Radical-transfer hydroamination of olefins with N-aminated dihydropyridines

Article abstract of DOI:10.1002/asia.201000881

An efficient synthesis of N-phthalimidyl, benzamidyl, acetamidyl, carbamoyl, and ureayl derivatives of dihydropyridines and the application of these reagents as precursors for N-centered radicals are presented. These aminated dihydropyridines could be used in radical-transfer hydroamination reactions of various electron-rich as well as nonactivated olefins in the presence of thiols as polarity-reversal catalysts. These reactions worked without the aid of any transition metal. Steric and electronic effects exerted by the N-substitutents of the N-centered radicals are discussed. In contrast to most metal-catalyzed processes, the radical hydroamination delivered the opposite regioisomer with excellent anti-Markovnikov selectivity. Hydroamination products were obtained as protected amines that are readily isolated. Festival of amination: We have presented an efficient synthesis of N-phthalimidyl, benzamidyl, acetamidyl, carbamoyl, and ureayl derivatives of dihydropyridines and the application of these reagents as precursors for N-centered radicals (see scheme). These aminated dihydropyridines can be used in radical-transfer hydroamination reactions.

Full text of DOI:10.1002/asia.201000881

DOI: 10.1002/asia.201000881
Radical-Transfer Hydroamination of Olefins with N-Aminated
Dihydropyridines
Chih-Ming Chou, Joyram Guin, Christian Mꢀck-Lichtenfeld, Stefan Grimme, and
Armido Studer*[a]
Abstract: An efficient synthesis of N-
phthalimidyl, benzamidyl, acetamidyl,
carbamoyl, and ureayl derivatives of
dihydropyridines and the application of
these reagents as precursors for N-cen-
tered radicals are presented. These
aminated dihydropyridines could be
used in radical-transfer hydroamination
reactions of various electron-rich as
well as nonactivated olefins in the pres-
ence of thiols as polarity-reversal cata-
lysts. These reactions worked without
the aid of any transition metal. Steric
and electronic effects exerted by the
N-substitutents of the N-centered radi-
cals are discussed. In contrast to most
metal-catalyzed processes, the radical
hydroamination delivered the opposite
regioisomer with excellent anti-Mar-
kovnikov selectivity. Hydroamination
products were obtained as protected
amines that are readily isolated.
Keywords: dihydropyridines
·
hydroamination · olefins · polarity-
reversal catalysis · radical reactions
Introduction
Walton and our group have shown that substituted 1,4-cy-
clohexadienes of type 1 can be used as precursors for C-
and Si-centered radicals (Scheme 1). The cyclohexadienyl
Hydroamination of a nonactivated double bond is a very
challenging task. Despite intensive research in that field, no
general method has been reported for that very important
reaction. Note that most of the pharmaceutical compounds
and many natural products contain nitrogen and the devel-
ꢀ
opment of novel methods for C N bond formation is there-
fore important. Transition-metal and Brønsted acid-cata-
lyzed hydroamination of olefins has been intensively stud-
ied. However, the reported methods still lack generality and
most of the processes are limited to activated olefins.[1] In
addition, most of the reported methods deliver Markovni-
kov addition products[2] and functional group tolerance is
low. In contrast, radical reactions show high functional
group tolerance, and addition of N-centered radicals to ole-
fins delivers the anti-Markovnikov products. Therefore, we
regard the radical approach[3] towards hydroamination of
olefins as a highly promising complementary alternative to
Brønsted acid and transition-metal-catalyzed hydroamina-
tion.
Scheme 1. Proaromatic dienes as radical precursors.
radicals 2 are readily generated by hydrogen-transfer reac-
tions and this allows compounds 1 to be used in radical
chain reactions.[4] The driving force for the generation of the
Si- or C-centered radicals from cyclohexadienyls of type 2 is
the arene resonance energy gained in the radical-fragmenta-
tion reaction.
[a] Dr. C.-M. Chou, Dr. J. Guin, Dr. C. Mꢀck-Lichtenfeld,
Prof. Dr. S. Grimme, Prof. Dr. A. Studer
Organisch-Chemisches Institut
Westfꢁlische Wilhelms-Universitꢁt Mꢀnster
Corrensstrasse 40, 48149 Mꢀnster (Germany)
Fax : (+49)251-8336523
E-mail: studer@uni-muenster.de
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FULL PAPERS
Based on these results, we further expanded the concept
of using cyclohexadienyl radicals as proaromatic radical pre-
cursors for the generation of N-centered radicals.[5–7] For ex-
ample, the aminated cyclohexadiene 3, which upon hydro-
gen transfer provides cyclohexadienyl radical 4, turned out
to be an efficient precursor for the corresponding carbamoyl
radical.[5] We successfully used reagent 3 in tin-free[8] radi-
cal-transfer hydroamination reactions of various nonactivat-
ed olefins. Unfortunately, large-scale synthesis of aminated
cyclohexadiene 3 turned out to be tedious, and this radical
precursor is unstable under acidic conditions. Moreover, hy-
droaminations with 3 had to be conducted at elevated tem-
peratures. We were therefore looking for an alternative and
found in the aminated dihydropyridine 5a an improved re-
agent that can react through radical 6a and subsequent fast
fragmentation to a carbamoyl radical and the corresponding
pyridine derivative. We communicated that the N-aminated
dihydropyridine 5a acts as a nontoxic radical-transfer hydro-
amination reagent.[9] Herein, we present in full detail that
N-aminated dihydropyridines are readily prepared stable
and efficient N-radical precursors, which can be used as re-
agents for the transition-metal-free hydroamination of unac-
tivated olefins. An improved synthesis to compounds of type
5 was developed and this allowed the N-substituents at the
amidyl radical to be systematically varied to study steric and
electronic effects. Moreover, computational results on the
fragmentation of radical 5 will be presented.
dienyl radical 6. Fragmentation of 6 will lead to pyridine 7
and the corresponding N-centered radical that sustains the
ꢀ
chain. However, hydrogen-transfer reactions from C H to
C-centered radicals are generally inefficient processes, even
ꢀ
if the C H bond is activated by appropriate substituents as
for the dihydropyridines studied herein (reaction of 8 with 5
is likely to be slow). This problem can be solved by adding a
thiol as a catalyst, an application of the concept of polarity-
reversal catalysis (PRC).[10] In the presence of a catalytic
amount of a thiol, the slow reduction of a C-radical 8 with
the N-aminated dihydropyridine 5 is replaced by an efficient
hydrogen-transfer process from a thiol. The thiyl radical
thus generated undergoes hydrogen abstraction from the N-
aminated dihydropyridine due to polarity match to eventual-
ly regenerate the thiol catalyst and 6, which should readily
aromatize to generate the corresponding N-centered radical
and pyridine 7. The driving force for the aromatization is
ꢀ
the resonance energy of the pyridine and the weak N N
bond.
Synthesis of N-Aminated Dihydropyridines
The synthesis of the hydroamination reagents studied herein
is shown in Scheme 3. We found that the protocol recently
communicated by our group turned out to be not very gen-
eral.[9] The reported procedure did not allow modification of
the N-protecting group at the aminated dihydropyridine 5.
Therefore, an optimized sequence for preparation of 5 was
developed. Ketoesters 9a–d were readily prepared accord-
ing to a literature procedure by a-methylenation of b-ke-
Results and Discussion
Concept
The mechanism of the radical-chain-transfer hydroamination
of olefins with aminated dihydropyridines of type 5 is de-
picted in Scheme 2. An N-centered radical is allowed to add
to an olefin to give adduct radical 8, which can then be re-
duced with reagent 5 to the hydroamination product and
Scheme 3. Synthesis of the hydroamination reagents 5a–5m (Boc=tert-
butyloxycarbonyl; Moc=methyloxycarbonyl; Alloc=allyloxycarbonyl).
Scheme 2. Thiol-catalyzed radical-transfer hydroamination.
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Hydroamination of Olefins
toesters with CH2Br2/HNEt2.[11] Treatment of 9a–d with vari-
ous protected hydrazines in the presence of a catalytic
amount of HCl afforded the targeted hydroamination re-
agents 5a–m in moderate to good yields. We found that the
N-aminophthalimidyl (5 f), benzamidyl (5h), acetamidyl
(5l), and ureayl (5m) derivatives are quite stable under air,
whereas carbamate derivatives 5a–e slowly decompose upon
exposure to air.
initiator, some thiol catalyst was consumed through disulfide
formation during the reaction. Therefore, the bulkier 2,6-di-
methylthiophenol was tested to suppress disulfide formation.
However, a similar result was obtained by replacing PhSH
with the bulky 2,6-dimethylthiophenol as PRC (compare en-
tries 6 and 9). Reactions in the absence of any PhSH or V70
resulted in lower yields (entries 7 and 8). Hydroamination
by using 2-naphthylthiol or b-d-thioglucose-tetraacetate as
PRCs were low yielding (entries 10 and 11). Ph3SiSH
(entry 12) and methyl thioglycolate (entry 13) provided
slightly lower yields compared to the yield achieved with
PhSH. A worse result was noted by using the electron-defi-
cient pentafluorothiophenol as a PRC (15%, entry 14). We
next varied the amount of norbornene or the catalyst and
initiator loading. However, all experiments conducted along
this line showed a decrease in the yield (entries 15–18).
From these initial optimization studies, we can conclude that
the best result was achieved with the cheap and commercial-
ly available PhSH as the PRC. Therefore, the following ex-
periments were performed by using either 0.05 or
0.15 equivalents of PhSH in combination with 1.5–10 equiva-
lents of an olefin.
Hydroamination of Norbornene with Reagent 5a: Variation
of the PRC and Radical Initiator
We first studied radical hydroamination of norbornene as
the acceptor with reagent 5a by using various PRCs and
radical initiators under different conditions. Treatment of
norbornene (10 equiv) with 5a (1 equiv) in benzene at 808C
in the presence of 30 mol% a,a’-azobisisobutyronitrile
(AIBN) and 15 mol% PhSH afforded exo-hydroamination
product 10 in 54% yield (Table 1, entry 1). It has previously
been shown that radical additions onto norbornene occur
with excellent exo-selectivity.[12] Hydroamination at room
temperature with Et3B/O2 as an initiator (10 mol%) and
15 mol% PhSH afforded 10a in 60% yield (Table 1,
entry 3), and a similar result was obtained in the absence of
Et3B with air as the initiator (entry 2). Thioacids as PRCs
delivered lower yields under otherwise identical conditions
(entries 4 and 5). Catalyst loading could be reduced to
5 mol% without diminishing the yield. Thus, 61% yield was
noted for the reaction with 2,2’-azobis(2,4-dimethyl-4-me-
thoxyvaleronitrile) (V70) as the initiator (5 mol%) and
PhSH (5 mol%) as PRC at room temperature in dichloro-
methane (entry 6). We thought that by using dioxygen as an
Hydroamination of Norbornene with Various Aminated
Dihydropyridines
We first investigated the substituent effect at the ester
moiety of the N-aminated dihydropyridine. Reactions with
reagents 5a–d were conducted under optimized conditions
in the presence of PhSH (5 mol%) and V70 (5 mol%) in di-
chloromethane at room temperature for 18 hours to afford
10a (Scheme 4). We found that the reaction yield steadily
decreased by increasing the size
of the alkyl substituent at the
ester moiety in going from the
Table 1. Hydroamination of norbornene with 5a under different conditions.
methyl (64%), ethyl (61%),
and isopropyl (47%) to the tert-
butyl ester (28%). It seems that
hydrogen abstraction by the
Entry
Solvent
Norbornene [equiv]
RSH [mol%]
Initiator [mol%][a]
Yield [%][b]
thiyl radical from the dihydro-
pyridine is strongly affected by
the ester moiety for steric rea-
sons.
By replacing the bulky Boc
group in the reagent by a small-
er Moc (methyloxycarbonyl)
group, a slight decrease in the
yield was observed and 10b was
isolated in 50% yield. Disap-
pointingly, the benzoyl- and the
1
2
3
4
5
6
7
8
C6H6
C6H6
C6H6
C6H6
C6H6
10
10
10
10
10
10
10
10
10
10
10
10
10
10
4
PhSH (15)
PhSH (15)
PhSH (15)
AIBN[c]
air
54
57
60
15
7
[d]
Et3B/O2
Et3B/O2
Et3B/O2
[d]
PhCOSH (15)
1-Ad-thioacid (15)[e]
PhSH (5)
[d]
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
V70(5)
V70(5)
–
61
40
35
58
47
46
33
37
15
20
37
47
45
–
PhSH (5)
9
2,6-Me2-PhSH (5)
2-naphthyl-SH (5)
b-d-glucose-SH (5)
Ph3SiSH (5)
MeO2CCH2SH (5)
C6F5SH (5)
V70(5)
V70(5)
V70(5)
V70(5)
V70(5)
V70(5)
V70(2)
V70(5)
V70(5)
V70(5)
10
11
12
13
14
15
16
17
18
acetyl-protected
dihydropyri-
dines 5h and 5l did not deliver
any hydroamination product
under optimized conditions.
Therefore, the fluorinated benz-
amides were not tested with
this particular substrate. The
PhSH (2)
PhSH (2)
PhSH (5)
PhSH (5)
4
4
2
[a] 10 mol% of Et3B or 30 mol% of AIBN were used. [b] Isolated yields. [c] Conducted at 808C. [d] Air was
used as an O2 source and the reaction was conducted at RT. [e] Ad=adamantyl.
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Scheme 4. Hydroamination of norbornene with various reagents.
phthalimidyl and ureayl reagents 5 f and 5m did not work as
well under these conditions. With 5m we faced solubility
problems. At least for norbornene as a radical acceptor, the
carbamoyl-protected dihydropyridines delivered the highest
yields. Moreover, the ester moiety at the reagent should be
charged with a linear alkyl group.
Hydroamination of Various Alkenes with Various Reagents
under Optimized Conditions
To study the scope and limitations of our method, various
olefins were treated with various reagents under different
conditions. Reagents that failed in the hydroamination of
norbornene were also included in these studies. Hydroami-
nations were conducted at room temperature with V70 as
an initiator in dichloromethane (method A), and with AIBN
in benzene at 808C as an initiator (method B). All yields re-
ported are based on isolated material. In Scheme 5, hydroa-
mination products 11–19 successfully prepared by hydroami-
nation of 1-octene, cyclohexene, and various enol ethers are
depicted; yields and method used are given in brackets.
We found that hydroamination of 1-octene did not pro-
ceed with perfect regiochemistry. Reaction of 5a with 1-
octene using method A delivered 11a in 48% yield along
with its regioisomeric Markovnikov product (6%, not
shown in the figure). Cyclohexene was successfully hydroa-
minated with reagent 5a (!12: 52%). As for the norbor-
nene system, the benzoylated hydroamination reagent 5h
was not efficient for hydroamination of 1-octene. As the
amidyl radicals have an electrophilic character, higher yields
should be obtained in the hydroamination of electron-rich
enol ethers. Indeed, products 13–19 were isolated in 22–
92% yield with perfect anti-Markovnikov selectivity. Butyl
vinyl ether reacted at room temperature efficiently with car-
bamoyl-protected aminated dihydropyridines 5a and 5e,
and the protected amino alcohols 13a and 13b were isolated
in 67 and 65% yield, respectively. Pleasingly, for this elec-
tron-rich substrate we found that the benzoylated reagent
5h provided adduct 13c in a satisfactory yield (44%) using
method B. Increasing the electrophilicity of the amidyl radi-
cals by introducing F-substituents (see reagents 5j and 5k)
led to a further increase in the yield (!13d: 60%; !13e:
Scheme 5. Hydroamination of 1-octene, cyclohexene, and enol ethers
with various reagents Method A: with 2 to 10 equivalents of olefin;
5 mol% V70, 5 mol% PhSH, RT, CH2Cl2. Method B: with 1.5 to
10 equivalents of olefin; 30 mol% AIBN, 15 mol% PhSH, reflux, ben-
zene. [a] Isolated as a mixture with pyridine 7.
65%). Even higher yields (up to 92%) were achieved with
tert-butyl vinyl ether as a radical acceptor. Again, for the
benzamidyl radical series, the introduction of F-substituents
led to improved yields: two F-substituents are better than
one F-substituent, probably for electronic reasons, and the
2,6-isomer afforded slightly lower yields than the 3,5-di-
fluoro-substituted benzamidyl radical, probably for steric
reasons.
Protected secondary alkyl-substituted amines can readily
be prepared regioselectively starting with dihydropyrane. As
for most substrates tested so far, the Boc-protected reagent
5a turned out to be more reactive than the benzoylated ami-
nation reagent 5h (!15a: 75%; !15b: 36%). Again, in-
creasing electrophilicity of the benzamidyl radical provided
an improved yield (!15c: 50%). Similar reactivity trends
were observed in the reaction of silyl enol ethers derived
from acetophenone derivatives (see 16a–d). For this com-
pound class, we also tested the acetyl- and ureayl-protected
aminodihydropyridine 5l and 5m and found that both com-
pounds were not efficient hydroamination reagents. As ex-
pected, decreasing the nucleophilicity of the silyl enol ether
by introducing a bromine substituent at the arene moiety
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Hydroamination of Olefins
led to a decrease in the yields (see 17a–e) and increasing
nucleophilicity afforded higher yields (!18: 62%; !19:
59%). It is important to note that these amino alcohols are
biologically interesting compounds.
Enamides could also be regioselectively hydroaminated
with reagent 5a. For this substrate class we found that the
Et3B/O2 initiation method was best suited to run the transfer
hydroaminations (Scheme 6). Reactions were conducted at
Figure 1. Structure and spin density of the N-NH-Moc-substituted radical
6’e. The isosurface represents a value of (1aꢀ1b)=+0.004 a.u.
Table 2. DFT reaction energies for the aromatization reaction of 6’e, 6b,
and 6’j.
Leaving radical
DEdiss [kcalmolꢀ1
PBE-D/def2-TZVP B2PLYP-D/def2-QZVP[a]
]
6’e NH-Moc
6b NH-Boc
6’j NH-CO-2,4-F2C6H3 +7.2
+11.3
+11.5
+9.6
+10.2
+4.2
Scheme 6. Hydroamination of enamides with reagent 5a and Et3B
(15 mol%)/O2 as an initiator at RT in benzene.
[a] PBE-D/def2-TZVP geometries.
room temperature and protected vicinal diamines 20–23
were isolated in 52 to 58% yield (Scheme 4). Under these
conditions, the acylated dihydropyridines did not show any
reactivity. We could also show that the chiral enecarbamate
24 was hydroaminated with high diastereoselectivity (diaste-
reomeric ratio (d.r.=13:1) to give 25 in 48% yield, thereby
showing the potential of our method for the preparation of
enantiomerically pure diamines.[13]
those with NH-Moc as a leaving radical. Hence, the addi-
tional nitrogen atom in the ring does not influence reaction
energies to a large extent. Dissociation barriers were only
slightly higher (1–5 kcalmolꢀ1) than the reaction energies. It
is therefore fair to regard the dissociation also here as a
facile process within the reaction cycle. The pyridine as a
product has no considerable impact on the energy of the dis-
sociation step.
Notably, the dissociation of 6b (NH-Boc) and 6’e (NH-
Moc) is more endoenergetic than the dissociation of the 2,4-
difluorophenylcarbonyl intermediate 6’j, even more so with
the more reliable B2PLYP-D double-hybrid functional,
which gives an energy of only 4.2 kcalmolꢀ1 for the step.
Analysis of Radical Fragmentation by DFT Calculations
Finally, we used DFT methods to evaluate the dissociation
energy of three dienyl radicals 6’ (methyl esters) that bore
different N-substitutents -NHR1 as leaving radicals. The geo-
metries of the intermediates were optimized with the gener-
alized gradient approximation functional proposed by
Perdew, Burke, and Ernzerhof (PBE),[14] using a triple-zeta
basis set (def2-TZVP)[15] and an atom pair-wise dispersion
correction.[16] Only the most stable conformers were consid-
ered in the reactions. Single-point energies of these con-
formers were also obtained with the double-hybrid function-
Conclusion
An efficient synthesis of benzamidyl, acetamidyl, and urea
derivatives of N-aminated dihydropyridines and the applica-
tion of these reagents as precursors for N-centered radicals
have been presented. The novel synthesis allowed us to pre-
pare N-aminated dihydropyridines that were not accessible
by using known procedures. These dihydropyridines have
successfully been used in the radical-transfer hydroamina-
tion of various electron-rich as well as nonactivated olefins
in the presence of a polarity-reversal catalyst. Thiophenol
turned out to be best suited as a PRC among the tested
thiols. The size of the alkyl group at the ester moiety of the
reagents strongly influenced the hydroamination reaction.
The best yields have been obtained with primary alkyl
esters. The N-protecting group at the N-centered radical,
al B2-PLYP[17] and
a quadruple-zeta basis set (def2-
QZVP),[15] also adding a dispersion correction.[18] All calcu-
lations were performed with Turbomole 6.0.[19 ]
Figure 1 shows the spin density of the NH-Moc-substitut-
ed intermediate 6’e. The nitrogen of the dihydropyridine is
already involved in the delocalization of the radical, which
ꢀ
facilitates the N N bond scission in the fragmentation.
As Table 2 reveals, the dissociation is an endoenergetic
process. We have shown this before for similar, unsymetri-
cally substituted cyclohexadienyl radicals.[5b] For those sys-
tems, dissociation energies were found to be very similar to
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A. Studer et al.
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perature and the solvent was removed under reduced pressure. The
crude mixture was purified by flash column chromatography (silica gel)
to afford the desired hydroamination product.
which influences the electrophilicity of the radical, showed a
strong electronic effect on the reaction outcome. In general,
the best yields were achieved with carbamate derivatives as
hydroamination reagents. The carbamate derivatives worked
on aliphatic alkenes, on enol ethers, on enamides, and on
enecarbamates. However, the benzamidyl-protected aminat-
ed dihydropyridines reacted efficiently only with enol ethers
as substrates. We found that increasing the electrophilicity
of the N-centered radical by introducing F-substituents at
the arene of the benzamidyl group led to higher yields in
the hydroamination of enol ethers. Reactions with the car-
bamate-protected reagents could be performed at room
temperature, whereas higher reaction temperatures were
necessary when applying benzamidyl, acetamidyl, and urea
derivatives as hydroamination reagents. In contrast to
metal-catalyzed processes, the radical hydroamination deliv-
ered products with excellent anti-Markovnikov selectivities.
Moreover, the radical hydroaminations described herein are
environmentally benign tin-free processes.
General Procedure IIIC (Hydroamination of Olefins at Room
Temperature)
A solution of the appropriate olefin (2.5 to 10 equiv) and Et3B (0.10 to
0.15 equiv, 1m solution in n-hexane) in dry benzene was stirred in a
screw-cap Schlenk tube under argon. A solution of the hydroamination
reagent (1.0 equiv) and thiophenol (0.15 equiv) in dry benzene was
added slowly to the reaction mixture over 10 to 12 h at room temperature
using a syringe pump. The argon supply was then removed from the reac-
tion mixture. The reaction was initiated by addition of a small amount of
air through a syringe into the Schlenk tube and immediately adding the
reagent by using a syringe pump. After complete addition of the reagent,
the solvent was removed under reduced pressure. Purification by flash
column chromatography (silica gel) afforded the desired hydroamination
product.
2,4-Diacetylpentanedioic Acid Dimethyl Ester (9a)
Prepared according to general procedure
I using CH2Br2 (26.0 mL,
372.0 mmol), HNEt2 (5.1 mL, 49.5 mmol), and methyl acetoaccetate
(2.7 mL, 24.8 mmol) in CH2Cl2 (50 mL). Purification by flash column
chromatography (methyl tert-butyl ether (MTBE)/pentane, 1:2) provided
9a as a yellow liquid (2.20 g, 72%). 1H NMR (300 MHz, CDCl3): d=
2.22–2.45 (m, 8H; COCH3 and CH), 3.53–3.59 (m, 2H; CH2), 3.74 ppm
(s, 6H; CO2CH3); 13C NMR (75 MHz, CDCl3): d=25.5 (CH2), 29.3
(CH3), 52.6 (CH3), 56.4 (CH), 169.5 (C), 202.1 ppm (C); IR (neat): n˜ =
3005, 2957, 1743, 1717, 1437, 1361, 1248, 1151 cmꢀ1; HRMS (ESI): m/z:
calcd for C11H16O6Na [M+Na]+: 267.0839; found: 267.0835.
Experimental Section
General Procedure I (a-Methylenation of Ketones)[11]
A mixture of dibromomethane (15 equiv) and diethylamine (2 equiv) was
stirred at 558C for 1.5 h and was then cooled to room temperature. A
preheated mixture of dibromomethane/diethylamine was added at room
temperature to a solution of alkyl acetoacetate (1 equiv) in CH2Cl2. The
resulting mixture was then stirred for 1 h. The reaction mixture was con-
centrated under reduced pressure. Diethyl ether was added, and most of
the ammonium salt was precipitated. After filtration of the precipitation,
the solid was thoroughly washed with diethyl ether. The combined dieth-
yl ether layers were concentrated and then purified by flash column chro-
matography (silica gel) to give the corresponding 2,4-diacetylpentanedio-
ic acid dialkyl ester.
2,4-Diacetylpentanedioic Acid Diethyl Ester (9b)
Prepared according to general procedure
I using CH2Br2 (52.0 mL,
742.5 mmol), HNEt2 (10.28 mL, 99.1 mmol), and methyl acetoaccetate
(6.44 mL, 49.5 mmol) in CH2Cl2 (100 mL). Purification by flash column
chromatography (ethyl acetate (EtOAc)/pentane, 1:3) provided 9b as a
yellow liquid (4.37 g, 65%). 1H NMR (300 MHz, CDCl3): d=1.21–1.33
(m, 6H; CH2CH3), 2.05–2.65 (m, 8H; COCH3 and CH), 3.53–3.65 (m,
2H; CH2), 4.21–4.55 ppm (m, 4H; CH2CH3). Physical data are in agree-
ment with those reported in the literature.[11]
General Procedure II (Preparation of N-Aminodihydropyridines)
2,4-Diacetylpentanedioic Acid Diisopropyl Ester (9c)
HCl (1n, 0.5 equiv) and the corresponding hydrazide (1.0–1.2 equiv)
were added to a stirred solution of 2,4-diacetylpentanedioic acid dialkyl
ester (1.0 equiv) in ethanol (same volume as HCl solution) at room tem-
perature, and the resulting solution was stirred for 18 h under argon. The
reaction mixture was then extracted with CH2Cl2 and washed with
NaHCO3 (aq.), then dried over Na2SO4. The solvent was removed under
reduced pressure and the crude material was purified by flash column
chromatography (silica gel) or precipitated by adding diethyl ether to
afford the corresponding N-aminated dihydropyridines.
Prepared according to general procedure
I using CH2Br2 (26.0 mL,
372.0 mmol), HNEt2 (5.1 mL, 49.5 mmol), and methyl acetoaccetate
(3.6 mL, 24.8 mmol) in CH2Cl2 (50 mL). Purification by flash column
chromatography (MTBE/pentane, 1:3) provided 9c as a yellow liquid
(2.60 g, 70%). 1H NMR (300 MHz, CDCl3): d=1.19–1.30 (m, 12H; CH-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
d=21.6 (CH3), 25.4 (CH2), 29.2 (CH3), 56.9 (CH), 69.4 (CH), 168.5 (C),
202.2 ppm (C); IR (neat): n˜ =2983, 2940, 1731, 1714, 1375, 1359, 1248,
1182, 1148, 1104 cmꢀ1
; HRMS (ESI): m/z: calcd for C15H24O6Na
General Procedure IIIA (Hydroamination of Olefins at Room
Temperature)
[M+Na]+: 323.1465; found: 323.1460.
2,4-Diacetylpentanedioic Acid Di-tert-butyl Ester (9d)
A mixture of the hydroamination reagent (1 equiv), the olefin (2 to
10 equiv), the initiator V70 (0.05 equiv), and thiophenol (0.05 equiv) in
dry CH2Cl2 was placed in a sealed tube under argon. The reaction mix-
ture was stirred in the sealed tube under argon at room temperature for
18 h. Solvent was removed under reduced pressure and the resulting resi-
due was purified by flash column chromatography (silica gel) to afford
the desired hydroamination product.
Prepared according to general procedure
I using CH2Br2 (21.0 mL,
300.0 mmol), HNEt2 (4.2 mL, 40.0 mmol), and methyl acetoaccetate
(3.3 mL, 20.0 mmol) in CH2Cl2 (50 mL). Purification by flash column
chromatography (MTBE/pentane, 1:3) provided 9d as a yellow liquid
(1.3 g, 40%). 1H NMR (300 MHz, CDCl3): d=1.45 (s, 27H; (CH3)3),
2.16–2.36 (m, 8H; COCH3 and CH), 3.41 ppm (t, J=7.5 Hz, 2H; CH2);
13C NMR (75 MHz, CDCl3): d=25.6 (CH2), 27.9 (CH3), 29.2 (CH3), 57.8
(CH), 82.4 (CH), 168.1 (C), 202.6 ppm (C); IR (neat): n˜ =2979, 2934,
1737, 1714, 1369, 1252, 1122, 845 cmꢀ1; HRMS (ESI): m/z: calcd for
C17H28O6Na [M+Na]+: 351.1778; found: 351.1787.
General Procedure IIIB (Hydroamination of Olefins at 808C)
A mixture of the hydroamination reagent (1 equiv), the olefin (1.5 to
10 equiv), the initiator AIBN (0.30 equiv) and thiophenol (0.15 equiv) in
dry benzene was placed in a sealed tube under argon. The reaction mix-
ture was heated in the sealed tube under argon at 808C (oil bath temper-
ature) for 18 h. The reaction mixture was allowed to cool to room tem-
1202
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1197 – 1209

Hydroamination of Olefins
1-tert-Butoxycarbonylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diethyl Ester (5a)
1087, 1049 cmꢀ1; HRMS (ESI): m/z: calcd for C15H22N2O6Na [M+Na]+:
349.1370; found: 349.1377; elemental analysis calcd (%) for C15H22N2O6:
C 55.21, H 6.79, N 8.58; found: C 55.20, H 6.84, N 8.53.
Prepared according to general procedure II using 9b (272 mg, 1.0 mmol),
N-Boc-hydrazide (132 mg, 1.0 mmol), and HCl (1n, 0.5 mL, 0.5 mmol) in
EtOH (0.5 mL). Purification by flash column chromatography (MTBE/
1-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylic Acid Diethyl Ester (5 f)
pentane, 1:3) provided 5a as
1H NMR (300 MHz, CDCl3): d=0.97 (t, J=7.1 Hz, 6H; CH2CH3), 1.28
(s, 9H; C(CH3)3), 2.34 (s, 6H; CH3-vinylic), 3.61 (s, 2H; CH2-vinylic),
a light yellow solid (313 mg, 85%).
Prepared according to general procedure II using 9b (136 mg, 0.5 mmol),
N-aminophthalimide (81 mg, 0.5 mmol), and HCl (4n, 0.2 mL, 0.8 mmol)
in EtOH (1.0 mL). Purification by flash column chromatography
(MTBE/pentane, 1:2) provided 5 f as a light yellow solid (111 mg, 56%).
ACHTUNGTRENNUNG
4.01 (q, J=7.1 Hz, 4H; CH2CH3), 6.31–5.86 ppm (br, 1H; NH). Physical
data are in agreement with those reported in the literature.[9]
1
M.p. 135–1368C; H NMR (300 MHz, CDCl3): d=1.29 (t, J=7.5 Hz, 6H;
1-tert-Butoxycarbonylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Dimethyl Ester (5b)
CH2CH3), 2.10 (s, 6H; CH3-vinylic), 3.38 (s, 2H; CH2-vinylic), 4.19 (q,
J=7.5 Hz, 4H; CH2CH3), 7.85–7.88 (m, 2H; CH-aromatic), 7.96–
7.98 ppm (m, 2H; CH-aromatic); 13C NMR (75 MHz, CDCl3): d=14.2
(CH3), 14.3 (CH3), 24.9 (CH2), 60.0 (CH2), 104.1 (C), 124.5 (C), 129.0
(CH), 135.4 (C), 146.6 (CH), 165.5 (C), 167.4 ppm (C); IR (neat): n˜ =
2981, 1739, 1701, 1616, 1388, 1285, 1199, 1107, 879, 718 cmꢀ1; HRMS
(ESI): m/z: calcd for C21H22N2O6Na [M+Na]+: 421.1370; found:
421.1375.
Prepared according to general procedure II using 9a (2.0 g, 8.2 mmol),
N-Boc-hydrazide (1.1 g, 8.5 mmol), and HCl (1n, 4.1 mL, 4.1 mmol) in
EtOH (4.1 mL). Purified by precipitation provided 5b as a light yellow
solid (2.0 g, 72%). M.p. 108–1098C; 1H NMR (300 MHz, CDCl3): d=
1.47 (s, 9H; CACHTUNGTRENNUNG(CH3)3), 2.25 (s, 6H; CH3-vinylic), 3.25 (s, CH2-vinylic),
3.70 (s, 6H; OCH3), 6.57–6.81 ppm (m, 1H; NH); 13C NMR (75 MHz,
CDCl3): d=14.7 (CH3), 24.6 (CH2), 28.1 (CH3), 51.3 (CH3), 82.3 (C),
102.2 (C), 149.6 (C), 154.4 (C), 168.1 ppm (C); IR (neat): n˜ =3294, 2982,
2951, 1703, 1604, 1504, 1434, 1390, 1201, 1159, 1083, 1019 cmꢀ1; HRMS
(ESI): m/z: calcd for C16H24N2O6Na [M+Na]+: 363.1527; found:
363.1534; elemental analysis calcd (%) for C16H24N2O6: C 56.46, H 7.11,
N 8.23; found: C 56.53, H 7.16, N 8.22.
1-Allyloxycarbonylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diethyl Ester (5g)
Prepared according to general procedure II using 9b (1.45 g, 5.34 mmol),
but-3-enoic acid hydrazide[20] (620 mg, 5.34 mmol), and HCl (1n, 2.7 mL,
2.7 mmol) in EtOH (2.7 mL). Purification by flash column chromatogra-
phy (MTBE/pentane, 1:3) provided 5g as a light green solid (714 mg,
38%). M.p. 105–1068C; 1H NMR (400 MHz, CDCl3): d=1.25–1.30 (m,
6H; CH2CH3), 2.23 (s, 6H; CH3-vinylic), 3.24 (s; CH2-vinylic), 4.13–4.17
(m, 4H; CH2CH3), 4.65 (d, J=4 Hz, 2H; OCH2-vinylic), 5.27 (d, J=
12 Hz, 1H; CHH-vinylic), 5.33 (d, J=16 Hz, 1H; CHH-vinylic), 5.86–
5.96 (m, 1H; CH-vinylic), 7.00–7.21 ppm (br, 1H; NH); 13C NMR
(100 MHz, CDCl3): d=14.3 (CH3), 14.6 (CH3), 24.6 (CH2), 66.1 (CH2),
66.8 (CH2), 102.7 (CH), 118.9 (CH2), 131.7 (C), 148.8 (C), 155.3 (C),
167.8 ppm (C); IR (neat): n˜ =3264, 2982, 1698, 1607, 1521, 1390, 1259,
1195, 1051 cmꢀ1; HRMS (ESI): m/z: calcd for C17H24N2O6Na [M+Na]+:
375.1527; found: 375.1530.
1-tert-Butoxycarbonylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diisopropyl Ester (5c)
Prepared according to general procedure II using 9c (2.4 g, 8.0 mmol),
N-Boc-hydrazide (1.06 g, 8.0 mmol), and HCl (1n, 4.0 mL, 4.0 mmol) in
EtOH (4.0 mL). Purification by flash column chromatography (MTBE/
pentane, 1:4) provided 5c as a light green solid (1.15 g, 36%). M.p. 135–
1368C; 1H NMR (300 MHz, CDCl3): d=1.24 (d, J=8 Hz, 12H; CH-
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
13C NMR (75 MHz, CDCl3): d=14.7 (CH3), 22.0 (CH3), 24.7 (CH2), 28.2
(CH3), 68.2 (CH), 82.1 (C), 102.8 (C), 148.8 (C), 154.6 (C), 167.4 ppm
(C); IR (neat): n˜ =3300, 2980, 1697, 1604, 1387, 1371, 1245, 1201, 1160,
1-Benzoylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic Acid
Diethyl Ester (5h)
1109 cmꢀ1
;
HRMS (ESI): m/z: calcd for C20H32N2O6Na [M+Na]+:
419.1789; found: 419.2154; elemental analysis calcd (%) for C20H32N2O6:
C 60.59, H 8.14, N 7.07; found: C 60.26, H 8.15, N 7.00.
Prepared according to general procedure II using 9b (140 mg,
0.51 mmol), benzoic acid hydrazide (68 mg, 0.5 mmol), and HCl (1n,
0.25 mL, 0.25 mmol) in EtOH (0.25 mL). Purification by flash column
chromatography (MTBE/pentane, 1:1) provided 5h as a light green solid
(500 mg, 67%). M.p. 130–1318C; 1H NMR (300 MHz, CDCl3): d=1.26
(t, J=7.5 Hz, 6H; CH2CH3), 2.25 (s, 6H; CH3-vinylic), 3.24 (d, J=
19.5 Hz, 1H; CHH), 3.34 (d, J=19.5 Hz, 1H; CHH), 4.07–4.20 (m, 4H;
CH3CH2), 7.45–7.50 (m, 2H; CH-aromatic), 7.55–7.61 (m, 1H; CH-aro-
matic), 7.83–7.86 (m, 2H; CH-aromatic), 8.74 ppm (s, 1H; NH);
13C NMR (75 MHz, CDCl3): d=14.3 (CH3), 14.8 (CH3), 24.8 (CH2), 60.2
(CH2), 102.4 (C), 127.3 (CH), 129.0 (CH), 131.2 (C), 132.8 (CH), 148.7
(C), 167.0 (C), 168.1 ppm (C); IR (neat): n˜ =3274, 2981, 1695, 1603, 1517,
1388, 1292, 1267, 1195, 1100, 1053 cmꢀ1; HRMS (ESI): m/z: calcd for
C20H24N2O5Na [M+Na]+: 395.1577; found: 395.1576; elemental analysis
calcd (%) for C20H24N2O5: C 64.50, H 6.50, N 7.52; found: C 64.02, H
6.43, N 7.42.
(2,3,5,6-Tetramethyl-4H-pyridin-1-yl)carbamic Acid tert-Butyl Ester (5d)
Prepared according to general procedure II using 9d (0.91 g, 2.77 mmol),
N-Boc-hydrazide (0.37 g, 2.80 mmol), and HCl (1n, 1.4 mL, 1.4 mmol) in
EtOH (1.4 mL). Purification by flash column chromatography (MTBE/
pentane, 1:4) provided 5d as a light green solid (0.32 g, 27%). M.p. 126–
1278C; 1H NMR (300 MHz, CDCl3): d=1.47 (s, 27H; C
ACTHUNGTRNEUNG(CH3)3), 2.19 (s,
6H; CH3-vinylic), 3.15 (s; CH2-vinylic), 6.57–6.61 ppm (m, 1H; NH);
13C NMR (75 MHz, CDCl3): d=14.6 (CH3), 25.3 (CH2), 28.2 (CH3), 28.3
(CH3), 79.8 (C), 82.0 (C), 104.0 (C), 147.9 (C), 154.6 (C), 167.3 ppm (C);
IR (neat): n˜ =3307, 2977, 1684, 1606, 1367, 1243, 1158, 1005 cmꢀ1; HRMS
(ESI): m/z: calcd for C22H36N2O6Na [M+Na]+: 447.2466; found:
447.2458; elemental analysis calcd (%) for C22H36N2O6: C 62.24, H 8.55,
N 6.60; found: C 62.14, H 8.51, N 6.50.
1-Methoxycarbonylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-
1-(4-Fluorobenzoylamino)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diethyl Ester (5e)
dicarboxylic Acid Diethyl Ester (5i)
Prepared according to general procedure II using 9b (1.09 g, 4.0 mmol),
N-Moc-hydrazide (360 mg, 4.0 mmol), and HCl (1n, 2.0 mL, 2.0 mmol) in
EtOH (2.0 mL). Purification by flash column chromatography (MTBE/
pentane, 1:1) provided 5e as a light green solid (1.1 g, 84%). M.p. 133–
1348C; 1H NMR (300 MHz, CDCl3): d=1.28 (t, J=7.5 Hz, 6H;
CH2CH3), 2.25 (s, 6H; CH3-vinylic), 3.25 (s, 2H; CH2-vinylic), 3.79 (s,
3H; OCH3), 4.18 (q, J=7.5 Hz, 4H; CH2CH3), 6.65–6.79 ppm (br, 1H;
NH); 13C NMR (75 MHz, CDCl3): d=14.3 (CH3), 14.6 (CH3), 24.5
(CH2), 53.3 (CH3), 60.0 (CH2), 96.5 (C), 102.5 (C), 149.0 (C), 167.8 ppm
(C); IR (neat): n˜ =3260, 2988, 1714, 1700, 1606, 1528, 1383, 1274, 1197,
Prepared according to general procedure II using 9b (1.63 g, 6.0 mmol),
4-fluorobenzoic acid hydrazide (0.92 g, 6.0 mmol), and HCl (1n, 3.0 mL,
3.0 mmol) in EtOH (3.0 mL). Purification by flash column chromatogra-
phy (MTBE/pentane, 2:1) provided 5i as a light green solid (1.43 g,
61%). M.p. 137–1388C; 1H NMR (300 MHz, CDCl3): d=1.26 (t, J=
7.5 Hz, 6H; CH2CH3), 2.22 (s, 6H; CH3-vinylic), 3.22 (d, J=18 Hz, 1H;
CHH), 3.32 (d, J=18 Hz, 1H; CHH), 4.11–4.20 (m, 4H; CH3CH2), 7.12–
7.18 (m, 2H; CH-aromatic), 7.87–7.92 (m, 2H; CH-aromatic), 8.89 ppm
(s, 1H; NH); 13C NMR (75 MHz, CDCl3): d=14.3 (CH3), 14.8 (CH3),
24.9 (CH2), 60.2 (CH2), 102.5 (C), 116.15 (d, J=22.5 Hz, CH), 127.3 (C),
Chem. Asian J. 2011, 6, 1197 – 1209
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1203

A. Studer et al.
FULL PAPERS
129.86 (d, J=9.0 Hz, CH), 148.5 (C), 165.5 (d, J=252.8 Hz, C), 166.0 (C),
168.1 ppm (C); IR (neat): n˜ =3300, 2984, 1695, 1604, 1498, 1388, 1292,
1237, 1193, 1096, 1053, 852, 766 cmꢀ1; HRMS (ESI): m/z: calcd for
C20H23FN2O5Na [M+Na]+: 413.1483; found: 413.1478; elemental analysis
calcd (%) for C20H23FN2O5: C 61.53, H 5.94, N 7.18; found: C 61.60, H
5.93, N 6.97.
1-(3-Ethylureido)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic Acid
Diethyl Ester (5m)
Prepared according to general procedure II using 9b (2.72 g, 10.0 mmol),
ethylurea hydrazide[21] (1.30 g, 12.6 mmol), and HCl (1n, 5.0 mL,
5.0 mmol) in EtOH (5.0 mL). Purification by precipitation provided 5m
as
a
light yellow solid (2.64 g, 78%). M.p. 164–1658C; 1H NMR
1-(2,6-Difluorobenzoylamino)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diethyl Ester (5j)
(300 MHz, [D6]DMSO): d=1.01 (t, J=7.5 Hz, 3H; NCH2CH3), 1.22 (t,
J=7.5 Hz, 6H; CH2CH3), 2.16 (s, 6H; CH3-vinylic), 3.02–3.25 (m, 4H;
CH2-vinylic and NCH2CH3), 4.08–4.15 (m, 4H; CH2CH3), 6.65–6.75 (br,
1H; NH), 8.57 ppm (s, 1H; NH); 13C NMR (75 MHz, [D6]DMSO): d=
14.8 (CH3), 15.4 (CH3), 16.0 (CH3), 25.0 (CH2), 34.6 (CH2), 59.9 (CH2),
100.4 (C), 151.3 (C), 157.4 (C), 167.4 ppm (C); IR (neat): n˜ =3306, 2979,
1696, 1641, 1598, 1387, 1289, 1198, 1077, 1060, 760 cmꢀ1; HRMS (ESI):
m/z: calcd for C16H25N3O5Na [M+Na]+: 362.1686; found: 362.1687.
Prepared according to general procedure II using 9b (1.63 g, 6 mmol),
2,6-difluorobenzoic acid hydrazide (1.50 g, 8.7 mmol), and HCl (1n,
3.0 mL, 3.0 mmol) in EtOH (3.0 mL). Purification by precipitation pro-
vided 5j as a white solid (2.04 g, 83%). M.p. 157–1588C; 1H NMR
(300 MHz, CDCl3): d=1.27 (t, J=7.5 Hz, 6H; CH2CH3), 2.28 (s, 6H;
CH3-vinylic), 3.24 (s, 2H; CH2-vinylic), 4.08–4.20 (m, 4H; CH3CH2),
6.95–7.01 (m, 2H; CH-aromatic), 7.39–7.49 (m, 1H; CH-aromatic),
8.56 ppm (s, 1H; NH); 13C NMR (75 MHz, CDCl3): d=14.3 (CH3), 14.7
(CH3), 24.7 (CH2), 60.1 (CH2), 102.8 (C), 111.5 (t, J=21.8 Hz; C), 112.2
(d, J=21.8 Hz; CH), 132.9 (t, J=9.0 Hz; CH), 148.2 (C), 160.5 (C), 160.1
(dd, J1 =6.8 Hz and J2 =251.3 Hz; C), 168.0 ppm (C); IR (neat): n˜ =3232,
2986, 1699, 1667, 1611, 1470, 1392, 1291, 1192, 1118, 1060, 1007, 789,
BicycloACHTNUTRGNE[NUG 2.2.1]hept-2-yl-carbamic Acid tert-Butyl Ester (10a)
Prepared according to general procedure IIIA using 5a (74 mg,
0.20 mmol), norbornene (188 mg, 2.0 mmol), V70 (3.08 mg, 0.01 mmol),
and thiophenol (1.1 mg, 0.01 mmol) in dry CH2Cl2 (1.0 mL). Purification
by flash column chromatography (MTBE/pentane, 1:9) provided 10a as a
1
759 cmꢀ1
;
HRMS (ESI): m/z: calcd for C20H22F2N2O5Na [M+Na]+:
white solid (26 mg, 61%). H NMR (300 MHz, CDCl3): d=1.09–1.50 (m,
7H; CH2), 1.48 (s, 9H; CACTHNUGTRNEUNG(CH3)3), 1.60–1.74 (m, 1H; CH2), 2.16–19 (br,
431.1389; found: 431.1388; elemental analysis calcd (%) for
C20H22F2N2O5: C 58.82, H 5.43, N 6.86; found: C 58.61, H 5.39, N 6.79.
1H; CH), 2.22–2.24 (br, 1H; CH), 3.43–3.46 (br, 1H; NHCH), 4.38–
4.44 ppm (br, 1H; NH). Physical data are in agreement with those re-
ported in the literature.[9]
1-(3,5-Difluorobenzoylamino)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylic Acid Diethyl Ester (5k)
BicycloACHTNUTRGNE[UNG 2.2.1]hept-2-yl-carbamic Acid Methyl Ester (10b)
Prepared according to general procedure II using 9b (1.63 g, 6 mmol),
3,5-difluorobenzoic acid hydrazide (1.20 g, 7.0 mmol), and HCl (1n,
3.0 mL, 3.0 mmol) in EtOH (3.0 mL). Purification by precipitation pro-
vided 5k as a white solid (1.92 g, 78%). M.p. 168–1698C; 1H NMR
(300 MHz, CDCl3): d=1.27 (t, J=7.5 Hz, 6H; CH2CH3), 2.20 (s, 6H;
CH3-vinylic), 3.22 (d, J=18 Hz, 1H; CHH), 3.31 (d, J=18 Hz, 1H;
CHH), 4.10–4.24 (m, 4H; CH3CH2), 7.01–7.07 (m, 1H; CH-aromatic),
7.40–7.43 (m, 2H; CH-aromatic), 9.03 ppm (s, 1H; NH); 13C NMR
(75 MHz, CDCl3): d=14.3 (CH3), 14.7 (CH3), 24.8 (CH2), 60.1 (CH2),
102.5 (C), 108.1 (t, J=25.1 Hz; CH), 110.8 (dd, J1 =9.0 Hz and J2 =
17.3 Hz; CH), 134.4 (t, J=8.3 Hz; C), 148.3 (C), 163.1 (dd, J1 =12.0 Hz
and J2 =250.5 Hz; C), 164.8 (C), 168.3 ppm (C); IR (neat): n˜ =3233, 2984,
1698, 1666, 1597, 1518, 1441, 1390, 1338, 1285, 1177, 1125, 1059, 990, 873,
Prepared according to general procedure IIIA using 5e (65 mg,
0.20 mmol), norbornene (188 mg, 2.0 mmol), V70 (3.08 mg, 0.01 mmol),
and thiophenol (1.1 mg, 0.01 mmol) in dry CH2Cl2 (0.5 mL). Purification
by flash column chromatography (MTBE/pentane, 1:6) provided 10b as a
1
white solid (26 mg, 61%). H NMR (300 MHz, CDCl3): d=1.07–1.52 (m,
7H; CH2), 1.74–1.81 (m, 1H; CH2), 2.16–19 (br, 1H; CH), 2.23–2.26 (br,
1H; CH), 3.48–3.53 (br, 1H; NHCH), 3.64 (s, 9H; OCH3), 4.48–4.54 ppm
(br, 1H; NH). Physical data are in agreement with those reported in the
literature.[5b]
Octylcarbamic Acid tert-Butyl Ester (11a)
Prepared according to general procedure IIIA using 5a (110 mg,
0.30 mmol), 1-octene (168 mg, 1.5 mmol), V70 (4.62 mg, 0.015 mmol),
and thiophenol (1.65 mg, 0.015 mmol) in dry CH2Cl2 (1.0 mL). Purifica-
tion by flash column chromatography (MTBE/pentane, 1:9) provided 11a
as a colorless oil that contained the other regioisomer in a 1:6 ratio (de-
termined by 1H NMR spectroscopic analysis; 33 mg, 48%, combined
yield of both isomers). 1H NMR (300 MHz, CDCl3): d=0.87 (t, J=6 Hz,
759 cmꢀ1
;
HRMS (ESI): m/z: calcd for C20H22F2N2O5Na [M+Na]+:
431.1389; found: 431.1386; elemental analysis calcd (%) for
C20H22F2N2O5: C 58.82, H 5.43, N 6.86; found: C 58.74, H 5.29, N 6.70.
1-Acetylamino-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic Acid
Diethyl Ester (5l)
Prepared according to general procedure II using 9b (1.09 g, 4.0 mmol),
acetic acid hydrazide (296 mg, 4.0 mmol), and HCl (1n, 2.0 mL,
2.0 mmol) in EtOH (2.0 mL). Purification by flash column chromatogra-
phy (100% MTBE) provided 5l as a white solid (990 mg, 80%). M.p.
146–1478C; 1H NMR (300 MHz, CDCl3): d=1.25–1.32 (m, 6H;
CH2CH3), 2.01 (s, 3H; CH3-vinylic, rotamer-1), 2.07 (s, 3H; CCH3, rota-
mer-1), 2.19 (s, 3H; CCH3, rotamer-2), 2.25 (s, 3H; CH3-vinylic, rotamer-
2), (s, 6H; CH3-vinylic), 2.95 (d, J=18 Hz, 1H; CHH, rotamer-1), 3.20
(d, J=18 Hz, 1H; CHH, rotamer-2), 3.30 (d, J=18 Hz, 1H; CHH, rota-
mer-2), 3.54 (d, J=19.5 Hz, 1H; CHH, rotamer-1), 4.11–4.23 (m, 4H;
CH3CH2), 7.68 (s, 1H; NH, rotamer-1), 7.94 ppm (s, 1H; NH, rotamer-2);
13C NMR (75 MHz, CDCl3): d=14.3 (CH3), 14.7 (CH3), 15.1 (CH3), 19.0
(CH3), 19.3 (CH3), 20.3 (CH3), 24.4 (CH2), 24.7 (CH2), 60.1 (CH2), 60.4
(CH2), 102.3 (C), 103.4 (C), 148.4 (C), 148.5 (C), 167.4 (C), 168.0 (C),
169.4 (C), 174.8 ppm (C); IR (neat): n˜ =3238, 2990, 1696, 1673, 1601,
1380, 1294, 1186, 1063 cmꢀ1; HRMS (ESI): m/z: calcd for C15H22N2O5Na
[M+Na]+: 333.1421; found: 333.1413; elemental analysis calcd (%) for
C15H22N2O5: C 58.05, H 7.15, N 9.03; found: C 57.78, H 6.94, N 8.99.
3H; CH3), 1.20–1.35 (m, 12H; CH2), 1.44 (s, 9H; CACTHNURGTNEUNG(CH3)3), 3.06–3.13 (m,
2H; NCH2), 4.45–4.53 ppm (br, 1H; NH). Physical data are in agreement
with those reported in the literature.[9]
Cyclohexylcarbamic Acid tert-Butyl Ester (12)
Prepared according to general procedure IIIB using 5a (100 mg,
0.27 mmol), cyclohexene (110 mg, 1.4 mmol), AIBN (13 mg, 0.08 mmol),
and thiophenol (4.36 mg, 0.04 mmol) in dry benzene (0.7 mL). Purifica-
tion by flash column chromatography (pentane/Et2O, 10:1) provided 12
as a white solid (28 mg, 52%). M.p. 76–688C; 1H NMR (300 MHz,
C6D6): d=0.71–0.92 (m, 3H; CH2, CHH), 0.98–1.12 (m, 2H; CH2), 1.26–
1.41 (m, 3H; CH2, CHH), 1.48 (s, 9H; CACTHNUTRGNEUNG(CH3)3), 1.74–1.78 (m, 2H;
CH2), 3.52–3.55 (m, 1H; CHNH), 4.08–4.10 ppm (br, 1H; NH);
13C NMR (75 MHz, C6D6): d=25.1 (CH2), 25.8 (CH2), 28.6 (CH3), 33.4
(CH2), 49.5 (CH), 78.4 (C), 155.0 ppm (C); IR (neat): n˜ =3364, 2933,
2853, 1681, 1523, 1448, 1388, 1365, 1316, 1278, 1251, 1233, 1168, 1047,
1026, 902 cmꢀ1; HRMS (ESI): m/z: calcd for C11H21NO2Na [M+Na]+:
222.1465; found: 222.1472.
(2-Butoxyethyl)carbamic Acid Methyl Ester (13b)
Prepared according to general procedure IIIA using 5e (65 mg,
0.20 mmol), tert-butyl vinyl ether (200 mg, 2.0 mmol), V70 (3.08 mg,
1204
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1197 – 1209

Hydroamination of Olefins
0.01 mmol), and thiophenol (1.1 mg, 0.01 mmol) in dry CH2Cl2 (0.75 mL).
Purification by flash column chromatography (MTBE/pentane, 1:3) pro-
vided 13b as a colorless oil (22.7 mg, 65%): H NMR (300 MHz, CDCl3):
d=0.92 (t, J=7.5 Hz, 3H; CH3), 1.25–1.42 (m, 2H; CH2), 1.50–1.59 (m,
2H; CH2), 3.27–3.50 (m, 6H; OCH2CH2, NCH2 and OCH2), 3.61 (s, 3H;
OCH3), 5.02–5.12 ppm (br, 1H; NH). Physical data are in agreement
with those reported in the literature.[5b]
5.18 (br, 1H; NH), 5.20 (dd, J1 =3.0 Hz and J2 =18.0 Hz, 1H; CHH-vinyl-
ic), 5.30 (dd, J1 =3.0 Hz and J2 =18.0 Hz, 1H; CHH-vinylic), 5.85–
5.98 ppm (m, 1H; CH-vinylic); 13C NMR (75 MHz, CDCl3): d=27.5
(CH3), 41.6 (CH2), 60.5 (CH2), 65.4 (CH2), 73.1 (C), 117.5 (CH2), 133.0
(CH), 156.3 ppm (C); IR (neat): n˜ =3340, 2975, 2937, 2874, 1724, 1522,
1364, 1252, 1196, 1091, 995, 931 cmꢀ1; HRMS (ESI): m/z: calcd for
C10H19NO3Na [M+Na]+: 224.1527; found: 224.1263.
1
N-(2-tert-Butoxyethyl)benzamide (14c)
N-(2-Butoxyethyl)benzamide (13c)
Prepared according to general procedure IIIB using 5h (111.6 mg,
0.30 mmol), tert-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 1:1) provided 14c as a light yellow oil (48.9 mg, 74%). 1H NMR
Prepared according to general procedure IIIB using 5h (111.6 mg,
0.30 mmol), n-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 1:2) provided 13c as a light yellow oil (29.2 mg, 44%). 1H NMR
(300 MHz, CDCl3): d=0.92 (t, J=7.5 Hz, 3H; CH2CH3), 1.30–1.40 (m,
2H; CH2CH3), 1.51–1.59 (m, 2H; CH2), 3.47 (t, J=7.5 Hz, 2H; OCH2),
3.57–3.60 (m, 2H; NCH2), 3.60–3.67 (m, 2H; OCH2), 6.54–6.62 (br, 1H;
NH), 7.39–7.52 (m, 3H; CH-aromatic), 7.76–7.79 ppm (m, 2H; CH-aro-
matic); 13C NMR (75 MHz, CDCl3): d=13.9 (CH3), 19.3 (CH2), 31.6
(CH2), 39.8 (CH2), 69.2 (CH2), 70.1 (CH2), 126.9 (CH), 128.5 (CH), 131.4
(CH), 134.6 (C), 167.4 ppm (C); IR (neat): n˜ =3332, 2958, 2933, 2870,
1640, 1540, 1489, 1305, 1117, 712, 694 cmꢀ1; HRMS (ESI): m/z: calcd for
C13H19NO2Na [M+Na]+: 244.1308; found: 244.1300.
(300 MHz, CDCl3): d=1.20 (s, 9H; CACHTUNGRTNEUNG(CH3)3), 3.51–3.54 (m, 2H; NCH2),
3.57–3.62 (m, 2H; OCH2), 6.58–6.62 (br, 1H; NH), 7.39–7.51 (m, 3H;
CH-aromatic), 7.74–7.78 ppm (m, 2H; CH-aromatic); 13C NMR
(75 MHz, CDCl3): d=27.5 (CH3), 40.4 (CH2), 60.4 (CH2), 73.2 (C), 126.8
(CH), 128.5 (CH), 131.3 (CH), 134.8 (C), 167.4 ppm (C); IR (neat): n˜ =
3323, 2974, 1638, 1539, 1489, 1363, 1305, 1195, 1087, 866, 694 cmꢀ1
;
HRMS (ESI): m/z: calcd for C13H19NO2Na [M+Na]+: 244.1308; found:
244.1302.
N-(2-tert-Butoxyethyl)-2,6-difluorobenzamide (14d)
N-(2-Butoxyethyl)-2,6-difluorobenzamide (13d)
Prepared according to general procedure IIIB using 5j (122.4 mg,
0.30 mmol), tert-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
Prepared according to general procedure IIIB using 5j (122.4 mg,
0.30 mmol), n-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 2:3) provided 14d as
a
colorless oil (68 mg, 88%). 1H NMR
(CH3)3), 3.51–3.55 (m, 2H; NCH2),
(300 MHz, CDCl3): d=1.19 (s, 9H; CAHCNUTGTRENNUNG
tane, 2:3) provided 13d as
a
colorless oil (46 mg, 60%). 1H NMR
3.59–3.64 (m, 2H; OCH2), 6.36–6.44 (br, 1H; NH), 6.91–6.97 (m, 2H;
CH-aromatic), 7.30–7.40 ppm (m, 2H; CH-aromatic); 13C NMR
(75 MHz, CDCl3): d=27.5 (CH3), 40.3 (CH2), 60.2 (CH2), 73.2 (C), 112.0
(dd, J1 =2.3 Hz and J2 =23.3 Hz; CH), 114.5 (t, J=21.4 Hz; C), 131.5 (t,
J=9.8 Hz; CH), 160.0 (dd, J1 =7.5 Hz and J2 =262.5 Hz; C), 160.2 ppm
(C); IR (neat): n˜ =3295, 3079, 2976, 2937, 1656, 1626, 1548, 1467, 1364,
1302, 1236, 1196, 1092, 1007, 793 cmꢀ1; HRMS (ESI): m/z: calcd for
C13H17F2NO2Na [M+Na]+: 280.1120; found: 280.1119.
(300 MHz, CDCl3): d=0.90 (t, J=7.5 Hz, 9H; CH2CH3), 1.28–1.41 (m,
2H; CH2CH2CH3), 1.49–1.58 (m, 2H; CH2CH2CH3), 3.45 (t, J=6.0 Hz,
2H; OCH2CH2), 3.55–3.66 (m, 4H; NCH2 and OCH2), 6.34–6.44 (br, 1H;
NH), 6.90–6.95 (m, 2H; CH-aromatic), 7.29–7.39 ppm (m, 1H; CH-aro-
matic); 13C NMR (75 MHz, CDCl3): d=13.8 (CH3), 19.2 (CH2), 31.6
(CH2), 39.8 (CH2), 68.9 (CH2), 71.0 (CH2), 111.9 (dd, J1 =3.0 Hz and J2 =
23.3 Hz; CH), 114.4 (t, J=19.9 Hz; C), 131.5 (t, J=10.1 Hz; CH), 160.0
(d, J1 =7.5 Hz and J2 =251.3 Hz; C), 160.3 ppm (C); IR (neat) n˜ =3288,
3078, 2959, 2934, 2870, 1653, 1625, 1546, 1466, 1301, 1235, 1117, 1006,
N-(2-tert-Butoxyethyl)-3,5-difluorobenzamide (14e)
792 cmꢀ1
;
HRMS (ESI): m/z: calcd for C13H17F2NO2Na [M+Na]+:
Prepared according to general procedure IIIB using 5k (122.4 mg,
0.30 mmol), tert-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 2:3) provided 14e as a white solid (71 mg, 92%). M.p. 55–568C;
280.1120; found: 280.1104.
N-(2-Butoxyethyl)-3,5-difluorobenzamide (13e)
Prepared according to general procedure IIIB using 5k(122.4 mg,
0.30 mmol), n-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 2:3) provided 13e as a white solid (50 mg, 65%). M.p. 49–508C;
1H NMR (300 MHz, CDCl3): d=0.95 (t, J=7.5 Hz, 9H; CH2CH3), 1.36–
1.44 (m, 2H; CH2CH2CH3), 1.55–1.65 (m, 2H; CH2CH2CH3), 3.50 (t, J=
6.0 Hz, 2H; OCH2CH2), 3.59–3.68 (m, 4H; NCH2 and OCH2), 6.52–6.62
(br, 1H; NH), 6.92–7.92 (m, 1H; CH-aromatic), 7.28–7.35 ppm (m, 2H;
CH-aromatic); 13C NMR (75 MHz, CDCl3): d=13.8 (CH3), 19.3 (CH2),
31.6 (CH2), 40.0 (CH2), 68.9 (CH2), 71.0 (CH2), 106.7 (t, J=25.1 Hz;
CH), 110.2 (dd, J1 =8.3 Hz and J2 =18.3 Hz; CH), 138.0 (t, J=8.3 Hz; C),
162.9 (d, J1 =12.0 Hz and J2 =249 Hz; C), 165.0 ppm (C); IR (neat): n˜ =
3315, 3088, 2959, 2935, 2868, 1644, 1593, 1545, 1438, 1326, 1122, 988, 854,
766, 671 cmꢀ1; HRMS (ESI): m/z: calcd for C13H17F2NO2Na [M+Na]+:
280.1120; found: 280.1117.
1H NMR (300 MHz, CDCl3): d=1.13 (s, 9H; C
ACTHNUGTRNEG(UN CH3)3), 3.44–3.54 (m,
4H; NCH2 and OCH2), 6.52–6.58 (br, 1H; NH), 6.80–6.91 (m, 1H; CH-
aromatic), 7.18–7.24 ppm (m, 2H; CH-aromatic); 13C NMR (75 MHz,
CDCl3): d=27.5 (CH3), 40.6 (CH2), 60.1 (CH2), 73.3 (C), 106.6 (t, J=
25.1 Hz; CH), 110.1 (dd, J1 =8.3 Hz and J2 =17.3 Hz; CH), 138.1 (t, J=
8.3 Hz; C), 162.9 (dd, J1 =12.0 Hz and J2 =249.0 Hz; C), 164.9 ppm (C);
IR (neat): n˜ =3322, 3091, 2975, 2938, 2874, 1644, 1593, 1545, 1438, 1363,
1328, 1194, 1123, 1090, 987, 867, 763, 671 cmꢀ1; HRMS (ESI): m/z: calcd
for C13H17F2NO2Na [M+Na]+: 280.1120; found: 280.1119.
N-(2-tert-Butoxyethyl)-4-fluorobenzamide (14 f)
Prepared according to general procedure IIIB using 5i (117 mg,
0.30 mmol), tert-butyl vinyl ether (300 mg, 3 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 1:1) provided 14 f as a light yellow solid (61 mg, 85%). M.p. 53–
(2-tert-Butoxyethyl)carbamic Acid Allyl Ester (14b)
548C; 1H NMR (300 MHz, CDCl3): d=1.20 (s, 9H; C
ACHTNUGTRNEUNG(CH3)3), 3.51–3.62
Prepared according to general procedure IIIA using 5g (106 mg,
0.30 mmol), tert-butyl vinyl ether (300 mg, 3 mmol), V70 (4.62 mg,
0.015 mmol), and thiophenol (1.65 mg, 0.015 mmol) in dry CH2Cl2
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 1:5) provided 14b as a light yellow oil (32 mg, 53%). 1H NMR
(m, 4H; NCH2 and OCH2), 6.48–6.54 (br, 1H; NH), 7.07–7.13 (m, 2H;
CH-aromatic), 7.74–7.80 ppm (m, 2H; CH-aromatic); 13C NMR
(75 MHz, CDCl3): d=27.6 (CH3), 40.5 (CH2), 60.4 (CH2), 73.3 (C), 115.5
(d, J=21.8 Hz; CH), 129.2 (d, J=9.0 Hz; CH), 130.9 (d, J=3.0 Hz; C),
163.0 (C), 166.3 ppm (C); IR (neat): n˜ =3332, 2975, 1639, 1603, 1545,
(300 MHz, CDCl3): d=1.17 (s, 9H; C
ACHTUGNTRENUN(GN CH3)3), 3.30–3.34 (m, 2H; NCH2),
3.40–3.43 (m, 2H; OCH2), 4.56 (d, J=6.0 Hz, 2H; OCH2-vinylic), 5.12–
Chem. Asian J. 2011, 6, 1197 – 1209
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1205

A. Studer et al.
FULL PAPERS
1501, 1363, 1231, 1194, 1160, 1088, 850, 765 cmꢀ1; HRMS (ESI): m/z:
calcd for C13H18FNO2Na [M+Na]+: 262.1214; found: 262.1209.
matic), 7.25 ppm (d, J=7.4 Hz, 2H; CH-aromatic); 13C NMR (75 MHz,
C6D6): d=4.9 (CH3), ꢀ4.6 (CH3), 18.4 (C), 26.0 (CH3), 28.5 (CH3), 49.6
(CH2), 74.3 (CH), 78.7 (C), 126.3 (CH), 128.5 (CH), 143.0 (C), 155.8 ppm
(C); IR (neat): n˜ =3374, 2956, 2930, 2857, 1718, 1503, 1472, 1454, 1390,
1254, 1171, 1098, 1066, 977, 940, 830, 778, 753, 700 cmꢀ1; HRMS (ESI):
m/z: calcd for C19H33NSiO3Na [M+Na]+: 374.2122; found: 374.2126.
(Tetrahydropyran-3-yl)carbamic Acid tert-Butyl Ester (15a)
Prepared according to general procedure IIIA using 5a (110 mg,
0.30 mmol), 3,4-dihydro-2H-pyran (126 mg, 1.5 mmol), V70 (4.62 mg,
0.015 mmol), and thiophenol (1.65 mg, 0.015 mmol) in dry CH2Cl2
(1.0 mL). Purification by flash column chromatography (MTBE/pentane,
1:3) provided 15a as a light yellow solid containing the other regioisomer
in a 1:8 ratio (determined by 1H NMR spectroscopic analysis; 45 mg,
75%, combined yield of both isomers). M.p. 66–678C; 1H NMR
N-[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]benzamide (16b)
Prepared according to general procedure IIIB using 5h (111.6 mg,
0.30 mmol),
tert-butyldimethyl(1-phenylvinyloxy)silane
(140 mg,
0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
(300 MHz, CDCl3): d=1.43–1.89 (m, 4H; CH2), 1.43 (s, 9H; CACTHNUTRGNEUNG(CH3)3),
3.36–3.39 (m, 1H; CHNH), 3.3.58–3.66 (m, 3H; OCH2 and OCHH),
3.74–3.79 (m, 1H; OCHH), 4.75–4.84 ppm (br, 1H; NH); 13C NMR
(75 MHz, CDCl3): d=23.3 (CH2), 28.4 (CH3), 29.1 (CH2), 46.0 (CH),
68.1 (CH2), 71.7 (CH2), 79.3 (C), 155.2 ppm (C); IR (neat): n˜ =3330,
2975, 2940, 2851, 1712, 1695, 1522, 1366, 1308, 1244, 1172, 1094,
matography (MTBE/pentane, 1:6) provided 16b as a light yellow oil
1
ꢀ
(48 mg, 45%). H NMR (300 MHz, CDCl3): d=ꢀ0.11 (s, 3H; Si CH3),
ꢀ
0.02 (s, 3H; Si CH3), 0.90 (s, 9H; SiC
N
CHHNH), 3.78–3.84 (m, 1H; CHHNH), 4.90–4.94 (m, 1H; OCH), 6.38–
6.47 (br, 1H; NH), 7.26–7.52 (m, 8H; CH-aromatic), 7.73 ppm (d, J=
9.0 Hz, 2H; CH-aromatic); 13C NMR (75 MHz, CDCl3): d=ꢀ4.9 (CH3),
ꢀ4.6 (CH3), 18.2 (C), 25.8 (CH3), 48.2 (CH2), 73.6 (CH), 126.0 (CH),
126.8 (CH), 127.7 (CH), 128.4 (CH), 128.6 (CH), 131.4 (CH), 134.6 (C),
142.3 (C), 167.2 ppm (C); IR (neat): n˜ =3309, 3064, 3031, 2955, 2929,
2886, 2857, 1641, 1540, 1490, 1293, 1253, 1100, 959, 864, 836, 778,
1023 cmꢀ1 HRMS (ESI): m/z: calcd for C10H19F2NO3Na [M+Na]+:
;
224.1257; found: 224.1242.
N-(Tetrahydropyran-3-yl)benzamide (15b)
Prepared according to general procedure IIIB using 5h (111.6 mg,
0.30 mmol), 3,4-dihydro-2H-pyran (126 mg, 1.5 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 3:1) provided 15b as a colorless oil containing the other regioiso-
700 cmꢀ1
;
HRMS (ESI): m/z: calcd for C21H29NO2SiNa [M+Na]+:
378.1860; found: 378.1854.
N-[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]-2,6-difluorobenzamide
(16c)
1
mer in a 1:6 ratio (determined by H NMR spectroscopic analysis; 22 mg,
36%, combined yield of both isomers). 1H NMR (300 MHz, CDCl3): d=
1.57–1.93 (m, 4H; CH2), 3.60–3.64 (m, 2H; OCH2), 3.67–3.74 (m, 1H;
OCHH), 3.81–3.86 (m, 1H; OCHH), 4.18–4.23 (m, 1H; CHNH), 6.47–
6.55 (br, 1H; NH), 7.40–7.53 (m, 3H; CH-aromatic), 7.77–7.81 ppm (m,
2H; CH-aromatic); 13C NMR (75 MHz, CDCl3): d=22.8 (CH2), 28.4
(CH2), 45.3 (CH), 68.4 (CH2), 71.4 (CH2), 126.9 (CH), 128.6 (CH), 131.5
(CH), 134.6 (C), 166.8 ppm (C); IR (neat): n˜ =3307, 3062, 2944, 2854,
1637, 1539, 1490, 1324, 1094, 1031 cmꢀ1; HRMS (ESI): m/z: calcd for
C12H15NO2Na [M+Na]+: 228.0995; found: 228.0990.
Prepared according to general procedure IIIB using 5j (122.4 mg,
0.30 mmol),
tert-butyldimethyl(1-phenyl-vinyloxy)silane
(140 mg,
0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
matography (MTBE/pentane, 1:6) provided 16c as a colorless oil (52 mg,
1
ꢀ
44%). H NMR (300 MHz, CDCl3): d=ꢀ0.12 (s, 3H; Si CH3), 0.05 (s,
ꢀ
3H; Si CH3), 0.88 (s, 9H; SiC
N
3.77–3.85 (m, 1H; CHHNH), 4.90–4.94 (m, 1H; OCH), 6.18–6.27 (br,
1H; NH), 6.90–6.97 (m, 2H; CH-aromatic), 7.27–7.40 ppm (m, 6H; CH-
aromatic); 13C NMR (75 MHz, CDCl3): d=ꢀ5.2 (CH3), ꢀ4.7 (CH3), 18.1
(C), 25.7 (CH3), 48.1 (CH2), 73.4 (CH), 111.9 (dd, J1 =2.3 Hz and J2 =
23.3 Hz; CH), 114.2 (t, J=18.8 Hz; C), 126.1 (CH), 126.8 (CH), 127.8
(CH), 128.3 (CH), 131.6 (t, J=10.1 Hz; CH), 142.0 (C), 160.1 (d, J1 =
6.8 Hz and J2 =251.3 Hz; C), 160.2 ppm (C); IR (neat): n˜ =3289, 3067,
3034, 2960, 2930, 2886, 2858, 1656, 1621, 1547, 1467, 1292, 1255, 1098,
1006, 837, 778, 700 cmꢀ1; HRMS (ESI): m/z: calcd for C21H27F2NO2SiNa
[M+Na]+: 414.1671; found: 414.1668.
3,5-Difluoro-N-(tetrahydropyran-3-yl)benzamide (15c)
Prepared according to general procedure IIIB using 5k (122.4 mg,
0.30 mmol), 3,4-dihydro-2H-pyran (126 mg, 1.5 mmol), AIBN (14.8 mg,
0.09 mmol), and thiophenol (4.9 mg, 0.045 mmol) in dry benzene
(0.75 mL). Purification by flash column chromatography (MTBE/pen-
tane, 3:2) provided 15c as a colorless oil containing the other regioisomer
in a 1:6 ratio (determined by 1H NMR spectroscopic analysis; 36 mg,
50%, combined yield of both isomers). 1H NMR (300 MHz, CDCl3): d=
1.57–1.96 (m, 4H; CH2), 3.62–3.66 (m, 2H; OCH2), 3.78–3.83 (m, 2H;
OCHH and OCHH), 4.12–4.20 (m, 1H; CHNH), 6.48–6.57 (br, 1H;
NH), 6.93–6.97 (m, 1H; CH-aromatic), 7.25–7.33 ppm (m, 2H; CH-aro-
matic); 13C NMR (75 MHz, CDCl3): d=22.7 (CH2), 28.1 (CH2), 45.6
(CH), 68.3 (CH2), 71.1 (CH2), 106.8 (t, J=25.1 Hz; CH), 110.3 (dd, J1 =
9.0 Hz and J2 =17.3 Hz; CH), 138.0 (t, J=7.9 Hz; C), 163.0 (d, J1 =
12.0 Hz and J2 =249 Hz; C), 164.4 ppm (C); IR (neat): n˜ =3287, 3081,
N-[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]-3,5-difluorobenzamide
(16d)
Prepared according to general procedure IIIB using 5k (122.4 mg,
0.30 mmol),
tert-butyldimethyl(1-phenylvinyloxy)silane
(140 mg,
0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
matography (MTBE/pentane, 1:6) provided 16d as a colorless oil (58 mg,
2944, 2848, 1637, 1594, 1540, 1435, 1342, 1120, 1096, 1094, 984 cmꢀ1
;
49%). H NMR (300 MHz, CDCl3): d=ꢀ0.11 (s, 3H; Si CH3), 0.02 (s,
1
ꢀ
HRMS (ESI): m/z: calcd for C12H13F2NO2Na [M+Na]+: 264.0807; found:
3H; Si CH3), 0.90 (s, 9H; SiC
A
ꢀ
264.0805.
3.73–3.82 (m, 1H; CHHNH), 4.89–4.96 (m, 1H; OCH), 6.38–6.47 (br,
1H; NH), 6.94–6.97 (m, 1H; CH-aromatic), 7.22–7.44 ppm (m, 7H; CH-
aromatic); 13C NMR (75 MHz, CDCl3): d=ꢀ5.1 (CH3), ꢀ4.7 (CH3), 18.1
(C), 25.6 (CH3), 48.3 (CH2), 73.3 (CH), 106.8 (t, J=25.1 Hz; CH), 110.1
(dd, J1 =9.0 Hz and J2 =17.3 Hz; CH), 125.9 (CH), 127.8 (CH), 128.4
(CH), 138.0 (t, J=8.3 Hz; C), 141.9 (C), 163.4 (d, J1 =12.0 Hz and J2 =
249 Hz; C), 164.8 ppm (C); IR (neat): n˜ =3347, 2930, 2858, 1645, 1594,
1542, 1438, 1333, 1251, 1123, 1095, 988, 835, 776, 700 cmꢀ1; HRMS (ESI):
m/z: calcd for C21H27F2NO2SiNa [M+Na]+: 414.1671; found: 414.1663.
[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]carbamic Acid tert-Butyl
Ester (16a)
Prepared according to general procedure IIIB using 5a (100 mg,
0.27 mmol),
tert-butyldimethyl(1-phenylvinyloxy)silane
(160 mg,
0.68 mmol), AIBN (13 mg, 0.08 mmol), and thiophenol (4.4 mg,
0.04 mmol) in dry benzene (0.7 mL). Purification by flash column chro-
matography (Et2O/pentane, 1:12) provided 16a as a colorless oil (56 mg,
1
ꢀ
59%). H NMR (300 MHz, C6D6): d=0.10 (s, 3H; Si CH3), 0.05 (s, 3H;
N-[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]acetamide (16e)
(CH3)3), 3.06 (ddd, J1 =
ꢀ
Si CH3), 0.93 (s, 9H; SiC
G
13.4 Hz, J2 =7.6 Hz and J3 =5.3 Hz, 1H; CHHNH), 3.39–3.47 (m, 1H;
CHHNH), 4.50–4.60 (br, 1H; NH), 4.82 (dd, J1 =7.6 and J2 =4.1 Hz, 1H;
OCH), 7.01–7.05 (m, 1H; CH-aromatic), 7.10 (d, J=7.4 Hz, 2H; CH-aro-
Prepared according to general procedure IIIB using 5l (93 mg,
0.30 mmol),
tert-butyldimethyl(1-phenylvinyloxy)silane
(140 mg,
0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
1206
www.chemasianj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1197 – 1209

Hydroamination of Olefins
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
N-[2-(4-Bromophenyl)-2-(tert-butyldimethylsilanyloxy)ethyl]-4-
matography (MTBE/pentane, 1:1) provided 16e as a colorless oil (33 mg,
fluorobenzamide (17c)
1
ꢀ
38%). H NMR (300 MHz, CDCl3): d=ꢀ0.16 (s, 3H; Si CH3), ꢀ0.02 (s,
Prepared according to general procedure IIIB using 5i (117 mg,
ꢀ
3H; Si CH3), 0.84 (s, 9H; SiC
N
0.30 mmol),
[1-(4-bromophenyl)vinyloxy]-tert-butyldimethylsilane
1H; CHHNH), 3.51–3.60 (m, 1H; CHHNH), 4.71–4.75 (m, 1H; OCH),
5.65–5.74 (br, 1H; NH), 7.20–7.27 ppm (m, 5H; CH-aromatic); 13C NMR
(75 MHz, CDCl3): d=ꢀ5.0 (CH3), ꢀ4.7 (CH3), 18.2 (C), 23.3 (CH3), 25.8
(CH3), 47.8 (CH2), 73.6 (CH), 126.0 (CH), 127.6 (CH), 128.3 (CH), 142.2
(C), 169.8 ppm (C); IR (neat): n˜ =3289, 3067, 3031, 2955, 2929, 2857,
1651, 1552, 1453, 1373, 1255, 1096, 964, 835, 777, 700 cmꢀ1; HRMS (ESI):
m/z: calcd for C16H27NO2SiNa [M+Na]+: 316.1703; found: 316.1706.
(187 mg, 0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (1.5 mL). Purification by flash column chro-
matography (MTBE/pentane, 1:6) provided 17c as a colorless oil (42 mg,
1
ꢀ
31%). H NMR (300 MHz, CDCl3): d=0.11 (s, 3H; Si CH3), 0.00 (s,
ꢀ
3H; Si CH3), 0.89 (s, 9H; SiC
(CH3)3), 3.32–3.40 (m, 1H; CHHNH),
3.70–3.78 (m, 1H; CHHNH), 4.86–4.90 (m, 1H; OCH), 6.35–6.44 (br,
1H; NH), 7.07–7.14 (m, 2H; CH-aromatic), 7.25 (d, J=9.0 Hz, 2H; CH-
aromatic), 7.45–7.49 (m, 2H; CH-aromatic), 7.71–7.77 ppm (m, 2H; CH-
aromatic); 13C NMR (75 MHz, CDCl3): d=5.0 (CH3), ꢀ4.7 (CH3), 18.1
(C), 25.8 (CH3), 48.2 (CH2), 72.9 (CH), 115.6 (d, J=21.8 Hz; CH), 121.6
(C) , 127.7 (CH), 129.1 (d, J=9.0 Hz, CH), 131.6 (CH), 133.4 (C), 141.4
(C), 145.4 (C), 166.2 ppm (C); IR (neat): n˜ =3317, 2954, 2929, 2886, 2857,
1640, 1603, 1542, 1501, 1286, 1235, 1160, 1090, 958, 835, 776 cmꢀ1; HRMS
(ESI): m/z: calcd for (C21H27Br79FNO2Si)2Na [M+Na]+: 925.1849; found:
925.1844.
1-[2-(tert-Butyldimethylsilanyloxy)-2-phenylethyl]-3-ethylurea (16 f)
Prepared according to general procedure IIIB using 5m (101.7 mg,
0.30 mmol),
tert-butyldimethyl(1-phenylvinyloxy)silane
(140 mg,
0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (2 mL). Purification by flash column chroma-
tography (MTBE/pentane, 1:1) provided 16 f as a colorless oil (26 mg,
1
ꢀ
27%). H NMR (300 MHz, CDCl3): d=ꢀ0.16 (s, 3H; Si CH3), ꢀ0.01 (s,
ꢀ
3H; Si CH3), 0.84 (s, 9H; SiC
N
3.07–3.16 (m, 3H; CHHNH and CH2CH3), 3.34–3.43 (m, 1H; CHHNH),
4.40–4.49 (br, 1H; NH), 4.52–4.61 (br, 1H; NH), 4.72–4.76 (m, 1H;
OCH), 7.18–7.27 ppm (m, 5H; CH-aromatic); 13C NMR (75 MHz,
CDCl3): d=ꢀ5.0 (CH3), ꢀ4.7 (CH3), 15.5 (CH3), 18.2 (C), 25.8 (CH3),
35.4 (CH2), 49.2 (CH2), 74.4 (CH), 126.1 (CH), 127.5 (CH), 128.2 (CH),
142.5 (C), 158.2 ppm (C); IR (neat): n˜ =3322, 2956, 2929, 2885, 2857,
1631, 1571, 1472, 1362, 1252, 1096, 1068, 938, 835, 777, 700 cmꢀ1; HRMS
(ESI): m/z: calcd for C17H30N2O2SiNa [M+Na]+: 345.1969; found:
345.1968.
N-[2-(4-Bromophenyl)-2-(tert-butyldimethylsilanyloxy)ethyl]acetamide
(17d)
Prepared according to general procedure IIIB using 5l (93 mg,
0.30 mmol),
[1-(4-bromophenyl)vinyloxy]-tert-butyldimethylsilane
(187 mg, 0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
matography (MTBE/pentane, 1:1) provided 17d as a light yellow oil
1
ꢀ
(30 mg, 27%). H NMR (300 MHz, CDCl3): d=ꢀ0.11 (s, 3H; Si CH3),
ꢀ
0.03 (s, 3H; Si CH3), 0.90 (s, 9H; SiC
(CH3)3), 1.95 (s, 3H; CCH3), 3.09–
[2-(4-Bromophenyl)-2-(tert-butyldimethylsilanyloxy)ethyl]carbamic Acid
tert-Butyl Ester (17a)
3.17 (m, 1H; CHHNH), 3.51–3.59 (m, 1H; CHHNH), 4.73–4.77 (m, 1H;
OCH), 5.68–5.76 (br, 1H; NH), 7.19 (d, J=9.0 Hz, 2H; CH-aromatic),
7.45 ppm (d, J=9.0 Hz, 2H; CH-aromatic); 13C NMR (75 MHz, CDCl3):
d=ꢀ5.0 (CH3), ꢀ4.7 (CH3), 18.2 (C), 23.3 (CH3), 25.8 (CH3), 47.7 (CH2),
73.0 (CH), 121.5 (C), 127.7 (CH), 131.5 (CH), 141.4 (C), 169.8 ppm (C);
IR (neat): n˜ =3290, 3082, 2955, 2929, 2886, 2857, 1652, 1553, 1487, 1362,
1252, 1110, 1088, 1010, 966, 836, 777 cmꢀ1; HRMS (ESI): m/z: calcd for
C16H26Br79NO2SiNa [M+Na]+: 394.0808; found: 384.0807.
Prepared according to general procedure IIIB using 5a (100 mg,
0.27 mmol),
[1-(4-bromophenyl)vinyloxy]-tert-butyldimethylsilane
(210 mg, 0.68 mmol), AIBN (13 mg, 0.08 mmol), and thiophenol (4.4 mg,
0.04 mmol) in dry benzene (0.7 mL). Purification by flash column chro-
matography (Et2O/pentane, 1:12) provided 17a as a colorless oil (49 mg,
1
ꢀ
42%). H NMR (300 MHz, C6D6): d=0.15 (s, 3H; Si CH3), 0.01 (s, 3H;
ꢀ
ꢀ
Si CH3), 0.89 (s, 9H; Si C
(CH3)3), 1.43 (s, 9H; C
C
1-[2-(4-Bromophenyl)-2-(tert-butyldimethylsilanyloxy)ethyl]-3-ethylurea
(17e)
1H; CHHNH), 3.28 (ddd, J1 =11.5 Hz, J2 =7.1 Hz and J3 =4.3 Hz, 1H;
CHHNH), 4.44–4.52 (br, 1H; NH), 4.67 (dd, J1 =7.1 Hz and J2 =4.1 Hz,
1H; OCH), 6.90 (d, J=8.3 Hz, 2H; CH-aromatic), 7.21 ppm (d, J=
8.3 Hz, 2H; CH-aromatic); 13C NMR (75 MHz, C6D6): d=4.9 (CH3),
ꢀ4.7 (CH3), 18.4 (C), 25.9 (CH3), 28.5 (CH3), 49.4 (CH2), 73.6 (CH), 78.9
(C), 121.7 (CH), 131.7 (CH), 131.1 (C), 141.9 (C), 155.7 ppm (C); IR
(neat): n˜ =3372, 2930, 2857, 1718, 1501, 1391, 1365, 1254, 1169, 1091,
1010, 939, 836, 778 cmꢀ1; HRMS (ESI): m/z: calcd for C19H32Br79NO3Na
[M+Na]+: 454.1209; found: 454.1212.
Prepared according to general procedure IIIB using 5m (101.7 mg,
0.30 mmol),
[1-(4-bromophenyl)vinyloxy]-tert-butyldimethylsilane
(187 mg, 0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
matography (MTBE/pentane, 1:1) provided 17e as a colorless oil (26 mg,
1
ꢀ
22%). H NMR (300 MHz, CDCl3): d=ꢀ0.10 (s, 3H; Si CH3), 0.03 (s,
ꢀ
3H; Si CH3), 0.88 (s, 9H; SiC
(CH3)3), 1.11 (t, J=6.0 Hz, 3H; CH2CH3),
3.09–3.20 (m, 3H; CHHNH and CH2CH3), 3.34–3.43 (m, 1H; CHHNH),
4.42–4.49 (br, 1H; NH), 4.56–4.64 (br, 1H; NH), 4.74–4.78 (m, 1H;
OCH), 7.19 (d, J=9.0 Hz, 2H; CH-aromatic), 7.44 ppm (d, J=9.0 Hz,
2H; CH-aromatic); 13C NMR (75 MHz, CDCl3): d=ꢀ5.0 (CH3), ꢀ4.7
(CH3), 15.5 (CH3), 18.2 (C), 25.8 (CH3), 35.4 (CH2), 49.0 (CH2), 73.7
(CH), 121.3 (C), 127.8 (CH), 131.4 (CH), 141.7 (C), 158.0 ppm (C); IR
(neat): n˜ =3318, 2956, 2929, 2886, 2857, 1633, 1572, 1486, 1258, 1089,
N-[2-(4-Bromophenyl)-2-(tert-butyldimethylsilanyloxy)ethyl]benzamide
(17b)
Prepared according to general procedure IIIB using 5h (111.6 mg,
0.30 mmol),
[1-(4-bromophenyl)vinyloxy]-tert-butyldimethylsilane
(187 mg, 0.6 mmol), AIBN (14.8 mg, 0.09 mmol), and thiophenol (4.9 mg,
0.045 mmol) in dry benzene (0.75 mL). Purification by flash column chro-
1011, 937, 835, 779 cmꢀ1
;
HRMS (ESI): m/z: calcd for
matography (MTBE/pentane, 1:6) provided 17b as a light yellow oil
C17H29Br79N2O2SiNa [M+Na]+: 423.1074; found: 423.1068.
1
ꢀ
(41 mg, 32%). H NMR (300 MHz, CDCl3): d=ꢀ0.12 (s, 3H; Si CH3),
ꢀ
0.00 (s, 3H; Si CH3), 0.89 (s, 9H; SiC
N
[2-(tert-Butyldimethylsilanyloxy)-2-(3,4-dimethoxyphenyl)ethyl]carbamic
CHHNH), 3.71–3.79 (m, 1H; CHHNH), 4.86–4.90 (m, 1H; OCH), 6.39–
6.47 (br, 1H; NH), 7.25 (d, J=9.0 Hz, 2H; CH-aromatic), 7.39–7.52 (m,
5H; CH-aromatic), 7.72 ppm (d, J=9.0 Hz, 2H; CH-aromatic); 13C NMR
(75 MHz, CDCl3): d=ꢀ5.0 (CH3), ꢀ4.7 (CH3), 18.1 (C), 25.8 (CH3), 48.1
(CH2), 73.0 (CH), 121.6 (C), 126.8 (CH) , 127.7 (CH), 128.6 (CH), 131.5
(CH), 134.4 (C), 141.4 (C), 167.3 ppm (C); IR (neat): n˜ =3316, 3064,
2955, 2928, 2886, 2856, 1639, 1538, 1486, 1362, 1295, 1251, 1088, 1010,
958, 835, 776, 693 cmꢀ1; HRMS (ESI): m/z: calcd for C21H28Br79NO2SiNa
[M+Na]+: 456.0965; found: 456.0996.
Acid tert-Butyl Ester (18)
Prepared according to general procedure IIIB using 5a (100 mg,
0.27 mmol),
tert-butyl[1-(3,4-dimethoxyphenyl)vinyloxy]dimethylsilane
(120 mg, 0.41 mmol), AIBN (13 mg, 0.08 mmol), and thiophenol (4.4 mg,
0.04 mmol) in dry benzene (0.7 mL). Purification by flash column chro-
matography (MTBE/pentane, 7:1) provided 18 as a colorless oil (68 mg,
1
ꢀ
62%). H NMR (300 MHz, C6D6): d=0.03 (s, 3H; Si CH3), ꢀ0.10 (s,
ꢀ
ꢀ
3H; Si CH3), 0.97 (s, 9H; Si CACTHNUGTRENN(UG CH3)3), 1.46 (s, 9H; CACHUTGNTREN(NUGN CH3)3) 3.14 (ddd,
J1 =13.5 Hz, J2 =7.8 Hz and J3 =5.3 Hz, 1H; CHHNH), 3.37 (s, 3H;
OCH3), 3.44 (s, 3H; OCH3), 3.49–3.57 (m, 1H; CHHNH), 4.63–4.66 (br,
Chem. Asian J. 2011, 6, 1197 – 1209
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1207

A. Studer et al.
FULL PAPERS
1H; NH), 4.86 (dd, J1 =7.8 Hz and J2 =4.1 Hz, 1H; OCH), 6.54 (d, J=
8.2 Hz, 1H; CH-aromatic), 6.84 (dd, J1 =8.2 Hz and J2 =1.6 Hz, 1H; CH-
aromatic), 6.89 ppm (d, J=1.6 Hz, 1H; CH-aromatic); 13C NMR
(75 MHz, C6D6): d=4.8 (CH3), ꢀ4.5 (CH3), 18.5 (C), 26.1 (CH3), 28.5
(CH3), 49.8 (CH2), 55.6 (CH3), 55.5 (CH3), 74.2 (CH), 78.8 (C), 110.2
(CH), 112.2 (CH), 118.5 (CH), 135.6 (C), 149.7 (C), 150.3 (C), 155.9 ppm
(C); IR (neat): n˜ =3386, 2931, 2856, 1711, 1594, 1515, 1464, 1365, 1260,
(m, 1H; CHNH), 4.94 ppm (d, J=8.4 Hz, 1H; NH); 13C NMR (75 MHz,
C6D6): d=10.4 (CH3), 18.1 (CH2), 26.1 (CH2), 28.5 (CH3), 30.8 (CH2),
46.7 (CH2), 47.1 (CH2), 50.6 (CH), 78.3 (C), 156.2 (C), 174.8 ppm (C); IR
(neat): n˜ =3285, 2927, 1702, 1677, 1538, 1388, 1316, 1373, 1242, 1164,
1076, 990, 751 cmꢀ1
; HRMS (ESI): m/z: calcd for C13H24N2O3Na
[M+Na]+: 279.1679; found: 279.1678.
[2-(Acetylmethylamino)ethyl]carbamic Acid tert-Butyl Ester (23)
1158, 1092, 1030, 834, 777 cmꢀ1
; HRMS (ESI): m/z: calcd for
C21H37SiNO5Na [M+Na]+: 434.2333; found: 434.2361.
Prepared according to general procedure IIIC using 5a (100 mg,
0.27 mmol), N-methyl-N-vinylacetamide (67 mg, 0.68 mmol), Et3B
(30 mL, 0.03 mmol), and thiophenol (4.4 mg, 0.04 mmol) in dry benzene
(0.7 mL). Purification by flash column chromatography (acetone/pentane,
[2-(1,3-Benzodioxol-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]carbamic
Acid tert-Butyl Ester (19)
1:2) provided 23 as
1H NMR (300 MHz, C6D6): d=1.41 (s, 9H; C
9H; C(CH3)3, rotamer-2), 1.48 (s, 3H; CH3CO, rotamer-1), 1.58 (s, 3H;
a
white solid (32 mg, 55%). M.p. 105–1078C;
Prepared according to general procedure IIIB using 5a (100 mg,
AHCTUNGTRENNUNG
0.27 mmol),
1-(1,3-benzodioxol-5-yl)vinyloxy-tert-butyldimethylsilane
AHCTUNGTRENNUNG
(190 mg, 0.68 mmol), AIBN (13 mg, 0.08 mmol), and thiophenol (4.4 mg,
0.04 mmol) in dry benzene (0.7 mL). Purification by flash column chro-
CH3CO, rotamer-2), 1.89 (s, 3H; NCH3, rotamer-1), 2.18 (s, 3H; NCH3,
rotamer-2), 2.65 (br, 2H; NCH2, rotamer-1), 2.81 (br, 2H; CH2NH, rota-
mer-1), 3.13 (br, 4H; NCH2CH2NH, rotamer-2), 5.25 (br, 1H; NH, rota-
mer-1), 5.36 ppm (br, 1H; NH, rotamer-2); 13C NMR (75 MHz, C6D6):
d=20.9 (CH3, rotamer-1), 21.4 (CH3, rotamer-2), 28.5 (CH3, rotamer-1),
28.5 (CH3, rotamer-2), 32.9 (CH3, rotamer-1), 35.7 (CH3, rotamer-2), 38.8
(CH2, rotamer-1), 39.3 (CH2, rotamer-2), 47.1 (CH2, rotamer-2), 49.8
(CH2, rotamer-1), 78.4 (C, rotamer-2), 78.8 (C, rotamer-1), 156.0 (C, rota-
mer-1), 156.3 (C, rotamer-2), 169.9 (C, rotamer-1), 170.7 ppm (C, rota-
mer-2); IR (neat): n˜ =3285, 2927, 1702, 1677, 1538, 1388, 1316, 1373,
matography (Et2O/pentane, 7:1) provided 19 as a colorless oil (63 mg,
1
ꢀ
59%). H NMR (300 MHz, C6D6): d=0.09 (s, 3H; Si CH3), 0.04 (s, 3H;
ꢀ
ꢀ
Si CH3), 0.90 (s, 9H; Si C
G
G
1H; CHHNH), 3.35–3.40 (m, 1H; CHHNH), 4.54–4.62 (br, 1H; NH),
4.71 (dd, J1 =7.0 Hz and J2 =3.96 Hz, 1H; OCH), 5.29 (s, 2H; OCH2),
6.54–6.65 (m, 2H; CH-aromatic), 6.83–6.90 ppm (br, 1H; CH-aromatic);
13C NMR (75 MHz, C6D6): d=4.9 (CH3), ꢀ4.6 (CH3), 18.4 (C), 26.0
(CH3), 28.5 (CH3), 49.7 (CH2), 74.1 (CH), 78.7 (C), 100.9 (CH2), 106.8
(CH), 108.2 (CH), 119.7 (CH), 137.1 (C), 147.5 (C), 148.2 (C), 155.8 ppm
(C); IR (neat): n˜ =3377, 2930, 2857, 1716, 1504, 1488, 1442, 1390, 1365,
1248, 1172, 1089, 1041, 938, 870, 778 cmꢀ1; HRMS (ESI): m/z: calcd for
C20H33NSiO5Na [M+Na]+: 418.2020; found: 418.2032.
1242, 1164, 1076, 990, 751 cmꢀ1
; HRMS (ESI): m/z: calcd for
C10H20N2O3Na [M+Na]+: 239.1366; found: 239.1371.
{(S)-1-[(S)-4-Isopropyl-2-oxooxazolidin-3-ylmethyl]pentyl}carbamic Acid
tert-Butyl Ester (25)
[2-(2-Oxo-pyrrolidin-1-yl)ethyl]carbamic Acid tert-Butyl Ester (20)
Prepared according to general procedure IIIC using 5a (160 mg,
0.43 mmol), 24[9] (60 mg, 0.28 mmol), Et3B (43 mL, 0.04 mmol), and thio-
phenol (4.4 mg, 0.04 mmol) in dry benzene (0.6 mL). Purification by flash
column chromatography (MTBE/pentane, 1:2) provided 25 as a white
solid that contained the other diastereoisomer in a 1:13 ratio (diastereo-
meric ratio was determined by GC analysis of the crude reaction mix-
ture; 45 mg, 48%, combined yield of both diastereoisomers). Physical
data of the major diastereoisomer are given. M.p. 90–928C; [a]D =ꢀ36.0
(c=1.0 in C6H6). 1H NMR (400 MHz, C6D6): d=0.44 (d, J=7.0 Hz, 3H;
Prepared according to general procedure IIIC using 5a (100 mg,
0.27 mmol), 1-vinylpyrrolidin-2-one (90 mg, 0.82 mmol), Et3B (30 mL,
0.03 mmol), and thiophenol (4.4 mg, 0.04 mmol) in dry benzene (0.7 mL).
Purification by flash column chromatography (acetone/pentane, 1:2) pro-
vided 20 as a colorless oil (35 mg, 58%). 1H NMR (300 MHz, C6D6): d=
1.31–1.21 (m, 2H; CH2), 1.43 (s, 9H; CACHTNUTRGNEUGN(CH3)3), 1.94 (t, J=8.1 Hz, 2H;
CH2CO), 2.71 (t, J=7.0 Hz, 2H; CH2N), 3.05–3.08 (m, 4H;
NCH2CH2NH), 5.32–5.39 ppm (br, 1H; NH); 13C NMR (75 MHz, C6D6):
d=17.9 (CH2), 28.5 (CH3), 30.7 (CH2), 38.9 (CH2), 42.6 (CH2), 46.8
(CH2), 78.6 (C), 156.3 (C), 174.9 ppm (C); IR (neat): n˜ =3331, 2926,
1674, 1523, 1463, 1391, 1365, 1271, 1170, 856 cmꢀ1; HRMS (ESI): m/z:
calcd for C11H20N2O3Na [M+Na]+: 251.1366; found: 251.1385.
CH
CH3), 1.19–0.94 (m, 6H; CH2), 1.46 (s, 9H; C
CH
(CH3)2), 2.64 (dd, J1 =14.3 Hz and J2 =3.3 Hz, 1H; NCHH), 3.44 (dd,
ACHTUGTNRENNGU(CH3)2), 0.55 (d, J=6.9 Hz, 3H; CHCAHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
J1 =14.3 Hz and J2 =11.0 Hz, 1H; NCHH), 3.60 (dd, J1 =7.7 Hz and J2 =
4.5 Hz, 1H; OCHH), 3.75–3.91 (m, 3H; NHCH, OCHH, NCH),
4.62 ppm (d, J=9.4 Hz, 1H; NH); 13C NMR (100 MHz, C6D6): d=14.1
(CH3), 14.3 (CH3), 17.3 (CH3), 22.9 (CH2), 27.5 (CH2), 28.3 (CH), 28.4
(CH3), 32.7 (CH2), 46.4 (CH2), 48.2 (CH), 58.1 (CH), 62.7 (CH2), 78.7
(C), 156.4 (C), 159.1 ppm (C); IR (neat): n˜ =3331, 2961, 2932, 1745, 1703,
1523, 1440, 1391, 1365, 1252, 1172, 1050, 767 cmꢀ1; HRMS (ESI): m/z:
calcd for C17H32N2O4Na [M+Na]+: 351.2254; found: 351.2260.
[2-(2-Oxo-perhydroazepin-1-yl)ethyl]carbamic Acid tert-Butyl Ester (21)
Prepared according to general procedure IIIC using 5a (100 mg,
0.27 mmol), 1-vinylperhydroazepin-2-one (110 mg, 0.82 mmol), Et3B
(30 mL, 0.03 mmol), and thiophenol (4.4 mg, 0.04 mmol) in dry benzene
(0.7 mL). Purification by flash column chromatography (acetone/pentane,
1:4) provided 21 as a colorless oil (38 mg, 55%). 1H NMR (300 MHz,
C6D6): d=1.08–1.18 (m, 4H; CH2), 1.26–1.28 (m, 2H; CH2), 1.44 (s, 9H;
CACHTUNGTRENNUNG(CH3)3), 2.21–2.25 (m, 2H; CH2CO), 2.67–2.69 (m, 2H; CH2N), 3.15–
3.25 (m, 4H; NCH2CH2NH), 5.46–5.53 ppm (br, 1H; NH); 13C NMR
(75 MHz, C6D6): d=23.5 (CH2), 28.5 (CH3), 28.7 (CH2), 29.9 (CH2), 37.2
(CH2), 40.1 (CH2), 47.9 (CH2), 49.6 (CH2), 78.4 (C), 156.4 (C), 175.9 ppm
(C); IR (neat): n˜ =3330, 2930s, 1710, 1633, 1520, 1446, 1391, 1250, 1172,
Acknowledgements
857 cmꢀ1
;
HRMS (ESI): m/z: calcd for C13H24N2O3Na [M+Na]+:
279.1679; found: 279.1670.
We thank the Alexander von Humboldt-Foundation for their generous fi-
nancial support (stipend to C.-M. C.).
[1-(2-Oxo-pyrrolidin-1-ylmethyl)propyl]carbamic Acid tert-Butyl Ester
(22)
Prepared according to general procedure IIIC using 5a (100 mg,
0.27 mmol), ((E)-1-but-1-enyl)pyrrolidin-2-one (110 mg, 0.82 mmol), Et3B
(30 mL, 0.03 mmol), and thiophenol (4.4 mg, 0.04 mmol) in dry benzene
(0.7 mL). Purification by flash column chromatography (acetone/pentane,
1:3) provided 22 as a white solid (27 mg, 52%). M.p. 98–1008C; H NMR
(300 MHz, C6D6): d=0.87–0.94 (m, 3H; CH3), 1.16–1.47 (m, 4H; CH2),
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1208
www.chemasianj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1197 – 1209

Hydroamination of Olefins
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Received: January 18, 2011
Published online: March 7, 2011
Chem. Asian J. 2011, 6, 1197 – 1209
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1209