Rational and practical synthesis of α,α-difluoro-γ- lactams

Article abstract of DOI:10.1016/j.jfluchem.2011.10.013

Treatment of N-phenyl-iododifluoroacetamide (1) with terminal alkenes (2) in the presence of Na₂S₂O₄ and NaHCO ₃ in CH₃CN/H₂O gave good yields of N-phenyl-2,2-difluoro-4-iodoalkanamide (3),

Full text of DOI:10.1016/j.jfluchem.2011.10.013

Journal of Fluorine Chemistry 133 (2012) 163–166
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Rational and practical synthesis of
a,a-difluoro-g-lactams
Bin-Hui Li a, Ke-Lai Li a,b,1, Qing-Yun Chen a,
*
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
b College of Chemistry and Chemical Engineering, Hunan University (HNU), Changsha 410082, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Treatment of N-phenyl-iododifluoroacetamide (1) with terminal alkenes (2) in the presence of Na2S2O4
and NaHCO3 in CH3CN/H2O gave good yields of N-phenyl-2,2-difluoro-4-iodoalkanamide (3), which
Received 22 June 2011
Received in revised form 16 October 2011
Accepted 19 October 2011
Available online 25 October 2011
cyclized under strong basic conditions to afford N-phenyl-a,a-difluoro-g-lactams (4). Or simply, these
lactams 4 can be directly prepared in one-pot from 1 and 2 in the presence of Na2S2O4 and NaOH.
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
N-phenyl-a,a-difluoro-g-lactam
Sulfinatodehalogenation reaction
Cyclization
1. Introduction
addition of N-phenyl-iododifluoroacetamide to alkenes could give
N-phenyl-2,2-difluoro-4-iodoalkanamide, which might undergo
Lactams and their benzo-/hetero-fused analogues represent an
important class of organic azaheterocycles for their presence in
numerous natural products and synthetic organic compounds
along with diverse bio-, physio- and pharmacological activities [1].
Introduction of a difluoromethylene group into lactams is of great
interest due to the fact that difluoromethylenation of natural
products and drugs has demonstrated significant improvements of
their activities and properties [2]. Extensive work has generated
cyclization under basic conditions to afford N-phenyl-
a,a-
difluoro- -lactams. Herein we present the results.
g
2. Results and discussion
The starting material, N-phenyl-iododifluoroacetamide (1) was
easily prepared from N-phenyl- -fluorosulfonyldifluoroacetamide
a
in 66% yield according to the literature method [5] (Scheme 1).
Then, 1 was subjected to the typical sulfinatodehalogenation [6]
conditions, i.e., 1 was treated with 1-hexene (2a) in the presence of
Na2S2O4 and NaHCO3 in a mixture solvent of CH3CN/H2O at 10–
15 8C. TLC analysis revealed that the reaction was completed
within 20 min. After work-up and purification by chromatography,
a pale yellow solid was obtained. To our delight, the solid was
characterized to be the desired N-phenyl-2,2-difluoro-4-iodo-
octanamide (3a) by its NMR, MS, IR and HRMS. Under similar
conditions, the reaction of 1 with other terminal alkenes also
proceeded smoothly to give the addition products 3b–3e in good
yields (Table 1).
several synthetic approaches to
a,a-difluoro-g-lactams [3],
including intramolecular cyclization of N-allylhalodifluoroaceta-
mides [3a] or difluoropropargyl amides [3b], the reaction of ethyl
2,2-difluoro-4-iodo-4-(trimethylsilyl)butanolate with primary
amines [3c], and the transformation of the
a-carbonyl group of
cyclic -keto amide to difluoromethylene group by utilization of
a
Deoxofluor [3d]. Each of these approaches represents an important
advance toward the objective of a general method for the synthesis
of
a,a-difluoro-g-lactams. However, they are still more or less
limited in their use by their lack of generality, poor yields, or the
difficulties in obtaining the starting materials. In light of this,
development of efficient synthetic approaches from easily
available starting materials for such fluorine-containing hetero-
cycles is still in demand.
With these N-phenyl-2,2-difluoro-4-iodo-alkanamide in hands,
we next examined their reactions under basic conditions expecting
to prepare N-phenyl-a,a-difluoro-g-lactams via intramolecular
In connection with our ongoing interest in fluoroalkylation of
organic compounds [4], we envisioned that Na2S2O4 induced
substitution reaction. As illustrated in Table 2, when 1.0 equiv. of
NaHCO3 was used, no reaction occurred (entry 1, Table 2). Even
when 6.0 equiv. of NaHCO3 was used, only a trace amount of
cyclization product 4a was observed (entry 2, Table 2). Then,
stronger bases were examined. The addition of 3.0 equiv. of K2CO3
instead of NaHCO3 led to a significant increase in the yield of 4a to
47% (entry 3, Table 2). The best result was obtained by using
1.0 equiv. NaOH in aqueous acetonitrile solution (entry 4, Table 2).
* Corresponding author. Tel.: +86 21 54925196; fax: +86 21 64166128.
E-mail address: chenqy@mail.sioc.ac.cn (Q.-Y. Chen).
1
Ke-Lai Li had ever studied in SIOC as a joint student of HNU and SIOC, and now
has been working in SIOC as a temporary scientific research member since his
graduation in March 2011.
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.10.013

164
B.-H. Li et al. / Journal of Fluorine Chemistry 133 (2012) 163–166
Scheme 1. Preparation of iododifluoroacetamide 1.
Table 1
The reaction of N-phenyl-iododifluoroacetamide with terminal alkenes.a
.
Entry
R
Product
Yield (%)b
1
2
3
4
5
1-Butyl
3a
3b
3c
3d
3e
83
84
78
75
76
Trimethylsilyl
CH2OH–
C6H5CH2–
CH3(O)COCH2–
a
Reaction conditions: 2.0 equiv. alkene, 1.2 equiv. Na2S2O4, 1.2 equiv. NaHCO3, CH3CN (5 mL), H2O (3 mL), under nitrogen, 10–15 8C, 20 min, at 2.0 mmol scale.
Isolated yields.
b
Having established a two-step procedure for 4a, and considering
that the two steps were both performed under basic conditions, we
turnedourattentiontoachieveaone-potmethodforthesynthesisof
The intermediate A abstracted iodine from RfI to afford 4-iodo-
alkanamide 3. The amide 3 could form anions B by deprotonation of
the nitrogen in the presence of strong base. Finally, the intramolec-
ular N-alkylation of intermediate B led to the formation of lactams 4.
In conclusion, a rational and practical synthetic method for N-
N-phenyl-
hexene (2a) in the presence of Na2S2O4 and NaOH in CH3CN/H2O
at 10–15 8C, and N-phenyl- -difluoro- -lactam 4a was indeed
formed in 72% yield (entry 1, Table 3). When other terminal alkenes
were used (entry 2–5, Table 3), the corresponding N-phenyl-
difluoro- -lactams 4 can also be obtained in good yields except the
a,a-difluoro-g-lactams. Thus, 1 was treated with 1-
a,a
g
phenyl-a,a-difluoro-g-lactams had been developed. A possible
mechanism for the formation of N-phenyl-2,2-difluoro-4-iodo-
alkanamides and N-phenyl-a,a-difluoro-g-lactams is proposed.
a,a-
g
one bearing a hydroxymethyl group (entry 3, Table 3). The low yield
of 4c might be attributed to the involvement of the hydroxymethyl
group in the reaction under strong basic conditions. It should be
noted that in the case of 4d, the addition of another portion of NaOH
was needed, otherwise 4d could only be produced in 36% yield, and
3d was obtained in 40% yield in the meantime (entry 4, Table 3). The
structures of these cyclization products were fully characterized.
Among them, the structure of 4e was unambiguously determined by
the X-ray crystallography (Fig. 1).
On the basis of the above experimental results together with the
relatedreports[7], a possiblemechanismfortheformationof3and 4
is proposed and depicted in Scheme 2. Initially, RfI 1 accepted one
electron from the radical anion of sulfur dioxide, which was
produced by decomposition of Na2S2O4, and dissociated to give Rfꢀ
and IÀ [8]. The Rfꢀ added to terminal alkenes to form intermediate A.
3. Experimental
3.1. General experimental procedures
Unless otherwise mentioned, solvents and regents were
commercially available and used as received. N-phenyl- -fluor-
a
osulfonyldifluoroacetamide was prepared according to the litera-
ture method. All melting points were uncorrected. IR spectra were
taken on Nicolet AV-360 spectrophotometer. 1H NMR spectra were
recorded on Bruker 300 or Mercury 300 spectrometers with Me4Si
as internal standard. 19F NMR spectra were recorded on Bruker 300
or Mercury 300 spectrometers with CFCl3 as external standard.
Mass spectra were obtained on a HP5989A spectrometer.
Table 3
One-pot synthesis of N-phenyl-a,a-difluoro-g .
-lactam derivatives.a
Table 2
Optimization of conditions for the cyclization of N-phenyl-2,2-difluoro-4-iodo-
alkanamide. .
Entry
R
Product
Yield (%)b
1
1-Butyl
4a
4b
4c
4d
4e
72
79
40
66
64
2
Trimethylsilyl
CH2OH–
Entry
Base
Equivalent
Time (h)
Yield (%)a
3
4c
5
C6H5CH2–
1
2
3
4
NaHCO3
NaHCO3
K2CO3
1.0
6.0
3.0
1.0
10
10
6
0b
Traceb
47c
92
CH3(O)COCH2–
a
Reaction conditions: 2.0 equiv. alkene, 1.5 equiv. Na2S2O4, 1.5 equiv. NaOH,
NaOH
0.5
CH3CN (5 mL), H2O (3 mL), under nitrogen, 10–15 8C, 30 min, at 1.0 mmol scale.
b
a
Isolated yields.
Isolated yields.
c
b
c
After being stirred for 30 min, another portion of NaOH (1.5 equiv.) was added
Recovery of starting material was 99%.
Recovery of starting material was 50%.
to the reaction mixture, and the stirring was continued for 30 min.

B.-H. Li et al. / Journal of Fluorine Chemistry 133 (2012) 163–166
165
EI-MS m/z (%): 297 (98.57), 170 (55.10), 120 (100.00), 77 (60.31).
HRMS calcd. for C8H6F2INO: 296.9462, found: 296.9464.
3.3. General procedure for the preparation of compounds 3
Under a nitrogen atmosphere, to a mixture of N-phenyl-
iododifluoroacetamide 1 (594 mg, 2.0 mmol), alkenes (4.0 mmol,
2.0 equiv.), H2O (3 mL), and CH3CN (5 mL) stirred magnetically at
10–15 8C was added a mixture of Na2S2O4 (418 mg, 2.4 mmol,
1.2 equiv.) and NaHCO3 (202 mg, 2.4 mmol, 1.2 equiv.). The
mixture was stirred at the same temperature for ca. 20 min until
the reaction had finished (monitored by TLC). The mixture was
poured into H2O (20 mL) and extracted with ether (3 Â 20 mL).
The combined organic layer was washed with saturated brine
and dried over anhydrous sodium sulfate. After the evaporation
of ether, the residue was purified by column chromatography to
give 3.
3.3.1. N-Phenyl-2,2-difluoro-4-iodo-octanamide (3a)
Pale yellow solid, mp: 39.2–40.8 8C. IR (KBr):
2930, 1690, 1603, 1542, 1450, 1448 cmÀ1 1H NMR (300 MHz,
CDCl3, TMS) : 8.11 (s, 1H), 7.58 (d, J = 8.1 Hz, 2H), 7.38 (t, J = 7.7 Hz,
2H), 7.21 (t, J = 7.4 Hz, 1H), 4.25 (q, J = 6.6 Hz, 1H), 2.79–3.09 (m,
2H), 1.72–1.86 (m, 2H), 1.26–1.50 (m, 4H), 0.91 (t, J = 6.9 Hz, 3H).
nmax: 3310, 2957,
.
d
Fig. 1. Top view of the X-ray crystal structure of 4e.
3.2. Preparation of N-phenyl-iododifluoroacetamide (1)
19F NMR (282 MHz, CDCl3)
À105.6 (dt, J = 258.6, 15.9 Hz, 1F). EI-MS m/z (%): 381 (3.47), 254
(100.00), 120 (31.20), 77 (26.26). HRMS calcd. for C14H18F2INO:
381.0401, found: 381.0396.
d
: À102.6 (dt, J = 258.3, 16.6 Hz, 1F),
Under
1.2 equiv.) and NaHCO3 (2.02 g, 24 mmol, 2.4 equiv.) were added
in several portions to the mixture of N-phenyl- -fluorosulfonyldi-
a nitrogen atmosphere, Na2SO3 (1.51 g, 12 mmol,
a
fluoroacetamide (2.53 g, 10 mmol) and water (40 mL) at 15–20 8C
with stirring. And the stirring was continued for 1 h at the same
temperature. Then, I2 (5.08 g, 20 mmol, 2.0 equiv.) and KI (2.49 g,
15 mmol, 1.5 equiv.) were added. The reaction mixture was heated
at 80 8C for 1 h. After being cooled to room temperature, the resulted
mixture was extracted with ether (3 Â 40 mL). The combined
organic extracts were washed with 10% Na2SO3 (30 mL), water
(3 Â 30 mL), dried over anhydrous Na2SO4, filtered, and concentrat-
ed under reduced pressure to yield the crude product, which was
purified by column chromatography to give pure N-phenyl-
iododifluoroacetamide 1 as a white solid (2.25 g, 76%).
3.3.2. N-Phenyl-2,2-difluoro-4-iodo-4-(trimethylsilyl)butanamide
(3b)
Pale yellow oil. IR (KBr):
n
max: 3320, 2955, 1695, 1602, 1541,
1448, 1252, 842 cmÀ1 1H NMR (300 MHz, CDCl3, TMS)
.
d
: 8.24 (s,
1H), 7.61 (d, J = 8.1 Hz, 2H), 7.37 (t, J = 7.7 Hz, 2H), 7.21 (t, J = 7.4 Hz,
3H), 3.11 (d, J = 11.4 Hz, 1H), 2.59–2.90 (m, 2H), 0.19 (s, 9H). 19F
NMR (282 MHz, CDCl3)
d
: À103.3 (dt, J = 267.3, 17.2 Hz, 1F),
À105.2 (dt, J = 254.6, 15.2 Hz, 1F). EI-MS m/z (%): 397 (11.05), 270
(35.68), 178 (35.62), 77 (54.15), 73 (100.00). HRMS calcd. for
C13H18F2INOSi: 397.0171, found: 397.0174.
3.3.3. N-Phenyl-2,2-difluoro-5-hydroxyl-4-iodo-pentanamide (3c)
White solid, mp: 60.4–61.9 8C. IR (KBr): max: 3323, 1686, 1600,
1536, 1449, 751 cmÀ1 1H NMR (300 MHz, CDCl3, TMS)
: 8.15 (s,
3.2.1. N-phenyl-iododifluoroacetamide (1)
n
White solid, mp: 112.0–113.6 8C. IR (KBr):
1608, 1552, 1448, 1134, 1119, 933 cmÀ1. 1H NMR (300 MHz, CDCl3,
TMS) : 8.00 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 7.8 Hz, 2H),
7.22 (t, J = 7.2 Hz, 1H). 19F NMR (282 MHz, CDCl3)
: À57.3 (s, 2F).
n
max: 3330, 1695,
.
d
1H), 7.57 (d, J = 8.1 Hz, 2H), 7.38 (t, J = 8.1 Hz, 2H), 7.21 (t, J = 7.4 Hz,
1H), 4.37 (q, J = 6.1 Hz, 1H), 3.80 (d, J = 5.4 Hz, 2H), 2.81–3.16 (m,
d
d
2H), 2.50 (s, 1H). 19F NMR (282 MHz, CDCl3)
d
: À103.3 (dt, J = 256.6,
Scheme 2. Proposed mechanisms for the formation of 3 and 4.

166
B.-H. Li et al. / Journal of Fluorine Chemistry 133 (2012) 163–166
17.3 Hz, 1F), À104.7 (dt, J = 257.7, 16.8 Hz, 1F). EI-MS m/z (%): 355
(11.97), 228 (100.00), 210 (62.49), 120 (63.91), 77 (44.71). HRMS
calcd. for C11H12F2INO2: 354.9881, found: 354.9879.
J = 270.8, 12.1 Hz, 1F), À103.0 (dt, J = 271.2, 12.6 Hz, 1F). EI-MS m/z
(%): 227 (38.42), 196 (100.00), 104 (78.04), 77 (36.11). Anal. calcd.
for C11H11F2NO2: C, 58.15; H, 4.88; N, 6.16. Found: C, 58.09; H,
4.94; N, 5.97.
3.3.4. N-Phenyl-2,2-difluoro-4-iodo-5-phenyl-pentanamide (3d)
White solid, mp: 83.1–84.5 8C. IR (KBr):
n
max: 3318, 1687, 1601,
3.4.4. N-Phenyl-
White solid, mp: 90.5–91.0 8C. IR (KBr):
1494, 1315, 1138 cmÀ1 1H NMR (300 MHz, CDCl3, TMS)
d
7.55 (m, 4H), 7.29–7.36 (m, 4H), 7.12 (d, J = 7.2 Hz, 2H), 4.43–4.53
(m, 1H), 3.15 (d, J = 13.2 Hz, 1H), 2.58 (d, J = 13.2 Hz, 1H), 2.33–2.64
g
-benzyl-
a
,
a
-difluoro-
g
-lactam (4d)
max: 2888, 1732, 1598,
: 7.47–
1539, 1448, 1180 cmÀ1. 1H NMR (300 MHz, CDCl3, TMS)
d
: 8.04 (s,
n
1H), 7.59 (d, J = 7.5 Hz, 2H), 7.30–7.42 (m, 5H), 7.20–7.25 (m, 3H),
4.40–4.45 (m, 1H), 3.19–3.34 (m, 2H), 2.85–3.11 (m, 2H). 19F NMR
.
(282 MHz, CDCl3)
J = 256.3, 16.1 Hz, 1F). EI-MS m/z (%): 415 (3.28), 288 (100), 77
d
: À101.4 (dt, J = 256.3, 16.6 Hz, 1F), À104.7 (dt,
(m, 2H). 19F NMR (282 MHz, CDCl3)
d
: À100.8 (dt, J = 270.4,
(22.59). HRMS calcd. for C17H16F2INO: 415.0245, found: 415.0247.
16.4 Hz, 1F), À105.5 (dt, J = 270.1, 14.2 Hz, 1F). EI-MS m/z (%): 287
(19.39), 196 (100.00), 104 (45.35), 77 (21.26). Anal. calcd. for
3.3.5. N-Phenyl-5-acetyloxy-2,2-difluoro-4-iodo-pentanamide (3e)
C17H15F2NO: C, 71.07; H, 5.26; N, 4.88. Found: C, 71.44; H, 5.49; N,
Pale yellow oil. IR (KBr):
n
max: 3331, 1734, 1702, 1603, 1546,
4.73.
1448, 1236 cmÀ1 1H NMR (300 MHz, CDCl3, TMS)
.
d
: 8.28 (s, 1H),
7.57 (d, J = 7.8 Hz, 2H), 7.37 (t, J = 8.0 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H),
3.4.5. N-Phenyl-
g
-acetyloxymethyl-
a
,
a
-difluoro-
g
-lactam (4e)
max: 3065, 2966,
1738, 1716, 1594, 1496, 1431, 1340, 1249 cmÀ1 1H NMR
(300 MHz, CDCl3, TMS) : 7.40–7.49 (m, 4H), 7.33 (t, J = 6.6 Hz,
1H), 4.48–4.52 (m, 1H), 4.27 (dd, J = 12, 3.3 Hz, 1H), 4.01 (dd, J = 12,
4.5 Hz, 1H), 2.72–2.91 (m, 1H), 2.49–2.64 (m, 1H), 2.00 (s, 3H). 19
NMR (282 MHz, CDCl3)
4.23–4.41 (m, 3H). 2.80–3.10 (m, 2H), 2.11 (s, 3H). 19F NMR
White solid, mp: 124.3–125.0 8C. IR (KBr): n
(282 MHz, CDCl3)
d
: À103.1 (dt, J = 260.0, 15.4 Hz, 1F), À105.4 (dt,
.
J = 260.3, 15.6 Hz, 1F). EI-MS m/z (%): 397 (14.12), 270 (100.00),
210 (85.98), 120 (70.43), 77 (32.83). HRMS calcd. for C13H14F2INO3:
396.9987, found: 396.9985.
d
F
d
: À100.6 (dtd, J = 271.0, 17.2, 4.2 Hz, 1F),
3.4. Preparation of N-phenyl-
a,
a
-difluoro-
g
-lactam derivatives
À104.0 (ddd, J = 271.5, 15.8, 9.0 Hz, 1F). EI-MS m/z (%): 269 (18.89),
196 (100.00), 104 (88.73), 77 (39.47), 43 (18.99). Anal. calcd. for
Under a nitrogen atmosphere, to a mixture of N-phenyliododi-
fluoroacetamide (297 mg, 1.0 mmol), alkenes (2.0 mmol,
C
13H13F2NO3: C, 57.99; H, 4.87; N, 5.20. Found: C, 57.85; H, 4.92; N,
5.07.
13H13F2NO3 (4e) crystallized by diffusion of petroleum ether
dichloromethane solution. Crystal data. M = 269.24,
1
2.0 equiv.), H2O (3 mL), and CH3CN (5 mL) stirred magnetically
at 10–15 8C was added a mixture of Na2S2O4 (261 mg, 1.5 mmol,
1.5 equiv.) and NaOH (60 mg, 1.5 mmol, 1.5 equiv.). The mixture
was stirred at the same temperature for ca. 30 min until the
reaction had finished (monitored by TLC). The mixture was poured
into H2O (20 mL) and extracted with ether (3 Â 20 mL). The
combined organic layer was washed with saturated brine and
dried over anhydrous sodium sulfate. After the evaporation of
ether, the residue was purified by column chromatography to give
4. The results are given in Table 3.
C
into
a
monoclinic, space group C2/c, a = 31.900(4), b = 6.0408(8),
˚
c = 12.9384(16) A,
a
= 90.00,
b
= 97.099(2),
g
= 90.008,
(mo
V = 2474.1(5) A , T = 293(2) K, Z = 8, Dc = 1.446 g cmÀ3
,
m
3
˚
Ka
) = 0.122 mmÀ1, 6473 reflections measured, 2425 unique which
were used in all calculations. R1 (all data) = 0.0593. R1 = 0.0511.
CCDC 822545.
Acknowledgements
3.4.1. N-Phenyl-
White solid, mp: 46.0–47.5 8C. IR (KBr):
2861, 1714, 1679, 1599, 1500, 1340 cmÀ1
CDCl3, TMS) : 7.39–7.48 (m, 4H), 7.28–7.33 (m, 1H), 4.19–4.24 (m,
1H), 2.70–2.87 (m, 1H), 2.26–2.42 (m, 1H), 1.67–1.79 (m, 1H),
1.22–1.45 (m, 5H), 0.85 (t, J = 6.6 Hz, 3H). 19F NMR (282 MHz,
a
,
a
-difluoro-
g
-(n-butyl)-
g
-lactam (4a)
max: 2970, 2950, 2930,
1H NMR (300 MHz,
The authors are grateful to Associate Professor Jie Sun (Shanghai
Institute of Organic Chemistry) for the measurement and analysis
of the X-ray crystal structures. We also thank the National Natural
Science Foundation of China for the financial support (Nos.
20272076, 20772146 and D20032010).
n
.
d
References
CDCl3)
d
: À101.5 (dtd, J = 266.8, 16.4, 5.6 Hz, 1F), À104.7 (ddd,
J = 268.1, 18.6, 14.4 Hz, 1F). EI-MS m/z (%): 253 (35.36), 196
(100.00), 104 (41.48), 77 (20.76). Anal. calcd. for C14H17F2NO: C,
66.39; H, 6.77; N, 5.53. Found: C, 66.34; H, 6.94; N, 5.47.
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3.4.2. N-Phenyl-
White solid, mp: 107.6–108.3 8C. IR (KBr):
2961, 1714, 1673, 1597, 1495, 1253, 1052 cmÀ1. 1H NMR (300 MHz,
a
,
a
-difluoro-
g
-trimethylsilyl-
g
-lactam (4b)
nmax: 3060, 2990,
(c) S.K. Kim, Z.F. Xie, C.S. Jun, T.H. Kwon, S.R. Ryu, K.Y. Chai, Bull. Korean Chem. Soc.
28 (2007) 2319–2323;
CDCl3, TMS) d: 7.28–7.45 (m, 5H), 3.81–3.87 (m, 1H), 2.68–2.85 (m,
1H), 2.32–2.51 (m, 1H), À0.12 (s, 9H). 19F NMR (282 MHz, CDCl3)
d:
(d) R.P. Singh, U. Majumder, J.M. Shreeve, J. Org. Chem. 66 (2001) 6263–6267.
[4] (a) Q.Y. Chen, J. Fluorine Chem. 72 (1995) 241–246;
(b) A.R. Li, Q.Y. Chen, J. Fluorine Chem. 82 (1997) 151–155;
(c) L.M. Jin, Z. Zeng, C.C. Guo, Q.Y. Chen, J. Org. Chem. 68 (2003) 3912–3917.
[5] (a) Y.F. Zhang, L. Lu, W.Y. Huang, Chin. J. Org. Chem. 9 (1989) 441–444;
(b) D.C. England, M.A. Dietrich, R.V. Lindsey, J. Am. Chem. Soc. 82 (1960) 6181–
6188.
À103.5 (ddd, J = 267.3, 16.1, 12.7 Hz, 1F), À105.2 (dt, J = 266.8,
17.8 Hz, 1F). EI-MS m/z (%): 269 (68.53), 149 (89.84), 104 (58.98), 77
(59.19), 73 (100.00). Anal. calcd. for C13H17F2NOSi: C, 57.97; H, 6.36;
N, 5.20. Found: C, 57.96; H, 6.95; N, 5.19.
[6] (a) W.Y. Huang, W. Wang, B.N. Huang, Acta Chim. Sinica 43 (1985) 409–410;
(b) W.Y. Huang, L. Lu, Y.F. Zhang, Chin. J. Chem. 8 (1990) 68–74;
(c) W.Y. Huang, L. Lu, Y.F. Zhang, Chin. J. Chem. 8 (1990) 175–181;
(d) W.Y. Huang, L. Lu, Y.F. Zhang, Chin. J. Chem. 8 (1990) 281–288;
(e) W.Y. Huang, L. Lu, Y.F. Zhang, Chin. J. Chem. 8 (1990) 350–354.
[7] W.Y. Huang, J. Fluorine Chem. 32 (1986) 179–195.
3.4.3. N-Phenyl-
White solid, mp: 78.6–79.2 8C. IR (KBr):
1708, 1675, 1599, 1496, 1426, 1018 cmÀ1
CDCl3, TMS) : 7.38–7.47 (m, 4H), 7.32 (t, J = 6.8 Hz, 1H), 4.31 (d,
J = 2.7 Hz, 1H), 3.57–3.68 (m, 2H), 2.71 (dt, J = 15.5, 6.3 Hz, 2H),
2.17 (t, J = 5.1 Hz, 1H). 19F NMR (282 MHz, CDCl3)
: À101.8 (dt,
a
,
a
-difluoro-
g
-hydroxymethyl-
max: 3298, 3068, 2972,
1H NMR (300 MHz,
g-lactam (4c)
n
.
d
[8] (a) W.Y. Huang, J. Fluorine Chem. 58 (1992) 1–8;
d
(b) Z.Y. Long, Q.Y. Chen, J. Org. Chem. 64 (1999) 4775–4782.