Visible-Light-Mediated Amination of π-Nucleophiles with N-Aminopyridinium Salts

Article abstract of DOI:10.1021/acs.joc.9b02073

N-Aminopyridinium salts generate nitrogen-centered radicals by means of photoredox catalysis. Herein, we report that they can be trapped by enol equivalents to give α-amino carbonyl compounds in excellent yields. The broad synthetic utility of this method is demonstrated by functionalization of ketones, aldehydes, esters enol equivalents, vinyl ethers, and 1,3-diketones without the need for prior conversion to enol derivatives. The developed method is easily scalable, offers broad substrate scope, high chemoselectivity.

Full text of DOI:10.1021/acs.joc.9b02073

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Article
Visible-Light-Mediated Amination of #-
Nucleophiles with N-Aminopyridinium Salts
Katarzyna Goliszewska, Katarzyna Rybicka-Jasi#ska, Jakub Szurmak, and Dorota Gryko
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02073 • Publication Date (Web): 08 Oct 2019
Downloaded from pubs.acs.org on October 13, 2019
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Visible-Light-Mediated Amination of
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π-Nucleophiles with N-aminopyridinium Salts
Katarzyna Goliszewska,a Katarzyna Rybicka-Jasińska,a Jakub Szurmaka,b and Dorota Gryko*a
aInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224
Warsaw, Poland
bFaculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw,
Poland
KEYWORDS: photocatalysis, amidyl radicals, N-aminopyridinium salts, enols, carbonyl
compounds
ABSTRACT
N-aminopyridinium salts generate nitrogen-centered radicals by means of photoredox catalysis.
Herein, we report that they can be trapped by enol equivalents to give α-amino carbonyl
compounds in excellent yields. The broad synthetic utility of this method is demonstrated by
functionalization of ketones, aldehydes, esters enol equivalents, vinyl ethers and 1,3-diketones
without the need for prior conversion to enol derivatives. The developed method is easily scalable,
offers broad substrate scope, high chemoselectivity, and mild conditions.
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INTRODUCTION
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Nitrogen containing compounds not only play a crucial role in living organisms (e.g. proteins,
nucleic acids, amino acids), medicine and materials science but are also extensively utilized as
synthetic intermediates and coordinating ligands in organic synthesis.1,2 Of the functional groups
containing nitrogen atoms, the amine group is one of the most ubiquitous and thus selective and
efficient methods leading to the formation of C-N bonds are highly desirable.
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In addition to the well-established nucleophilic and electrophilic3 direct amination reactions,
recently methods utilizing nitrogen-centered radicals have attracted considerable attention.4 Up to
date developments in photoredox catalysis5 indicate that nitrogen radicals can be generated under
mild reaction conditions from stable starting materials including phtalimides,6-7 sulfonamides,8-10
hydrazones,11–13 aryloxyamides14–16 or amides.17 Recently, Studer and coworkers added N-
aminopyridinium salts to this list.18 Due to the simplicity of their large-scale synthesis from
commercially available pyrylium salts and hydrazine derivatives or from N-aminopyridinium
iodide and acid chlorides, shelf life stability, and a variety of compatible protecting groups of the
amine functionality they became attractive starting materials. Photochemically generated amidyl
radicals easily react with electron-rich arenes, heteroarenes,18 and styrene derivatives19-20 enabling,
among others, the facile synthesis of vicinal aminoalcohols,21 imidazolines or oxazolines.22
N-aminopyridinium salts are also a source of nitrenium ions and as such they react with various
nucleophiles.23-24 In this line, Falvey and coworkers reported that under UV irradiation N,N-
(diphenylamino)-2,4,6-trimethylpyridinium salt (1a) reacts with π-nucleophiles to give the
addition products from the reaction at para- and ortho- positions on one of the phenyl rings and
N-phenyl indole (Scheme 1A).25 Generally amination of an electron rich double bond is not
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observed, and only for silyl ketene acetals traces of α-amino acid form. But, the addition of radicals
to enols represents a convenient method for the synthesis of α-substituted ketones. This approach
has been adopted for practical alkylations,26 fluoroalkylations,27 oxyamination,28 and azidation.27b
Given our long standing interest in photoredox catalysis we envisioned that electrophilic N-
centered radicals generated from N-aminopyridinium salts should be trapped by nucleophilic enol
derivatives leading to the formation of the C-N bond (Scheme 1B). Such reactivity would pose a
novel approach towards amination of carbonyl compounds allowing convenient access to α-amino
ketones, aldehydes, unnatural amino acids etc. – compounds of significance for synthetic
chemists.29
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Scheme 1. The Reactivity of N-Aminopyridinium Salts Towards Enol Derivatives
RESULTS AND DISCUSSION
To confirm our hypothesis, we initiated our studies by exploring the reactivity of N,N-
(diphenylamino)pyridinium salt (1a) towards enol acetate 2a. Under light irradiation the
envisioned reaction catalyzed by fac-Ir(ppy)3 did not furnish the desired product. As it is known
that the diphenyl substituted iminyl radical is stabilized by the aromatic ring leading to spin-stable
delocalized systems,30 we turned our attention to less stable amidyl radicals. Replacing diphenyl
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salt 1a with N-Me,N-Ts-derivative 1b enabled the formation of product 3a in 51% yield (Table 1,
entry 1). Background experiments proved that both the Ir-catalyst and light are essential to trigger
the radical reaction (entries 2 and 3). Even though the reduction potential of salt 1b (Ered = 0.7 V
2+
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vs Ag/AgCl in MeCN) is accessible to other photocatalysts including Ru(bpy)3 and that the
reported by Studer et al. amidation of arenes is catalyzed by the Ru-complex,18 these were not
effective in promoting our model reaction. Optimization studies indicated that MeCN may be
exchanged with chlorinated solvents (DCM or CHCl3) without diminishing the yield, while protic
solvents are not compatible with the reaction due to plausible protonation of the amidyl radical.
Table 1. Optimization Studiesa
Entry
Catalyst
[mol%]
Light
Yield [%]b
1
2
2
blue LED
blue LED
none
67(51)c,d
none
0
0
3
2
1
1
1
1
1
4
blue LED
blue LED
blue LED
blue LED
blue LED
66
5e
6e,h
7e,f
8e,g
93
96 (95)c
traces
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aReaction conditions: enol 2a (0.1 mmol), salt 1b (1 equiv.), fac-Ir(ppy)3, dry MeCN (c = 0.05
b
M), ambient temperature (20-22 °C), 16 h, under Ar atmosphere, light source: LED diode. GC
yield. cIsolated yield. dNot dry MeCN. eSalt 1b (1.2 equiv.). fAir atmosphere. gWith H2O (4 equiv.).
h1 h.
Notably, we were able to lower the catalyst loading to as low as 1 mol% with no significant
changes in the reaction yield (entry 4). The highest increase in yield was observed when a small
excess of salt 1b (1.2 equiv.) was used (entry 5). In the model reaction enol 2a was completely
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consumed after just 1 h giving product 3a in an excellent yield (95%, entry 6). The presence of
oxygen, a quencher of the excited triplet state, suppresses the reaction almost completely (entry 7)
while the addition of water causes only a slight drop in the reaction yield (entry 8).
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Having the optimized reaction conditions, the scope and limitations of the developed amination
were examined. Evaluation commenced by testing a selection of enol equivalents including esters
2a-c, silyl ethers 2d and 2e, and acetamide 2f (Table 2).
Table 2. Scope of Enol Derivativesa
Entry
1
X
OAc
Enol
2a
Product
3a
Yield%
95
2b
3b
4
OBz
2b
2c
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45
OTf
3a
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OTMS
OTBDMS
NHAc
2d
2e
3a
83
5
3a
99
6b
2f
3a
44c
aReaction conditions (isolated yields): enol derivative 2 (0.25 mmol), salt 1b (1.2 equiv.), fac-
Ir(ppy)3 (1 mol%), dry MeCN (c = 0.05 M), ambient temperature (20-22 °C), 1 h, under Ar
atmosphere, light source: LED diode. b16 h. cAcidic work-up required.
The reaction is tolerant of the most commonly used and easily accessible acyl and silyl
derivatives giving the desired product 3a in yields of up to 99%, with the highest being for TBDMS
enol ether 2e (entry 5). Notably, the use of the benzoyl group enables amination of enolate 2b
without simultaneous deprotection furnishing derivative 4 with a highly functionalized double
bond with the enol reactivity retained (entry 2). Enolates 2b, 2c and enamide 2f are less reactive
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under the optimized reaction conditions which manifests in longer reaction times and lower yields
(entries 2, 3, 6).
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Following the evaluation of different enol equivalents we sought to establish the reactivity of
enols derived from various carbonyl compounds. The synthesis of α-amino acetophenones (3b-i)
tolerates a wide range of halogens (Br, Cl, I), electron-donating (OMe) and electron-withdrawing
(CO2Me, CN) groups at the phenyl ring (Scheme 2). Enols with lower electron density at the α
atom need more time to reach full conversion but the corresponding α-amino ketones (3g and 3h,
16 h) form with comparable yields. Importantly, the developed method may be applied to
heterocyclic derivatives enabling chemoselective amination at the α-position to the carbonyl group
(no amination of the ring was observed) (3j-3l). Enols derived from aliphatic ketones react equally
well giving α-amino products 5a-5d in good yields. It is important to note that even very
challenging quaternary centers such as in 5c can be effectively generated. For cyclic enols the yield
gradually increases with the size of the ring. Having higher cyclic tension, 5- and 6-membered
cyclic enol ethers gave α-aminated products 5e-f in moderate yields while 7- and 8-membered
substrates furnished α-amino ketones 5g-h in excellent yields.
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The developed method is not limited to the amination of ketones, enol equivalents derived from
aldehydes or even 1,3-diketones without the need for enol derivatization are also suitable
substrates providing they exist predominantly in the enol form. α-Amino aldehyde 6a with a
terminal double bond was synthesized through chemoselective functionalization at the α-position.
Moreover, our preliminary results indicated that N-aminopyridinium salts might be applied in the
synthesis of α-aminoesters 8 or selective functionalization of vinyl ethers (9a-b), though fine
tuning of the reaction conditions is still required and will be reported in due course.
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Scheme 2. Scope of Carbonyl Compoundsa
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aReaction conditions (isolated yields): enol (0.25 mmol), salt 1b (1.2 equiv.), fac-Ir(ppy)3 (1
mol%), dry MeCN (c = 0.05 M), ambient temperature (20-22 °C), specified time, under Ar
b
c
atmosphere, light source: LED diode. Enolate with TMS protecting group. Substrate used
without prior enolate formation. dWith CySH (2 equiv.).
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The choice of protecting groups on the amine functionality is crucial as they profoundly
influence the design of synthetic strategies towards complex molecules. To this end, we evaluated
amino-pyridinium salts 1 with common protecting groups for the amine functionality (Table 3).
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Table 3. Influence of the Salt Structurea
(0)
Entry
Salt
Ered
Time
[h]
1
Product
Yield
[%]
89
R1
Me
Me
Me
Ph
H
R2, R3
[V]d,e
-0.68
-1.14
-0.76
-1.17
-0.77
-0.77
-0.98
-0.86
-0.82
1b
2b
3b
4b
5b
6c
7c
8c
9c
Boc, Me
Cbz, Me
Pht
1c
1d
1e
1f
10a
10b
-
1
42
22
1
trace
32
Boc, Me
Ts, H
10a
10c
10c
10d
10e
10f
1g
1g
1h
1i
1
0
H
Ts, H
16
48
16
19
92
H
Cbz, H
C6F5CO, H
CF3CO, H
48
H
57
H
1j
72
aReaction conditions (isolated yields): enol 2a or 2e (0.25 mmol), salt 1c-j (1.2 equiv.), fac-
Ir(ppy)3 (1 mol%), dry MeCN (c = 0.05 M), ambient temperature (20-22 °C), under Ar atmosphere,
light source: LED diode. bEnolate with TBDMS protecting group (2e). cEnolate with Ac protecting
group (2a). dCyclic voltammograms of N-aminopyridinium salts 1a-j for MeCN in the presence of
100 mM N(n-Bu)4ClO4 recorded at a scan rate,  = 100 mVs–1 (three-electrode cell equipped with
a glassy carbon working electrode, a 25 mm platinum wire as the counter electrode and Ag/AgCl
(3.0 M NaCl) electrode as the reference electrode). eV vs SCE.
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Both mono- and diprotected N-aminopyridinium salts generate N-centered radicals, however,
some differences in reactivity do exist. Among diprotected derivatives 1c-f the most effective is
salt 1c with N-Me,N-Boc-amino functionality. The analogous Cbz-derivative 1d affords product
10b in 42% yield, while only traces of the desired product with N-phthalolyl-protection formed
(entries 1-3). The character of the pyridinium salt has a strong impact on the reactivity; the
replacement of methyl groups with phenyls on the pyridine moiety leads to a substantial decrease
in the yield due to predominating hydrolysis of enol ether 2e (entry 4). Monosubstituted salts 1g-j
tolerates only acyl enolates 2a as in their presence silyl enol ether 2e undergoes fast hydrolysis
(compare entry 5 and 6).
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For structurally similar mono-protected salts 1g-j, a higher reduction potential results corresponds
to a higher reaction yield (Figure 1). Such a strong correlation is not valid for diprotected N-
aminopyridinium salts (Table 3) for which steric and electronic factors may also play a role,30
though the trend is preserved.
Figure 1. Comparison of reduction potentials for salts 1g-j.
To show the practical utility of the developed amination of enol derivatives, we proved that the
process is easily scalable by synthesizing product 3a on a 1.0 mmol scale in 7 h 86% yield. We
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also employed our strategy for the synthesis of adrenalone (14), an adrenergic agonist used as a
topical vasoconstrictor and hemostatic (Scheme 3). Starting from commercially available 3,4-
dihydroxyacetophenone (11) in just two steps we were able to synthesize derivative 13 which may
be quantitatively hydrolyzed to the desired adrenalone (14) (overall yield 74% from ketone 11).
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Scheme 3. The Synthesis of Adrenalone via Developed Amination Strategy
Based on previous work18,21 we postulated that the reaction proceeds through a radical mechanism.
To support this hypothesis the reaction of enol 2a with N-aminopyridinium salt 1b in the presence
of TEMPO was performed, and, as expected the reaction was completely suppressed. The presence
of a paramagnetic species was confirmed by EPR measurements performed for N-aminopyridinum
salt 1b and for the reaction mixture both after irradiation with blue LEDs and with DMPO as a
spin trap (Figure 2a). The recorded signals have the same pattern suggesting the presence of the
same paramagnetic species. The assumed formation of an amidyl radical is confirmed by HRMS
analysis, the signal at m/z = 297.1273 [M+H]+ corresponds to the adduct 15 formed with the
DMPO spin trap (Figure 2b).
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a)
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b)
Figure 2. a) EPR spectra of N-aminopyridinium salt 1b in the presence and of the reaction
mixture in the presence of DMPO, b) the structure of adduct 15.
As the fac-Ir(ppy)3 catalyst is able to operate via both reductive and oxidative quenching,31 we
performed Stern-Volmer experiments for the reaction components to examine the role of the
photocatalyst (Figure 3). N-Aminopyridinium salt 1b quenches the luminescence of the Ir-catalyst
effectively with the quenching rate constant kq(2a) = 5.90 ×108 M-1s-1, while for enol 2a quenching
was not observed. Furthermore, the quantum yield of the photocatalytic model reaction was
determined (see the SI). The estimated value of Φ = 9.1 ± 1.3% indicates that efficient radical
chain processes are unlikely.
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Figure 3. Stern-Volmer experiments.
On the basis of the mechanistic experiments and previous reports, we propose the plausible
reaction mechanism presented in Scheme 4. Upon excitation by visible-light, the Ir-catalyst
reduces N-aminopyridinium salt A via single-electron transfer to pyridyl radical B which
undergoes fragmentation to N-centered radical C and a rearomatized pyridine derivative. Radical
C adds to the π-nucleophile D to produce radical E which after oxidation to cation F maintains the
catalytic cycle by regenerating the Ir-catalyst. Subsequent steps may involve either nucleophilic
addition to cation F, similarly to that reported by Akita,20 or deprotection of the ketone.
18
Experiments with the addition of H2 O (see SI) excluded the former possibility as no traces of the
product with incorporated 18O were detected, and hence, in our case the deprotection of the acyl
or silyl group leading to the final α-amino ketone G occurs faster.
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Scheme 4. Plausible Mechanism of the Amination with N-Aminopyridinum Salts
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CONCLUSIONS
In summary, we have developed a visible-light induced amination reaction for electron-rich olefins
with N-protected-aminopyridinium salts leading to α-amnio carbonyl compounds. The reactivity
of the generated electrophilic N-centered radicals is controlled by the substitution pattern of the
salt. Boc, trifluoroacetyl or pentafluorobenzoyl substituents enable effective enol functionalization
while N-Cbz protected salts are less reactive.
Our high-yielding, widely applicable transformation occurring under mild reaction conditions can
be applied for late-stage diversification of synthetic compounds and functionalization of complex
molecules. The extension of the methodology for other π-nucleophiles than ketones, aldehydes,
esters, vinyl ethers is currently the subject of our investigations.
Experimental Section
General Information. All solvents and commercially available reagents were purchased as
reagent grade and were used without further purification. Reactions were monitored by thin layer
chromatography (TLC), using 0.20 mm Merck silica plates (60F-254) or 0.20 mm Merck
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aluminum oxide plates (60F-254) and visualised using UV-light or cerium molybdate stain with
heat as a developing agent. Photo-induced reactions were performed in a photoreactor (6 blue LED
diods, 455-475 nm, 3W) with cooling by Huber MiniChiller 300. Colum chromatography was
performed using Merck silica gel 60 (230-400 mesh) or Merck Al2O3 neutral (50-300 mesh)
deactivated with 15 wt% of H2O. NMR spectra were recorded on Bruker 400 MHz, Varian 500 or
600 MHz and calibrated using residual undeuterated solvent or TMS as an internal reference. High-
resolution mass spectra (HRMS) were recorded on a Waters AutoSpec Premier instrument using
electron ionization (EI) or a Waters SYNAPT G2-S HDMS instrument using electrospray
ionization (ESI) with time of flight detector (TOF). Elemental analysis (C, H, N, S) were
performed using a PERKIN-ELMER 240 Elemental Analyzer. Cyclic voltammograms were
recorded using Bio-Logic SP-50 potentiostat. GC-MS analyses were performed using Shimadzu
GCMS-QP2010 SE gas chromatograph with FID detector and Zebron ZB 5MSi column.
Fluorescence quenching experiments were performed using a Hitachi F-7000 fluorescence
spectrophotometer. EPR spectrum was recorded on Magnettech MS200 spectrometer. Enol
derivatives 2a-f were prepared according to literature procedures.32-36 N-aminopyridinium salts 1a-
c, 1e, 1g, 1i-j were prepared according to literature procedures.18,21,25
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General procedure A for preparation of TBDMS enol ethers. To a precooled to 0 °C solution
of ketone (5.0 mmol, 1.0 equiv.) and KI (6.5 mmol, 1.3 equiv.) in anhydrous MeCN (0.5 M) under
Ar atmosphere, Et3N (6.5 mmol, 1.3 equiv) was added dropwise followed by the addition of
TBDMSCl (6.5 mmol, 1.3 equiv. in one portion). The mixture was stirred for 16-24 h (determined
by TLC) at room temperature. The reaction was quenched with NaCl(sat.) and then extracted with
DCM. The organic solution was dried over Na2SO4, filtered, and concentrated in vacuo. The crude
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product was purified by flash column chromatography on deactivated Al2O3 (neutral Al2O3 treated
with 15 wt% of H2O) using hexane as eluent.
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General procedure B for preparation of N-aminopirydinium salts from hydrazines. 2,4,6-
Trimethylpyrylium tetrafluoroborate (2.0 mmol, 1.0 equiv.) or 2,4,6-triphenylpyridinium
tetrafluoroborate (2.0 mmol, 1.0 equiv.) was suspended in absolute EtOH (5 ml). Subsequently,
hydrazine (2.4 mmol, 1.2 equiv.) was added and the reaction mixture was stirred at room
temperature for 16 h. After this time, Et2O was added to the mixture. The resulting precipitate was
filtered off, washed with Et2O and dried under vacuum.
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General procedure C for preparation of N-aminopirydinium salts from N-aminopyridinium
iodide. To a precooled to 0 °C solution of N-aminopyridinium iodide (4.0 mmol, 1.0 equiv.) in
anhydrous MeCN (0.2 M) was added 4-dimethylaminopyridine (DMAP, 0.04 mmol, 0.01 equiv.),
K2CO3 (12.0 mmol, 3 equiv.) and acyl chloride (4.4 mmol, 1.1 equiv.) under Ar atmosphere. Then,
the mixture was stirred for 16-24 h at room temperature (conversion determined by TLC). The
resulting suspension was filtered and filtrate was concentrated in vacuo. The resulting solid was
suspended in DCM and filtered to remove inorganic impurities. After the solvent was removed
under reduced pressure, the crude product was purified by flash column chromatography on
deactivated Al2O3 (neutral Al2O3 treated with 15 wt% of H2O) using DCM/MeOH mixture as
eluent. The obtained ylide was disolved in DCM (0.5 M) and tetrafluoroboric acid (4.8 mmol, 1.2
equiv., 42 wt.% in H2O) or TfOH (4.8 mmol, 1.2 equiv.) was added to the solution at room
temperature. The reaction mixture was stirred for 30 min, then the product was precipitated with
Et2O. The resulting precipitate was filtered off, washed with Et2O and dried under vacuum.
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General procedure D for visible-light mediated amination of electron-rich olefins. A glass
vial equipped with a stirring bar and sealed with septum was charged with enol (if solid, 0.25
mmol, 1.0 equiv.), fac-Ir(ppy)3 (0.04 mmol, 1.0 mol%) and N-aminopyridinium salt (0.3 mmol,
1.2 equiv.). Anhydrous MeCN (5 ml) was added and the resulting mixture was degassed by argon
bubbling for 20 minutes. Subsequently, (enol if liquid, 0.25 mmol, 1.0 equiv. was added) the
reaction mixture was placed in a photoreactor and irradiated with blue LED for the specified time.
After the removal of solvent, a crude product was purified flash column chromatography using
hexane/Et2O mixture (100% hexane to 50% Et2O in hexane) as eluent.
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((2H-chromen-4-yl)oxy)(tert-butyl)dimethylsilane. Following the general procedure A the title
compound was obtained from 4-chromanone (5.0 mmol). The crude product was purified by
column chromatography to afford 1.1 g of a colorless oil (Yield = 87%, 16 h). 1H NMR (400 MHz,
CDCl3): δ 7.36 (dd, J = 7.6 Hz, J = 1.7 Hz, 1H), 7.13 (td, J = 8.1 Hz, 1.7 Hz, 1H), 6.90 (td, J = 7.5
Hz, J = 1.2 Hz, 1H), 6.78 (dd, J = 8.1 Hz, J = 1.1 Hz, 1H), 4.89-4.87 (m, 1H), 4.84 (d, J = 3.6 Hz,
2H), 1.02 (s, 9H), 0.23 (s, 6H). 13C {1H} NMR (100 MHz, CDCl3): δ 155.7, 146.0, 129.5, 122.5,
122.4, 120.9, 115.4, 97.9, 65.8, 25.8, 18.3, -4.6. HRMS (ESI, m/z) calcd for C15H23O2Si (M + H)+
263.1103, found 263.1102.
tert-butyldimethyl(undeca-1,10-dien-1-yloxy)silane (Z/E mixture). Following the general
procedure A the title compound was obtained from 10-undecenal (5.0 mmol). The crude product
was purified by column chromatography to afford 1.2 g of a colorless oil (Yield = 90%, 16 h, Z/E
ratio: 8:1). 1H NMR (400 MHz, CDCl3): δ 6.16 (dt, J = 5.9 Hz, J = 1.6 Hz, 1H), 5.86-5.75 (m, 1H),
5.02-4.95 (m, 1H), 4.94-4.91 (m, 1H), 4.46-4.41 (m, 1H), 2.06-2.03 (m, 4H), 1.37-1.30 (m, 10H),
0.92 (s, 9H), 0.11 (s, 6H). 13C {1H} NMR (100 MHz, CDCl3): δ 139.2, 138.3, 114.0, 110.8, 33.8,
29.7, 29.3, 29.2, 29.1, 28.9, 25.6, 23.6, 18.3, -5.4. HRMS (ESI, m/z) calcd for C17H35OSi (M + H)+
283.2457, found 283.2447.
tert-butyl 4-(2-((2-(trimethylsilyl)propan-2-yl)oxy)vinyl)piperidine-1-carboxylate (E/Z mixture).
Following the general procedure A the title compound was obtained from N-Boc-4-
piperidineacetaldehyde (5.0 mmol). The crude product was purified by column chromatography
to afford 1.2 g of a colorless oil (Yield = 83%, 16 h, E/Z ratio: 9/1). 1H NMR (400 MHz, CDCl3):
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δ 6.25 (dd, J =0.8 Hz, J = 12.0 Hz, 1H), 6.12 (dd, J = 5.9 Hz, J = 1.7 Hz, 1H), 5.24-5.22 (m, 1H),
4.95-4.91 (m, 1H), 4.28 (dd, J = 8.5 Hz, J = 5.9 Hz, 1H), 4.07-3.93 (m, 2H + m, 2H), 2.82-2.72
(m, 2H + m, 2H), 2.03-1.94 (m, 1H), 1.69-1.56 (m, 2H), 1.45 (s, 9H + s, 9H), 1.29-1.18 (m, 3H +
m, 3H), 0.90 (s, 9H), 0.87 (s, 9H), 0.11 (s, 6H), 0.06 (s, 6H). 13C {1H} NMR (100 MHz, CDCl3):
δ 154.9, 138.1, 114.3, 32.0, 31.4, 28.5, 25.7, 25.6, 18.3, 17.9, -3.4, -5.4. HRMS (ESI, m/z) calcd
for C18H35NO3SiNa (M + Na)+ 364.2284, found 364.2271.
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1-(((benzyloxy)carbonyl)(methyl)amino)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate (1d).
Following the general procedure B compound 1d was obtained from 2,4,6-trimethylpyridinium
tetrafluoroborate (2.0 mmol) and benzyl 1-methylhydrazinecarboxylate (1.2 equiv.) as a white
solid (0.68 g, Yield = 92%). 1H NMR (400 MHz, CDCl3): mixture of rotamers, δ 7.59 (s, 1H, first
rotamer), 7.56 (s, 1H, second rotamer), 7.41 (s, 3H + second rotamer 3H), 7.37-7.33 (m, 1H +
second rotamer 1H), 7.25 (m, 1H + second rotamer 1H), 7.23-7.18 (m, 1H + second rotamer 1H),
5.31 (s, 2H, first rotamer), 5.16 (s, 2H, second rotamer), 3.59 (s, 3H, first rotamer), 3.52 (s, 3H,
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second rotamer), 2.59 (s, 9H, first rotamer), 2.50 (s, 9H, second rotamer). C {1H} NMR (100
MHz, CDCl3): mixture of rotamers, δ 162.2, 161.8, 156.7, 156.4, 153.0, 151.7, 134.5, 134.3, 129.3,
129.1, 129.0, 128.94, 128.88, 128.85, 128.5, 123.6, 70.1, 69.8, 37.5, 36.5, 22.1, 21.1, 18.7, 18.6.
19F NMR (375 MHz, CDCl3): δ -152.80 (11BF4), -152.86 (10BF4). HRMS (ESI, m/z) calcd for
+
C17H21N2O2 (M-BF4)+ 285.1603, found 285.1602.
1-((tert-butoxycarbonyl)(methyl)amino)-2,4,6-triphenylpyridin-1-ium tetrafluoroborate (1f).
Following the general procedure B compound 1f was obtained from 2,4,6-triphenylpyridinium
tetrafluoroborate (2.0 mmol) and tert-butyl 1-methylhydrazinecarboxylate (1.2 equiv.) as a white
solid (0.91 g, Yield = 91%). 1H NMR (400 MHz, CD3CN) mixture of rotamers, δ 8.38 (s, 1H, first
rotamer), 8.36 (s, 1H, second rotamer), 8.10-8.03 (m, 1H + second rotamer 1H), 7.74-7.59 (m,
15H + second rotamer 15H), 2.90 (s, 3H, first rotamer), 2.81 (s, 3H, second rotamer), 1.29 (s, 9H,
first rotamer), 1.27 (s, 9H, second rotamer). 13C {1H} NMR (100 MHz, CD3CN): mixture of
rotamers, δ 158.5, 158.3, 158.1, 158.0, 152.7, 150.0, 133.5, 133.4, 133.2, 133.1, 131.7, 131.6,
130.8, 130.6, 129.9, 129.8, 129.1, 129.0, 128.9, 128.8, 128.5, 127.0, 126.9, 85.5, 84.6, 39.2, 39.0,
27.0, 26.9. 19F NMR (375 MHz, CD3CN): δ -151.85 (11BF4), -151.91 (10BF4). HRMS (ESI, m/z)
+
calcd for C29H29N2O2 (M-BF4)+ 437.2229, found 437.2231.
1-(((benzyloxy)carbonyl)amino)pyridin-1-ium tetrafluoroborate (1h). Following the general
procedure C compound 1h was obtained from N-aminopyridinium iodide (4.0 mmol) and benzyl
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chloroformate (1.2 equiv.) as a white solid (0.77 g, Yield = 61%). 1H NMR (400 MHz, CD3CN):
δ 10.42 (brs, 1H), 8.78 (d, J = 5.6 Hz, 2H), 8.66 (t, J = 7.9 Hz, 1H), 8.17-8.13 (m, 2H), 7.44-7.38
(m, 5H), 5.29 (s, 2H). 13C {1H} NMR (100 MHz, CD3CN): δ 154.0, 147.9, 146.6, 135.0, 129.0,
128.8, 128.7, 128.4, 69.2. 19F NMR (375 MHz, CD3CN): δ -151.7 (11BF4), -151.8 (10BF4). HRMS
+
(ESI, m/z) calcd for C13H13N2O2 (M-BF4)+ 229.0977, found 229.0977.
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2-(Me,Ts-amino)-1-phenylethanone (3a). Following the general procedure D compound 3a was
obtained from enol 2a (0.25 mmol) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 72 mg of compound 3a as beige solid (Yield =
95%, 1 h). 1H NMR (400 MHz, CDCl3): δ 8.00-7.94 (m, 2H), 7.72 (d, J = 8.2 Hz, 2H), 7.60 (t, J
= 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 4.56 (s, 2H), 2.82 (s, 3H), 2.44
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(s, 3H). C {1H} NMR (100 MHz, CDCl3): δ 193.7, 143.6, 134.9, 134.8, 133.8, 129.7, 128.8,
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128.3, 127.6, 56.1, 35.6, 21.5. The observed characterization data (1H and C) were consistent
with those previously reported.37
2-(Me,Ts-amino)-1-(4-chlorophenyl)ethanone (3b). Following the general procedure D compound
3b was obtained from 1-(4-chlorophenyl)vinyl acetate (0.25 mmol, prepared according to literature
procedure38) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified by
column chromatography to afford 79 mg of compound 3b as white solid (Yield = 94%, 5 h). 1H
NMR (400 MHz, CDCl3): δ 7.96-7.93 (m, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.48-7.43 (m, 2H), 7.34
(d, J = 8.0 Hz, 2H), 4.48 (s, 2H), 2.79 (s, 3H), 2.44 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
192.8, 143.8, 140.4, 134.5, 133.1, 129.8, 129.7, 129.2, 127.6, 56.1, 35.6, 21.5. The observed
characterization data (1H and 13C) were consistent with those previously reported.37
2-(Me,Ts-amino)-1-(4-bromophenyl)ethanone (3c). Following the general procedure D compound
3c was obtained from 1-(4-bromophenyl)vinyl acetate (0.25 mmol, prepared according to literature
procedure32) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified by
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column chromatography to afford 80 mg of compound 3c as white solid (Yield = 87%, 5 h). H
NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.6 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.7 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 4.47 (s, 2H), 2.79 (s, 3H), 2.45 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ 193.0, 143.8, 134.5, 133.5, 132.2, 129.9, 129.8, 129.1, 127.6, 56.1, 35.6, 21.5. The
observed characterization data (1H and 13C) were consistent with those previously reported.37
2-(Me,Ts-amino)-1-(4-iodophenyl)ethanone (3d). Following the general procedure D compound
3d was obtained from 1-(4-iodophenyl)vinyl acetate (0.25 mmol, prepared according to literature
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procedure39) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified by
column chromatography to afford 89 mg of compound 3d as white solid (Yield = 83%, 5 h).1H
NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.6 Hz, 2H), 7.76-7.58 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H),
4.46 (s, 2H), 2.79 (s, 3H), 2.44 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 193.3, 143.8, 138.2,
134.5, 134.0, 129.7, 129.7, 127.6, 102.0, 56.1, 35.6, 21.6. HRMS (ESI, m/z) calcd for C16H17INO3S
(M + H)+ 429.9974, found 429.9973. Anal. Calcd for C16H16INO3S: C, 44.77; H, 3.76; N, 3.26; S,
7.47; found: C, 44.94; H, 3.73; N, 3.25; S, 7.42.
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2-(Me,Ts-amino)-1-(2-methoxyphenyl)ethanone (3e). Following the general procedure D
compound 3e was obtained from 1-(2-methoxyphenyl)vinyl acetate (0.25 mmol, prepared
according to literature procedure40) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 67 mg of compound 3e as white solid (Yield =
80%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.77-7.69 (m, 3H), 7.53-7.46 (m, 1H), 7.30 (d, J = 8.0
Hz, 2H), 6.99 (dd, J = 16.5, 8.1 Hz, 2H), 4.63 (s, 2H), 3.93 (s, 3H), 2.87 (s, 3H), 2.43 (s, 3H). 13C
{1H} NMR (100 MHz, CDCl3): δ 195.1, 159.1, 143.2, 135.9, 134.6, 130.8, 129.5, 127.6, 125.5,
120.9, 111.5, 60.1, 55.6, 35.7, 21.5. HRMS (ESI, m/z) calcd for C17H19NO4SNa (M + Na)+
356.0932, found 356.0923. Anal. Calcd for C17H19NO4S: C, 61.24; H, 5.74; N, 4.20; S, 9.62;
found: C, 61.25; H, 5.89; N, 4.08; S, 9.68.
2-(Me,Ts-amino)-1-(3-methoxyphenyl)ethanone (3f). Following the general procedure D
compound 3f was obtained from 1-(3-methoxyphenyl)vinyl acetate (0.25 mmol, prepared
according to literature procedure39) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 56 mg of compound 3f as white solid (Yield =
67%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.2 Hz, 2H), 7.57-7.52 (m, 1H), 7.50 (dd,
J = 2.6, 1.3 Hz, 1H), 7.41-7.29 (m, 3H), 7.16-7.10 (m, 1H), 4.53 (s, 2H), 3.85 (s, 3H), 2.82 (s, 3H),
2.43 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 193.6, 159.9, 143.6, 136.1, 134.9, 129.8, 129.7,
127.6, 120.8, 120.5, 112.5, 56.2, 55.5, 35.6, 21.5. HRMS (ESI, m/z) calcd for C17H19NO4SNa (M
+ Na)+ 356.0932, found 356.0929. Anal. Calcd for C17H19NO4S: C, 61.24; H, 5.74; N, 4.20; S,
9.62; found: C, 61.09; H, 5.64; N, 4.10; S, 9.48.
2-(Me,Ts-amino)-1-(4-methoxyphenyl)ethanone (3g) Following the general procedure D
compound 3g was obtained from 1-(4-methoxyphenyl)vinyl acetate (0.25 mmol, prepared
according to literature procedure32) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 79 mg of compound 3g as white solid (Yield =
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95%, 4 h). 1H NMR (400 MHz, CDCl3): δ 7.98-7.96 (m, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.32 (d, J
= 8.0 Hz, 2H), 6.95-6.92 (m, 2H), 4.46 (s, 2H), 3.86 (s, 3H), 2.79 (s, 3H), 2.43 (s, 3H). 13C {1H}
NMR (100 MHz, CDCl3): δ 192.2, 164.1, 143.6, 134.7, 130.7, 129.7, 127.8, 127.6, 114.0, 55.9,
55.5, 35.6, 21.5. The observed characterization data (1H and 13C) were consistent with those
previously reported.37
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Methyl 4-(2-(Me,Ts-amino)acetyl)benzoate (3h). Following the general procedure D compound
3h was obtained from methyl 4-(1-acetoxyvinyl)benzoate (0.25 mmol, prepared according to
literature procedure32) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified
by column chromatography to afford 70 mg of compound 3h as white solid (Yield = 77%, 16 h).
1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.6 Hz, 2H), 8.03 (d, J = 8.6 Hz, 2H), 7.72 (d, J = 8.3
Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.56 (s, 2H), 3.95 (s, 3H), 2.82 (s, 3H), 2.44 (s, 3H). 13C {1H}
NMR (100 MHz, CDCl3): δ 193.7, 166.2, 143.9, 138.1, 134.9, 134.7, 130.1, 129.9, 128.4, 127.7,
56.5, 52.7, 35.8, 21.7. HRMS (ESI, m/z) calcd for C18H19NO5SNa (M + Na)+ 384.0882, found
384.0869. Anal. Calcd for C18H19NO5S: C, 59.82; H, 5.30; N, 3.88; S, 8.87; found: C, 59.65; H,
5.43; N, 3.81; S, 8.88.
2-(Me,Ts-amino)-1-(4-cyanophenyl)ethanone (3i). Following the general procedure D compound
3i was obtained from 1-(4-cyanophenyl)vinyl acetate (0.25 mmol, prepared according to literature
procedure38) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified by
column chromatography to afford 66 mg of compound 3i as white solid (Yield = 80%, 16 h). 1H
NMR (400 MHz, CDCl3): δ 8.11-8.09 (m, 2H), 7.79-7.77 (m, 2H), 7.71-7.69 (m, 2H), 7.35-7.33
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(m, 2H), 4.48 (s, 2H), 2.78 (s, 3H), 2.44 (s, 3H). C {1H} NMR (100 MHz, CDCl3): δ 193.0,
144.0, 137.7, 134.2, 132.6, 129.8, 128.9, 127.6, 117.7, 117.1, 56.5, 35.7, 21.6. HRMS (ESI, m/z)
calcd for C17H16N2O3SNa (M + Na)+ 351.0779, found 351.0770. Anal. Calcd for C17H16N2O3S: C,
62.18; H, 4.91; N, 8.53; S, 9.76; found: C, 61.90; H, 4.75; N, 8.63; S, 9.86.
2-(Me,Ts-amino)-1-(thiophen-2-yl)ethanone (3j). Following the general procedure D compound
3j was obtained from tert-butyldimethyl((1-(thiophen-2-yl)vinyl)oxy)silane (0.25 mmol, prepared
according to literature procedure33) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
,67%, 24 h). 1H NMR (400 MHz, CDCl3): δ 7.95 (dd, J = 3.8 Hz, J = 1.1 Hz, 1H), 7.72-7.68 (m,
3H), 7.34-7.31 (m, 2H), 7.17-7.15 (m, 1H), 4.41 (s, 2H), 2.83 (s. 3H), 2.43 (s, 3H). 13C {1H} NMR
(100 MHz, CDCl3): δ 186.8, 143.7, 141.0, 134.5, 134.4, 133.2, 129.7, 128.4, 127.5, 56.3, 35.7,
21.5. HRMS (ESI, m/z) calcd for C14H15NO3S2Na (M + Na)+ 332.0391, found 332.0388. Anal.
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Calcd for C14H15NO3S2: C, 54.35; H, 4.89; N, 4.53; S, 20.72; found: C, 54.55; H, 4.86; N, 4.55; S,
20.67.
2-(Me,Ts-amino)-1-(pyridin-4-yl)ethanone (3k). Following the general procedure D compound 3k
was obtained from 4-(1-((tert-butyldimethylsilyl)oxy)vinyl)pyridine (0.25 mmol, prepared
according to literature procedure41) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 46 mg of compound 3k as white solid (Yield =
60%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.85-7.83 (m, 2H), 7.78-7.76 (m, 2H), 7.72-7.70 (m,
2H), 7.36-7.34 (m, 2H), 4.51 (s, 2H), 2.81 (s, 3H), 2.45 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3):
δ 193.7, 151.1, 143.9, 140.5, 134.4, 129.8, 127.5, 121.1, 56.4, 35.7, 21.5. HRMS (ESI, m/z) calcd
for C15H17N2O3S (M + H)+ 305.0960, found 305.0961. Anal. Calcd for C15H16N2O3S: C, 59.19; H,
5.30; N, 9.20; S, 10.53; found: C, 59.20; H, 5.32; N, 9.05; S, 10.62.
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1-(benzofuran-2-yl)-2-(Me,Ts-amino)ethanone (3l). Following the general procedure D compound
3l was obtained from ((1-(benzofuran-2-yl)vinyl)oxy)(tert-butyl)dimethylsilane (0.25 mmol,
prepared according to literature procedure33) and N-aminopyridinium salt 1b (0.3 mmol). The
crude product was purified by column chromatography to afford 67 mg of compound 3l as white
solid (Yield = 78%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.75-7.72 (m, 4H), 7.58-7.56 (m, 1H),
7.52-7.48 (m, 1H), 7.35-7.31 (m, 3H), 4.53 (s, 2H), 2.89 (s, 3H), 2.44 (s, 3H). 13C {1H} NMR (100
MHz, CDCl3): δ 184.8, 155.7, 150.5, 143.7, 134.8, 129.7, 128.8, 127.5, 126.8, 124.2, 123.6, 114.6,
112.4, 56.0, 35.8, 21.5; HRMS (ESI, m/z) calcd for C18H18NO4S (M + H)+ 344.0957, found
344.0954. Anal. Calcd for C18H17NO4S: C, 62.96; H, 4.99; N, 4.08; S, 9.34; found: C, 62.85; H,
4.89; N, 3.93; S, 9.15.
2-(N,4-Dimethylphenylsulfonamido)-1-phenylvinyl benzoate (4). Following the general procedure
D compound 4 was obtained from enol 2b (0.25 mmol) and N-aminopyridinium salt 1b (0.3
mmol). The crude product was purified by column chromatography to afford 46 mg of compound
4 as beige solid (Yield = 45%, 16 h). 1H NMR (500 MHz, CDCl3): δ 8.03-7.98 (m, 4H), 7.64-7.59
(m, 4H), 7.49 (t, J = 7.8 Hz, 4H), 7.24 (d, J = 8.1 Hz, 2H), 7.20 (s, 1H), 2.96 (s, 3H), 2.41 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3): δ 193.6, 143.8, 135.3, 134.9, 134.4, 129.6, 129.1, 128.6, 127.6,
65.2, 32.4, 21.6. HRMS (ESI, m/z) calcd for C23H21NO4SNa (M + Na)+ 430.1089, found 430.1094.
Anal. Calcd for C23H21NO4S: C, 67.79; H, 5.19; N, 3.44; S, 7.87; found: C, 67.62; H, 5.20; N,
3.26; S, 8.01.
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1-(Me,Ts-amino)-3,3-dimethylbutan-2-one (5a). Following the general procedure D compound 5a
was obtained from ((3,3-dimethylbut-1-en-2-yl)oxy)trimethylsilane (0.25 mmol) and N-
aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column chromatography
to afford 56 mg of compound 5a as colorless oil (Yield = 79%, 5 h). 1H NMR (400 MHz, CDCl3):
δ 7.68 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 4.20 (s, 2H), 2.80 (s, 3H), 2.42 (s, 3H), 1.14
(s, 9H). 13C {1H} NMR (100 MHz, CDCl3): δ 209.1, 143.3, 135.7, 129.5, 127.4, 77.3, 77.0, 76.7,
53.7, 43.3, 35.4, 26.2, 21.5. HRMS (ESI, m/z) calcd for C14H21NO3SNa (M + Na)+ 306.1140, found
306.1129. Anal. Calcd for C14H21NO3S: C, 59.34; H, 7.47; N, 4.94; S, 11.31; found: C, 59.56; H,
7.43; N, 4.78; S, 11.28.
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2-(Me,Ts-amino)pentan-3-one (5b). Following the general procedure D compound 5b was
obtained from tert-butyldimethyl(pent-2-en-3-yloxy)silane (0.25 mmol, E/Z mixture, prepared
according to literature procedure42) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 44 mg of compound 5b as colorless oil (Yield
= 65%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H),
4.57 (q, J = 7 Hz, 1H), 2.69-2.61 (m, 4H), 2.58-2.52 (m, 1H), 2.40 (s, 3H), 1.01 (t, J = 7.3 Hz, 3H),
0.95 (d, J = 7.0 Hz 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 209.1, 143.6, 136.0, 129.8, 127.1,
59.9, 32.4, 30.0, 21.5, 11.4, 7.7. HRMS (ESI, m/z) calcd for C13H19NO3SNa (M + Na)+ 292.0983,
found 292.0979. Anal. Calcd for C13H19NO3S: C, 57.97; H, 7.11; N, 5.20; S, 11.90; found: C,
57.83; H, 6.97; N, 5.04; S, 12.06.
2-(Me,Ts-amino)-2,4-dimethylpentan-3-one (5c). Following the general procedure D compound
5c was obtained from tert-butyl((2,4-dimethylpent-2-en-3-yl)oxy)dimethylsilane (0.25 mmol,
prepared according to literature procedure33) and N-aminopyridinium salt 1b (0.3 mmol). The
crude product was purified by column chromatography to afford 38 mg of compound 5c as
colorless oil (Yield = 52%, 24 h). 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 8.3 Hz, 2H), 7.29
(d, J = 8.0 Hz, 2H), 3.42-3.32 (m, 1H), 2.75 (s, 3H), 2.42 (s, 3H), 1.40 (s, 6H), 1.17 (d, J = 6.7 Hz,
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6H). C {1H} NMR (100 MHz, CDCl3): δ 215.0, 143.4, 137.2, 129.5, 127.8, 68.0, 34.3, 32.0,
23.7, 21.5, 20.9. HRMS (ESI, m/z) calcd for C15H23NO3SNa (M + Na)+ 320.1289, found 320.1296.
Anal. Calcd for C15H23NO3S: C, 60.58; H, 7.80; N, 4.71; S, 10.78; found: C, 60.48; H, 7.68; N,
4.76; S, 10.81.
2-(Me,Ts-amino)-1-phenylpropan-1-one (5d). Following the general procedure D compound 5d
was obtained from tert-butyldimethyl((1-phenylprop-1-en-1-yl)oxy)silane (0.25 mmol, E/Z
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mixture, prepared according to literature procedure43) and N-aminopyridinium salt 1b (0.3 mmol).
The crude product was purified by column chromatography to afford 72 mg of compound 5d as
beige solid (Yield = 91%, 16 h). 1H NMR (400 MHz, CDCl3): δ 8.12-8.07 (m, 2H), 7.66 (d, J =
8.3 Hz, 2H), 7.62-7.55 (m, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.26 (d, J = 7.3 Hz, 2H), 5.66 (q, J = 6.9
Hz, 1H), 2.70 (s, 3H), 2.41 (s, 3H), 1.16 (d, J = 6.9 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3):
δ 197.5, 143.6, 136.0, 135.1, 133.5, 129.7, 129.0, 128.71, 127.4, 55.3, 29.8, 21.5, 12.4. HRMS
(ESI, m/z) calcd for C17H20NO3S (M + H)+ 318.1164, found 318.1161. Anal. Calcd for
C17H19NO3S: C, 64.33; H, 6.03; N, 4.41; S, 10.10; found: C, 64.08; H, 5.99; N, 4.31; S, 10.21.
2-(Me,Ts-amino)cyclopentanone (5e). Following the general procedure D compound 5e was
obtained from tert-butyl(cyclopent-1-en-1-yloxy)dimethylsilane (0.25 mmol, prepared according
to literature procedure44) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was
purified by column chromatography to afford 29 mg of compound 5e as colorless oil (Yield =
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44%, 24 h). H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H),
4.46-4.41 (m, 1H), 2.64 (s, 3H), 2.41 (s, 3H), 2.33-2.25 (m, 1H), 2.20-2.14 (m, 1H), 2.06-1.99 (m,
2H), 1.87-1.78 (m, 2H). 13C {1H} NMR (100 MHz, CDCl3): δ 212.8, 143.3, 136.4, 129.5, 127.4,
64.8, 35.4, 30.4, 25.7, 21.4, 17.8. HRMS (ESI, m/z) calcd for C13H18NO3S (M + H)+ 268.1007,
found 268.1002. Anal. Calcd for C13H17NO3S: C, 58.41; H, 6.41; N, 5.24; S, 11.99; found: C,
58.66; H, 6.28; N, 5.15; S, 11.82.
2-(Me,Ts-amino)cyclohexanone (5f). Following the general procedure D compound 5f was
obtained from tert-butyl(cyclohex-1-en-1-yloxy)dimethylsilane (0.25 mmol, prepared according
to literature procedure45) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was
purified by column chromatography to afford 38 mg of compound 5f as colorless oil (Yield = 54%,
24 h). 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 4.65 (dd,
J = 11.7 Hz, J = 6.1 Hz, 1H), 2.80 (s, 3H), 2.45-2.42 (m, 1H), 2.40 (s, 3H), 2.33-2.25 (m, 1H),
2.15-2.02 (m, 2H), 1.99-1.93 (m, 1H), 1.87-1.75 (m, 2H), 1.62-1.53 (m, 1H). 13C {1H} NMR (100
MHz, CDCl3): δ 205.6, 143.1, 136.7, 129.5, 127.2, 64.6, 41.8, 32.2, 30.5, 26.6, 24.7, 21.5. HRMS
(ESI, m/z) calcd for C14H20NO3S (M + H)+ 282.1164, found 282.1155. Anal. Calcd for
C14H19NO3S: C, 59.76; H, 6.81; N, 4.98; S, 11.39; found: C, 59.75; H, 6.79; N, 4.90; S, 11.46.
2-(Me,Ts-amino)cycloheptanone (5g). Following the general procedure D compound 5g was
obtained from tert-butyl(cyclohept-1-en-1-yloxy)dimethylsilane (0.25 mmol, prepared according
to literature procedure46) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was
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purified by column chromatography to afford 62 mg of compound 5g as colorless oil (Yield =
84%, 24 h). 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3Hz, 2H), 4.74
(dd, J = 9.5 Hz, J = 2.9 Hz, 1H), 2.82 (s, 3H), 2.54 (ddd, J = 16.4 Hz, J = 5.9 Hz, J = 2.3 Hz, 1H),
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2.42 (s, 3H), 2.35-2.27 (m, 1H), 1.95-1.76 (m, 4H,), 1.73-1.60 (m, 3H), 1.36-1.26 (m, 1H). C
{1H} NMR (100 MHz, CDCl3): δ 209.0, 143.1, 136.6, 129.5, 127.2, 65.4, 42.0, 30.8, 30.3, 29.5,
28.3, 23.3, 21.5. HRMS (ESI, m/z) calcd for C15H21NO3SNa (M + Na)+ 318.1140, found 318.1133.
Anal. Calcd for C15H21NO3S: C, 60.99; H, 7.17; N, 4.74; S, 10.85; found: C, 60.93; H, 7.21; N,
4.55; S, 10.69.
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2-(Me,Ts-amino)cyclooctanone (5h). Following the general procedure D compound 5h was
obtained from tert-butyl(cyclohept-1-en-1-yloxy)dimethylsilane (0.25 mmol, prepared according
to literature procedure44) and N-aminopyridinium salt 1b (0.3 mmol). The crude product was
purified by column chromatography to afford 70 mg of compound 5h as colorless oil (Yield =
90%, 24 h). 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.2 Hz, 2H), 4.76
(dd, J = 10.1 Hz, J = 4.1 Hz, 1H), 3.00 (s, 3H), 2.50 (ddd, J = 8.0 Hz, J = 3.2 Hz, 1H), 2.40 (s,
3H), 2.22-2.15 (m, 1H), 2.06-1.94 (m, 1H), 1.85-1.62 (m, 5H), 1.56-1.43 (m, 3H), 1.13-1.07 (m,
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1H). C {1H} NMR (100 MHz, CDCl3): δ 213.9, 143.3, 136.5, 129.6, 127.0, 60.2, 42.6, 31.5,
31.2, 27.8, 24.9, 23.6, 23.6, 21.5. HRMS (ESI, m/z) calcd for C16H23NO3SNa (M + Na)+ 332.1296,
found 332.1286. Anal. Calcd for C16H23NO3S: C, 62.11; H, 7.49; N, 4.53; S, 10.36; found: C,
62.26; H, 7.40; N, 4.36; S, 10.47.
6-(Me,Ts-amino)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enone (5i). Following the general
procedure D compound 5i was obtained from tert-butyldimethyl((6-methyl-3-(prop-1-en-2-
yl)cyclohexa-1,5-dien-1-yl)oxy)silane (0.25 mmol, prepared according to literature procedure47)
and N-aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column
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chromatography to afford 33 mg of compound 5i as colorless oil (Yield = 39%, 5 h). H NMR
(400 MHz, CDCl3): δ 7.72 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.72-6.70 (m, 1H), 4.93-
4.90 (m, 2H), 4.86 (d, J = 13.0 Hz, 1H), 3.01-2.94 (m, 1H), 2.72-2.65 (m, 1H), 2.63 (s, 3H), 2.41
(s, 3H), 2.40-2.37 (m, 1H), 1.91 (s, 3H), 1.73 (m, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 195.4,
144.0, 143.9, 142.9, 136.6, 135.4, 129.1, 128.0, 114.8, 65.3, 48.4, 31.6, 29.6, 21.5, 17.7, 15.7.
HRMS (ESI, m/z) calcd for C18H24NO3S (M + H)+ 334.1477, found 334.1468. Anal. Calcd for
C18H23NO3S: C, 64.84; H, 6.95; N, 4.20; S, 9.61; found: C, 64.62; H, 6.93; N, 4.25; S, 9.44.
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2-(Me,Ts-amino)-3,4-dihydronaphthalen-1(2H)-one (5j). Following the general procedure D
compound 5j was obtained from tert-butyl((3,4-dihydronaphthalen-1-yl)oxy)dimethylsilane (0.25
mmol, prepared according to literature procedure41) and N-aminopyridinium salt 1b (0.3 mmol).
The crude product was purified by column chromatography to afford 47 mg of compound 5j as
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beige solid (Yield = 57%, 16 h). H NMR (400 MHz, CDCl3): δ 7.97 (dd, J = 7.9, 1.3 Hz, 1H),
7.78 (d, J = 8.3 Hz, 2H), 7.49 (td, J = 7.5, 1.4 Hz, 1H), 7.32-7.30 (m, 2H), 7.29-7.23 (m, 2H), 4.93
(dd, J = 12.8, 5.5 Hz, 1H), 3.26 (ddd, J = 17.3, 12.2, 5.3 Hz, 1H), 3.10-3.02 (m, 1H), 2.80 (s, 3H),
2.44 (s, 3H), 2.40-2.29 (m, 2H). 13C {1H} NMR (100 MHz, CDCl3): δ 193.4, 143.3, 143.2, 136.8,
133.9, 132.3, 129.5, 128.7, 127.8, 127.5, 126.9, 63.5, 30.3, 29.3, 29.2, 21.6. HRMS (ESI, m/z)
calcd for C18H19NO3SNa (M + Na)+ 352.0983, found 352.0978. Anal. Calcd for C18H19NO3S: C,
65.63; H, 5.81; N, 4.25; S, 9.73; found: C, 65.52; H, 5.85, N, 4.25; S, 9.73.
3-(Me,Ts-amino)chroman-4-one (5k). Following the general procedure D compound 5k was
obtained from ((2H-chromen-4-yl)oxy)(tert-butyl)dimethylsilane (0.25 mmol) and N-
aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column chromatography
to afford 36 mg of compound 5k as white solid (Yield = 44%, 24 h). 1H NMR (400 MHz, CDCl3):
δ 7.81 (dd, J = 7.9 Hz, J = 1.8 Hz, 1H), 7.71 (d, J = 8.3Hz, 2H), 7.51-7.46 (m, 1H), 7.32 (d, J =
7.8 Hz, 2H), 7.04-6.97 (m, 2H), 5.11 (dd, J = 12.6 Hz, J = 5.9 Hz, 1H), 4.61 (dd, J = 10.8 Hz, J =
5.9 Hz, 1H), 4.46 (dd, J = 12.6 Hz, J = 10.9 Hz, 1H), 2.83 (s, 3H), 2.44 (s, 3H). 13C {1H} NMR
(100 MHz, CDCl3): δ 188.6, 161.4, 143.6, 136.5, 135.9, 129.6, 127.5, 127.5, 122.0, 120.8, 118.0,
69.3, 59.6, 31.3, 21.6. HRMS (ESI, m/z) calcd for C17H18NO4S (M + H)+ 332.0957, found
332.0941. Anal. Calcd for C17H17NO4S: C, 61.62; H, 5.17; N, 4.23; S, 9.67; found: C, 61.71; H,
5.12; N, 4.12; S, 9.86.
2-(Me,Ts-amino)undec-10-enal (6a). Following the general procedure D compound 6a was
obtained from tert-butyldimethyl(penta-1,4-dien-1-yloxy)silane (0.25 mmol, E/Z mixture) and N-
aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column chromatography
to afford 59 mg of compound 6a as colorless oil (Yield = 67%, 16 h). 1H NMR (400 MHz, CDCl3):
δ 9.47 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 5.86-5.75 (m, 1H), 5.02-4.96 (m,
1H), 4.95-4.91 (m, 1H), 4.41 (dd, J = 9.3 Hz, J = 5.5 Hz, 1H), 2.77 (s, 3H), 2.43 (s, 3H), 2.06-2.01
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(m, 2H), 1.87-1.78 (m, 1H), 1.44-1.24 (m, 11H). C {1H} NMR (100 MHz, CDCl3): δ 199.3,
143.6, 139.0, 136.6, 129.7, 127.2, 114.2, 65.6, 33.7, 30.4, 29.1, 29.0, 28.9, 28.8, 25.9, 25.6, 21.5.
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HRMS (ESI, m/z) calcd for C19H29NO3SNa (M + Na)+ 374.1766, found 374.1761. Anal. Calcd for
C19H29NO3S: C, 64.92; H, 8.32; N, 3.98; S, 9.12; found: C, 65.03; H, 8.34; N, 3.96; S, 9.19.
2-(Me,Ts-amino)-2-phenylpropanal (6b). Following the general procedure D compound 6b was
obtained from tert-butyldimethyl((2-phenylprop-1-en-1-yl)oxy)silane (0.25 mmol, E/Z mixture
prepared according to literature procedure48) and N-aminopyridinium salt 1b (0.3 mmol). The
crude product was purified by column chromatography to afford 72 mg of compound 6b as
colourless oil (Yield = 91%, 10 h). 1H NMR (400 MHz, CDCl3): δ 9.74 (s, 1H), 7.80 (d, J = 8.3
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Hz, 2H), 7.42-7.32 (m, 7H), 2.48 (s, 3H), 2.46 (s, 3H), 1.71 (s, 3H). C {1H} NMR (100 MHz,
CDCl3): δ 191.9, 144.1, 135.9, 135.7, 129.8, 129.4, 128.8, 128.1, 127.5, 72.7, 31.7, 21.6, 14.6.
HRMS (ESI, m/z) calcd for C17H19NO3SNa (M + Na)+ 340.0983, found 340.0973. Anal. Calcd for
C17H19NO3S: C, 64.33; H, 6.03; N, 4.41; S, 10.10; found: C, 64.07; H, 5.93; N, 4.38; S, 9.94.
tert-Butyl 4-(1-(Me,Ts-amino)-2-oxoethyl)piperidine-1-carboxylate (6c). Following the general
procedure
D
compound
6c
was
obtained
from
tert-butyl
4-(2-((tert-
butyldimethylsilyl)oxy)vinyl)piperidine-1-carboxylate (0.25 mmol, E/Z mixture) and N-
aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column chromatography
to afford 48 mg of compound 6c as colorless oil (Yield = 47%, 7 h). 1H NMR (400 MHz, CDCl3):
δ 9.44 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 4.25 (d, J = 7.9 Hz, 1H), 4.13-
4.08 (m, 2H), 2.76 (s, 3H), 2.72-2.65 (m, 1H), 2.43 (s, 3H), 2.01-1.93 (m, 1H), 1.85-1.80 (m, 1H),
1.59-1.52 (m, 1H), 1.45 (s, 9H), 1.33-1.17 (m, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 197.6,
154.6, 143.9, 136.4, 129.8, 127.2, 79.6, 68.7, 33.8, 30.9, 29.5, 28.7, 28.4, 21.5. HRMS (ESI, m/z)
calcd for C20H30N2O5SNa (M + Na)+ 433.1773, found 433.1773. Anal. Calcd for C20H30N2O5S: C,
58.51; H, 7.37; N, 6.82; S, 7.81; found: C, 58.40; H, 7.34; N, 6.79; S, 7.94.
2-(Me,Ts-amino)-1,3-diphenylpropane-1,3-dione (7a). Following the general procedure D
compound 7a was obtained from 1,3-diphenylpropane-1,3-dione (0.25 mmol) and N-
aminopyridinium salt 1b (0.3 mmol). The crude product was purified by column chromatography
to afford 47 mg of compound 7a as beige solid (Yield = 46%, 16 h). 1H NMR (400 MHz, CDCl3):
δ 8.00 (dd, J = 8.4, 1.2 Hz, 4H), 7.65-7.59 (m, 4H), 7.49 (t, J = 7.7 Hz, 4H), 7.24 (d, J = 8.0 Hz,
2H), 7.20 (s, 1H), 2.96 (s, 3H), 2.41 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 193.6, 143.8,
135.3, 134.9, 134.2, 129.6, 129.1, 128.6, 127.6, 65.2, 32.4, 21.6. HRMS (ESI, m/z) calcd for
C23H21NO4SNa (M + Na)+ 430.1089, found 430.1081. Anal. Calcd for C23H21NO4S: C, 67.79; H,
5.19; N, 3.44; S, 7.87; found: C, 67.72; H, 5.30; N, 3.36; S, 7.86.
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2-(Me,Ts-amino)-1,3-di(thiophen-2-yl)propane-1,3-dione (7b). Following the general procedure
D compound 7b was obtained from 1,3-di(thiophen-2-yl)propane-1,3-dione (0.25 mmol, prepared
according to literature procedure49) and N-aminopyridinium salt 1b (0.3 mmol). The crude product
was purified by column chromatography to afford 47 mg of compound 7b as yellow solid (Yield
= 45%, 16 h). 1H NMR (400 MHz, CDCl3): δ 8.00-7.95 (m, 2H), 7.73 (dd, J = 4.9, 0.7 Hz, 2H),
7.61 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 7.18 (dd, J = 4.8, 4.1 Hz, 2H), 6.86 (s, 1H), 3.03
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(s, 3H), 2.40 (s, 3H). C {1H} NMR (100 MHz, CDCl3): δ 185.6, 144.0, 141.6, 135.5, 135.1,
133.9, 129.6, 128.8, 127.5, 66.6, 32.7, 21.6. HRMS (ESI, m/z) calcd for C19H17NO4S3Na (M +
Na)+ 442.0217, found 442.0210. Anal. Calcd for C19H17NO4S3: C, 54.39; H, 4.08; N, 3.34; S,
22.93; found: C, 54.43; H, 3.96; N, 3.42; S, 22.87.
ethyl 2-(Me,Ts-amino)-2-phenylacetate (8). Following the general procedure D compound 8 was
obtained from tert-butyl((1-ethoxy-2-phenylvinyl)oxy)dimethylsilane (0.25 mmol, E/Z mixture
prepared according to literature procedure50) and N-aminopyridinium salt 1b (0.3 mmol). The
crude product was purified by column chromatography to afford 9 mg of compound 8 as colorless
oil (Yield = 10%, 24 h). 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.3 Hz, 2H), 7.35-7.22 (m,
7H), 5.85 (s, 1H), 4.08-4.02 (m, 2H), 2.75 (s, 3H), 2.43 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). 13C {1H}
NMR (100 MHz, CDCl3): δ 169.6, 143.4, 136.3, 133.8, 129.5, 128.8, 128.6, 128.6, 127.3, 62.4,
61.2, 30.8, 21.5, 14.0. HRMS (ESI, m/z) calcd for C18H21NO4SNa (M + Na)+ 370.1089, found
370.1073.
N-Me-N-Ts-3,4-dihydro-2H-pyran-5-amine (9a). Following the general procedure D compound
9a was obtained from 3,4-dihydro-2H-pyran (0.25 mmol) and N-aminopyridinium salt 1b (0.3
mmol). The crude product was purified by column chromatography to afford 8 mg of compound
9a as colorless oil (Yield = 12%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.3 Hz, 2H),
7.31-7.26 (m, 2H), 6.28 (s, 1H), 3.91-3.85 (m, 2H), 2.97 (s, 3H), 2.42 (s, 3H), 2.02 (td, J = 6.2, 1.2
13
Hz, 2H), 1.87-1.78 (m, 2H). C {1H} NMR (100 MHz, CDCl3): δ 145.9, 143.3, 135.6, 129.4,
127.6, 117.6, 65.6, 37.5, 22.8, 22.0, 21.5. HRMS (ESI, m/z) calcd for C13H17NO3SNa (M + Na)+
290.0827, found 290.0831.
N-Me-N-Ts-tetrahydro-2H-pyran-3-amine (9b). Following the general procedure D compound 9b
was obtained from 3,4-dihydro-2H-pyran (0.25 mmol) and N-aminopyridinium salt 1b (0.3 mmol)
with addition of cyclohexanethiol (2 equiv.). The crude product was purified by column
chromatography to afford 22 mg of compound 9b as colorless oil (Yield = 33%, 16 h). 1H NMR
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(400 MHz, CDCl3): δ 7.70 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 3.94-3.85 (m, 1H), 3.85-
3.78 (m, 1H), 3.69-3.62 (m, 1H), 3.24-3.15 (m, 2H), 2.78 (s, 3H), 2.42 (s, 3H), 1.69-1.59 (m, 3H),
1.58-1.55 (m, 1H). 13C {1H} NMR (100 MHz, CDCl3): δ 143.3, 137.0, 129.8, 127.0, 69.3, 67.6,
53.1, 29.7, 27.2, 25.8, 21.5. HRMS (ESI, m/z) calcd for C13H19NO3SNa (M + Na)+: 292.0983,
found 292.0978.
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2-(Me,Boc-amino)-1-phenylethanone (10a). Following the general procedure D compound 10a
was obtained from enol 2e (0.25 mmol) and N-aminopyridinium salt 1c (0.3 mmol). The crude
product was purified by column chromatography to afford 55 mg of compound 10a as colourless
1
oil (Yield = 89%, 1 h). H NMR (400 MHz, CDCl3): mixture of rotamers, δ 7.92 (t, J = 7.4 Hz,
2H + second rotamer 2H), 7.60 – 7.54 (m, 1H + second rotamer 1H), 7.49-7.42 (m, 2H + second
rotamer 2H), 4.66 (s, 2H, first rotamer), 4.57 (s, 2H, second rotamer), 2.96 (s, 3H, second
rotamer), 2.93 (s, 3H, first rotamer), 1.48 (s, 9H, first rotamer), 1.37 (s, 9H, second rotamer). 13C
{1H} NMR (100 MHz, CDCl3): mixture of rotamers, δ 195.2, 194.8, 156.2, 155.7, 135.3, 133.4,
128.8, 128.7, 127.9, 127.7, 80.00, 55.7, 55.1, 35.7, 35.6, 28.4, 28.2. The observed characterization
data (1H and 13C) were consistent with those previously reported.51
2-(Me,Cbz-amino)-1-phenylethanone (10b). Following the general procedure D compound 10b
was obtained from enol 2e (0.25 mmol) and N-aminopyridinium salt 1d (0.3 mmol). The crude
product was purified by column chromatography to afford 30 mg of compound 10b as colorless
oil (Yield = 42%, 1 h). 1H NMR (400 MHz, CDCl3): mixture of rotamers, δ 7.97 – 7.86 (m, 2H +
second rotamer 2H), 7.62 – 7.55 (m, 1H + second rotamer 1H), 7.50-7.20 (m, 7H + second rotamer
7H), 5.19 (s, 2H, first rotamer), 5.11 (s, 2H, second rotamer), 4.74 (s, 2H, first rotamer), 4.68 (s,
2H, second rotamer), 3.04 (s, 3H), 3.03 (s, 3H, second rotamer). 13C {1H} NMR (100 MHz,
CDCl3): mixture of rotamers, δ 194.6, 194.2, 156.9, 156.4, 136.7, 136.6, 135.2, 135.1, 133.63,
133.60, 128.81, 128.76, 128.5, 128.4, 128.0, 127.91, 127.89, 127.80, 127.78, 67.5, 67.3, 55.6, 55.3,
36.2, 35.5. HRMS (ESI, m/z) calcd for C17H17NO3Na (M + Na)+ 306.1106, found 306.1092. Anal.
Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94; found: C, 72.35; H, 5.99; N, 4.74.
2-(Ts-amino)-1-phenylethanone (10c). Following the general procedure D compound 10c was
obtained from enol 2a (0.25 mmol) and N-aminopyridinium salt 1g (0.3 mmol). The crude product
was purified by column chromatography to afford 67 mg of compound 10c as white solid (Yield
= 92%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 7.5 Hz, 2H), 7.77 (d, J = 8.2 Hz, 2H),
7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 5.68 (s, 1H), 4.45 (d, J
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= 4.5 Hz, 2H), 2.38 (s, 3H). C {1H} NMR (100 MHz, CDCl3): δ 192.6, 143.7, 136.2, 134.4,
133.8, 129.8, 129.0, 127.9, 127.2, 48.7, 21.5. The observed characterization data (1H and 13C) were
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obtained from enol 2a (0.25 mmol) and N-aminopyridinium salt 1h (0.3 mmol). The crude product
was purified by column chromatography to afford 32 mg of compound 10d as colorless oil (Yield
= 48%, 48 h). 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H),
7.49 (t, J = 7.7 Hz, 2H), 7.41-7.29 (m, 5H), 5.80 (brs, 1H), 5.16 (s, 2H), 4.72 (d, J = 4.4 Hz, 2H).
13C {1H} NMR (100 MHz, CDCl3): δ 194.0, 156.3, 136.4, 134.4, 134.0, 128.9, 128.5, 128.2, 128.1,
127.9, 67.0, 47.9. The observed characterization data (1H and 13C) were consistent with those
previously reported.52
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2,3,4,5,6-pentafluoro-N-(2-oxo-2-phenylethyl)benzamide (10e). Following the general procedure
D compound 10e was obtained from enol 2a (0.25 mmol) and N-aminopyridinium salt 1i (0.3
mmol). The crude product was purified by column chromatography to afford 47 mg of compound
10e as white solid (Yield = 57%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.98 (dd, J = 8.4, 1.2 Hz,
2H), 7.69 -7.60 (m, 1H), 7.52 (t, J = 7.7 Hz, 2H), 7.25 (brs, 1H), 4.96 (d, J = 4.3 Hz, 2H). 13C {1H}
NMR (100 MHz, CDCl3): δ 193.0, 157.4, 145.4 (m), 143.4 (m), 141.4 (m), 138.7 (m), 136.7 (m),
134.5, 133.9, 129.0, 128.0, 111.0 (t, J = 18.5 Hz), 46.9. 19F NMR (375 MHz, CDCl3): δ -139.92-
140.18 (m, 2F), -150.30 (tt, J = 20.7, 3.2 Hz, 1F), -159.82-160.18 (m, 2F). HRMS (ESI, m/z) calcd
for C15H8NO2F5Na (M + Na)+ 352.0373, found 352.0365. Anal. Calcd for C15H8F5NO2: C, 54.72;
H, 2.45; N, 4.25; found: C, 54.66; H, 2.39; N, 4.44.
2,2,2-trifluoro-N-(2-oxo-2-phenylethyl)acetamide (10f). Following the general procedure D
compound 10f was obtained from enol 2a (0.25 mmol) and N-aminopyridinium salt 1j (0.3 mmol).
The crude product was purified by column chromatography to afford 42 mg of compound 10f as
white solid (Yield = 72%, 16 h). 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 7.7 Hz, 2H), 7.67 (t,
J = 7.4 Hz, 1H), 7.54 (t, J = 7.8 Hz, 2H), 7.48 (brs, 1H), 4.82 (d, J = 4.3 Hz, 2H). 13C {1H} NMR
(100 MHz, CDCl3): δ 192.0, 157.2 (q, J = 37.8 Hz), 134.7, 133.7, 129.1, 128.0, 115.7 (q, J = 287.3
Hz), 46.2. 19F NMR (375 MHz, CDCl3): δ -75.7. The observed characterization data (1H and 13C)
were consistent with those previously reported.53
((4-(1-((tert-butyldimethylsilyl)oxy)vinyl)-1,2-phenylene)bis(oxy))bis(tert-butyldimethylsilane)
(12). Commercially available ketone 11 (0.5 mmol, 1.0 equiv) was placed in an oven-dried flask
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