Preparation of SF5 aromatics by vicarious nucleophilic substitution reactions of nitro(pentafluorosulfanyl)benzenes with carbanions

Article abstract of DOI:10.1021/jo200618p

Vicarious nucleophilic substitutions (VNS) of hydrogen in 1-nitro-4-(pentafluorosulfanyl)benzene with carbanions provide 2-substituted 1-nitro-4-(pentafluorosulfanyl)benzenes in good to high yields. VNS of 1-nitro-3-(pentafluorosulfanyl)benzene gives a mi

Full text of DOI:10.1021/jo200618p

NOTE
pubs.acs.org/joc
Preparation of SF5 Aromatics by Vicarious Nucleophilic Substitution
Reactions of Nitro(pentafluorosulfanyl)benzenes with Carbanions
Petr Beier, Tereza Pastꢀyꢁríkovꢀa, and George Iakobson
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nꢀam. 2, 166 10 Prague,
Czech Republic
S Supporting Information
b
ABSTRACT: Vicarious nucleophilic substitutions (VNS) of
hydrogen in 1-nitro-4-(pentafluorosulfanyl)benzene with carba-
nions provide 2-substituted 1-nitro-4-(pentafluorosulfanyl)-
benzenes in good to high yields. VNS of 1-nitro-3-(pentafluo-
rosulfanyl)benzene gives a mixture of 6- and 4-substituted
1-nitro-3-(pentafluorosulfanyl)benzenes in 85:15 to >98:2 ratio
and good to high yields. In basic media, the VNS reactions lead to
the formation of carbanions that can be alkylated by alkyl halides
affording the corresponding alkylated products in moderate
yields. Transformation of primary products to substituted
(pentafluorosulfanyl)anilines and 3- or 4-substituted (penta-
fluorosulfanyl)benzenes is also described.
he introduction of a strongly electron-withdrawing and
highly lipophilic pentafluorosulfanyl (SF5) group into
with alkoxides and thiolates.7 This method provides straightforward
access to substituted 4- and 3-(pentafluorosulfanyl)benzenes.
Vicarious nucleophilic substitution of hydrogen (VNS) is a
process that has been known for more than 30 years.8 It is a
reaction of electron-deficient aromatic or heteroaromatic sys-
tems with a nucleophile, having a leaving group at the nucleo-
philic center. In VNS reactions, the aromatic hydrogen is
substituted for the nucleophile, with concomitant departure of
the leaving group. The VNS reaction has been studied mainly on
nitrobenzene derivatives and represents a good method for
introducing carbon, oxygen, and nitrogen functional groups into
aromatic systems. With the aim of providing a new route to
obtain functionalized aromatic intermediates containing the SF5
group, we began to investigate nucleophilic aromatic substitution
for hydrogen (rather than the nitro group), starting from nitro-
(pentafluorosulfanyl)benzenes. Here, we report our findings
concerning VNS reactions starting from 1 and 2 using carbon
nucleophiles.
At first, we explored the reaction of 1 with chloromethyl
phenyl sulfone (3a) in the presence of excess base, KOH, in
DMSO or t-BuOK in DMF, according to Makosza and co-
workers.9 We found t-BuOK/DMF to be a better base system in
terms of reaction yield and ease of product isolation. The reaction
was finished in less than 30 min at ꢀ40 °C, providing 1-nitro-
2-((phenylsulfonyl)methyl)-4-(pentafluorosufanyl)benzene
(4a) in 84% yield (Table 1, entry 1). Typically, dropwise addition
of a solution of 1 and 3a (1 equiv) in DMF to a cooled solution of
t-BuOK (3ꢀ4 equiv) in DMF resulted in the formation of a deep
T
organic molecules can dramatically alter their properties. The SF5
group is highly hydrolytically stable, and in recent years, increas-
ing numbers of publications (mostly patents) have appeared
describing a variety of applications for this class of compounds,
including liquid crystals, energetic materials, advanced polymer
materials, agrochemicals, and even pharmaceuticals.1,2 However,
a general lack of synthetic methodologies and inaccessibility of
basic building blocks for the synthesis of SF5-containing com-
pounds are the main constraints to broader utilization of these
compounds. For SF5 benzenes, there are two main synthetic
procedures available. The first is based on direct fluorination of
bis(nitrophenyl)disulfides and provides economical access to
1-nitro-4-(pentafluorosulfanyl)benzene (1) and 1-nitro-3-(penta-
fluorosulfanyl)benzene (2).3 Another route is the recently dis-
closed two-step procedure for the conversion of diaryl di-
sulfides to (pentafluorosulfanyl)arenes.4 Compounds 1 and 2
are strongly deactivated toward electrophilic aromatic substitu-
tion, and their functionalization using SEAr chemistry has not
been achieved. Nucleophilic aromatic substitutions of halogen of
halonitro(pentafluorosulfanyl)benzenes are known;5 however,
no publications have reported that 1 or 2 are reactive toward
nucleophiles by nucleophilic aromatic substitution, despite the
electronic suitability of the system for such reactions. The only
reported synthetic transformation starting from 1 or 2 and
yielding SF5-benzenes is the reduction of the nitro group to a
corresponding (pentafluorosulfanyl)aniline, which was further
acylated, halogenated (using electrophilic halogenation), or dia-
zotized (with follow up reactions).2a,b,3b,6 We have recently
reported efficient SNAr of the nitro group in compounds 1 and 2
Received: March 29, 2011
Published: May 05, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
NOTE
violet mixture, and the reaction was terminated by the addition of
aqueous hydrochloric acid. The substitution took place exclu-
sively at the ortho-position relative to the nitro group. Excellent
reactivities were also observed with esters of chloroacetic or
dichloroacetic10 acids (Table 1, entries 2ꢀ4), while for the case
of methyl 2-chloropropionate (3e)11 the yield was low (Table 1,
entry 5) and could not be improved by changing the reaction
temperature or time. With diethyl chloromethylphosphonate
(3f), the VNS reaction took place in less than 10 min at
ꢀ60 °C, with a respectable 84% yield (Table 1, entry 6). Because
chloroacetonitrile is unstable in basic media, phenyoxyacetoni-
trile was used for installation of the cyanomethyl group. In this
case, the leaving group was phenolate rather than chloride, and the
reaction required ambient temperature (Table 1, entry 7). Chloro-
form and bromoform could also be used as pronucleophiles;
however, the generated trihalomethyl carbanions are unstable,
and good product yields required a combination of very short
reaction times (1ꢀ2 min) and low temperature in a THF/DMF
solvent mixture (Table 1, entries 8 and 9).12
Compound 2 was found to be much less reactive for nucleo-
philic aromatic substitution of the nitro group in reactions with
alcoholates or thiolates than compound 1 because the nitro
group in 2 is located in a position that is not conjugated with the
SF5 group.7 However, in VNS reactions the situation is different.
Compound 2 should be more reactive that 1 in VNS reactions
because in the former case the reaction proceeds via addition in
positions conjugated with both of the activating groups. Indeed,
VNS reactions with 2 took place with efficiencies similar to those
observed with 1 (Table 2). The product mixture contained two
compounds: the major product 5, with the substituent in the
ortho position relative to the nitro group (para to SF5), and the
minor product 6, with the substituent in the para position relative
to the nitro group. The octahedral coordination geometry of
the SF5 group exerts higher steric effect than the nitro group
planar to the benzene ring. This is evident, for example, from the
crystal structure of compound 2.13 Products were obtained either
as pure major isomers 5a, 5d, 5h, or 5i or a mixture of isomers in
73ꢀ94% yields. The product ratio ranged from 85:15 for
phenoxyacetonitrile to more than 98:2 for the case of bromoform
(Table 2). More sterically demanding carbanions, derived from
methyl dichloroacetate (3d), chloroform (3h), or bromoform
(3i), appear to have provided the highest 5:6 product ratio.
Considering a reaction mechanism analogous to the one
reported for VNS reactions with nitrobenzene derivatives,8 the
first step is attack of the carbanion generated from 3 to the
aromatic ring of 1 or 2 in the ortho position relative to the nitro
group and the formation of σH-adduct A. In compound 2, the
attack also takes place to a small extent in the para position.
Adduct A undergoes base-induced β-elimination of HX1 to form
anion B. Anion B can be protonated to give products 4 and 5 or
alkylated with primary alkyl halides to give 7 and 8 (Scheme 1).
This reaction sequence was demonstrated on nitrobenzene and
its derivatives.14 Our results from a one-pot VNS/alkylation
sequence are shown in Table 3.
Table 1. VNS Reactions of 1a
entry
X
R1
R2
PhSO2
temp (°C) time (min) yield b (%)
1
2
3
4
5
6
7
8
9
3a Cl
H
H
H
ꢀ40
ꢀ30
ꢀ30
ꢀ30
ꢀ5
30
10
10
10
6
4a, 84
4b, 76
4c, 91
4d, 83
4e, 9
3b Cl
3c Cl
3d Cl
3e Cl
3f Cl
3g PhO
3h Cl
3i Br
CO2Et
CO2Bu-t
Cl CO2Me
Me CO2Me
H
H
P(O)(OEt)2
CN
ꢀ60
rt
10
4f, 84
4g, 74
4h, 74
4i, 74
10
Cl Cl
ꢀ70
ꢀ70
2c
2c
Br Br
a Reactions were carried out using 1 (1.0 mmol), 3 (1.0 mmol), and
t-BuOK (3.0ꢀ4.0 mmol) in DMF (3.5 mL). b Isolated yields. c Reactions
were conducted in THF/DMF (1:1) solvent mixture.
Table 2. VNS Reactions of 2a
entry
X
R1
R2
PhSO2
temp (°C)
time (min)
product, yield b (%)
5:6c
1
3a
3c
3d
3f
Cl
H
H
Cl
H
H
Cl
Br
ꢀ40
ꢀ30
ꢀ30
ꢀ60
rt
30
10
10
10
10
2
5a, 90; 6a, 4
5c þ 6c, 94
5d, 79
96:4
94:6
2
Cl
CO2Bu-t
CO2Me
P(O)(OEt)2
CN
3
Cl
98:2
4
Cl
5f þ 6f, 73
5 g þ 6 g, 73
5h, 91
95:5
5
3g
3h
3i
PhO
Cl
85:15
96:4
6d
7d
Cl
ꢀ70
ꢀ70
Br
Br
2
5i, 84
>98:2
a Reactions were carried out using 2 (1.0 mmol), 3 (1.0 mmol), and t-BuOK (3.0ꢀ4.0 mmol) in DMF (3.5 mL). b Isolated yields. c Determined by 19
F
NMR of the crude product mixture. d Reactions were conducted in a THF/DMF (1:1) solvent mixture.
4782
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NOTE
Scheme 1. Proposed Mechanism of the VNS Reactions of 1
and 2
Table 4. Synthesis of (Pentafluorosulfanyl)anilines 9 or 10a
and Substituted (Pentafluorosulfanyl)benzenes 11f or 12ab
entry
R2
cat.
yield c (%)
yield c (%)
1
2
3
4c
4f
CO2Bu-t
P(O)(OEt)2
SO2Ph
Ra-Ni
Pd/C
Ra-Ni
9c, 97
9f, 77
11f, 72
12a, 65
5a
10a, 79
a Reactions were carried out using 4 or 5 with 10% Pd/C (cat.) in THF
or with Ra-Ni (cat.) in EtOH at rt for 4ꢀ15 h. b Reactions were carried
out using 9f or 10a (0.18 mmol), HCl (excess), NaNO2 (3ꢀ5 equiv),
H3PO2 (excess) in water, ꢀ10 °C to rt, 1ꢀ1.5 h. c Isolated yields.
Table 3. VNS/Alkylation Sequence of 1 and 2a
yields. High regioselectivities were obtained for VNS reactions of 2.
These reactions were performed under kinetic conditions (low
reaction temperatures, short reaction times, and equimolar amounts
of 3), unlike the nucleophilic aromatic substitutions for the nitro
group of 1 and 2.7 The VNS/alkylation sequence enabled synthesis
of alkylated derivatives 7 and 8 in one-pot reaction from 1 and 2,
respectively. Follow-up transformation of the primary products 4
and 5 expanded the scope of the synthetic method and provided
substituted (pentafluorosulfanyl)anilines 9 and 10 and substituted
(pentafluorosulfanyl)benzenes 11f and 12a.
temp time yield b
entry
X1 R1
R2
X2
R3
(°C) (min) (%)
1
2
3
4
1
1
2
2
Cl
H
H
H
CO2Et Br PhCH2
CN CH3
ꢀ30
10 7b, 59
10 7g, 57
30 8a, 84
10 8d, 0
OPh
Cl
I
rt
’ EXPERIMENTAL SECTION
PhSO2 Br CH2dCHCH2 ꢀ40
n-Bu
Cl
Cl CO2Me
I
ꢀ30
General Procedure for the Synthesis of Compounds 4ꢀ6.
A solution of 1 or 2 (1.0 mmol) and 3 (1.0 mmol) in DMF (1.0 mL) was
added dropwise to a solution of t-BuOK (3.0ꢀ4.0 mmol) in DMF
(2.5 mL) or a mixture of DMF (0.8 mL) and THF (1.7 mL) at an
appropriate temperature. The reaction was terminated after a given time
by addition of aq HCl (10 mL, 1 M), followed by extraction into
t-BuOMe or CH2Cl2 (3 ꢁ 15 mL). The combined organic phase was
washed with brine (15 mL), dried (MgSO4), and concentrated under
reduced pressure. Purification by column chromatography (silica gel,
PEꢀEtOAc) gave the desired products 4ꢀ6.
a Reactions were carried out using 1 or 2 (1.0 mmol), 3 (1.0 mmol),
and t-BuOK (3.0 mmol) in DMF (3.5 mL) followed by addition of R3X2
(2.0 mmol), rt, 30 min. b Isolated yields.
Reactions with alkyl halides, such as methyl iodide, allyl
bromide, or benzyl bromide, gave moderate to good yields of
the desired alkylated products (Table 3, entries 1ꢀ3); however,
an attempt to create a quaternary carbon center was not
successful, and 5d, 6d, and other unidentified products were
formed instead of the expected 8d (Table 3, entry 4).
To demonstrate the versatility of this methodology for the
synthesis of functionalized SF5-benzenes, several transforma-
tions of primary products 4 and 5 were performed. Catalytic
hydrogenation provided substituted (pentafluorosulfanyl)anilines
9 and 10 (Table 4). The choice of catalyst was crucial for the
outcome of these reactions. While employment of 10% Pd/C in
the reaction with 4f gave good yields of the aniline derivative 9f,
the formation of N-hydroxylamine derivatives was observed with
compounds 4c and 5a. On the other hand, with Raney nickel,
good to high yields of aniline derivatives 9c and 10a were
obtained (Table 4, entries 1 and 3). Finally, the amino groups
in 9f and 10a were substituted for hydrogen atoms under
standard diazotation conditions in the presence of H3PO2,
providing meta- or para-substituted SF5-benzenes 11f and 12a,
respectively, in good yields (Table 4, entries 2 and 3).
4a: white solid (84%); mp 124ꢀ125 °C; Rf 0.45 (PEꢀEtOAc, 3:1); IR
(KBr) νmax 3117, 3097, 3073, 3045, 3020, 2957, 2884, 1613, 1585, 1539,
1357, 1325, 1155, 1085, 835; 1H NMR (400 MHz, CDCl3) δ 4.96 (s, 2H),
7.50ꢀ7.54 (m, 2H), 7.61ꢀ7.62 (m, 1H), 7.66ꢀ7.69 (m, 3H), 7.91ꢀ7.93
(m, 1H), 8.08ꢀ8.11 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 58.2, 124.4,
126.0, 127.8 (quin, J = 4.6 Hz), 128.2, 129.4, 131.7 (quin, J = 4.7 Hz), 134.5,
137.3, 150.6, 156.6 (quin, J = 19.6 Hz); 19F NMR (376 MHz, CDCl3) δ
62.2 (dm, J= 151.0 Hz, 4F), 79.3ꢀ80.9 (m, 1F); MS (EI) m/z264 (6), 263
(9), 262 (100), 245 (24), 141 (51), 77 (88). Anal. Calcd for C13H10F5-
NO4S2: C, 38.71; H, 2.50; N, 3.47. Found: C, 38.90; H, 2.58; N, 3.29.
4b: pale yellow oil (76%); Rf 0.40 (PEꢀEtOAc, 9:1); FTIR (film)
νmax 3120, 3100, 3076, 3047, 2987, 2942, 2878, 1738, 1618, 1584, 1537,
1
1355, 1223, 1183, 1028, 836; H NMR (400 MHz, CDCl3) δ 1.27
(t, 3H, J = 7.1 Hz), 4.09 (s, 2H), 4.20 (q, 2H, J = 7.3 Hz), 7.77ꢀ7.79
(m, 1H), 7.86ꢀ7.90 (m, 1H), 8.15ꢀ8.20 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.0, 38.6, 61.7, 125.6ꢀ125.8 (m), 126.4ꢀ126.7 (m), 130.8ꢀ
131.1 (m), 130.9, 150.1ꢀ150.3 (m), 155.8ꢀ156.5 (m), 168.8; 19F NMR
(376 MHz, CDCl3) δ 62.2 (dm, 4F, J = 150.3 Hz), 79.9ꢀ81.5 (m, 1F);
MS (EI) m/z 316 (7), 290 (42), 289 (47), 262 (87), 261 (58), 246
(100), 119 (49), 107 (23), 89 (29), 77 (24); HRMS (ESIꢀ) m/z calcd
for C10H9F5NO4S [M ꢀ H]ꢀ 334.01724, found 334.01779.
In summary, in the present work, vicarious nucleophilic substitu-
tions of hydrogen of p- and m-nitro(pentafluorosulfanyl)benzenes
(1 and 2) with a range of carbanions have been shown to provide
novel substituted nitro(pentafluorosulfanyl)benzenes 4ꢀ6 in good
4783
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The Journal of Organic Chemistry
NOTE
4c: pale yellow solid (91%); mp 85ꢀ87 °C; Rf 0.47 (PEꢀEtOAc,
9:1); FTIR (film) νmax 3119, 3100, 3075, 3045, 2983, 2935, 1732, 1617,
1584, 1537, 1481, 1395, 1370, 1354, 1232, 1153, 851; H NMR (400
4i: pale yellow oil (74%); Rf 0.72 (PEꢀEtOAc, 9:1); FTIR (film) νmax
3113, 3068, 2927, 2874, 1611, 1584, 1538, 1477, 1350, 1312, 1144, 1120,
1068, 922, 855; 1H NMR (400 MHz, CDCl3) δ 7.40 (s, 1H), 7.89ꢀ7.92
(m, 1H), 8.01ꢀ8.04 (m, 1H), 8.62ꢀ8.63 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 32.1, 125.1, 128.2 (quin, J = 4.7 Hz), 130.8 (quin, J = 4.9
Hz), 137.3, 145.2, 157.0 (quin, J = 20.0 Hz); 19F NMR (376 MHz,
CDCl3) δ 62.0 (dm, 4F, J = 151.1 Hz), 78.9ꢀ80.5 (m, 1F); MS (EI) m/z
342 (47), 340 (46), 262 (10), 261 (100), 245 (7), 230 (11), 215 (9), 205
(11), 186 (8), 174 (7), 169 (8), 109 (26), 107 (32), 103 (13), 95 (18),
89 (27), 88 (21), 87 (22), 86 (16), 78 (34), 76 (19), 75 (40); HRMS
(CI) m/z calcd for C7H5Br2F5NO2S [M þ H]þ 419.8328, found
419.8320.
1
MHz, CDCl3) δ 1.45 (s, 9H), 4.01 (s, 2H), 7.75ꢀ7.76 (m, 1H),
7.84ꢀ7.87 (m, 1H), 8.14ꢀ8.17 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 27.9, 40.8, 82.6, 125.5, 126.3 (quin, J = 4.7 Hz), 130.9 (quin, J = 4.7 Hz),
131.5, 150.2, 155.9ꢀ156.5 (m), 167.9; 19F NMR (376 MHz, CDCl3) δ
62.2 (dm, 4F, J = 150.8 Hz), 80.0ꢀ81.6 (m, 1F); MS (EI) m/z 290 (22),
262 (22), 241 (7), 89 (11), 57 (100), 56 (18), 41 (47). Anal. Calcd for
C12H14F5NO4S: C, 39.67; H, 3.88; N, 3.86. Found: C, 39.91; H, 3.90;
N, 3.65.
4d: pale yellow solid (83%); mp 75ꢀ77 °C; Rf 0.10 (PEꢀEtOAc,
49:1); FTIR (film) νmax 3121, 3073, 3044, 3012, 2960, 1751, 1614, 1584,
5a and 6a. 5a: pale yellow solid (90%); mp 173ꢀ175 °C; Rf 0.15
(PEꢀEtOAc, 4:1); FTIR (film) νmax 3107, 3062, 3042, 2958, 2924,
1615, 1576, 1538, 1348, 1324, 1151, 839; 1H NMR (400 MHz, CDCl3)
δ 4.98 (s, 2H), 7.53ꢀ7.57 (m, 2H), 7.63ꢀ7.66 (m, 1H), 7.68ꢀ7.72 (m,
1
1540, 1354, 1169, 840; H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H),
6.10 (s, 1H), 7.97ꢀ8.00 (m, 1H), 8.17ꢀ8.21 (m, 1H), 8.37ꢀ8.39
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 53.8, 54.1, 125.6, 127.9 (quin,
J = 4.7 Hz), 129.3 (quin, J = 4.9 Hz), 131.9, 148.7, 156.7 (quin, J = 19.6 Hz),
167.0; 19F NMR (376 MHz, CDCl3) δ 62.1 (dm, 4F, J = 150.8 Hz),
79.2ꢀ80.8 (m, 1F); MS (EI) m/z 309 (14), 296 (23), 261 (37), 246
(35), 230 (16), 217 (16), 140 (14), 123 (22), 107 (17), 89 (27), 75 (34),
59 (100). Anal. Calcd for C9H7ClF5NO4S: C, 30.39; H, 1.98; N, 3.94.
Found: C, 30.62; H, 2.15; N, 3.69.
1H), 7.75ꢀ7.77 (m, 2H), 7.99ꢀ8.01 (m, 1H), 8.39ꢀ8.40 (m, 1H); 13
C
NMR (100 MHz, CDCl3) δ 58.1, 123.6 (quin, J = 4.9 Hz), 126.8, 128.3,
129.5, 130.3 (quin, J = 4.6 Hz), 134.6, 134.9, 137.9, 148.9, 154.0 (quin,
J = 20.6 Hz); 19F NMR (376 MHz, CDCl3) δ 62.3 (dm, 4F, J = 151.2 Hz),
79.1ꢀ80.7 (m, 1F); MS (EI) m/z 263 (10), 262 (97), 245 (17), 244 (5),
141 (60), 89 (11), 78 (11), 77 (100); HRMS (CI) m/z calcd for
C13H11F5NO4S2 [M þ H]þ 404.0050, found 404.0059. 6a: pale yellow
solid (4%); mp 157ꢀ160 °C; Rf 0.23 (PEꢀEtOAc, 4:1); FTIR (film)
νmax 3107, 2970, 1605, 1586, 1525, 1353, 1320, 1305, 1151, 1085, 856,
837, 821, 805; 1H NMR (400 MHz, CDCl3) δ 4.78 (s, 2H), 7.53ꢀ7.58
(m, 2H), 7.68ꢀ7.76 (m, 3H), 8.16ꢀ8.18 (m, 1H), 8.42ꢀ8.44 (m, 1H),
8.68ꢀ8.69 (m, 1H); 13C NMR (150.9 MHz, CDCl3) δ 59.9 (quin, J =
3.0 Hz), 124.1 (quin, J = 5.4 Hz), 125.8, 128.3, 129.5, 131.6, 134.6, 135.0,
138.6, 147.4, 154.2 (quin, J = 18.4 Hz); 19F NMR (376 MHz, CDCl3)
δ 67.8 (dm, 4F, J = 150.6 Hz), 81.3ꢀ82.9 (m, 1F); MS (EI) m/z 403 [M]þ
(4), 281 (14), 207 (50), 141 (100), 108 (17), 107 (19), 96 (17), 89 (28),
77 (89); HRMS (EI) m/z calcd for C13H10F5NO4S2 [M]þ 402.9971,
found 402.9977.
4e: pale yellow oil (9%); Rf 0.15 (PEꢀEtOAc, 49:1); FTIR (film)
νmax 3119, 3042, 2956, 2925, 2854, 1742, 1614, 1582, 1537, 1359, 1176,
1
835; H NMR (400 MHz, CDCl3) δ 1.66 (d, 3H, J = 7.2 Hz), 3.70
(s, 3H), 4.33 (q, 1H, J = 7.2 Hz), 7.82ꢀ7.85 (m, 1H), 7.90 (m, 1H),
7.99ꢀ8.01 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 17.7, 41.3, 52.6,
125.2, 126.1 (quin, J = 4.7 Hz), 128.0 (quin, J = 4.7 Hz), 136.1, 150.3,
155.8ꢀ157.0 (m), 172.5; 19F NMR (376 MHz, CDCl3) δ 62.0 (dm, 4F,
J = 150.7 Hz), 80.0ꢀ81.6 (m, 1F); MS (EI) m/z 316 (5), 304 (13), 290
(12), 289 (100), 276 (63), 260 (18), 259 (17), 246 (11), 231 (20), 230
(16), 133 (27), 102 (27), 93 (20), 89 (23), 77 (27); HRMS (ESIꢀ) m/z
calcd for C10H9F5NO4S [M ꢀ H]ꢀ 334.01724, found 334.01738.
4f: pale yellow oil (84%); Rf 0.47 (PEꢀEtOAc, 1:1); FTIR (film)
νmax 3115, 3070, 3039, 2988, 2935, 2912, 1614,1583,1482, 1539, 1358,
1253, 1052,1027, 851; 1H NMR (400 MHz, CDCl3) δ 1.27 (dt, 6H, J =
7.1, 0.5 Hz), 3.76 (d, 2H, J = 23.0 Hz), 4.03ꢀ4.12 (m, 4H), 7.59ꢀ7.65
(m, 1H), 7.91ꢀ7.96 (m, 1H), 8.36ꢀ8.38 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 16.2 (d, J = 5.9 Hz), 30.6 (d, J = 136.9 Hz), 62.7 (d, J = 6.6 Hz),
125.6 (d, J = 2.9 Hz), 125.7ꢀ126.0 (m), 129.0 (d, JCP = 10.3 Hz),
130.8ꢀ131.1 (m), 150.3ꢀ150.5 (m), 155.4ꢀ156.0 (m); 19F NMR (376
5c and 6c: pale yellow solid (94%, 5c:6c = 94:6); Rf 0.29
(PEꢀEtOAc, 9:1); FTIR (film) νmax 3122, 3107, 2983, 2936, 1733,
1617, 1575, 1539, 1395, 1370, 1352, 1153, 851. Anal. Calcd for
C12H14F5NO4S: C, 39.67; H, 3.88; N, 3.86. Found: C, 39.98; H, 3.93;
N, 3.61. 5c: 1H NMR (400 MHz, CDCl3) δ 1.45 (s, 9H), 4.02 (s, 2H),
7.48ꢀ7.51 (m, 1H), 7.95ꢀ7.97 (m, 1H), 8.50ꢀ8.51 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 27.9, 40.6, 82.6, 123.3 (quin, J = 4.8 Hz), 130.3
(quin, J = 4.6 Hz), 133.8, 134.1, 148.5, 152.4ꢀ153.2 (m), 168.0; 19F
NMR (376 MHz, CDCl3) δ 62.4 (dm, 4F, J = 151.0 Hz), 80.0ꢀ81.6
(m, 1F); MS (EI) m/z 290 (25), 262 (21), 261 (24), 246 (12), 89 (14),
63 (13), 57 (100). 6c: 19F NMR (376 MHz, CDCl3) δ 66.1 (dm, 4F, J =
149.4 Hz), 81.9ꢀ83.4 (m, 1F).
MHz, CDCl3) δ 62.5 (dm, 4F, J = 151.4 Hz), 79.9ꢀ81.5 (m, 1F); 31
P
NMR (162 MHz, CDCl3) δ 22.0 (s); MS (EI) m/z 354 (19), 353 (54),
326 (16), 325 (15), 313 (18), 297 (100), 233 (17), 233 (17), 218 (14),
119 (11), 109 (55), 91 (20), 81 (36); HRMS (ESI) m/z calcd for
C11H16F5NO5PS [M þ H]þ 400.04015, found 400.03968.
5d: pale yellow oil (79%); Rf 0.06 (PEꢀEtOAc, 46:1); FTIR (film)
νmax 3122, 3049, 3011, 2960, 1751, 1615, 1575, 1542, 1439, 1351, 1168,
835; 1H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H), 6.14 (s, 1H),
8.11ꢀ8.17 (m, 2H), 8.49ꢀ8.50 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 53.8, 54.2, 123.1 (quin, J = 4.9 Hz), 130.9 (quin, J = 4.6 Hz), 132.1,
134.2, 147.1, 153.7 (quin, J = 20.8 Hz), 167.1; 19F NMR (376 MHz,
CDCl3) δ 62.3 (dm, 4F, J = 151.0 Hz), 79.1ꢀ80.7 (m, 1F); MS (EI) m/z
336 (10), 324 (9), 309 (18), 296 (21), 261 (34), 260 (20), 246 (29), 230
(16), 217 (16), 204 (13), 123 (25), 108 (16), 107 (17), 89 (28), 75 (34),
59 (100); HRMS (CI) m/z calcd for C9H8ClF5NO4S [M þ H]þ:
355.9783, found 355.9789.
4g: pale yellow oil (74%); Rf 0.15 (PEꢀEtOAc, 9:1); FTIR (film)
νmax 3121, 3078, 3049, 2255, 1618, 1587, 1538, 1353, 1122, 911, 835; 1H
NMR (400 MHz, CDCl3) δ 4.25 (s, 2H), 7.98ꢀ8.00 (m, 1H),
8.10ꢀ8.11 (m, 1H), 8.27ꢀ8.30 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 22.6, 115.3, 126.4, 127.0, 127.7 (quin, J = 4.7 Hz), 129.2 (quin, J = 4.8
Hz), 148.7, 156.8 (quin, J = 20.0 Hz); 19F NMR (376 MHz, CDCl3) δ
62.2 (dm, 4F, J = 150.9 Hz), 78.9ꢀ80.5 (m, 1F); MS (EI) m/z 269 (14),
261 (100), 144 (20), 134 (26), 114 (36), 107 (50), 89 (39); HRMS (EI)
m/z calcd for C8H5F5N2O2S [M]þ 287.9992, found 288.0005.
4h: pale yellow oil (74%); Rf 0.50 (PEꢀEtOAc, 9:1); FTIR (film) νmax
3116, 3070, 1613, 1585, 1542, 1351, 1315, 1210, 1191, 1070, 923, 841; 1H
NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.95ꢀ7.98 (m, 1H), 8.09ꢀ8.11
(m, 1H), 8.57ꢀ8.58 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 64.7,
125.4, 128.2 (quin, J = 4.9 Hz), 128.6 (quin, J = 4.6 Hz), 135.9, 146.5,
157.0 (quin, J = 20.5 Hz); 19F NMR (376 MHz, CDCl3) δ 62.0 (dm, 4F,
J = 151.2 Hz), 78.8ꢀ80.4 (m, 1F); MS (EI) m/z 314 (3), 312 (4), 298 (7),
296 (16), 261 (15), 260 (100), 230 (26), 123 (18), 75 (16); HRMS (EI)
m/z calcd for C7H4Cl2F4NO2S [M ꢀ F]þ 311.9276, found 311.9268.
5f and 6f: pale yellow solid (73%, 5f:6f = 95:5); Rf 0.26 (PEꢀEtOAc,
1:1); FTIR (film) νmax 3120, 3102, 3045, 2988, 2935, 2911, 1613, 1574,
1541, 1488, 1355, 1254, 1053, 1027, 850; MS (EI) m/z 380 (6), 354
(19), 353 (54), 326 (16), 325 (15), 297 (100), 245 (11), 109 (46), 91
(18), 89 (14), 81 (35); HRMS (ESI) m/z calcd for C11H15F5NNaO5PS
1
[M þ Na]þ 422.02209, found 422.02185. 5f: H NMR (400 MHz,
CDCl3) δ 1.26 (dt, 6H, J = 7.1, 0.5 Hz), 3.74 (d, 2H, J = 23.0 Hz),
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The Journal of Organic Chemistry
NOTE
4.03ꢀ4.15 (m, 4H), 7.81ꢀ7.84 (m, 1H), 7.91ꢀ7.96 (m, 1H),
8.36ꢀ8.38 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 16.2 (d, J = 5.9
Hz), 30.6 (d, J = 136.9 Hz), 62.7 (d, J = 6.6 Hz), 123.2ꢀ123.4 (m),
129.7ꢀ130.0 (m), 131.6ꢀ131.7 (m), 133.6ꢀ133.7 (m), 148.6ꢀ148.7
(m), 152.1ꢀ152.6 (m); 19F NMR (376 MHz, CDCl3) δ 62.5 (dm, 4F,
(100 MHz, CDCl3) δ 20.9, 28.2, 119.5, 126.2, 127,5 (quin, J = 4.7 Hz),
127.6 (quin, J = 4.8 Hz), 133.4, 148.7, 156.7ꢀ157.3; 19F NMR (376
MHz, CDCl3) δ 62.1 (dm, 4F, J = 151.0 Hz), 78.9ꢀ80.5 (m, 1F); MS
(EI) m/z 275 (100), 260 (27), 230 (20), 158 (17), 129 (30), 118 (42),
109 (26), 102 (39), 101 (35), 89 (45), 75 (37); HRMS (CI) m/z calcd
for C9H7F5N2O2S [M þ H]þ 303.0227, found 303.0224.
J = 151.4 Hz), 79.9ꢀ81.7 (m, 1F); 31P NMR (CDCl3) δ 22.2 (s). 6f: 19
F
NMR (376 MHz, CDCl3) δ 67.2 (dm, 4F, J = 149.1 Hz), 82.0ꢀ83.7
8a: pale yellow oil (84%); Rf 0.26 (PEꢀEtOAc, 9:1); FTIR (film)
νmax 3120, 3095, 3070, 2987, 1643, 1610, 1573, 1540, 1448, 1353, 1324,
1310, 1151, 1085, 899, 851; 1H NMR (400 MHz, CDCl3) δ 2.92ꢀ3.00
(m, 1H), 3.10ꢀ3.17 (m, 1H), 5.00ꢀ5.08 (m, 2H), 5.45ꢀ5.58 (m, 2H),
7.48ꢀ7.53 (m, 2H), 7.65ꢀ7.69 (m, 3H), 7.95ꢀ7.97 (m, 1H),
8.02ꢀ8.05 (m, 1H), 8.17ꢀ8.18 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 32.5, 62.5, 119.8, 122.9 (quin, J = 4.9 Hz), 128.7, 129.4, 129.8 (quin, J =
4.6 Hz), 130.6, 131.1, 131.4, 134.5, 136.8, 150.3, 153.4 (quin, J = 20.2
Hz); 19F NMR (470.4 MHz, CDCl3) δ 62.3 (dm, 4F, J = 151.2 Hz),
79.4ꢀ80.6 (m, 1F); MS (EI) m/z 302 (100), 272 (68), 256 (23), 245
(13), 175 (12), 128 (26), 77 (40); HRMS (CI) m/z calcd for
C16H15F5NO4S2 [M þ H]þ 444.0363, found 444.0373.
(m, 1F); 31P NMR (CDCl3) δ 22.6 (s).
5g and 6g: pale yellow oil (73%, 5g:6g = 85:15); Rf 0.13 (PEꢀEtOAc,
93:7); FTIR (film) νmax 3124, 3106, 3052, 2255, 1618, 1574, 1540, 1353,
903, 849; HRMS (EI) m/z calcd for C8H5F5N2O2S [M]þ 287.9992,
1
found 287.9979. 5g: H NMR (400 MHz, CDCl3) δ 4.30 (s, 2H),
7.93ꢀ7.96 (m, 1H), 8.11ꢀ8.14 (m, 1H), 8.59ꢀ8.60 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 22.6, 115.3, 123.9 (quin, J = 4.9 Hz), 129.5, 131.4
(quin, J = 4.6 Hz), 131.9, 147.1, 153.7 (quin, J = 20.4 Hz); 19F NMR
(376 MHz, CDCl3) δ 62.4 (dm, 4F, J = 151.2 Hz), 79.0ꢀ80.6 (m, 1F);
MS (EI) m/z 269 (16), 261 (100), 205 (19), 134 (49), 114 (38), 107
(42), 89 (35), 88 (26). 6g: 1H NMR (400 MHz, CDCl3) δ 4.24 (s, 2H),
8.00ꢀ8.02 (m, 1H), 8.45ꢀ8.47 (m, 1H), 8.75ꢀ8.76 (m, 1H); 19F NMR
(376 MHz, CDCl3) δ 65.8 (dm, 4F, J = 149.1 Hz), 80.7ꢀ82.3 (m, 1F).
5h: colorless oil (91%); Rf 0.30 (PE); FTIR (film) νmax 3120, 3062,
1613, 1574, 1544, 1350, 1201, 1123, 910, 854, 820; 1H NMR (400 MHz,
CDCl3) δ 7.57 (s, 1H), 8.13ꢀ8.16 (m, 1H), 8.34ꢀ8.36 (m, 1H),
8.41ꢀ8.42 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 64.6, 123.0 (quin,
J = 5.0 Hz), 130.9, 131.3 (quin, J = 4.6 Hz), 138.0, 144.9, 154.3 (quin, J =
20.0 Hz); 19F NMR (376 MHz, CDCl3) δ 62.3 (dm, 4F, J = 151.4 Hz),
78.7ꢀ80.3 (m, 1F); MS (EI) m/z 314 (3), 312 (4), 298 (5), 296 (13),
261 (14), 260 (100), 230 (25), 123 (17), 75 (14); HRMS (EI) m/z calcd
for C7H4Cl2F4NO2S [M ꢀ F]þ 311.9276, found 311.9265.
9c. A suspension of Raney nickel (100 mg) was washed with ethanol
(3 ꢁ 10 mL). Ethanol (10 mL) and 4c (130 mg, 0.36 mmol) were added,
a balloon filled with hydrogen was attached, and the mixture was stirred
at rt for 4 h, followed by filtration, washing with hot THF (3 ꢁ 5 mL),
and concentration of filtrate under reduced pressure. The resulting
residue contained pure 9c (116 mg, 97%) as a white solid: Rf 0.36
(PEꢀEtOAc, 4:1); mp 83 °C; FTIR (film) νmax 3479, 3381, 3255, 2993,
2920, 2851, 1710, 1640, 1603, 1502, 1394, 1372, 1336, 1325, 1137, 920,
852, 832; 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 3.47 (s, 2H), 4.47
(br s, 2H), 6.62ꢀ6.67 (m, 1H), 7.41ꢀ7.44 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 27.9, 39.9, 82.0, 114.8, 118.8, 126.2 (quin, J = 4.6 Hz),
128.2 (quin, J = 4.6 Hz), 144.2ꢀ144.8 (m), 148.3, 170.3; 19F NMR (376
MHz, CDCl3) δ 64.2 (dm, 4F, J = 150.3 Hz), 86.2ꢀ87.9 (m, 1F); MS
(EI) m/z 333 [M]þ (14), 278 (10), 277 (100), 260 (44), 259 (68), 233
(19), 231 (15), 230 (22), 104 (26), 77 (12), 57 (74). Anal. Calcd for
C12H16F5NO2S: C, 43.22; H, 4.84; N, 4.20. Found: C, 43.09; H, 4.77;
N, 4.07.
9f. Pd/C (10%, 70 mg) was added to a solution of 4f (570 mg,
1.43 mmol) in THF (20 mL). A balloon filled with hydrogen was attached,
and the mixture was stirred at rt for 15 h, followed by filtration, washing
with hot THF (3 ꢁ 5 mL), and concentration of filtrate under reduced
pressure. Chromatography purification (silica gel, EtOAc) gave 9f
(406 mg, 77%) as a pale yellow liquid: Rf 0.36 (EtOAc); FTIR (film) νmax
3355, 3245, 2988, 2934, 2911, 1647, 1602, 1580, 1503, 1230, 1053, 1029,
838, 806; 1H NMR (400 MHz, CDCl3) δ 1.25 (t, 6H, J = 7.1 Hz), 3.11
(d, 2H, J = 21.0 Hz), 3.99ꢀ4.09 (m, 4H), 4.72 (br s, 2H), 6.65ꢀ6.69 (m,
1H), 7.40ꢀ7.47 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 16.2 (d, J =
5.9 Hz), 30.8 (d, J = 139.8 Hz), 62.8 (d, J = 7.3 Hz), 115.5ꢀ115.6 (m),
116.3ꢀ116.6 (m), 125.9ꢀ126.2 (m), 129.1ꢀ129.4 (m), 148.8ꢀ148.9
(m), 164.6ꢀ164.7 (m); 19F NMR (376 MHz, CDCl3) δ 64.1 (dm, 4F,
J = 150.3 Hz), 88.0ꢀ87.8 (m, 1F); 31P NMR (162 MHz, CDCl3) δ 26.7
(s); MS (EI) m/z 370 (10), 369 (76), 341 (11), 295 (31), 246 (16), 241
(19), 233 (20), 232 (100), 185 (23), 168 (19), 104 (25); HRMS (ESI)
m/z calcd for C11H17F5NNaO3PS [M þ Na]þ 392.04791, found
392.04773.
5i: pale yellow solid (84%); mp 39ꢀ41 °C; Rf 0.11 (PE); FTIR (film)
νmax 3116, 3085, 3065, 2926, 2876, 1610, 1573, 1539, 1485, 1349, 1121,
853; 1H NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 8.09ꢀ8.12 (m, 1H),
8.34ꢀ8.35 (m, 1H), 8.38ꢀ8.41 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 32.1, 122.7 (quin, J = 5.0 Hz), 131.3 (quin, J = 4.6 Hz), 135.5, 139.3,
143.7, 153.9 (quin, J = 20.4 Hz); 19F NMR (376 MHz, CDCl3) δ 62.3
(dm, 4F, J = 151.4 Hz), 78.8ꢀ80.4 (m, 1F); MS (EI) m/z 342 (43), 340
(42), 314 (38), 312 (52), 262 (12), 261 (100), 205 (26), 109 (21),
107 (34), 103 (14), 95 (19), 89 (26), 88 (29), 87 (24), 86 (19), 78 (26),
76 (23), 75 (37); HRMS (CI) m/z calcd for C7H5Br2F5NO2S [M þ H]þ
419.8328, found 419.8318.
General Procedure for the Synthesis of Compounds 7 and
8. To a solution of 1 or 2 (1.0 mmol) and 3 (1.0 mmol) in DMF
(1.5 mL) was added dropwise a solution of t-BuOK (3.0 mmol) in DMF
(3.0 mL) at an appropriate temperature. Alkyl halide (2.0 mmol) was
added after a given time; the reaction mixture was warmed to rt during
10 min and stirred for 30 min followed by workup similar to that for
compounds 4ꢀ6.
7b: colorless liquid (59%); Rf 0.25 (PEꢀEtOAc, 9:1); FTIR (film)
νmax 3116, 3091, 3067, 3032, 2985, 2939, 1733, 1613, 1584, 1537, 1497,
1356, 1164, 855; 1H NMR (400 MHz, CDCl3) δ 1.15 (t, 3H, J = 7.1 Hz),
3.20 (dd, 1H, J = 13.7, 7.6 Hz), 3.51 (dd, 1H, J = 13.7, 7.6 Hz), 4.12
(q, 2H, J = 7.1 Hz), 4.47 (t, 1H, J = 7.6 Hz), 7.08ꢀ7.10 (m, 2H), 7.19ꢀ7.25
(m, 3H), 7.58ꢀ7.79 (m, 1H), 7.86ꢀ7.87 (m, 1H), 7.89ꢀ7.91 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 13.8, 39.0, 48.8, 61.7, 125.0, 126.0
(quin, J = 4.6 Hz), 126.9, 128.6, 128.8 (quin, J = 4.7 Hz), 128.9, 134.1,
137.3, 150.5, 155.6ꢀ156.1 (m), 170.9; 19F NMR (470.4 MHz, CDCl3)
δ 62.0 (dm, 4F, J = 150.8 Hz), 80.1ꢀ81.4 (m, 1F); MS (EI) m/z 380 (4),
361 (7), 334 (21), 318 (7), 306 (7), 246 (52), 178 (9), 107 (12), 105
(14), 91 (100); HRMS (CI) m/z calcd for C17H17F5NO4S [M þ H]þ
426.0798, found 426.0783.
10a. Prepared according to 9c from 5a in 15 h giving 10a (79%) as a
white solid: Rf 0.30 (PEꢀEtOAc, 3:2); mp (subl) 250 °C; FTIR (KBr)
νmax 3468, 3386, 3235, 3100, 3068, 2988, 2934, 1635, 1606, 1580, 1499,
1
1288, 1151, 1083, 937, 835; H NMR (400 MHz, DMSO-d6) δ 4.68
(s, 2H), 5.71 (s, 2H), 6.88ꢀ6.91 (m, 1H), 7.01ꢀ7.04 (m, 1H), 7.10ꢀ7.11
(m, 1H), 7.59ꢀ7.63 (m, 2H), 7.72ꢀ7.76 (m, 1H), 7.82ꢀ7.84 (m, 2H);
13C NMR (100 MHz, DMSO-d6) δ 56.0, 111.6, 111.9, 114.7, 128.0,
129.0, 133.2, 133.8, 138.7, 148.7, 153.6ꢀ154.0 (m); 19F NMR (470.4
MHz, DMSO-d6) δ 63.9 (dm, 4F, J = 150.1 Hz), 88.1ꢀ89.7 (m, 1F); MS
(EI) m/z 373 [M]þ (7), 232 (100), 124 (21), 104 (8), 77 (11); HRMS
(EI) m/z calcd for C13H12F5NO2S2 [M]þ 273.0230, found 373.0225.
7g: pale yellow liquid (57%); Rf 0.48 (PEꢀEtOAc, 9:1); FTIR (film)
νmax 3117, 3100, 3076, 3046, 2994, 2947, 2248, 1615, 1600, 1586, 1539,
1356, 835; 1H NMR (400 MHz, CDCl3) δ 1.77 (d, 3H, J = 7.1 Hz), 4.75
(q, 1H, J = 7.1 Hz), 7.93ꢀ7.96 (m, 1H), 8.13ꢀ8.17 (m, 2H); 13C NMR
4785
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The Journal of Organic Chemistry
NOTE
11f. Aqueous HCl (35%, 1.9 mL) was added to 9f (68 mg, 0.17
mmol), and the mixture was stirred for 10 min at rt before it was cooled
to ꢀ10 °C. Aqueous H3PO2 (50%, 1.8 mL) was added followed by the
addition of NaNO2 (64 mg, 0.92 mmol) in water (0.6 mL). The mixture
was warmed to rt during 1.5 h, water (10 mL) was added, and the
product was extracted into Et2O (4 ꢁ 10 mL), dried, and concentrated
under reduced pressure. The resulting residue was purified by flash
column chromatograpy to give 11f (43 mg, 72%) as a pale yellow liquid:
Rf 0.30 (EtOAc); FTIR (film) νmax 3073, 2987, 2914, 1606, 1541, 1486,
1441, 1393, 1249, 1055, 1030, 845; 1H NMR (400 MHz, CDCl3) δ 1.26
(t, 6H, J = 7.1 Hz), 3.21 (d, 2H, J = 21.7 Hz), 4.01ꢀ4.10 (m, 4H),
7.38ꢀ7.50 (m, 2H), 7.62ꢀ7.71 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 16.2 (d, J = 5.9 Hz), 33.7 (d, J = 139.0 Hz), 62.4 (d, J = 6.6 Hz),
124.3ꢀ124.6 (m), 127.0ꢀ127.3 (m), 128.7ꢀ128.9 (m), 132.8ꢀ133.0
(m), 132.8ꢀ133.0 (m), 153.7ꢀ154.2 (m); 19F NMR (376 MHz,
CDCl3) δ 62.2 (dm, 4F, J = 149.2 Hz), 83.0ꢀ84.7 (m, 1F); 31P NMR
(162 MHz, CDCl3) δ 24.7 (s); MS (EI) m/z 333 (14), 278 (10), 277
(100), 260 (44), 259 (72), 233 (78), 231 (15), 230 (25), 104 (27), 77
(13), 57 (71); HRMS (ESI) m/z calcd for C11H16F5NaO3PS [M þ
Na]þ 377.03701, found 377.03697.
12a. Prepared according to 11f from 10a (66 mg, 0.18 mmol) and
NaNO2 (37 mg, 0.53 mmol) giving 12a (65%) as a white solid: Rf 0.26
(PEꢀEtOAc, 4:1); mp (subl) 207 °C; FTIR (film) νmax 3058, 1599,
1583, 1494, 1309, 1153, 834; 1H NMR (400 MHz, DMSO-d6) δ 4.83
(s, 2H), 7.40ꢀ7.42 (m, 2H), 7.59ꢀ7.63 (m, 2H), 7.71ꢀ7.78 (m, 3H),
7.82ꢀ7.84 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ 59.5, 125.6
(quin, J = 4.6 Hz), 127.8, 129.0, 131.7, 133.2, 133.8, 138.1, 152.2ꢀ152.8;
19F NMR (376 MHz, DMSO-d6) δ 64.3 (dm, 4F, J = 150.6 Hz),
86.3ꢀ87.9 (m, 1F); MS (EI) m/z 217 (100), 109 (29), 89 (11), 77 (13);
HRMS (ESIꢀ) m/z calcd for C13H10F5O2S2 [M ꢀ H]ꢀ 357.00462,
found 357.00479.
(3) (a) Bowden, R. D.; Greenhall, M. P.; Moilliet, J. S.; Thomson,
J. US 5741935, 1997, and WO 9705106, 1997. (b) Bowden, R. D.;
Comina, P. J.; Greenhall, M. P.; Kariuki, B. M.; Loveday, A.; Philp, D.
Tetrahedron 2000, 56, 3399–3408. (c) Chambers, R. D.; Spink, R. C. H.
Chem. Commun. 1999, 883–884.
(4) Umemoto, T. WO 2008/118787, 2008.
(5) (a) Sipyagin, A. M.; Bateman, C. P.; Tan, Y.-T.; Thrasher, J. S.
J. Fluorine Chem. 2001, 112, 287–295. (b) Sipyagin, A. M.; Enshov, V. S.;
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’ ASSOCIATED CONTENT
Supporting Information. copies of 1H, 13C, 19F, and 31
P
S
b
NMR spectra of newly synthesized products. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
beier@uochb.cas.cz
’ ACKNOWLEDGMENT
Support for this work from the Academy of Sciences of the
Czech Republic (Research Plan AVZ40550506) is gratefully
acknowledged.
’ REFERENCES
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