
Ar
O
C
Br
Ar
OH
Ar
+
N
OTES
C
O
N
E. coli
(Gotor-Fernandez, ref.
16e)
NBS
Pd(OAc)2/ZnF2
(Baudoin, ref. 16d)
(Yeung, ref. 16c)
Scheme 1 Synthetic routes to 1-oxoisochromans
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
M.-Y. Chang et al.
Paper
Synthesis
routes affording diversified 1-oxoisochroman, a direct in-
tramolecular oxidative lactonization of o-allyl arylaldehyde
employing the combination of tBuO2H/Cu(acac)2 to generate
benzofused -lactone has yet to be developed via three car-
bon–oxygen (C–O) bond formations.
sults, Cu(acac)2 was the preferred choice to screen the reac-
tion conditions. Next, by decreasing the equivalents of
Cu(acac)2 from 1.0 to 0.5, the isolated yield of 4a was 38%
(entry 11). By increasing the stoichiometric amounts of
Cu(acac)2 from 1.5 equivalents, the yield of 6a was similar
to the 1.0 equivalent (76%, entry 12). The results show that
a 1.0 equivalent of Cu(acac)2 was suitable for the reaction
condition. Then, two solvents having different boiling
points, such as DMF and CH2Cl2, were tested. Using DMF,
complex unknown products were detected due to the high
refluxing temperature (153 °C) that resulted (entry 13). For
the low boiling point solvent, CH2Cl2 showed that only trace
amounts of 5a were isolated, and the starting 4a was recov-
ered as the major component (entry 14). Next, changing the
times to 1 hour or 6 hours showed that the afforded yields
of 6a decreased to 56% or 70%, respectively (entries 15, 16).
Furthermore, after adjusting the temperature to reflux
(100 °C) or room temperature (25 °C), no reactions were
observed for 3 hours (Table 1, entry 17). Even though the
reaction time was increased to 10 hours, no desired prod-
uct was observed at 25 °C (entry 18). After changing the re-
action concentration (10 → 5 or 15 mL), the yields (72% or
79%) of 6a were maintained (entries 19, 20). By diminishing
the amounts of tBuO2H to 1.0 equivalent, only 5a was isolat-
ed in a 79% yield (entry 21). Even with the addition of io-
dine (0.2 equiv),11 the isolated yield (75%) of 6a could not be
improved (entry 22). To understand the protic solvent ef-
Continuing our research on the synthetic application of
o-allyl arylaldehydes for the formation of benzofused het-
erocycles and carbocycles,17a–d we present the
tBuO2H/Cu(acac)2-mediated synthesis of 1-oxoisochromans
in the presence of HCO2H via a one-pot tandem process, in-
cluding: (i) the dual oxidation of formyl and olefinic groups,
(ii) intramolecular lactonization of the corresponding car-
boxylic acid and dioxygenated moieties, and (iii) subse-
quent formylation of the resulting primary hydroxyl group
with HCO2H. These starting di- or mono-oxygenated o-allyl
arylaldehydes 4 were synthesized easily from commercially
available 3-hydroxy-4-methoxybenzaldehyde (1a), 3-hy-
droxy-5-methoxybenzaldehyde (1b), and 3-hydroxybenzal-
dehyde (1c) via a three-step synthetic route, including (1)
O-allylation (R = H) or O-crotylation (R = Me) of 1, and (2)
Claisen rearrangement of 2 in refluxing decalin, with O-al-
kylation of 3 with different alkyl halides (R′–X) according to
our previous reports (Scheme 2).17
K2CO3
R
OH
3
O
R
OH
Ar
R
OR'
Ar
decalin
reflux
K2CO3
R'–X
4
5
Br
R = H, Me
R
Ar
Ar
1
CHO
CHO
CHO
CHO
t
1
2
3
4
fect HCO2H was changed to BuOH [should be generated in
t
situ from BuO2H/Cu(acac)2]. However, no tert-butoxylated
Scheme 2 Synthetic route to the starting materials 4
product was obtained, and only 5a was isolated in 71% yield
due to tert-butyl group exhibiting a bulkier steric hindrance
(entry 23). Changing the solvent to co-solvent
tBuOH/HCO2H (v/v = 10:1), only 15% yield of 6a was pro-
duced along with 56% yield of 5a (entry 24). The results
showed that HCO2H was a better protic solvent than tBuOH.
On the other hand, we understood that in situ generated
The initial study commenced with the treatment of the
model material 4a [Ar = 3,4-(MeO)2C6H2, R1 = H, 1.0 mmol]
with tBuO2H (5.0 equiv, 5 M in decane) and CuO (1.0 equiv)
in HCO2H (10 mL) at reflux (100 °C) for 3 hours. Only o-all-
ylbenzoic acid 5a was produced in 65% yield (Table 1, entry
1). Six copper salts [Cu(acac)2, Cu(OAc)2, Cu(OTf)2, CuSO4,
CuCl2, and CuI] were studied in the presence of tBuO2H and
HCO2H at reflux for 3 hours (entries 2–7). However, all of
them obtained higher yields (10–80%) of 6a than CuO. Also,
Cu(acac)2 and Cu(OAc)2 provided similar yields (80% and
73%). By the use of Cu(OTf)2 and CuSO4, low yields (43% and
36%) were observed. Among them, CuCl2 and CuI provided
6a in only 16% and 10% yield, respectively, along with a
complex unknown mixture as the major products. These
results show that Cu(acac)2 gave a better yield of 6a than
other copper complexes due to the appropriate bidentate
acac (acetylacetone) ligand. Furthermore, three kinds of
metal salts having the acac ligand were examined (entries
8, 9). Fe(acac)3 and VO(acac)2 provided slightly poorer
yields (74% and 68%) than Cu(acac)2. However, only 5a was
produced in a 51% yield by the Pd(acac)2-mediated treat-
ment of 4a (entry 10). According to the experimental re-
t
tBuOH (from BuO2H) could not trigger the generation of
tert-butoxylated 1-oxoisochroman. The structure of 6a was
determined by single-crystal X-ray analysis (Figure 1).18
From the above phenomenon, we envisioned that the com-
bination of refluxing HCO2H (10 mL) and a 3 hours time pe-
riod performed better for the formation of 6a in the
tBuO2H/Cu(acac)2-mediated formation of 6a.19
Figure 1 X-ray structure of 6a
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

C
M.-Y. Chang et al.
Paper
Synthesis
Table 1 Reaction Conditionsa
OMe
MeO
OMe
3
OMe
tBuO2H
MeO
MeO
O
4
O
Cu(II) salt
conditions
O
OH
O
H
O
O
4a
6a (X-ray, CCDC 1947902)
5a
Entry
Metal salts (equiv)
CuO (1.0)
Solvent
Time (h)
Temp (°C)
Yield of 6a (%)b
c
1
2
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
DMF (10)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
1
6
3
10
3
3
3
3
3
3
100
100
100
100
100
100
100
100
100
100
100
100
153
40
–
Cu(acac)2 (1.0)
Cu(OAc)2 (1.0)
Cu(OTf)2 (1.0)
CuSO4 (1.0)
80
73
43
36
16d
10d
74
68
3
4
5
6
CuCl2 (1.0)
7
CuI (1.0)
8
Fe(acac)3 (1.0)
VO(acac)2 (1.0)
Pd(acac)2 (1.0)
Cu(acac)2 (0.5)
Cu(acac)2 (1.5)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
Cu(acac)2 (1.0)
9
c
10
11
12
13
14
15
16
17
18
19
20
21f
22g
23
24h
–
38
76
d
–
c
CH2Cl2 (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (10)
HCO2H (5)
HCO2H (15)
HCO2H (10)
HCO2H (10)
tBuOH (10)
tBuOH (10)
–
100
100
25
56
70
e
–
e
25
–
100
100
100
100
100
100
72
79
c
–
75
c
–
15c
a The reactions were run on a 1.0 mmol scale with 4a, tBuO2H (5.0 M in decane, 5 equiv), metal salts (equiv), solvent (mL), time (h), temp ( °C).
b Isolated yields.
c Compound 5a was isolated (entry 1, 65%; entry 10, 51%; entry 14, trace; entry 21, 79%; entry 23, 71%; entry 24, 56%).
d Complex product was isolated.
e No reaction.
f tBuO2H (5 M in decane, 1 equiv).
g I2 (0.2 equiv) was added.
h HCO2H (1 mL) was added.
On the basis of experimental results, a plausible mecha-
benzaldehyde 4a to C is proposed. And, in situ oxidation
step from C to A could be formed simultaneously. Subse-
quently, HCO2H-mediated ring-opening of the epoxide on C
achieves D. After the migration of the formyl group be-
tween D and E, a -lactol ring on F is produced via the intra-
molecular cyclization. Next, tBuO2H-mediated in situ oxida-
tion of F provides 6a. Finally, another pathway for the for-
mation of 6a is also proposed via HCO2H-mediated ring
opening of A, the exchange of formyl group from G to H, and
intramolecular lactonization of H. Under tBuO2H/Cu(acac)2-
mediated standard reaction conditions, 5a could be con-
nism for the formation of 6a is illustrated in Scheme 3. Ini-
t
tially, BuO2H-mediated oxidation of o-allyl benzaldehyde
4a forms o-allyl benzoic acid 5a via the first C–O bond for-
mation (see green mark). Then, by the involvement of ex-
cess amounts of tBuO2H, epoxidation of the olefinic moiety
of 5a affords A. Following, HCO2H-mediated intramolecular
ring-closure of A provides B via the second C–O bond for-
mation. Furthermore, esterification of B and HCO2H gener-
ates 6a via the third C–O bond formation. On the other rea-
t
sonable way, BuO2H-mediated the conversion from o-allyl
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

D
M.-Y. Chang et al.
Paper
Synthesis
R
O
R
O
OCHO
+
R
O
OH
R
OAc
verted into 6a in an 81% yield, and this supports the path-
way via intermediate A. Compared with Patel’s reports on
tBuO2H-mediated radical reactions,20 the result demon-
strated that this mechanism is a cationic pathway.
tBuO2H
Ar
Ar
Ar
Ar
+
O
O
O
Cu(acac)2
solvent
O
4a–n
6a–n (for HCO2H)
6o–u (for H2O)
6w (for AcOH)
CHO
OCHO
OCHO
HCO2H
OMe
OMe
OMe
OMe
OCHO
MeO
OnBu
OCHO
OBn
OCHO
MeO
OH
OCHO
O
HO
OH
MeO
MeO
MeO
MeO
MeO
MeO
MeO
O
OH
OH
O
O
O
O
O
O
O
O
O
H
G
6a
O
O
O
O
6a (80%)
OMe Me
*
6b (84%)
OiPr Me
*
6c (86%)
OBn Me
*
6d (82%)
HCO2H
OCHO
MeO
OCHO
MeO
OCHO
MeO
OnBu
Me
OCHO
OMe
OMe
OMe
MeO
MeO
MeO
*
tBuO2H
tBuO2H
Cu(acac)2
*
O
*
O
*
O
*
O
O
OH
OH
Cu(acac)2
HCO2H
O
O
O
O
O
O
A
4a
5a
6e (76%, 7:4)
6f (73%, 1:1)
6g (70%, 1:1)
6h (70%, 1:1)
tBuO2H
Cu(acac)2
tBuO2H
Cu(acac)2
HCO2H
O
Me
*
OCHO OMe
OCHO
OBn
OCHO
OnBu
OCHO
OMe
OMe
OMe
MeO
MeO
MeO
*
O
HCO2H
OH
OH
O
O
O
O
O
O
O
MeO
MeO
MeO
CHO
O
O
O
O
O
D
C
B
6i (64%, 1:1)
6j (82%)
6k (80%)
6l (83%)
HCO2H
OMe
OCHO
OCHO
MeO
OMe
OH
OnBu
OH
MeO
OMe
OCHO
OH
OMe
OCHO
OMe
OCHO
O
O
O
O
MeO
MeO
MeO
tBuO2H
Cu(acac)2
O
O
O
6o (70%)
O
O
OH
O
6m (80%)
6n (76%)
6p (76%)
O
O
E
F
6a
OiPr
Me
OH
OBn
OH
OnBu Me OH
O
OH
Me
Me
Scheme 3 Plausible mechanism
MeO
MeO
MeO
MeO
*
*
*
*
*
*
*
*
O
O
O
O
To study the scope and limitations of this approach, ox-
ygenated o-allyl arylaldehydes were examined further to af-
ford diverse 1-oxoisochromans by tBuO2H/Cu(acac)2/
HCO2H-mediated one-pot intramolecular oxidative lacton-
ization, as shown in Scheme 4. With optimal conditions es-
tablished (Table 1, entry 2) and a plausible reaction mecha-
nism proposed (Scheme 3), we found that the route could
allow a direct synthesis of oxygenated 1-oxoisochromans
6a–n in moderate to good yields (64–86%). For the electron-
ic nature of an Ar substituent of 4, electron-donating di-
and mono-oxygenated groups, and electron-neutral groups
were appropriate. However, when the R substituent was the
methyl (Me) group, an unseparated mixture of 6e–i was ob-
tained in a nearly 1:1 ratio. The ratios of diastereomers
O
O
O
O
6q (62%, 1:1)
6r (70%, 1:1)
6s (72%, 1:1)
6t (68%, 1:1)
OMe
OH
OH
OMe
OAc
MeO
O
O
O
MeO
O
O
O
6u (65%)
6v (66%)
6w (80%)
Scheme 4 Synthesis of 6a–w
diated reaction process in boiling water for 3 hours, only 6o
was isolated in a 51% yield. Although the starting substrate
4 was limited to the oxygenated aryl (Ar) group, it still pro-
vided a novel and efficient route from o-allyl arylaldehydes
to 1-oxoisochromans.
1
were determined by H NMR analysis. Therefore, efficient
formation of 6a–n showed that the substituents (4, Ar, R)
did not affect the distribution of the provided yields.
On the other hand, as an extension of the
tBuO2H/Cu(acac)2-mediated synthetic route, 4o with a
butenyl side (internal olefin) chain was examined. However,
the naphthalene skeleton 7a was isolated in a 53% yield, and
no desired 1-oxoisochroman was detected (Scheme 5, eq 1).
A possible reason could be that an intramolecular carbonyl-
ene Prins-type cyclocondensation of 4o (via carbocation I
followed by removal of water) was preferred to be initiated
rather than the oxidation of the formyl group under a re-
fluxing HCO2H condition. With the results in mind, adjust-
ing the acidic condition from HCO2H to pTsOH was tested
Furthermore, when changing the solvent from HCO2H to
H2O, 6o–v were also generated in a range of 62–76% yields,
while 6q–t were observed as the diastereomers (R = Me, ra-
tio = 1:1). Compared with HCO2H, the experiments showed
that water could provide similar results via an environmen-
tally friendly transformation. On the other hand, AcOH
could be chosen as the solvent to screen the one-pot trans-
formation. Under the above reaction conditions, 6w was
produced in an 80% yield. Especially, when 4a was treated
t
t
with benzoic acid (1.0 equiv) by the BuO2H/Cu(acac)2 me-
next. As shown in Scheme 5, eq 2, BuO2H/Cu(acac)2 medi-
ated treatment of 4a with pTsOH in (CH2Cl)2 provided 8a in
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

E
M.-Y. Chang et al.
Paper
Synthesis
H
a 78% yield. A similar reaction pathway was also observed
for the conversion from 4e (R = Me) to 8b (68%, ratio 1:1).
The results demonstrate that pTsOH triggered the intramo-
lecular lactonization of benzoic acid with a terminal olefin
(via carbocation II) easier than tBuO2H/Cu(acac)2-mediated
lactonization. As shown in Scheme 5, eq 3, when changing
the formyl to a nitro group, 9a provided the epoxy-contain-
ing phenyl formate 10a in a 68% yield along with a 10% yield
of dihydrobenzofuran 10b. The generation of 10a and 10b
tBuO2H
Cu(acac)2
MeO
MeO
MeO
MeO
MeO
MeO
(1)
HCO2H
Me
Me
Me
H2O
O
R
OH
I
4o
7a (53%)
R
H
R
O
OMe
OMe
OMe
Me
MeO
MeO
MeO
tBuO2H, Cu(acac)2
(2)
OH
O
pTsOH, (CH2Cl)2
O
O
II
4a, R = H
4e, R = Me
8a, R = H (78%)
8b, R = Me (68%, 1:1)
t
demonstrated that BuO2H/Cu(acac)2 could furnish the ep-
oxidation and formylation or intramolecular phenolate
annulation from the skeleton of o-allyl nitrobenzene. Next,
o-allyl benzonitrile 9b was screened (Scheme 5, eq 4). How-
ever, only 10c was isolated in a 76% yield and no dihydro-
benzofuran product was detected. Also, 9c (R′′ = Me, a
methylate of 9b) yielded 10d with two formate groups in a
74% yield. For the resulting phenomenon, we envisioned
that tBuO2H/Cu(acac)2 could make the terminal olefin epox-
idize in the presence of cyano group such that 10c and 10d
were generated. Then, by the use of MeNO2 as the solvent,
OH
OH
OCHO
O
O
MeO
MeO
MeO
tBuO2H, Cu(acac)2
HCO2H
(3)
+
NO2
NO2
NO2
10b (10%)
OMe
9a
10a (68%)
OR"
OCHO
OCHO
OCHO
O
MeO
MeO
MeO
tBuO2H, Cu(acac)2
HCO2H
or
(4)
CN
9b, R" = H
CN
CN
10c (for 9b, 76%)
10d (for 9c, 74%)
9c, R" = Me
t
we found that treatment of 4d with BuO2H/Cu(acac)2 pro-
Me
O
OH
OH
duced the Henry adducts 11a and 11b at 10% and 46%
yields, respectively (Scheme 5, eq 5). In particular, the ni-
troaldol condensation of the formyl group with MeNO2 was
favored rather than the oxidation of the formyl group. For
the formation of 11b with a benzofuran core and two ni-
tromethyl arms,21 a double installation of MeNO2 and an
oxidative cyclization was observed. The structure of 11b
was determined by single-crystal X-ray analysis.18
MeO
MeO
MeO
tBuO2H, Cu(acac)2
MeNO2
(5)
+
CHO
NO2
NO2
NO2
4d
11a (10%)
11b (46%)
Scheme 5 Synthesis of 7a, 8a,b, 10a–d, and 11a,b
Cu(acac)2
In summary, we have developed a concise route for the ef-
fective synthesis of 1-oxoisochromans via BuO2H/Cu(acac)2
A solution of CuCl2·2H2O (23.5 mmol, 4.0 g) in H2O (25 mL) was slowly
added to a solution of acetylacetone (46.9 mmol, 4.7 g) in MeOH (5
mL) with rapid stirring. Now, a solution of NaOAc (83 mmol, 6.8 g) in
H2O (15 mL) was added to the resulting mixture dropwise. The mix-
ture was then heated to about 80 °C for 15 min while the rapid stir-
ring was maintained. The reaction mixture was first cooled to 25 °C,
and then cooled further in ice bath. The blue grey product was col-
lected by vacuum filtration and washed with cold distilled H2O (100
mL). The product was dried at 110 °C in an oven. The crude product
was recrystallized from hot MeOH; yield: 4.6 g (75%).
t
mediating the direct intramolecular oxidative lactonization
of o-allyl arylaldehydes in the presence of HCO2H, H2O or
AcOH in moderate to good yields under refluxing reaction
conditions. The process provides a cascade pathway of
three carbon–oxygen bond formations. Related plausible
mechanisms have been proposed. Further studies regarding
the synthetic applications of o-allyl arylaldehydes will be
conducted and published in due course.
Compounds 5a, 6a–w, and 7a; General Procedure
tBuO2H (5.0 M in decane, 5.0 mmol, 1.0 mL) was added to a solution of
respective compound 4a–o (1.0 mmol) in HCO2H (for 6a–n, 10 mL),
H2O (10 mL, for 6o–v) or AcOH (10 mL, for 6w). Cu(acac)2 (270 mg,
1.0 mmol) was added to the reaction mixture at 25 °C. The mixture
was stirred at reflux for 3 h and cooled to 25 °C. H2O (1 mL) was added
to the mixture at 25 °C and the solvent was concentrated under re-
duced pressure. The residue was diluted with H2O (10 mL) and the
mixture was extracted with EtOAc (3 × 20 mL). The combined organic
layers were washed with brine, dried, filtered, and evaporated to af-
ford crude products. Purification on silica gel (hexanes/EtOAc: 15:1 to
3:1) afforded compounds 5a, 6a–w, and 7a.
All reagents and solvents were obtained from commercial sources
and used without further purification. Reactions were routinely car-
ried out under an atmosphere of dry N2 with magnetic stirring. Prod-
ucts in organic solvents were dried with anhyd MgSO4 before concen-
tration in vacuo. Melting points were determined with a SMP3 melt-
ing apparatus. 1H and 13C NMR spectra were recorded on a Varian
INOVA-400 spectrometer operating at 400 and at 100 MHz, respec-
tively. Chemical shifts () are reported in parts per million (ppm) and
the coupling constants (J) are given in hertz (Hz). High-resolution
mass spectra (HRMS) were measured with a mass spectrometer Fin-
nigan/Thermo Quest MAT 95XL. X-ray crystal structures were ob-
tained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa
CCD).
2-Allyl-3,4-dimethoxybenzoic Acid (5a)
Table 1, entry 1: CuO (80 mg, 1.0 mmol); yield: 144 mg (65%); color-
less solid; mp 145–147 °C (hexanes and EtOAc).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

F
M.-Y. Chang et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 7.90 (d, J = 8.8 Hz, 1 H), 6.84 (d, J = 8.8
Hz, 1 H), 6.09–5.99 (m, 1 H), 5.02–4.97 (m, 2 H), 3.93 (s, 3 H), 3.95–
3.90 (m, 2 H), 3.82 (s, 3 H).
Formic Acid 5-Hydroxy-6-methoxy-1-oxoisochroman-3-ylmethyl
Ester (6d)
Yield: 207 mg (82%); colorless solid; mp 154–155 °C (hexanes and
EtOAc).
13C NMR (100 MHz, CDCl3):  = 172.5, 156.7, 147.6, 137.5, 137.3,
1H NMR (400 MHz, CDCl3):  = 8.13 (d, J = 0.8 Hz, 1 H), 7.73 (d, J = 8.8
Hz, 1 H), 6.90 (d, J = 8.8 Hz, 1 H), 5.81 (br s, 1 H), 4.78–4.71 (m, 1 H),
4.462 (d, J = 5.2 Hz, 1 H), 4.460 (d, J = 4.8 Hz, 1 H), 3.98 (s, 3 H), 3.19
(dd, J = 3.6, 16.8 Hz, 1 H), 2.88 (dd, J = 3.6, 16.8 Hz, 1 H).
129.0, 121.2, 114.9, 109.3, 60.9, 55.7, 30.8.
HRMS (ESI): m/z (M+ + 1) calcd for C12H15O4: 223.0970; found:
223.0972.
Formic Acid 5,6-Dimethoxy-1-oxoisochroman-3-ylmethyl Ester
(6a)
13C{1H} NMR (100 MHz, CDCl3):  = 164.5, 160.4, 150.5, 141.4, 123.7,
123.5, 117.6, 109.3, 75.2, 64.4, 56.2, 23.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H13O6: 253.0712; found:
Yield: 213 mg (80%); colorless solid; mp 79–80 °C (hexanes and EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.13 (s, 1 H), 7.89 (d, J = 8.4 Hz, 1 H),
6.94 (d, J = 8.4 Hz, 1 H), 4.75–4.69 (m, 1 H), 4.46 (d, J = 4.4 Hz, 2 H),
3.94 (s, 3 H), 3.83 (s, 3 H), 3.21 (dd, J = 3.6, 16.8 Hz, 1 H), 2.89 (dd, J =
3.6, 16.8 Hz, 1 H).
253.0707.
Formic Acid 5,6-Dimethoxy-4-methyl-1-oxoisochroman-3-yl-
methyl Ester (6e)
13C{1H} NMR (100 MHz, CDCl3):  = 164.3, 160.4, 157.1, 144.7, 132.0,
Two isomers (ratio = 7:4); yield: 213 mg (76%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.13 (s, 7/11 H), 8.00 (s, 4/11 H), 7.89
(d, J = 8.4 Hz, 7/11 H), 7.88 (d, J = 8.8 Hz, 4/11 H), 6.95 (d, J = 8.4 Hz,
7/11 H), 6.93 (d, J = 8.4 Hz, 4/11 H), 4.74–4.68 (m, 1 H), 4.51 (dd, J =
7.6, 11.6 Hz, 7/11 H), 4.42 (dd, J = 5.2, 12.0 Hz, 7/11 H), 4.29 (dd, J =
7.2, 12.0 Hz, 4/11 H), 4.10 (dd, J = 6.0, 11.6 Hz, 4/11 H), 3.950 (s, 21/11
H), 3.947 (s, 12/11 H), 3.91 (s, 21/11 H), 3.88 (s, 12/11 H), 3.40–3.36
(m, 1 H), 1.40 (d, J = 7.2 Hz, 12/11 H), 1.20 (d, J = 7.2 Hz, 21/11 H).
127.7, 117.3, 111.1, 75.1, 64.3, 60.7, 55.9, 23.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H15O6: 267.0869; found:
267.0871.
X-ray Crystal Data
Single-crystal of compound 6a was grown by slow diffusion of EtOAc
into a solution of compound 6a in CH2Cl2 to yield a colorless prism.
The compound crystallized in the triclinic crystal system, space group
P-1, a = 6.1163(3) Å, b = 8.9922(5) Å, c = 11.6892(7) Å, V = 606.52(6)
Å3, Z = 2, dcalcd = 1.458 g/cm3, F(000) = 280, 2θ range 1.792 to 26.519°,
R indices (all data) R1 = 0.0406, wR2 = 0.0838.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H17O6: 281.1025; found:
281.1033.
Formic Acid 5-Isopropoxy-6-methoxy-4-methyl-1-oxoisochro-
man-3-ylmethyl Ester (6f)
Formic Acid 5-Butoxy-6-methoxy-1-oxoisochroman-3-ylmethyl
Ester (6b)
Two isomers (ratio = 1:1); yield: 225 mg (73%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.11 (s, 1/2 H), 8.00 (s, 1/2 H), 7.83 (d,
J = 8.8 Hz, 1 H), 6.91 (d, J = 7.6 Hz, 1/2 H), 6.89 (d, J = 7.6 Hz, 1/2 H),
4.71–4.63 (m, 2 H), 4.50 (dd, J = 7.6, 11.6 Hz, 1/2 H), 4.41 (dd, J = 4.8,
12.0 Hz, 1/2 H), 4.28 (dd, J = 7.2, 12.0 Hz, 1/2 H), 4.05 (dd, J = 6.0, 11.6
Hz, 1/2 H), 3.905 (s, 3/2 H), 3.901 (s, 3/2 H), 3.41–3.35 (m, 1 H), 1.37–
1.34 (m, 6 H), 1.19 (d, J = 6.4 Hz, 3/2 H), 1.15 (d, J = 6.4 Hz, 3/2 H).
Yield: 259 mg (84%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.11 (s, 1 H), 7.85 (d, J = 8.8 Hz, 1 H),
6.91 (d, J = 8.8 Hz, 1 H), 4.72–4.66 (m, 1 H), 4.47–4.39 (m, 2 H), 3.99–
3.88 (m, 2 H), 3.91 (s, 3 H), 3.19 (dd, J = 3.2, 16.8 Hz, 1 H), 2.86 (dd, J =
12.0, 16.8 Hz, 1 H), 1.75–1.68 (m, 2 H), 1.51–1.42 (m, 2 H), 0.95 (t, J =
7.6 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H21O6: 309.1338; found:
13C{1H} NMR (100 MHz, CDCl3):  = 164.3, 160.4, 157.2, 144.0, 132.0,
309.1342.
127.3, 117.2, 111.0, 75.1, 73.0, 64.3, 55.8, 31.2, 24.1, 19.0, 13.8.
Formic Acid 5-Benzyloxy-6-methoxy-4-methyl-1-oxoisochroman-
3-ylmethyl Ester (6g)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H21O6: 309.1338; found:
309.1332.
Two isomers (ratio = 1:1); yield: 249 mg (70%); colorless oil.
Formic Acid 5-Benzyloxy-6-methoxy-1-oxoisochroman-3-ylmeth-
yl Ester (6c)
1H NMR (400 MHz, CDCl3):  = 8.07 (s, 1/2 H), 7.94 (s, 1/2 H), 7.887 (d,
J = 8.8 Hz, 1/2 H), 7.885 (d, J = 8.4 Hz, 1/2 H), 7.38–7.33 (m, 5 H), 6.98
(d, J = 8.4 Hz, 1/2 H), 6.96 (d, J = 8.8 Hz, 1/2 H), 5.104 (s, 1 H), 5.100 (s,
1 H), 4.57 (dd, J = 1.6, 8.0 Hz, 1/2 H), 4.43–4.37 (m, 1 H), 4.27–4.21 (m,
1/2 H), 4.01 (dd, J = 8.0, 12.0 Hz, 1/2 H), 3.99 (s, 3 H), 3.73 (dd, J = 4.8,
11.6 Hz, 1/2 H), 3.13 (q, J = 7.2 Hz, 1/2 H), 3.06 (dq, J = 2.4, 7.2 Hz, 1/2
H), 1.31 (d, J = 7.2 Hz, 3/2 H), 1.07 (d, J = 7.2 Hz, 3/2 H).
Yield: 294 mg (86%); colorless solid; mp 119–121 °C (hexanes and
EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.08 (s, 1 H), 7.90 (d, J = 8.4 Hz, 1 H),
7.38–7.31 (m, 5 H), 6.98 (d, J = 8.8 Hz, 1 H), 5.06 (d, J = 11.2 Hz, 1 H),
5.01 (d, J = 11.2 Hz, 1 H), 4.48–4.42 (m, 1 H), 4.29 (d, J = 4.8 Hz, 2 H),
3.99 (s, 3 H), 2.89 (dd, J = 3.2, 16.8 Hz, 1 H), 2.51 (dd, J = 11.6, 16.8 Hz,
1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21O6: 357.1338; found:
357.1334.
13C{1H} NMR (100 MHz, CDCl3):  = 164.4, 160.3, 157.2, 142.9, 132.8,
130.1, 128.8 (2 ×), 128.54 (2x), 128.46, 127.8, 117.3, 111.1, 75.1, 74.9,
64.2, 56.0, 24.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H19O6: 343.1182; found:
343.1188.
Formic Acid 5-Butoxy-6-methoxy-4-methyl-1-oxoisochroman-3-
ylmethyl Ester (6h)
Two isomers (ratio = 1:1); yield: 225 mg (70%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.12 (s, 1/2 H), 8.00 (s, 1/2 H), 7.861 (d,
J = 8.8 Hz, 1 H), 7.857 (d, J = 8.8 Hz, 1/2 H), 6.93 (d, J = 8.4 Hz, 1/2 H),
6.91 (d, J = 7.6 Hz, 1/2 H), 4.73–4.68 (m, 1 H), 4.50 (dd, J = 8.0, 12.0 Hz,
1/2 H), 4.43 (dd, J = 4.4, 11.6 Hz, 1/2 H), 4.28 (dd, J = 7.6, 12.0 Hz, 1/2
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

G
M.-Y. Chang et al.
Paper
Synthesis
H), 4.09–3.95 (m, 2 H), 3.924 (s, 3/2 H), 3.921 (s, 3/2 H), 3.40–3.34 (m,
1 H), 1.80–1.72 (m, 2 H), 1.55–1.43 (m, 2 H), 1.39 (d, J = 7.2 Hz, 3/2 H),
1.19 (d, J = 7.2 Hz, 3/2 H), 0.988 (d, J = 7.2 Hz, 3/2 H), 0.984 (d, J = 7.2
Hz, 3/2 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H20O6: 309.1338; found:
309.1330.
Formic Acid 5-Methoxy-1-oxoisochroman-3-ylmethyl Ester (6m)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H23O6: 323.1495; found:
Yield: 189 mg (80%); colorless oil.
323.1502.
1H NMR (400 MHz, CDCl3):  = 8.12 (d, J = 0.4 Hz, 1 H), 7.70 (dd, J = 1.2,
8.0 Hz, 1 H), 7.36 (t, J = 7.6 Hz, 1 H), 7.09 (dd, J = 0.8, 8.4 Hz, 1 H), 4.77–
4.71 (m, 1 H), 4.46 (d, J = 4.8 Hz, 2 H), 3.87 (s, 3 H), 3.13 (dd, J = 3.6,
16.8 Hz, 1 H), 2.81 (dd, J = 12.0, 16.8 Hz, 1 H).
Formic Acid 5-Cyclopentyloxy-6-methoxy-4-methyl-1-oxoiso-
chroman-3-ylmethyl Ester (6i)
Two isomers (ratio = 1:1); yield: 214 mg (64%); colorless oil.
13C{1H} NMR (100 MHz, CDCl3):  = 164.4, 160.4, 155.6, 128.2, 126.9,
1H NMR (400 MHz, CDCl3):  = 8.11 (s, 1/2 H), 8.00 (s, 1/2 H), 7.829 (d,
J = 8.8 Hz, 1/2 H), 7.826 (d, J = 8.8 Hz, 1/2 H), 6.914 (d, J = 8.8 Hz, 1/2
H), 6.90 (d, J = 8.4 Hz, 1/2 H), 5.01–4.97 (m, 1 H), 4.71–4.66 (m, 1 H),
4.50 (dd, J = 4.4, 11.6 Hz, 1/2 H), 4.44 (dd, J = 7.6, 12.0 Hz, 1/2 H), 4.30
(ddd, J = 0.8, 7.2, 11.6 Hz, 1/2 H), 4.06 (ddd, J = 0.8, 6.4, 11.6 Hz, 1/2 H),
3.910 (s, 3/2 H), 3.908 (s, 3/2 H), 3.34–3.29 (m, 1 H), 1.95–1.72 (m, 3
H), 1.68–1.57 (m, 5 H), 1.35 (d, J = 6.8 Hz, 3/2 H), 1.15 (d, J = 6.8 Hz, 3/2
H).
125.5, 121.9, 115.0, 75.2, 64.4, 55.8, 23.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H13O5: 237.0763; found:
237.0769.
Formic Acid 1-Oxoisochroman-3-ylmethyl Ester (6n)
Yield: 157 mg (76%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.13 (s, 1 H), 8.10 (d, J = 7.6 Hz, 1 H),
7.56 (dt, J = 1.2, 7.6 Hz, 1 H), 7.42 (t, J = 7.6 Hz, 1 H), 7.27 (d, J = 7.6 Hz,
1 H), 4.83–4.77 (m, 1 H), 4.47 (d, J = 4.8 Hz, 2 H), 3.15 (dd, J = 12.0,
16.4 Hz, 1 H), 2.96 (dd, J = 3.6, 16.4 Hz, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H23O7: 335.1495; found:
335.1499.
13C{1H} NMR (100 MHz, CDCl3):  = 164.4, 160.4, 137.9, 134.1, 130.5,
128.0, 127.5, 124.6, 75.4, 64.2, 29.6.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H11O4: 207.0657; found:
Formic Acid 5,7-Dimethoxy-1-oxoisochroman-3-ylmethyl Ester
(6j)
Yield: 218 mg (82%); colorless oil.
207.0660.
1H NMR (400 MHz, CDCl3):  = 8.12 (s, 1 H), 7.17 (d, J = 2.4 Hz, 1 H),
6.66 (d, J = 2.4 Hz, 1 H), 4.75–4.69 (m, 1 H), 4.45 (d, J = 4.8 Hz, 2 H),
3.84 (s, 3 H), 3.83 (s, 3 H), 3.08 (dd, J = 3.2, 16.8 Hz, 1 H), 2.75 (dd, J =
11.6, 16.8 Hz, 1 H).
3-Hydroxymethyl-5,6-dimethoxyisochroman-1-one (6o)
Yield: 167 mg (70%); colorless solid; mp 131–132 °C (hexanes and
EtOAc).
13C{1H} NMR (100 MHz, CDCl3):  = 164.5, 160.4, 159.8, 156.8, 125.7,
119.9, 104.5, 103.6, 75.5, 64.4, 55.8, 55.7, 22.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H15O6: 267.0869; found:
267.0875.
1H NMR (400 MHz, CDCl3):  = 7.86 (d, J = 8.8 Hz, 1 H), 6.91 (d, J = 8.8
Hz, 1 H), 4.58–4.52 (m, 1 H), 3.95 (dd, J = 3.2, 12.4 Hz, 1 H), 3.92 (s, 3
H), 3.84 (dd, J = 5.2, 12.4 Hz, 1 H), 3.81 (s, 3 H), 3.13 (dd, J = 3.2, 16.8
Hz, 1 H), 2.94 (dd, J = 12.0, 16.8 Hz, 1 H), 2.80 (br s, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 165.2, 157.1, 144.7, 132.9, 127.5,
117.4, 110.8, 78.8, 64.3, 60.6, 55.8, 23.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H15O5: 239.0920; found:
239.0926.
Formic Acid 5-Benzyloxy-7-methoxy-1-oxoisochroman-3-ylmeth-
yl Ester (6k)
Yield: 274 mg (80%); colorless solid; mp 124–125 °C (hexanes and
EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.10 (s, 1 H), 7.41–7.32 (m, 5 H), 7.19
(d, J = 2.4 Hz, 1 H), 6.73 (d, J = 2.4 Hz, 1 H), 5.07 (d, J = 11.6 Hz, 1 H),
5.03 (d, J = 11.6 Hz, 1 H), 4.75–4.69 (m, 1 H), 4.46–4.38 (m, 2 H), 3.81
(s, 3 H), 3.11 (dd, J = 3.2, 16.8 Hz, 1 H), 2.78 (dd, J = 12.0, 16.8 Hz, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 164.4, 160.4, 159.6, 155.8, 135.9,
128.6 (2 ×), 128.2, 127.3 (2 ×), 125.8, 120.2, 105.7, 103.9, 75.5, 70.5,
64.3, 55.6, 22.9.
5-Butoxy-3-hydroxymethyl-6-methoxyisochroman-1-one (6p)
Yield: 213 mg (76%); colorless solid; mp 97–98 °C (hexanes and EtOAc)
1H NMR (400 MHz, CDCl3):  = 7.87 (d, J = 8.8 Hz, 1 H), 6.92 (d, J = 8.8
Hz, 1 H), 4.57–4.51 (m, 1 H), 4.00–3.82 (m, 4 H), 3.92 (s, 3 H), 3.13 (dd,
J = 3.2, 16.8 Hz, 1 H), 2.93 (dd, J = 12.0, 16.8 Hz, 1 H), 2.35 (br s, 1 H),
1.76–1.69 (m, 2 H), 1.52–1.43 (m, 2 H), 0.97 (t, J = 7.2 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H19O6: 343.1182; found:
13C{1H} NMR (100 MHz, CDCl3):  = 165.2, 157.2, 144.1, 133.0, 127.3,
343.1189.
117.4, 110.8, 78.8, 73.1, 64.4, 55.8, 32.2, 23.6, 19.1, 13.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H21O5: 281.1389; found:
281.1393.
Formic Acid 5-Butoxy-7-methoxy-1-oxoisochroman-3-ylmethyl
Ester (6l)
Yield: 256 mg (83%); colorless oil.
3-Hydroxymethyl-5-isopropoxy-6-methoxy-4-methylisochro-
man-1-one (6q)
1H NMR (400 MHz, CDCl3):  = 8.13 (s, 1 H), 7.16 (d, J = 2.4 Hz, 1 H),
6.64 (d, J = 2.4 Hz, 1 H), 4.76–4.70 (m, 1 H), 4.48–4.42 (m, 2 H), 4.01–
3.88 (m, 2 H), 3.83 (s, 3 H), 3.08 (dd, J = 3.6, 16.8 Hz, 1 H), 2.75 (dd, J =
12.0, 16.8 Hz, 1 H), 1.82–1.75 (m, 2 H), 1.54–1.44 (m, 2 H), 0.98 (t, J =
7.6 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 164.6, 160.4, 159.7, 156.3, 125.7,
120.1, 105.2, 103.4, 75.5, 68.3, 64.4, 55.7, 31.0, 22.9, 19.2, 13.8.
Two isomers (ratio = 1:1); yield: 174 mg (62%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.83 (d, J = 8.8 Hz, 1/2 H), 7.82 (d, J =
8.8 Hz, 1/2 H), 6.90 (d, J = 8.4 Hz, 1/2 H), 6.87 (d, J = 8.8 Hz, 1/2 H),
4.69–4.60 (m, 1 H), 4.57–4.52 (m, 1 H), 4.03 (dd, J = 8.0, 12.0 Hz, 1/2
H), 3.903 (3/2 H), 3.895 (s, 3/2 H), 3.78 (dd, J = 4.0, 12.0 Hz, 1/2 H),
3.73 (dd, J = 7.6, 12.0 Hz, 1/2 H), 3.51 (dd, J = 5.6, 11.2 Hz, 1/2 H), 3.39
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

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M.-Y. Chang et al.
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Synthesis
(dd, J = 5.6, 12.0 Hz, 1/2 H), 3.36 (dd, J = 5.6, 12.0 Hz, 1/2 H), 2.40 (br s,
3-Hydroxymethylisochroman-1-one (6v)
1 H), 1.37–1.29 (m, 9/2 H), 1.20–1.17 (m, 3 H), 1.10 (d, J = 6.4 Hz, 3/2
H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H21O5: 281.1389; found:
281.1396.
Yield: 118 mg (66%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.07 (dd, J = 1.2, 7.6 Hz, 1 H), 7.54 (dt,
J = 1.2, 7.6 Hz, 1 H), 7.38 (dt, J = 1.2, 7.6 Hz, 1 H), 7.27 (d, J = 7.6 Hz, 1
H), 4.67–4.61 (m, 1 H), 3.96 (dd, J = 3.6, 12.4 Hz, 1 H), 3.85 (dd, J = 5.2,
12.4 Hz, 1 H), 3.22 (dd, J = 12.4, 16.4 Hz, 1 H), 2.90 (br s, 1 H), 2.86 (dd,
J = 3.2, 16.4 Hz, 1 H).
5-Benzyloxy-3-hydroxymethyl-6-methoxy-4-methylisochroman-
1-one (6r)
13C{1H} NMR (100 MHz, CDCl3):  = 165.3, 138.8, 134.0, 130.3, 127.7,
Two isomers (ratio = 1:1); yield: 230 mg (70%); colorless oil.
127.6, 124.6, 79.0, 64.1, 29.1.
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 8.4 Hz, 1/2 H), 7.86 (d, J =
8.4 Hz, 1/2 H), 7.39–7.33 (m, 5 H), 6.97 (d, J = 8.8 Hz, 1/2 H), 6.94 (d,
J = 8.4 Hz, 1/2 H), 5.14 (d, J = 11.6 Hz, 1/2 H), 5.09 (s, 1 H), 5.07 (d, J =
11.2 Hz, 1/2 H ), 4.43–4.40 (m, 1/2 H ), 4.30–4.26 (m, 1/2 H ), 3.983 (s,
3/2 H), 3.981 (s, 3/2 H), 3.93 (dd, J = 8.0, 12.0 Hz, 1/2 H), 3.61 (dd, J =
4.0, 12.0 Hz, 1/2 H), 3.46 (dd, J = 7.6, 12.0 Hz, 1/2 H), 3.19–3.12 (m, 3/2
H), 3.08–3.05 (m, 1/2 H), 2.18 (br s, 1 H), 1.29 (d, J = 6.8 Hz, 3/2 H),
1.04 (d, J = 6.8 Hz, 3/2 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H11O3: 179.0708; found:
179.0715.
Acetic Acid 5,6-Dimethoxy-1-oxoisochroman-3-ylmethyl Ester
(6w)
Yield: 224 mg (80%); colorless solid; mp 69–70 °C (hexanes and EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.87 (d, J = 8.4 Hz, 1 H), 6.93 (d, J = 8.4
Hz, 1 H), 4.71–4.65 (m, 1 H), 4.37–4.30 (m, 2 H), 3.93 (s, 3 H), 3.82 (s, 3
H), 3.17 (dd, J = 3.6, 16.8 Hz, 1 H), 2.86 (dd, J = 3.6, 16.8 Hz, 1 H), 2.10
(s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H21O5: 329.1389; found:
329.1398.
13C{1H} NMR (100 MHz, CDCl3):  = 170.7, 164.5, 157.1, 144.7, 132.1,
127.6, 117.4, 111.0, 75.4, 65.1, 60.7, 55.9, 23.9, 20.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H17O6: 281.1025; found:
281.1032.
5-Butoxy-3-hydroxymethyl-6-methoxy-4-methylisochroman-1-
one (6s)
Two isomers (ratio = 1:1); yield: 212 mg (72%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.85 (d, J = 8.8 Hz, 1/2 H), 7.84 (d, J =
8.8 Hz, 1/2 H), 6.92 (d, J = 8.8 Hz, 1/2 H), 6.89 (d, J = 8.8 Hz, 1/2 H),
4.58–4.54 (m, 1 H), 4.07–3.92 (m, 7/2 H), 3.92 (s, 3/2 H), 3.91 (s, 3/2
H), 3.79 (dd, J = 4.0, 12.0 Hz, 1/2 H), 3.72 (dd, J = 7.6, 12.0 Hz, 1/2 H),
3.51 (dd, J = 5.6, 11.2 Hz, 1/2 H), 3.40–3.34 (m, 1 H), 1.79–1.72 (m, 2
H), 1.53–1.47 (m, 2 H), 1.38 (d, J = 7.2 Hz, 3/2 H), 1.15 (d, J = 7.2 Hz, 3/2
H), 0.98 (t, J = 7.2 Hz, 3 H).
2,3-Dimethoxy-6-methylnaphthalene (7a)
Yield: 107 mg (53%); colorless solid; mp 97–98 °C (hexanes and EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.59 (d, J = 8.4 Hz, 1 H), 7.47 (s, 1 H),
7.18 (dd, J = 1.6, 8.4 Hz, 1 H), 7.09 (s, 1 H), 7.05 (s, 1 H), 3.992 (s, 3 H),
3.988 (s, 3 H), 2.48 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H23O5: 295.1546; found:
13C{1H} NMR (100 MHz, CDCl3):  = 149.5, 148.8, 133.6, 129.3, 127.1,
295.1555.
126.3, 126.1, 125.5, 106.2, 105.8, 55.8 (2 ×), 21.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H15O2: 203.1072; found:
203.1079.
5-Cyclopentyloxy-3-hydroxymethyl-6-methoxy-4-methylisochro-
man-1-one (6t)
Two isomers (ratio = 1:1); yield: 208 mg (68%); colorless oil.
Compounds 8a,b; General Procedure
1H NMR (400 MHz, CDCl3):  = 7.82 (d, J = 8.8 Hz, 1/2 H), 7.81 (d, J =
8.8 Hz, 1/2 H), 6.90 (d, J = 8.8 Hz, 1/2 H), 6.88 (d, J = 9.2 Hz, 1/2 H),
5.00–4.95 (m, 1 H), 4.58–4.52 (m, 1 H), 4.03 (dd, J = 7.6, 12.0 Hz, 1/2
H), 3.91 (s, 3/2 H), 3.90 (s, 3/2 H), 3.78 (dd, J = 4.0, 12.0 Hz, 1/2 H), 3.74
(dd, J = 7.6, 12.0 Hz, 1/2 H), 3.52 (dd, J = 5.6, 11.2 Hz, 1/2 H), 3.36–3.28
(m, 1 H), 2.60 (br s, 1 H), 1.96–1.89 (m, 3 H), 1.88–1.58 (m, 5 H), 1.32
(d, J = 7.2 Hz, 3/2 H), 1.10 (d, J = 6.8 Hz, 3/2 H).
tBuO2H (5.0 M in decane, 5.5 mmol, 1.0 mL) was added to a solution of
4a or 4e (1.0 mmol) in (CH2Cl)2 (10 mL). p-TsOH (178 mg, 1.0 mmol)
and Cu(acac)2 (270 mg, 1 mmol) were added to the reaction mixture
at 25 °C. The mixture was stirred at reflux for 3 h and cooled to 25 °C.
H2O (1 mL) was added to the mixture at 25 °C and the solvent was
removed under reduced pressure. The residue was diluted with H2O
(10 mL) and the mixture was extracted with EtOAc (3 × 20 mL). The
combined organic layers were washed with brine, dried, filtered, and
evaporated to afford crude product. Purification on silica gel (hex-
anes/EtOAc 15:1 → 3:1) afforded compounds 8a,b.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H23O5: 307.1546; found:
307.1552.
3-Hydroxymethyl-5,7-dimethoxyisochroman-1-one (6u)
5,6-Dimethoxy-3-methylisochroman-1-one (8a)
Yield: 155 mg (65%); colorless solid; mp 110–112 °C (hexanes and
EtOAc).
Yield: 173 mg (78%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.89 (d, J = 8.8 Hz, 1 H), 6.92 (d, J = 8.4
Hz, 1 H), 4.64–4.56 (m, 1 H), 3.94 (s, 3 H), 3.82 (s, 3 H), 3.18 (dd, J =
3.2, 16.8 Hz, 1 H), 2.72 (dd, J = 11.6, 16.8 Hz, 1 H), 1.52 (d, J = 6.4 Hz, 3
H).
13C{1H} NMR (100 MHz, CDCl3):  = 165.6, 156.9, 144.5, 133.2, 127.5,
117.9, 110.8, 74.8, 60.7, 55.9, 29.1, 21.0.
1H NMR (400 MHz, CDCl3):  = 7.18 (d, J = 2.4 Hz, 1 H), 6.66 (d, J = 2.4
Hz, 1 H), 4.61–4.55 (m, 1 H), 3.94 (dd, J = 4.4, 16.4 Hz, 1 H), 3.85 (dd,
J = 12.0, 16.8 Hz, 1 H), 3.84 (s, 3 H), 3.83 (s, 3 H), 3.01 (dd, J = 3.2, 16.8
Hz, 1 H), 2.78 (dd, J = 12.4, 16.8 Hz, 1 H), 2.21 (br s, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 165.2, 159.6, 156.9, 125.8, 120.8,
104.5, 103.5, 79.2, 64.5, 55.8, 55.7, 22.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H15O4: 223.0970; found:
223.0977.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H15O5: 239.0920; found:
239.0928.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

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5,6-Dimethoxy-3,4-dimethylisochroman-1-one (8b)
1H NMR (400 MHz, CDCl3):  = 8.10 (s, 1 H), 7.18 (d, J = 8.4 Hz, 1 H),
6.80 (d, J = 8.4 Hz, 1 H), 5.23–5.16 (m, 1 H), 4.47 (ddd, J = 0.8, 3.6, 12.0
Hz, 1 H), 4.38 (ddd, J = 0.8, 6.0, 12.0 Hz, 1 H), 3.92 (s, 3 H), 3.53 (dd, J =
9.6, 16.4 Hz, 1 H), 3.24 (dd, J = 7.6, 16.4 Hz, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 160.5, 148.2, 147.8, 130.6, 126.4,
117.5, 111.9, 100.6, 80.8, 64.4, 56.2, 32.1.
Two isomers (ratio = 1:1); yield: 161 mg (68%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 8.8 Hz, 1 H), 6.92 (d, J = 8.4
Hz, 1/2 H), 6.91 (d, J = 8.8 Hz, 1/2 H), 4.69–4.60 (m, 1 H), 3.944 (s, 3/2
H), 3.941 (s, 3/2 H), 3.90 (s, 3/2 H), 3.88 (s, 3/2 H), 3.21–3.13 (m, 1 H),
1.47 (d, J = 6.4 Hz, 3/2 H), 1.36 (d, J = 6.8 Hz, 3/2 H), 1.29 (d, J = 6.8 Hz,
3/2 H), 1.18 (d, J = 7.2 Hz, 3/2 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H12NO4: 234.0766; found:
13C{1H} NMR (100 MHz, CDCl3):  = 165.8 (1 C), 157.0 (1/2 C), 156.8
(1/2 C), 145.3 (1/2 C), 144.0 (1/2 C), 140.2 (1/2 C), 137.1 (1/2 C), 127.5
(1/2 C), 127.4 (1/2 C), 116.9 (1 C), 110.9 (1/2 C), 110.6 (1/2 C), 79.8
(1/2 C), 76.9 (1/2 C), 61.1 (1/2 C), 61.0 (1/2 C), 55.84 (1/2 C), 55.79 (1/2
C), 32.3 (1/2 C), 31.6 (1/2 C), 20.6 (1/2 C), 20.4 (1/2 C), 17.8 (1/2 C),
12.8 (1/2 C).
234.0772.
Formic Acid 3-(6-Cyano-2,3-dimethoxyphenyl)-2-formyloxypro-
pyl Ester (10d)
Yield: 217 mg (74%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.08 (s, 1 H), 8.00 (s, 1 H), 7.38 (d, J =
8.4 Hz, 1 H), 6.88 (d, J = 8.8 Hz, 1 H), 5.61–5.55 (m, 1 H), 4.43 (dd, J =
3.6, 12.0 Hz, 1 H), 4.22 (dd, J = 6.0, 12.0 Hz, 1 H), 3.92 (s, 3 H), 3.90 (s,
3 H), 3.23 (dd, J = 8.0, 14.0 Hz, 1 H), 3.18 (dd, J = 5.6, 13.6 Hz, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H17O4: 237.1127; found:
237.1134.
Compounds 10a–d; General Procedure
13C{1H} NMR (100 MHz, CDCl3):  = 160.4, 160.0, 156.3, 148.0, 133.1,
tBuO2H (5.0 M in decane, 5.0 mmol, 1.0 mL) was added to a solution of
respective compound 9a–c (1.0 mmol) in HCO2H (10 mL). Cu(acac)2
(270 mg, 1 mmol) was added to the reaction mixture at 25 °C and the
mixture was stirred at reflux for 3 h. The reaction mixture was cooled
to 25 °C and H2O (1 mL) was added at 25 °C. The solvent was concen-
trated under reduced pressure. The residue was diluted with H2O (10
mL) and the mixture was extracted with EtOAc (3 × 20 mL). The com-
bined organic layers were washed with brine, dried, filtered, and
evaporated to afford crude product. Purification on silica gel (hex-
anes/EtOAc 10:1 → 6:1) afforded compounds 10a–d.
129.4, 118.0, 111.7, 105.8, 70.1, 63.7, 60.8, 55.9, 30.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H16NO6: 294.0978; found:
294.0984.
Compounds 11a,b
tBuO2H (5.0 M in decane, 5.0 mmol, 1.0 mL) was added to a solution of
compound 4d (192 mg, 1.0 mmol) in MeNO2 (10 mL). Cu(acac)2 (270
mg, 1 mmol) was added to the reaction mixture at 25 °C. The reaction
mixture was stirred at reflux for 3 h and cooled to 25 °C. H2O (1 mL)
was added to the mixture at 25 ° and the solvent was removed under
reduced pressure. The residue was diluted with H2O (10 mL) and the
mixture was extracted with EtOAc (3 × 20 mL). The combined organic
layers were washed with brine, dried, filtered, and evaporated to af-
ford crude product. Purification on silica gel (hexanes/EtOAc 10:1 →
6:1) afforded compounds 11a,b.
Formic Acid 6-Methoxy-3-nitro-2-oxiranylmethylphenyl Ester
(10a)
Yield: 172 mg (68%); colorless solid; mp 105–107 °C (hexanes and
EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.10 (d, J = 0.4 Hz, 1 H), 7.82 (d, J = 8.8
Hz, 1 H), 6.85 (d, J = 8.8 Hz, 1 H), 5.25–5.18 (m, 1 H), 4.49 (ddd, J = 0.8,
3.6, 12.0 Hz, 1 H), 4.39 (ddd, J = 0.8, 1.6, 12.0 Hz, 1 H), 3.97 (s, 3 H),
3.86 (dd, J = 10.0, 17.6 Hz, 1 H), 3.56 (dd, J = 7.6, 18.0 Hz, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 160.5, 149.4, 142.4, 134.6, 124.1,
118.6, 111.0, 81.2, 64.6, 56.4, 34.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H12NO6: 254.0665; found:
254.0670.
2-Allyl-6-methoxy-3-(2-nitrovinyl)phenol (11a)
Yield: 24 mg (10%); colorless solid; mp 65–67 °C (hexanes and EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.22 (d, J = 13.6 Hz, 1 H), 7.45 (d, J =
13.2 Hz, 1 H), 7.15 (d, J = 8.4 Hz, 1 H), 6.81 (d, J = 8.8 Hz, 1 H), 6.00–
5.90 (m, 1 H), 5.87 (s, 1 H), 5.05 (dq, J = 1.6, 10.0 Hz, 1 H), 4.95 (dt, J =
1.6, 16.8 Hz, 1 H), 3.95 (s, 3 H), 3.59 (dt, J = 1.6, 6.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 119.1, 144.0, 137.0, 136.3, 135.4,
126.5, 122.6, 119.8, 115.9, 108.9, 56.1, 29.8.
HRMS (ESI): m/z (M+ + 1): calcd for C12H14NO4: 236.0923; found:
236.0931.
(7-Methoxy-4-nitro-2,3-dihydrobenzofuran-2-yl)methanol (10b)
Yield: 23 mg (10%); colorless solid; mp 116–118 °C (hexanes and EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.79 (d, J = 8.8 Hz, 1 H), 6.83 (d, J = 8.8
Hz, 1 H), 5.11–5.05 (m, 1 H), 3.98 (dd, J = 3.2, 12.0 Hz, 1 H), 3.97 (s, 3
H), 3.79 (dd, J = 5.2, 12.0 Hz, 1 H), 3.77 (dd, J = 9.6, 17.6 Hz, 1 H), 3.59
(dd, J = 7.6, 17.6 Hz, 1 H), 1.80 (br s, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 159.6, 149.2, 138.4, 125.2, 118.3,
110.6, 84.9, 64.3, 56.3, 33.4.
7-Methoxy-2-methyl-4-(2-nitro-1-nitromethylethyl)benzofuran
(11b)
Yield: 135 mg (46%); colorless solid; mp 147–148 °C (hexanes and
EtOAc).
1H NMR (400 MHz, CDCl3):  = 6.90 (d, J = 8.0 Hz, 1 H), 6.67 (d, J = 8.4
Hz, 1 H), 6.44 (d, J = 0.8 Hz, 1 H), 4.84–4.75 (m, 4 H), 4.56–4.49 (m, 1
H), 3.95 (s, 3 H), 2.46 (d, J = 0.8 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C10H12NO5: 226.0716; found:
226.0724.
13C NMR (100 MHz, CDCl3):  = 156.9, 145.1, 143.7, 129.5, 121.1,
117.6, 105.7, 100.5, 76.2 (2 ×), 55.9, 38.9, 13.9.
HRMS (ESI): m/z (M+ + 1) calcd for C13H15N2O6 295.0930; found;
295.0935.
Formic Acid 3-Cyano-6-methoxy-2-oxiranylmethylphenyl Ester
(10c)
Yield: 177 mg (76%); colorless solid; mp 68–69 °C (hexanes and EtOAc).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

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M.-Y. Chang et al.
Paper
Synthesis
X-ray Crystal Data
(10) For Bi(III), see: (a) Malik, P.; Chakraborty, D. Synthesis 2010,
3736. (b) Bonvin, Y.; Callens, E.; Larrosa, I.; Henderson, D. A.;
Oldham, J.; Burton, A. J.; Barrett, A. G. M. Org. Lett. 2005, 7, 4549.
(11) For I2, see: (a) Vadagaonkar, K. S.; Kalmode, H. P.; Prakash, S.;
Chaskar, A. C. Synlett 2015, 26, 1677. (b) Reddi, R. N.; Prasad, A.
Org. Lett. 2014, 16, 5674. (c) Aruri, H.; Singh, U.; Kumar, S.;
Kushwaha, M.; Gupta, A. P.; Vishwakarma, R. A.; Singh, P. P. Org.
Lett. 2016, 18, 3638. (d) Singh, R.; Allam, B. K.; Singh, N.; Kumari,
K.; Singh, S. K.; Singh, K. N. Org. Lett. 2015, 17, 2656. (e) Lei, X.;
Zheng, L.; Zhang, C.; Shi, X.; Chen, Y. J. Org. Chem. 2018, 83,
1772. (f) Meesin, J.; Katrun, P.; Pareseecharoen, C.; Pohmakotr,
M.; Reutrakul, V.; Soorukram, D.; Kuhakam, C. J. Org. Chem.
2016, 81, 2744. (g) Jiang, H.; Huang, H.; Cao, H.; Qi, C. Org. Lett.
2010, 12, 5561. (h) Wan, C.; Gao, L.; Wang, Q.; Zhang, J.; Wang,
Z. Org. Lett. 2010, 12, 3902. (i) Gao, W.-C.; Hu, F.; Huo, Y.-M.;
Chang, H.-H.; Li, X.; Wei, W.-L. Org. Lett. 2015, 17, 3914.
(j) Ilangovan, A.; Satish, G. J. Org. Chem. 2014, 79, 4984.
(k) Zhang, J.; Zhu, D.; Yu, C.; Wan, C.; Wang, Z. Org. Lett. 2010,
12, 2841. (l) Gupta, A.; Deshmuk, M. S.; Jain, N. J. Org. Chem.
2107, 82, 4748.
Single-crystal of compound 11b was grown by slow diffusion of EtOAc
into a solution of compound 11b in CH2Cl2 to yield a colorless prism.
The compound crystallizes in the monoclinic crystal system, space
group P 21/c, a = 7.064(2)Å, b = 17.088(6) Å, c = 11.083(4) Å, V =
1317.3(8) Å3, Z = 4, dcalcd = 1.484 g/cm3, F(000) = 616, 2θ range 2.214 to
26.397°, R indices (all data) R1 = 0.0976, wR2 = 0.3080.
Funding Information
Ministry of Science and Technology of the Republic of China (MOST
109-2113-M-037-014-MY3).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706469. Su
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(12) For NIS, see: Yan, Y.; Zhang, Y.; Zha, Z.; Wang, Z. Org. Lett. 2013,
15, 2274.
References
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(14) For biological
activities of
1-oxoisochromans,
see:
(a) Shimojima, Y.; Shirai, T.; Baba, T.; Hayashi, H. J. Med. Chem.
1985, 28, 3. (b) Shinkaruk, S.; Bennetau, B.; Babin, P.; Schmitter,
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Prod. Res. 2013, 27, 2240. (e) Guimaraes, K. G.; de Freitas, R. P.;
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

K
M.-Y. Chang et al.
Paper
Synthesis
t
(18) CCDC 1947902 (6a) and 1947903 (11b) contain the supplemen-
tary crystallographic data for this paper. The data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/getstructures.
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K