A new entry for the preparation of substituted aromatic carbonyl compounds mediated by Samarium(II) iodide

Article abstract of DOI:10.1081/SCC-120017130

A new route to substituted aromatic lactones and lactams via SMI₂-promoted desulfurization is described. Direct replacement of the phenylthio substituent by hydroxyalkylated groups featuring the novel accessible process for the construction of continuous quaternary carbon centers could be accomplished when the same type of reactions was undertaken with carbonyl compounds in the presence of SmI₂.

Full text of DOI:10.1081/SCC-120017130

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A New Entry for the Preparation of Substituted
Aromatic Carbonyl Compounds Mediated by
Samarium(II) Iodide
Hidemi Yoda a , Naoki Kohata a & Kunihiko Takabe a
a Department of Molecular Science , Faculty of Engineering , Shizuoka University , Johoku,
Hamamatsu, Japan
Published online: 21 Aug 2006.
To cite this article: Hidemi Yoda , Naoki Kohata & Kunihiko Takabe (2003) A New Entry for the Preparation of Substituted
Aromatic Carbonyl Compounds Mediated by Samarium(II) Iodide, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:7, 1087-1094, DOI: 10.1081/SCC-120017130
To link to this article: http://dx.doi.org/10.1081/SCC-120017130
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 7, pp. 1087–1094, 2003
A New Entry for the Preparation of Substituted
Aromatic Carbonyl Compounds Mediated by
Samarium(II) Iodide
*
Hidemi Yoda, Naoki Kohata,and Kunihiko Takabe
Department of Molecular Science,
Faculty of Engineering, Shizuoka University,
Johoku, Hamamatsu, Japan
ABSTRACT
A new route to substituted aromatic lactones and lactams via
SmI2-promoted desulfurization is described. Direct replacement of
the phenylthio substituent by hydroxyalkylated groups featuring
the novel accessible process for the construction of continuous
quaternary carbon centers could be accomplished when the same
type of reactions was undertaken with carbonyl compounds in the
presence of SmI2.
*Correspondence: Hidemi Yoda, Department of Molecular Science, Faculty of
Engineering, Shizuoka University, Johoku 3-5-1, Hamamatsu 432-8561, Japan;
E-mail: tchyoda@ipc.shizuoka.ac.jp.
1087
DOI: 10.1081/SCC-120017130
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1088
Yoda,Kohata,and Takabe
Key Words: Aromatic lactone; Aromatic lactam; Desulfurization;
Samarium(II) iodide; Reductive coupling.
INTRODUCTION
During the past 10 years, many studies have been devoted to reac-
tivity of Samarium(II) species[1] with a variety of carbonyl compounds
(aldehydes, ketones, esters,[2] acid chlorides,[3] and acid anhydrides[4]) for
ring closure and/or C–C bond formation reactions. In addition, intramo-
lecular and intermolecular Barbier-type reactions with haloalkanes
toward the carbonyl group of ketones[5] and imides[6] have been reported.
In this connection recent disclosures from this laboratory have demon-
strated the first pinacolic cross-coupling reaction between phthalimides
and carbonyl compounds and its application to two types of complete
threo-selective reactions.[7] Although significant progress, thus, has been
made in advancing the versatility of Samarium(II) compounds, the lack
of studies concerning the reactivity toward simple amides is surprising
except in some special cases.[8] This low reactivity sometimes permits
some selective transformations, for example Barbier-type reaction with
amide ketones[9] orselective side chain introduction onto small peptides
mediated by SmI2.[10] Herein we wish to report our new successful entry
for the preparation of substituted aromatic lactones and lactams via
desulfurization mediated by SmI2, and the coupling reactions with car-
bonyl compounds[11] undermild conditions, leading to the continuous
quaternary a-hydroxyalkylated lactams (Sch. 1), since little effort with
SmI2 has been made for the utilization to desulfurization reactions.
Scheme 1.

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Substituted Aromatic Lactones and Lactams
RESULTS AND DISCUSSION
1089
Experiments have been initially performed on SmI2-promoted desul-
furization reaction employing g-alkyl substituted derivatives 3 obtained
from alkylation of sulfur-containing phthalides 2.[12] The results from our
survey are summarized in Table 1. To begin with, treatment of allylated
phenylsulfonyl- orphenylthio-phthalide 3 with 2.0 equiv. of SmI2 at
ambient temperature provided the desired desulfurized product 4 but in
low yield, respectively (Entries 1,6) together with the recovered starting
material. The use of 3 equiv. of this reagent (Entries 2,7) or the presence
of an additive such as HMPA (Entries 3,8) or t-BuOH (Entries 4,9) had
an effect on the rate to some extent, giving 4 in moderate yield (up to
42%) within 5 min. Finally, we found that the use of excess SmI2 (Entries
10,11) could effect these reactions in reasonable yield (up to 68%) with-
out by products.
Table 1. SmI2-promoted desulfurization reaction of lactones (3) afteralkylation
of (2).
Yield of
3 (%)a
SmI2
(equiv.)
Additives
(equiv.)
Yield of
4 (%)a
Entry
n
R
1
2
2
2
2
2
2
0
0
0
0
0
0
0
0
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH2¼CHCH2
CH3
85
—
—
—
—
64
—
—
—
—
—
92
90
2.0
3.0
3.0
3.0
5.0
2.0
3.0
3.0
3.0
5.0
10.0
5.0
5.0
—
—
6
20
24
42
42
11
38
38
42
61
68
32
37
3
HMPA (3.0)
t-BuOH (1.0)
4
5
—
—
6
7
—
HMPA (3.0)
t-BuOH (1.0)
8
9
10
11
12
13
—
—
—
—
CH2Ph
aIsolated yield.

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1090
Yoda,Kohata,and Takabe
Table 2. SmI2-promoted desulfurization reaction of lactams (7) afteralkylation
of (6).
Yield of SmI2
7 (%)a (equiv.)
Additives
(equiv.)
Yield of
8 (%)a
Entry
n
R1
R2
1
2
2
2
0
0
0
0
0
0
0
0
0
0
0
0
CH2Ph CH2¼CHCH2
CH2Ph CH2¼CHCH2
CH2Ph CH2¼CHCH2
CH2Ph CH2¼CHCH2
CH2Ph CH2¼CHCH2
CH2Ph CH3
78
—
96
—
—
96
—
—
—
92
—
96
92
95
2.0
3.0
2.0
3.0
3.0
3.0
3.0
3.0
5.0
3.0
5.0
5.0
5.0
5.0
—
—
19
17
12
52
73
53
43
72
88
73
90
93
84
89
3
—
—
4
5
HMPA (3.0)
HMPA (3.0)
t-BuOH (1.0)
HMPA (3.0)
HMPA (3.0)
HMPA (3.0)
HMPA (3.0)
HMPA (3.0)
HMPA (3.0)
HMPA (3.0)
6
7
CH2Ph CH3
CH2Ph CH3
8
9
CH2Ph CH3
CH2Ph CH2Ph
CH2Ph CH2Ph
10
11
12
13
14
CH3
CH3
CH3
CH2¼CHCH2
CH3
CH2Ph
aIsolated yield.
Next, we examined the same type of reactions by the use of sulfur-
substituted lactams 7 prepared from 5 in a similarmanneras described
above. As shown in Table 2, the reactions with allylated N-benzyl phe-
nylsulfonyl lactam did not proceed in satisfactory yield when a small
excess of SmI2 were again used (Entries 1,2), whereas the desulfurization
reactions of phenylthio derivative changed the results and rapidly
brought about the desired product 8 in 52% yield underthe same reac-
tion conditions along with the starting lactam (Entry 4). The further
beneficial result was obtained in reaction employing HMPA as an addi-
tive (Entry 5) to afford 8 in 73% isolated yield. Furthermore, it became
apparent that this procedure was applicable for the production of a wide
range of lactams through replacement of the g-substituents togetherwith
a change of the N-functional groups. Especially, we were delighted to find
that 5 equiv. of this reagent in the presence of HMPA (3.0 equiv.) effect

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Substituted Aromatic Lactones and Lactams
1091
these reactions in excellent yield (up to 93%) to provide various types of
g- and N-substituted lactams 8 (Entries 9,11–14).
Although an in-depth mechanistic investigation of the above experi-
ments was not pursued, a tentative explanation of these results could be
possible. Thus, the presence of the nitrogen atom in the substrate would
stabilize the Sm(III) species obtained from subsequent reduction of the
desulfurization-derived benzyl radical with the excess equiv. of SmI2.
As a further illustration of the scope of the above outcome, we
turned our attention to the construction of the quaternary carbon
center via direct replacement of the sulfur substrate to alkyl groups.
The reactions of lactam 7 with haloalkane did not proceed under any
conditions even in the use of excess SmI2. When 7 was, however, in turn
treated with butanal (3.0 equiv.) in the presence of SmI2 as shown in
Table 3 (Entry 1), it afforded the desired coupling product 9 with the
crucial hydroxyalkylated quaternary carbon center (41%) accompanying
the formation of the normal desulfurized compound 8 (51%). It will be of
interest to note that enhancement of the yield was observed upon employ-
ing the sterically more hindered ketones (up to 71%), leading to the
various types of coupling products containing the continuous quaternary
carbon centers (Entries 2,3,5,6).
Table 3. SmI2-promoted coupling reactions of substituted lactams (7) with
carbonyl compounds.a
Yield of
9 (%)b
Yield of
8 (%)b
Entry
R1
R2
R3
R4
1
2
3
4
5
6
CH2Ph
CH2Ph
CH3
CH3
CH3
n-C3H1
CH3
CH3
H
41
62
47
33
71
61
51
33
51
66
25
34
CH3
CH3
H
CH2Ph
CH3
CH3
CH3
CH3
n-C3H1
CH3
CH3
CH3
n-C3H1
CH3
CH3
aAll reactions employed 3.0 equiv. of carbonyl compounds.
bIsolated yield.

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1092
Yoda,Kohata,and Takabe
In summary, we have achieved a short and easily accessible entry not
only for the preparation of a variety of substituted aromatic carbonyl
compounds but also forthe development of the coupling reaction with
several carbonyl compounds via desulfurization mediated by SmI2, lead-
ing to the continuous quaternary a-hydroxyalkylated lactams. This pro-
cedure will find more convenient alternative to existing desulfurization
reactions and proved to be a superior quaternary C–C bond formation
method.
EXPERIMENTAL
Typical experimental conditions (Entry 5 in Table 3). To a deep-blue
THF (5 mL) solution prepared from Samarium metal powder (0.228 g,
1.53 mmol) and diiodomethane (0.393 g, 1.474 mmol) underArwas
added
a solution of N-methyl-3-methyl-3-phenylthiophthalimidine
(0.079 g, 0.295 mmol) and acetone (0.051 g, 0.885 mmol) in THF (1 mL)
at 0ꢀC. After the mixture was stirred for 1 h at room temperature, it was
poured into a dilute HCl (4 mL) and extracted with ethyl acetate. The
product was chromatographed after evaporation (eluted with hexane-
ethyl acetate (1:1)) to give N-methyl-3-methyl-3-(1-methyl-1-hydro-
xyethyl)phthalimidine (0.046 g, 0.21 mmol) in 71% and N-methyl-3-
methylphthalimidine (0.012 g, 0.074 mmol) in 25% yields, respectively.
N-benzyl-3-methyl-3-(1-hydroxybutyl)phthalimidine (Entry 1 in Table
3). IR (thin film) 3255, 1661, 766, 701 cmꢁ1; 1H NMR (CDCl3) ꢀ 0.62–0.96
(t, J ¼ 6.6 Hz, 3H), 0.96–1.62 (m, 4H), 1.42 (s, 3H), 3.71 (br, 1H), 4.01 (t,
J ¼ 6.6 Hz, 1H), 4.83 (s, 2H), 7.05–7.62 (m, 8H), 7.71–8.13 (m, 1H). Anal.
calcd. forC 20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.75; H,
7.42; N, 4.39.
N-benzyl-3-methyl-3-(1-methyl-1-hydroxyethyl)phthalimidine (Entry 2
1
in Table 3). IR (thin film) 3266, 1656, 760, 705 cmꢁ1; H NMR (CDCl3)
ꢀ 0.83 (s, 3H), 1.35 (s, 3H), 1.51 (s, 3H), 2.12 (br, 1H), 4.98 (s, 2H),
7.11–7.68 (m, 8H), 7.75–7.82 (m, 1H). Anal. calcd. forC 19H21NO2: C,
77.26; H, 7.17; N, 4.74. Found: C, 77.29; H, 7.11; N, 4.71.
N-methyl-3-benzyl-3-(1-methyl-1-hydroxyethyl)phthalimidine (Entry 3
1
in Table 3). IR (thin film) 3286, 1672, 756, 698 cmꢁ1; H NMR (CDCl3)
ꢀ 1.01 (s, 3H), 1.33 (s, 3H), 2.38 (br, 1H), 3.20 (s, 3H), 3.48, 3.53 (2s, 2H),
7.48–7.05 (m, 5H), 7.15–7.81 (m, 4H). Anal. calcd. forC 19H21NO2: C,
77.26; H, 7.17; N, 4.74. Found: C, 77.38; H, 7.09; N, 4.66.
N-methyl-3-methyl-3-(1-hydroxybutyl)phthalimidine (Entry 4 in Table
3). IR (thin film) 3266, 1655, 746, 703 cmꢁ1
;
1H NMR (CDCl3)
ꢀ 0.59–0.93 (t, J ¼ 6.6 Hz, 3H), 0.96–1.75 (m, 4H), 1.36, 1.45 (2s, 3H),

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Substituted Aromatic Lactones and Lactams
1093
2.49 (br, 1H), 2.88, 3.01 (2s, 3H), 3.71 (br, 1H), 4.05 (t, J ¼ 5.6 Hz, 1H),
7.15–7.56 (m, 3H), 7.61–7.94 (m, 1H). Anal. calcd. forC 14H19NO2: C,
72.07; H, 8.21; N, 6.00. Found: C, 71.94; H, 8.19; N, 6.13.
N-methyl-3-methyl-3-(1-methyl-1-hydroxyethyl)phthalimidine (Entry 5
in Table 3). IR (thin film) 3250, 1668, 756, 700 cmꢁ1; 1H NMR (CDCl3) ꢀ
0.87 (s, 3H), 1.18 (s, 3H), 1.50 (s, 3H), 2.62 (br, 1H), 3.07 (s, 3H),
7.03–7.50 (m, 3H), 7.60–7.92 (m, 1H). Anal. calcd. forC 13H17NO2: C,
71.21; H, 7.81; N, 6.39. Found: C, 71.40; H, 7.79; N, 6.31.
N-methyl-3-methyl-3-(1-methyl-1-hydroxybutyl)phthalimidine (Entry
;
6 in Table 3). IR (thin film) 3286, 1659, 766, 699 cmꢁ1 1H NMR
(CDCl3) ꢀ 0.55–0.85 (t, J ¼ 6.6 Hz, 3H), 0.96–1.45 (m, 4H), 0.85, 1.18
(2s, 3H), 1.50 (s, 3H), 2.45 (br, 1H), 3.03 (s, 3H), 7.15–7.61 (m, 3H),
7.61–7.91 (m, 1H). Anal. calcd. forC 15H21NO2: C, 72.84; H, 8.56; N,
5.66. Found: C, 72.96; H, 8.47; N, 5.71.
ACKNOWLEDGMENTS
This work was partially supported by a Grant-in Aid (No. 13640530)
from the Ministry of Education, Science, Sports and Culture of Japan.
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Received in Japan February 18, 2002