Metal-free reduction of secondary and tertiary N-phenyl amides by tris(pentafluorophenyl)boron-catalyzed hydrosilylation

Article abstract of DOI:10.1021/jo501299j

Tris(pentafluorophenyl)boron B(C₆F₅)₃ is an effective catalyst for the hydrosilylative reduction of tertiary and N-phenyl secondary amides. It allows for the mild reduction of a variety of these amides in near quantitative yield, with minimal purification, at low temperatures, and with short reaction times. This reduction shows functional group tolerance for alkenes, nitro groups, and aryl halides, including aryl iodides.

Full text of DOI:10.1021/jo501299j

Note
pubs.acs.org/joc
Metal-Free Reduction of Secondary and Tertiary N‑Phenyl Amides by
Tris(pentafluorophenyl)boron-Catalyzed Hydrosilylation
Ryan C. Chadwick, Vladimir Kardelis, Philip Lim, and Alex Adronov*
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada
S
* Supporting Information
ABSTRACT: Tris(pentafluorophenyl)boron B(C6F5)3 is an effec-
tive catalyst for the hydrosilylative reduction of tertiary and N-phenyl
secondary amides. It allows for the mild reduction of a variety of
these amides in near quantitative yield, with minimal purification, at
low temperatures, and with short reaction times. This reduction
shows functional group tolerance for alkenes, nitro groups, and aryl
halides, including aryl iodides.
ild reduction of the amide functionality to the
corresponding amine is a valuable transformation in
methods. For example, the reduction of a wide variety of
secondary and tertiary amides was demonstrated with
remarkable substrate scope and functional group tolerance
using Zn(OTf)2.19
M
organic synthesis. Traditionally, the most common procedures
for the transformation of amides to amines have involved the
use of metal hydride reagents in stoichiometric amounts.1
These reagents are not generally selective and result in
byproduct mixtures that are difficult to purify. More recently,
catalytic reductions of amides have received significant
attention. Although ideal, reports of direct catalytic hydro-
genation of amides to amines are quite rare, and limited in
scope and versatility. Most early reports utilized very harsh
conditions and were substrate-specific.2 A 2007 report by
Magro et al. utilized a ruthenium-triphos catalyst to achieve a
general reduction of amides, but the reaction required high
temperatures (164 °C) and moderately high pressures (40 bar
H2).3 More recently, a lower pressure (10 mbar), but higher
temperature (200 °C), optimized protocol that is effective for
reducing secondary and aryl amides has been reported.4 Burch
et al. succeeded in developing a reduction that operated at
lower temperatures and pressures (120 °C, 20 bar, H2), but the
substrate scope was not widely explored.5 Most recently, Stein
and Breit developed a Pt/Re system that is general and high
yielding, but still requires moderately high temperatures (160
°C, 30 bar H2).2 In addition, these reductions generally exhibit
insufficient functional group tolerance, precluding the presence
of alkenes and other easily hydrogenated functionalities. It
should also be noted that mild methods are available to reduce
amides to other functionalities, such as alcohols6 and
aldehydes.7
Alternatively, the state-of-the-art “metal-free” method relies
on the use of triflic anhydride and the “Hantzsch” ester to
facilitate the reduction.21 This method is remarkable, resulting
in high yields of amine without the need for column
chromatography. Charette and co-workers demonstrated the
utility of this approach with both tertiary21 and secondary22
amides, which allowed formation of imines, amines, or
aldehydes through control of the workup procedure following
formation of the intermediate iminium triflate ion.22 While
synthetically ideal from a control and tolerance perspective, this
procedure requires expensive cofactors, highly reactive and
expensive triflic anhydride, and cryogenic temperatures, making
it somewhat onerous.
Recently, we attempted to reduce the secondary amides 1
and 2 (Scheme 1) by a number of conventional methods.
Scheme 1. Reduction of Model Amides 1 and 2
However, the combination of functional groups within these
structures made it difficult to achieve high-yielding reduction.23
In our attempts, LiAlH4 rapidly dehalogenated the aryl halide
groups, while DIBAL-H allowed the reduction of the dibromide
in modest yield (ca. 50%), but also dehalogenated the diiodide.
Surprisingly, in situ generated alane (AlH3) reduced the double
bond. Attempts to use borohydrides or boranes failed, due
In contrast, catalytic hydrosilylation as a methodology for
amide reduction has received significant recent attention, and a
number of reports utilizing transition-metal catalysts (Rh,8
Mn,9 Ru,9−11 Os,9 Ir,9,12 Pt,9,13 Pd,9 Re,9 Fe,14−16 In17) have
appeared. However, many of these catalysts are expensive, and
reaction conditions involve high temperatures that decrease
compatibility with thermally sensitive functional groups. More
recently, Beller and co-workers have developed amide
reduction methods using Cu,18 Fe,15 and Zn19,20 containing
Lewis acids that overcome most of the limitations of previous
Received: June 10, 2014
Published: July 17, 2014
© 2014 American Chemical Society
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Note
ab c
, ,
Table 1. Amines from the Hydrosilylation of Amides
a
b
Conditions: amide (1 mmol), TDMS (4 mmol, 8 equiv Si-H), B(C6F5)3 (0.05 mmol as 0.05 M solution in toluene), toluene (3 mL), Ar(g). Only
c
starting materials were isolated. Multiple products.
either to insufficient reactivity or to reduction of the alkene
functionality. We thus turned to the use of Zn(OTf)2 and
tetramethyldisiloxane (TMDS) in toluene, as developed by Das
et al.19 These conditions were effective for the reduction of
both 1 and 2, but required unusually high temperatures. No
reduction was observed at 110 °C (over 3 days), and even at
elevated temperatures of 130 °C, reaction times were long (48
h) and the use of a high-pressure vessel was required. Attempts
to reduce the reaction time by heating to 150 °C drastically
reduced the yield. Additionally, we hypothesize that catalyst
decomposition occurred during the course of the reaction
(some black precipitate was produced at high temperature),
resulting in partial dehalogenation of the substrate, and
although yields were acceptable (ca. 80%), purification from
these dehalogenated side products was generally difficult.
To circumvent these issues, we turned our attention to other,
more powerful Lewis acids for this hydrosilylative reduction.
Tris(pentafluorophenyl)boron (B(C6F5)3) is a powerful Lewis
acid, having activity intermediate to BCl3 and BF3, yet it is
relatively water stable.24−27 Piers and colleagues, among others,
have described the use of this catalyst for the hydrosilylation of
many functional groups, including alcohols and ethers,28
carbonyl groups,29−31 as well as imines and nitriles.27,32,33 In
addition, it has been shown to be particularly effective for the
silylation of various alcohols,34 as well as the condensation of
hydrosilanes and alkoxysilanes to produce branched and linear
silicones with well-defined structures (Piers−Rubinsztajn
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Note
reaction).35−39 It is also capable of a rapid cross-linking reaction
as an alternative room-temperature vulcanization method for
making silicone rubbers and silicone foams.40 However, to the
best of our knowledge, only one report exists in the literature
detailing the use of B(C6F5)3 for the hydrosilylative reduction
of amides.41 This report utilized diphenylsilane as the reducing
agent for three aliphatic N-aryl amides. Considering the vast
literature on the reduction of imines, nitriles, and carbonyl
groups with B(C6F5)3, including in-depth discussions of the
reduction mechanism,27,29,32,33 we found it surprising that the
scope of the corresponding amide reduction has not been
explored, nor was the reaction protocol optimized.41
In our experiments, we rapidly discovered that the use of 5
mol % B(C6F5)3 as a substitute for Zn(OTf)2 in the reduction
of 1 and 2 to the corresponding amines proceeded in near
quantitative yield at mild temperatures (50 °C, Table 1). The
use of less catalyst (1−2 mol %) prevented complete reaction
in a reasonable amount of time, while the addition of more
catalyst (10 mol %) decreased the reaction time markedly, to
less than 1 h (though 5% was always enough to ensure
complete conversion). It is known that B(C6F5)3 forms
complexes with imine and amine reagents, and we expect the
product poisons the catalyst to some degree, dramatically
slowing the reaction when low catalyst loading is used.42 Most
notably, when sufficient catalyst quantities are present, no side
products appear to be produced, and purification requires only
standard flash chromatographic purification to remove excess
silane, spent siloxane, and the residual boron catalyst.
benzyl, or N-allyl amides, though it appears that it is not
essential that the system be conjugated through the carbonyl
side (entries 11, 13−16).41 Furthermore, while nitro groups
were well-tolerated (entry 6), it was found that nitriles
underwent reduction, leading to multiple products (entry 12).
In the cases where reduction was not observed, isolation of the
starting material allowed for approximately 95% recovery. We
speculate the mechanism of reaction follows a similar pathway
as the reduction of esters.42 This differs from the mechanism of
B(C6F5)3 reduction of imines in that no Si−N bond is formed.
Accordingly, we were unable to reduce secondary tert-butyl
amides, in contrast to results by Blackwell et al. with tert-butyl
imines.42
In order to determine the mechanism of inhibition for
secondary N-alkyl amides, we attempted a reduction of N-
benzylbenzamide using 25% loading of B(C6F5)3. We were able
to obtain ca. 70% recovery of our starting material; however, we
also observed a highly polar product by TLC (Rf = 0.2, 1:9
MeOH:EtOAc). When isolated via chromatography (ca. 15%
yield), the solid product produced a 1H NMR spectrum
consistent with dibenzylamine. This is consistent with the
production of a strong B(C6F5)3 adduct. In fact, the literature
confirms that the adducts of B(C6F5)3 are especially strong due
to a bifurcated F−H−F hydrogen bond between the amine
proton and two of the ring fluorine atoms.43−45 On the basis of
this evidence, we hypothesize that the variation in rate across
amide types is primarily dependent on the strength of the
amine−B(C6F5)3 complex. N-Phenyl amines are considerably
less basic than aliphatic amines, and would be expected to form
a much weaker complex. Tertiary amines are more basic, but
lack the presence of an amine N-hydrogen to form additional
hydrogen bonds. Secondary N-alkyl amines form strong
bifurcated H-bonds with the B(C6F5)3 ring fluorides,43 and
we speculate that this H-bonded complex is too strong to
permit catalyst turnover, thus poisoning the catalyst after a
single cycle.
As this method was mild, rapid, and capable of cleanly
reducing amides 1 and 2, we set out to investigate its scope.
The functional group tolerance of B(C6F5)3 is well-
established,29,30,34,42 so our primary aim was to determine the
structural variability of amides that could be reduced by this
methodology. The structures of the different amides that were
attempted, along with the corresponding amines, are presented
in Table 1.
Lastly, reductions of N-phenylamide (3) with silanes other
than TMDS were also successful. Diphenylsilane (DPS),
diphenylmethylsilane (DPMS), and polymethylhydrosiloxane
(PMHS, Gelest; Mn: ca. 2 kDa) were equally efficient for these
reductions (Table 2). However, in each case, purification was
Generally, this method was capable of reducing N-phenyl
amides in excellent yield (Table 1, entries 1−7) and was also
effective at reducing tertiary benzyl amides (Table 1, entry 8).
These substrates were all reduced in high yield in 4 h or less.
The reaction rate for these substrates appeared to be primarily
controlled by their solubility. Entries 1 and 6 involved amide
structures that were poorly soluble in toluene and, therefore,
required a 4 h reaction time to reach completion. The other N-
phenyl amides in the first seven entries of Table 1 required 1.5
h or less at 50 °C. The presence of halogens, or electron-
withdrawing substituents did not substantially affect the
reaction rate or yield. Entry 5 was significantly faster than the
other N-phenyl amides, only requiring 2 h at room temper-
ature. This increased reaction rate may result from the extra
coordination to boron afforded by the furan oxygen.32 Heptane
was also a suitable solvent for these reductions, but all reactions
were found to be slower, again due to the reduced solubility in
this solvent. It should be noted that, despite longer reaction
times for the less soluble structures, product yields were
generally high.
Table 2. Product Yield from Hydrosilylative Reduction
a
Using Different Silanes
silane
yield %
TMDS
DPS
96
95
95
80
DPMS
PMHS
a
Conditions: N-phenylamide 3 (1 mmol), silane (4 mmol), B(C6F5)3
(0.05 mmol as 0.05 M solution in toluene), toluene (3 mL), Ar(g)
.
less facile. The phenyl silanes had similar Rf values to the
product amines, due to their more polar nature. While ideal
from a cost standpoint and its status as an industrial byproduct,
the use of PMHS as a reducing agent produces a cross-linked
gel that makes product isolation tedious.
In conclusion, the use of B(C6F5)3 leads to efficient, mild,
and selective reduction of both secondary and tertiary N-phenyl
amides, as well as conjugated tertiary amides. The scope and
limitations for the reductions of amides appear to mirror those
found in the literature for imines.42 In particular, we have found
As noted in the previous report,41 reduction of aliphatic
tertiary amides with aromatic substituents on the carbonyl
carbon proceeded smoothly (entry 9). However, in the case
where aliphatic substituents were present on both sides of the
amide, the reductions were more difficult and yields suffered
accordingly (entry 10). Interestingly, this method appears to be
unable to reduce primary amides or secondary N-alkyl, N-
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Note
without purification. Monitoring the reaction by thin-layer chromatog-
raphy showed the product at Rf = 0.35 (Et2O/n-hexanes, 1:4).
The crude 10-bromo-3,7-diiodo-10,11-dihydro-5H-dibenzo[a,d][7]-
annulen-5-one (2.34 g, 4.35 mmol), Et3N (12 mL), and benzene (25
mL) were added to a 100 mL round-bottom flask equipped with a
reflux condenser. The light brown mixture was stirred at reflux for 7 h
and then slowly cooled to 0 °C and filtered. The light yellow filtered
solid was stirred in 1 M HCl (50 mL), filtered, and washed again with
water (50 mL), followed by MeOH (20 mL). The crude solid was
purified via recrystallization from toluene to yield 1.39 g, 3.00 mmol
(70%) of a light yellow crystalline solid. 1H NMR (700 MHz;
DMSO): δ 8.36 (s, 2H), 8.11 (d, J = 8.0, 2H), 7.56 (d, J = 6.8, 2H),
7.23 (s, 2H). 13C NMR (176 MHz; DMSO): δ 189.0, 141.1, 138.7,
138.0, 133.9, 133.2, 131.5, 95.8. HRMS (ESI+) (m/z) calculated for
C15H9OI2 [M + H]+ 458.8743, measured 458.8728.
this to be very useful in the reduction of amides in the presence
of alkenes and aryl iodides.
EXPERIMENTAL SECTION
■
General. All reactions were run under an argon atmosphere. The
toluene used for the reductions was dried via an alumina column in a
solvent purification system. All amides, except for entries 1 and 2, were
synthesized from their respective amines and acyl chlorides using a
modified literature method.19 Amide 1 was synthesized via a previously
reported procedure.23 An analogous synthesis of amide 2, following
modified literature procedures, is reported below. All yields are
isolated yields. Solutions were deoxygenated by sparging with argon
while sonicating. All NMR chemical shifts (δ) are reported in ppm and
coupling constants (J) in Hz.
(Z)-3,8-Diiododibenzo[b,f ]azocin-6(5H)-one.48,49 3,7-Diiodo-5H-
dibenzo[a,d][7]annulen-5-one (1.39 g, 3.03 mmol) was added to a
mixture of H2NOH·HCl (1.05 g, 15.2 mmol) and pyridine (10 mL) in
a 25 mL round-bottom flask equipped with a reflux condenser. The
yellow reaction mixture was stirred while refluxing for 4 h and then
diluted with CH2Cl2 (200 mL). The solution was washed with 5%
HCl(aq) (2 × 100 mL) and brine (1 × 100 mL) and then dried over
MgSO4 and evaporated under reduced pressure to yield 1.43 g (quant.
recovery) of a pale yellow powder. The mildly moisture sensitive
compound was used immediately. Monitoring the reaction by thin-
layer chromatography showed a single product at Rf = 0.15 (Et2O/n-
hexanes, 1:4).
General Procedure for the Reduction of Amides. A dry 50 mL
Schlenk tube, or round-bottom flask, was charged with the amide (1
mmol) and dry toluene (3 mL). The mixture was degassed with argon
in an ultrasonicator for 15 min before adding TMDS (537 mg, 4
mmol). While stirring at 50 °C, a 0.05 M degassed solution of
B(C6F5)3 in dry toluene (1 mL, 0.05 mmol) was added in two aliquots,
over 30 min, resulting in gas evolution. The reaction was monitored by
thin-layer chromatography. Upon completion, the remaining toluene
was evaporated under reduced pressure, leaving behind a crude
mixture that was purified via a short basic alumina column eluting with
hexanes to remove silyl compounds, followed by CH2Cl2 to elute
product.
Eaton’s reagent (10 mL) was added to a dry 50 mL round-bottom
flask containing the crude 3,7-diiodo-5H-dibenzo[a,d][7]annulen-5-
one oxime (1.43 g, 3.03 mmol). The brown reaction mixture was
stirred at 100 °C for 30 min before being slowly cooled to room
temperature and quenching via dropwise addition of water (30 mL)
over an ice bath. The resulting precipitate was filtered and rinsed with
5% NaHCO3(aq) (2 × 30 mL), followed by MeOH (10 mL). The tan
solid was dried under vacuum to a yield of 1.29 g, 2.73 mmol (90%).
An analytically pure product can be obtained by recrystallizing from
CHCl3. 1H NMR (700 MHz; CDCl3): δ 7.79 (s, 1H), 7.64 (d, J = 8.0,
1H), 7.53 (d, J = 8.9, 2H), 7.46 (s, 1H), 6.86 (m, 2H), 6.77 (t, J = 11.3,
2H). 13C NMR (176 MHz; CDCl3): δ 171.4, 138.9, 137.1, 136.5,
136.2, 136.1, 135.3, 134.6, 133.3, 132.9, 130.7, 129.9, 129.5, 93.2, 93.0.
HRMS (ESI+) (m/z) calculated for C15H10NOI2 [M + H]+ 473.8852,
measured 473.8842.
Characterization of Amines. (Z)-3,8-Dibromo-5,6-
dihydrodibenzo[b,f ]azocine, (1). Yield: 336 mg, 0.92 mmol (92%),
bright yellow crystalline solid. Oxidizes readily to a light orange solid.
1H NMR (700 MHz; CDCl3): δ 7.58 (dd, J = 8.1, 1.7, 1H), 7.56 (s,
1H), 6.98−6.96 (m, 2H), 6.87 (d, J = 8.0, 1H), 6.65 (d, J = 8.2, 1H),
6.50 (d, J = 12.9, 1H), 6.34 (d, J = 12.9, 1H), 5.79 (s, 1H), 4.51 (s,
2H). 13C NMR (176 MHz; CDCl3): δ 146.2, 138.8, 138.6, 138.1,
137.1, 135.4, 132.4, 131.7, 128.22, 128.10, 127.1, 122.5, 93.6, 92.5,
49.1. HRMS (ESI+) (m/z) calculated for C15H12NBr2 [M + H]+
363.9336, measured 363.9337.
Procedure for the Reduction of 1-(Piperidin-1-yl)heptan-1-
one. A dry pressure vessel of appropriate size was charged with 1-
(piperidin-1-yl)heptan-1-one (197 mg, 1 mmol), B(C6F5)3 (25.6 mg,
0.05 mmol), and toluene (4 mL). The mixture was degassed with
argon in an ultrasonicator for 15 min before adding TMDS (537 mg, 4
mmol). The pressure vessel was sealed with a stir bar and submerged
in an oil bath at 130 °C for 24 h. The vessel was removed from the oil
bath and allowed to cool to room temperature before being opened.
After evaporating the remaining toluene under reduced pressure, the
oily residue was purified via column chromatography using silica gel
passivated with Et3N in EtOAc/n-hexanes 1:4.
Synthesis of Amide 2:23 3,7-Diiodo-10,11-dihydro-dibenzo-
[a,d]cyclohepten-5-one.46 Dibenzosuberone (10.50 g, 50 mmol), I2
(16.50 g, 65 mmol), and acetic acid (100 mL) were added to a 500 mL
2-N round-bottom flask equipped with a condenser and addition
funnel, forming a red-violet mixture. A mixture of HNO3 (4 mL) and
H2SO4 (10 mL) was then added dropwise to the stirring reaction,
followed by CCl4 (5 mL). The reaction was heated and stirred at reflux
for 5 h, then partitioned between water (500 mL) and chloroform
(500 mL) while molten. The aqueous phase was further extracted with
chloroform (3 × 100 mL). The organic phases were combined and
washed with 2 M NaSO3 (4 × 150 mL), 5% NaHCO3 (3 × 150 mL),
and brine (1 × 150 mL). The organic phase was dried over magnesium
sulfate and then filtered and evaporated under reduced pressure to
yield a crude reddish solid. The crude material was passed through a
silica plug and purified via recrystallization from 1:8 1,4-dioxane/
EtOH to yield 6.44 g, 14.0 mmol (28%) of an off-white crystalline
solid. 1H NMR (700 MHz; CDCl3): δ 8.29 (d, J = 1.6, 2H), 7.74 (dd, J
= 8.0, 1.7, 2H), 6.97 (d, J = 8.0, 2H), 3.12 (s, 4H). 13C NMR (176
MHz; CDCl3): δ 192.5, 141.42, 141.37, 139.7, 139.4, 131.4, 91.8, 34.4.
HRMS (ESI+) (m/z) calculated for C15H11OI2 [M + H]+ 460.8899,
measured 460.8919.
(Z)-3,8-Diiodo-5,6-dihydrodibenzo[b,f ]azocine, (2). Yield: 394
mg, 0.86 mmol (86%), bright yellow crystalline solid. Oxidizes readily
1
to a dark orange solid. H NMR (700 MHz; CDCl3): δ 7.58 (dd, J =
8.0, 1.7, 1H), 7.55 (s, 1H), 6.91 (dd, J = 8.2, 1.5, 1H), 6.88 (d, J = 8.1,
1H), 6.85 (s, 1H), 6.63 (d, J = 8.2, 1H), 6.46 (d, J = 13.0, 1H), 6.27 (d,
J = 13.0, 1H), 4.60 (s, 1H), 4.49 (s, 2H). 13C NMR (176 MHz;
CDCl3): δ 147.5, 139.7, 138.7, 138.0, 137.0, 135.8, 132.7, 131.8, 127.5,
127.2, 126.5, 121.5, 93.6, 92.4, 48.8. HRMS (ESI+) (m/z) calculated
for C15H12NI2 [M + H]+ 459.9059, measured 459.9072.
N-Benzylaniline, (3). Yield: 176 mg, 0.96 mmol (96%), clear,
colorless liquid. 1H NMR (700 MHz; CDCl3): δ 7.40 (d, J = 7.5, 2H),
7.37 (t, J = 7.5, 2H), 7.30 (t, J = 7.2, 1H), 7.21−7.19 (m, 2H), 6.75 (t,
J = 7.3, 1H), 6.67−6.66 (m, 2H), 4.35 (s, 2H), 4.09 (s, 1H). 13C NMR
(176 MHz; CDCl3): δ 148.2, 139.5, 129.4, 128.8, 127.6, 127.4, 117.7,
113.0, 48.5. HRMS (ESI+) (m/z) calculated for C13H14N [M + H]+
184.1126, measured 184.1132.
3,7-Diiodo-5H-dibenzo[a,d][7]annulen-5-one.47 A mixture of 3,7-
diiodo-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one (2.00 g, 4.35
mmol), N-bromosuccinimide (1.01 g, 5.65 mmol), benzoyl peroxide
(42 mg, 0.17 mmol), and 1,2-dichloromethane (30 mL) was added to
a 100 mL round-bottom flask equipped with a reflux condenser. The
light brown mixture was stirred at reflux for 4 h and then slowly cooled
to room temperature. The precipitate was dissolved in dichloro-
methane before washing with 5% NaOH (3 × 75 mL), water (1 × 75
mL), and brine (1 × 75 mL). The organic phase was dried over
MgSO4 and evaporated under reduced pressure to yield 2.34 g (quant.
recovery) of a tan powder that was moved on to the next reaction
N-Benzyl-4-iodoaniline, (4). Yield: 303 mg, 0.98 mmol (98%),
white crystalline solid. Oxidizes readily to a green solid. 1H NMR (700
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Note
MHz; CDCl3): δ 7.41 (d, J = 8.8, 2H), 7.35−7.34 (m, 4H), 7.28 (m,
1H), 6.42 (d, J = 8.8, 2H), 4.30 (s, 2H), 4.20 (s, 1H). 13C NMR (176
MHz; CDCl3): δ 147.7, 138.9, 137.9, 128.9, 127.5, 115.3, 78.4, 48.3.
HRMS (ESI+) (m/z) calculated for C13H13NI [M + H]+ 310.0093,
measured 310.0099.
(2) Stein, M.; Breit, B. Angew. Chem., Int. Ed. 2013, 52, 2231−2234.
(3) Nunez Magro, A. A.; Eastham, G. R.; Cole-Hamilton, D. J. Chem.
Commun. 2007, 3154−3156.
́
̃
(4) Coetzee, J.; Dodds, D. L.; Klankermayer, J.; Brosinski, S.; Leitner,
W.; Slawin, A. M. Z.; Cole-Hamilton, D. J. Chem. Eur. J. 2013, 19,
11039−11050.
N-(Furan-2-ylmethyl)aniline, (5). Yield: 157 mg, 0.91 mmol (91%),
1
clear, colorless liquid. H NMR (700 MHz; CDCl3): δ 7.40 (s, 1H),
(5) Burch, R.; Paun, C.; Cao, X. M.; Crawford, P.; Goodrich, P.;
7.23 (t, J = 7.9, 2H), 6.79 (t, J = 7.3, 1H), 6.71 (d, J = 7.7, 2H), 6.36 (s,
1H), 6.27 (s, 1H), 4.35 (s, 2H), 4.04 (s, 1H). 13C NMR (176 MHz;
CDCl3): δ 152.8, 147.7, 142.0, 129.3, 118.1, 113.2, 110.4, 107.1, 41.5.
HRMS (ESI+) (m/z) calculated for C11H12NO [M + H]+ 174.0919,
measured 174.0912.
Hardacre, C.; Hu, P.; McLaughlin, L.; Sa,
2011, 283, 89−97.
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J.; Thompson, J. M. J. Catal.
(6) Szostak, M.; Spain, M.; Eberhart, A. J.; Procter, D. J. J. Am. Chem.
Soc. 2014, 136, 2268−2271.
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Chem. Soc. 2007, 129, 3408−3419.
N-(4-Nitrobenzyl)aniline, (6). Yield: 210 mg, 0.92 mmol (92%),
bright yellow liquid. Oxidizes readily to a dark brown liquid. 1H NMR
(700 MHz; CDCl3): δ 8.17 (d, J = 8.6, 2H), 7.51 (d, J = 8.3, 2H), 7.15
(t, J = 8.0, 2H), 6.73 (t, J = 7.3, 1H), 6.57 (d, J = 7.7, 2H), 4.46 (s,
2H), 4.28 (s, 1H). 13C NMR (176 MHz; CDCl3): δ 147.58, 147.39,
147.31, 129.5, 127.8, 124.0, 118.4, 113.1, 47.8. HRMS (ESI+) (m/z)
calculated for C13H13N2O2 [M + H]+ 229.0977, measured 229.0969.
N-Benzyl-N-methylaniline, (7). Yield: 193 mg, 0.98 mmol (98%),
clear, colorless liquid. 1H NMR (700 MHz; CDCl3): δ 7.35 (t, J = 7.5,
2H), 7.28−7.25 (m, 5H), 6.80 (d, J = 7.8, 2H), 6.75 (t, J = 6.9, 1H),
4.57 (s, 2H), 3.05 (s, 3H). 13C NMR (176 MHz; CDCl3): δ 149.9,
139.1, 129.3, 128.7, 126.99, 126.87, 116.7, 112.5, 56.8, 38.6. HRMS
(ESI+) (m/z) calculated for C14H16N [M + H]+ 198.1283, measured
198.1273.
N-Benzyl-N-methyl-1-phenylmethanamine, (8). Yield: 207 mg,
0.98 mmol (98%), clear, colorless liquid. 1H NMR (700 MHz;
CDCl3): δ 7.37 (d, J = 7.5, 4H), 7.33 (t, J = 7.5, 4H), 7.26−7.24 (m,
2H), 3.53 (s, 4H), 2.20 (s, 3H). 13C NMR (176 MHz; CDCl3): δ
139.5, 129.1, 128.4, 127.1, 62.0, 42.4. HRMS (ESI+) (m/z) calculated
for C15H18N [M + H]+ 212.1439, measured 212.1433.
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1
colorless liquid. H NMR (700 MHz; CDCl3): δ 7.32−7.30 (m, 4H),
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7.25−7.23 (m, 1H), 3.48 (s, 2H), 2.38 (s, 4H), 1.58 (quintet, J = 5.5,
4H), 1.43 (s, 2H). 13C NMR (176 MHz; CDCl3): δ 138.8, 129.4,
128.2, 126.9, 64.0, 54.6, 26.1, 24.5. HRMS (ESI+) (m/z) calculated for
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1-Heptylpiperidine, (10). Yield: 119 mg, 0.65 mmol 65%, clear,
1
colorless liquid. H NMR (600 MHz; CDCl3): δ 2.35 (m, 4H), 2.25
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(dd, J = 9.2, 6.7, 2H), 1.57 (quintet, J = 5.7, 4H), 1.48−1.46 (m, 2H),
1.41 (m, 2H), 1.29−1.24 (m, 8H), 0.86 (t, J = 7.0, 3H). 13C NMR
(176 MHz; CDCl3): δ 59.9, 54.8, 32.0, 29.4, 27.9, 27.1, 26.1, 24.7,
22.8, 14.2. HRMS (ESI+) (m/z) calculated for C12H26N [M + H]+
184.2065, measured 184.2069.
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ASSOCIATED CONTENT
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S
* Supporting Information
1H and 13C NMR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: adronov@mcmaster.ca. Tel: (905) 525-9140, ext.
23514. Fax: (905) 521-2773.
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Notes
The authors declare no competing financial interest
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ACKNOWLEDGMENTS
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5047−5056.
■
Financial support for this work was provided by the Natural
Science and Engineering Research Council of Canada
(NSERC). R.C.C. is grateful for the support through the
Ontario Graduate Scholarships (OGS) program.
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