Smooth photocatalytic preparation of 2-substituted 1,3-benzodioxoles

Article abstract of DOI:10.1002/chem.201002546

A mild and general method for the synthesis of potentially bioactive 2-substituted-1,3-benzodioxoles is presented. This is based on the photocatalyzed activation of methylene hydrogen atoms in the presence of tetrabutylammonium decatungstate (TBADT). The method gave yields ranging from 46-77% with no interference by benzene ring substituents, such as OR, COOMe, Me, or CHO. The OH group interfered, but protection regenerated the reactivity. 5-Chloro-1,3-benzodioxole was converted into a safrole derivative through a one-pot process involving two consecutive irradiations, at 366 nm for the photocatalyzed alkylation at position 2 and at 310 nm for the alkylation at position 5.

Full text of DOI:10.1002/chem.201002546

DOI: 10.1002/chem.201002546
Smooth Photocatalytic Preparation of 2-Substituted 1,3-Benzodioxoles
Davide Ravelli, Angelo Albini, and Maurizio Fagnoni*[a]
Abstract: A mild and general method
for the synthesis of potentially bioac-
tive 2-substituted-1,3-benzodioxoles is
presented. This is based on the photo-
catalyzed activation of methylene hy-
drogen atoms in the presence of tetra-
ence by benzene ring substituents, such
as OR, COOMe, Me, or CHO. The
OH group interfered, but protection
regenerated the reactivity. 5-Chloro-
1,3-benzodioxole was converted into a
safrole derivative through a one-pot
process involving two consecutive irra-
diations, at 366 nm for the photocata-
lyzed alkylation at position 2 and at
310 nm for the alkylation at position 5.
Keywords: alkylation · benzodiox-
butylammonium
decatungstate
À
oles · C H activation · photocataly-
(TBADT). The method gave yields
ranging from 46–77% with no interfer-
sis · radical reactions
Introduction
substituted alkyl group at position 2 modifies the activity[5]
or makes it specific towards some classes of enzymes (e.g.
for epoxide hydrolase)[6] rather than eliminating it. These
compounds are usually prepared by condensation of a (sub-
stituted) catechol and a carbonyl derivative,[7,8] although the
method is unsatisfactory when using low-boiling aldehydes
or ketones.[9] The alternative derivatization at position 2 of
the preformed 1,3-benzodioxole ring has likewise been ap-
plied with some success for the introduction of a chlorine or
of a O-bonded substituent.[10,11]
The introduction of a C-bonded substituent has been
rarely reported (see the Discussion Section). An appealing
entry would involve H abstraction leading to the 1,3-benzo-
dioxol-2-yl radical and trapping, a process for which photo-
catalysis[12] has been shown to be a valid option. In particu-
The 1,3-benzodioxole moiety is present in many biologically
active molecules with antitumor, antioxidant, antibacterial,
and insecticidal activity. A few examples among many are
Tadalafil (a PDE5 inhibitor used for the treatment of erec-
tile dysfunction with the commercial name of Cialis), the
well-known methamphetamine Ecstasy (a psychoactive
drug), Safrole (a sassafras plant extract, formerly used in
perfumery but nowadays banned because of its weak carci-
nogenic activity), and piperonyl butoxide (widely employed
as a pesticide synergist). The marked biological activity that
the 1,3-benzodioxole fragment imparts to these molecules
depends on the presence of the methylenedioxy moiety,
which is known to inhibit some enzymes and to promote Cy-
tochrome P-450 induction.[1,2] This has stimulated studies
aimed both at the preparation of 1,3-benzodioxole deriva-
tives in view of their possible cytotoxic and antitumor activi-
ty[3] and to the isolation from plants of bioactive constituents
of such a structure.[4]
lar,
tetrabutylammonium
decatungstate
salt
((nBu4N)4W10O32, TBADT) is a robust and easily pre-
pared[13] photocatalyst[14] that has proven effective for the ac-
À
tivation of C H bonds in various classes of organic mole-
cules, including aldehydes,[15] amides,[16] and even cycloal-
kanes.[17] Excited TBADT abstracts a hydrogen atom from
the reagent and is regenerated by back H transfer in the last
step of the reaction, so that light is actually the stoichiomet-
ric reagent[18] (see Scheme 12). The carbon radical thus
formed is the key intermediate for the mild alkylation of
enones, unsaturated esters, and nitriles.[14a] Preliminary ex-
periments[13,19] showed that a-oxyalkyl radicals were likewise
easily obtained by hydrogen abstraction from a few ethers
and one acetal. Accordingly, it appeared worthwhile to test
the alkylation at position 2 of 1,3-benzodioxoles by TBADT
photocatalysis.
Less attention has been paid to 2-substituted-1,3-benzo-
dioxoles, considered to be less bioactive. However, there is
some indication in the literature that introducing an alkyl or
[a] D. Ravelli, Prof. A. Albini, Prof. M. Fagnoni
Department of Organic Chemistry
University of Pavia, Via Taramelli 10 (Italy)
Fax : (+39)0382-987316
E-mail: fagnoni@unipv.it
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002546.
572
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FULL PAPER
Table 1. Photocatalyzed preparation of 2-substituted-1,3-benzodioxoles.[a]
Results
The TBADT-photocatalyzed reaction of a few 1,3-benzo-
dioxoles (1–8) with electrophilic alkenes (9–18) was studied
to assess the feasibility and the scope of the reaction. Blank
experiments showed that parent 1,3-benzodioxole (1) was
not appreciably consumed when irradiated in neat acetoni-
trile for 40 h by means of phosphor-coated lamps (lirr =
366 nm, see the Experimental Section and Supporting infor-
mation) and to a modest degree (ca. 10%) when in the pres-
ence of TBADT (2 mol%), although no byproducts were
detected by GC analysis. Moreover, in the absence of
TBADT, 1 was likewise unreactive when irradiated in the
presence of acrylonitrile (9).
Entry
Benzodioxole
(0.11m)
1 (R=R1 =H)
1
1
Olefin
(0.1m)
Products
ACHTUNGTRENNUNG
(yields [%])[b]
G
R
1
2
3
4
9
19 (32), 20 (22)
10
11
12
13
14
15
16
17
18
17
10
14
9
21 (63, 65[c]
22 (56)
)
1
1
23 (69)[d]
5[e]
6
24 (66), 25 (22)
26 (65)
27 (56)
28 (51)
29 (70)
30 (46)
31 (61)
32 (60)
33 (75)
2 (R=COOMe; R1 =H)
3 (R=Cl; R1 =H)
3
7
8
9
10
11
12
13
14
15[e]
4 (R=CH3; R1 =H)
5 (R=CH2OAc; R1 =H)
5
Parent benzodioxole: The photolysis of an acetonitrile mix-
ture of 1 (0.11m), 9 (0.1m), and TBADT (2ꢁ10À3 m) effi-
ciently led to the formation of nitrile 19 as the major prod-
uct (32% yield) along with dinitrile 20 (22%, Scheme 1).
6 (R=CHO; R1 =H)
7 (R=OCOOEt; R1 =H)
8 (R=H; R1 =Me
8
34 (65)
35 (77)
13
[a] Reaction conditions: 1–8, (0.11m), 9–18 (0.1m), TBADT (2ꢁ10À3 m) in
MeCN irradiated at 366 nm until the olefin was consumed (40 h). [b] Iso-
lated yields; no other significant photoproduct was detected by GC-MS
analysis. [c] 1, (0.22m), 10 (0.2m). [d] The endo isomer has been obtained
exclusively. [e] Irradiation time: 24 h.
the aldehyde hydrogen atom that could compete with the di-
oxolane CH2 as a hydrogen donor; a bulky a,b-unsaturated
ketone such as 12 gave the endo isomer[20] of norbornanone
23 as the exclusive product in 69% yield (Scheme 2).
The alkylation was extended to tetrasubstituted electro-
philic alkenes by using 1,1-dinitrile 13. With 13 the reaction
was successful, although the expected product 24 (66%
yield) was accompanied by an open-chain byproduct in
which malononitrile was lost (25, 22%, Scheme 3). To assess
whether compound 25 was a secondary photoproduct, a
MeCN solution of 24 (0.1m) was irradiated at 366 nm for
18 h but the starting dinitrile was not consumed.
On the other hand, 24 reacted (60% consumption) when
irradiated in the presence of TBADT for the same time as
in the original reaction, with the formation of a significant
amount of 25. The photocatalyzed reaction between 1 and
Scheme 1.
The use of a slight excess of 1 was required to obtain the
best overall alkylation yield. To our delight, the reaction
with dimethyl maleate (10) under the same conditions gave
diester 21 in 63% yield as the exclusive product (Scheme 2
and Table 1). Doubling the concentrations of both reagents
(1: 0.22m, 10: 0.2m) led likewise to the formation of 21 in
similar yields and with a comparable irradiation time (40 h).
Moreover, (E)-2-hexenal gave substituted aldehyde 22 in a
satisfactory yield (56%), with no competitive activation of
Scheme 2.
Scheme 3.
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573

M. Fagnoni et al.
13 was further explored under buffered conditions in the
presence of solid NaHCO3. In this case, the yield of com-
pound 24 was unaffected, whereas a new compound with
m/z: 202 (as detected by GC-MS analysis, see the Discussion
Section) was formed at the expense of 25.
Scheme 6.
Substituted 1,3-benzodioxoles: A few derivatives were next
considered to determine the tolerance of substituents. Ester
2 was tested with tetrasubstituted olefins. With isopropyli-
dene malonate only a sluggish photoreaction occurred,
albeit formation of the desired adduct was detected by GC
analysis. With isopropylidene cyanoacetate (14), however, it
reacted completely (40 h irradiation) and functionalized
benzodioxole 26 was formed as the only adduct in a satisfac-
tory yield (65%, Scheme 4). With piperonylic acid, on the
other hand, no useful reaction occurred.
ole 5) was more effective and under these conditions a com-
plete reaction and formation of alkylated products 30 (46%
isolated yield with cyclopentenone 18) and 31 (61% with cy-
anoester 17, Scheme 7) were achieved.
Scheme 7.
Piperonal (6) was chosen to assess the competition with
the aromatic aldehyde group, recently demonstrated to be
effectively activated by TBADT photocatalysis.[13,15b,21] In
the experiment, activation of the benzodioxole CH2 was ex-
clusive, as witnessed by the reaction with maleate 10 to
yield 32 (Scheme 8).
Scheme 4.
5-Chloro-1,3-benzodioxole (3) is known to undergo
À
smooth heterolytic cleavage of the Ar Cl bond upon direct
irradiation.[22,23] Under the present photocatalytic conditions,
however, no chloride-free products were detected in the
presence of either methyl crotonate (15) or cyclohexenone
(16), in which the alkylation products 27 and 28, respective-
ly, were formed in a decent yield (50–60%, Scheme 5).
5-Methyl-1,3-benzodioxole (4) gave the expected cya-
noester 29 in 70% isolated yield in the presence of the
olefin 17 and TBADT (Scheme 6), with no interference by
benzylic hydrogen atoms.
Scheme 8.
A phenolic group interfered, however, and 3,4-methylene-
dioxyphenol (sesamol) was only partially consumed (ca.
30%) under photocatalyzed conditions in the presence of
alkene 14, but no adduct was detected. Protection of the
OH group as a carbonate (7), however, regenerated the re-
activity, as illustrated in Scheme 9.
On the contrary, piperonyl alcohol gave no adduct after
40 h irradiation in the presence of cyclopentenone 18 and
TBADT. On the other hand, protection of the benzylic
À
À
OH group as a tert-butyldimethylsilyl ether ( OTBS) al-
lowed the sluggish formation of a new product, as deter-
mined by GC analysis. Protection as an acetate (benzodiox-
Interference by substituents at the CH2 group was next in-
vestigated by reacting the 2-methyl derivative 8. A clean
photocatalyzed addition was obtained both with a b-unsub-
stituted (acrylonitrile 9, to give nitrile 34 in 65% isolated
yield) and with a b,b-disubstituted alkene (dinitrile 13, to
give benzodioxole 35 in a 77% yield, Scheme 10).
Scheme 5.
Scheme 9.
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Smooth Photocatalytic Preparation of 2-Substituted-1,3-Benzodioxoles
FULL PAPER
dures require a large amount of activator and a large excess
of the ether (from 15 to 250 equiv, in some cases used as the
reaction medium[27a]).
As for the specific case of 1,3-benzodioxole, only sparse
results have been reported.[28,29] Thus, generation of the 1,3-
benzodioxol-2-yl radical by using tert-butoxyl radicals as ini-
tiators at 1408C led to ring opening[28] and only a poor alky-
lation occurred in the presence of nucleophilic olefins.[28] a-
Oxy radicals have been recently generated from 1,3-benzo-
dioxole by using dimethylzinc (6 equiv)/air and shown to
add to N-sulfinyl imines in a satisfactory yield, but the start-
ing dioxole had to be used in a large excess (250 equiv).[29]
To our knowledge, no substituted 1,3-benzodioxoles have
been tested in such reactions.
On the other hand, the anionic activation in 1,3-benzo-
dioxole derivatives is troublesome due to the low acidity of
the CH2 hydrogen atoms, which require a strong base for de-
protonation. Furthermore, the treatment of 1,3-benzodiox-
ole with lithium or sodium diethylamide leads to reductive
cleavage of the ether bond and to ring opening[30] and more
elaborate alternatives have been considered, for example, a
preliminary chlorination.[31]
Scheme 10.
One-pot, consecutive photochemical functionalization: The
last reaction considered was a proof of concept for the one-
pot functionalization of 1,3-benzodioxole based on two con-
secutive photochemical steps, namely, both the photocatalyt-
ic reaction described in the present work and the recently
reported arylation via a phenyl cation.[23,24] As mentioned
above, chlorobenzodioxole 3 was functionalized only at the
CH2 under TBADT photocatalysis (Scheme 5). The reaction
was repeated with alkene 14 and, by the usual irradiation at
366 nm, afforded adduct 36 (not isolated, Scheme 11). Addi-
tion of water and allyltrimethylsilane (37) to the crude pho-
tolysate and further irradiation at a shorter wavelength
À
(310 nm) caused Ar Cl bond scission and the formation of
On the contrary, the present method by means of
TBADT photocatalysis, summarized in Scheme 12, was
demonstrated to be a viable alternative for the mild prepa-
ration of 2-substituted-1,3-benzodioxoles via radicals. The
reaction requires only 10% excess reagent, operates at a
reasonable starting concentration, and is experimentally
very simple. The effective activation at room temperature
avoids the above-mentioned cleavage of radicals[28] and
avoids inhibition by an alkyl substituent at position 2 (see
the case of 2-methylbenzodioxole 8). On the other hand,
this characteristic may lead to double alkylation, as seen in
the formation of compound 20 from 1 and acrylonitrile, a
phenomenon that is limited to this nonhindered alkene,
however. In the other cases the alkylation is indeed clean
and general in scope. Apparently, as long as a hydrogen
atom is present at position 2, alkylation at this position is
safrole derivative 38 in 35% yield (from 14) along with
some byproducts (such as dechlorinated compound 1 and sa-
frole, <5% overall) arising from excess 3 still present
during the second photochemical step. The role of water is
that of enhancing polarity and favoring chloride anion
loss,[22] while hindering a possible second TBADT photoca-
talytic alkylation.[25]
Discussion
The generation of a-oxy and a,a-dioxy radicals from ethers
or 1,3-dioxolanes is easily obtained.[26,27] As an example,
such radicals are generated by treatment of ethers with py-
rophoric Me2Zn (2 equiv) and BF3·Et2O (2 equiv),[26a] with
N-hydroxyphthalimide as the catalyst in the presence of
benzoyl peroxide at 808C[26c] or under a Et3B (6 equiv)/air
system.[26d] The photochemical activation of the a-oxy C H
À
bonds likewise occurs by using a 40% equivalent of a photo-
mediator, such as benzophenone.[27] Thus, the known proce-
Scheme 11.
Scheme 12. EWG=electron-withdrawing group.
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575

M. Fagnoni et al.
exclusive as shown in the cases of intramolecular selectivity
above. For example, no significant (<1%) reaction at a ben-
zylic position (4, 5) or at an aromatic aldehyde group (6)
takes place.
irradiation times were obtained, despite the sterical hin-
drance in the b-position (see the Experimental Section).
In the case of 5-chloro-1,3-benzodioxole (3), either the
À
À
Ar Cl or the methylene C H bonds were photoactivated
depending on the irradiation wavelength and the reaction
media used and an uncommon one-pot synthesis by two
consecutive photochemical reactions was achieved (see
Scheme 11).
À
However, the phenolic O H bond in sesamol (BDE esti-
mated around 86–88 kcalmolÀ1)[32] interfered and the benzyl-
ic hydrogen atoms in piperonyl alcohol (87.5 kcalmolÀ1 for
benzyl alcohol)[32] completely inhibited the reaction. In both
cases, however, protection of the OH group as a carbonate
or as an ester regenerated the reactivity and allowed an
easy derivatization of the benzodioxole. A detailed study on
the origin of such an interesting chemoselectivity is current-
ly under investigation.
Conclusion
A smooth synthesis of (mostly new) 2-substituted-1,3-benzo-
dioxoles has been disclosed. This exploits the TBADT pho-
tocatalytic (2% equiv) chemoselective activation of the
methylene hydrogen atoms in 1,3-benzodioxole derivatives.
The reaction takes place under mild conditions and offers
an unprecedented, general access for the preparation of a
class of compounds of potential biological activity.
In a single case a secondary process was detected, namely,
the reaction between 1 and dinitrile 13 in which loss of ma-
lononitrile from the primary product is significant (see
Scheme 13).[33] This can be rationalized by a secondary hy-
drogen abstraction from 24 to yield radical 24a and, by loss
of the stable dicyanomethyl radical,[34] vinyl acetal 24b (m/z:
202, identified by GC-MS) and ester 25 via 24c by addition
of adventitious water. The last reaction was catalyzed by a
trace of acid since addition of bicarbonate prevented any
thermal reaction of 24b.[35] This secondary conversion prob-
ably occurs to some degree in all of the reactions from ben-
zodioxoles 1–7, but has no consequence because back hy-
drogen transfer from reduced TBADT is faster than addi-
tion to alkenes, except when a nonhindered radical reacts
with the least-hindered alkene, namely, acrylonitrile, as
indeed for the case of 20 from 19 (Scheme 12). This general
scheme was confirmed by the preparation of 35 for which
stability was assured by the lack of any methylene hydrogen
atom in position 2 (see Scheme 10).
Experimental Section
General: NMR spectra were recorded on a 300 MHz spectrometer. The
attributions were made on the basis of 1H and 13C NMR spectra, as well
as DEPT experiments; chemical shifts are reported in ppm downfield
from TMS. Compounds 1, 3, 4, 6, 9–12, 15, 16, 18, and 37 were commer-
cially available and compounds 1, 3, 4, 9–12, 15, 16, 18, and 37 were
freshly distilled before use. Acetonitrile (HPLC purity grade) was pur-
chased from Carlo Erba and used as received. Compound 5 was synthe-
sized by starting from equimolar amounts of piperonyl alcohol and acetyl
chloride in CH2Cl2 in the presence of 1.1 equiv of triethylamine (colorless
oil, quantitative yield). Spectroscopic data of compound 5 are in accord-
ance with the literature.[37] Compounds 2,[38] 7,[39] 8,[9] 13,[40] 14,[41] and
17[42] were synthesized according to published procedures.
1,1-Disubstituted olefins, such as 13, 14, and 17, have
been proven to be the best radical traps among the olefins
tested in this work. In fact, high alkylation yields and short
General procedure for the photocatalyzed synthesis of 2-substituted 1,3-
benzodioxole: A solution (30 mL) of a 1,3-benzodioxole (1–8, 0.11m) and
an olefin (9–18, 0.1m) in the presence of TBADT[13] (200 mg, 2ꢁ10À3 m)
in MeCN was poured in quartz tubes and purged for 10 min with nitro-
gen, serum capped, and then irradiated for 24–40 h with 12 15 W phos-
phor-coated lamps (emission centered at 366 nm) by means of a multi-
lamps apparatus (Helios Italquartz, Italy). The solvent was removed in
vacuo from the photolyzed solutions and the products isolated by purifi-
cation of the residue by column chromatography (cyclohexane/ethyl ace-
tate as eluants).
Photochemical reaction between 1,3-benzodioxole (1) and acrylonitrile
(9): 1,3-benzodioxole (1, 380 mL, 3.3 mmol, 0.11m), acrylonitrile (9,
200 mL, 3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m)
were dissolved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm.
After removing the solvent in vacuo and purification of the residue by
column chromatography (silica gel, eluent: cyclohexane/ethyl acetate
99:1), 3-(1,3-benzodioxol-2-yl)propanenitrile (19, 168 mg, 32%) and 3,3’-
(1,3-benzodioxol-2,2-diyl)dipropanenitrile (20, 151 mg, 22%) were ob-
tained as colorless oils (overall yield: 54%). Compound 20 solidified
upon standing.
3-(1,3-Benzodioxol-2-yl)propanenitrile (19): 1H NMR (CDCl3): d=2.3
(dt, J=8, 4 Hz, 2H), 2.6 (t, J=8 Hz, 2H), 6.2 (d, J=4 Hz, 1H), 6.8–
6.9 ppm (m, 4H); 13C NMR (CDCl3): d=10.8 (CH2), 30.0 (CH2), 108.4
(CH), 108.7 (CH), 118.5, 121.8 (CH), 147.0 ppm; IR (neat): n˜ =1236,
1485, 2252 cmÀ1; elemental analysis calcd (%) for C10H9NO2: C 68.56, H
5.18, N 8.00; found: C 68.5, H 5.2 N 8.1.
3,3’-(1,3-Benzodioxol-2,2-diyl)dipropanenitrile (20): M.p. 68–718C;
1H NMR (CDCl3): d=2.3 (t, J=8 Hz, 4H), 2.6 (t, J=8 Hz, 4H), 6.8–
Scheme 13.
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Smooth Photocatalytic Preparation of 2-Substituted-1,3-Benzodioxoles
FULL PAPER
6.9 ppm (m, 4H); 13C NMR (CDCl3): d=10.9 (CH2), 33.7 (CH2), 108.8
(CH), 115.5, 118.4 , 122.2 (CH), 146.6 ppm; IR (KBr): n˜ =1237, 1485,
2250 cmÀ1; elemental analysis calcd (%) for C13H12N2O2: C 68.41, H 5.30,
N 12.27; found: C 68.4, H 5.4, N 12.1.
(dt, J=11, 4 Hz, 1H), 5.7 (brs, 1H), 6.8–7.0 (m, 2H), 7.0–7.2 ppm (m,
2H); 13C NMR (CDCl3): d=25.2 (2 CH2), 25.5 (CH2), 28.9 (2 CH2), 43.1
(CH), 117.7 (CH), 120.8 (CH), 122.2 (CH), 126.7 (CH), 138.7, 147.1,
174.6 ppm; IR (neat): n˜ =3403, 1732, 1598, 1231, 1162 cmÀ1; elemental
analysis calcd for C13H16O3: C 70.89, H 7.32; found: C 70.8, H 7.3; MS m/
z: 220 [M]+ (10), 110 (80), 83 (80), 55 (100); the same reaction, when
performed in the presence of NaHCO3 (200 mg) yielded malononitrile 24
again and a new byproduct, namely, 2-cyclohexylidene-1,3-benzodioxole
(24b), as identified by GC-MS analysis (MS m/z: 203 [M+1]+ (100), 174
(30), 146 (20), 135 (20), 83 (20)).
Dimethyl 2-(1,3-benzodioxol-2-yl)succinate (21): 1,3-Benzodioxole (1,
380 mL, 3.3 mmol, 0.11m), dimethyl maleate (10, 375 mL, 3.0 mmol,
0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dissolved in
acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After removing
the solvent in vacuo and purification of the residue by column chroma-
tography (silica gel, eluant: cyclohexane/ethyl acetate 9:1), dimethyl 2-
(1,3-benzodioxol-2-yl)succinate (21, 503 mg, 63%) was obtained as a col-
orless oil, which solidified upon standing. A similar yield (65%) was ob-
tained when a solution containing 1 (0.22m) and 10 (0.2m) was irradiated
for 40 h. M.p. 76–798C; 1H NMR (CDCl3): d=2.7–3.0 (2H; AB part of
an ABX system), 3.4–3.5 (1H; X part of an ABX system), 3.8 (s, 3H),
3.9 (s, 3H), 6.4 (d, J=4 Hz, 1H), 6.8–6.9 ppm (m, 4H); 13C NMR
(CDCl3): d=29.1 (CH2), 46.3 (CH), 51.9 (CH3), 52.5 (CH3), 108.5 (CH),
109.0 (CH), 121.8 (CH), 146.9, 170.0, 171.6 ppm; IR (KBr): n˜ =1238,
1488, 1728 cmÀ1; elemental analysis calcd (%) for C13H14O6: C 58.64, H
5.30; found: C 58.7, H 5.3.
Methyl 2-(3-cyano-4-ethoxy-2-methyl-4-oxobutan-2-yl)-1,3-benzodioxole-
5-carboxylate (26): Methyl 1,3-benzodioxole-5-carboxylate (2, 595 mg,
3.3 mmol, 0.11m), ethyl isopropylidene cyanoacetate (14, 460 mg,
3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dis-
solved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After re-
moving the solvent in vacuo and purification of the residue by column
chromatography (silica gel, eluant: cyclohexane/ethyl acetate 9:1),
methyl 2-(3-cyano-4-ethoxy-2-methyl-4-oxobutan-2-yl)-1,3-benzodioxole-
5-carboxylate (26, 650 mg, 65%, equimolar mixture of two diastereoiso-
mers) was obtained as a colorless oil. 1H NMR (CDCl3, mixture of diaste-
reoisomers): d=1.2 (s, 3H), 1.25 (t, J=7 Hz, 3H), 1.3 (s, 3H), 3.8 (s,
1H), 3.9 (s, 3H), 4.3 (q, J=7 Hz, 2H), 6.2 (s, 1H), 6.8 (dd, J=8, 4 Hz,
1H), 7.5 (dd, J=4, 2 Hz, 1H), 7.7 ppm (dt, J=8, 2 Hz, 1H); 13C NMR
(CDCl3, mixture of diastereoisomers): d=13.8 (CH3), 18.4 (CH3), 18.5
(CH3), 19.7 (CH3), 42.0, 43.4 (CH), 43.5 (CH), 52.0 (CH3), 62.8 (CH2),
107.7 (CH), 107.8 (CH), 109.2 (CH), 109.3 (CH), 114.0 (CH), 114.8,
124.3, 124.4, 125.3 (CH), 125.4 (CH), 147.5, 147.6, 151.2, 151.3, 164.2,
166.1 ppm; IR (neat): n˜ =1259, 1284, 1497, 1719, 1745, 2251 cmÀ1; ele-
mental analysis calcd for C17H19NO6: C 61.25, H 5.75, N 4.20; found: C
61.2, H 5.8, N 4.3.
3-(1,3-Benzodioxol-2-yl)hexanal (22): 1,3-Benzodioxole (1, 380 mL,
3.3 mmol, 0.11m), trans-2-hexenal (11, 350 mL, 3.0 mmol, 0.10m), and
TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dissolved in acetonitrile
(30 mL) and irradiated for 40 h at 366 nm. After removing the solvent in
vacuo and purification of the residue by column chromatography (silica
gel, eluant: cyclohexane/ethyl acetate 95:5), 3-(1,3-benzodioxol-2-yl)-
hexanal (22, 370 mg, 56%) was obtained as a colorless oil. 1H NMR
(CDCl3): d=0.9–1.1 (m, 3H), 1.3–1.5 (m, 3H), 1.5–1.7 (m, 1H), 2.3–2.5
(m, 1H), 2.5–2.7 (m, 2H), 6.1 (d, J=5 Hz, 1H), 6.7–6.8 (m, 4H), 9.8 ppm
(s, 1H); 13C NMR (CDCl3): d=14.0 (CH3), 20.0 (CH2), 31.3 (CH2), 37.4
(CH), 42.2 (CH2), 108.3 (CH), 112.2 (CH), 121.5 (CH), 147.4, 147.5,
200.9 ppm; IR (neat): n˜ =1236, 1486, 1727 cmÀ1; elemental analysis calcd
(%) for C13H16O3: C 70.89, H 7.32; found: C 70.8, H 7.4.
Methyl 3-(5-chloro-1,3-benzodioxol-2-yl)butanoate (27): 5-Chloro-1,3-
benzodioxole (3, 385 mL, 3.3 mmol, 0.11m), methyl crotonate (15, 320 mL,
3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dis-
solved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After re-
moving the solvent in vacuo and purification of the residue by column
chromatography (silica gel, eluant: cyclohexane/ethyl acetate 95:5),
methyl 3-(5-chloro-1,3-benzodioxol-2-yl)butanoate (27, 431 mg, 56%,
equimolar mixture of two diastereoisomers) was obtained as a colorless
oil. 1H NMR (CDCl3, mixture of diastereoisomers): d=1.1 (d, J=7 Hz,
3H), 2.2–2.4 (m, 1H), 3.6–3.7 (m, 2H), 3.7 (s, 3H), 6.1 (d, J=4 Hz, 1H),
6.6–6.7 (m, 1H), 6.7–6.8 ppm (m, 2H); 13C NMR (CDCl3, mixture of dia-
stereoisomers): d=13.3 (CH3), 13.3 (CH3), 34.7 (CH2), 34.7 (CH), 51.6
(CH3), 108.4 (CH), 109.1 (CH), 114.1 (CH), 121.0 (CH), 125.9, 146.6,
148.4, 172.3 ppm; IR (neat): n˜ =1236, 1484, 1737 cmÀ1; elemental analysis
calcd (%) for C12H13ClO4: C 56.15, H 5.10; found: C 56.0, H 5.1.
3-(1,3-Benzodioxol-2-ylmethyl)bicycloACTHNUGTRNEUNG[2.2.1]heptan-2-one (23): 1,3-Ben-
zodioxole (1, 380 mL, 3.3 mmol, 0.11m), 3-methylene-2-norbornanone (12,
370 mL, 3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m)
were dissolved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm.
After removing the solvent in vacuo and purification of the residue by
column chromatography (silica gel, eluant: cyclohexane/ethyl acetate
9:1),
3-(1,3-benzodioxol-2-ylmethyl)bicyclo
G
(23,
506 mg, 69%, endo isomer) was obtained as a colorless oil, which solidi-
fied upon standing. M.p. 45–478C; 1H NMR (CDCl3): d=1.3–1.5 (m,
1H), 1.5–1.8 (m, 4H), 1.8–2.0 (m, 2H), 2.2–2.4 (m, 2H), 2.6–2.8 (m, 2H),
6.2 (d, J=4 Hz, 1H), 6.8–6.9 ppm (m, 4H); 13C NMR (CDCl3): d=21.3
(CH2), 25.3 (CH2), 30.9 (CH2), 37.1 (CH2), 39.2 (CH), 48.6 (CH), 49.8
(CH), 108.4 (CH), 110.5 (CH), 121.4 (CH), 147.3, 147.4, 218.2 ppm; IR
3-(5-Chloro-1,3-benzodioxol-2-yl)cyclohexanone (28): 5-Chloro-1,3-ben-
zodioxole (3, 385 mL, 3.3 mmol, 0.11m), 2-cyclohexenone (16, 290 mL,
3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dis-
solved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After re-
moving the solvent in vacuo and purification of the residue by column
chromatography (silica gel, eluant: cyclohexane/ethyl acetate 95:5),
methyl 3-(5-chloro-1,3-benzodioxol-2-yl)cyclohexanone (28, 431 mg,
51%, equimolar mixture of two diastereoisomers) was obtained as a col-
(KBr): n˜ =1234, 1484, 1742 cmÀ1
; elemental analysis calcd (%) for
C15H16O3: C 73.75, H 6.60; found: C 73.8, H 6.5.
Photochemical reaction between 1,3-benzodioxole (1) and cyclohexyli-
dene malononitrile (13): 1,3-Benzodioxole (1, 380 mL, 3.3 mmol, 0.11m),
cyclohexylidene malononitrile (13, 430 mL, 3.0 mmol, 0.10m), and
TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dissolved in acetonitrile
(30 mL) and irradiated for 24 h at 366 nm. After removing the solvent in
vacuo and purification of the residue by column chromatography (silica
gel, eluant: cyclohexane/ethyl acetate 9:1), 2-[1-(1,3-benzodioxol-2-yl)cy-
clohexyl]malononitrile (24, 531 mg, 66%) and 2-hydroxyphenyl cyclohex-
anecarboxylate (25, 145 mg, 22%) were obtained as colorless oils (overall
yield: 88%). Compound 24 solidified upon standing.
1
orless oil. H NMR (CDCl3, mixture of diastereoisomers): d=1.6–1.8 (m,
2H), 2.0–2.1 (m, 1H), 2.1–2.2 (m, 1H), 2.3–2.5 (m, 4H), 2.5–2.6 (m, 1H),
6.0 (d, J=3 Hz, 1H), 6.6–6.7 (m, 1H), 6.7–6.8 ppm (m, 2H); 13C NMR
(CDCl3, mixture of diastereoisomers): d=24.4 (CH2), 40.6 (CH2), 41.2
(CH2), 42.7 (CH), 108.5 (CH), 109.2 (CH), 113.3 (CH), 121.1 (CH),
126.1, 146.4, 148.2, 209.4 ppm; IR (neat): n˜ =1238, 1485, 1715 cmÀ1; ele-
mental analysis calcd (%) for C13H13ClO3: C 61.79, H 5.19; found: C
61.9; H 5.0.
2-[1-(1,3-Benzodioxol-2-yl)cyclohexyl]malononitrile (24): M.p. 80–838C;
1H NMR (CDCl3): d=1.5–1.8 (m, 6H), 1.8–1.9 (m, 2H), 2.0–2.1 (m, 2H),
4.1 (s, 1H), 6.3 (s, 1H), 6.8–6.9 ppm (m, 4H); 13C NMR (CDCl3): d=20.8
(2CH2), 24.6 (CH2), 27.5 (CH), 28.6 (2CH2), 44.1, 109.0 (2CH), 110.5
(CH), 111.2, 122.2 (2CH), 146.7 ppm; IR (KBr): n˜ =1234, 1484,
2251 cmÀ1; elemental analysis calcd (%) for C16H16N2O2: C 71.62, H 6.01,
N 10.44; found: C 71.7, H 6.0, N 10.5; MS m/z: 269 [M+1]+ (20), 122
(100).
Ethyl
2-cyano-2-[1-(5-methyl-1,3-benzodioxol-2-yl)cyclopentyl]acetate
(29): 5-Methyl-1,3-benzodioxole (4, 3.3 mmol, 0.11m), cyclopentylidene
cyanoacetate (17, 538 mg, 3.0 mmol, 0.10m), and TBADT (200 mg,
0.06 mmol, 2ꢁ10À3 m) were dissolved in acetonitrile (30 mL) and irradiat-
ed for 40 h at 366 nm. After removing the solvent in vacuo and purifica-
tion of the residue by column chromatography (silica gel, eluant: cyclo-
hexane/ethyl acetate 95:5), ethyl 2-cyano-2-[1-(5-methyl-1,3-benzodioxol-
2-Hydroxyphenyl cyclohexanecarboxylate (25): 1H NMR (CDCl3): d=
1.3–1.5 (m, 3H), 1.6–1.8 (m, 3H), 1.8–1.9 (m, 2H), 2.0–2.2 (m, 2H), 2.6
Chem. Eur. J. 2011, 17, 572 – 579
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
577

M. Fagnoni et al.
2-yl)cyclopentyl]acetate (29, 70%, 662 mg, equimolar mixture of two dia-
stereoisomers) was obtained as a colorless oil. 1H NMR (CDCl3, mixture
of diastereoisomers): d=1.2 (t, J=7 Hz, 3H), 1.7–1.9 (m, 4H), 1.9–2.1
(m, 4H), 2.3 (s, 3H), 3.8 (s, 1H), 4.2 (q, J=7 Hz, 2H), 6.1 (s, 1H), 6.5–
6.7 ppm (m, 3H); 13C NMR (CDCl3, mixture of diastereoisomers): d=
13.6 (CH3), 21.1 (CH3), 25.7 (CH2), 26.1 (CH2), 31.2 (CH2), 32.2 (CH2),
42.6 (CH), 52.1, 62.7 (CH2), 107.7 (CH), 107.8 (CH), 109.3 (CH), 109.4
(CH), 112.7 (CH), 115.8, 121.5 (CH), 121.6 (CH), 131.5, 131.6, 145.3,
Ethyl 2-cyano-3-[5-(ethoxycarbonyloxy)1,3-benzodioxol-2-yl]-3-methyl-
butanoate (33): 1,3-Benzodioxol-5-yl ethyl carbonate (7, 694 mg,
3.3 mmol, 0.11m), ethyl isopropylidene cyanoacetate (14, 460 mg,
3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dis-
solved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After re-
moving the solvent in vacuo and purification of the residue by column
chromatography (silica gel, eluant: cyclohexane/ethyl acetate 9:1), ethyl
2-cyano-3-[5-(ethoxycarbonyloxy)1,3-benzodioxol-2-yl]-3-methylbuta-
noate (33, 818 mg, 75%, equimolar mixture of two diastereoisomers) was
obtained as a colorless oil. 1H NMR (CDCl3, mixture of diastereoiso-
mers): d=1.2 (s, 3H), 1.25 (t, J=7 Hz, 3H), 1.3 (s, 3H), 1.4 (t, J=7 Hz, 3
H), 3.8 (s, 1H), 4.2 (q, J=7 Hz, 2H), 4.3 (q, J=7 Hz, 2H), 6.1 (s, 1H),
6.6–6.8 ppm (m, 3H); 13C NMR (CDCl3, mixture of diastereoisomers):
d=13.8 (CH3), 14.1 (CH3), 18.6 (CH3), 20.0 (CH3), 41.9 (C), 43.4 (CH),
43.5 (CH), 62.9 (CH2), 64.9 (CH2), 103.2 (CH), 103.2 (CH), 107.7 (CH),
107.8 (CH), 113.7 (CH), 113.8 (CH), 114.1 (CH), 114.9 (C), 145.3, 145.5,
145.4, 147.5, 147.6, 164.9 ppm; IR (neat): n˜ =1246, 1495, 1746, 2249 cmÀ1
;
elemental analysis calcd (%) for C18H21NO4: C 68.55, H 6.71, N 4.44;
found: C 68.6, H 6.7, N 4.3.
[2-(3-Oxocyclopentyl)-1,3-benzodioxol-5-yl]methyl acetate (30): 1,3-Ben-
zodioxol-5-ylmethyl acetate (5, 641 mg, 3.3 mmol, 0.11m), 2-cyclopente-
none (18, 250 mL, 3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ
10À3 m) were dissolved in acetonitrile (30 mL) and irradiated for 40 h at
366 nm. After removing the solvent in vacuo and purification of the resi-
due by column chromatography (silica gel, eluant: cyclohexane/ethyl ace-
tate 9:1), [2-(3-oxocyclopentyl)-1,3-benzodioxol-5-yl]methyl acetate (30,
381 mg, 46%, equimolar mixture of two diastereoisomers) was obtained
147.7, 153.7, 164.3 ppm; IR (neat): n˜ =1240, 1494, 1746, 1760, 2251 cmÀ1
;
elemental analysis calcd (%) for C18H21NO7: C 59.50, H 5.83, N 3.85;
found: C 59.5, H 5.8, N 3.7.
1
3-(2-Methyl-1,3-benzodioxol-2-yl)propanenitrile (34): 2-Methyl-1,3-ben-
zodioxole (8, 449 mg, 3.3 mmol, 0.11m), acrylonitrile (9, 200 mL,
3.0 mmol, 0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dis-
solved in acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After re-
moving the solvent in vacuo and purification of the residue by column
chromatography (silica gel, eluant: cyclohexane/ethyl acetate 95:5), 3-(2-
methyl-1,3-benzodioxol-2-yl)propanenitrile (34, 369 mg, 65%) was ob-
tained as a colorless oil. 1H NMR (CDCl3): d=1.6 (s, 3H), 2.3 (t, J=
7 Hz, 2H), 2.6 (t, J=7 Hz, 2H), 6.7–6.8 ppm (m, 4H); 13C NMR
(CDCl3): d=10.9 (CH2), 24.0 (CH3), 34.3 (CH2), 108.3 (CH), 115.9, 118.5,
121.2 (CH), 146.4 ppm; IR (neat): n˜ =1239, 1487, 2252 cmÀ1; elemental
analysis calcd (%) for C11H11NO2: C 69.83, H 5.86, N 7.40; found: C 69.8,
H 5.8, N 7.3.
as a colorless oil. H NMR (CDCl3, mixture of diastereoisomers): d=2.0–
2.2 (m, 1H), 2.1 (s, 3H), 2.2–2.5 (m, 5H), 2.8–2.9 (m, 1H), 5.0 (s, 2H),
6.1 (d, J=4 Hz, 1H), 6.6–6.7 (m, 1H), 6.8–6.9 ppm (m, 2H); 13C NMR
(CDCl3, mixture of diastereoisomers): d=20.9 (CH3), 22.8 (CH2), 37.3
(CH2), 38.3 (CH2), 40.3 (CH), 66.1 (CH2), 107.9 (CH), 108.7 (CH), 108.8
(CH), 112.8 (CH), 122.2 (CH), 129.6, 147.7, 170.8, 216.9 ppm; IR (neat):
n˜ =1244, 1499, 1742 cmÀ1; elemental analysis calcd (%) for C15H16O5: C
65.21, H 5.84; found: C 65.3, H 5.9.
When the irradiation was performed on piperonyl alcohol protected as
À
tert-butyldimethylsilyl ether ( OTBS, prepared by standard reaction with
TBSCl[43]) the formation of a new product was likewise observed, though
in a sluggish way.
Ethyl
2-{1-[5-(acetoxymethyl)-1,3-benzodioxol-2-yl]cyclopentyl}-2-cya-
2-[1-(2-Methyl-1,3-benzodioxol-2-yl)cyclohexyl]malononitrile (35): 2-
Methyl-1,3-benzodioxole (8, 449 mg, 3.3 mmol, 0.11m), cyclohexylidene
malononitrile (13, 430 mL, 3.0 mmol, 0.10m), and TBADT (200 mg,
0.06 mmol, 2ꢁ10À3 m) were dissolved in acetonitrile (30 mL) and irradiat-
ed for 24 h at 366 nm. After removing the solvent in vacuo and purifica-
tion of the residue by column chromatography (silica gel, eluant: cyclo-
hexane/ethyl acetate 95:5), 2-[1-(2-methyl-1,3-benzodioxol-2-yl)cyclohex-
yl]malononitrile (35, 652 mg, 77%) was obtained as a colorless solid
(m.p.: 165–1678C). 1H NMR (CDCl3): d=1.2–1.4 (m, 3H), 1.7 (s, 3H),
1.7–1.9 (m, 5H), 2.1–2.2 (m, 2H), 4.3 (s, 1H), 6.8–6.9 ppm (m, 4H);
13C NMR (CDCl3): d=20.8 (CH2), 20.9 (CH), 24.4 (CH2), 24.4 (CH3),
27.9 (CH2), 49.0, 108.9 (CH), 111.8, 119.6, 121.8 (CH), 146.4 ppm; IR
noacetate (31): 1,3-Benzodioxol-5-ylmethyl acetate (5, 641 mg, 3.3 mmol,
0.11m), cyclopentylidene cyanoacetate (17, 538 mg, 3.0 mmol, 0.10m),
and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dissolved in acetoni-
trile (30 mL) and irradiated for 40 h at 366 nm. After removing the sol-
vent in vacuo and purification of the residue by column chromatography
(silica gel, eluant: cyclohexane/ethyl acetate 9:1), ethyl 2-{1-[5-(acetoxy-
methyl)-1,3-benzodioxol-2-yl]cyclopentyl}-2-cyanoacetate (31, 61%, equi-
molar mixture of two diastereoisomers) was obtained as a colorless oil.
1H NMR (CDCl3, mixture of diastereoisomers): d=1.2 (t, J=7 Hz, 3H),
1.6–1.8 (m, 4H), 1.8–2.0 (m, 4H), 2.1 (s, 3H), 3.8 (s, 1H), 4.2 (q, J=7 Hz,
2H), 4.9 (s, 2H), 6.1 (s, 1H), 6.6–6.8 ppm (m, 3H); 13C NMR (CDCl3,
mixture of diastereoisomers): d=13.6 (CH3), 20.8 (CH3), 25.7 (CH2), 26.0
(CH2), 31.2 (CH2), 32.1 (CH2), 42.7 (CH), 52.1 (C), 62.7 (CH2), 65.9
(CH2), 107.9 (CH), 108.0 (CH), 108.7 (CH), 108.8 (CH), 113.2 (CH),
115.7, 122.2 (CH), 122.3 (CH), 129.8, 129.9, 147.5, 147.6, 147.7, 147.8,
164.8, 170.6 ppm; IR (neat): n˜ =1239, 1499, 1738, 2250 cmÀ1; elemental
analysis calcd (%) for C20H23NO6: C 64.33, H 6.21, N 3.75; found: C 64.3,
H 6.2, N 3.7.
(KBr): n˜ =1241, 1486, 2251 cmÀ1
; elemental analysis calcd (%) for
C17H18N2O2: C 72.32, H 6.43, N 9.92; found: C 72.2, H 6.5, N 9.9.
Ethyl 3-(5-allyl-1,3-benzodioxol-2-yl)-2-cyano-3-methylbutanoate (38): 5-
Chloro-1,3-benzodioxole (3, 385 mL, 3.3 mmol, 0.11m), ethyl isopropyli-
dene cyanoacetate (14, 460 mg, 3.0 mmol, 0.10m), and TBADT (200 mg,
0.06 mmol, 2ꢁ10À3 m) was dissolved in acetonitrile (30 mL) and irradiated
for 40 h at 366 nm. Water (6 mL) and allyltrimethylsilane (37, 2.87 mL,
18 mmol, 0.5m) were added to the crude photolyzed mixture. The result-
ing solution was purged for 10 min with nitrogen, serum capped, and
then irradiated with 10 15 W phosphor-coated lamps (emission centered
at 310 nm) for 24 h. After removing the solvent in vacuo and purification
of the residue by column chromatography (silica gel, eluant: cyclohex-
ane/ethyl acetate 95:5), ethyl 3-(5-allyl-1,3-benzodioxol-2-yl)-2-cyano-3-
methylbutanoate (38, 331 mg, 35%, as a mixture of diastereoisomers)
Dimethyl 2-(5-formyl-1,3-benzodioxol-2-yl)succinate (32): Piperonal (6,
495 mg, 3.3 mmol, 0.11m), dimethyl maleate (10, 375 mL, 3.0 mmol,
0.10m), and TBADT (200 mg, 0.06 mmol, 2ꢁ10À3 m) were dissolved in
acetonitrile (30 mL) and irradiated for 40 h at 366 nm. After removing
the solvent in vacuo and purification of the residue by column chroma-
tography (silica gel, eluant: cyclohexane/ethyl acetate 8:2), dimethyl 2-(5-
formyl-1,3-benzodioxol-2-yl)succinate (32, 530 mg, 60%, equimolar mix-
ture of two diastereoisomers) was obtained as a colorless oil. 1H NMR
(CDCl3, mixture of diastereoisomers): d=2.6–2.9 (2H; AB part of an
ABX system), 3.5–3.6 (1H; X part of an ABX system), 3.7 (s, 3H), 3.8 (s,
3H), 6.6 (d, J=4 Hz, 1H), 6.8–6.9 (m, 1H), 7.2–7.3 (m, 1H), 7.4–7.5 (m,
1H), 9.8 ppm (s, 1H); 13C NMR (CDCl3, mixture of diastereoisomers):
d=29.0 (CH2), 29.3 (CH2), 46.2 (CH), 52.0 (CH3), 52.6 (CH3), 106.9
(CH), 108.3 (CH), 110.7 (CH), 128.5 (CH), 128.6 (CH), 131.9, 148.2,
1
was obtained as a colorless oil. H NMR (CDCl3, mixture of diastereoiso-
mers): d=1.2 (s, 3H), 1.25 (t, J=7 Hz, 3H), 1.3 (s, 3H), 3.3 (m, 2H), 3.8
(s, 1H), 4.3 (q, J=7 Hz, 2H), 5.1–5.2 (m, 2H), 5.8–6.0 (m, 1H), 6.1 (s,
1H), 6.6–6.8 ppm (m, 3H); 13C NMR (CDCl3, mixture of diastereoiso-
mers): d=13.7 (CH3), 18.6 (CH3), 20.0 (CH3), 39.8 (CH2), 41.9, 43.5
(CH), 62.7 (CH2), 107.8 (CH), 107.9 (CH), 108.7 (CH), 108.8 (CH), 113.0
(CH), 115.0 (C), 115.7 (CH2), 121.3 (CH), 121.4 (CH), 134.0, 134.1, 137.3
(CH), 145.7, 145.8, 147.5, 147.6, 164.4 ppm; IR (neat): n˜ =1259, 1496,
1746, 2250 cmÀ1; elemental analysis calcd (%) for C18H21NO4: C 68.55, H
6.71, N 4.44; found: C 68.6, H 6.7, N 4.3.
152.4, 169.5, 171.3, 190.0 ppm; IR (neat): n˜ =1257, 1493, 1690, 1740 cmÀ1
;
elemental analysis calcd for C14H14O7: C 57.14, H 4.80; found: C 57.2, H
4.9.
578
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 572 – 579

Smooth Photocatalytic Preparation of 2-Substituted-1,3-Benzodioxoles
FULL PAPER
[21] D. Ravelli, M. Zema, M. Mella, M. Fagnoni, A. Albini, Org.
Biomol. Chem. 2010, 8, 4158–4164.
Acknowledgements
[22] S. Protti, M. Fagnoni, A. Albini, Org. Biomol. Chem. 2005, 3, 2868–
2871.
Partial support of this work by Murst, Rome is gratefully acknowledged.
We also thank M. Zoccolillo (University of Pavia) for precious help.
[23] V. Dichiarante, M. Fagnoni, Synlett 2008, 787–800.
[24] A. B. PeÇꢆÇory, J. E. Argꢇello in Handbook of Synthetic Photo-
chemistry (Eds: A. Albini, M. Fagnoni) Wiley-VCH, Weinheim 2010
pp. 319–351.
[25] It was found that in the TBADT photocatalytic activation of amides,
the process became more sluggish when performed in MeCN/water
7:1 rather than in neat MeCN; see ref. [16].
[26] a) K. Yamada, M. Maekawa, T. Akindele, M. Nakano, Y. Yamamo-
to, K. Tomioka, J. Org. Chem. 2008, 73, 9535–9538; b) K. Yamada,
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Received: September 2, 2010
Published online: November 16, 2010
Chem. Eur. J. 2011, 17, 572 – 579
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