Palladium-Catalyzed Markovnikov-Selective Hydroselenation of N-Vinyl Lactams with Selenols Affording N,Se-Acetals

Article abstract of DOI:10.1021/acs.joc.5b02431

The highly regioselective hydroselenation of N-vinyl lactams has been revealed to successfully afford the corresponding N,Se-acetals as Markovnikov adducts. In the case of terminal N-vinyl lactams, Markovnikov-selective hydroselenation proceeds efficiently in the absence of any catalyst (or additive), owing to the acidity of the selenols. In contrast, the self-promoted hydroselenation is inefficient with internal N-vinyl lactams. In the presence of palladium diacetate (Pd(OAc)₂), however, the desired hydroselenation of internal N-vinyl lactams proceeds efficiently to afford the corresponding N,Se-acetals.

Full text of DOI:10.1021/acs.joc.5b02431

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Note
Palladium-Catalyzed Markovnikov-Selective Hydroselenation
of N-Vinyl Lactams with Selenols Affording N,Se-Acetals
Taichi Tamai, Megumi Yoshikawa, Shinya Higashimae, Akihiro Nomoto, and Akiya Ogawa
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02431 • Publication Date (Web): 30 Nov 2015
Downloaded from http://pubs.acs.org on December 1, 2015
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PalladiumꢀCatalyzed MarkovnikovꢀSelective
Hydroselenation of NꢀVinyl Lactams with Selenols
Affording N,SeꢀAcetals
Taichi Tamai, Megumi Yoshikawa, Shinya Higashimae, Akihiro Nomoto, Akiya Ogawa*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1ꢀ1
Gakuenꢀcho, Nakaku, Sakai, Osaka 599ꢀ8531, Japan
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ogawa@chem.osakafuꢀu.ac.jp
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
CORRESPONDING AUTHOR FOOTNOTE. Phone: +81ꢀ72ꢀ254ꢀ9290, fax: +81ꢀ72ꢀ254ꢀ9290, and eꢀ
mail: ogawa@chem.osakafuꢀu.ac.jp
TABLE of CONTENTS
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ABSTRACT. The highly regioselective hydroselenation of Nꢀvinyl lactams has been revealed to
successfully afford the corresponding N,Seꢀacetals as Markovnikov adducts. In the case of terminal Nꢀ
vinyl lactams, Markovnikovꢀselective hydroselenation proceeds efficiently in the absence of any catalyst
(or additive), owing to the acidity of the selenols. In contrast, the selfꢀpromoted hydroselenation is
inefficient with internal Nꢀvinyl lactams. In the presence of palladium diacetate (Pd(OAc)2), however,
the desired hydroselenation of internal Nꢀvinyl lactams proceeds efficiently to afford the corresponding
N,Seꢀacetals.
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KEYWORDS. Hydroselenation, Selenol, NꢀVinyl lactam, Selfꢀpromoted addition, Palladium catalyst
A number of organoselenium compounds serve as synthetic intermediates, bioactive compounds, and
functional materials.1 Among them, Se,Se-, O,Se-, and N,Se-acetals are excellent synthetic intermediates
as protecting groups for carbonyl and iminyl moieties, and especially, Se,Seꢀacetals have been used as
practical umpolung species.2 Seleniumꢀcontaining acetals are usually prepared by the nucleophilic
addition of selenols to carbonyl and iminyl groups. The regioselective addition of selenols to enol ethers
and enamines is a promising alternative method to synthesize acetal derivatives. Herein, we report the
Markovnikovꢀselective hydroselenation of Nꢀvinyl lactams with selenols as an alternative approach
towards N,Seꢀacetals (eq. 1).
To date, numerous regioselective addition reactions of heteroatomꢀcontaining compounds such as
boron, silicon, phosphorus, and sulfur to CꢀC unsaturated bonds have been developed, e.g., radical, ionic,
and transitionꢀmetalꢀcatalyzed additions.3 Although the addition of selenols to alkynes has been
established in acidꢀ or baseꢀassisted ionic reactions, radical reactions, and transitionꢀmetalꢀcatalyzed
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reactions, the corresponding addition to alkenes has considerable limitations.4,5,6,7 In general, the radical
addition of selenols to alkenes gives anti-Markovnikov adducts regioselectively, and limited examples
of Markovnikovꢀselective hydroselenations are known.5 Although Markovnikov adducts may be
synthesized by transitionꢀmetalꢀcatalyzed reactions, catalyst poisoning by selenols often hinders catalytic
reactions.7,8 Moreover, most known Markovnikovꢀselective hydroselenation reactions require additives,
such as Brønsted acids, to promote the addition. Very recently, we overcame similar limitation in
transitionꢀmetalꢀcatalyzed hydrothiolations by using alkenes bearing alkoxyl or amino group directly
bonded to carbonꢀcarbon double bond.9
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In this study, we found that selenols promote the hydroselenation of terminal Nꢀvinyl lactams. This
selfꢀpromoted hydroselenation requires no additives; therefore, this method exhibits high atom economy.
Furthermore, the hydroselenation of internal Nꢀvinyl lactams proceeds with excellent regioselectivity
(Markovnikovꢀselective) in the presence of palladium catalysts such as Pd(OAc)2.
First, we investigated the addition of benzeneselenol to Nꢀvinyl pyrolidone, as a manageable terminal
Nꢀvinyl lactam, without the addition of any additives (Table 1). When Nꢀvinyl pyrrolidone (1a) was
o
reacted with benzeneselenol (2a) at 45 C for 20 h in THF, the Markovnikovꢀtype adduct was obtained
regioselectively in 93% yield without formation of antiꢀMarkovnikov adduct (entry 1). When CH3CN
and toluene were used as solvents, the yield of the desired hydroselenation product decreased (entries 2
and 3). The reaction in EtOH or in the absence of solvent was also examined to produce the
corresponding adduct in good yield, respectively (entries 4 and 5). Next, we examined the effects of
reaction time and temperature (entries 6ꢀ9). Furthermore, when the reaction in the presence of pꢀTsOH
as a strong acid was conducted, the desired hydrothiolation did not proceed (entry 10). This is probably
because pꢀTsOH promoted the porimerization of Nꢀvinyl pyrrolidone. The results clearly indicated that
the optimal reaction conditions were 45 oC for 20 h in THF.
Table 1. Optimization of Hydroselenation of Terminal N-Vinyl Pyrrolidone a
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temp., °C
entry
solvent
THF
time, h
20
yield, % b
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1
2
45
45
93
60
CH3CN
20
3
4
toluene
EtOH
none
THF
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6
45
27
89
45
5
45
82
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73
7
THF
3
45
53
9
8
THF
20
20
6
reflux
r.t.
45
93
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9
10 c
THF
67
THF
trace
a
Reaction conditions: Nꢀvinyl pyrrolidone (1a, 0.5 mmol), benzeneselenol (2a, 0.5 mmol), and
b
1
c
solvent (0.3 mL). Determined by H NMR analysis. Reaction was conducted in the presence of pꢀ
TsOH as a strong acid.
Next, the hydroselenation of internal Nꢀvinyl lactams was conducted under similar reaction conditions
(in the absence of additives); however, the corresponding hydroselenation product could not be
obtained. Therefore, we examined the Pdꢀcatalyzed hydroselenation of internal Nꢀvinyl lactams (Scheme
1). When the 5 mol% of Pd(OAc)2 was used as the catalyst, the desired Markovnikov hydroselenation
proceeded very efficiently. When a lowꢀvalent palladium catalyst, Pd(PPh3)4, was employed, the
hydroselenation product was obtained in only 12% yield. This result indicated that Pd(0) was not
effective for the hydroselenation of internal Nꢀvinyl lactams. Thus, the hydroselenation was examined in
the presence of Pd(II) catalysts, such as PdCl2(PhCN)2, PdCl2(cod), and PdCl2(PPh3)2. The tested Pd(II)
complexes catalyzed the hydroselenation of internal Nꢀvinyl lactam 1b to produce Markovnikovꢀadduct
3ba in moderate to good yields.
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Scheme 1. Optimization of Hydroselenation of Internal N-Vinyl Pyrrolidone
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Next, the scope of viable Nꢀvinyl lactams was examined under the optimized reaction conditions
(Table 2). When terminal Nꢀvinyl lactams 1a and 1c were used for the hydroselenation in the absence of
a catalyst, the corresponding hydroselenation products 3aa and 3ca were obtained in 93% and 57%
yields, respectively (entries 1 and 3). In the case of Nꢀvinyl caprolactam 1c, the yield was dramatically
improved by the addition of 5 mol% of Pd(OAc)2 (entry 4). In the case of internal Nꢀvinyl lactams 1b,
1d, 1e, and 1f, the desired hydroselenation was ineffective in the absence of a catalyst (entries 5, 7, 9,
11). However, the Pd(OAc)2ꢀcatalyzed hydroselenation proceeded successfully and the corresponding
hydroselenation products were obtained in good to excellent yields (entries 6, 8, 10, 12). These results
indicated that a Pd(II) catalyst was essential for the efficient hydroselenation of internal Nꢀvinyl lactams.
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Table 2. Hydroselenation of Several N-Vinyl Lactams a
entry
1
catalyst
——
product
yield, % b
(93)
3
3aa
2
3
Pd(OAc)2
96
(57)
95
——
3ca
3ba
3da
3ea
3fa
4
Pd(OAc)2
SePh
O
5
(13)
82
——
C3H7
N
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Pd(OAc)2
7
(28)
80
——
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Pd(OAc)2
9
(7)
85
——
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12
Pd(OAc)2
SePh
O
ND
——
Ph
N
Pd(OAc)2
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a Reaction conditions: Nꢀvinyl pyrrolidone (1, 0.5 mmol), benzeneselenol (2a, 0.5 mmol), solvent (0.3
mL). b The yields in parenthesis are determined by 1H NMR analysis.
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The hydroselenation of Nꢀvinyl lactams using several selenols was performed; the results are
summarized in Table 3. Recently, we developed a convenient method to prepare areneselenols by the
reduction of the corresponding diaryl diselenides with diphenylphospine oxide. In general, selenols are
airꢀsensitive and foulꢀsmelling, and therefore, in situ generation and direct use are desired.10 By using
this method, the hydroselenation of Nꢀvinyl pyrrolidone with various areneselenols in the absence of a
Pd catalyst was successfully accomplished, as shown in Table 3. Diaryl diselenides bearing either
electronꢀdonating group such as pꢀmethoxy or ꢀwithdrawing groups such as mꢀmethoxy, chloro, fluoro,
and trifluoromethyl moieties, afforded the corresponding hydroselenation products 3ab, 3ac, 3ad, 3ae,
3af, 3ag, and 3ah, respectively (entries 2−8). In the case of dinaphthyl diselenide, the desired
hydroselenation product 3ai was obtained in a moderate yield (entry 9). When dibenzyl diselenide as an
aliphatic organoselenide was used for the hydroselenation, the corresponding hydroselenation product
3aj was obtained in 16% yield (entry 10).
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Table 3. Self-Promoted Hydroselenation of N-Vinyl Lactams Using Several Diselenides a
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entry
1
product
yield, %
94
(RSe)2, 4
3aa
4a
4b
3ab
3ac
3ad
3ae
3af
2
3
4
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79
85
70
64
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MeO
Se
2
4c
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F
F
O
O
N
Se
Se
F
Se
N
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3ag
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4g
F3C
Se
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Reaction conditions: Nꢀvinyl pyrrolidone (1a, 0.25 mmol), diselenide (4, 0.25 mmol), THF (0.15
mL), diphenylphosphine oxide (0.3 mmol), 45 °C, 20 h.
The Pdꢀcatalyzed hydroselenation of Nꢀvinyl pyrroridone 1a using diphenyl diselenides and
diphenylphosphine oxide was carried out (Scheme 2). When dinaphthyl diselenide 4i and dibenzyl
diselenide 4j were employed, the yields of the desired hydroselenation products, 3ai and 3aj, were
dramatically improved. The results clearly indicated that the palladium diacetateꢀcatalyzed
hydroselenation in the presence of diselenides and diphenylphosphine oxide could serve as a convenient
tool to synthesize N,Seꢀacetal derivatives.
Scheme 2. Pd-Catalyzed Hydroselenation of Terminal N-Vinyl Pyrolidone Using Diselenides
Finally, the hydroselenation of Nꢀvinyl lactam was evaluated in the large scale reaction using 0.39 g of
o
the Nꢀvinyl pyrrolidone. The reaction was completed in 48 h at 45 C and 92% of the isolated yield of
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the hydroselenation product was obtained selectively (Scheme 3). These N,Seꢀacetal derivatives can be
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transformed into the corresponding aldehydes under the radical reaction.2f
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Scheme 3. Hydroselenation of NꢀVinyl Pyrrolidone with Benzeneselenol in the Large Scale
A plausible reaction pathway for the present hydroselenation of Nꢀvinyl lactams is shown in Scheme
4. In the absence of the Pdꢀcatalyst, firstly, the terminal Nꢀvinyl lactam is easily protonated by selenol.
Then, the generated cation of terminal Nꢀvinyl lactam is stabilized by electron donation from nitrogen
atom. Finally, selenol attacks the cation of terminal Nꢀvinyl lactam to give the Markovnikovꢀtype
hydroselenation product regioselectively. In the case of the Pdꢀcatalyzed hydroselenation, the Pd(OAc)2
catalyst initially reacts with selenol to form Pd selenide complex A . Then, Nꢀvinyl lactam coordinates to
Pd selenide complex A, providing Pd selenideꢀalkene complex B, where heteroatoms might coordinate
to palladium, thereby stabilizing complex B. Subsequent selenopalladation takes place regioselectively
to generate palladium intermediate C. Protonation of palladium intermediate C with the selenol provides
the Markovnikov hydroselenation product regioselectively, with regeneration of Pd selenide complex A.
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Scheme 4. A Possible Reaction Pathway for Hydroselenation of N-Vinyl Lactams
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In conclusion, the highly selective hydroselenation of Nꢀvinyl lactams to produce N,Seꢀacetal
derivatives was developed. The hydroselenation of terminal Nꢀvinyl lactams proceeded smoothly to give
Markovnikovꢀtype adducts selectively. Palladium(II) diacetate catalyzed the hydroselenation of internal
Nꢀvinyl lactams, despite the inefficiency of the selfꢀpromoted hydroselenation. Furthermore,
Markovnikovꢀselective hydroselenation was demonstrated using a series of areneselenols, which were
generated in situ from the corresponding diselenides and diphenyl phosphine oxide.
Experimental Section
General Information.
Unless otherwise stated, all starting materials and catalysts were purchased form commercial sources
and used without further purification. The following substrates were prepared by using dehydrative
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condensation of pyrrolidinone and the corresponding aldehyde with pꢀTsOH: (E)ꢀ1ꢀ(1ꢀpentenyl)ꢀ2ꢀ
pyrrolidinone, (E)ꢀ1ꢀ(3ꢀphenylꢀ1ꢀpropenyl)ꢀ2ꢀpyrrolidinone, (E)ꢀ1ꢀ(3,3ꢀdimethylꢀ1ꢀbutenyl)ꢀ2ꢀ
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pyrrolidinone, (E)ꢀ1ꢀstyrylꢀ2ꢀpyrrolidinone.11 The all diorganyl diselenides were synthesized according
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to the literature.12 THF as solvent was used after distillation from CaH2. H NMR spectra (400 MHz),
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13C NMR spectra (100 MHz) were taken in CDCl3 with Me4Si as an internal standard. 19F NMR spectra
(373 MHz) were taken in CDCl3 with CFCl3 as an external standard. 77Se NMR spectra (75 MHz) were
taken in CDCl3 with Me2Se as an external standard. Chemical shifts in 1H NMR were measured relative
to CDCl3 and converted to δ (Me4Si) values by using δ (CDCl3) 7.26 ppm. Chemical shifts in 13C NMR
were measured relative to CDCl3 and converted to δ (Me4Si) values by using δ (CDCl3) 77.00 ppm. IR
spectra were reported in wave numbers (cmꢀ1). ESI and EI mass spectra were obtained by employing
double focusing mass spectrometers.
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General Procedure for Self-Promoted Hydroselenation of N-Vinyl Lactams.
In a twoꢀnecked 10 mL flask with a magnetic stirring bar under N2 atmosphere were placed freshly
distilled THF (0.3 mL), Nꢀvinyl lactam (0.5 mmol) and selenol (0.5 mmol). The reaction was conducted
at 45 oC for 20 h, and then the resulting solution was concentrated in vacuo. The product was purified by
preparative TLC (silica gel, eluent: hexane; AcOEt = 2:1) to afford the hydroselenation product.
General Procedure for Pd-Catalyzed Hydroselenation of N-Vinyl Lactams.
In a twoꢀnecked 10 mL flask with a magnetic stirring bar under N2 atmosphere were placed Pd(OAc)2
(5.6 mg, 0.025 mmol), freshly distilled THF (0.3 mL), Nꢀvinyl lactam (0.5 mmol), and selenol (0.5
mmol), in that order. The reaction was conducted at 45 oC for 20 h, and then the resulting solution was
filtered through Celite with ethyl acetate as an eluent. Concentration in vacuo, and purification by
preparative TLC (silica gel, eluent: hexane; AcOEt = 2:1) provided the hydroselenation product.
General Procedure for Pd-Catalyzed Hydroselenation of N-Vinyl Lactam by Using Selenols
Generated from Diselenides.
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In a twoꢀnecked 10 mL flask with a magnetic stirring bar under N2 atmosphere were placed
diphenylphosphine oxide (60.7 mg, 0.3 mmol), freshly distilled THF (0.15 mL), diselenide (0.25 mmol),
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6
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and Nꢀvinyl lactam (0.25 mmol). The reaction was conducted at 45 C for 20 h, and then the resulting
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solution was filtered through Celite with ethyl acetate as an eluent. Concentration in vacuo, and
purification by preparative TLC (silica gel, eluent: hexane; AcOEt = 2:1) provided the hydroselenation
product.
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1-[(1-Phenylseleno)ethyl]-2-pyrrolidinone (3aa):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (53.2 ꢁL, 0.5 mmol) and benzeneselenol
(53.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed hydroselenation of Nꢀvinyl lactam.
1
Isolated as a pale yellow oil (128.9 mg, 96%); H NMR (400 MHz, CDCl3, ppm) δ 1.57 (d, J = 6.9 Hz,
3H), 1.69−1.80 (m, 1H), 1.85−1.94 (m, 1H), 1.96−2.05 (m, 1H), 2.18−2.27 (m, 1H), 3.29−3.35 (m, 1H),
3.48−3.54 (m, 1H), 6.04 (q, J = 6.9 Hz, 1H), 7.22−7.30 (m, 3H), 7.54−7.56 (m, 2H); 13C{1H} NMR
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(100 MHz, CDCl3, ppm) δ 17.3, 19.8, 30.8, 42.0, 49.4, 127.9, 128.6 (overlap), 135.3, 173.9; Se NMR
(75 MHz, CDCl3, ppm) δ 409.7; IR (NaCl) 3510, 3055, 2976, 2879, 1696, 1576, 1477, 1410, 1352,
1283, 1184, 1021, 999, 952, 845, 740, 692 cmꢀ1; HRMS (EI) Calcd for C12H15NOSe [M]+: 269.0319,
Found: 269.0324.
1-[(1-Phenylseleno)pentyl]-2-pyrrolidinone (3ba):
This compound was prepared from 1ꢀ(1ꢀpentenyl)ꢀ2ꢀpyrrolidinone (76.6 mg, 0.5 mmol) and
benzenethiol (51.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed hydrothiolation of Nꢀ
vinyl lactam. Isolated as a yellow oil (127.6 mg, 82%); 1H NMR (400 MHz, CDCl3, ppm) δ 0.88 (t, J =
6.9 Hz, 3H), 1.24−1.37 (m, 4H), 1.58−1.75 (m, 1H), 1.76−2.02 (m, 4H), 2.18−2.26 (m, 1H), 3.20−3.26
(m, 1H), 3.46−3.52 (m, 1H), 5.91 (dd, J = 6.3 Hz, 9.1 Hz, 1H), 7.21−7.27 (m, 3H), 7.53−7.55 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 13.7, 17.4, 21.8, 29.0, 30.8, 33.2, 42.1, 54.5, 127.8, 128.6
(overlap), 135.3, 174.5; 77Se NMR (75 MHz, CDCl3, ppm) δ 391.4; IR (NaCl) 3472, 3061, 2956, 2930,
2871, 1685, 1577, 1476, 1410, 1363, 1265, 1160, 1112, 1072, 1022, 923, 843, 741, 692 cmꢀ1; HRMS
(ESI) Calcd for C15H21NONaSe [M+Na]+: 334.0686, Found: 334.0681.
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1-(1-Phenylseleno)ethyl-2-caprolactam (3ca):
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This compound was prepared from 1ꢀvinylꢀ2ꢀcaprolactam (69.6 mg, 0.5 mmol) and benzeneselenol
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(53.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed hydroselenation of Nꢀvinyl lactam.
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Isolated as a pale yellow oil (140.7 mg, 95%); H NMR (400 MHz, CDCl3, ppm) δ 1.42−1.71 (m, 6H),
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1.52 (d, J = 6.9 Hz, 3H), 2.26−2.41 (m, 2H), 3.26−3.28 (m, 1H), 3.42−3.48 (m, 1H), 6.62 (q, J = 6.9 Hz,
1H), 7.22−7.26 (m, 3H), 7.49−7.53 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 20.0, 23.1, 28.9,
29.7, 37.2, 43.9, 52.4, 127.4, 128.8, 128.9, 134.1, 175.3; 77Se NMR (75 MHz, CDCl3, ppm) δ 408.3; IR
(NaCl) 3515, 3049, 2928, 2855, 1642, 1476, 1437, 1410, 1363, 1308, 1259, 1226, 1193, 1144, 1082,
1022, 976, 928, 885, 846, 739, 691 cmꢀ1; HRMS (ESI) Calcd for C14H19NONaSe [M+Na]+: 320.0530,
Found: 320.0534.
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1-[3-Phenyl-(1-phenylseleno)propyl]-2-pyrrolidinone (3da):
This compound was prepared from 1ꢀ(3ꢀPhenylꢀ1ꢀpropenyl)ꢀ2ꢀpyrrolidinone (112 mg, 0.5 mmol) and
benzeneselenol (53.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed hydroselenation of
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Nꢀvinyl lactam. Isolated as a yellow oil (143.3 mg, 80%); H NMR (400 MHz, CDCl3, ppm) δ
1.60−1.83 (m, 2H), 1.93−2.04 (m, 1H), 2.13−2.23 (m, 3H), 2.56−2.63 (m, 1H), 2.68−2.76 (m, 1H),
3.14−3.20 (m, 1H), 3.44−3.50 (m, 1H), 5.97 (dd, J = 6.3 Hz, 8.6 Hz, 1H), 7.15−7.29 (m, 8H), 7.54−7.55
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(m, 2H); C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.4, 31.0, 33.7, 35.3, 42.4, 54.5, 126.1, 127.7,
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128.0, 128.3, 128.4, 128.8, 135.5, 140.4, 174.7; Se NMR (75 MHz, CDCl3, ppm) δ 394.7; IR (NaCl)
3500, 3062, 3018, 2938, 2878, 1684, 1602, 1496, 1490, 1476, 1437, 1409, 1361, 1283, 1265, 1222,
1071, 1022, 996, 907, 843, 741, 700 cmꢀ1; HRMS (ESI) Calcd for C19H21NONaSe [M+Na]+: 382.0686,
Found: 382.0684.
1-[3,3-Dimethyl-(1-Phenylseleno)butyl]-2-pyrrolidinone (3ea):
This compound was prepared from 1ꢀ(3,3ꢀdimethylꢀ1ꢀbutenyl)ꢀ2ꢀpyrrolidinone (83.6 mg, 0.5 mmol)
and benzeneselenol (53.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed
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hydroselenation of Nꢀvinyl lactam. Isolated as a yellow oil (138.2 mg, 85%); H NMR (400 MHz,
CDCl3, ppm) δ 0.93 (s, 9H), 1.54−1.65 (m, 2H), 1.77−1.94 (m, 3H), 2.08−2.16 (m, 1H ), 3.29−3.35 (m,
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1H), 3.45−3.51 (m, 1H), 6.19 (dd, J = 2.7 Hz, 10.9 Hz, 1H), 7.22−7.30 (m, 3H), 7.54−7.56 (m, 2H);
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13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 29.2, 31.1, 31.8, 42.2, 45.4, 52.1, 128.0, 128.2, 128.7,
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135.7, 174.3; Se NMR (75 MHz, CDCl3, ppm) δ 405.3; IR (NaCl) 3512, 3057, 2952, 2906, 1692,
1575, 1476, 1437, 1410, 1366, 1283, 1265, 1147, 1069, 891, 843, 739, 691 cmꢀ1; HRMS (ESI) Calcd for
C16H23NONaSe [M+Na]+: 348.0843, Found: 348.0848.
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1-[2-Phenyl-(1-phenylseleno)ethyl]-2-pyrrolidinone (3fa):
This compound was prepared from 1ꢀstyrylꢀ2ꢀpyrrolidinone (93.5 mg, 0.5 mmol) and benzeneselenol
(53.1 ꢁL, 0.5 mmol) following the general procedure of Pdꢀcatalyzed hydroselenation of Nꢀvinyl lactam.
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Isolated as a yellow oil (86.1 mg, 50%); H NMR (400 MHz, CDCl3, ppm) δ 1.59−1.81 (m, 2H),
1.86−1.94 (m, 1H), 2.02−2.10 (m, 1H), 3.10−3.16 (m, 1H), 3.20−3.30 (m, 2H), 3.47−3.53 (m, 1H), 6.22
(dd, J = 6.8 Hz, 9.5 Hz, 1H), 7.20−7.30 (m, 8H), 7.54−7.56 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3,
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ppm) δ 17.5, 30.8, 39.8, 42.6, 54.7, 126.9, 127.7, 128.0, 128.5, 128.8, 129.1, 135.6, 136.9, 174.5; Se
NMR (75 MHz, CDCl3, ppm) δ 396.1; IR (NaCl) 3491, 3058, 3027, 2975, 1681, 1577, 1497, 1476,
1455, 1409, 1284, 1266, 1155, 1071, 1021, 984, 928, 845, 741, 693 cmꢀ1; HRMS (ESI) Calcd for
C18H19NONaSe [M+Na]+: 368.0530, Found: 368.0536.
1-{[1-(p-Methoxyphenyl)seleno]ethyl}-2-pyrrolidinone (3ab):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(4ꢀ
methoxyphenyl) diselenide (93.0 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol)
following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from
diselenides. Isolated as a pale yellow oil (58.8 mg, 79%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.55 (d, J
= 7.3 Hz, 3H), 1.74−1.85 (m, 1H), 1.88−2.07 (m, 2H), 2.20−2.28 (m, 1H), 3.30−3.36 (m, 1H),
3.51−3.57 (m, 1H), 3.78 (s, 3H), 5.95 (q, J = 7.3 Hz, 1H), 6.77−6.81 (m, 2H), 7.46−7.49 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 19.8, 31.1, 42.1, 49.7, 55.2, 114.4, 118.2, 137.7, 159.9,
174.1; 77Se NMR (75 MHz, CDCl3, ppm) δ 394.6; IR (NaCl) 3466, 3058, 2980, 2848, 1685, 1590, 1570,
1461, 1440, 1377, 1286, 1244, 1181, 1130, 1095, 1022, 998, 803, 753, 730, 698 cmꢀ1; HRMS (ESI)
Calcd for C13H17NO2NaSe [M+Na]+: 322.0322, Found: 322.0323.
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1-{[1-(m-Methoxyphenyl)seleno]ethyl}-2-pyrrolidinone (3ac):
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This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(3ꢀ
methoxyphenyl) diselenide (93.1 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol)
following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from
diselenides. Isolated as a pale yellow oil (63.6 mg, 85%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.59 (d, J
= 7.3 Hz, 3H), 1.72−1.83 (m, 1H), 1.87−1.98 (m, 1H), 2.02−2.11 (m, 1H), 2.22−2.31 (m, 1H),
3.31−3.37 (m, 1H), 3.49−3.55 (m, 1H), 3.79 (s, 3H), 6.08 (q, J = 7.3 Hz, 1H), 6.80−6.82 (m, 1H),
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7.11−7.18 (m, 3H); C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 20.0, 31.1, 42.2, 49.5, 55.3, 114.1,
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119.9, 127.0, 129.1, 129.5, 159.5, 174.1; Se NMR (75 MHz, CDCl3, ppm) δ 414.0; IR (NaCl) 3490,
3062, 2963, 2828, 1685, 1586, 1573, 1476, 1412, 1353, 1312, 1283, 1245, 1228, 1184, 1095, 1037, 991,
953, 840, 780, 689 cmꢀ1; HRMS (ESI) Calcd for C13H17NO2NaSe [M+Na]+: 322.0322, Found: 322.0326.
1-{[1-(p-Chlorophenyl)seleno]ethyl}-2-pyrrolidinone (3ad):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(4ꢀ
chlorophenyl) diselenide (96.6 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol)
following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from
diselenides. Isolated as a pale yellow oil (53.0 mg, 70%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.58 (d, J
= 6.8 Hz, 3H), 1.72−1.86 (m, 1H), 1.90−2.00 (m, 1H), 2.03−2.12 (m, 1H), 2.23−2.32 (m, 1H),
3.32−3.38 (m, 1H), 3.47−3.53 (m, 1H), 6.05 (q, J = 6.9 Hz, 1H), 7.21−7.23 (m, 2H), 7.47−7.49 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 19.9, 31.0, 42.1, 49.9, 126.3, 129.0, 134.3, 136.6, 174.2;
77Se NMR (75 MHz, CDCl3, ppm) δ 406.0; IR (NaCl) 3485, 3055, 2976, 2880, 1693, 1472, 1410, 1352,
1267, 1185, 1089, 1053, 1011, 953, 816, 730, 743 cmꢀ1; HRMS (ESI) Calcd for C12H14NONaClSe
[M+Na]+: 325.9827, Found: 325.9823.
1-{[1-(p-Fluorophenyl)seleno]ethyl}-2-pyrrolidinone (3ae):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(4ꢀ
fluorophenyl) diselenide (87.0 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol)
following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from
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diselenides. Isolated as a pale yellow oil (91.4mg, 64%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.57 (d, J
= 6.8 Hz, 3H), 1.72−2.10 (m, 3H), 2.22−2.30 (m, 1H), 3.31−3.37 (m, 1H), 3.49−3.55 (m, 1H), 6.01 (q, J
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= 6.8 Hz, 1H), 6.92−6.98 (m, 2H), 7.51−7.55 (m, 2H); C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5,
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19.9, 31.0, 42.1, 50.0, 116.0 (d, JCꢀF = 21.0 Hz), 122.7 (d, JCꢀF = 2.9 Hz), 137.8 (d, JCꢀF = 8.6 Hz), 162.9
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(d, JCꢀF = 248.0 Hz), 174.1; 19F NMR (373 MHz, CDCl3, ppm) δ ꢀ112.8; Se NMR (75 MHz, CDCl3,
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ppm) δ 402.4; IR (NaCl) 3466, 2979, 2889, 1685, 1583, 1486, 1458, 1412, 1285, 1268, 1223, 1184,
1157, 1089, 1012, 828, 743 cmꢀ1; HRMS (ESI) Calcd for C12H14NOFNaSe [M+Na]+: 310.0122, Found:
310.0125.
1-{[1-(m-Fluorophenyl)seleno]ethyl}-2-pyrrolidinone (3af):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(3ꢀ
fluorophenyl) diselenide (87.1 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol)
following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from
diselenides. Isolated as a pale yellow oil (50.8 mg, 71%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.59 (d, J
= 6.8 Hz, 3H), 1.78−1.89 (m, 1H), 1.91−2.02 (m, 1H), 2.06−2.15 (m, 1H) , 2.24−2.33 (m, 1H),
3.30−3.39 (m, 1H), 3.50−3.56 (m, 1H), 6.07 (q, J = 6.8 Hz, 1H), 6.96−7.01 (m, 1H), 7.20−7.35 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 20.0, 31.1, 42.2, 50.1, 115.1 (d, JCꢀF = 21.0 Hz), 121.9
(d, JCꢀF = 21.0 Hz), 129.7 (d, JCꢀF = 6.7 Hz), 130.1 (d, JCꢀF = 7.6 Hz), 130.9 (d, JCꢀF = 2.9 Hz), 162.2 (d,
J
CꢀF = 250 Hz), 174.2; 19F NMR (373 MHz, CDCl3, ppm) δ ꢀ111.9; 77Se NMR (75 MHz, CDCl3, ppm) δ
418.2; IR (NaCl) 3491, 3068, 2977, 2881, 1693, 1591, 1471, 1411, 1352, 1284, 1263, 1210, 1185, 1053,
1000, 954, 858, 782, 743, 682 cmꢀ1; HRMS (ESI) Calcd for C12H14NOFNaSe [M+Na]+: 310.0122,
Found: 310.0130.
1-{[1-(p-Trifluoromethylphenyl)seleno]ethyl}-2-pyrrolidinone (3ag):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(4ꢀ
trifluoromethylphenyl) diselenide (112.0 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3
mmol) following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated
from diselenides. Isolated as a pale yellow oil (82.2 mg, 98%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.62
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(d, J = 7.3 Hz, 3H), 1.74−1.85 (m, 1H), 1.91−2.02 (m, 1H), 2.05−2.13 (m, 1H), 2.26−2.34 (m, 1H),
3.34−3.40 (m, 1H), 3.46−3.52 (m, 1H), 6.17 (q, J = 7.3 Hz, 1H), 7.48−7.50 (m, 2H), 7.64−7.66 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.5, 20.1, 31.1, 42.3, 49.8, 124.0 (q, JCꢀF = 272.6 Hz), 125.6
(q, JCꢀF = 3.8 Hz), 129.7 (d, JCꢀF = 33.4 Hz), 133.6, 134.3, 174.3; 19F NMR (373 MHz, CDCl3, ppm) δ ꢀ
62.6; 77Se NMR (75 MHz, CDCl3, ppm) δ 416.1; IR (NaCl) 3491, 3068, 2929, 2882, 1672, 1601, 1490,
1459, 1399, 1324, 1269, 1163, 1110, 1078, 1057, 1014, 954, 831, 775, 744 cmꢀ1; HRMS (ESI) Calcd for
C13H14NOF3NaSe [M+Na]+: 360.0090, Found: 360.0091.
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1-{[1-(m-Trifluoromethylphenyl)seleno]ethyl}-2-pyrrolidinone (3ah):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.5 mmol) and bis(3ꢀ
trifluoromethylphenyl) diselenide (112.0 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3
mmol) following the general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated
from diselenides. Isolated as a pale yellow oil (66.5 mg, 79%); 1H NMR (400 MHz, CDCl3, ppm) δ 1.60
(d, J = 7.3 Hz, 3H), 1.76−1.87 (m, 1H), 1.92−2.09 (m, 2H), 2.22−2.31 (m, 1H), 3.33−3.39 (m, 1H),
3.51−3.57 (m, 1H), 6.09 (q, J = 7.3 Hz, 1H), 7.37−7.41 (m, 1H), 7.53−7.55 (m, 1H), 7.76−7.81 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.3, 19.9, 30.9, 42.0, 50.4, 123.6 (q, JCꢀF = 271.8 Hz), 124.7
(q, JCꢀF = 3.8 Hz), 129.2, 131.0 (q, JCꢀF = 33.4 Hz), 131.8 (q, JCꢀF = 2.9 Hz), 138.9, 174.1; 19F NMR (373
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MHz, CDCl3, ppm) δ ꢀ62.6; Se NMR (75 MHz, CDCl3, ppm) δ 417.0; IR (NaCl) 3490, 3062, 2988,
2889, 1694, 1495, 1458, 1414, 1322, 1271, 1165, 1126, 1098, 1069, 993, 895, 798, 695 cmꢀ1; HRMS
(ESI) Calcd for C13H14NOF3NaSe [M+Na]+: 360.0090, Found: 360.0091.
1-{[1-(1-Naphthyl)seleno]ethyl}-2-pyrrolidinone (3ai):
This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(1ꢀnaphthyl)
diselenide (103.1 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol) following the
general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from diselenides.
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Isolated as a pale yellow oil (23.8 mg, 30%); H NMR (400 MHz, CDCl3, ppm) δ 1.49−1.64 (m, 1H),
1.61 (d, J = 6.8 Hz, 3H), 1.75−1.86 (m, 2H), 2.07−2.16 (m, 1H), 3.25−3.31 (m, 1H), 3.43−3.49 (m, 1H),
6.03 (q, J = 6.8 Hz, 1H), 7.35−7.39 (m, 1H), 7.47−7.59 (m, 2H), 7.80−7.90 (m, 3H), 8.49−8.51 (m, 1H);
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13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.3, 20.2, 30.8, 42.4, 50.4, 125.6, 126.1, 126.7, 127.9, 128.0,
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128.6, 129.5, 133.8, 135.2, 135.9, 173.9; Se NMR (75 MHz, CDCl3, ppm) δ 339.8; IR (NaCl) 3473,
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3051, 2964, 2881, 1681, 1587, 1557, 1500, 1456, 1411, 1374, 1313, 1269, 1182, 1099, 1020, 957, 798,
771 cmꢀ1; HRMS (ESI) Calcd for C16H17NONaSe [M+Na]+: 342.0373, Found: 342.0380.
1-{[(Phenylmethylseleno)ethyl]}-2-pyrrolidinone (3aj):
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This compound was prepared from 1ꢀvinylꢀ2ꢀpyrrolidinone (26.6 ꢁL, 0.25 mmol) and bis(phenylmethyl)
diselenide (85.0 mg, 0.25 mmol) and diphenylphosphine oxide (60.7 mg, 0.3 mmol) following the
general procedure of hydroselenation of Nꢀvinyl lactam by using selenols generated from diselenides.
1
Isolated as a pale yellow oil (11.1 mg, 16%); H NMR (400 MHz, CDCl3, ppm) δ 1.47 (d, J = 6.9 Hz,
3H), 1.57−1.68 (m, 1H), 1.84−1.95 (m, 1H), 2.15−2.24 (m, 1H), 2.28−2.37 (m, 1H), 3.22−3.28 (m, 1H),
3.38−3.44 (m, 1H), 3.75 (d, J = 12.7 Hz, 1H), 3.86 (d, J = 12. Hz, 1H), 5.91 (q, J = 6.9 Hz, 1H),
7.17−7.20 (m, 1H), 7.25−7.34 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 17.3, 20.3, 28.0, 31.5,
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42.0, 47.0, 125.5, 126.6, 128.4, 128.7, 174.4; Se NMR (75 MHz, CDCl3, ppm) δ 352.9; IR (NaCl)
3478, 3024, 2975, 2926, 1685, 1494, 1452, 1412, 1350, 1313, 1268, 1178, 1096, 1054, 1029, 956, 759,
730 cmꢀ1; HRMS (ESI) Calcd for C13H17NONaSe [M+Na]+: 306.0373, Found: 306.0375.
ACKNOWLEDGMENT. This work was supported by a GrantꢀinꢀAid for Scientific Research for
JSPS Fellows (1381002900). T.T. thanks the Japan Society for the Promotion of Science for the
Research Fellowship for Young Scientists.
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Supporting Information Available: H NMR, C NMR, F NMR, and Se NMR spectra of all
compounds. This material is available free of charge via the Internet at http://pubs.acs.org.
REFERENCES and FOOTNOTE.
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