Practical access to amines by platinum-catalyzed reduction of carboxamides with hydrosilanes: Synergy of dual Si-H groups leads to high efficiency and selectivity

Article abstract of DOI:10.1021/ja9055307

The synergetic effect of two Si-H groups leads to efficient reduction of carboxamides to amines by platinum catalysts under mild conditions. The rate of the reaction is dependent on the distance of two Si-H groups; 1,1,3,3-tetramethyldisiloxane (TMDS) and 1,2-bis(dimethylsilyl)benzene are found to be an effective reducing reagent. The reduction of amides having other reducible functional groups such as NO₂, CO₂R, CN, CdC, Cl, and Br moieties proceeds with these groups remaining intact, providing a reliable method for the access to functionalized amine derivatives. The platinum-catalyzed reduction of amides with polymethylhydrosiloxane (PMHS) also proceeds under mild conditions. The reaction is accompanied by automatic removal of both platinum and silicon wastes as insoluble silicone resin, and the product is obtained by simple extraction. A mechanism involving double oxidative addition of TMDS to a platinum center is discussed.

Full text of DOI:10.1021/ja9055307

Published on Web 09/28/2009
Practical Access to Amines by Platinum-Catalyzed Reduction
of Carboxamides with Hydrosilanes: Synergy of Dual Si-H
Groups Leads to High Efficiency and Selectivity
Shiori Hanada, Emi Tsutsumi, Yukihiro Motoyama, and Hideo Nagashima*
Graduate School of Engineering Sciences, Institute for Materials Chemistry and Engineering,
Kyushu UniVersity, Kasuga, Fukuoka 816-8580, Japan
Received July 6, 2009; E-mail: nagasima@cm.kyushu-u.ac.jp
Abstract: The synergetic effect of two Si-H groups leads to efficient reduction of carboxamides to amines
by platinum catalysts under mild conditions. The rate of the reaction is dependent on the distance of two
Si-H groups; 1,1,3,3-tetramethyldisiloxane (TMDS) and 1,2-bis(dimethylsilyl)benzene are found to be an
effective reducing reagent. The reduction of amides having other reducible functional groups such as NO2,
CO2R, CN, CdC, Cl, and Br moieties proceeds with these groups remaining intact, providing a reliable
method for the access to functionalized amine derivatives. The platinum-catalyzed reduction of amides
with polymethylhydrosiloxane (PMHS) also proceeds under mild conditions. The reaction is accompanied
by automatic removal of both platinum and silicon wastes as insoluble silicone resin, and the product is
obtained by simple extraction. A mechanism involving double oxidative addition of TMDS to a platinum
center is discussed.
1. Introduction
to the fact that hydrosilylation of ketones with trialkyl- or
diarylsilanes is efficiently catalyzed by rhodium, cobalt, ruthe-
nium, and iridium complexes.4 In particular, rhodium-catalyzed
hydrosilylation has now become a standard methodology for
the reduction of ketones in organic synthesis including asym-
metric production of alcohols. In this context, we found it
curious when we began the research described here that platinum
catalysts do not work well to reduce carbonyl compounds,
though some Rh, Co, Ru, and Ir compounds are useful for
hydrosilylation of both the CdO and CdC bonds.4
Hydrosilylation is a term which describes the addition reaction
of organosilicon compounds having one or more Si-H bonds
to unsaturated organic molecules. It is well-known that certain
transition metal salts and complexes effectively catalyze hy-
drosilylation. In particular, platinum-catalyzed hydrosilylation
reactions of alkenes and alkynes is one of the most powerful
methods of producing a variety of organosilicon compounds
on both laboratory and industrial scales.1 Several platinum
compounds are easily available from commercial sources, and
reactions rapidly proceed with only a small amount of the
catalyst, being highly tolerant to various functional groups.2 In
contrast to numerous papers and patents reporting that platinum-
catalyzed hydrosilylation successfully occurs to carbon-carbon
multiple bonds, there is a surprisingly small number of papers
which refer to the catalysis of hydrosilylation of carbon-oxygen
double bonds by platinum compounds.3 This is in sharp contrast
Among carbonyl compounds, it is well-known that carboxa-
mides are hardly reducible with alumino- or borohydrides.5 In
this sense, application of the metal-promoted reduction of amides
to amines with hydrosilanes under mild conditions is a challenge
to be solved. The first successful example was reported by
Buchwald et al. who found the reduction of tertiary amides to
aldehydes with Ph2SiH2 using a stoichiometric amount of
(i-PrO)4Ti.6 Stimulated by this, further efforts were made to
achieve catalytic reduction with hydrosilanes. Harrod et al.
reported the Cp2TiF2-catalyzed reduction of tertiary amides to
tertiary amines with PhMeSiH2;7 Ito and Ohta et al. showed
that rhodium-triphenylphosphine complexes are also effective
catalysts for the reduction of tertiary- and secondary amides
(1) (a) Ojima, I. In The Chemistry of Organic Silicon Compounds; Patai,
S., Rappoport, Z., Eds.; John Wiley & Sons: New York, 1989; Part 2,
Chapter 25, pp 1479-1526. (b) Marciniec, B. ComprehensiVe
Handbook on Hydrosilylation; Pergamon Press: Oxford, 1992. (c)
Marciniec, B. In Applied Homogeneous Catalysis with Organometallic
Compounds; Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH:
Weinheim, 1996, Vol. 1, Chapter 2. (d) Brook, M. A. Silicon in
Organic, Organometallic, and Polymer Chemistry; John Wiley & Sons:
New York, 2000.
(2) (a) Sabourault, N.; Mignani, G.; Wagner, A.; Mioskowski, C. Org.
Lett. 2002, 4, 2117–2119. (b) Hamze, A.; Provot, O.; Alami, M.; Brion,
J.-D. Org. Lett. 2005, 7, 5625–5628. (c) Chauhan, B. P. S.; Rathore,
J. S. J. Am. Chem. Soc. 2005, 127, 5790–5791.
(4) (a) Nishiyama, H.; Itoh, K. In Catalytic Asymmetric Synthesis, 2nd
ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 111-143. (b)
Carpentier, J.-F.; Bette, V. Curr. Org. Chem. 2002, 6, 913–936. (c)
Riant, O.; Mostefa¨ı, N.; Courmarcel, J. Synthesis 2004, 2943–2958.
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Mechanisms, and Structure, 6th ed.; Wiley-VCH: 2007.
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Engl. 1996, 35, 1515–1516.
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1972, 46, C65–C67. (b) Hayashi, T.; Yamamoto, K.; Kumada, M. J.
Organomet. Chem. 1976, 112, 253–262. (c) Barlow, A. P.; Boag,
N. M.; Stone, F. G. A. J. Organomet. Chem. 1980, 191, 39–47. (d)
Cullen, W. R.; Evans, S. V.; Han, N.-F.; Trotter, J. Inorg. Chem. 1987,
26, 514–519. (e) Zuev, V. V.; de Vekki, D. A. Phosphorus, Sulfur,
Silicon Relat. Elem. 2005, 180, 2071–2083.
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82, 1244–1248.
9
15032 J. AM. CHEM. SOC. 2009, 131, 15032–15040
10.1021/ja9055307 CCC: $40.75  2009 American Chemical Society

Efficient Pt-Catalyzed Hydrosilylation of Carboxamides
A R T I C L E S
Table 1. Structural Effect of Hydrosilanesa
using Ph2SiH2 as a reducing agent.8 Reduction of tertiary and
secondary amides with PhSiH3 was accomplished by catalysis
of MoO2Cl2.9 Our research group showed that a triruthenium
cluster, (µ3,η2:η3:η5-acenaphthylene)Ru3(CO)7, efficiently cata-
lyzes the reduction of tertiary amides with hydrosilanes.10 The
reaction is exothermic, giving the corresponding tertiary amines
in high yields under mild conditions. There are three notable
features for this reduction: The first is the possible use of
trialkylsilanes, which are more easily handled than PhSiH3 and
Ph2SiH2. Fuchikami et al. reported that several metal complexes
of groups 8-10 catalyzed the reduction of amides with Et3SiH.11
However, these reactions require application of high temperature
in the presence of cocatalysts such as haloalkanes and/or amines.
The second feature is a significant rate enhancement using
hydrosilanes having dual Si-H groups, which made possible
the reduction of secondary amides to secondary amines, a result
not achievable with common monohydrosilanes under mild
conditions.10d The third feature is the automatic removal of the
catalyst species, which was first achieved when polymethylhy-
drosiloxane (PMHS) was used as the hydrosilane.10c Entrainment
of the catalyst species in the silicone resin formed occurs during
the reduction of amides to amines. In a typical example,
reduction of certain amides with PMHS proceeds at room
temperature and 99.75% of the charged ruthenium was retained
by the insoluble silicone resin formed. The desired amine
containing only 15 ppm of Ru was isolated by simple extraction
of the silicone resin by ether.
Success of the catalytic reduction of amides by combination
of the ruthenium catalyst 1 and judicious choice of hydrosilanes,
particularly those having dual proximate Si-H moieties in the
molecule, prompted us to reconsider use of platinum catalysts
for the reduction of carboxamides with hydrosilanes under mild
conditions. The target of the improvement was the reaction
conditions, following up on a brief comment by Fuchikami and
co-workers that N-acetylpiperidine was reduced to N-ethylpi-
peridine using Et3SiH at 100 °C for 16 h in the presence of
PtCl2 (1 mol %) and Et2NH as a cocatalyst (5 mol %).11 Our
efforts to reduce the reaction temperature and reaction time were
crowned with success by using the “dual Si-H effect” previ-
ously experienced in the ruthenium-catalyzed reduction of
amides.10d Use of hydrosilanes containing two proximate Si-H
groups in a molecule such as 1,1,3,3-tetramethyldisiloxane
(TMDS) and 1,2-bis(dimethylsilyl)benzene made the reduction
of amides possible in the presence of commercially available
platinum compounds such as chloroplatinic acid12 and Karstedt’s
catalyst.13 Reaction proceeds under mild conditions, showing
high amido-group selectivity in the presence of other reducible
functional groups. Furthermore, extension of the two proximate
Si-H group effects to polyproximate Si-H moieties results in
a All reactions were carried out with 1a (1 mmol), H2PtCl6 ·6H2O
(0.01 mmol), and hydrosilane (Si-H ) 3 equivalent) in THF (0.5 mL)
at 50 °C for 3 h. b Determined by 1H NMR analysis with ferrocene as
an internal standard. c Isolated yield after alumina column chromato-
graphy. d For 10 h. e For 8 h. f 4 equiv of Si-H was used.
both reduction of amides under mild conditions and facile
separation of the amine product from the silicon and platinum
residues by self-entrainment of the catalyst species into the
insoluble silicone resin. A preliminary account has appeared in
an earlier communication,14 and we report here the scope of
this reaction mainly from the standpoint of practical organic
synthesis. The utility of this reaction is unequivocally supported
by scale-up of the experiments.
2. Results and Discussion
2.1. Two Proximate Si-H Effects from Structural Varia-
tion of Hydrosilanes. The “dual Si-H effect” in the platinum-
catalyzed reduction of amides was monitored by the reduction
of N,N-dimethyl-3-phenylpropionamide (1a) with several hy-
drosilanes (Si-H ) 3 equivalent to 1a) using H2PtCl6 ·6H2O
(1 mol %) as a catalyst in THF at 50 °C (Table 1). No reaction
took place with hydrosilanes containing one Si-H group in the
molecule, PhMe2SiH, EtMe2SiH, (EtO)3SiH, or Me3SiOSiMe2H,
as shown in entries 1-4. Although Ph2SiH2 is known to be a
powerful reducing reagent for a number of transition metal-
catalyzed reductions of carbonyl compounds, only starting amide
was recovered quantitatively under these conditions (entry 5).
In sharp contrast, reactions using hydrosilanes containing two
proximate Si-H groups in the molecule afforded the N,N-
dimethyl-3-phenylpropylamine (2a) in good to high yields. In
typical examples, treatment of 1a with 1,1,3,3-tetramethyldisi-
loxane (TMDS) in the presence of H2PtCl6 ·6H2O at 50 °C for
(8) (a) Kuwano, R.; Takahashi, M.; Ito, Y. Tetrahedron Lett. 1998, 39,
1017–1020. (b) Ohta, T.; Kamiya, M.; Nobumoto, M.; Kusui, K.;
Furukawa, I. Bull. Chem. Soc. Jpn. 2005, 78, 1856–1861.
(9) Fernandes, A. C.; Roma˜o, C. C. J. Mol. Catal. A: Chem. 2007, 272,
60–63.
(10) (a) Matsubara, K.; Iura, T.; Maki, T.; Nagashima, H. J. Org. Chem.
2002, 67, 4985–4988. (b) Motoyama, Y.; Itonaga, C.; Ishida, T.;
Takasaki, M.; Nagashima, H. Org. Synth. 2005, 82, 188–195. (c)
Motoyama, Y.; Mitsui, K.; Ishida, T.; Nagashima, H. J. Am. Chem.
Soc. 2005, 127, 13150–13151. (d) Hanada, S.; Ishida, T.; Motoyama,
Y.; Nagashima, H. J. Org. Chem. 2007, 72, 7551–7559. (e) Sasakuma,
H.; Motoyama, Y.; Nagashima, H. Chem. Commun. 2007, 4916–4918.
(11) Igarashi, M.; Fuchikami, T. Tetrahedron Lett. 2001, 42, 1945–1947.
(12) Speier, J. L.; Webster, J. A.; Barnes, G. H. J. Am. Chem. Soc. 1957,
79, 974–979.
(13) Hitchcock, P. B.; Lappert, M. F.; Warhurst, J. W. Angew. Chem., Int.
Ed. Engl. 1991, 30, 438–440.
(14) Hanada, S.; Motoyama, Y.; Nagashima, H. Tetrahedron Lett. 2006,
47, 6173–6177.
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A R T I C L E S
Hanada et al.
Table 2. Reduction of 1a with TMDS by Various Pt Catalystsa
reaction at room temperature (entry 6) and when 0.05 mol %
of the catalyst was used (entry 7). Other platinum compounds
such as Karstedt’s catalyst, Pt(dba)2, PtCl2(cod), and Pt/C also
act as a catalysts for the reduction of amides under mild
conditions (entries 8-11). In all cases, the amide 1a was
consumed smoothly, but a small amount of enamine 3a was
formed as the byproduct.
yield (%)b
entry
Pt catalyst (mol %)
solvent
conv (%)b
2a
3a
2.3. Reduction of Various Tertiary Amides with TMDS. In
Tables 3 and 4 are summarized the results obtained for the
reduction of various tertiary amides 1a-r with TMDS (Si-H
) 5 equivalent to 1) in toluene. In the presence of H2PtCl6 (0.1
mol %) at 50 °C, the corresponding amine 2a was produced in
85% isolated yield after 5 h (Table 3, entry 1). Lactams 1e and
1f were reduced even at room temperature to form the
corresponding cyclic amines 2e and 2f in high yields (entries 7
and 8). In contrast, reduction of an aromatic amide 1g required
somewhat higher temperature (75 °C) as shown in entry 9.
Formation of enamine was observed when there were crowded
steric circumstances of the amide oxygen in the substrate. The
amide 1b is an example of such substrate having a bulky
substituent on the nitrogen atom, whereas 1c is a substrate
having a bulky cyclohexyl group adjacent to the carbonyl group.
Although significant amounts of enamine were concomitantly
formed with H2PtCl6 (entries 2 and 4), use of Karstedt’s catalyst
effectively suppressed the production of enamine in these cases
(entries 3 and 5). The reaction of N-benzyl-N-methylpivaloy-
lamide (2d) was slow due to the steric circumstances around
the carbonyl group; however, no enamine formation was
observed with Karstedt’s catalyst.
1
2
3
4
H2PtCl6 ·6H2O (1.0)
H2PtCl6 ·6H2O (0.1)
H2PtCl6 ·6H2O (0.1)
H2PtCl6 ·6H2O (0.1)
H2PtCl6 ·6H2O (0.1)
H2PtCl6 ·6H2O (0.1)
H2PtCl6 ·6H2O (0.05)
Karstedt’s cat. (0.1)
Pt(dba)2 (0.1)
THF
THF
THP
DME
toluene
toluene
toluene
toluene
toluene
toluene
toluene
>98
>98
>98
>98
>98
>98
>98
95
>98
92
>98
>98
>98
87
92
69
76
88
<2
7
<2
<2
<2
13
8
14
8
7
5
6c,d
7
8
9
90
>95
89
10
PtCl2(cod) (0.1)
11d
Pt/C (1.0)e
76
13
a All reactions were carried out with 1a (1 mmol), Pt catalyst
(0.05-1 mol %), and TMDS (2.5 mmol, Si-H ) 5 equivalent) in
solvent (0.5 mL) at 50 °C for 5 h. b Determined by 1H NMR analysis
with ferrocene as an internal standard. c At 25 °C. d For 24 h.
e Purchased from Aldrich (5 wt % Pt).
3 h resulted in formation of 2a quantitatively, and the product
was obtained in 90% yield after alumina column chromatog-
raphy (entry 6). 1,1,1,3,5,7,7,7-Octamethyltetrasiloxane, which
has a structure similar to that of TMDS, was also an effective
reducing reagent for the platinum-catalyzed reaction of 1a (entry
7). The reaction with 1,2-bis(dimethylsilyl)benzene also pro-
ceeded smoothly to afford 2a in quantitative yield (entry 8).
The reactivity vs structure of the hydrosilane is much different
from our findings previously reported in RhCl(PPh3)3-catalyzed
hydrosilylation of ketones15 and the Ru3 cluster-catalyzed
hydrosilylation of carbonyl compounds16 in that Me2HSi-
(CH2)2SiHMe2, which was generally a reactive hydrosilane in
the previous cases, was not effective for the platinum-catalyzed
reduction of amides (entry 9). This may imply that “the dual
Si-H effect” in the platinum-catalyzed reduction may be more
sensitive to the distance between two Si-H groups than Rh- or
Ru3-catalyzed reactions.
2.2. Optimal Conditions of the Reaction with TMDS. Com-
mercially available and inexpensive TMDS is a practically useful
reductant. Optimization of the reaction conditions was carried
out using N,N-dimethyl-3-phenylpropionamide (1a), TMDS, and
several Pt compounds as the amide, the hydrosilane, and the
catalyst, respectively (Table 2). With all of the platinum catalysts
including heterogeneous Pt/C, conversion of the amide reached
over 89% after 5 h. One problem is a side reaction to produce
enamine (3a). For instance, the reaction with 1.0 mol % of
H2PtCl6 ·6H2O in THF afforded 2a exclusively, whereas lower-
ing the catalyst concentration to 0.1 mol % caused formation
of a small amount of enamine 3a (7%) as a byproduct (entries
1 and 2). When 0.1 mol % of H2PtCl6 ·6H2O was used,
appropriate selection of the solvent was important for the
selective formation of 2a; tetrahydropyran (THP), 1,2-dimethox-
yethane (DME), and toluene effectively suppressed the forma-
tion of 3a (entries 3-5). Formation of 3a was observed in the
Chemoselective reduction of amides with other functional
groups remaining intact is a challenge to be developed in the
organic synthesis of multifunctional molecules. In Table 4,
entries 1-8 summarize the reduction of a series of para-
substituted benzamides. The first two benzamides having OMe
and NMe2 group were reduced to the corresponding amines in
high yields as we expected (entries 1 and 2). The next six
substrates have a functional group which potentially reacts with
hydrosilanes. Reductive dehalogenation was not seen in the
reactions of chloro- or bromobenzamides as shown in entries 3
and 4, whereas there was no reduction of the NO2, CN, and
CO2R groups in the substrates shown in entries 5-7. In these
cases, the corresponding amines were isolated in over 80%
yields as a single product. In the reaction of keto amide 1o,
reduction of the amide function was competitive with that of
the keto group to give a mixture of products. With the higher
catalyst loading (2 mol %) and addition of larger amounts of
hydrosilane, both the keto- and amide functions were completely
reduced to give the corresponding amino alcohol in good yield
(entry 8). The reaction of R-phenoxyacetamide 1p proceeded
smoothly to afford 2-N,N-dimethylaminoethyl phenyl ether (2p)
in 79% yield (entry 9); this is a good entry to production of
ꢀ-amino alcohol derivatives. It is known that H2PtCl6 is a
powerful catalyst for hydrosilylation of CdC bonds; the rate
was decreased in the order, monosubstituted > disubstituted >
trisubstituted alkenes. Hydrosilylation of R,ꢀ-unsaturated car-
bonyl compounds proceeds in the manner of 1,4-addition. As
shown in entries 10 and 11, the amide bearing a 1,2-disubstituted
or 1,1,2-trisubstituted CdC bond underwent the reaction of
TMDS to give the corresponding amine with the CdC bond
remaining intact. In contrast, complicated mixtures of products
were formed in the reaction of amides with terminal alkenes
and R,ꢀ-unsaturated amides.
(15) (a) Nagashima, H.; Tatebe, K.; Ishibashi, T.; Sakakibara, J.; Itoh, K.
Organometallics 1989, 8, 2495–2496. (b) Nagashima, H.; Tatebe, K.;
Ishibashi, T.; Nakaoka, A.; Sakakibara, J.; Itoh, K. Organometallics
1995, 14, 2868–2879.
(16) Nagashima, H.; Suzuki, A.; Iura, T.; Ryu, K.; Matsubara, K.
Organometallics 2000, 19, 3579–3590.
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Efficient Pt-Catalyzed Hydrosilylation of Carboxamides
A R T I C L E S
Table 3. Reduction of Various Tertiary Amidesa
a All reactions were carried out with 1 (1 mmol), Pt catalyst (0.1-1 mol %), and TMDS (2.5 mmol, Si-H ) 5 equivalent) in toluene (0.5 mL). b A:
c
1
H2PtCl6 ·6H2O, B: Karstedt’s catalyst. Determined by H NMR analysis with ferrocene as an internal standard. The yield in parentheses was the yield
of enamine.
2.4. Reduction of Secondary and Primary Amides with
Table 4. Reduction of Functionalized Tertiary Amidesa
TMDS. It is known that the hydride reduction of secondary
amides is generally more difficult than that of tertiary amides.
Catalytic reduction of secondary amides with hydrosilanes has
the same problem; no reaction took place in some cases,8a
whereas high reaction temperature was required in other
cases.9,11 In our ruthenium cluster-catalyzed reduction of amides,
reduction of secondary amides did not take place under the same
conditions as those for the reaction of tertiary amides. We have
solved this problem by combining the “dual Si-H effect” and
application of higher concentration of the catalyst (3 mol %) at
slightly higher temperature.10d A similar approach was effective
for the platinum-catalyzed reduction of secondary amides as
shown in Table 5; three amides 4a, 4c, and 4d were converted
to the corresponding amines in good yields by the reactions
using 3 mol % of H2PtCl6 and TMDS (Si-H ) 10 equivalent
to 4) at 75 °C. Similar to the reduction of tertiary amides, the
lactam 4d was easily reducible, whereas benzamide 4c required
longer reaction time. A bulky amide 4b reacted with TMDS
much more slowly than the others to give the amine in moderate
yield. The secondary amine was isolated as the ammonium salt
by treatment of the reaction mixture with conc. HCl. Attempted
Pt-catalyzed reduction of primary amides such as decanamide
and p-toluamide with TMDS led to vigorous hydrogen gas
evolution, but aqueous workup resulted in quantitative recovery
of the starting materials. Neither reduction nor dehydration took
place.
2.5. Multigram-Scale Synthesis of Tertiary Amines. General
procedures for the reduction of carboxamides by alumino- and
borohydrides have safety problems due to their air- and moisture
a All reactions were carried out with 1 (1 mmol), H2PtCl6 ·6H2O
(0.01 mmol), and TMDS (2.5 mmol, Si-H ) 5 equivalent) in toluene
(0.5 mL). b For 3 h. c TMDS (5 mmol, Si-H ) 10 equivalent to 1k)
was used. d Amino alcohol was obtained as a product. e Karstedt’s
catalyst was used.
(17) (a) Hudlicky, M. Reductions in Organic Chemistry; Wiley: New York,
1984. (b) Trost, B. M., Fleming, I., Eds. ComprehensiVe Organic
Synthesis; Pergamon: Oxford, 1992; Vol. 8. (c) Seyden-Penne, J.
Reductions by the Alumino- and Borohydrides in Organic Synthesis,
2nd ed.; Wiley: New York, 1997.
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A R T I C L E S
Hanada et al.
Table 5. Reduction of Secondary Amidesa
Figure 1. Photos of the Pt/PMHS system. (A) Initial homogeneous solution,
(B) after the reaction (gel), (C) extraction with ether, (D) insoluble silicone
resin containing platinum residue.
of both of the phases suggested that the aqueous phase contained
the ammonium salt of 2a as a single organic component, while
the siloxane residue was in the organic phase. The aqueous phase
was separated and treated with potassium hydroxide. Extraction
with ether followed by concentration gave crude amine, of which
distillation under reduced pressure gave 2a in 81% (3.7 g) (entry
1). Similarly, reactions of benzamide 1g and lactam 1e afforded
the corresponding amines 2g and 2e in 83% (3.8 g) and 63%
(2.9 g) yields, respectively (entries 2 and 4). In the reaction of
N,N-dimethyl-p-nitrobenzamide (1L), the product 2L was
isolated by alumina column chromatography in 85% yield (3.9
g) (entry 3).
a All reactions were carried out with 4 (1 mmol), H2PtCl6 ·6H2O
(0.03 mmol), and TMDS (Si-H ) 10 equivalent) in THF (3 mL) at 75
°C. b Product was obtained as an ammonium salt by treatment of
secondary amine 5 with HCl/Et2O. c At 40 °C.
2.6. Reduction of Amides with PMHS: Automatic Removal
of Silicone and Platinum Wastes. Recently, removal of metal
catalysts and reactant residues from products has been recog-
nized as a problem to be solved from an environmental point
of view. Our previous papers provide one of the clear solutions
for this problem: a triruthenium cluster-catalyzed reduction of
carboxamides with PMHS giving the desired amine in good
yield is accompanied by formation of insoluble silicone resin,
into which almost all of the metal species (>99.7%) are
soaked.10c Thus, both ruthenium and silicon wastes are auto-
matically removed from the reaction mixture as a Ru-containing
siloxane resin, and the product is obtained in high purity by
simple filtration. Similar automatic removal of the catalyst and
silicon wastes can also be achieved in the present Pt-catalyzed
deoxygenative reduction of carboxamides. In a typical example,
the reaction of N,N-dimethyl-3-phenylpropionamide (1a) (1
mmol) with PMHS [n ) 25.6 (average), Si-H ) 4 equivalent
to 1a], and H2PtCl6 ·6H2O (1 mol %) was carried out using THF
as the solvent (0.6 mL) at 50 °C. After the reaction mixture
was stirred for 30 min, the initial homogeneous solution set to
gel (Figure 1, AfB). After 3 h, washing the gel with ether
gave a clear, colorless solution containing the amine 3a and a
light-yellow solid (Figure 1, CfD). ICP mass analysis revealed
that the extracted amine contained approximately 138 ppm of
platinum species. In other words, over 98.9% of the charged
platinum species was removed by this simple purification
procedure. The product was obtained from the extract in 88%
yield after a short-path alumina column with less than 1 ppm
of platinum content (Table 7, entry 1). It is noteworthy that the
encapsulated platinum species is still active in the silicone resin
and is reusable; the recovered platinum-containing resin (0.01
mmol of Pt species) catalyzed the reduction of 1a (1 mmol)
with PMHS (Si-H ) 3.7 equivalent to 1a) to afford the desired
amine 2a, although the conversion of amide was somewhat
decreased (first: 100%, second: 84%, third: 76%).
Table 6. Multigram-Scale Synthesis of Tertiary Aminesa
a All reactions were carried out with amide (5 g), H2PtCl6 ·6H2O (0.1
or 1 mol %), and TMDS (Si-H ) 5 equivalent) in toluene (13-17 mL)
at 25-75 °C. Product was isolated by distillation. b Isolated by alumina
column chromatography.
sensitivity.17 Separation of the product from aluminum or boron
wastes is often problematic. Since hydrosilanes are more
advantageous than the conventional hydride reagents due to their
ease of handling, the present platinum-catalyzed reduction of
amides with hydrosilanes deserves further attention, especially
when the reaction can be adaptable to production of amines in
large quantity. In Table 6 are summarized results of four
reactions in a scale where 5 g of the carboxamides was used as
the substrate. In all of these reactions, the desired amine is
formed quantitatively. Removal of the siloxanes concomitantly
produced is easily achieved by treatment of the reaction mixture
by strong acid to convert the amine to the corresponding
ammonium salt soluble to water. The ammonium salt without
contamination of the siloxane waste is extracted to the aqueous
phase, from which the desired amine is isolated by treatment
with base. In a typical example, amide 1a (5 g, 28.2 mmol)
and TMDS (Si-H ) 5 equivalent to 1a) were treated with
H2PtCl6 ·6H2O (0.1 mol %) in toluene at 50 °C. The starting
material was consumed within 5 h. Addition of 6 N HCl aq to
the reaction mixture gave a biphasic mixture; 1H NMR spectra
Reduction of 1a with PMHS also proceeded smoothly with
Pt(II)Cl2(cod) and a Pt(0)-vinylsiloxane complex (Karstedt’s
catalyst) to afford 2a in good yields along with the formation
of the Pt-encapsulating gel (entries 2 and 3). In these reactions,
>99% of the charged platinum species was also absorbed by
the silicon resin formed. It is noteworthy that the activity of
the platinum catalysts increased in the order H2PtCl6
PtCl2(cod) < Karstedt’s catalyst; lower-valent platinum species
<
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15036 J. AM. CHEM. SOC. VOL. 131, NO. 41, 2009

Efficient Pt-Catalyzed Hydrosilylation of Carboxamides
A R T I C L E S
Table 7. Pt-Catalyzed Reduction of 1a with PMHSa
1,1,3,3-tetramethyldisiloxane (TMDS) as shown in Table 1 to
be a clue to achieving the platinum-catalyzed reduction of
amides efficiently. Three hydrosilanes having two Si-H groups
located close together reacted with amides under mild conditions
where the reaction with other hydrosilanes listed in Table 1 did
not occur. The enormous acceleration of the reaction rate by
synergy of two proximate Si-H groups was first reported in
the RhCl(PPh3)3-catalyzed hydrosilylation of ketones, in which
the rate of the reaction of acetone with Me2HSi(CH2)2SiHMe2
is 50 times faster than that with EtMe2SiH, leading to selective
conversion of one Si-H group to the corresponding i-PrO-Si
group, with the other Si-H moiety remaining intact.15 The effect
is sensitive to the distance of two Si-H moieties; for instance,
EtMe2SiH ) Me2HSiCH2SiHMe2 ) Me2HSi(CH2)4SiHMe2 ,
Me2HSi(CH2)2SiHMe2 < Me2HSi(CH2)3SiHMe2. Effects of
hydrosilanes, which cannot be explained by conventional
consideration on the basis of the electronic structure of hy-
drosilanes or steric circumstances around the Si-H groups, were
later investigated in detail by studies on the oxidative addition
of 1,2-bis(dimethylsilyl)benzene with RhCl(PPh3)3 in which
catalytic cycles involving disilametallacyclic intermediates were
proposed.20 Thus, double oxidative addition of 1,2-bis(dimeth-
ylsilyl)benzene to RhCl(PPh3)3 is accompanied by replacement
of the chloride by hydride to form the Rh(V)-trihydride
disilarhodacyclic complex (Scheme 1, E). The species E is stable
in solution under hydrogen atmosphere, and loses H2 upon
removal of the solvent under reduced pressure to form the
Rh(III) monohydride species F. The reaction of RhCl(PPh3)3
with two equivalents of 1,2-bis(dimethylsilyl)benzene forms G.
It seems plausible to assume that similar double oxidative
addition of 1,2-bis(dimethylsilyl)benzene to Pt(0) species pro-
ceeds. In fact, it is known that double oxidative addition of 1,2-
bis(dimethylsilyl)benzene to certain Pt(0) precursors followed
by elimination of H2 results in the formation of disilaplatinacy-
clopentane;21,22 the reaction pathway is analogous to the double
oxidative addition to form the platinum analogue of E followed
by H2 elimination to give the platinum analogue of F. It is
important that the disilaplatinacyclopentanes previously reported
are synthesized by the double oxidative addition of 1,2-
bis(dimethylsilyl)benzene and 1,1,3,3-tetramethyldisiloxane.
Tanaka reported that reaction of platinum(0) complex and
o-disilylbenzene derivatives resulted in the formation of disi-
laplatinapentane through multiple oxidative additions of Si-H
groups.21 Curtis et al. and Milstein et al. reported that oxadisi-
laplatinacyclobutanes are synthesized by reaction of platinum(0)
species and 1,3-dihydrodisiloxane derivatives.22 This is in accord
with the results summarized in Table 1, in which platinum-
catalyzed reduction of amides took place with 1,2-bis(dimeth-
ylsilyl)benzene and 1,1,3,3-tetramethyldisiloxane. These results
strongly support the mechanisms involving interaction of two
proximate Si-H groups located to the platinum center.
Pt amount in crude 2a
entry
Pt catalyst
temp (°C)
(ppm)b
(%)c
yield (%)d
1
2
3
H2PtCl6 ·6H2O
PtCl2(cod)
Karstedt’s cat.
50
40
0
138
106
36
1.1
0.9
0.3
84
77
86
a All reactions were carried out with 1a (1 mmol), H2PtCl6 ·6H2O
(0.01 mmol), and PMHS (Si-H ) 3.7 equivalent) in THF (0.6 mL) at
0-50 °C for 3 h. b Determined by ICP-mass analysis. c Calculated by
the charged Pt species. d Purified by short-pass alumina column.
showed higher catalytic activity, and the reaction using Karstedt’s
catalyst proceeded even at 0 °C.
Table 8 summarizes the reactions of various tertiary amides
(1a-u) and secondary amides (4e-h) with PMHS in THF using
H2PtCl6 ·6H2O as the catalyst. Gel formation occurred in all
cases, and the corresponding amines were obtained in good to
high yields. Similar to the results obtained by the reactions with
TMDS, both aliphatic and aromatic tertiary amides underwent
the reduction below 80 °C within a few hours. As shown in
entries 7-11, the reaction is tolerant to several reducible
functional groups, Cl, Br, NO2, CN, and CO2Me. Amides
containing a di- or trisubstituted CdC bond underwent the
reduction with the CdC bond remaining intact (entries 12 and
13). In all cases, extraction of the reaction mixture with ether
gave a solution containing the desired amine as a single product.
In the reaction of 1s with PMHS, no organic product was
detected in the extracts due to hydrosilylation of a terminal CdC
bond. The hydrosilylation leads to immobilization of the product
derived from 1s in the insoluble silicone resin; this is supported
by 29Si solid state NMR of the silicone resin formed.18
Secondary amides having bulky N-i-Pr and N-t-Bu groups
underwent the reduction at somewhat elevated temperatures.
Extraction of the silicone resin that formed gave the corre-
sponding secondary amine in good yields. In contrast, no organic
product was extractable from the gel formed by the reaction of
secondary amides having a less bulky N-Me or N-Et group. As
reported previously, the secondary amine formed by the
reduction of secondary amides with PMHS is potentially linkable
to the silicone resin through a Si-N bond.10d It is likely that
bulky substituents on the nitrogen atom would disturb the Si-N
bond formation; this is the reason why the amine products from
4g or 4h were extractable, whereas those from 4e and 4f were
not.19
2.7. Mechanistic Consideration. As described in the Introduc-
tion, platinum compounds are excellent catalysts for hydrosi-
lylation of alkenes, but not for reduction of carbonyl compounds.
Our discovery is the use of hydrosilanes such as 1,2-bis(dim-
ethylsilyl)benzene, 1,1,1,3,5,7,7,7-octamethyltetrasiloxane, and
Although our efforts to capture the silylplatinum intermediates
in the actual catalytic system have thus far been unsuccessful,
(20) Sunada, Y.; Fujimura, Y.; Nagashima, H. Organometallics 2008, 27,
3502–3513.
(18) It is known that 29Si resonances due to-OSi(R)2O-moieties are
generally seen around δ-20 ppm. 29Si CP-MAS NMR spectrum of
the siloxane resin showed a broad signal at δ-19.8 ppm. See:
Engelhardt, G.; Jancke, H. J. Organomet. Chem. 1981, 210, 295–301.
(19) Since the Si-O-Si linkage of polysiloxanes is cleaved under strongly
basic conditions, it was confirmed from 1H NMR spectrum that
treatment of polysiloxane gels entrapping a secondary amine, 4e or
4f, with NaOH/MeOH actually released the amine. Attempted separa-
tion of 4e or 4f from a complicated mixture of siloxane and silanols
has thus far been unsuccessful.
(21) (a) Shimada, S.; Tanaka, M.; Honda, K. J. Am. Chem. Soc. 1995, 117,
8289–8290. (b) Shiamada, S.; Tanaka, M. Coord. Chem. ReV. 2006,
250, 991–1011, and references therein.
(22) (a) Eaborn, C.; Metham, T. N.; Pidcock, A. J. Organomet. Chem. 1973,
54, C3–C4. (b) Curtis, M. D.; Greene, J. J. Am. Chem. Soc. 1978,
100, 6362–6367. (c) Greene, J.; Curtis, M. D. J. Am. Chem. Soc. 1977,
99, 5176–5177. (d) Curtis, M. D.; Greene, J.; Butler, W. M. J.
Organomet. Chem. 1979, 164, 371–380. (e) Golkhman, R.; Karakuz,
T.; Shimon, L. J. W.; Leitus, G.; Milstein, D. Can. J. Chem. 2005,
83, 786–792.
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A R T I C L E S
Hanada et al.
Table 8. Reduction of Various Amides by the H2PtCl6 ·6H2O/PMHS Systema
a All reactions were carried out with amide (1 mmol), H2PtCl6 ·6H2O (0.01 mmol), and PMHS (Si-H ) 3.7-6 equivalent) in THF (0.5 mL) at
25-70 °C for 3-24 h. The amine product was purified by short-pass alumina column. b In DME. c 36% of 1 L was recovered. d Purified by short-pass
silica gel column. e 3.0 mL of THF and 3.0 mol % of catalyst were used.
mechanisms analogous to those proposed for the rate enhance-
ment that occurred in the RhCl(PPh3)3-catalyzed hydrosilylation
of acetone with 1,2-bis(dimethylsilyl)benzene seem to have been
adopted for the explanation of platinum-catalyzed reduction of
amides with 1,1,3,3-tetramethyldisiloxane or 1,2-bis(dimethyl-
silyl)benzene. In the mechanism involving Pt(IV) intermediates
shown in the left-hand side in Scheme 2, double oxidative
addition of proximate Si-H groups affords Pt(IV)H2Si2 species,
which is followed by the reaction of amides in retaining the
disilaplatinacyclopentane structures until the final step. In
contrast, the right-hand side in Scheme 2 shows a mechanism
involving redox between Pt(0) and Pt(II), in which the Pt(IV)
species may form in the reaction medium, but act as a precursor
reversibly generating Pt(II)HSi species. The rate acceleration
in the Pt(II) cycle occurs in the reductive elimination of the
product, which is triggered by intramolecular oxidative addition
of the second Si-H bond to the platinum center. These
mechanisms can be adapted to explain the reduction of amides
with PMHS.
A well-known proposal related to the mechanisms of platinum-
catalyzed hydrosilylation by Lewis et al. is that the colloidal
platinum(0) species are often formed during platinum-catalyzed
hydrosilylation of alkenes and alkynes.23 It seems worthwhile
to discuss the possibility that platinum nanoparticles may be
involved in the catalytic cycle. While the colloidal platinum
species by Lewis is reported to be dark brown, the platinum-
catalyzed reduction of amides with TMDS is homogeneous and
retains a clear, pale-yellow color solution throughout the
reaction. In the reaction with PMHS, all of the platinum species
is soaked up to insoluble silicone resin formed during the
reaction, and the color of the resin is also pale-yellow. High-
resolution TEM analysis of the siloxane resin, by which metal
particles 1-2 nm in size are detectable, did not show any
platinum nanoparticles. These results indicate that the net
(23) (a) Lewis, L. N.; Lewis, N. J. Am. Chem. Soc. 1986, 108, 7228–7231.
(b) Lewis, L. N. J. Am. Chem. Soc. 1990, 112, 5998–6004.
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15038 J. AM. CHEM. SOC. VOL. 131, NO. 41, 2009

Efficient Pt-Catalyzed Hydrosilylation of Carboxamides
A R T I C L E S
Scheme 1. Disilametallacycle Formation by Reaction of Wilkinson’s
Complex and 1,2-Bis(dimethylsilyl)benzene
in toluene (0.5 mL) was added a THF solution of H2PtCl6 ·6H2O
(0.1-1 mol % based on the amide). The solution was stirred at
25-75 °C for 3-54 h. After complete consumption of 1 was
confirmed by TLC analysis, the reaction mixture was passed through
a Florisil column with Celite putting on the head. After removal of
the solvent, purification of the residue by alumina column chro-
matography gave the amine 2.
N-Ethyl-N-(p-methoxyphenyl)-3-phenylpropylamine (2b): IR
(neat) ν 3025, 2934, 2830, 1509, 1453, 1371, 1243, 1180, 1040,
1
813, 748, 700 cm-1; H NMR (270 MHz, CDCl3) δ 1.12 (t, J )
7.0 Hz, 3H), 1.92 (tt, J ) 7.8, 7.4 Hz, 2H), 2.69 (t, J ) 7.8 Hz,
2H), 3.24 (t, J ) 7.4 Hz, 2H), 3.30 (q, J ) 7.0 Hz, 2H), 3.79 (s,
3H), 6.70 (d, J ) 9.0 Hz, 2H), 6.85 (d, J ) 9.0 Hz, 2H), 7.18-7.36
(m, 5H); 13C NMR (67.8 MHz, CDCl3) δ 29.1, 33.5, 46.1, 50.9,
55.9, 114.9, 115.3, 125.9, 128.39, 128.42, 142.0, 143.0, 151.6;
HRMS (EI) calcd for C18H23NO 269.1780, found 269.1778.
General Procedure for the Reduction of Secondary Amides
with TMDS. To a stirred solution of secondary amide 4 (1 mmol)
and H2PtCl6 ·6H2O (3 mol % based on the amide) in toluene was
added TMDS (5.0 mmol, 910 µL, 10 equivalent Si-H to 4) at
40-75 °C. After the reaction was complete, the resulting mixture
was passed through a Florisil column with Celite putting on the
head. After removal of the volatiles, the residue was dissolved in
Et2O. Hydrochloric acid (1.0 M Et2O, 2.0 mL) was added to the
solution. The ammonium chloride precipitated was separated,
washed with Et2O, and dried under reduced pressure. The corre-
sponding amine from the ammonium salt was reported earlier.10d
Azepane Hydrochloride (5d ·HCl): 10d IR (KBr) ν 2957, 2819,
catalyst species in our reaction would be molecular platinum
species and not colloidal platinum(0) species.
1
2761, 1601, 1462, 1105 cm-1; H NMR (270 MHz, CDCl3) δ
1.63-1.79 (m, 4H), 1.85-2.01 (m, 4H), 3.12-3.30 (m, 4H), 9.54
(bs, 2H); 13C NMR (67.8 MHz, CDCl3) δ 25.2, 26.8, 45.8.
General Procedure for the Reduction of Tertiary Amides
with PMHS. A solution of amide 1 (1 mmol) and PMHS (3.7-4.0
equivalent Si-H to 1) was treated with a THF solution of
H2PtCl6 ·6H2O (1 mol % based on the amide) at 25-80 °C. The
homogeneous solution became gradually viscous, and set to gel.
After it was allowed to stand for 3-4 h, the reaction mixture was
extracted with Et2O. The extracts were passed through a pad of
cotton to remove the fine resins. After removal of ether, purification
of residue by alumina column chromatography gave the amine 2.
(p-Dimethylaminomethyl)bromobenzene (2k): IR (neat) ν
3. Conclusion
As described in the Introduction, platinum catalysts are very
useful for the hydrosilylation of alkenes but usually not for
reduction of carbonyl compounds. A key discovery that the
reduction of amides to amines proceeds under mild conditions
was the “dual Si-H effect”, in which two proximate Si-H
groups cooperatively accelerate the reaction. In particular, it is
of practical importance that inexpensive TMDS can be used as
the reductant, whereas use of PMHS is accompanied by
automatic removal of the silicone and platinum species from
the product. It is known that conventional hydride reduction of
amide with LiAlH4 is useful for reduction of amides in
laboratory-scale experiments; however, the reagent is sensitive
to oxygen and moisture, and separation of aluminum wastes
from the product is often problematic. Stable hydrosilanes are
advantageous for handling, and the reduction reported here is
tolerant to several reducible functional groups such as NO2, CN,
esters, and halides. Compared with the ruthenium cluster (µ3,η2:
η3:η5-acenaphthylene)Ru3(CO)7 previously reported by our
research group, the present platinum-catalyzed reactions require
somewhat higher reaction temperatures; however, they have an
advantage that commercially available platinum compounds,
typically H2PtCl6, can be used as the catalyst. We believe that
the present results accelerate the practical use of metal-catalyzed
silane reduction of amides for the synthesis of various amines,
and studies including experiments to elucidate the mechanisms
are underway.
2941, 2815, 1487, 1361, 1259, 1173, 1070, 1011, 856, 796 cm-1
;
1H NMR (600 MHz, CDCl3) δ 2.22 (s, 6H), 3.36 (s, 2H), 7.18 (d,
J ) 8.4 Hz, 2H), 7.44 (d, J ) 8.4 Hz, 2H); 13C NMR (150 MHz,
CDCl3) δ 45.4, 63.7, 120.9, 130.7, 131.4, 138.1; HRMS (EI) calcd
for C9H12NBr 213.0153, found 213.0157.
General Procedure for the Reduction of Secondary Amides
with PMHS. To a stirred solution of amide 4 (1 mmol) and PMHS
(400 µL, 6 equivalent Si-H to 4) in THF (2.7 mL) was added a
THF solution of H2PtCl6 ·6H2O (0.1 N, 300 µL, 3 mol % based on
the amide) at 75 °C. The homogeneous solution became gradually
viscous, and set to gel. After it was allowed to stand for 24 h, the
reaction mixture was extracted ten times with Et2O (20 mL in total).
The extracts contained fine siloxane resins, which were filtered off
by passing through a pad of cotton. After removal of ether,
purification of the residue by alumina column chromatography gave
the desired amine.
N-tert-Butyl-3-phenylpropylamine (5h):10d 1H NMR (396
MHz, CDCl3) δ 1.11 (s, 9H), 1.83 (tt, J ) 7.9, 7.6 Hz, 2H), 2.61
(t, J ) 7.6 Hz, 2H), 2.66 (t, J ) 7.9 Hz, 2H), 7.14-7.30 (m, 5H);
13C NMR (99.5 MHz, CDCl3) δ 28.9, 32.4, 33.8, 42.1, 50.7, 125.8,
128.3, 128.4, 142.1.
A Procedure for Gram-Scale Production of Amines. As a
representatiVe experimental procedure, that shown in Table 6, entry
1 is described. To a stirred solution of N,N-dimethyl-3-phenylpro-
pionamide (1a) (5.0 g, 28.2 mmol) and TMDS (12.8 mL, 70.5
mmol) in toluene (14 mL) was added a THF solution of
H2PtCl6 ·6H2O (0.01 N, 2.82 mL, 0.1 mol % based on the amide)
at 50 °C. After 5 h, the resultant mixture was filtered through a
4. Experimental Section
Typical experimental procedures and representative spectroscopic
data of the products are described. Further experimental details and
the compound data are summarized in the Supporting Information.
General Procedure for the Reduction of Tertiary Amides
with TMDS. To a solution of amide 1 (1 mmol) and 1,1,3,3-
tetramethyldisiloxane (TMDS: 2.5 mmol, 5 equivalent Si-H to 1)
9
J. AM. CHEM. SOC. VOL. 131, NO. 41, 2009 15039

A R T I C L E S
Hanada et al.
Scheme 2. Plausible Reaction Mechanisms
pad of Celite and Florisil. The solvents were removed under reduced
pressure, and the residue was dissolved in Et2O. The solution was
washed three times with conc. HCl (totally 30 mL), and the
combined aqueous layers were treated with KOH (∼40 g). The
mixture was extracted three times with ether (30 mL in total). The
combined extracts were dried over MgSO4, and concentrated.
Distillation (52-53 °C/3.0 Torr) of the residue gave N,N-dimethyl-
3-phenylpropylamine (2a) in 81% yield (3.70 g).
13C NMR (150 MHz, CDCl3) δ 29.5, 33.7, 45.5, 59.3, 125.7, 128.3,
128.4, 142.3.
Acknowledgment. This work was partially supported by a
Grant-in Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. S.H. is grateful
to the Japan Society for the Promotion of Science for Young
Scientists for a Research Fellowship.
N,N-Dimethyl-3-phenylpropylamine (2a):24 IR (neat) ν 3062,
1
3026, 2942, 2764, 1603, 1496, 1454, 1265, 1030 cm-1; H NMR
Supporting Information Available: Detailed experimental
procedures, characterization data of both the substrates and the
products. This material is available free of charge via the Internet
at http://pubs.acs.org.
(600 MHz, CDCl3) δ 1.81 (tt, J ) 7.8, 7.5 Hz, 2H), 2.24 (s, 6H),
2.31 (t, J ) 7.5 Hz, 2H), 2.65 (t, J ) 7.8 Hz, 2H), 7.19 (t, J ) 7.6
Hz, 1H), 7.20 (d, J ) 7.1 Hz, 2H), 7.29 (dd, J ) 7.6, 7.1 Hz, 2H);
(24) Bhattacharyya, S. J. Org. Chem. 1995, 60, 4928. See also ref 10b.
JA9055307
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15040 J. AM. CHEM. SOC. VOL. 131, NO. 41, 2009