Potassium Hydroxide-Catalyzed Chemoselective Reduction of Cyclic Imides with Hydrosilanes: Synthesis of ω-Hydroxylactams and Lactams

Article abstract of DOI:10.1002/adsc.201501093

Potassium hydroxide-catalyzed hydrosilylation exhibits excellent activity and chemoselectivity for the reduction of cyclic imides under mild reaction conditions. The chemoselectivity of the reduction system may be readily tuned by changing the identity an

Full text of DOI:10.1002/adsc.201501093

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DOI: 10.1002/adsc.201501093
Potassium Hydroxide-Catalyzed Chemoselective Reduction of
Cyclic Imides with Hydrosilanes: Synthesis of w-Hydroxylactams
and Lactams
Guangni Ding,a Chengjun Li,a Yifan Shen,b Bin Lu,a Zhaoguo Zhang,a,c,*
and Xiaomin Xiea,*
a
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240,
Peopleꢀs Republic of China
Fax: (+86)-21-5474-8925; phone: (+86)-21-5474-8925; e-mail: zhaoguo@sjtu.edu.cn or xiaominxie@sjtu.edu.cn
Zhiyuan College, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, Peopleꢀs Republic of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 345 Lingling Road,
b
c
Shanghai 200032, Peopleꢀs Republic of China
Received: November 30, 2015; Revised: January 24, 2016; Published online: March 3, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501093.
Abstract: Potassium hydroxide-catalyzed hydrosilyla- in 70–94% yield, while the diphenylsilane (Ph2SiH2)/
tion exhibits excellent activity and chemoselectivity potassium hydroxide reduction system selectively af-
for the reduction of cyclic imides under mild reaction forded the aryl lactams in 33–95% yield. These cata-
conditions. The chemoselectivity of the reduction lytic protocols tolerate diverse functional groups and
system may be readily tuned by changing the identity are easy to scale up.
and stoichiometry of the hydrosilanes: a polymethyl-
hydrosiloxane (PMHS)/potassium hydroxide reduc-
tion system resulted in the reduction of various Keywords: base catalysis; cyclic imides; hydrosilyla-
cyclic imides to the corresponding w-hydroxylactams tion; w-hydroxylactams; lactams
Introduction
and pyrrolidines were obtained with pyrroles as by-
products.[4a,10] Therefore, it is an important synthetic
The reduction of carbonyl groups is an important challenge to develop a mild and highly selective re-
transformation in organic synthesis, and the chemose- duction method to access the cyclic compounds.
lective reduction of multi-functionalized carbonyl
The use of organosilicon hydrides is an appealing
compounds under mild conditions is challenging.[1] methodology for the selective reduction. In contrast
The reduction of cyclic imides gives several nitrogen- to metal hydride reducing agents, hydrosilanes are
containing products, such as w-hydroxylactams,[2] lac- mild air- and water-stable sources of hydride and can
tams,[3] substituted pyrroles,[4] pyrrolidines[5] and 4-hy- be activated under mild conditions.[11] Furthermore,
droxybutyric amides (ring-opening products).[6] Most the chemo- and regioselectivity of the reduction with
of these compounds are important structure motifs in silanes can be easily tuned by changing the substitu-
natural products and pharmaceuticals and are versa- ents on the silicon atom of the hydrosilanes and the
tile building blocks for organic synthesis.[4f,7] The employed catalysts.[12]
highly chemoselective reduction of cyclic imides
The metal/Lewis acid-catalyzed hydrosilylation of
would provide an efficient and straightforward access carbonyl compounds has been well-explored and
to these nitrogen-containing products. Typical reduc- a series of the highly chemo-, regio-, and/or stereose-
tion conditions using LiAlH4 or NaBH4 require harsh lective reduction methods of ketones,[13] esters,[14] am-
[15k,16]
conditions and laborious set-ups (i.e., anhydrous con- ides,[15]and CO2
have been developed. Beside
ditions and low reaction temperatures), and the re- these, Lewis base-catalyzed hydrosilylation of carbon-
duction reactions were accompanied with over-reduc- yl compounds has also drawn much attention, due to
tion by-products.[1,8] For example, 4-hydroxybutyric the more environmentally benign and mild condi-
amides (ring-opening products) were always formed tions.[17] Fluoride ion used as a Lewis base catalyst
as by-products in the synthesis of w-hydroxylactams,[9] displayed high efficiency in the hydrosilylation of
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Guangni Ding et al.
ketones and hydroxy esters.[17a,b,e] The reduction of
a-keto amides with hydrosilanes catalyzed by
tetrabutylammonium flouride (TBAF) selectively af-
forded a-hydroxy amides or b-amino alcohols by
tuning the hydrosilanes and the stoichiometry of the
active hydride.[18] Moreover, lithium methoxide was
also used as a catalyst in the reduction of epoxy ke-
Table 1. The solvent effect on the base-catalyzed selective
reduction of cyclic imides (1a) to w-hydroxylactams (2a)
with PhSiH3
[a]
tones and hydroxy esters with hydrosilanes.[17l,m]
[17h]
Lately, base (KOH,[17f,g,i] Cs2CO3
or t-BuOK[17j]
)
Entry
Solvent
Time
Conversion[b]
Yield[b]
catalyzed reductions of non-functionalized esters or
amides with hydrosilanes were realized.
1
2
3
4
5
6
7
8
9
10
no solvent
hexane
cyclohexane
toluene
THF
dioxane
HMPA
DMF
12 h
12 h
12 h
12 h
12 h
12 h
3 h
3 h
3 h
12 h
14%
–
–
80%
45%
85%
>97%
>97%
>97%
50%
14%
–
–
80%
45%
85%
>97%
>97%
>97%
45%
There are a few literature examples that explore
the chemoselective reduction of imides with hydrosi-
lanes. N-Benzylsuccinimide was reduced with Ph2SiH2
catalyzed by RhH(CO)(PPh3)3 to give the corre-
sponding pyrrolidine,[15a] the fluoride-catalyzed hydro-
silylation of aryl imides with polymethylhydrosiloxane
(PMHS) afforded the lactams,[19] and recently we de-
veloped a zinc-catalyzed selective hydrosilylation of
imides to access w-hydroxylactams.[20] However, con-
trolling the chemoselective reduction of cyclic imides
by choosing the appropriate hydrosilane and/or cata-
lyst has not been reported. Herein, we report a base-
catalyzed reduction of cyclic imides with hydrosilanes
which focused on tuning the chemoselectivity of the
reduction system by changing the identity and stoi-
chiometry of the hydrosilanes.
DMA
NMP
[a]
Reaction conditions: N-benzylphthalimide (1a, 3 mmol),
PhSiH3 (1.1 equiv. of H, 1.1 mmol), KOH (4 mol%), sol-
vent (3 mL), 258C.
[b]
Conversion and yields were determined by 1H NMR
analysis (internal standard: 4,4’-di-tert-butyl-1,1’-biphen-
yl).
without over-reduced or hydrolyzed compounds
(Table 1, entry 7). This may be ascribed to the fact
that HMPA can serve as a silaphilic nucleophile to
form the hexacoordinated silicate [HSiR3F(HMPA)]
Results and Discussion
The reduction of N-benzylphthalimide (1a) was as the active hydride species, which accelerated the
chosen as the model reaction to explore the chemose- TBAF-catalyzed reduction of aldehydes and ketones
lectivity of the base-catalyzed reduction of cyclic with hydrosilanes.[17e,22] High activity and chemoselec-
imides with hydrosilanes. Our initial effort was fo- tivity were still observed when DMF or DMA was
cused on developing a catalytic system for selective used as the solvent (Table 1, entries 8 and 9). Using
reduction of cyclic imides (1) to afford w-hydroxylac- NMP (N-methylpyrrolidin-2-one) as the solvent led to
tams (2) which serve as important precursors of N- a decrease in the conversion (Table 1, entry 10). Con-
acyliminium ions.[21] We tested the reduction of N- sequently, DMF was chosen as the solvent for the fol-
benzylphthalimide (1a) with PhSiH3 and KOH as lowing exploration.
a catalyst at room temperature based on the hydrosi-
The effect of bases and hydrosilanes on the reduc-
lylation of amides.[17g] Without solvent, the reaction tion of cyclic imides was then explored. A number of
selectively gave w-hydroxylactam (2a), but only 14% inorganic bases were tested in the reduction of N-ben-
of N-benzylphthalimide (1a) was consumed after 12 h zylphthalimide (1a) with PhSiH3 and excellent chemo-
(Table 1, entry 1). To enhance the homogeneity of re- selectivity and yields were achieved (Table 2, en-
action system, a series of solvents were explored. No tries 1–8). Hydroxide and alkoxide displayed good
conversion occurred at room temperature in non- catalytic activity to afford an almost quantitative yield
polar solvents such as hexane and cyclohexane of w-hydroxylactam (2a) within 4 h at room tempera-
(Table 1, entries 2 and 3), while the reduction afford- ture (Table 2, entries 1–4), while using the weaker
ed selectively the target product (2a) in 80% yield in bases required longer reaction time (Table 2, en-
toluene (entry 4), in which better solubility of the tries 5–8). Omission of the base or hydrosilane result-
imide (1a) was achieved. The use of ethereal solvent ed in no desired reduction of the imide (1a) (Table 2,
did not improve the conversion significantly (Table 1, entries 9 and 10). The conversion of 1a was decreased
entries 5 and 6). The reduction was then tested in when PhSiH3 was replaced with (EtO)3SiH (Table 2,
more polar solvents. The imide (1a) was converted entries 11 and 12). Gratifyingly, other accessible hy-
completely in HMPA (hexamethylphosphoramide) drosilanes were efficient for this reductive system and
after 3 h at room temperature to form selectively 2a excellent selectivity and activity were also obtained
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Potassium Hydroxide-Catalyzed Chemoselective Reduction of Cyclic Imides
Table 2. The effect of bases and silanes on the base-cata-
lyzed selective reduction of cyclic imides (1a) to w-hydroxy-
lactams (2a).[a]
Table 3. The selective reduction of cyclic imides (1) to w-hy-
droxylactams (2) with hydrosilanes.[a]
Entry Silane
Base
Time Yield[b]
1
2
3
4
5
6
7
8
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
–
KOH
3 h
4 h
4 h
4 h
>97%
85%
NaOH
t-BuOK
t-BuONa
Cs2CO3
K2CO3
K3PO4
Na2CO3
–
>97%
>97%
>97%
>97%
>97%
>97%
–
22 h
22 h
22 h
22 h
22 h
22 h
22 h
22 h
3 h
22 h
6 h
22 h
3 h
9
10
11
12
13
14
15
16
17
18
19
KOH
–
(EtO)3SiH KOH
(EtO)3SiH Na2CO3
85%
45%
Ph2SiH2
Ph2SiH2
PMHS
PMHS
PMHS
PMHS
PMHS
KOH
Na2CO3
KOH
Na2CO3
KOH (10 mmol%)
KOH (2.5 mmol%) 6 h
KOH (1.0 mmol%) 22 h
>97%
>97%
>97%
84%
>97%
>97%
>97%
[a]
Reaction conditions: N-benzylphthalimide (1a, 3 mmol),
silanes (1.1 equiv. of H), base (4 mol%), DMF (3 mL),
258C.
[b]
Yields were determined by 1H NMR analysis (internal
standard: 4,4’-di-tert-butyl-1,1’-biphenyl).
(Table 2, entries 13–16). Especially noteworthy is the
use of PMHS, a safe and inexpensive silane, which af-
forded the w-hydroxylactam (2a) in quantitative yield
after 6 h. Furthermore, increasing the loading of
KOH shortened the reaction time, and no hydrolyzed
compounds were observed. A quantitative yield of 2a
was obtained in 6 h even when the KOH loading was
lowered to 2.5 mol%.
[a]
Reaction conditions: imide (1, 3.0 mmol), PMHS
(1.1 equiv. of H, 200 mg), KOH (2.5 mol%), DMF
(3 mL), 258C, isolated yield.
The reduction was conducted on a 5.0 g scale.
[b]
The scope of the base-catalyzed chemoselective re-
duction of the cyclic imides (1) to w-hydroxylactams
(2) was probed under the optimized conditions. As
shown in Table 3, the reduction reactions led to effi- aliphatic and polycyclic substrates. The polycyclic ali-
cient formation of a number of w-hydroxylactams (2) phatic w-hydroxylactams (2g) and (2h) were generat-
at room temperature. The electronic nature and steric ed in 90% and 82% yield, respectively. Furthermore,
hindrance of the substituents at the nitrogen atom did the reduction system tolerates diverse functional
not affect the selective reduction to w-hydroxylactams groups, including alkene, nitrile, ester, amide, carbam-
(2). Both N-(4-methyl)benzylphthalimide (1b) and N- ic ester, and aromatic heterocycle. This broad func-
(4-trifluoromethyl)benzylphthalimide (1c) were re- tional group tolerance contrasts with the reactivity
duced chemoselectively in excellent yields. The reduc- observed with typical metal hydride reagents in which
tion of bulkier N-isopropylphthalimide also afforded functional groups such as esters and nitriles are not
the corresponding product (2e) in 88% yield. High re- tolerated. Notable examples include the reduction of
activity and selectivity were observed with aromatic, a phthalimide with a pendant ethyl ester (1k) and
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Guangni Ding et al.
a Boc-protected amine (1n). It is interesting that the Ph2SiH2/KOH system due to the commercial availa-
reduction of N-benzyl-2,3-pyridinedicarboximide (1o) bility and lower cost of Ph2SiH2 than that of PhSiH3.
proceeded smoothly with good chemoselectivity, and
The scope of base-catalyzed chemoselective reduc-
displayed a modest regioselective reduction at the car- tion of cyclic imides (1) to lactams (3) was further ex-
bonyl adjacent to the nitrogen atom of pyridine in amined (Table 5). Aromatic cyclic imides (1) were re-
a 2:1 ratio with 70% overall yield of the w-hydroxy- duced smoothly to the corresponding lactams (3) in
lactams. The scaled-up reduction ran effectively and excellent yield under optimized reduction conditions.
a 5 g scale reduction of N-benzylphthalimide (1a) The reduction reaction afforded N-benzyllactam (3a)
with PMHS afforded a 90% isolated yield of 2a. We in 90% yield. Lactam (3b) with an electron-donating
can also easily scale-up the reduction to access 1-(5,5- group at the nitrogen atom also was obtained in 89%
dimethoxypentyl)-5-hydroxypyrrolidin-2-one (2t), an yield. However, electron-withdrawing groups at the
important intermediate of bioactive Tashiromine, in nitrogen atom inhibited the reaction and the yield of
80% yield.[23]
the corresponding lactam (3c) decreased to 52% and
Following the realization of the base-catalyzed selec- 47% of the intermediate, w-hydroxylactam derivative,
tive reduction of cyclic imides to w-hydroxylactams, we was observed. The steric profile of the carbonyl group
then explored reaction conditions for selective reduc- did not appear to affect the reduction of 2-methyl-4-
tion of cyclic imides (1) to afford lactams (3) (Table 4). propylisoindoline-1,3-dione (1s), giving a mixture of
Increasing the equivalent of PMHS to provide 2.1 the two possible lactams (3s and 3s’) in a 1:1 ratio.
equivalents of hydride resulted in 25% lactam (3a) and The reduction system tolerated several functional
75% w-hydroxylactam (2a) (Table 4, entry 2). Increas- groups, such as alkene (3i), nitrile (3j), ester (3k),
ing the hydride equivalents to 6.0 and prolonging the amide (3m), carbamic ester (3n) and aromatic hetero-
reaction time increased the yield of lactam (3a) to cycles (3o and 3o’). The aromatic heterocyclic lactam
79%, while 18% of w-hydroxylactam (2a) remained (3r) was obtained in 42% yield. In the cases of the re-
(Table 4, entry 3). Elevated temperatures did not im- duction of the imides (3p, 3k and 3q) with the ester
prove the outcome significantly (Table 4, entry 4). group on the substituent chain at the nitrogen atom,
Using more reactive silanes, PhSiH3 or Ph2SiH2 the corresponding lactams were generated in moder-
(2.1 equiv. of H) resulted in quantitative yield of ate yield because of incomplete conversion of the w-
lactam (3a) within 3 h. In addition, the effect of bases hydroxylactam derivative. In addition, the reduction
on the selective reduction to afford lactams (3) was in- was easily scaled up to a 5.0 g scale reaction, and
vestigated with Ph2SiH2. The intermediate (2a) could KOH-catalyzed reduction of N-benzylphthalimide
not be converted completely to the product with either (1a) with Ph2SiH2 (1.1 equiv.) afforded the lactam
a stronger base (t-BuOK), or a weaker base (NaOH or (3a) with 92% isolated yield. Unfortunately, the re-
K3PO4) as catalyst. The substrate scope for the reduc- duction of aliphatic cyclic imides to the corresponding
tion of imides to lactams was explored with the lactams was not successful under these conditions.
Table 4. The effect of silanes and bases on the selective reduction of cyclic imides (1a) to lactams (3a) with hydrosilanes.[a]
Entry
Silane
Base
Time
Yield[b]
2a
3a
1
2
PMHS (1.1 equiv. H)
PMHS (2.1 equiv. H)
PMHS (6.0 equiv. H)
PMHS (6.0 equiv. H)
Ph2SiH2
PhSiH3
Ph2SiH2
Ph2SiH2
Ph2SiH2
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
t-BuOK
K3PO4
6 h
6 h
22 h
22 h
3 h
3 h
3 h
3 h
22 h
>97%
72%
18%
10%
–
–
25%
79%
80%
>97%
>97%
84%
91%
90%
3
4[c]
5
6
7
8
9
–
15%
8%
8%
[a]
Reaction conditions: N-benzylphthalimide (1a, 3 mmol), silanes (2.1 equiv. of H), base (2.5 mol%), DMF (3 mL), 258C.
Yields were determined by H NMR analysis (internal standard: 4,4’-di-tert-butyl-1,1’-biphenyl).
Reaction temperature: 708C.
[b]
[c]
1
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Potassium Hydroxide-Catalyzed Chemoselective Reduction of Cyclic Imides
Table 5. The selective reduction of cyclic imides (1) to lac-
tams (3) with hydrosilanes.[a]
Figure 1. Reaction profiles of the base-catalyzed reduction
of N-benzylphthalimide (1a) with Ph2SiH2. Reaction condi-
tions: 1a (3.0 mmol), Ph2SiH2 (2.1 equiv. of H, 3.15 mmol),
KOH (2.5 mol%), 258C, DMF (3 mL) as solvent.
to the w-hydroxylactam derivative, and support the
highly chemoselective experimental findings reported
herein.
Conclusions
In summary, the chemoselective reduction of cyclic
imides under mild reaction conditions can be ach-
ieved with a KOH-catalyzed hydrosilylation system.
Various cyclic imides were selectively reduced to w-
hydroxylactams in high yields with PMHS (1.1 equiv.
of H) and catalytic amounts of KOH (2.5 mol%). Ad-
justing the reduction system to Ph2SiH2 (2.1 equiv. of
H)/KOH (2.5 mol%) selectively provided lactams in
good to excellent yields. In addition, this catalytic
system exhibited good functional group tolerance.
[a]
Reaction conditions: imide (1, 3.0 mmol), Ph2SiH2
(2.1 equiv. of H, 3.15 mmol), KOH (2.5 mol%), DMF
(3 mL), 258C, isolated yield.
The reduction was conducted on a 5.0 g scale.
[b]
Experimental Section
To investigate the process of the chemoselective,
base-catalyzed reduction of the cyclic imides, the re-
action profile for the reduction of the imide (1a) with
Typical Procedure for the Hydrosilylation of Cyclic
Imides (1) to the w-Hydroxylactams (2)
Ph2SiH2 (2.1 equiv. of H)/KOH (2.5 mol%) was moni-
1
tored by H NMR spectroscopy (Figure 1). Build-up To the mixture of KOH (2.5 mol%) and cyclic imide
(3.0 mmol) in DMF (3 mL), was added PMHS (1.1 equiv.
based on H) slowly under an atmosphere of nitrogen. The
reaction mixture was stirred at 258C under an atmosphere
of nitrogen. After the imide was consumed completely (de-
tected by TLC), the reaction mixture was quenched by
adding NH3·H2O (1 mL) and stirred at room temperature
for one hour. Then the mixture was treated with water
(15 mL) and extracted with CH2Cl2 (10 mL”3). The com-
bined organic phase was dried over Na2SO4, after removing
the solvent under vacuum, the residue was purified by
and decay of the w-hydroxylactam derivative is evi-
dent during the course of the reduction and supports
that the w-hydroxylactam derivative is an intermedi-
ate in the reduction of the imide (1) to the lactam (3).
The conversion of imide (1a) was accomplished
within five minutes, and the yield of w-hydroxylactam
(2a) reached 95% in one minute, while the transfor-
mation of w-hydroxylactam derivative to lactam (3)
reached completion in about 2 h. These results high-
light the very different reactivity of imides compared column chromatography to give the product.
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Guangni Ding et al.
2-Benzyl-3-hydroxyisoindolin-1-one (2a):[24] White solid;
yield: 653.3 mg (2.7 mmol, 91%); mp 141.7–143.88C;
1H NMR (400 MHz, CDCl3): d=7.78–7.77 (m, 1H), 7.58–
7.56 (m, 2H), 7.50–7.48 (m, 1H), 7.35–7.31 (m, 5H), 5.63 (d,
J=11.6 Hz, 1H), 5.03 (d, J=14.8 Hz, 1H), 4.35 (d, J=
14.8 Hz, 1H), 2.63 (d, J=11.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=167.6, 144.2, 136.8, 132.5, 131.2, 129.8, 128.8,
128.5, 127.8, 123.6, 123.4, 81.1, 42.6.
2-Benzyl-3-hydroxyoctahydro-1H-4,7-methanoisoindol-1-
one (2h):[20] White solid; yield: 632.9 mg (2.5 mmol, 82%);
mp 148.5–157.18C; 1H NMR (400 MHz, CDCl3): d=7.32–
7.26 (m, 5H), 5.08–5.04 (m, 1H), 4.80 (d, J=14.8 Hz, 1H),
4.25 (d, J=14.8 Hz, 1H), 2.85–2.81 (m, 1H), 2.70–2.63 (m,
2H), 2.51–2.45 (m, 1H), 2.35–2.33 (m, 1H), 1.78–1.73 (m,
1H), 1.62–1.59 (m, 1H), 1.55–1.47 (m, 4H); 13C NMR
(100 MHz, CDCl3): d=174.5, 136.9, 128.7, 128.6, 127.5, 81.7,
48.6, 44.1, 43.5, 41.7, 40.1, 38.8, 25.3, 24.3.
3-Hydroxy-2-(4-methylbenzyl)isoindolin-1-one
(2b):
White solid; yield: 713.7 mg (2.8 mmol, 94%); mp 140.8–
142.18C; 1H NMR (400 MHz, CDCl3): d=7.72–7.71 (m,
1H), 7.56–7.55 (m, 2H), 7.49–7.45 (m, 1H), 7.23–7.21 (m,
2H), 7.12–7.10 (m, 2H), 5.60 (d, J=11.6 Hz, 1H), 4.92 (d,
J=14.8 Hz, 1H), 4.26 (d, J=14.8 Hz, 1H), 2.99 (br, 1H),
2.31 (s, 3H); 13C NMR (100 MHz, CDCl3): d=167.5, 144.2,
137.4, 133.8, 132.4, 131.3, 129.7, 129.5, 128.6, 123.5, 123.4,
81.0, 42.4, 21.2; HR-MS-ESI: m/z=254.1184, calculated for
C16H15NO2 (M+H)+: 254.1181.
3-Hydroxy-2-[4-(trifluoromethyl)benzyl]isoindolin-1-one
(2c): White solid; yield: 921.6 mg (2.7 mmol, 91%); mp
138.6–139.98C; 1H NMR (400 MHz, CDCl3): d=7.79–7.76
(m, 1H), 7.59–7.56 (m, 4H), 7.54–7.50 (m, 1H), 7.47–7.45
(m, 2H), 5.63 (d, J=12.0 Hz, 1H), 5.00 (d, J=14.8 Hz, 1H),
4.45 (d, J=14.8 Hz, 1H), 2.72 (d, J=12.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=167.7, 144.1, 140.9, 132.8,
131.0, 130.2, 130.0, 129.9, 128.7, 125.86, 125.83, 125.79,
125.75, 125.5, 123.7, 123.5, 122.8, 81.3, 42.34; HR-MS-ESI;
m/z=308.0899, calculated for C16H12F3NO2 (M+H)+:
308.0898.
2-Allyl-3-hydroxyisoindolin-1-one (2i):[28] White solid;
1
yield: 522.2 mg (2.8 mmol, 92%); mp 86.8–89.38C; H NMR
(400 MHz, CDCl3): d=7.61–7.54 (m, 3H), 7.47–7.42 (m,
1H), 5.81–5.71 (m, 2H), 5.21–5.15 (m, 2H), 4.14–4.07 (m,
1H), 3.78–3.72 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
167.5, 144.2, 132.5, 132.4, 131.2, 129.7, 123.5, 123.3, 118.0,
81.3, 41.4.
5-(1-Hydroxy-3-oxoisoindolin-2-yl)pentanenitrile
(2j):
Colourless oil; yield: 552.7 mg (2.4 mmol, 80%); 1H NMR
(400 MHz, CDCl3): d=7.62–7.54 (m, 3H), 7.48–7.44 (m,
1H), 5.74 (s, 1H), 4.09 (br, 1H), 3.52–3.38 (m, 2H), 2.39–
2.35 (m, 2H), 1.82–1.72 (m, 2H), 1.70–1.60 (m, 2H);
13C NMR (100 MHz, CDCl3): d=167.8, 144.0, 132.4, 131.2,
129.7, 123.4, 123.1, 119.6, 81.9, 38.3, 27.4, 22.7, 16.7; HR-MS-
ESI: m/z=231.1131, calculated for C13H14N2O2 (M+H)+:
231.1134.
Ethyl 4-(1-hydroxy-3-oxoisoindolin-2-yl)butanoate (2k):[20]
1
Pale yellow oil; yield: 710.9 mg (2.7 mmol, 90%); H NMR
(400 MHz, CDCl3): d=7.68–7.66 (m, 1H), 7.61–7.54 (m,
2H), 7.48–7.44 (m, 1H), 5.78 (d, J=10.8 Hz, 1H), 4.00 (q,
J=7.2 Hz, 2H), 3.92 (d, J=10.8 Hz, 1H), 3.60–3.48 (m,
2H), 2.45–2.31 (m, 2H), 2.10–1.91 (m, 2H), 1.18 (t, J=
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=173.6, 167.7,
144.1, 132.2, 131.4, 129.6, 123.4, 123.0, 82.1, 60.6, 38.8, 31.8,
23.7, 14.2.
2-Benzyl-3-hydroxy-2,3,3a,4,7,7a-hexahydro-1H-4,7-meth-
anoisoindol-1-one (2l):[29] White solid; yield: 681.6 mg
(2.7 mmol, 89%); mp 119.5–126.08C; 1H NMR (400 MHz,
CDCl3): d=7.32–7.23 (m, 5H), 6.26–6.21 (m, 2H), 5.02–4.97
(m, 1H), 4.65 (d, J=14.8 Hz, 1H), 4.10 (d, J=14.8 Hz, 1H),
3.34–3.32 (m, 1H), 3.21–3.18 (m, 1H), 3.09–3.08 (m, 1H),
3.04–3.00 (m, 1H), 1.84–1.80 (m, 1H), 1.63–1.60 (m, 1H),
1.45–1.43 (m, 1H); 13C NMR (100 MHz, CDCl3): d=173.6,
136.8, 135.9, 134.5, 128.7, 128.5, 127.6, 81.9, 52.3, 49.9, 45.9,
44.7, 43.4, 43.2.
2-Ethyl-3-hydroxyisoindolin-1-one (2d):[25] White solid;
yield: 489.1 mg (2.8 mmol, 92%); mp 105.0–107.28C;
1H NMR (400 MHz, CDCl3): d=7.63–7.60 (m, 2H), 7.58–
7.54 (m, 1H), 7.48–7.43 (m, 1H), 5.77 (d, J=12.0 Hz, 1H),
3.65–3.56 (m, 1H), 3.40–3.31 (m, 1H), 3.12 (d, J=12.0 Hz,
1H), 1.21 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=167.4, 144.1, 132.1, 131.6, 129.6, 123.4, 123.1, 81.3, 33.8,
13.5.
3-Hydroxy-2-isopropylisoindolin-1-one (2e):[26] White
solid; yield: 504.8 mg (2.6 mmol, 88%); mp 95.4–97.28C;
1H NMR (400 MHz, CDCl3): d=7.7–7.70 (m, 1H), 7.60–7.54
(m, 2H), 7.51–7.46 (m, 1H), 5.92 (d, J=11.8 Hz, 1H), 4.45–
4.37 (m, 1H), 2.43 (d, J=11.8 Hz, 1H), 1.43 (d, J=4.2 Hz,
3H), 1.41 (d, J=4.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=167.2, 144.2, 132.0, 129.5, 123.1, 81.4, 44.0, 22.0, 20.2.
1-Benzyl-5-hydroxypyrrolidin-2-one (2f):[27] White solid;
yield: 430.2 mg (2.2 mmol, 75%); mp 108.3–110.18C;
1H NMR (400 MHz, CDCl3): d=7.36–7.28 (m, 5H), 5.11–
5.08 (m, 1H), 4.83 (d, J=14.8 Hz, 1H), 4.24 (d, J=14.8 Hz,
1H), 2.68–2.60 (m, 1H), 2.43–2.25 (m, 2H), 2.23–2.21 (m,
1H), 1.93–1.85 (m, 1H); 13C NMR (100 MHz, CDCl3): d=
174.9, 136.6, 128.9, 128.5, 127.8, 82.7, 43.6, 29.0, 28.3.
3-(1-Hydroxy-3-oxoisoindolin-2-yl)-N,N-dimethylpropana-
mide (2m):[20] White solid; yieldf: 655.5 mg (2.6 mmol,
1
88%); mp 112.1–115.38C; H NMR (400 MHz, CDCl3): d=
7.76–7.74 (m, 1H), 7.60–7.53 (m, 2H), 7.48–7.44 (m, 1H),
6.20 (d, J=4.4 Hz, 1H), 5.88 (d, J=4.4 Hz, 1H), 3.98–3.85
(m, 2H), 3.01 (s, 3H), 2.96 (s, 3H), 2.94–2.89 (m, 1H), 2.68–
2.61 (m, 1H); 13C NMR (100 MHz, CDCl3): d=172.4, 168.0,
144.2, 132.1, 131.7, 129.4, 123.3, 123.0, 82.6, 37.3, 35.9, 35.7,
32.8.
tert-Butyl 4-[4-(1-hydroxy-3-oxoisoindolin-2-yl)butyl]pi-
perazine-1-carboxylate (2n):[20] White solid; yield: 1074.7 mg
(2.8 mmol, 92%); mp 108.4–111.68C; 1H NMR (400 MHz,
CDCl3): d=7.75–7.73 (m, 1H), 7.61–7.54 (m, 2H), 7.50–7.46
(m, 1H), 5.80 (s, 1H), 3.85–3.81 (m, 1H), 3.52–3.46 (m, 1H),
3.27–3.24 (m, 4H), 2.39–2.33 (m, 1H), 2.31–2.26 (m, 2H),
2.21–2.15 (m, 1H), 2.03–1.99 (m, 3H), 1.73–1.58 (m, 4H),
1.42 (s, 9H); 13C NMR (100 MHz, CDCl3): d=167.5, 154.7,
2-Benzyl-3-hydroxyoctahydro-1H-isoindol-1-one
(2g):
White solid; yield: 735.9 mg (2.7 mmol, 90%); mp 104.2–
106.78C; 1H NMR (400 MHz, CDCl3): d=7.35–7.28 (m,
5H), 4.81 (d, J=14.8 Hz, 1H), 4.55 (d, J=4.8 Hz, 1H), 4.22
(dd, J=14.8, 4.8 Hz, 1H), 2.84–2.80 (m, 1H), 2.20–2.15 (m,
1H), 2.09–2.05 (m, 1H), 1.69–1.64 (m, 1H), 1.60–1.50 (m,
4H), 1.20–1.14 (m, 2H), 0.96–0.86 (m, 1H); 13C NMR
(100 MHz, CDCl3): d=176.7, 136.8, 128.8, 128.5, 127.7, 85.8,
43.9, 41.0, 38.9, 26.1, 23.4, 23.3, 23.1; HR-MS-ESI: m/z=
246.1492, calculated for C15H19NO2 (M+H)+: 246.1494.
1246
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FULL PAPERS
Potassium Hydroxide-Catalyzed Chemoselective Reduction of Cyclic Imides
144.7, 132.2, 131.7, 129.7, 123.2, 123.2, 82.8, 79.9, 57.4, 52.7,
40.0, 28.5, 25.9, 24.0.
124.28C; 1H NMR (400 MHz, CDCl3): d=7.92–7.90 (m,
1H), 7.60–7.58 (m, 2H), 7.57–7.47 (m, 2H), 7.43–7.40 (m,
3H), 4.87 (s, 2H), 4.29 (s, 2H); 13C NMR (100 MHz,
CDCl3): d=168.7, 141.3, 141.2, 132.4, 131.7, 130.6, 130.3,
129.9, 129.6, 128.4, 128.3, 125.9, 125.9, 125.9, 125.8, 125.5,
124.1, 123.0, 122.8, 49.6, 46.1; HR.MS-ESI: m/z=292.0951,
calculated for C16H12F3NO (M+H)+: 292.0949.
6-Benzyl-7-hydroxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-
5-one (2o):[30] White solid; yield: 320.2 mg (1.3 mmol, 46%);
mp 183.1–186.78C; 1H NMR (400 MHz, DMSO): d=8.79–
8.77 (m, 1H), 8.12–8.10 (m, 1H), 7.58–7.55 (m, 1H), 7.34–
7.32 (m, 4H), 7.30–7.25 (m, 1H), 6.99 (d, J=8.4 Hz, 1H),
5.64 (d, J=8.4 Hz, 1H), 4.93 (d, J=15.6 Hz, 1H), 4.41 (d,
J=15.6 Hz, 1H); 13C NMR (100 MHz, DMSO): d=164.8,
163.9, 152.8, 137.5, 131.2, 128.5, 127.8, 127.2, 125.2, 124.7,
80.8, 42.2.
6-Benzyl-5-hydroxy-5H-pyrrolo[3,4-b]pyridin-7(6H)-one
(2o’):[30] White solid; yield: 176.7 mg (0.7 mmol, 24%); mp
198.1–202.68C; 1H NMR (400 MHz, DMSO): d=8.77–8.75
(m, 1H), 8.05–8.03 (m, 1H), 7.62–7.59 (m, 1H), 7.34–7.32
(m, 4H), 7.30–7.25 (m, 1H), 6.89 (d, J=8.8 Hz, 1H), 5.74
(d, J=8.8 Hz, 1H), 4.94 (d, J=15.6 Hz, 1H), 4.42 (d, J=
15.6 Hz, 1H); 13C NMR (100 MHz, DMSO): d=164.7,
151.4, 149.8, 139.2, 137.4, 132.2, 128.5, 127.8, 127.2, 126.1,
78.5, 42.4.
1-(5,5-Dimethoxypentyl)-5-hydroxypyrrolidin-2-one
(2t):[23] Pale yellow oil; yield: 490.9 mg (2.6 mmol, 87%);
1H NMR (400 MHz, CDCl3): d=5.21 (t, J=5.6 Hz, 1H),
4.34 (t, J=6.0 Hz, 1H), 3.49–3.42 (m, 1H), 3.30 (s, 6H),
3.21–3.14 (m, 1H), 2.57–2.51 (m, 1H), 2.37–2.26 (m, 2H),
1.92–1.85 (m, 1H), 1.75 (br, 1H), 1.64–1.55 (m, 4H), 1.41–
1.33 (m, 2H); 13C NMR (100 MHz, CDCl3): d=175.0, 104.5,
83.2, 52.9, 39.8, 32.2, 29.1, 28.3, 27.5, 22.0.
2-Ethylisoindolin-1-one (3d):[19] Pale yellow oil; yield:
1
451.4 mg (2.8 mmol, 92%); H NMR (400 MHz, CDCl3): d=
7.85–7.82 (m, 1H), 7.53–7.49 (m, 1H), 7.46–7.42 (m, 2H),
4.37 (s, 2H), 3.67 (q, J=7.2 Hz, 2H), 1.26 (t, J=7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=168.1, 141.1, 133.0,
131.0, 127.9, 123.4, 122.6, 49.2, 36.9, 13.5.
2-Isopropylisoindolin-1-one (3e):[19] White solid; yield:
473.0 mg (2.7 mmol, 90%); mp 89.3–91.68C; 1H NMR
(400 MHz, CDCl3): d=7.85–7.83 (m, 1H), 7.54–7.50 (m,
1H), 7.46–7.43 (m, 2H), 4.73–4.63 (m, 1H), 4.34 (s, 2H),
1.30 (s, 3H), 1.28 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
167.9, 141.2, 133.4, 131.1, 128.0, 123.6, 122.8, 45.1, 42.7, 20.9.
2-Allylisoindolin-1-one (3i): Pale yellow oil; yield:
1
441.7 mg (2.5 mmol, 85%); H NMR (400 MHz, CDCl3): d=
7.86–7.84 (m, 1H), 7.55–7.50 (m, 1H), 7.47–7.42 (m, 2H),
5.91–5.81 (m, 1H), 5.26–5.20 (m, 2H), 4.35 (s, 2H), 4.24–
4.22 (m, 2H); 13C NMR (100 MHz, CDCl3): d=168.2, 141.2,
133.0, 132.7, 131.3, 127.9, 123.7, 122.7, 117.9, 49.5, 45.0; HR-
MS-ESI: m/z=174.0914, calculated for C11H11NO (M+H)+:
174.0919.
5-(1-Oxoisoindolin-2-yl)pentanenitrile (3j): Pale yellow
oil; yield: 572.2 mg (2.7 mmol, 89%); 1H NMR (400 MHz,
CDCl3): d=7.80–7.78 (m, 1H), 7.53–7.49 (m, 1H), 7.44–7.41
(m, 2H), 4.35 (s, 2H), 3.64 (t, J=7.2 Hz, 2H), 2.42 (t, J=
7.2 Hz, 2H), 1.85–1.78 (m, 2H), 1.71–1.63 (m, 2H);
13C NMR (100 MHz, CDCl3): d=168.8, 141.0, 132.5, 131.4,
128.1, 123.6, 122.8, 119.4, 49.8, 41.0, 27.2, 22.4, 16.7; HR-MS-
ESI: m/z=215.1179, calculated for C13H14N2O (M+H)+:
215.1184.
Ethyl 4-(1-oxoisoindolin-2-yl)butanoate (3k): Pale yellow
oil; yield: 430.3 mg (1.7 mmol, 58%); 1H NMR (400 MHz,
CDCl3): d=7.84–7.82 (m, 1H), 7.54–7.50 (m, 1H), 7.46–7.43
(m, 2H), 4.39 (s, 2H), 4.06 (q, J=7.2 Hz, 2H), 3.66 (t, J=
7.2 Hz, 2H), 2.38 (t, J=7.2 Hz, 2H), 2.00 (p, J=7.2 Hz,
2H), 1.21 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=173.1, 168.7, 141.2, 132.7, 131.3, 128.0, 123.6, 122.7, 60.5,
50.0, 41.7, 31.5, 23.7, 14.2; HR-MS-ESI: m/z=248.1286, cal-
culated for C14H17NO3 (M+H)+: 248.1287.
N,N-Dimethyl-3-(1-oxoisoindolin-2-yl)propanamide (3m):
Pale yellow solid; yield: 206.7 mg (2.7 mmol, 89%); mp
99.8–102.48C; 1H NMR (400 MHz, CDCl3): d=7.82–7.81
(m, 1H), 7.53–7.49 (m, 1H), 7.45–7.41 (m, 2H), 4.55 (s, 2H),
3.92 (t, J=6.4 Hz, 2H), 2.99 (s, 3H), 2.93 (s, 3H), 2.76 (t,
J=6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=170.9,
168.9, 141.8, 132.7, 131.2, 127.8, 123.3, 122.7, 51.6, 38.9, 37.2,
35.4, 32.4; HR-MS-ESI: m/z=233.1292, calculated for
C13H16N2O2 (M+H)+: 233.1290.
Typical Procedure for the Hydrosilylation of Cyclic
Imides (1) to the Lactams (3)
To the mixture of KOH (2.5 mol%) and cyclic imide
(3.0 mmol) in DMF, was added Ph2SiH2 (2.1 equiv. based on
H) slowly under an atmosphere of nitrogen. The reaction
mixture was stirred at 258C under an atmosphere of nitro-
gen. After the imide was consumed completely (detected by
TLC), the reaction mixture was quenched by adding
NH3·H2O (1 mL) and stirred at room temperature for one
hour. Then the mixture was treated with water (15 mL) and
extracted with CH2Cl2 (10 mL”3). The combined organic
phase was dried over Na2SO4, after removing the solvent
under vacuum, the residue was purified by column chroma-
tography to give the product.
2-Benzylisoindolin-1-one (3a):[19] Pale yellow solid; yield:
602.9 mg (2.7 mmol, 90%); mp 83.3–84.58C; 1H NMR
(400 MHz, CDCl3): d=7.91–7.89 (m, 1H), 7.54–7.45 (m,
2H), 7.39–7.36 (m, 1H), 7.34–7.26 (m, 5H), 4.81 (s, 2H),
4.27 (s, 2H); 13C NMR (100 MHz, CDCl3): d=168.5, 141.3,
137.1, 132.7, 131.4, 128.8, 128.2, 128.1, 127.7, 123.9, 122.8,
49.5, 46.4.
2-(4-Methylbenzyl)isoindolin-1-one (3b): Pale yellow
solid; yield: 640.7 mg (2.7 mmol, 89%); mp 64.3–66.48C;
1H NMR (400 MHz, CDCl3): d=7.89–7.87 (m, 1H), 7.51–
7.42 (m, 2H), 7.36–7.34 (m, 1H), 7.20–7.18 (m, 2H), 7.14–
7.12 (m, 2H), 4.75 (s, 2H), 4.22 (s, 2H), 2.32 (s, 3H);
13C NMR (100 MHz, CDCl3): d=168.4, 141.3, 137.4, 134.0,
132.7, 131.3, 129.5, 128.2, 128.0, 123.8, 122.8, 49.4, 46.1, 21.1;
HR-MS-ESI: m/z=238.1232, calculated for C16H15NO (M+
H)+: 238.1232.
tert-Butyl
4-[4-(1-oxoisoindolin-2-yl)butyl]piperazine-1-
carboxylate (3n): Pale yellow solid; 986.0 mg (2.6 mmol,
88%); mp 99.1–102.18C; 1H NMR (400 MHz, CDCl3): d=
7.84–7.82 (m, 1H), 7.54–7.50 (m, 1H), 7.47–7.42 (m, 2H),
4.37 (s, 2H), 3.64 (t, J=7.2 Hz, 2H), 3.40 (t, J=4.8 Hz, 2H),
2.39–2.35 (m, 6H), 1.73–1.66 (m, 2H), 1.57–1.50 (m, 2H),
1.44 (s, 9H); 13C NMR (100 MHz, CDCl3): d=168.5, 154.7,
141.0, 132.9, 131.2, 128.0, 123.6, 122.6, 79.5, 58.0, 53.0, 49.8,
2-[4-(Trifluoromethyl)benzyl]isoindolin-1-one (3c): Pale
yellow solid; yield: 454.4 mg (1.6 mmol, 52%); mp 122.2–
Adv. Synth. Catal. 2016, 358, 1241 – 1250
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1247

FULL PAPERS
Guangni Ding et al.
43.7, 43.3, 42.1, 28.4, 26.2, 24.0; HR-MS-ESI: m/z=
Acknowledgements
374.2441, calculated for C21H31N3O3 (M+H)+: 374.2444.
6-Benzyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one
(3o):[31] Pale yellow solid; yield:195.1 mg (0.9 mmol, 29%);
mp 136.1–138.78C; 1H NMR (400 MHz, CDCl3): d=8.71–
8.69 (m, 1H), 8.16–8.14 (m, 1H), 7.42–7.38 (m, 1H), 7.37–
7.30 (m, 5H), 4.84 (s, 2H), 4.34 (s, 2H); 13C NMR
(100 MHz, CDCl3): d=166.8, 162.3, 152.6, 136.6, 132.0,
129.0, 128.3, 128.0, 126.5, 123.3, 51.2, 46.4.
We thank the National Natural Science Foundation of China
for financial support and Instrumental Analysis Center of
Shanghai Jiao Tong University for microanalysis.
References
6-Benzyl-5H-pyrrolo[3,4-b]pyridin-7(6H)-one
(3o’):[32]
[1] J. Mµlek, in: Organic Reactions, John Wiley & Sons,
Inc., 2004.
Pale yellow solid; yield: 157.8 mg (0.7 mmol, 23%); mp
153.2–155.18C; 1H NMR (400 MHz, CDCl3): d=8.80–8.79
(m, 1H), 7.76–7.74 (m, 1H), 7.43–7.39 (m, 1H), 7.37–7.30
(m, 5H), 4.87 (s, 2H), 4.27 (s, 2H); 13C NMR (100 MHz,
CDCl3): d=166.5, 151.0, 150.8, 136.5, 135.2, 131.3, 129.0,
128.5, 128.0, 125.3, 47.3, 47.0.
Ethyl 3-(1-oxoisoindolin-2-yl)propanoate (3p): Pale
yellow oil; yield: 233.3 mg (1.0 mmol, 33%); 1H NMR
(400 MHz, CDCl3): d=7.85–7.83 (m, 1H), 7.55–7.51 (m,
1H), 7.47–7.42 (m, 2H), 4.47 (s, 2H), 4.15 (q, J=7.2 Hz,
2H), 3.91 (t, J=6.4 Hz, 2H), 2.73 (t, J=6.4 Hz, 2H), 1.24 (t,
J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=172.1,
168.8, 141.5, 134.6, 131.5, 128.2, 123.8, 122.8, 61.0, 51.0, 38.7,
33.7, 14.3; HR-MS-ESI: m/z=234.1134, calculated for
C13H15NO3 (M+H)+: 234.1130.
Ethyl 5-(1-oxoisoindolin-2-yl)pentanoate (3q): Colourless
oil; yield: 376.6 mg (1.4 mmol, 48%); 1H NMR (400 MHz,
CDCl3): d=7.82–7.80 (m, 1H), 7.52–7.48 (m, 1H), 7.44–7.40
(m, 2H), 4.36 (s, 2H), 4.08 (q, J=7.2 Hz, 2H), 3.61 (t, J=
6.8 Hz, 2H), 2.34 (t, J=6.8 Hz, 2H), 1.69–1.65 (m, 4H), 1.21
(t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=173.4,
168.6, 141.2, 133.0, 131.2, 128.1, 123.7, 122.7, 60.4, 49.9, 41.9,
33.8, 27.8, 22.2, 14.3; HR-MS-ESI: m/z=262.1441, calculat-
ed for C15H19NO3 (M+H)+: 262.1443.
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droxylactams with metal hydrides, see: a) J. C. Hubert,
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31, 1437–1441; b) T. Zielinski, J. Epsztajn, M. Jatczak,
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Overman, J. Am. Chem. Soc. 1987, 109, 6097–6107;
e) M. Shimizu, Y. Nishigaki, A. Wakabayashi, Tetrahe-
dron Lett. 1999, 40, 8873–8876.
[3] For examples of the reduction of the imides to lactams
with metal hydrides or metals, see: a) J. H. Brewster,
A. M. Fusco, L. E. Carosino, B. G. Corman, J. Org.
ˇ
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Chem. 1963, 28, 498–501; b) M. Cerny, J. Mµlek, M.
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Capka, V. Chvalovsky, Collect. Czech. Chem. Commun.
1969, 34, 1033–1041; c) A. J. McAlees, R. McCrindle,
D. W. Sneddon, J. Chem. Soc. Perkin Trans. 1 1977,
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6-Benzyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one (3r):
Pale yellow solid; yield: 283.7 mg (1.3 mmol, 42%); mp
1
189.3–191.88C; H NMR (400 MHz, CDCl3): d=8.77 (d, J=
2.4 Hz, 1H), 8.65 (d, J=2.4 Hz, 1H), 7.39–7.32 (m, 5H),
4.90 (s, 2H), 4.37 (s, 2H); 13C NMR (100 MHz, CDCl3): d=
164.8, 156.3, 146.4, 145.9, 145.0, 136.0, 129.1, 128.5, 128.3,
48.7, 47.0; HR-MS-ESI: m/z=226.0976, calculated for
C13H11N3O (M+H)+: 226.0980.
2-Methyl-7-propylisoindolin-1-one (3s): Pale yellow solid;
1
yield: 283.9 mg (1.5 mmol, 50%); mp 49.6–51.28C; H NMR
(400 MHz, CDCl3): d=7.41–7.37 (m, 1H), 7.24–7.18 (m,
2H), 4.31 (s, 2H), 3.16 (s, 3H), 3.13 (t, J=7.2 Hz, 2H),
1.74–1.64 (m, 2H), 0.98 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=169.2, 142.4, 141.7, 130.7, 129.5,
129.1, 120.1, 51.4, 32.8, 29.2, 24.8, 14.1; HR-MS-ESI: m/z=
190.1232, calculated for C12H15NO (M+H)+: 190.1232.
2-Methyl-4-propylisoindolin-1-one (3s’): Pale yellow oil;
yield: 255.4 mg (1.4 mmol, 45%); 1H NMR (400 MHz,
CDCl3): d=7.68–7.66 (m, 1H), 7.40–7.37 (m, 1H), 7.33–7.31
(m, 1H), 4.33 (s, 2H), 3.20 (s, 3H), 2.61 (t, J=7.2 Hz, 2H),
1.73–1.63 (m, 2H), 0.97 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=169.2, 139.5, 137.0, 132.7, 131.2,
128.3, 121.2, 51.3, 34.1, 29.5, 23.2, 14.0; HR-MS-ESI: m/z=
190.1228, calculated for C12H15NO (M+H)+: 190.1232.
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