Photoinduced addition and addition-elimination reactions of perfluoroalkyl iodides to electron-deficient olefins

Article abstract of DOI:10.1016/j.tet.2012.06.028

Photoinduced radical perfluoroalkylation of various simple electron-deficient olefins was achieved in the presence of an aqueous Na ₂S₂O₃ solution. The reactions proceeded smoothly to give addition or addition-elimination

Full text of DOI:10.1016/j.tet.2012.06.028

Tetrahedron 68 (2012) 6856e6861
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Photoinduced addition and additioneelimination reactions of perfluoroalkyl
iodides to electron-deficient olefins
*
Tomoko Yajima , Ishrat Jahan, Takayuki Tonoi, Manami Shinmen, Aya Nishikawa, Kanako Yamaguchi,
Izumi Sekine, Hajime Nagano
Department of Chemistry, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Photoinduced radical perfluoroalkylation of various simple electron-deficient olefins was achieved in the
presence of an aqueous Na2S2O3 solution. The reactions proceeded smoothly to give addition or addi-
tioneelimination products. The ability of the products to be used as radical precursors or Michael
acceptors was also demonstrated.
Received 14 March 2012
Received in revised form 5 June 2012
Accepted 7 June 2012
Available online 15 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Iodoperfluoroalkylation
Additioneelimination reaction
Electron-deficient olefin
Photoinduced radical reaction
1. Introduction
electron-deficient olefins and would be a new, efficient synthetic
method for fluorine-containing building blocks. In this context, we
Perfluoroalkyl compounds have received considerable attention
not only as pharmaceuticals but also as new materials, and the de-
velopment of methods for their synthesis is desirable.1 The radical
addition of perfluoroalkyl iodides to olefins is one of the most effi-
cient and direct methods for the introduction of perfluoroalkyl
groups into organic compounds. Many examples of radical additions
of perfluoroalkyl iodides to electron-rich olefins have been reported
under various conditions and with high yields.2 However studies on
the addition of the perfluoroalkyl radical to electron-deficient ole-
fins are scarce, despite the versatility of the products as fluorine-
containing building blocks or monomers.3 Although Burton et al.
reported the photoinduced radical addition of perfluoroalkyl iodide
with electron-deficient olefins, side reactions, such as oligomeri-
zation were observed in most cases, and the examples were limited
report herein an efficient photoinduced radical perfluoroalkylation
of various simple electron-deficient olefins.
2. Results and discussion
First, the photoinduced reaction of perfluorohexyl iodide and
various acrylic-type compounds was examined (Table 1). On the
basis of the conditions used in our previous study, the reactions of
1aek (1 equiv) with perfluorohexyl iodide (5 equiv) were carried
out in the presence of aqueous Na2S2O3 under UV irradiation in
CH2Cl2. The reactions of methyl, ethyl, and benzyl acrylates 1aec
afforded the corresponding iodoperfluorohexylated products 2aec
in good yields, respectively (entries 1e3). Under these conditions,
the yields were not affected by the bulkiness of the alkyl moiety in
the ester group, although Burton et al. reported that small acrylate,
such as methyl acrylates afforded telomerized side products.3b Ethyl
crotonate (1d) also gave the iodoperfluorohexylated product 2d in
62% yield (entry 4). In addition, iodoperfluorohexylations of acrylic
acid (1e), acrolein (1f), and alkyl vinyl ketones (1g,1h,1i) proceeded,
although the yields of ketones (2g, 2h, 2i) were lower than the
others (entries 5e9). Amide 1j, nitrile 1k, and sulfone 1l also un-
derwent the reaction (entries 10e12). However, the reaction of ethyl
to several acrylic derivatives.3b Thus,
a novel, efficient per-
fluoroalkylation of electron-deficient olefins is desirable.
Recently, we reported an effective radical iodoper-
fluoroalkylation of acrylic acid derivatives bearing a chiral auxiliary
in the presence of an aqueous Na2S2O3 solution under UV irradia-
tion.4 The acrylic acid derivatives used in our previous study had
a bulky chiral auxiliary and exhibited low reactivity toward oligo-
merization. Therefore, we were interested in whether our reaction
conditions would be suitable for simple, easy-to-polymerize,
cinnamate (1m) gave the a
-perfluoroalkylated conjugated olefin 3.5
Second, the reactions of acrylates 1a and 1c with several fluo-
roalkyl iodides were investigated (Table 2). The addition of ethyl
difluoroiodoacetate to ethyl acrylate (1a) afforded product 4a in
* Corresponding author. E-mail address: yajima.tomoko@ocha.ac.jp (T. Yajima).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.028

T. Yajima et al. / Tetrahedron 68 (2012) 6856e6861
6857
Table 1
Photoinduced reaction of perfluorohexyl iodide with acrylic-type compounds6
Table 3
Photoinduced reaction of perfluorohexyl iodide with
a
-substituted electron-
deficient olefins6
Entry
Substrate
Time (h)
Product
Yield (%)
1
2
3
4
5
6
7
8
Ethyl acrylate (1a)
1
1
3
1
3
4
1
1
1
3
5
4
4
2a
2b
2c
2d
2e
2f
2g
2h
2i
97
91
76
62a
81
87
40
57
52
85
49
87
87
Entry
Substrate
Time (h)
Product
Yield (%)
E/Za
Methyl acrylate (1b)
Benzyl acrylate (1c)
Ethyl crotonate (1d)
Acrylic acid (1e)
1
2
3
4
5
5a (R¼H, E¼CO2Et)
1.5
16
2
2
8
6a
7
6b
6c
6d
91
76
81
63
70
d
5a (R¼H, E¼CO2Et)
100:0
54:46
100:0
40:60
5b (R¼PhCH2, E¼CO2Et)
5c (R¼PhCH2, E¼CN)
5d (R¼CO2Et, E¼CO2Et)
Acrolein (1f)
Methyl vinyl ketone (1g)
Ethyl vinyl ketone (1h)
n-Pentyl vinyl ketone (1i)
N,N-Dimethylacrylamide (1j)
Acrylonitrile (1k)
a
E/Z ratio was determined by 1H NMR. E/Z geometry was determined by NOE.
9
10
11
12
13
2j
2k
2l
Because perfluoroalkylated olefins are useful fluorine-
containing building blocks or monomers for fluorine-containing
polymers,6 we also investigated the one-pot additioneelimination
reactions of perfluorohexyl iodide with acrylic-type olefins 1a, 1d,
and 1h (Table 4). When the photoirradiation reaction was com-
pleted, DBU was added to the reaction mixture, and the solutionwas
stirred for an additional 1 h. The additioneelimination reaction
proceeded smoothly to yield the corresponding (E)-olefins.5b
Phenyl vinyl sulfone (1l)
Ethyl cinnamate (1m)
3
a
Diastereomeric ratio of the products (70:30) was determined by 1H NMR. The
relative configurations of the products were not determined.
Table 2
Photoinduced reaction of fluoroalkyl iodides with electron-deficient olefins
Table 4
One-pot additioneelimination reaction of perfluorohexyl iodide with electron-
deficient olefinsa
Entry
Substrate
Rf
Time (h)
Product
Yield (%)
1
2
3
4
Ethyl acrylate (1a)
Benzyl acrylate (1c)
Benzyl acrylate (1c)
Benzyl acrylate (1c)
CF2CO2Et
CF3
3
6
3
3
4a
4b
4c
4d
80
50
87
89
n-C3F7
iC3F7
Entry
Substrate
Time (h)b
Product
Yield (%)
1
2
3
Ethyl acrylate (1a)
Ethyl crotonate (1d)
N,N-Dimethylacrylamide (1h)
1þ1
1þ1
4þ1
9a
9b
9c
82
58
71
80% yield (entry 1). Thus, this reaction could be effectively utilized
for the synthesis of difluoro compounds. The reaction of 1c with
trifluoromethyl iodide also afforded the iodotrifluoromethylated
product 4b, although the yield was lower than those with other
iodides (entry 2). The addition of n-perfluoropropyl and i-per-
fluoropropyl iodides to benzyl acrylate (1c) proceeded smoothly to
give the corresponding iodoperfluoroalkylated products in good
yields (entries 3 and 4, respectively).
a
After the photoinduced reaction was complete, DBU was added to the mixture
and the solution was stirred at rt.
b
(The reaction time of photoirradiation)þ(the reaction time after the addition of
DBU).
To demonstrate the synthetic utility of the perfluoroalkylated
olefins, wecarriedoutthe synthesisof a b-amino ester prepared from
Next, the radical perfluoroalkylation of a-substituted electron-
the additioneelimination product 9a (Scheme 2). The aza-Michael
addition of N-benzylhydroxylamine to perfluoroalkylated olefin 9a
proceeded smoothly to give adduct 10 in 89% yield.7 The reduction of
the N-benzylhydroxylamino group followed by acetylation gave the
deficient olefins 5aed was investigated (Table 3). In all these
cases, the additioneelimination reaction occurred to afford olefinic
products 6. The reaction of ethyl methacrylate (5a) afforded 6a in
91% yield (entry 1).
A longer reaction time led to diper-
perfluoroalkylated acetyl
b-amino ester in good yield.
fluoroalkylation and gave the product 7 (entry 2). While the ester
substrate 5b gave 6b in 81% yield with E/Z¼54:46, the cyanide
substrate 5c exclusively afforded (E)-6c exclusively in 63% yield
(entries 3 and 4). Reaction of diethyl itaconate (5d) proceeds with
an E/Z selectivity of 40:60, and the E/Z isomers were easily sepa-
rated by silica gel column chromatography (entry 5).
To demonstrate the applicability of the perfluoroalkyl products
of this new addition reaction, the radical allylation of 2a was then
carried out using allyltributyltin and triethylborane. The iodoper-
fluoroalkylated product 2a acted as a good radical precursor and
was transformed to the desired product 8 in good yield (79%)
(Scheme 1).
Scheme 2.
The proposed mechanisms of the reactions are shown in
Scheme 3. First, perfluoroalkyl iodide can be homolytically
cleaved to generate
irradiation (Eq. 1).
a perfluoroalkyl radical under photo-
Scheme 1.

6858
T. Yajima et al. / Tetrahedron 68 (2012) 6856e6861
Scheme 3.
Perfluorohexyl iodide exhibits an absorption maximum at
270 nm (Fig. 1). The photoinduced reactions were proceeded
rapidly in Pyrex tube or quartz tube and the use of
a
a
a 330e470 nm transmission filter also drive the reaction, al-
though a longer reaction time is needed to complete the reaction
(5 h). To confirm the generation of the perfluoroalkyl radical,
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) was reacted with
perfluorohexyl iodide under photoirradiation in Pyrex tube, and
TEMPO adduct 12 was obtained.8 Moreover, when TEMPO was
added in the standard reaction (Table 1, entry 1), the reaction did
not proceed.
Scheme 4.
3. Conclusion
We successfully carried out the photoinduced radical per-
fluoroalkylation of various simple electron-deficient olefins in the
presence of an aqueous Na2S2O3 solution. Perfluoroalkyl iodides
reacted readily with various electron-deficient terminal and
substituted olefins to afford iodoperfluoroalkylated products in
high yields. The photoinduced reaction of -substituted electron-
b-
a
deficient olefins gave olefinic products via an additioneelimina-
tion reaction. In addition, we demonstrated the ability of the
products to serve as radical precursors or Michael acceptors, thus
demonstrating the usefulness of the products as fluorine-
containing building blocks.
4. Experimental section
4.1. General
Fig. 1. UVevis spectrum of C6F13I in CH2Cl2.
All reactions were performed with a high-pressure Hg lamp
(Ushio, 450W). 1H NMR spectra were recorded on a JEOL AL-400
(400 MHz) or EX-400 (400 MHz) spectrometer with CDCl3 or
CD3OD as the solvent and tetramethylsilane as an internal standard
unless otherwise noted. 13C NMR spectra were recorded on the
instruments operating at 100.5 MHz with CDCl3 or CD3OD as the
Next, the formed perfluoroalkyl radical adds to the b-position
of olefin 1 and a radical intermediate is formed. Finally, the io-
dine atom transfers from perfluoroalkyl iodide to the in-
termediate radical, regenerating the initial perfluoroalkyl radical
and producing the iodoperfluoroalkylated product 2 (Eq. 2). In
the case of the reaction with ethyl cinnamate (R¼Ph), the per-
solvent and internal standard (d 77.0). IR spectra were taken on
a SHIMADZU FTIR-8700 spectrometer. Mass spectra (EIþ) were
obtained on a JEOL JMS-700 mass spectrometer. Mass spectra (ESI)
were obtained on a Thermo Exactive. Precoated Merck Kieselgel 60
F254 and Kanto silica gel 60 (spherical neutral) were used for thin
layer chromatography and flash chromatography, respectively.
fluoroalkyl radical initially adds to the a-position of the olefin to
afford a stable benzyl radical intermediate. After iodine atom
transfer, the resulting iodide is eliminated to give the conjugated
olefin 3 (Eq. 3). Moreover, the reaction with
5 also proceeds through the -iodo ester, although the tertiary
iodide is easily eliminated to give olefin 6 (Eq. 4). Despite the
presence of relatively acidic fluoroalkylated side -protons,
a-substituted olefin
a
b
4.2. Typical procedure for photoinduced perfluoroalkylation
dehydroiodination occurred on the R side of the methylene to
give alkene 6. The regioselectivity of the elimination is influ-
enced by the fluorine substitution on the
more, in the case of methacrylic-type product 6 (R¼H) with
longer reaction time, a second radical addition occurred (Eq. 4)
(Scheme 4).
In a Pyrex glass tube were placed olefin (0.2 mmol), per-
fluoroalkyl iodide (1.0 mmol), and CH2Cl2 (5 mL). Then Na2S2O3
(0.5 mmol, 79 mg) and water (1 mL) were added to the mixture.
After sealing the tube, the mixture was shaked and then irradiated
with a Hg lamp at room temperature. After the reaction was
b
-carbon.9 Further-

T. Yajima et al. / Tetrahedron 68 (2012) 6856e6861
6859
completed, the mixture was extracted with CH2Cl2. The extract was
washed with brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting residue was purified by silica
gel column chromatography to afford pure product.
1723, 1428, 1363, 1239, 1146, 1074, 813, 708; MS m/z 516 (Mþ, 11%),
370 (19), 43 (100), HRMS calcd for C10H6F13IO 515.9256, found
515.9244.
4.2.8. 3-Iodo-4-perfluorohexyl-2-pentanone (2h). Colorless oil; 1H
4.2.1. Ethyl 2-iodo-3-perfluorohexylpropanoate (2a). Colorless oil;
NMR (CDCl3)
d
1.18 (t, J¼7.2 Hz, 3H, CH3), 2.60 (dq, J¼17.4, 7.2 Hz,1H,
1H NMR (CDCl3)
d
1.29 (t, J¼7.6 Hz, 3H, CH3), 2.71 (m,1H, C6F13CHH),
CH3CHH), 2.69 (m, 1H, C6F3CHH), 3.00 (dq, J¼12.0, 7.2 Hz, 1H,
CH3CHH), 3.44 (m, 1H, C6F3CHH), 4.77 (dd, J¼8.8, 3.6 Hz, 1H, CHI);
3.33 (m, 1H, C6F13HH), 4.25 (q, J¼7.6 Hz, 2H, OCH2), 4.59 (dd, J¼3.2,
10.8 Hz, 1H, CH); 13C NMR (CDCl3)
d
5.4, 13.7, 38.6 (t, J¼20.4 Hz,
13C NMR (CDCl3)
d
8.5, 14.9, 32.1, 36.4 (t, J¼20.4 Hz, C6F13C), 203.0;
C6F13C), 62.5, 170.0; IR (neat, cmꢀ1) 2989, 1743, 1430, 1201, 1146,
961, 846, 730, 657, 530; MS m/z 546 (Mþ, 100%), 473 (58), 363 (49),
327 (42), 203 (10); HRMS calcd for C11H8F13IO2 545.9361, found
545.9349.
IR (neat, cmꢀ1) 2977, 1707, 1206, 1140, 704; HRMS (ESIþ) [MþNaþ]
calcd for C11H8F13INa 552.9305, found 552.9307.
4.2.9. 3-Iodo-4-perfluorohexyl-2-octanone (2i). Colorless oil; 1H
NMR (CDCl3)
d
0.90 (t, J¼6.8 Hz, 3H, CH3), 1.39e1.26 (m, 4H,
4.2.2. Methyl 2-iodo-3-perfluorohexylpropanoate (2b). Colorless
CH3C2H4), 1.66 (qui, J¼7.2 Hz, 2H, C3H7CH2), 2.61 (dd, J¼16.8, 7.2 Hz,
1H, C4H9CHH), 2.63 (m, 1H, C6F3CHH), 2.91 (dd, J¼16.8, 7.2 Hz, 1H,
C4H9CHH), 3.44 (m, 1H, C6F3CHH), 4.75 (dd, J¼10.2, 3.2 Hz, 1H, CHI);
oil; 1H NMR (CDCl3)
d 2.73 (m, 1H, C6F13CHH), 3.33 (m, 1H,
C6F13CHH), 3.80 (s, 3H, CH3), 4.62 (dd, J¼3.6, 10.4 Hz, 1H, CH); 13C
NMR (CDCl3)
d
4.4, 38.6 (t, J¼20.7 Hz, C6F13C), 53.5, 170.6; IR (neat,
13C NMR (CDCl3)
d
13.8, 15.7, 22.3, 23.8, 31.0, 36.3 (t, J¼21.0 Hz,
cmꢀ1) 2961, 1748, 1441, 1238, 1207, 1146, 846, 699; MS m/z 532 (Mþ,
67%), 473 (31), 386 (34), 59 (100); HRMS calcd for C10H6F13IO2
531.9205, found 531.9230.
C6F13C), 38.9, 202.3; IR (neat, cmꢀ1) 2960, 1715, 1352, 1245, 1145,
701; HRMS (ESIþ) [MþNaþ] calcd for C14H14F13INa 594.9774, found
594.9760.
4.2.3. Benzyl 2-iodo-3-perfluorohexylpropanoate (2c). Colorless oil;
4.2.10. N,N-Dimethyl-2-iodo-3-perfluorohexylbutanamide (2j). White
1H NMR (CDCl3)
d
2.72 (m, 1H, C6F13CHH), 3.34 (m, 1H,
powder; mp 50.7 ꢁC (from hexane/AcOEt 5:1); 1H NMR (CDCl3)
d 2.74
C6F13CHH), 4.65 (dd, J¼3.5, 10.6 Hz, 1H, CH), 5.19 (d, J¼12.4 Hz,
(m, 1H, C6F13CHH), 2.99 (s, 3H, CH3), 3.06 (s, 3H, CH3), 3.58 (m, 1H,
1H, PhCHH), 5.22 (d, J¼12.4 Hz, 1H, PhCHH), 7.37 (m, 5H, Ph); 13C
C6F13CHH), 4.78 (dd, J¼3.1, 9.4 Hz, 1H, CH); 13C NMR (CDCl3)
d 4.9,
NMR (CDCl3)
d
5.1 (t, J¼2.9 Hz, C6F13CH2C), 38.7 (t, J¼20.4 Hz,
36.8, 37.7, 38.4 (t, J¼19.4 Hz, C6F13C), 168.6; IR (KBr, cmꢀ1) 3020,
1658, 1362, 1243, 1216, 1146, 757, 668; MS m/z 545 (Mþ, 51%), 419
(14), 418 (100), 390 (84); HRMS calcd for C11H9F13INO 544.9522,
found 544.9515.
C6F13C), 68.4, 128.6, 128.8, 128.9, 134.8, 170.2; IR (neat, cmꢀ1
)
3009, 1734, 1452, 1391, 1235, 1202, 1144, 698; MS m/z 481 (MþꢀI,
65%), 107 (68), 91 (100); HRMS calcd for C16H10F13O2 481.0473,
found 481.0451.
4.2.11. 2-Iodo-3-perfluorohexylpropionitrile (2k). White powder;
4.2.4. Ethyl 2-iodo-3-perfluorohexylbutanoate (2d). Diastereomer
mixture (70:30); colorless oil; IR (neat, cmꢀ1) 2989, 1740, 1464,
1375, 1240, 1148, 1029, 809,762, 699, 653, 531; MS m/z 560 (Mþ,
100%), 487 (45), 433 (57), 405 (44), 385 (44), 341 (35), 337 (26);
HRMS calcd for C12H10F13IO2 559.9518, found 559.9518; major
mp 59.8 ꢁC (from hexane/AcOEt 5:1); 1H NMR (CDCl3)
d
2.88 (m,1H,
C6F13CHH), 3.12 (m, 1H, C6F13CHH), 4.50 (dd, J¼4.4, 10.4 Hz, 1H, CH);
13C NMR (CDCl3)
d
ꢀ20.3 (t, J¼4.8 Hz, C6F13CH2C), 40.3 (t, J¼21.4 Hz,
C6F13C), 117.7; IR (KBr, cmꢀ1) 2974, 1238, 1209, 1192, 1142, 799, 707,
527; MS m/z 499 (Mþ, 100%), 372 (81), 180 (38), 69 (56); HRMS;
calcd for C9H3F13IN 498.9103, found 498.9119.
isomer: 1H NMR (CDCl3)
d
1.28 (t, J¼7.2 Hz, 3H, CH3), 1.43 (d,
J¼7.2 Hz, 3H, CH3), 2.82 (m, 1H, CH), 4.23 (q, J¼7.2 Hz, 2H, CH2),
4.70 (d, J¼6.6 Hz, 1H, ICH); 13C NMR (CDCl3)
d
1.2, 13.8, 20.1, 38.3 (t,
4.2.12. (1-Iodo-2-perfluorohexylethyl)sulfonylbenzene (2l). White
J¼20.4 Hz, C6F13C), 62.6, 170.3; minor isomer: 1H NMR (CDCl3)
powder; mp 46.2 ꢁC (from CH2Cl2); 1H NMR (CDCl3)
d 2.80 (m, 1H,
d
1.27 (t, J¼7.2 Hz, 3H, CH3), 1.55 (d, J¼7.2 Hz, 3H, CH3), 2.87 (m,
C6F13CHH), 3.41 (m, 1H, C6F13CHH), 5.01 (dd, J¼1.6, 10.4 Hz, 1H, CH),
1H, CH), 4.21 (q, J¼7.2 Hz, 2H, CH2), 4.80 (d, J¼3.9 Hz, 1H, ICH); 13
C
7.57 (t, J¼7.6 Hz, 2H, Ph), 7.69 (t, J¼7.6 Hz, 1H, Ph), 7.92 (d, J¼7.6 Hz,
NMR (CDCl3)
170.0.
d
0.2, 13.9, 16.6, 43.2 (t, J¼20.4 Hz, C6F13C), 62.4,
2H, Ph); 13C NMR (CDCl3)
d
21.2, 35.2 (t, J¼21.3 Hz, C6F13C), 129.4,
130.0, 133.6, 135.1; IR (KBr, cmꢀ1) 2975, 1450, 1368, 1335, 1239,
1210, 1083, 1073, 739, 709, 537, 525; MS m/z 614 (Mþ, 23%), 125
(100), 77 (52); HRMS calcd for C14H8F13IO2S 613.9083, found
613.9055.
4.2.5. 2-Iodo-3-perfluorohexylpropanoic acid (2e). Colorless plate
crystal; mp 77.8 ꢁC; 1H NMR (CD3OD)
d 2.62 (m, 1H, C6F13CHH), 3.15
(m, 1H, C6F13CHH), 4.76 (dd, J¼3.6, 10.4 Hz, 1H, CH); 13C NMR
(CD3OD)
d
6.2, 40.1 (t, J¼21.4 Hz, C6F13C), 174.4; IR (KBr, cmꢀ1) 3006,
4.2.13. Ethyl (E)-2-perfluorohexyl-3-phenyl-2-propenoate (3). Colorless
1717, 1430, 1363, 1204, 1146, 913; MS m/z 518 (Mþ, 100%), 391 (30),
372 (36), 327 (55), 69 (75); HRMS calcd for C9H4F13IO2 517.9048,
found 517.9064.
oil; 1H NMR (CDCl3)
d
1.17 (t, J¼7.2 Hz, 3H, CH3), 4.23 (q, J¼7.2 Hz, 2H,
CH2), 7.30 (s, 1H, CH), 7.38 (m, 5H, Ph); 13C NMR (CDCl3)
d
13.5, 62.1,
123.5 (t, J¼22.3 Hz, C6F13C), 128.7, 128.9, 130.3, 132.5, 141.2 (t, J¼8.7 Hz,
C6F13C]C), 163.6 (t, J¼2.0 Hz, C]O); IR (neat, cmꢀ1) 2989, 1739, 1734,
1641, 1452, 1362, 1235, 1199, 1146, 1082, 1026, 806, 697, 667; MS m/z
449 (MþꢀOEt, 38), 449 (21), 177 (81), 84 (100); HRMS calcd for
C15H6F13O 449.0211, found 449.0229.
4.2.6. 2-Iodo-3-perfluorohexylpropanal (2f). Colorless plate crystal;
mp 39.5 ꢁC (from hexane/AcOEt 5:1); 1H NMR (CDCl3)
d
2.68 (m,1H,
C6F13CHH), 3.34 (m, 1H, C6F13CHH), 4.89 (ddd, J¼2.0, 5.2, 8.4 Hz, 1H,
CH), 9.24 (s, 1H, CHO); 13C NMR (CDCl3)
d
19.7, 34.1 (t, J¼22.3 Hz,
C6F13C), 188.1; IR (KBr, cmꢀ1) 2928, 1727, 1238, 1208, 1143, 708, 657;
MS m/z 502 (Mþ, 100%), 356 (24), 327 (60), 69 (33); HRMS calcd for
C9H4F13IO 501.9100, found 501.9120.
4.2.14. Diethyl 4,4-difluoro-2-iodopentanedioate (4a). Colorless oil;
1H NMR (CDCl3)
d
1.29 (t, J¼7.2 Hz, 3H, CH3), 1.37 (t, J¼7.2 Hz, 3H,
CH3), 2.73 (m, 1H, CF2CHH), 3.23 (m, 1H, CF2CHH), 4.26 (q, J¼7.2 Hz,
2H, OCH2), 4.33 (q, J¼7.2 Hz, 2H, OCH2), 4.57 (dd, J¼3.6, 10.0 Hz, 1H,
4.2.7. 3-Iodo-4-perfluorohexyl-2-butanone (2g). Colorless oil; 1H
CH); 13C NMR (CDCl3)
d
7.2 (t, J¼4.9 Hz, CF2CH2C), 13.6, 13.9, 41.6 (t,
NMR (CDCl3)
d
2.47 (s, 3H, CH3), 2.63 (m, 1H, C6F13CHH), 3.40 (m,
J¼23.1 Hz, CF2C), 62.3, 63.3, 114.2 (t, J¼251.6 Hz, CF2), 162.8 (t,
J¼31.3 Hz, CF2C]O), 170.4; IR (neat, cmꢀ1) 2987, 1770, 1736, 1376,
1304, 1198, 1132, 1093, 1016, 855; MS m/z 350 (Mþ, 19%), 304 (73),
1H, C6F13CHH), 4.77 (dd, J¼3.6, 14.2 Hz, 1H, CH); 13C NMR (CDCl3)
d
15.9, 25.8, 36.4 (t, J¼20.4 Hz, C6F13C), 199.6; IR (neat, cmꢀ1) 3006,

6860
T. Yajima et al. / Tetrahedron 68 (2012) 6856e6861
249 (41), 223 (92), 195 (83), 167 (100); HRMS calcd for C9H13F2IO4
349.9827, found 349.9799.
J¼18.8 Hz, 2H, C6F13CH2), 4.27 (q, J¼6.8 Hz, 2H, OCH2), 4.31 (q,
J¼6.8 Hz, 2H, OCH2), 7.09 (s, 1H, CH); 13C NMR (CDCl3)
d 14.2 (2C),
28.0 (t, J¼21.4 Hz, C6F13C), 61.6, 62.5, 133.2, 135.1, 165.0, 165.7; IR
(neat, cmꢀ1) 2990, 1734, 1730, 1239, 1205, 1145, 1126, 1072, 1033,
735, 708; MS m/z 504 (Mþ, 9%), 459 (97), 430 (75),161 (100); HRMS:
calcd for C15H13F13O4 504.0606, found 504.0590; (Z)-isomer: major,
4.2.15. Benzyl 2-iodo-4-trifluoromethylbutanoate (4b). Colorless oil;
1H NMR (CDCl3)
d 2.77 (m, 1H, CF3CHH), 3.26 (m, 1H, CF3CHH), 4.54
(dd, J¼4.4, 9.8 Hz, 1H, CH), 5.20 (s, 2H, PhCH2), 7.37 (m, 5H, Ph); 13
C
NMR (CDCl3)
d
5.9 (q, J¼3.3 Hz, CF3CH2C), 41.1 (q, J¼29.7 Hz, CF3C),
more polar isomer; Colorless oil; 1H NMR (CDCl3)
d
1.31 (t, J¼7.6 Hz,
68.1, 125.2 (q, J¼275.5 Hz, CF3), 128.3, 128.6, 134.6, 169.7; IR (neat,
cmꢀ1) 3037, 1734, 1457, 1260, 1151, 969, 753, 698; MS m/z 231
(MþꢀI, 84%), 107 (66), 91 (100); HRMS calcd for C11H10F3O2
231.0632, found 231.0654.
6H, CH3 ꢂ2), 3.18 (t, J¼18.0 Hz, 2H, C6F13CH2), 4.24 (q, J¼7.6 Hz, 2H,
OCH2), 4.29 (q, J¼7.6 Hz, 2H, OCH2), 6.24 (s,1H, CH); 13C NMR (CDCl3)
d
13.9, 14.2, 35.2 (t, J¼22.3 Hz, C6F13C), 61.6, 62.2, 130.8, 133.5, 164.5,
166.1; IR (neat, cmꢀ1) 2990, 1739, 1733, 1382, 1352, 1190, 1146, 1096,
1032, 829, 812, 733, 708; MS m/z 504 (Mþ, 5%), 459 (25), 431 (100);
HRMS: calcd for C15H13F13O4 504.0606, found 504.0585.
4.2.16. Benzyl 2-iodo-3-perfluoropropylbutanoate (4c). Colorless
oil; 1H NMR (CDCl3)
d 2.68 (m, 1H, C3F7CHH), 3.32 (m, 1H,
C3F7CHH), 4.65 (dd, J¼4.0, 10.8 Hz, 1H, CH), 5.19 (d, J¼12.4 Hz, 1H,
4.2.22. Ethyl 1-perfluorohexyl-2-(perfluorohexylmethyl)-2-propenoate
PhCHH), 5.22 (d, J¼12.4 Hz, 1H, PhCHH), 7.37 (m, 5H, Ph); 13C NMR
(7). Colorless oil; 1H NMR (CDCl3)
d
1.37 (3H, t, J¼7.6 Hz, OCH2CH3),
(CDCl3)
d
4.9 (t, J¼3.3 Hz, C3F7CH2C), 38.2 (t, J¼20.6 Hz, C3F7C),
3.52 (2H, m, C6F13CH2), 4.34 (2H, q, J¼7.6 Hz, OCH2), 6.99 (1H, m,
68.2, 128.3, 128.6, 128.7, 134.6, 169.9; IR (neat, cmꢀ1) 3038, 1739,
1354, 1225, 1186, 1127, 909, 737, 698; MS m/z 331 (MþꢀI, 71%), 107
(65), 91 (100); HRMS calcd for C13H10F7O2 331.0569, found
331.0591.
C6F13CH]C); 13C NMR (CDCl3)
d
13.8, 28.8 (t, JCeF¼57.4 Hz, C6F13C),
63.2, 129.4 (t, JCeF¼60.8 Hz, C6F13C), 164.4; MS m/z 705 (MþꢀOEt,
100%); HRMS calcd for C16H3O2F26 ([M-OEt]þ) 704.9769, found
704.9749.
4.2.17. Benzyl 2-iodo-3-perfluoroisopropylbutanoate (4d). Colorless
4.3. Synthesis of ethyl 2-(perfluorohexylmethyl)-4-
pentenoate (8)
oil; 1H NMR (CDCl3)
d
2.69 (m, 1H, iC3F7CHH), 3.42 (m, 1H,
iC3F7CHH), 4.66 (dd, J¼3.2, 11.2 Hz, 1H, CH), 5.18 (d, J¼12.8 Hz, 1H,
PhCHH), 5.20 (d, J¼12.8 Hz, 1H, PHCHH), 7.37 (m, 5H, Ph); 13C NMR
To a solutionof iodide 2a (0.15 mmol) in dry CH2Cl2 (1.5 cm3) were
added allyltributyltin (0.30 mmol, 2 equiv) and Et3B (1.06 mol dmꢀ3
in hexane; 0.15 mmol, 1 equiv). The mixture was stirred at room
temperature for 3 h. KF and water were added and the reaction
mixture was stirred at room temperature for 3 h. After filtration, the
solvent was evaporated in vacuo. The residue was purified by flash
chromatographyon silicagel to give the productin 79%yield.1H NMR
i
i
(CDCl3)
d
6.6 (d, J¼4.2 Hz, C3F7CH2C), 35.8 (d, J¼18.9 Hz, C3F7C),
68.2, 128.4, 128.5, 128.6, 134.5, 169.9; IR (neat, cmꢀ1) 3038, 1743,
1648,1225,1154, 1120,1054, 697; MS m/z 331 (MþꢀI, 67%),107 (67),
91 (100); HRMS calcd for C13H10F7O2 331.0569, found 331.0544.
4.2.18. Ethyl 2-(perfluorohexylmethyl)-2-propenoate (6a). Colorless
oil; 1H NMR (CDCl3)
d
1.32 (t, J¼7.2 Hz, 3H, CH3), 3.19 (t, J¼18.6 Hz, 2H,
(CDCl3)
d
1.27 (3H, t, J¼7.3 Hz, OCH2CH3), 2.18 (1H, m, C6F13CHH), 2.34
iC3F7CH2), 4.25 (q, J¼7.2 Hz, 2H, OCH2), 5.90 (s,1H, ]CHH), 6.55 (s,1H,
(1H, m, CH2]CHCHH), 2.46 (1H, m, CH2]CHCHH), 2.67 (1H, m,
C6F13CHH), 2.88 (1H, m, C6F13CH2CHCO2), 4.18 (2H, q, J¼7.3 Hz,
OCH2), 5.11 (2H, m, CH2]CH), 5.71 (1H, m, CH2]CH); 13C NMR
]CHH);13C NMR (CDCl3)
d
14.2, 32.4(t, J¼22.4Hz, C6F13C), 61.5,129.4,
131.9, 165.5; IR (neat, cmꢀ1) 2990, 1729, 1639, 1366, 1319, 1241, 1067,
1027, 964, 813, 701; MS m/z 432 (Mþ, 12%), 405 (16), 387 (100), 313
(28), 113 (61); HRMS calcd for C12H9F13O2 432.0395, found 432.0397.
(CDCl3) d
14.1, 36.9, 61.1,118.6,133.5,173.5; IR (neat, cmꢀ1) 2934,1742,
1241, 1193, 1146, 732, 708, 698, 655, 568; MS m/z 460 (Mþ, 100%);
HRMS calcd for C14H13O2F13 460.0708, found 460.0732.
4.2.19. Ethyl 2-(perfluorohexylmethyl)-4-phenyl-2-butenoate
(6b). E/Z¼54:46 mixture; colorless oil; 13C NMR (CDCl3)
d
14.2
4.4. Typical procedure for iodoperfluoro
alkylationeelimination
(2C), 28.1 (t, J¼23.3 Hz, C6F13C), 35.4 (t, J¼19.3 Hz, C6F13C), 35.6,
36.4, 61.2, 61.5, 121.2, 121.8, 126.7, 127.0, 128.7 (2C), 128.9, 129.0,
137.9, 139.2, 147.8, 149.0, 166.2, 166.5; IR (neat, cmꢀ1) 2987, 1717,
1653, 1365, 1307, 1241, 1146, 760, 707; MS m/z 522 (Mþ, 100%), 477
(49), 476 (46), 449 (81); HRMS: calcd for C19H15F13O2 522.0864,
In a Pyrex glass tubewere placed olefin (0.2 mmol), perfluoroalkyl
iodide (1.0 mmol), and CH2Cl2 (5 mL). Then Na2S2O3 (0.5 mmol,
79 mg) and water (1 mL) were added to the mixture. After sealing the
tube, the mixture was shaked and then irradiated with a Hg lamp at
room temperature. After the reaction was completed, DBU
found 522.0850. E-isomer: major isomer; 1H NMR (CDCl3)
d 1.30 (q,
J¼7.2 Hz, 3H, CH3), 3.56 (t, J¼18.4 Hz, 2H, C6F13CH2), 3.59 (d,
J¼7.6 Hz, 2H, PhCH2), 4.23 (q, J¼7.2 Hz, 2H, OCH2), 7.17e7.35 (m, 6H,
(0.3 mmol, 45 mL) was added and the reaction mixture was stirred at
CH, Ph); Z-isomer: minor isomer; 1H NMR (CDCl3)
d
1.30 (q,
room temperature. The reaction mixture was extracted with CH2Cl2.
The extract was washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure. The resulting residue was
purified by silica gel column chromatography to afford pure product.
J¼7.2 Hz, 3H, CH3), 3.16 (t, J¼18.8 Hz, 2H, C6F13CH2), 3.95 (d,
J¼7.6 Hz, 2H, PhCH2), 4.29 (q, J¼7.2 Hz, 2H, OCH2), 6.35 (t, J¼7.2 Hz,
1H, CH), 7.17e7.35 (m, 5H, Ph).
4.2.20. (Z)-2-(Perfluorohexylmethyl)-4-phenyl-2-butenenitrile
4.4.1. Ethyl (E)-3-perfluorohexylpropenoate (9a). Colorless oil; iso-
(6c). Colorless oil; 1H NMR (CDCl3)
d
3.03 (t, J¼17.6 Hz, 2H, C6F13CH2),
mer; 1H NMR (CDCl3)
d
1.34 (q, J¼7.6 Hz, 2H, CH3), 4.29 (q, J¼7.6 Hz,
2H, OCH2), 6.53 (td, J¼2.0, 15.6 Hz, 1H, ]CH), 6.85 (td, J¼11.6,
15.6 Hz, 1H, ]CH); 13C NMR (CDCl3)
14.1, 61.8, 130.59 (t,
3.80 (d, J¼7.6 Hz, 2H, PhCH2), 6.61 (t, J¼7.6 Hz, 1H, CH), 7.20 (d,
J¼8.0 Hz, 2H, Ph), 7.27 (t, J¼8.0 Hz, 1H, Ph), 7.34 (t, J¼8.0 Hz, 2H, Ph);
d
13C NMR (CDCl3)
d
35.8 (t, J¼22.4 Hz, C6F13C), 38.2, 103.0, 116.1, 127.1,
J¼24.0 Hz, C6F13C), 130.8 (t, J¼9.0 Hz, C6F13]C), 163.4; IR (neat,
cmꢀ1) 2991, 1738, 1371, 1319, 1240, 1199, 1146, 1031, 977, 720, 706,
535; MS m/z 373 (MþꢀOEt, 100%), 371 (14), 354 (6); HRMS: calcd
for C9H2F13O 372.9898, found 372.9884.
128.3, 128.9, 136.1, 154.3; IR (neat, cmꢀ1) 3034, 2226, 1604, 1498,
1456, 1434, 1352, 1239, 1146, 738, 699; MS m/z 475 (Mþ, 53%), 156
(100); HRMS: calcd for C17H10F13N 475.0605, found 475.0583.
4.2.21. Diethyl 2-(perfluorohexylmethyl)-2-butenenedioate (6d). (E)-
4.4.2. Ethyl (E)-3-perfluorohexyl-2-butenoate (9b). Colorless oil; 1H
Isomer: minor, less polar isomer; colorless oil; 1H NMR (CDCl3)
NMR (CDCl3)
d
1.32 (t, J¼7.2 Hz, 3H, CH2CH3), 2.27 (s, 3H, CH3), 4.24
d
1.32 (t, J¼6.8 Hz, 3H, CH3), 1.34 (t, J¼6.8 Hz, 3H, CH3), 3.90 (t,
(q, J¼7.2 Hz, 2H, CH2), 6.30 (s, 1H, CH); 13C NMR (CDCl3)
d 13.6, 14.4,

T. Yajima et al. / Tetrahedron 68 (2012) 6856e6861
6861
61.5, 125.8 (t, J¼8.9 Hz, C6F13C]C), 143.2 (t, J¼21.5 Hz, C6F13C]C),
4.6. Photoinduced reaction of perfluoroalkyl ioded with
TEMPO (12)
165.6; IR (neat, cmꢀ1) 2990, 1734, 1666, 1450, 1354, 1202, 1041, 888,
809, 746, 702, 648; MS m/z 432 (Mþ, 26%), 404 (32), 387 (90), 58
(100); HRMS: calcd for C12H9F13O2 432.0395, found 432.0415.
In
a Pyrex glass tube were placed perfluoroalkyl iodide
(0.1 mmol), TEMPO (0.1 mmol) and CH2Cl2 (2.5 mL). After sealing
the tube, the mixture was shaked and then irradiated with a Hg
lamp at room temperature for 1 h. After the reaction was com-
pleted, the mixture was concentrated under reduced pressure. The
resulting residue was purified by silica gel column chromatography
4.4.3. (E)-N,N-Dimethyl-3-perfluorohexylpropenamide (9c). Colorless
oil; 1H NMR (CDCl3)
d 3.06 (s, 3H, CH3), 3.14 (s, 3H, CH3), 6.78 (td,
J¼13.2, 13.2 Hz, 1H, CH]CH), 7.02 (d, J¼13.2 Hz, 1H, CH]CH); 13C
NMR (CDCl3)
d
35.9, 37.4, 128.1 (t, J¼22.3 Hz, C6F13C), 129.9 (t,
J¼7.8 Hz, C6F13CH]C), 163.2; IR (neat, cmꢀ1) 2942, 1679, 1645, 1499,
1404, 1366, 1239,1146, 1068, 970, 717; MS m/z 417 (Mþ, 58%), 398
(28), 373 (35), 370 (39); HRMS calcd for C11H8F13NO 417.0398, found
417.0360.
to afford pure product (12). 1H NMR (CDCl3)
d
1.19 (s, 12H, CH3ꢂ4),
1.55e1.64 (m, 6H, CH2ꢂ3); 13C NMR (CDCl3)
d 16.8, 20.7, 33.5 (t,
J¼4.8 Hz, OC), 40.4, 61.9; HRMS (ESIþ) [MþHþ] calcd for
C15H19F13NO 5476.1254, found 476.1248.
4.5. Synthesis of ethyl 2-(perfluorohexylmethyl)-3-
acetylaminopropane (11)
Acknowledgements
This work was supported by a grant from the Asahi Glass
Foundation.
To a solution of olefin 9a (0.2 mmol) in dry MeOH (4.0 cm3) was
added BnNHOH/HCl (0.22 mmol, 1.1 equiv) and Et3N (0.4 mmol,
2 equiv). The mixture was stirred at room temperature for 8 h. After
filtration, the solvent was evaporated in vacuo. The residue was
purified by flash chromatography on silica gel to give ethyl 2-
(perfluorohexylmethyl)-3-N-benzylhydroxylaminopropane (10) in
References and notes
1. (a) Kitazume, T.; Yamazaki, T. Experimental Methods in Organic Fluorine Chemis-
try; Kodansha Ltd.: Tokyo, 1998; (b) Welch, J. T.; Eswarakrishnan, S. Fluorine in
Bioorganic Chemistry; John Wiley & Sons: New York, NY, 1990; (c) Kirsh, P.
Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications; John Wiley &
Sons: New York, NY, 2004; (d) Uneyama, K. Organofluorine Chemistry; Blackwell:
89% yield. 1H NMR (CDCl3)
d
1.27 (t, 3H, J¼7.2 Hz, Me), 2.39 (m, 1H,
C6F13CHH), 2.67 (m,1H, C6F13CHH), 2.92 (m,1H, NCHH), 3.00 (m,1H,
NCHH), 3.20 (m, 1H, CH), 3.84 (d, 1H, J¼12.0 Hz, PhHH), 3.86 (d, 1H,
J¼12.0 Hz, PhHH), 4.19 (q, 2H, J¼7.2 Hz, OCH2), 4.87 (br s, 1H, OH),
ꢀ
ꢀ
United Kingdom, 2006; (e) Begue, J.-P.; Bonnet-Delpon, D. Bioorganic and Me-
dicinal Chemistry of Fluorine; John Wiley & Sons: New Jersey, 2008; (f) Fluorine in
Medicinal Chemistry and Chemical Biology; Ojima, I., Ed.; Blackwell: United
7.33 (m, 5H, Ph); 13C NMR (CDCl3)
d 14.0, 37.1, 60.9, 61.2, 65.0, 127.6,
ꢀ
128.4, 129.2, 172.7; IR (neat, cmꢀ1) 3414, 1733, 1652, 1240, 1200;
HRMS (ESIþ) [MþHþ] calcd for C19H19F13NO3 556.1157, found
556.1135.
Kingdom, 2009; (g) Fluorous Chemistry; Horvath, I. T., Ed.; Springer: Berlin, 2011;
(h) Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects
€
to Clinical Applications; Gouverneur, V., Muller, K., Eds.; Imperial College: London,
2012.
2. (a) Dolbier, W. R., Jr. Chem. Rev. 1996, 96, 1557e1584; (b) Takeyama, Y.; Ichinose,
Y.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1989, 30, 3159e3162; (c) Miura, K.;
Taniguchi, M.; Nozaki, K.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1990, 31,
6391e6394; (d) Miura, K.; Takeyama, Y.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
Jpn. 1991, 64, 1542e1553; (e) Yoshida, M.; Ohkoshi, M.; Aoki, N.; Ohnuma, Y.;
Iyoda, M. Tetrahedron Lett. 1999, 40, 5731e5734; (f) Tsuchii, K.; Imura, M.; Ka-
meda, N.; Hirao, T.; Ogawa, A. J. Org. Chem. 2004, 69, 6658e6665; (g) Barata-
Vallejo, S.; Postigo, A. J. Org. Chem. 2010, 75, 6141e6148.
3. For radical-mediated perfluoroalkylation reactions of electron-deficient olefins,
see: (a) Kamigata, N.; Fukushima, T.; Terakawa, Y.; Yoshida, M.; Iyoda, M. J. Chem.
Soc., Perkin Trans. 1 1991, 627e633; (b) Qiu, Z.-M.; Burton, D. J. J. Org. Chem. 1995,
60, 3465e3472.
To a solution of hydroxylamine 10 (0.2 mmol) in MeOH
(5.0 cm3) was added Pd/C (10%, 100 mg) and stirred under H2
atmosphere at room temperature for 8 h. After filtration, the sol-
vent was evaporated in vacuo. The residue was dissolved in dry
CH2Cl2 (2.0 cm3) and cooled to 0 ꢁC. Then Et3N (0.42 mmol,
2.1 equiv) and Ac2O (0.42 mmol, 2.1 equiv) were sequentially
added. After stirred at room temperature for 3 h, the mixture was
evaporated in vacuo. The residue was purified by flash chroma-
tography on silica gel to give ethyl 2-(perfluorohexylmethyl)-3-
acetylaminopropane (11) in 70% yield. 1H NMR (CDCl3)
d 1.29 (t,
4. Yajima, T.; Nagano, H. Org. Lett. 2007, 9, 2513e2515.
5. (a) Zhang, X.; Qing, F.-L.; Yu, Y. J. Org. Chem. 2000, 65, 7075e7082; (b) Kimura,
M.; Yamazaki, Y.; Kitazume, T.; Kubota, T. Org. Lett. 2004, 6, 4651e4654.
6. For a review, see: Billard, T. Chem.dEur. J. 2006, 12, 974e979.
7. Steurer, S.; Podlech, J. Eur. J. Org. Chem. 2002, 5, 899e916.
8. (a) Yamago, S.; Ukai, Y.; Matsumoto, A.; Nakamura, Y. J. Am. Chem. Soc. 2009, 131,
2100e2101; (b) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.; Zhang, Y.; Wang, J. J.
Am. Chem. Soc. 2011, 133, 16410e16413.
3H, J¼7.2 Hz, CH2CH3), 2.00 (s, 3H, C(O)CH3), 2.29 (m, 1H,
C6F13CHH), 2.63 (m, 1H, C6F13CHH), 3.04 (m, 1H, CH), 3.56 (m, 2H,
NCH2), 4.21 (q, 2H, J¼7.2 Hz, OCH2), 5.86 (br s, 1H, NH); 13C NMR
(CDCl3)
d )
14.0, 23.2, 38.4, 40.8, 61.6, 170.3, 172.7; IR (neat, cmꢀ1
3320, 3099, 2998, 1732, 1658; HRMS (ESIþ) [MþNaþ] calcd for
C14H14F13NO3Na 514.0664, found 514.0644.
9. Nicholas, P. P. J. Org. Chem. 1992, 57, 2741e2744.