Synthesis of tetrafluoroethyl- and tetrafluoroethylene-containing amines by the reaction of silanes with enamines under acidic conditions

Article abstract of DOI:10.1016/j.jfluchem.2014.08.004

Enamines with in situ formed hydrogen fluoride underwent efficient reaction with trimethyl(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)silane and trimethyl(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)silane. Radical or reductive desulfurization of the additio

Full text of DOI:10.1016/j.jfluchem.2014.08.004

Accepted Manuscript
Title: Synthesis of tetrafluoroethyl- and
tetrafluoroethylene-containing amines by the reaction of
silanes with enamines under acidic conditions
Author: Yana Chernykh Bronislav Jur a´ sek Petr Beier
PII:
S0022-1139(14)00231-0
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2014.08.004
FLUOR 8396
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
13-5-2014
30-7-2014
1-8-2014
Please cite this article as: Y. Chernykh, B. Jur a´ sek, P. Beier, Synthesis of
tetrafluoroethyl- and tetrafluoroethylene-containing amines by the reaction of silanes
with enamines under acidic conditions, Journal of Fluorine Chemistry (2014),
http://dx.doi.org/10.1016/j.jfluchem.2014.08.004
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Synthesis of tetrafluoroethyl- and tetrafluoroethylene-containing
amines by the reaction of silanes with enamines under acidic
conditions
*
Yana Chernykh, Bronislav Jurásek, Petr Beier
Institute of Organic Chemistry and Biochemistry, Academy of Siences of the Czech Republic,
v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
Keywords
Nucleophilic addition; Enamines; Iminium salts; Tetrafluoroethyl; Tetrafluoroethylene
Abstract
Enamines with in situ formed hydrogen fluoride underwent efficient reaction with
trimethyl(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)silane and trimethyl(1,1,2,2-tetrafluoro-2-
(phenylsulfonyl)ethyl)silane. Radical or reductive desulfurization of the addition products
provided amines containing the tetrafluoroethyl group.
1. Introduction
Fluoroalkyl-containing silanes are widely used and versatile reagents for the introduction of
fluoroalkyl groups. The most extensively studied member of the family – trimethyl
(trifluoromethyl)silane – represents not only a very useful nucleophilic trifluoromethylating
reagent [1] but also the source of trifluoromethyl radicals [2] and difluorocarbene [3]. Carbon
or heteroatom-substituted examples include RCF SiMe (R = PhS [4], PhSO [Error!
2
3
2
Bookmark not defined.j, [5], PO Et [Error! Bookmark not defined.e, Error! Bookmark
3
2
not defined.j, [6], CO Et [7], Ar [8], ArO [Error! Bookmark not defined.b], CN [9]) which
2
after activation by a Lewis base (typically fluoride anions) act as equivalents of fluorinated
carbanions. We have recently shown that PhSCF
2
CF
2 3
SiMe
(1) can be used as a tandem
•
‒
radical and anion synthon [ CF CF ] for the synthesis of tetrafluoroethyl-containing
2
2
alcohols, pyrrolidinones and isoindolinones, and tetrafluoroethylene-containing
tetrahydropyrans and 1-azabicyclic compounds [10]. The intermediate in the synthesis of 1,
*
Corresponding author. Tel. +420 220 183 409; fax: +420 233 331 733.
E-mail address: beier@uochb.cas.cz (P. Beier).
1
Page 1 of 28

•
•
•
•
PhSCF
2 2 2 2 2 2 2 2
CF Br, can serve as a [PhSCF CF ], [HCF CF ], and [ CF CF ] synthon in radical
additions to alkenes [11].
Fluorinated amines are very important in pharmaceutical research [12] and one of the ways to
their synthesis is nucleophilic fluoroalkyl addition of C=N bonds of imines, iminium ions,
nitrones or hydrazones [13]. Imines including activated imines such as N-sulfinyl or N-
sulfonylimines are widely used electrophilic substrates for nucleophilic additions [14]. They
have been successfully used as electrophilic partners in some nucleophilic fluoroalkylations
3 3 3 2 2 3 2 2 3
with fluorinated silanes (Me SiCF , Me SiCF CN, PhSCF SiMe , PhSO CF SiMe ) in the
presence of Lewis bases or under acidic conditions [Error! Bookmark not defined.d,
Error! Bookmark not defined.j, Error! Bookmark not defined.e, Error! Bookmark not
defined., Error! Bookmark not defined., [15,16] while the reaction of Me SiCF PO Et
3
2
3
2
with imines under acidic conditions was inefficient [Error! Bookmark not defined.j]. In
contrast to electrophilic imines, enamines are typical nucleophilic reagents. However, in the
presence of hydrogen fluoride generated in situ from KHF and either trifluoroacetic or triflic
2
acid, enamines are converted to electrophilic iminium salts. The bifluoride counterion is
capable to activate the silicon reagent, followed by the transfer of the fluorinated group onto
the C=N bond. This process has been successfully demonstrated in the reaction of enamines
2 3 2 3 2
with the following fluorinated silanes: RCF SiMe (R = F, CN, SPh, SO Ph, PO Et )
(
Scheme 1) [Error! Bookmark not defined.j, Error! Bookmark not defined.,17].
NR23
R1
R2
NR 3
2
CF
3
CO
2
H
KHF2
2 HF
R1
-
HF
2
-
CF CO K
R2
3
2
RCF SiMe3
2
CF R
2
F
F
Me
Me
NR23
Si Me
R1
R1
R
F
H
F
-
Me SiF
3
R2 NR23
R2
- HF
Scheme 1: Mechanism of nucleophilic fluoroalkyl group transfer to enamines under acidic
conditions [Error! Bookmark not defined.j, Error! Bookmark not defined., Error!
Bookmark not defined.].
In this paper, we investigate reactions of sulfur-containing silanes PhSCF CF SiMe (1) and
2
2
3
PhSO
2
CF
2
CF
2
SiMe
CF
(2) with imines and enamines under acidic conditions providing amines
3
with the CF
2
2
moiety in -position. There is one precedence to the synthesis of
2
Page 2 of 28

fluoroalkyl-containing (CF
enantiomerically pure lithium methyl or benzyl p-tolyl sulfoxides to fluorinated aldimines
18].
3 2 5 2 2
, C F , CF CF H) amines by asymmetric addition of
[
2
. Results and discussion
Synthesis of silane 1 was described in literature [Error! Bookmark not defined.f] and silane
is available in high yield by simple oxidation of 1 with aqueous hydrogen peroxide solution
in acetic acid (in 64% yield) or with mCPBA (in 91% yield) (Scheme 2).
2
3
0% H O2
2
AcOH, 60°C
4%
6
PhSH, NaH
Mg, Me SiCl
m-CPBA
CH Cl
3
BrCF CF Br
PhSCF CF SiMe
2 2 3
2
2
PhSCF CF Br
PhSO CF CF SiMe
2 2 2 3
2
2
DMF, -50°C to rt
THF, -78°C to rt
92%
2
2
90%
1
0°C to rt
1%
2
9
Scheme 2: Synthesis of silanes 1 and 2.
The investigations were started with the reaction of (S)-N-benzylidene-4-toluenesulfinamide
3) with 1 under various conditions. At best, 20% yield of the adduct 4 was achieved using
(
tetrabutylammonium acetate in DMF (Scheme 3). Other initiators (TMAF, TBAF, TBAT,
CsF in THF or DMF) provided low yields (0‒14%) of 4 often accompanied by the product of
protodesilylation of
1
(PhSCF
2
CF
2
H). Similarly, reaction of
1
with 2-
(
benzylideneamino)phenol in the presence of TFA or TfOH and KHF
2
in MeCN provided
only traces of expected addition product. Therefore attention was turned to reactions of
highly electrophilic iminium salts formed from enamines.
O
S
O
S
CF
2
CF
2
SPh
n-Bu N -OAc (1 equiv.)
+
4
+
PhSCF CF SiMe
2 2 3
4
-Tol
N
Ph
4-Tol
N
H
* Ph
DMF, -40 °C, 2 h
20%
3
1 (2 equiv.)
4
, dr 83:17
Scheme 3: Nucleophilic addition of silane 1 to (S)-N-benzylidene-4-toluenesulfinamide (3).
We found that enamines 5 derived from enolizable ketones such as cyclopentanone,
cyclohexanone, acetophenone, 1-phenylpropan-2-one and 2,3-dihydro-1H-inden-1-one and
secondary amines such as morpholine, pyrrolidine, N-methyl-1-phenylmethanamine and
dibenzylamine react with both fluorinated silanes 1 and 2 in the presence of potassium
hydrogenfluoride and trifluoroacetic acid in acetonitrile to form addition products 6 or 7
3
Page 3 of 28

(Table 1). Conditions described by Dilman and co-workers (1.5 equiv. of silane and TFA,
0
.75 equiv. of KHF
2
in MeCN) [Error! Bookmark not defined.j] were found to be optimal
in the reaction of 1 with 5a, therefore, they were used in the reaction scope study. Yields
were substrate dependent and ranged from modest to high. Bulky enamines 5f and 5g gave
the lowest yields. Silane 2 was less reactive than silane 1 in most cases. This can be explained
by lower nucleophilicity of the respective fluorinated carbanion species because of stronger
electron acceptor character of the phenylsulfonyl moiety compared to the phenylsulfanyl
group. Employment of enamines derived from morpholine and enolizable aldehydes such as
propionaldehyde or 2-phenylacetaldehyde did not lead to expected products 6 in reactions
with 1 or 2. In the latter case, the presence of product of acid catalyzed aldol condensation –
2,4-diphenylbut-2-enal – was identified by GCMS analysis of the reaction mixture.
a
Table 1: Addition of silanes 1 and 2 to enamines under acidic conditions
KHF2
TFA
RCF CF SiMe
+
3
Enamine
Product
2
2
MeCN, rt
1
2
R = PhS
R = PhSO2
5
6
or
7
b
Entry Silane
5
Enamine
Time (h) Product
Yields (%)
F F
N
O
Ph
1
1
5a
1
6a
S
N
N
68
F F
O
F F
Ph
2
3
2
1
5a
5b
2
7a
6b
S
93
43
O O F F
O
O
O
F F
Ph
N
Ph
S
N
O
2.5
F F
F F
Ph
Ph
Ph
N
Ph
S
4
5
2
1
5b
5c
4
2
7b
6c
40
91
O O F F
F F
Ph
N
Ph
S
N
F F
4
Page 4 of 28

F
F
Ph
Ph
6
7
8
2
5c
1
45
7
c
S
N
O O F F
F F
6d
7d
1
2
5d
5d
N
4
Ph
68
41
S
N
N
F F
F
F
1.5
Ph
S
O O F F
Ph
F F
N
Ph
9
1
6e
7e
6f
1
2
5e
5e
2
1
70
66
Me
S
N
Ph
Ph
Ph
F F Me
F F
0
1
Ph
S
N
O O F F Me
F F
Ph
Ph
N
Ph
1
1
2
5f
5f
4
S
N
N
28
20
F F
Ph
F
F
Ph
1
1
2
1.5
7f
S
Ph
O O F F
Ph
Et
NEt2
F F
3
4
1
2
5g
5g
4
1
6g
7g
Ph
38
20
S
N
F F Et
F F
1
Ph
Et
S
N
O O F F Et
a
Reactions were performed with 1 or 2 (1.5 equiv.), 5 (1 equiv.), KHF (0.75 equiv.), TFA
2
(1.5 equiv.) in MeCN at rt.
b
Isolated yield.
The nucleophilic fluoroalkylation reactions gave access to fluorinated tertiary amines 6 and 7.
In order to prepare primary or secondary amines we envisioned hydrogenolysis of benzyl
5
Page 5 of 28

groups in adducts formed from N-benzyl enamines 5e and 5f. Debenzylation of 7 with
hydrogen and catalytic palladium on charcoal provided N-methylamines 8 in high yields
(
Scheme 4). Debenzylation of 7f required the use of acidic medium and elevated temperature
Scheme 4). On the other hand, analogous reaction with sulfide 6e was not successful
(
presumably because of the catalyst poisoning with sulfur of the phenylsulfanyl moiety.
F
F
F
F
H (20 bar), 10% Pd/C (cat.)
2
Ph
Ph
S
N
Ph
S
NHMe
MeOH, rt, 3 h
O O F F Me
O O F F
89%
7
e
8e
F
F
F
F
H2 (1 bar), 10% Pd/C (cat.)
AcOH, 70°C, 24 h
Ph
Ph
S
N
Ph
S
NH
2
O O F F
O O F F
71%
Ph
7f
8f
Scheme 4: Debenzylation of adducts 7.
Next, we investigated substitutions of the phenylsulfanyl group in compounds 6 or
phenylsulfonyl group in compounds 7 for hydrogen atom. Substitution of phenylsulfanyl
group of 6a and 6e was achieved under radical conditions giving tetrafluoroethyl-substituted
amines 9 in good yields (Scheme 5). Reductive desulfonylation of 7a provided 9a also in
good yield (Scheme 5).
n-Bu SnH (1.5 equiv.)
AIBN (2 mol%)
F
F
3
F
F
F
Ph
Mg (30 equiv.)
MeOH, rt, 4 h
Ph
S
N
F
N
S
N
toluene, relux, 2 h
F F
O
F F
O O
F F
O
O
91%
80%
9a
7a
6a
n-Bu SnH (1.5 equiv.)
AIBN (2 mol%)
F
F
3
F
Ph
S
N
Ph
F
N
Ph
toluene, relux, 2 h
F F Me
F F
Me
64%
6
e
9e
Scheme 5: Radical and reductive desulfurization to provide tetrafluoroethyl-substituted
amines 9.
3. Conclusion
In conclusion, we demonstrated application of silanes 1 and 2 in hydrogen fluoride-mediated
nucleophilic tetrafluoroalkyl transfer to enamines giving adducts 6 and 7. Further chemical
modifications included desulfurization of adducts 6 and 7 and hydrogenolysis of N-benzyl-
6
Page 6 of 28

containing adducts 7. This method provided easy access to primary, secondary and tertiary
amines containing the tetrafluoroethyl group.
4. Experimental
4.1 General information
1
19
H and F NMR spectra were recorded on a Bruker 400 MHz instrument at ambient
13
3
temperature in CDCl at 400 and 376 MHz, respectively. C NMR spectra were recorded on
a Bruker 400 MHz, 500 MHz or 600 MHz at 100, 125 and 150 MHz, respectively. The
1
chemical shifts () are reported in parts per million (ppm) relative to Me
4
Si (0 ppm, for H
1
13
NMR), residual CHCl (7.26 ppm for H NMR), CDCl (77.0 ppm for C NMR), internal
3
3
19
13
19
3
CFCl (0 ppm for F NMR). Coupling constants (J) are given in Hertz. C and F NMR
spectra were proton decoupled. GCMS spectra were recorded on an Agilent 7890A gas
chromatograph coupled with a 5975C quadrupole mass-selective electron impact (EI)
detector (70 eV). High-resolution mass spectra (HRMS) were recorded on an Agilent 7890A
gas chromatograph coupled with a Waters GCT Premier orthogonal acceleration time-of-
flight detector using electron impact (EI) or chemical (CI) ionizations or on a LTQ Orbitrap
XL instrument using electrospray (ESI) ionization. Infrared spectra were measured on a FTIR
instrument. Reactions were conducted under the atmosphere of dry argon. Toluene and THF
were dried by distillation with sodium/benzophenone before the use. MeOH, DMF and
2 2
MeCN were dried using activated molecular sieves (3 Å). CH Cl and AcOH were used
without purification. Enamines 5 were prepared according to literature procedure [19]. All
other chemicals obtained from commercial suppliers and were used as received. PE refers to
petroleum ether with bp of 40‒60 °C. Purifications of products were performed by flash
chromatography using silica gel 60. TLC plates were visualized with ultraviolet light (254
4
nm) and/or with KMnO staining solution.
4
.2 Synthesis of trimethyl(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)silane (2)
Method A. m-CPBA (2.16 g, 12.5 mmol) was added to a solution of silane 1 (1.41 g, 5 mmol)
in CH Cl (50 mL) at 0 °C and the mixture was stirred 2 h at 0 °C. Cooling bath was removed
and the mixture was stirred for 24 h at room temperature. Saturated Na S O (20 mL) was
2
2
2
2
3
7
Page 7 of 28

added at 0°C, the mixture was filtered, extracted into CH
2
Cl
2
and the organic extract was
), filtered and
washed with aqueous NaHCO3. The combined organic phase was dried (MgSO
4
concentrated under vacuum. Resulting mixture was dissolved in PE‒EtOAc (90:10), filtered
and concentrated under vacuum to give 1.43 g (91% yield) of 2.
Method B. Silane 1 (1.41 g, 5 mmol) was added to a solution of 30% aqueous H
50 mmol) in AcOH (30 mL), the mixture was heated to 60 °C and stirred for 25 h. Water
15 mL) was added, the mixture was extracted into Et O and the organic extract was washed
with brine. The combined organic phase was dried (MgSO ), filtered and concentrated under
2
O (16 mL,
2
1
(
2
4
vacuum. The crude product was purified by column chromatography eluting with PE‒EtOAc
(
95:5) to give 1.00 g (64% yield) of 2. White solid, R
0.32 (PE‒EtOAc, 95:5); mp 37‒39 °C;
f
1
19
H NMR 
H
0.28 (s, 9H), 7.58‒7.71 (m, 3H), 7.98‒8.08 (m, 2H); F NMR
F
‒126.1 (s, 2F),
13
‒
109.2 (s, 2F); C NMR (100 MHz) ‒4.4, 117.3 (tt, J = 291.5, 32.6 Hz), 123.5 (tt, J =
C
273.4, 41.4 Hz), 129.3, 130.7, 135.6; MS (EI) m/z (rel. int.) 299 (15), 214 (14), 166 (50), 141
8
Page 8 of 28

+
15 4 2
(14), 135 (100), 77 (65), 73 (93); HRMS (CI) m/z calcd for C11H F O SSi [M + H]
315.0498, found 315.0496.
4.3 Synthesis of 4-methyl-N-(2,2,3,3-tetrafluoro-1-phenyl-3-(phenylthio)propyl)benzenesul-
finamide (4)
A solution of AcONBu (302 mg, 1 mmol) in dry DMF (2 mL) was added to (S)-N-
4
benzylidene-4-toluenesulfinamide (3) (243 mg, 1 mmol) and 1 (565 mg, 2 mmol) in dry DMF
(8 mL) at ‒40 °C. The reaction mixture was stirred at this temperature for 2 h, and then
allowed to warm up to room temperature within 1 h. Aqueous saturated NH Cl solution (10
4
2
mL) was added and the mixture was extracted with Et O, the combined organic phase was
washed with brine, water, dried (MgSO ) and concentrated under reduced pressure. The
4
crude product (dr 85:15) was purified by column chromatography eluting with PE‒EtOAc
(
95:5) to give 90 mg (20% yield, dr 83:17) of 4. Pale yellow solid, R
0.04 (PE‒EtOAc,
f
1
9
5:5); H NMR 
H
2.37 (s, 3H, major), 2.43 (s, 3H, minor), 4.58‒4.72 (m, 1H, major),
4.72‒4.78 (m, 1H, minor), 4.98‒5.12 (m, 2H, major + minor), 7.10‒7.70 (m, 28H, major +
9
Page 9 of 28

19
minor); F NMR ‒117.5 (dt, J = 266.0, 4.5 Hz, 1F, minor), ‒115.5 (dt, J = 268.4, 4.5 Hz,
F
1F, major), ‒114.5 (dt, J = 268.4, 4.5 Hz, 1F, major), ‒113.8 (dt, J = 266.0, 4.5 Hz, 1F,
13
minor), ‒85.3 (t, J = 4.5 Hz, 2F, minor), ‒84.8 (t, J = 4.5 Hz, 2F, major); C NMR (100
MHz)
C
(major) 21.3, 58.6 (dd, J = 24.4, 22.5 Hz), 125.6, 128.4, 128.6, 128.9, 129.2, 129.4,
130.5, 134.6, 137.2, 141.3, 141.7; MS (EI) m/z (rel. int.) 436 (15), 416 (11), 294 (12), 153
19 4 2
(11), 139 (12), 125 (100), 111 (50), 104 (30); HRMS (EI) m/z calcd for C22H F NaOS [M +
+
Na] 476.07364, found 476.07365.
4.4 General procedure for the synthesis of compounds 6 and 7
TFA (93 mL, 1.25 mmol) was added to a Schlenk flask containing a solution of 5 (1 mmol)
and KHF (59 mg, 0.75 mmol) in dry MeCN (2 mL) at 0 °C. The reaction mixture was stirred
2
at this temperature for 5 min, and then 1 or 2 (1.5 mmol) was added to the reaction mixture.
Ice bath was removed and the reaction mixture was stirred for appropriate time. Aqueous
saturated Na CO solution (5 mL) was added and the reaction mixture was extracted with
2
3
2 4
Et O. The combined organic phase was washed with brine and water, dried (MgSO ), and
concentrated under vacuum. The crude product was purified by flash or column
chromatography eluting with PE‒EtOAc to give pure product 6 or 7.
1
0
Page 10 of 28

4.4.1. 4-(1-(1,1,2,2-Tetrafluoro-2-(phenylthio)ethyl)cyclohexyl)morpholine (6a)
1
White solid (208 mg, 68% yield), R 0.28 (PE‒EtOAc, 98:2); mp 82‒84 °C; H NMR 
H
f
1
4
‒
.11‒1.31 (m, 1H), 1.36‒1.65 (m, 6H), 1.65‒1.75 (m, 1H), 1.96‒2.12 (m, 2H), 2.77‒2.98 (m,
19
H), 3.28‒3.96 (m, 4H), 7.32‒7.51 (m, 3H), 7.57‒7.69 (m, 2H); F NMR
F
‒110.3 (s, 2F),
13
C
82.4 (s, 2F); C NMR (100 MHz) 20.5, 25.9, 28.1 (t, J = 3.3 Hz), 46.7 (t, J = 2.7 Hz),
6
3.8 (t, J = 19.7 Hz), 68.4, 124.7, 129.0, 130.3, 137.3, CF
2
CF
2
carbons were not observed;
+
MS (EI) m/z (rel. int.) 168 (100), 109 (4); HRMS (EI) m/z calcd for C H F S [M + H]
18
24 4
378.1515, found 378.1515.
4.4.2. 4-(1-(1,1,2,2-Tetrafluoro-2-(phenylsulfonyl)ethyl)cyclohexyl)morpholine (7a)
1
White solid (341 mg, 93% yield), R
f
0.07 (PE‒EtOAc, 98:2); mp 98‒100 °C; H NMR 
H
1.11‒1.28 (m, 1H), 1.38‒1.63 (m, 6H), 1.65‒1.75 (m, 1H), 1.94‒2.10 (m, 2H), 2.77‒2.98 (m,
1
1
Page 11 of 28

19
4H), 3.17‒4.00 (m, 4H), 7.56‒7.66 (m, 2H), 7.71‒7.81 (m, 1H), 7.93‒8.05 (m, 2H);
F
13
NMR
F
‒112.2 to ‒111.9 (m, 2F), ‒107.9 to ‒107.7 (m, 2F); C NMR (100 MHz)
C
20.3, 25.6, 27.7 (t, J = 3.2 Hz), 46.6 (t, J = 2.5 Hz), 64.7 (tt, J = 19.4, 2.6 Hz), 68.4, 117.0 (tt,
J = 300.0, 43.0 Hz), 122.2 (tt, J = 264.0, 31.8 Hz), 129.3, 130.9, 134.8, 135.6; MS (CI) m/z
+
(rel. int.) 168 (100), 77 (7); HRMS (EI) m/z calcd for C18
H
23
F
4
NO
3
S [M + H] 410.1413,
found 410.1404.
4.4.3. 4-(3,3,4,4-Tetrafluoro-2-phenyl-4-(phenylthio)butan-2-yl)morpholine (6b)
1
Colorless oil (138 mg, 43% yield), R 0.24 (PE‒EtOAc, 98:2); H NMR 
H
1.74 (s, 3H),
f
2
2
.52‒2.78 (m, 4H), 3.71‒3.79 (m, 4H), 7.28‒7.48 (m, 6H), 7.53‒7.61 (m, 2H), 7.64‒7.74 (m,
19
13
H); F NMR ‒102.3 (d, J = 268.1 Hz, 1F), ‒81.6 to ‒80.4 (m, 3F); C NMR (100
F
MHz) 13.8, 48.2, 67.4, 68.1 (t, J = 19.8 Hz), 119.2 (tt, J = 270.4, 30.0 Hz), 124.8, 126.0
C
(tt, J = 292.5, 40.0 Hz), 127.8, 128.0, 128.9, 129.0, 130.1, 137.1, 138.5; MS (EI) m/z (rel.
1
2
Page 12 of 28

22 4
int.) 190 (100), 159 (6), 109 (3), 105 (4), 77 (6); HRMS (EI) m/z calcd for C20H F NOS [M
+
+
H] 400.1358, found 400.1356.
4.4.4. 4-(3,3,4,4-Tetrafluoro-2-phenyl-4-(phenylsulfonyl)butan-2-yl)morpholine (7b)
1
Pale yellow solid (135 mg, 40% yield), R 0.29 (PE‒EtOAc, 98:2); mp 88‒90 °C; H NMR
f

H
1.61 (s, 3H), 2.38‒2.68 (m, 4H), 3.56‒3.66 (m, 4H), 7.18‒7.28 (m, 3H), 7.45‒7.58 (m,
19
4
H), 7.63‒7.72 (m, 1H), 7.82‒7.92 (m, 2H); F NMR ‒112.0 to ‒110.0 (m, 1F), ‒108.3
F
13
C
to ‒104.4 (m, 2F), ‒102.4 (d, J = 281.6, 1F); C NMR (125 MHz) 13.2, 47.9, 67.4, 68.9
(t, J = 18.7 Hz), 116.8 (tdd, J = 303.5.5, 44.2, 40.0 Hz), 119.7 (tt, J = 262.7.5, 27.6 Hz),
128.0, 128.2, 129.3, 130.9, 133.5, 137.6; MS (EI) m/z (rel. int.) 190 (100), 105 (5), 77 (8);
+
HRMS (CI) m/z calcd for C20
H
22
F
4
NO
3
S [M + H] 432.1257, found 432.1255.
4.4.5. 1-(3,3,4,4-Tetrafluoro-2-methyl-1-phenyl-4-(phenylthio)butan-2-yl)pyrrolidine (6c)
1
3
Page 13 of 28

1
Pale yellow oil (174 mg, 91% yield), R
f
0.71 (PE‒EtOAc, 95:5); H NMR 
H
1.29 (d, J = 3.6
Hz, 3H), 1.59‒1.84 (m, 4H), 2.70‒2.92 (m, 3H), 3.03‒3.18 (m, 2H), 3.24‒3.37 (m, 1H),
1
9
7
2
7
.13‒7.29 (m, 5H), 7.34‒7.48 (m, 3H), 7.57‒7.70 (m, 2H); F NMR ‒112.6 (dd, J =
F
66.7, 7.5 Hz, 1F), ‒111.5 (ddd, J = 266.7, 10.7, 6.1 Hz, 1F), ‒85.8, (ddd, J = 219.9, 10.7,
13
C
.5 Hz, 1F), ‒78.1 (dd, J = 219.9, 6.1 Hz, 1F); C NMR (100 MHz) 19.7, 24.9, 35.6, 46.6,
62.8 (t, J = 20.6 Hz), 120.0 (tt, J = 271.2, 26.7 Hz), 125.5 (tt, J = 295.5, 37.0 Hz), 126.3,
127.8, 128.9, 129.9, 131.2, 136.9; MS (EI) m/z (rel. int.) 306 (100), 188 (35), 159 (4), 116
+
(
15), 109 (3), 91 (6), 77 (3); HRMS (EI) m/z calcd for C H F NS [M + H] 398.1566, found
21
24 4
398.1552.
4.4.6. 1-(3,3,4,4-Tetrafluoro-2-methyl-1-phenyl-4-(phenylsulfonyl)butan-2-yl)pyrrolidine (7c)
1
4
Page 14 of 28

1
White solid (110 mg, 45% yield), R
f
0.8 (PE‒EtOAc, 80:20); mp 71‒73 °C; H NMR 
H
1.19
(d, J = 1.12 Hz, 3H), 1.62‒1.80 (m, 4H), 2.70‒2.78 (m, 1H), 2.78‒2.88 (m, 2H), 3.00‒3.10
(m, 2H), 3.22‒3.32 (m, 1H), 7.09‒7.30 (m, 5H), 7.58‒7.68 (m, 2H), 7.73‒7.82 (m, 1H),
19
7
.98‒8.10 (m, 2H); F NMR ‒111.2 (ddd, J = 286.0, 14.9, 7.2 Hz, 1F), ‒109.0 (ddd, J =
F
251.3, 14.9, 6.2 Hz, 1F), ‒107.3, (ddd, J = 286.0, 11.0, 6.2 Hz, 1F), ‒106.3 (ddd, J = 251.3,
13
1
C
1.0, 7.2 Hz, 1F); C NMR (150 MHz) 19.3, 24.4, 36.4, 46.6, 64.3 (t, J = 20.0 Hz), 117.3
(tt, J = 302.0, 40.3 Hz), 121.4 (tdd, J = 267.0, 30.9, 26.9 Hz), 126.4, 127.9, 129.3, 130.9,
1
1
4
31.0, 133.9, 136.4, 135.5; MS (EI) m/z (rel. int.) 338 (100), 281 (13), 207 (40), 188 (45),
+
46 (23), 91 (12), 77 (18), 68 (17); HRMS (ESI) m/z calcd for C H F NO S [M + H]
21
24
4
2
30.1458, found 430.1458.
4.4.7. 1-(1-(1,1,2,2-Tetrafluoro-2-(phenylthio)ethyl)cyclopentyl)pyrrolidine (6d)
1
5
Page 15 of 28

1
Colorless oil (304 mg, 68% yield), R
f
0.22 (PE); H NMR 
H
1.54‒1.79 (m, 8H), 1.85‒2.10
19
(
m, 4H), 2.80‒2.95 (m, 4H), 7.34‒7.46 (m, 2H), 7.60‒7.68 (m, 3H); F NMR ‒111.3 (t, J
F
13
=
7.01 Hz, 2F), ‒83.8 (t, J = 7.01 Hz, 2F); C NMR (100 MHz) 24.4, 24.6, 31.0 (t, J = 1.8
C
Hz), 46.7 (t, J = 1.7 Hz), 70.2 (t, J = 22.1 Hz), 119.5 (tt, J = 263.6, 29.4 Hz), 125.7 (tt, J =
288.7, 34.8 Hz), 126.6, 128.8, 129.8, 136.8; MS (EI) m/z (rel. int.) 159 (1), 138 (100), 109
+
(5), 77 (3); HRMS (CI) m/z calcd for C17
H
22
F
4
NS [M + H] 348.1409, found 348.1411.
4.4.8. 1-(1-(1,1,2,2-Tetrafluoro-2-(phenylsulfonyl)ethyl)cyclopentyl)pyrrolidine (7d)
1
White solid (222 mg, 41% yield), R 0.82 (PE‒EtOAc, 80:20); mp 118‒120 °C; H NMR 
H
f
1
3
.51‒1.75 (m, 8H), 1.82‒2.03 (m, 4H), 2.64‒2.83 (m, 4H), 7.61‒7.72 (m, 2H), 8.00‒8.08 (m,
19
13
H); F NMR ‒108.5 to ‒108.3 (m, 2F), ‒108.0 to ‒107.8 (m, 2F); C NMR (100
F
1
6
Page 16 of 28

C 2 2
MHz) 24.3, 24.7, 30.8, 46.4, 129.2, 129.6, 130.9, 135.4, 136.4, CF CF carbons were not
22 4 2
observed; MS (EI) m/z (rel. int.) 138 (100), 77 (9); HRMS (CI) m/z calcd for C17H F NO S
+
[
M + H] 380.1307, found 380.1306.
4.4.9. N-Benzyl-N-methyl-1-(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)cyclohexanamine (6e)
1
Colorless oil (1.20 g, 70% yield), R 0.68 (PE‒EtOAc, 95:5); H NMR 
H
1.16‒1.33 (m, 1H),
f
1
1
‒
.43‒1.57 (m, 2H), 1.60‒2.84 (m, 5H), 2.16‒2.29 (m, 2H), 2.38 (s, 3H), 3.66 (s, 1H), 4.36 (s,
19
H), 7.16‒7.26 (m, 1H), 7.28‒7.52 (m, 7H), 7.59‒7.73 (m, 2H); F NMR ‒109.0 (s, 2F),
F
13
C
82.8 (d, J = 9.2 Hz, 2F); C NMR (100 MHz) 20.7, 25.8, 29.1 (t, J = 2.6 Hz), 34.4 (t, J =
2
1
9
.9 Hz), 53.8 (t, J = 3.0 Hz), 64.9 (tt, J = 19.3, 2.3 Hz), 126.3, 127.6, 128.2, 129.1, 130.3,
37.4, 141.2, CF CF carbons were not observed; MS (EI) m/z (rel. int.) 202 (100), 109 (5),
2
2
+
26 4
1 (40), 65 (3); HRMS (CI) m/z calcd for C22H F NS [M + H] 412.1722, found 412.1730.
4.4.10. N-Benzyl-N-methyl-1-(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)cyclohexanamine
(7e)
1
7
Page 17 of 28

1
White solid (1.121 g, 66% yield), R
f
0.8 (PE‒EtOAc, 80:20); mp 116-118 °C; H NMR 
H
1
3
7
.10‒1.34 (m, 1H), 1.39‒1.64 (m, 4H), 1.65‒1.87 (m, 3H), 2.13‒2.28 (m, 2H), 2.38 (s, 3H),
.67 (s, 1H), 4.34 (s, 1H), 7.16‒7.27 (m, 1H), 7.28‒7.39 (m, 4H), 7.57‒7.71 (m, 2H),
19
.73‒7.85 (m, 1H), 8.00‒8.10 (m, 2H); F NMR ‒111.3 (s, 2F), ‒107.9 (d, J = 88.7 Hz,
F
13
2
F); C NMR (100 MHz)
C
20.5, 25.6, 28.7 (t, J = 2.7 Hz), 34.2 (t, J = 2.8 Hz), 53.7 (t, J =
3.0 Hz), 65.7 (tt, J = 19.1, 2.3 Hz), 126.4, 127.5, 128.3, 129.3, 130.9, 133.9, 135.6, 140.7,
CF
2
CF
2
carbons were not observed; MS (EI) m/z (rel. int.) 202 (100), 91 (52); HRMS (CI)
+
m/z calcd for C22
H
26
F
4
NO
S [M + H] 444.1620, found 444.1628.
2
4.4.11. N,N-Dibenzyl-1-(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)cyclohexanamine (6f)
1
Colorless oil (263 mg, 28% yield), R 0.18 (PE); H NMR  1.16‒1.28 (m, 1H), 1.34‒1.42
H
f
(m, 2H), 1.57‒1.79 (m, 5H), 2.23‒2.35 (m, 2H), 3.87 (s, 2H), 4.40 (s, 2H), 6.91‒7.14 (m,
1
8
Page 18 of 28

19
13
1
0H), 7.34‒7.51 (m, 3H), 7.62‒7.77 (m, 2H); F NMR ‒82.5 (s, 2F), ‒107.1 (s, 2F); C
F
NMR (100 MHz) 20.8, 25.6, 30.1 (t, J = 2.9 Hz), 54.5 (t, J = 2.8 Hz), 67.1 (tt, J = 18.9,
C
2
1
1
.2 Hz), 121.7 (tt, J = 265.3, 34.8 Hz), 124.7, 126.1, 126.7 (tt, J = 290.3, 41.3 Hz), 127.6,
28.9, 129.1, 130.3, 137.4, 141.0; MS (EI) m/z (rel. int.) 280 (3), 278 (100), 186 (6), 181 (7),
+
09 (6), 91 (40), 77 (2), 65 (4); HRMS (ESI) m/z calcd for C28
H
30
F
4
NS [M + H] 398.1566,
found 488.2022.
4.4.12 N,N-Dibenzyl-1-(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)cyclohexanamine (7f)
1
White solid (200 mg, 20% yield), R 0.47 (PE‒EtOAc, 95:5); mp 138-140 °C; H NMR 
H
f
1
4
.12‒1.30 (m, 1H), 1.33‒1.47 (m, 2H), 1.53‒1.79 (m, 5H), 2.15‒2.33 (m, 2H), 3.90 (s, 2H),
.36 (s, 2H), 6.90‒7.16 (m, 10H), 7.58‒7.70 (m, 2H), 7.75‒7.86 (m, 1H), 7.97‒8.12 (m, 2H);
19
13
F NMR
F
‒82.5 to ‒109.6 (m, 2F), ‒107.7 to ‒107.5 (m, 2F); C NMR (100 MHz)
C
20.6, 25.5, 29.7 (t, J = 2.9 Hz), 54.2 (t, J = 3.1 Hz), 67.8 (tt, J = 18.9, 2.2 Hz), 117.5 (tt, J
=
300.9, 43.4 Hz), 122.8 (tt, J = 265.6, 32.4), 126.2, 127.7, 128.9, 129.3, 130.9, 133.9, 135.6,
1
9
Page 19 of 28

140.5; MS (EI) m/z (rel. int.) 277 (11), 244 (8), 207 (12), 186 (94), 140 (34), 106 (11), 105
(
3), 91 (100), 77 (58), 65 (17), 51 (19); HRMS (ESI) m/z calcd for C28 NNaO S [M +
H
29
F
4
2
+
Na] 542.1747, found 542.1748.
4.4.13.
N,N-Diethyl-1-(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)-2,3-dihydro-1H-inden-1-
amine (6g)
1
Yellow oil (122 mg, 38% yield), R
f
0.36 (PE‒EtOAc, 95:5); H NMR 
H
0.80 (t, J = 7.0, 6H),
2
3
.23‒2.41 (m, 2H), 2.63‒3.07 (m, 6H), 7.03‒7.20 (m, 3H), 7.22‒7.37 (m, 3H), 7.44‒7.59 (m,
19
H); F NMR ‒108.6 (dd, J = 273.6, 7.4, 1F), ‒106.5 (dd, J = 273.6, 6.3, 1F), ‒82.3, (dd,
F
13
C
J = 217.4, 7.4, 1F), ‒80.6 (dd, J = 217.4, 6.3, 1F); C NMR (150 MHz) 15.2, 30.5, 32.0 (t,
J = 2.2 Hz), 44.0 (t, J = 1.7 Hz), 119.2 (tt, J = 261.7, 29.0 Hz), 120.2 (tt, J = 264.0, 30.9 Hz),
124.6, 125.4, 127.7, 128.3, 129.0, 130.1, 137.2, 140.7, 145.0; MS (EI) m/z (rel. int.) 188
+
(
100), 159 (9), 115 (5), 109 (3), 77 (4); HRMS (ESI) m/z calcd for C H F NS [M + H]
21 24 4
398.1566, found 398.1557.
4.4.14. N,N-Diethyl-1-(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)-2,3-dihydro-1H-inden-1-
amine (7g)
2
0
Page 20 of 28

1
Yellow oil (74 mg, 20% yield), R
f
0.8 (PE‒EtOAc, 80:20); H NMR 
H
0.82 (t, J = 7.1, 6H),
2
1
2
.30‒2.47 (m, 2H), 2.68‒2.93 (m, 5H), 2.96‒3.10 (m, 1H), 7.07‒7.30 (m, 3H), 7.38‒7.47 (m,
19
H), 7.54‒7.64 (m, 2H), 7.68‒7.80 (m, 1H), 7.92‒8.04 (m, 2H); F NMR ‒107.1 (dt, J =
F
13
49.7, 3.5, 1F), ‒106.9 (t, J = 249.7, 3.5, 2F), ‒105.2, (dt, J = 249.7, 3.5, 1F); C NMR (100
MHz)
C
15.7, 30.3, 31.6 (t, J = 2.5 Hz), 44.3 (t, J = 2.1 Hz), 78.2 (tt, J = 20.3, 2.2 Hz), 116.9
(tt, J = 301.9, 43.6 Hz), 120.7 (tt, J = 263.2, 33.8 Hz), 124.6, 125.6, 127.1, 128.5, 129.2,
130.8, 133.7, 135.4, 139.7, 145.0; MS (EI) m/z (rel. int.) 188 (100), 77 (11); HRMS (ESI) m/z
+
calcd for C H F NNaO S [M + Na] 452.1278, found 452.1278.
21
23
4
2
4
4
.5 Synthesis of compounds 8
.5.1. N-Methyl-1-(1,1,2,2-tetrafluoro-2-(phenylsulfonyl)ethyl)cyclohexanamine (8e)
A mixture of 10% Pd/C (10 mg) and 7e (444 mg, 1 mmol) in MeOH (10 mL) was stirred for
h in an autoclave (H 20 bar) at room temperature. The solution was then filtered through
celite, the filtrate was concentrated under reduced pressure and purified by column
3
2
chromatography to give 314 mg of 8e (89% yield). Colorless oil, R
0.8 (PE‒EtOAc, 80:20);
f
2
1
Page 21 of 28

1
IR (film) 536, 591, 603, 1105, 1160, 1360, 2817, 2859, 2935, 3103, 3412; H NMR 
H
1.42‒1.58 (m, 7H), 1.60‒1.70 (m, 2H), 1.75‒1.86 (m, 2H), 2.41 (t, J = 1.8 Hz, 3H),
19
7
.58‒7.76 (m, 2H), 7.72‒7.80 (m, 1H), 7.98‒8.06 (m, 2H); F NMR
F
‒112.8 (d, J = 2.7
13
Hz, 2F), ‒107.9 (d, J = 3.3 Hz, 2F); C NMR (100 MHz) 20.4, 25.2, 27.7 (t, J = 2.5 Hz),
C
2
2
8.9 (t, J = 2.2 Hz), 60.8 (tt, J = 20.1, 1.4 Hz), 118.0 (tt, J = 300.7, 40.5 Hz), 120.4 (tt, J =
65.8, 27.9 Hz), 129.2, 130.9, 133.9, 135.4; MS (EI) m/z (rel. int.) 310 (4), 168 (3), 112
+
(100), 77 (10); HRMS (ESI) m/z calcd for C15
H
20
F
4
NO
2
S [M + H] 354.1145, found
354.1145
4.5.1. 1-(1,1,2,2-Tetrafluoro-2-(phenylsulfonyl)ethyl)cyclohexanamine (8f)
A mixture of 10% Pd/C (50 mg) and 7f (519mg, 1 mmol) in AcOH (30 mL) was stirred at 70
C for 24 h in a flask under atmospheric hydrogen pressure. The solution was then filtered
through celite, the filtrate was concentrated under reduced pressure and purified by column
°
chromatography to give 241 mg of 8f (71% yield). Colorless oil, R
0.14 (PE‒EtOAc, 90:10);
f
1
IR 535, 602, 1104, 1159, 1359, 1450, 2863, 2937, 3068, 3354, 3426; H NMR 
H
1.51‒1.76
2
2
Page 22 of 28

19
(m, 10H), 2.08 (s, 2H), 7.60‒7.67 (m, 2H), 7.74‒7.82 (m, 1H), 7.98‒8.08 (m, 2H);
F
13
NMR
F
C
‒107.2 (m, 2F), ‒119.2 (m, 2F); C NMR (100 MHz) 20.2, 25.4, 29.9 (t, J = 2.4
Hz), 58.1 (tt, J = 21.5, 2.2 Hz), 117.7 (tt, J = 300.5, 40.7 Hz), 119.2 (tt, J = 260.6, 27.4 Hz),
129.3, 130.9, 133.5, 135.6; MS (EI) m/z (rel. int.) 296 (14), 98 (100), 77 (13); HRMS (CI)
+
m/z calcd for C14
H
18
F
4
NO
2
S [M + H] 340.0994, found 340.1001
4.6 General procedure for the synthesis of compounds 9
Method A. A solution of n-Bu SnH (403 μL, 1.5 mmol) and AIBN (3 mg, 0.02 mmol) in dry
3
toluene (2 mL) was added to a refluxing solution of 6a or 6e (1 mmol) in dry toluene (3 mL).
The resulting mixture was refluxed for 3 h, followed by concentration under reduced pressure
and purification by flash column chromatography (PE–EtOAc) to give 9a (91% yield) and 9e
(64% yield), respectively.
Method B. I (40 mg, cat.) was added to Mg turnings (240 mg, 10 mmol), the mixture was
2
heated up with a heat gun and stirred for 10 minutes. Then, a solution of 7a (409 mg, 1
mmol) in MeOH (10 mL) was added, and the mixture was stirred for 1.5 h at room
temperature. A second portion of Mg (480 mg, 20 mmol) was added, and the reaction mixture
4
was stirred for 2.5 h at room temperature. Aqueous saturated NH Cl (15 mL) was added and
the reaction mixture was extracted with Et O. The combined organic phase was washed with
2
4
brine and water, dried (MgSO ), and concentrated under vacuum. The crude product was
purified by column chromatography eluting with PE‒EtOAc to give 9a (80% yield).
4.6.1 4-(1-(1,1,2,2-Tetrafluoroethyl)cyclohexyl)morpholine (9a)
2
3
Page 23 of 28

White solid (245 mg, 91% yield from 6a or 215 mg, 80% yield from 7a), R
0.30
f
1
(
PE‒EtOAc, 95:5); m.p. 56-58°C; H NMR 
H
1.12‒1.37 (m, 1H), 1.40‒1.67 (m, 6H),
19
1
.69‒1.80 (m, 1H), 2.05 (d, J = 13.0 Hz, 2H), 2.87 (s, 4H), 3.66 (s, 4H); F NMR ‒134.1

13
(
C
t, J = 4.7 Hz, 2F), ‒121.0 (s, 2F); C NMR (100 MHz) 20.3, 25.7, 27.4 (t, J = 2.3 Hz),
4
2
6.8 (t, J = 2.0 Hz), 61.7 (t, J = 18.9 Hz), 68.4, 110.5 (tt, J = 252.0, 36.3 Hz), 120.5 (tt, J =
60.6, 24.9 Hz); MS (EI) m/z (rel. int.) 182 (1), 168 (100), 101 (1); HRMS (CI) m/z calcd for
+
C H F NO [M + H] 270.1481, found 270.1486
12
20 4
4.6.2 N-Benzyl-N-methyl-1-(1,1,2,2-tetrafluoroethyl)cyclohexanamine (9e)
1
Colorless oil (194 mg, 64% yield), R
f
0.64 (PE); H NMR 
H
1.23‒1.35 (m, 2H), 1.45‒1.62
(m, 4H), 1.67‒1.86 (m, 3H), 2.09‒2.28 (m, 2H), 2.37 (s, 3H), 4.0 (s, 2H), 5.82 (tt, J = 52.9,
19
5
.9 Hz, 3H), 7.13‒7.52 (m, 5H); F NMR  ‒134.0 (t, J = 4.8 Hz, 2F), ‒120.8 to ‒119.6 (m,
F
2
4
Page 24 of 28

13
2
F); C NMR (100 MHz)
C
20.5, 25.8, 28.5, 34.4 (t, J = 2.2 Hz), 54.0 (t, J = 2.5 Hz), 62.4
(t, J = 18.7 Hz), 110.6 (tt, J = 251.9, 36.1 Hz), 120.9 (tt, J = 261.7, 25.0 Hz), 126.5, 127.6,
22 4
128.3, 140.7; MS (EI) m/z (rel. int.) 202 (100), 91 (64); HRMS (ESI) m/z calcd for C16H F N
+
[
M + H] 304.16829, found 304.1683
Acknowledgement
Financial support from the Academy of Sciences of the Czech Republic (Research Plan
RVO: 61388963) and the Grant Agency of the Czech Republic (207/11/0421) is gratefully
acknowledged.
References[1]
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2
6
Page 26 of 28

Highlights



 PhSCF
2
CF
2
TMS and PhSO
2
CF
2
CF TMS react with iminium salts formed from enamines and HF
2
to form products of nucleophilic addition.
 Radical or reductive desulfurization of the adducts affords amines with the tetrafluoroethyl
group.
 Primary, secondary and tertiary amines substituted with the CF CF group on -carbon are
2
2
accessed by this method.
2
7
Page 27 of 28

2 2
CF CF
R4
"
HF"
Me
Me
NR23
R CF
CF
SiMe
3
Si Me
2
3
2
4
4
NR
CF CF R
R1
2
2
3
R1
2
R1
F
H
F
R2
4
R2
R2 NR
R = PhS, PhSO
2
2
enamine
iminium
salt
4
CF CF R
CF CF H
R1
2
2
R1
2
2
R2 NH2
R2 NR23
2
8
Page 28 of 28