Reactions of α-difluoro azides with olefins

Article abstract of DOI:10.1007/s11172-010-0364-0

Reactions of α-difluoro azides with olefins result in oxidative fluoroamination or amination of the C=C bond.

Full text of DOI:10.1007/s11172-010-0364-0

Russian Chemical Bulletin, International Edition, Vol. 59, No. 11, pp. 2114—2121, November, 2010
2114
Reactions of αꢀdifluoro azides with olefins
S. A. Lermontov,a A. N. Pushin,a S. V. Shkavrov,a and A. G. Polivanovab
aInstitute of Physiologically Active Compounds, Russian Academy of Sciences,
1 Severnyi pr., 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (495) 785 7024. Eꢀmail: lermon@ipac.ac.ru
bD. I. Mendeleyev University of Chemical Technology of Russia,
9 Miusskaya pl., 125047 Moscow, Russian Federation.
Eꢀmail: zagchem@mail.ru
Reactions of αꢀdifluoro azides with olefins result in oxidative fluoroamination or amination
of the C=C bond.
Key words: αꢀdifluoro azides, olefins, cycloaddition, fluoroamination.
αꢀDifluoro azides (i.e., compounds with the fragment
Reactions of nonfluorinated azides with C=Cꢀcontainꢀ
ing compounds are understood fairly well: they usually
involve [3+2] cycloaddition followed by elimination of
molecular nitrogen from intermediate 1,2,3ꢀtriazoline9
(Scheme 4).
N3—CF2—) were first obtained and studied by Knunyants
et al.1—3 These stable (at least up to 200 °C) organic azides
are highly reactive. Their most interesting property is that
they are oxidative fluorinating reagents for a wide range
of organic compounds containing heteroelements4—6
(Scheme 1).
Scheme 4
Scheme 1
This reaction is often used for the synthesis of aziriꢀ
dines.
Reactions of αꢀdifluoro azides with monoꢀ and disubꢀ
stituted acetylenes in high yields afford triazoles fluorinatꢀ
ed in the side chain7 (Scheme 2).
It is easy to see that aziridines obtained from αꢀdifluoꢀ
ro azides possess an interesting structural feature, viz., the
presence of the αꢀfluoro amine fragment
, in
which the C—F bond is known10,11 to be very labile
(Scheme 5).
Scheme 2
Scheme 5
Earlier,8 it has been found that αꢀdifluoro azides are
inert to 2,3ꢀdimethylbutadiene but react with norbornene
to give amination products (Scheme 3).
Under favorable conditions, this would lead to inꢀ
tramolecular nucleophilic substitution affording a new
C—F bond (Scheme 6).
Scheme 3
It can be seen in Scheme 6 that nucleophilic substituꢀ
tion at one C—N bond in the aziridine produces a 2ꢀfluoro
amine derivative, while the substitution at two bonds yields
1,2ꢀdifluoride; these processes are equivalent to oxidative
aminofluorination and difluorination of olefins, resꢀ
pectively.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2060—2067, November, 2010.
1066ꢀ5285/10/5911ꢀ2114 © 2010 Springer Science+Business Media, Inc.

Reactions of αꢀdifluoro azides with olefins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2115
Scheme 6
The signal assignments in the spectrum of compound
2b were confirmed by COSY and NOESY experiments.
To confirm the 2ꢀexoꢀ7ꢀsynꢀconfiguration, the signal
of H(7) should unambiguously be assigned, separately
from H(1) and H(4). The COSY spectrum shows cross
peaks for H(1) and H(4) coupled with H(2) and H(3),
the latter two being unambiguously assigned from the
1D spectrum; such cross peaks for H(7) are absent. The
NOESY experiment revealed no coupling between H(7),
H(2), and H(3); instead, the spectrum contains cross
peaks of the signals of NH and one of the components
H(3) (not H(2)), which provides convincing evidence
for the exoꢀsynꢀconfiguration of the F atom and the
NH group. This is additionally confirmed by the cross
peak for H(7) and the OMe group attached to the benzene
ring, as well as by JF(2)—HN = 7.5 Hz in the 19F {HN}
NMR spectrum.
Several αꢀdifluoro azides have been documentꢀ
ed.1—3,12—14 We obtained two typical representatives of
this family of reagents: 2ꢀhydroperfluoropropyl azide (I)
and methyl 3ꢀazidotetrafluoropropionate (II).
The synꢀconfiguration of the amide group with respect
to the F atom suggests the exoꢀattack of the azide on the
C=C bond of norbornene and, accordingly, the exoꢀstrucꢀ
ture of the intermediate aziridine.
It turned out that azides I and II indeed react with
olefins, the reaction rate largely depending on the strucꢀ
ture of the latter. Norbornenes react with azides most
readily (even at room temperature or under slight heatꢀ
ing). For instance, substituted benzonorbornadiene 1
reacts with azides I and II to give fluorinated amides 2a,b
as the sole products (Scheme 7).
The formation of only rearranged fluorinated amides
suggests the presence of considerable amounts of the
"open" aziridine form (A), the opening being undoubtedly
facilitated by the strong electronegative polyfluorinated
substituent at the N atom. The final products are obtained
by hydrolysis of labile intermediate imidoyl fluorides (deꢀ
tected in the reaction mixture by 19F NMR spectroscopy
prior to the hydrolysis).
The formation of amido fluorides 2a,b is of considerꢀ
able interest because fluorinated amines (notably fluoriꢀ
nated amino acids) are widely known as physiologically
active compounds.15 Currently existing routes to similar
structures involve many steps and much labor. The first
(to the best of our knowledge) direct synthesis16 of comꢀ
pounds like 2a,b from olefins and XeF2 in the presence of
acetonitrile afforded the target amido fluorides in low yields
within complex mixtures of products. Alternative methꢀ
ods involve reactions of olefins with N—F compounds in
acetonitrile17 and electrochemical fluoroamination of oleꢀ
fins in acetonitrile—Et3N•3HF.18,19
Scheme 7
W—M stands for the Wagner—Meerwein rearrangement
2: R = CHFCF3 (a), CF2COOMe (b); the yields are 40 (a) and 34% (b)

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Lermontov et al.
Norbornene reacts with azides I and II to give more
complex mixtures of products than in the case of benꢀ
zonorbornadiene 1. However, the character of the reacꢀ
tion (oxidative fluorination) is generally retained (Scheme 8).
and endoꢀH(5) and H(6) is evidence for the synꢀconfiguꢀ
ration of the substituent.
The formation of unsaturated amide 4 can be attributꢀ
ed to either in situ dehydrofluorination of fluoride 3 (pathꢀ
way a) or a parallel reaction (pathway b) involving a transꢀ
formation of intermediate cation B into unsaturated imiꢀ
doyl fluoride C followed by its hydrolysis to the final amide
4 (Scheme 9).
Scheme 8
Scheme 9
3 : 4 : 5 : 6
3 : 3 : 3 : 1
4 : 4 : 5 : 1
Yield (%)
92
a (R = CF3CHF)
b (R = MeOCOCF2)
89
Pathway b seems to be more plausible for the formaꢀ
tion of unsaturated amide 4. This assumption is corroboꢀ
rated by the high chemical resistance of fluoro amide 3a to
hydrolysis on silica gel as well as to acid and basic hydrolꢀ
ysis (Scheme 10).
It follows from Scheme 8 that all four products result
from the oxidation of a norbornene molecule: aminoꢀ
fluorination (3), oxyfluorination (5 and 6), and oxidative
amination (i.e., formal replacement of the C—H bond in
norbornene by a C—N bond) (4).
The structure of fluoro amide 3b was determined using
COSY and NOESY experiments. The absence of coupling
between the H(2) and endoꢀH(6) atoms in the COSY specꢀ
trum, which is yet revealed by NOESY, suggests the endoꢀ
configuration of the H(2) proton (and, accordingly, the
exoꢀconfiguration of the F atom). The observed spinꢀspin
coupling between H(7) and H(2) (soꢀcalled W constant)
in the COSY spectrum without a coupling between H(7)
and endoꢀH(5) and endoꢀH(6) is unambiguous evidence
for the antiꢀconfiguration of H(7) and, consequently, the
synꢀconfiguration of the substituent.
Scheme 10
The synꢀconfiguration of the substituent in amide 4b
was determined using the NOESY experiment. The specꢀ
trum reveals a coupling between the H(7) and exoꢀH(5)
and H(6) protons, showing no couplings between H(7)
and the olefinic protons or between the NH proton and
exoꢀH(5) and H(6). This is sufficient proof for the antiꢀ
configuration of the H(7) proton.
Explanations should be given for the formation of oxyꢀ
genꢀcontaining products 5 and 6. We noticed several facts.
1. When the reactions of norbornene with azides I and
II are carried out in dry CH2Cl2, the amounts and ratio of
esters 5 and 6 are always nearly the same, regardless of the
material of the ware (glass, quartz, or Teflon) in which the
reaction mixtures are kept prior to hydrolysis.
The structure of ester 5b was also identified using COSY
and NOESY experiments. As with amide 3b, the absence
of spinꢀspin couplings of H(2) with endoꢀH(5) and H(6)
in the COSY spectrum, which is revealed by NOESY,
suggests the exoꢀconfiguration of the F atom. The presꢀ
ence of the couplings of H(7) with H(2) and endoꢀH(3) in
the COSY spectrum without such couplings between H(7)
2. When the reaction is carried out in a Teflon NMR
tube, the 19F NMR spectrum exhibits a signal of the acid
fluoride R—CF(=NX) (δ 22, br.d) and, in low concentraꢀ
tion, a signal of the fragment N—CF2 (AB system) that
does not relate to the starting azide. Both the signals disꢀ
appear rapidly after the reaction mixture has been transꢀ
ferred to a glass tube.

Reactions of αꢀdifluoro azides with olefins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2117
3. When the reaction is carried out in a Teflon vessel,
the reaction mixture produces a voluminous precipitate
that disappears after the reaction mixture has been transꢀ
ferred to a glass tube. We failed to isolate the precipitate
because it is easily prone to hydrolysis.
We suggest the following explanation to the observed
phenomena. The reaction mixture always contains a conꢀ
siderable amount of HF liberated in the formation of unꢀ
saturated amide 4. When in contact with glass or quartz
ware, HF produces water (Si—OH + HF → SiF + H2O)
and hence hydrolysis takes place (Scheme 11).
Little research has been concerned with reactions of
αꢀdifluoro azides with unstrained olefins.8 Our present
study was intended to fill the gap. We found that azide I
reacts with cyclohexene under substantially harsher conꢀ
ditions than with norbornenes, though the reaction folꢀ
lows a similar pattern involving oxidative aminofluorinaꢀ
tion and oxidative amination of the olefin (Scheme 12).
Scheme 11
Scheme 12
The yield of 7 + 8 is 50%; 7 : 8 = 1 : 1.
We assume that the substituents in product 7 are trans
to each other (3JH—H = 10.5 Hz). Compound 8 is formed
as two conformers because of hindered rotation about the
amide C—N bond.
It should be noted that compound 8 is structurally an
acylated enamine rather than an allylic amide (Scheme 13).
Scheme 13
R = CF2CHFCF3
In Teflon ware, HF reacts with intermediate triazoline
or aziridine to give hydrofluoride III insoluble in CH2Cl2
(white precipitate; lowꢀconcentration 19F NMR spectrum
shows a signal of the fragment N—CF2). When treated
with water or when in contact with glass, hydrofluoride III
undergoes hydrolysis.
Apparently, this is due to the fact that enamine imiꢀ
doyl fluoride intermediate (IV) is more stable than allylic
one (V) because of the conjugation between the double
bonds C=C and C=N.

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Lermontov et al.
One can assume that the reaction pattern is similar to
that observed for normal olefins (Scheme 16).
Experimental
1
H, 13C, and 19F NMR spectra were recorded on a Bruker
We also studied reactions of azide I with some phenylꢀ
containing olefins and found that styrene polymerizes under
the reaction conditions, while transꢀstilbene yields a mixꢀ
ture of two isomeric acylated enamines 9a,b (Scheme 14).
DPXꢀ200 spectrometer (200, 50.8, and 188 MHz, respectively)
with Me4Si and CF3COOH as the external standards. Correlaꢀ
tion spectra (COSY and NOESY) were recorded on a Bruker
AMꢀ500 spectrometer. Mass spectra were measured on a Finniꢀ
gan 4021 mass spectrometer. IR spectra were recorded on
a Bruker IFSꢀ113v spectrometer. Azides I (see Ref. 4) and II
(see Ref. 12) were prepared as described earlier. Solvents were
purified and dried in standard ways.
Scheme 14
Reaction of azide I with benzonorbornaꢀ2,5ꢀdiene (1). A soluꢀ
tion of 3´,6´ꢀdimethoxybenzonorbornaꢀ2,5ꢀdiene (1) (300 mg,
1.56 mmol) and azide I (0.8 g, 4.1 mmol) in dry CH2Cl2 (5 mL)
was stirred at ~20 °C for 6 h. The reaction mixture was poured
into moist acetonitrile (30 mL) containing silica (5 g) and stirred
for 2 h. The solution was filtered and the precipitate was washed
with acetonitrile. The solvent was removed and the residue was
chromatographed on silica (gradient elution with light petroꢀ
leum—ethyl acetate (10 : 1 → 3 : 1)). The yield of fluoro amide
2a as a 1 : 1 mixture of diastereomers was 0.22 g (40%), yellow
P stands for a polymer
The yield of 9a + 9b is 53%; 9a : 9b = 5 : 1.
1
oil. H NMR (CDCl3), δ: 2.06 (m, 2 H, AB part of the ABMX
The formation of rearranged enamine 9a as the major
product does not contradict the mechanism proposed to
explain the formation of products 2a and 2b from norborꢀ
nadiene 1: the phenyl group can undergo 1,2ꢀmigration in
a carbocation formed at one of the reaction steps.
A study of reactions of some aromatic compounds with
azide I revealed that phenol, anisole, and naphthalene
remain inert even at 200 °C. However, anthracene slowly
reacts with azide I at elevated temperature to give Nꢀacylꢀ
ated 9ꢀaminoanthracene 10 as the sole product, though its
conversion over 20 h is only 20% (Scheme 15).
system, CH(3)2); 3.75 (two s (diastereoisomerism with the sigꢀ
nals spaced at 14 Hz), 3 H, OCH3); 3.78 (two s (diastereoisoꢀ
merism with the signals spaced at 8 Hz), 3 H, OCH3); 3.84 (m, 2 H,
H(1), H(4)); 4.30 two d (diastereoisomerism with the signals
spaced at 8 Hz), 1 H, H(7), 3JH—H = 7.6 Hz); 4.93 (asymmetric
2
dm, 1 H, H(2), M part of the ABMX system, JH—F = 56 Hz);
5.08 (two dq (diastereoisomerism with the signals spaced at
2
3
3.5 Hz), 1 H, CHFCF3, JH—F = 46 Hz, JH—F= 6.4 Hz); 6.60
(2 H, AB (the signals are spaced at 2 Hz), H(4´), H(5´), 3JH—H
=
= 8.7 Hz); 7.4 (br.d, 1 H, NH). 19F NMR, δ: 1.08 (m, 3 F,
CF3CHF); –95.23 (m, 1 F, F(2)); –125.3 (dm, 1 F, CHFCF3,
2JH—F = 46 Hz). The 19F{1H} NMR spectrum with complete
proton decoupling reveals JF(2)—CF3 = 2.6 Hz; along with the
absence of the coupling JF(2)—CFH, this indicates the 2ꢀexoꢀ7ꢀ
synꢀconfiguration of the substituents in the norbornyl ring. Found
(%): C, 52.94; H, 4.60; N, 3.73. C16H16F5NO3. Calculated (%):
C, 52.61; H, 4.41; N, 3.83. MS (EI, 70 eV), m/z (Irel (%)):
365 [M+] (70), 345 [M – HF]+ (100), 330 [M – HF – Me]+ (65).
Reaction of azide II with benzonorbornadiene 1. A solution of
compound 1 (600 mg, 3.1 mmol) and azide II (1.4 g, 7 mmol) in
dry CH2Cl2 (10 mL) was stirred at ~20 °C for seven days. Then
moist acetonitrile (10 mL) and silica (5 g) were added and the
reaction mixture was stirred for an additional 2 h and filtered.
The filtrate was concentrated and the residue was chromatoꢀ
Scheme 15
i. I, 180 °C, 20 h.
Scheme 16

Reactions of αꢀdifluoro azides with olefins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2119
graphed on silica (gradient elution with light petroleum—ethyl
acetate (10 : 1 → 3 : 1)). This workup gave fluoro amide 2b (0.38 g,
34%) as yellowish crystals with m.p. 96 °C. 1H NMR, δ: 2.06
(m, 2 H, AB part of the ABMX system, H(3)); 3.76 (s, 3 H, OMe);
3.79 (s, 3 H, OMe); 3.88 (m, 2 H, H(1), H(4)); 3.95 (s, 3 H,
COOMe); 4.27 (d, 1 H, H(7), 3JH—H = 7.8 Hz); 4.95 (asymmetꢀ
ric dm, 1 H, M part of the ABMX system, H(2), 2JH—F = 56 Hz);
6.65 (2 H, AB (the signals are spaced at 2 Hz), H(4´), H(5´),
3JH—H = 8.7 Hz); 7.48 (br.t, 1 H, NH). 19F NMR (CDCl3), δ:
(dd, 3 F, CF3CHF, 3JH—F = 7 Hz, 3JF—F = 11 Hz); –124.87 (dq,
1 F, CHFCF3, 2JH—F = 44 Hz, 3JF—F = 11 Hz). MS (EI, 70 eV),
m/z (Irel (%)): 237 [M+] (2), 202 [M – C2H4]+ (2), 136
[M – CF3CHF]+ (10), 92 [C7H8]+ (100). Found (%): C, 51.02;
H, 4.85; N, 5.76. C10H11F4NO. Calculated (%): C, 50.64;
H, 4.67; N, 5.91. IR (CH2Cl2), ν/cm–1: 3431 (N—H); 2982,
2949, 2878 (C—H); 1697 (C=O); 1533 (N—H); 1200, 1146,
1086 (C—F).
Ester 5a (1 : 1 mixture of diastereomers), a highly hydrolyzꢀ
2
1
–34.8 (F(2), AB, CF2, JF—F = 269 Hz); –94.5 (m, 1 F, F(2)).
able colorless oil. H NMR, δ: 1.13 (m, 2 H, endoꢀH(5), endoꢀ
2
13C NMR, δ: 33.6 (d, C(3), JC—F = 20 Hz); 42.5 (C(4); 47.5
H(6)); 1.68 (m, 2 H, exoꢀH(5), exoꢀH(6)); 1.96 (m, 2 H, H(3)2);
(d, C(1), 2JC—F = 22 Hz); 53.6 (C(7)); 55.5, 55.6 (MeOAr); 63.8
2.48 (br.s, 1 H, H(4)); 2.75 (m, 1 H, H(1)); 4.71 (dm, 1 H, H(2),
1
(COOMe); 95.8 (d, C(2), JC—F = 184 Hz); 106.8 (t, CF2,
2JH—F = 55 Hz); 4.88 (two s (diastereoisomerism with the signals
1JC—F = 286 Hz); 109.5, 110.7 (CHAr); 126.2 (d, C(6), 3JC—F
=
spaced at 8 Hz), 1 H, H(7)); 5.07 (dq, 1 H, CHFCF3, JH—F
=
2
= 11 Hz); 134.5 (C(5)); 147.3, 148.3 (COMeAr); 159.8 (t, CONH,
= 45 Hz, 3JH—F = 6.8 Hz). 19F NMR, δ: 1.70 (two ddd (diastereoꢀ
2
2JC—F = 27 Hz); 161.2 (t, COOMe, JC—F = 31 Hz). IR
isomerism with the signals spaced at 21 Hz), 3 F, CF3CHF,
(CH2Cl2), ν/cm–1: 3434 (N—H); 3002, 2958, 2912, 2838 (C—H);
1786, 1769 sh (O=COMe); 1711 (HNC=O); 1533 (N—H); 1502,
1464, 1441 (C=C); 1200, 1148, 1084 (C—F). Found (%):
C, 55.12; H, 5.07; N, 3.65. C17H18F3NO5. Calculated (%):
C, 54.69; H, 4.86; N, 3.75. MS (EI, 70 eV), m/z (Irel (%)): 373
[M+] (2), 353 [M – HF]+ (50), 189 [M – NHCOCF2COOCH3 –
– OCH3 – H]+ (50), 176 [M – NHCOCF2COOCH3 – CH3] (100).
Reaction of azide I with norbornene. A solution of norbornene
(3.1 g, 33 mmol) and azide I (7.6 g, 40 mmol) in dry CH2Cl2
(20 mL) was stirred at ~20 °C for 24 h (until nitrogen ceased to
evolve). Then moist acetonitrile (15 mL) and silica (10 g) were
added and stirring was continued for an additional 2 h. The
reaction mixture was filtered, concentrated, and distilled in vacuo,
while collecting a fraction with b.p. 50—70 °C (20 Pa). The total
yield of products 3—6 was 92%. Their ratio was determined from
the intensity ratio of the signals for F(2) and CF3 in the 19F NMR
spectra of the distilled reaction mixture. The products obtained
were separated by column chromatography on silica (gradient
elution with light petroleum—ethyl acetate (10 : 1 → 3 : 1)). The
yields of fluoro amide 3a and amide 4a were 2.4 (29%) and 2.1 g
(26%), respectively. Fluorinated esters 5a and 6a obtained in
trace amounts undergo hydrolysis on silica; they were identified,
and their configurations were determined, upon hydrolysis to
the corresponding 2ꢀfluoronorbornanꢀ7ꢀols.
3JH—F = 6.3 Hz, JF—F = 12 Hz, JF—F(2) = 6.8 Hz in one
stereoisomer and 2.7 Hz in the other); –86.60 (m, 1 F, F(2), in
the 19F{1H} NMR spectrum, the multiplet breaks down into two
3
9
quartets at δ –85.73 (9JF—F(2) = 2.7 Hz) and –85.98 (9JF—F(2)
=
= 6.8 Hz)); –127.25 (m, 1 F, CHFCF3). Hydrolysis with ammoꢀ
nia in aqueous ethanol gave the corresponding alcohol 2ꢀexoꢀ
fluoroꢀ7ꢀsynꢀhydroxybicyclo[2.2.1]heptane, m.p. 76 °C (cf. Ref. 20:
1
m.p. 77—79 °C). H NMR, δ: 0.96 (m, 2 H, endoꢀH(5), endoꢀ
H(6)); 1.45 (m, H, exoꢀH(5)); 1.57 (m, 1 H, exoꢀH(6)); 1.83
(m, 1 H, endoꢀH(3)); 2.15 (m, 2 H, exoꢀH(3), H(4)); 2.34 (m, 1 H,
H(1)); 3.2 (br.s, 1 H, OH); 3.95 (s, 1 H, H(7)); 4.65 (dd, 1 H,
H(2), 2JH—F = 55 Hz, 3JH—H = 7 Hz). 19F NMR, δ: –81.15 (m).
MS (EI, 70 eV), m/z (Irel (%)): 130 [M]+ (traces), 110 [M – HF]+
(50), 79 [M – CF2 – H]+ (100). 1H NMR (60 MHz), δ:20 0.8—2.5
(m, 8 H); 3.9 (s, 1 H); 4.6 (asymmetric dm, 1 H, 2JH—F = 57 Hz).
MS, m/z (Irel (%)):20 130 [M]+ (traces), 110 (35), 79 (100).
Ester 6a was not isolated in the individual state because of its
low yield and extremely easy hydrolysis. The signal for F(2) in
the 19F NMR spectrum appeared at δ –83.38. Hydrolysis with
ammonia in aqueous ethanol gave the corresponding alcohol 2ꢀexoꢀ
fluoroꢀ7ꢀantiꢀhydroxybicyclo[2.2.1]heptane, m.p. 110—112 °C
(cf. Ref. 20: m.p. 111—113 °C). 1H NMR, δ: 0.85—2.3 (m, 8 H);
3.55 (s, 1 H, OH); 4.21 (s, 1 H, H(7)); 4.47 (asymmetric dm, 1 H,
H(2), 2JH—F = 57 Hz). 19F NMR, δ: –84.35 (m). MS (EI, 70 eV),
m/z (Irel (%)): 130 [M]+ (traces), 110 [M – HF]+ (50), 79
[M – CF2 – H]+ (100). 1H NMR (60 MHz), δ:20 0.8—2.5 (m, 8 H);
Fluoro amide 3a (1 : 1 mixture of diastereomers), colorless
oil. 1H NMR, δ: 1.0 (m, 2 H, endoꢀH(5), endoꢀH(6)); 1.58 (m, 2 H,
exoꢀH(5), exoꢀH(6)); 1.82 (m, 2 H, H(3)2); 2.34 (br.s, 2 H,
H(1), H(4)); 3.96 (two d, 1 H (diastereoisomerism with the sigꢀ
3.5 (s, 1 H, OH); 4.2 (s, 1 H); 4.4 (asymmetric dm, 1 H, 2JH—F
=
= 57 Hz). MS, m/z (Irel (%)):20 130 [M]+ (traces), 110 (17), 79 (100).
Reaction of azide II with norbornene. A solution of norbornene
(1.7 g, 18 mmol) and azide II (4.2 g, 21 mmol) in dry CH2Cl2
(10 mL) was stirred at ~20 °C for three days (until nitrogen
ceased to evolve). Then moist acetonitrile (15 mL) and silica
(6 g) were added and the reaction mixture was stirred for an
additional 2 h, filtered, and concentrated. The total yield of
products 3b—6b was 89%. Their ratio was determined from the
intensity ratio of the signals for F(2) and CF2 in the 19F NMR
spectra of the reaction mixture. The products obtained were
separated by column chromatography on silica (gradient elution
with light petroleum—ethyl acetate (10 : 1 → 3 : 1)). The yields
of fluoro amide 3b, amide 4b, and fluorinated ester 5b were 1.5
(31%), 1.35 (29%), and 0.6 g (12%), respectively. A small amount
of crude ester 6b was obtained (esters 5b and 6b also undergo
hydrolysis on silica; ester 3b was identified, and its configuration
was determined, upon hydrolysis to the corresponding 2ꢀfluoꢀ
ronorbornanꢀ7ꢀol).
3
nals spaced at 5 Hz), H(7), JH—H = 6 Hz); 4.74 (asymmetric
dm, 1 H, H(2)); 5.0 (two dq (diastereoisomerism with the signals
spaced at 4.2 Hz), 1 H, CHFCF3, 2JH—F = 46 Hz, 3JH—F = 6.8 Hz);
7.05 (br.s, 1 H, NH). 19F NMR, δ: 1.05 (two dd (diastereoisomꢀ
erism with the signals spaced at 31 Hz), 3 F, CF3CHF, 3JH—F
=
3
= 6.8 Hz, JF—F = 11 Hz); –79.80 (m, 1 F, F(2)); –125.28
(m, 1 F, CHFCF3). MS (EI, 70 eV), m/z (Irel (%)): 257 [M+] (5),
237 [M – HF]+ (20), 136 [M – HF – CF3CHF]+ (15),
92 [C7H8]+ (100). Found (%): C, 47.14; H, 4.86; N, 5.34.
C10H12F5NO. Calculated (%): C, 46.70; H, 4.70; N, 5.45. IR
(CH2Cl2), ν/cm–1: 3437 (N—H); 2988, 2980, 2926, 2885 (C—H);
1701 (HNC=O); 1537 (N—H); 1199, 1148, 1090 (C—F).
Amide 4a, m.p. 57 °C. 1H NMR, δ: 1.0 (m, 2 H, endoꢀH(5),
endoꢀH(6)); 1.78 (d, 2 H, exoꢀH(5), exoꢀH(6), 3JH—H = 7.8 Hz);
2.84 (br.s, 2 H, H(1), H(4)); 3.96 (d, 1 H, H(7), 3JH—H = 9 Hz);
2
3
5.0 (dq, 1 H, CHFCF3, JH—F = 44 Hz, JH—F = 7 Hz); 6.02
(s, 2 H, H(2), H(3)); 6.55 (br.s, 1 H, NH). 19F NMR, δ: 1.18

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010
Lermontov et al.
2
Fluoro amide 3b, colorless oil. 1H NMR (500 MHz), δ: 1.10
(m, 2 H, endoꢀH(5), endoꢀH(6)); 1.70 (m, 2 H, exoꢀH(5),
exoꢀH(6)); 1.92 (m, 1 H, H(4)); 1.98 (m, 1 H, endoꢀH(3)); 2.48
(m, 2 H, H(1), exoꢀH(3)); 3.92 (s, 3 H, OCH3); 4.00 (d, 1 H,
H(3), H(6)); 5.07 + 5.14 (dq, 1 H, CHFCF3, JH—F = 48 Hz,
3JH—F = 6.6 Hz); 6.27 + 6.65 (dd, 1 H, H(2), 3JH(3a)—H(2) = 2 Hz,
3JH(3e)—H(2) = 4 Hz); 7.27 + 7.45 (br.s, 1 H, NH). 19F NMR, δ:
1.09 (m, 3 F, CF3); –122.9, –125.6 (m, 1 F, CHFCF3).
IR (CH2Cl2), ν/cm–1: 3428 (N—H); 2964, 2870 (C—H); 1699
(C=O); 1538, 1524 (N—H); 1453, 1430 (C—N); 1353 (CHF);
1201, 1147, 1089 (C—F). MS (EI, 70 eV), m/z (Irel (%)): 225
[M]+ (40), 197 [M – C2H4]+ (25), 101 [CF3CHF]+ (25), 80
[C6H8]+ (100).
H(7), 3JH—H = 8 Hz); 4.83 (asymmetric dd, 1 H, H(2), 2JH—F
=
= 55 Hz); 7.12 (br.s, 1 H, NH). 19F NMR (470 MHz), δ: –36.02
2
(2 F, AB (the signals spaced at 55 Hz), CF2, JF—F = 267 Hz);
–80.22 (m, 1 F, F(2)). MS (EI, 70 eV), m/z (Irel (%)): 265 [M]+
(2), 245 [M – HF]+ (20), 149 [M – HF – CF2COO]+ (30),
92 [C7H8]+ (100). Found (%): C, 50.51; H, 5.43; N, 5.17.
C11H14F3NO3. Calculated (%): C, 49.81; H, 5.32; N, 5.28. IR
(CH2Cl2), ν/cm–1: 3434 (N—H); 2976, 2961, 2928, 2883 (C—H);
1784, 1771 sh (O=COMe); 1709 (HNC=O); 1539 (N—H).
Amide 4b, m.p. 41 °C. 1H NMR (500 MHz), δ: 0.98 (m, 2 H,
AB, endoꢀH(5), endoꢀH(6)); 1.78 (2 H, AB, exoꢀH(5), exoꢀH(6),
3JH—H = 8 Hz); 2.83 (s, 2 H, H(1), H(4)); 3.86 (m, 4 H, OCH3,
H(7)); 6.00 (s, 2 H, H(2), H(3)); 6.70 (br.s, 1 H, NH). 19F NMR,
δ: –35.7 (s). MS (EI, 70 eV), m/z (Irel (%)): 245 [M]+ (6), 217
[M – C2H4]+ (5), 154 [NH2COCF2COOCH3 + H]+ (80), 136
[M – CF2COMe]+ (40), 92 [C7H8]+ (100). Found (%): C, 54.27;
H, 5.52; N, 5.57. C11H13F2NO3. Calculated (%): C, 53.88;
H, 5.34; N, 5.71. IR (CH2Cl2), ν/cm–1: 3428 (N—H); 2988,
2947, 2880 (C—H); 1783, 1770 sh (O=COMe); 1704 (HNC=O);
1530 (N—H); 1167, 1098 (C—F).
Reaction of transꢀstilbene with azide I. A solution of transꢀ
stilbene (0.32 g, 1.88 mmol) and azide I (0.8 g, 4.1 mmol) in dry
CH2Cl2 (5 mL) was heated in a steel tube at 170 °C for 18 h. The
reaction mixture was chromatographed on silica with hexꢀ
ane—ethyl acetate (7 : 1) as an eluent. The yields of amides 9a
and 9b were 0.25 g (44%) and 50 mg (9%), respectively.
Amide 9a, colorless crystals, m.p. 84 °C. 1H NMR, δ: 5.45
(dq, 1 H, CHFCF3, 2JH—F = 45 Hz, 3JH—F = 6.2 Hz); 7.20—7.62
3
(m, 11 H, Ph, CHNH); 8.30 (br.d, 1 H, NH, JH—H = 10 Hz).
MS (EI, 70 eV), m/z (Irel (%)): 323 [M]+ (100), 222
[M – CF3CHF]+ (10), 194 [M – CF3CHFCO]+ (70), 178
[Ph2C2]+ (28). Found (%): C, 63.35; H, 4.42; N, 4.13.
C17H13F4NO. Calculated (%): C, 63.16; H, 4.05; N, 4.33. IR
(CH2Cl2), ν/cm–1: 3415 (N—H); 1711 (C=O); 1642 (C=C);
1510 (N—H); 1485, 1352 (CHF); 1201, 1147, 1090 (C—F).
Ester 5b, a hydrolyzable colorless oil. 1H NMR (500 MHz),
δ: 1.15 (m, 2 H, endoꢀH(5), endoꢀH(6)); 1.61 (m, 1 H, exoꢀ
H(5)); 1.73 (m, 1 H, exoꢀH(6)); 1.95 (m, 1 H, endoꢀH(3)); 2.10
(m, 1 H, exoꢀH(3)); 2.48 (br.s, 1 H, H(4)); 2.71 (m, 1 H, H(1));
Amide 9b, colorless crystals, m.p. 101 °C. H NMR, δ: 5.65
1
2
3
(dq, 1 H, CHFCF3, JH—F = 45 Hz, JH—F = 6.2 Hz); 6.96
(s, 1 H, PhCH); 7.30—7.70 (m, 10 H, Ph); 8.85 (br.s, 1 H, NH).
MS (EI, 70 eV), m/z (Irel (%)) : 323 [M]+ (70), 178 [Ph2C2]+
(10). Found (%): C, 63.25; H, 4.36; N, 4.15. C17H13F4NO. Calꢀ
culated (%): C, 63.16; H, 4.05; N, 4.33. IR (CH2Cl2), ν/cm–1
:
3399 (N—H); 1717 (C=O); 1506 (N—H); 1448, 1354 (CHF);
2
3.90 (s, 3 H, OCH3); 4.69 (dd, 1 H, H(2), JH—F = 56 Hz,
3JH—H = 7.2 Hz); 4.85 (s, 1 H, H(7)). 19F NMR (470 MHz), δ:
2
–35.9 (2 F, AB (the signals spaced at 16 Hz), CF2, JF—F
=
= 275 Hz); –86.43 (m, 1 F, F(2)).
1204, 1148, 1090 (C—F).
Ester 6b was not isolated in the individual state because of its
low yield and easy hydrolysis. 19F NMR, δ: –35.23 (s, 2 F, CF2);
–83.95 (m, 1 F, F(2)). Its structure was confirmed by hydrolysis
to the documented20 alcohol, which was obtained and identified
as described above for ester 6a.
Reaction of anthracene with azide I. A mixture of anthracene
(0.37 g, 2 mmol) and azide I (0.8 g, 4.1 mmol) in dry CH2Cl2
(5 mL) was heated in a steel tube (anthracene is poorly soluble in
CH2Cl2 at room temperature) at 180 °C for 6 h. The reaction
mixture was applied to silica (1 g) and chromatographed with
hexane—ethyl acetate (10 : 1) as an eluent. The yield of amide
10 was 0.13 g (20%); the starting anthracene (0.26 g, 75%) was
recovered.
Amide 10, yellow crystals, m.p. 177 °C. 1H NMR, δ: 5.70
(dq, 1 H, CHFCF3, 2JH—F = 45 Hz, 3JH—F = 6.2 Hz); 7.46—7.62
(m, 4 H, H(2), H(3), H(6), H(7)); 8.00—8.15 (m, 4 H, H(1),
H(4), H(5), H(8)); 8.60 (s, 1 H, H(10)); 9.27 (br.s, 1 H, NH).
19F NMR, δ: 1.4 (m, 3 F, CF3); –124.4 (m, 1 F, CHFCF3). MS
(EI, 70 eV), m/z (Irel (%)): 321 [M]+ (90), 220 [M – CF3CHF]+
(7), 192 [M – CF3CHFCO]+ (100). Found (%): C, 63.81;
H, 3.79; N, 4.20. C17H11F4NO. Calculated (%): C, 63.55;
H, 3.45; N, 4.36.
Reaction of cyclohexene with azide I. A solution of cycloꢀ
hexene (0.8 g, 10 mmol) and azide I (3 g, 15 mmol) in dry
CH2Cl2 (10 mL) was heated in a steel tube at 150 °C for 6 h. The
reaction mixture was cooled, poured into moist acetonitrile
(20 mL) containing silica (5 g), and stirred for 1 h. Then it
was filtered and concentrated and the residue was separated
on silica (gradient elution with light petroleum—ethyl acetate
(10 : 1 → 3 : 1)). The yields of fluoro amide 7 and cyclohexenyl
amide 8 were 0.6 (25%) and 0.5 g (25%), respectively.
Fluoro amide 7, colorless oil. 1H NMR, δ: 1.30—2.00 (m, 6 H,
H(4), H(5), H(6)); 2.15 (m, 2 H, H(3)); 4.02 (m, 1 H, H(1));
4.33 (dddd, 1 H, 2JH—F = 50.5 Hz, H(2), 3JH(1a)—H(2a) = 10.5 Hz,
3
3JH(3a)—H(2a) = 10.5 Hz, JH(3e)—H(2a) = 6.3 Hz); 5.08 (dq, 1 H,
CHFCF3, 2JH—F = 48 Hz, 3JH—F = 6.5 Hz); 6.5 (br.s, 1 H, NH).
References
19F NMR, δ: 1.54 (m, 3 F, CF3); –101.4 (dm, 1 F, F(2), 2JH—F
=
:
= 50.5 Hz); –124.6 (m, 1 F, CHFCF3). IR (CH2Cl2), ν/cm–1
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3419 (N—H); 2952, 2864 (C—H); 1704 (C=O); 1530 (N—H);
1450 (C—N); 1355 (CHF); 1201, 1148, 1093 (C—F).
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Cyclohexenyl amide 8 (2 : 1 mixture of two conformers).
1H NMR, δ: 1.63—1.80 (m, 4 H, H(4), H(5)); 2.15—2.40 (m, 4 H,

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in revised form September 22, 2010