Hydroamidation of alkenes with N-substituted formamides

Article abstract of DOI:10.1071/CH06010

Hydroamidation of olefins with N-substituted formamides is performed with dodecacarbonyltriruthenium (Ru₃(CO)₁₂) at 180°C under N₂ or CO atmosphere in toluene and in a series of ionic liquids. Yields of 99% with 94?97% exo selectivity are found in the addition of N-methylformamide to 2-norbornene under CO both in toluene and in the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [bmim][NTf₂]. The presence of CO or a phosphine is necessary for significant reaction to occur, with CO more effective than triphenylphosphine in all ionic liquids investigated. Reasonable yields are achieved at low pressures, in contrast to most reported hydroamidations. Conversion, exo-selectivity, and selectivity fall with increasing steric bulk of the N-formamide substituent, and disubstituted formamides are inactive. Of the terminal alkenes investigated, only styrene can be hydroamidated. CSIRO 2006.

Full text of DOI:10.1071/CH06010

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2006, 59, 218–224
www.publish.csiro.au/journals/ajc
Hydroamidation of Alkenes with N-Substituted Formamides
Dilip Chandra Deb Nath,A,B Christopher M. Fellows,A,C Toshiaki Kobayashi,B
and Teruyuki HayashiB
A Division of Chemistry, School of Biological, Biomedical, and Molecular Sciences, University of New England,
Armadale NSW 2351, Australia.
B Green Chemistry, Research Institute for Innovation in Sustainable Chemistry, National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
C Corresponding author. Email: cfellows@une.edu.au
Hydroamidation of olefins with N-substituted formamides is performed with dodecacarbonyltriruthenium
(Ru3(CO)12) at 180◦C under N2 or CO atmosphere in toluene and in a series of ionic liquids. Yields of 99% with
94–97% exo selectivity are found in the addition of N-methylformamide to 2-norbornene under CO both in toluene
and in the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [bmim][NTf2].Thepresence
ofCOoraphosphineisnecessaryforsignificantreactiontooccur, withCOmoreeffectivethantriphenylphosphinein
all ionic liquids investigated. Reasonable yields are achieved at low pressures, in contrast to most reported hydroami-
dations. Conversion, exo-selectivity, and selectivity fall with increasing steric bulk of the N-formamide substituent,
and disubstituted formamides are inactive. Of the terminal alkenes investigated, only styrene can be hydroamidated.
Manuscript received: 23 December 2005.
Final version: 15 February 2006.
Introduction
(benzyl-, methyl-, and 1-octyl-) to both terminal (hex-1-ene)
and internal alkenes (cyclohexene and cyclopentene) at 180–
200◦C under 20–40 kg cm−2 pressure of CO.[27] Yields of
the desired hydroamidation product were between 24 and
90%, with the internal alkenes giving a better yield than
hex-1-ene. The linear rather than the branched adduct was
preferentially formed by a factor of about 1.5:1. Kondo and
coworkers then investigated a modified catalytic system for
hydroamidation using phosphines combined with Ru3(CO)12
and with several other ruthenium complexes, notably the
trinuclear ruthenium carbonyl anion [PPN]Ru3H(CO)11
(PPN = bis(triphenylphosphine)iminium) for reactions at
170◦C under argon for 15 h.[32] The catalytic system gave
the desired addition of formanilide to 2-norbornene using
the additive tricyclohexylphosphine in combination with
[PPN]Ru3H(CO)11 (100% conversion of formanilide, 97%
addition product, 79% endo) and Ru3(CO)12 (26% conver-
sion of formanilide, 69% addition product, 84% endo). All
other combinations of ruthenium complexes and phosphines
investigated gave less than 30% conversion of formanilide to
the desired addition product.
The synthesis of amide-, amine-, and ketone-containing
cyclic and non-cyclic compounds with new carbon–carbon
bond formation by intermolecular and intramolecular addi-
tion is an attractive field of research in organic synthesis.
A wide range of N- and O-containing cyclic compounds
show biological activity and/or are potential intermediates for
medicinal and agricultural chemicals.[1] In recent years, ionic
liquids have been identified as new reaction media for a wide
variety of organic reactions to replace traditional solvents.[2]
The properties of ionic liquids — low flammability, non-
volatility, and stability at high temperature — reduce their
environmental impact and are valuable for organic syntheses
under conditions such as high temperature and pressure.[3]
In many cases the use of ionic liquids has been found to
enhance the yields and selectivities of reactions, typically by
immobilizing cluster catalysts.[4]
Addition reactions give an atom-economic strategy for the
synthesis of ester, ketone, amine, and amide derivative com-
pounds. Several reports have been made of intermolecular
and intramolecular addition reactions to alkenes or alkynes
of formates,[5–14] aldehydes,[15–19] and amines,[20–25] while a
limited number have appeared for the addition of formamides
to alkenes,[26–30] and only one report has appeared on the
addition of formamides to alkynes, for an intermolecular
rhodium-catalyzed hydroamidation.[31]
Chang and coworkers reported a strategy of chelation-
assisted activation of N-(2-pyridyl)formamide and alkenes
with good yields of the desired product (53–76%) in acetoni-
trile at 135◦C using Ru3(CO)12.[26] The conversion was above
95% in all cases after 13 h, and excellent exo-selectivity (99%
or greater) was achieved with bulky trimethylsilyl, 2,4,6-
trimethylcyclohexyl, and t-butyl groups α to the terminal
Kondo et al. reported the suitability of Ru3(CO)12 for the
hydroamidation reaction of N-monosubstituted formamides
© CSIRO 2006
10.1071/CH06010
0004-9425/06/030218

Hydroamidation of Alkenes with N-Substituted Formamides
219
olefin. In N,N-dimethylformamide (DMF) or propan-2-ol,
much lower yields of the addition product were achieved.
This paper reports on the direct addition reaction of
N-substituted formamides to alkenes in toluene and ionic
liquids with high yields under low to atmospheric pressure
of CO using the Ru3(CO)12 catalyst. In previously reported
work, high pressures have almost always been required in
order to effect hydroamidation. This is the first reported
application of ionic liquids as solvents in transition-metal cat-
alyzed hydroamidation. The observed dependence of conver-
sion, yield, and exo/endo selectivity on the alkene substrate
and the formamide N-substituent is discussed.
of N-benzylformamide and 2-norbornene. The active species
was apparently unstable upon loss of CO under the reac-
tion conditions, shown by the deposition of black particles of
ruthenium metal in the autoclave. (This phenomenon was
previously observed in the addition of N-octylformamide
to hex-1-ene under N2 atmosphere at 200◦C for 24 h by
Jun et al., for which the yield was only 16%.[15] Under a
20 kg cm−2 pressure of CO the yield for the same substrates
was increased to 63% and decomposition of the catalyst
was avoided.[15]) Accordingly, the reactions were carried out
under a CO atmosphere in order to stabilize the active species.
Under an atmospheric pressure of CO the rates of additions at
180◦C for 24 h of N-substituted formamides to 2-norbornene
were increased and the maximum yield of 99% along with
94% exo-selectivity was achieved from N-methylformamide
and 2-norbornene (Table 1, entries 4–6). When CO pressure
was increased from 1 atmosphere to 10 kg cm−2, the yield
increased dramatically with constant exo-selectivity. Both
conversion and yield followed the same order under both
low and high CO pressure, depending on the nature of the
substitution of N in the formamide compounds: CH3 (100%
conversion, 99% yield) > PhCH2 (56–100% conversion,
86–96% yield) > Ph (30–68% conversion, 73–85% yield)
(Table 1, entries 7–10). For monosubstituted formamides,
the least-bulky group had the highest activity, whereas for
disubstituted formamides, such as N,N-dibutylformamide
Results and Discussion
Hydroamidation of N-substituted formamides and alkenes
activated by Ru3(CO)12 was initially carried out at 180◦C
under N2 in toluene solution at a range of pressures of CO
for 24 h. The results of hydroamidations of 2-norbornene
with N-substituted formamides (Scheme 1) are shown below
(Table 1).
Under N2 at atmospheric pressure the catalyst was active
and showed considerable selectivity for the addition prod-
ucts in the addition of N-methylformamide, formanilide, and
N-benzylformamide to 2-norbornene (Table 1, entries 1–3).
However, the yields under nitrogen were low, with the max-
imum yield (43%, 93% exo-selectivity) obtained in the case
O
CH2 CH2
Linear
C
NR1R2
exo
CONR1R2
Ru3(CO)12
HCONR1R2
ϩ
ϩ
HCONR1R2
Ru3(CO)12
ϩ
ϩ
R
R
1 ϭ Ph, Me, PhCH2, Bu
2 ϭ H, Me, Bu
O
C
R1 ϭ H
2 ϭ H, Me, PhCH2
R
CH3 CH
NR1R2
endo
Branched
CONR1R2
Scheme 1. Hydroamidation of 2-norbornene.
Scheme 2. Hydroamidation of styrene.
Table 1. Hydroamidation reaction of N-substituted formamide
and 2-norbornene with Ru3(CO)12 catalytic systemA
Table 2. Hydroamidation reaction of formamides and styrene
with Ru3(CO)12 catalytic systemA
Run Amide
PCO
[kg cm−2
Conv.B YieldB exo/
Conv.B YieldB Linear/
[%]
]
[%]
[%]
endoB
Run Amide
PCO
[kg cm−2
]
[%] branchedB
1
2
3
4
5
6
7
8
N-Methylformamide
Formanilide
0
0
0
1
1
38
30
50
100
30
56
100
68
100
2
32
6
93/7
94/6
93/7
94/6
94/6
93/7
94/6
94/6
93/7
—
1
2
3
4
5
6
7
8
9
N-Methylformamide
N-Methylformamide
Formanilide
N-Benzylformamide
Formamide
Formanilide
N-Methylformamide
N-Benzylformamide
Formamide
0
1
1
1
1
10
10
10
10
10
10
0
32
15
58
0
65
91
54
100
2
0
22
12
48
0
59
83
49
91
0
—
N-Benzylformamide
N-Methylformamide
Formanilide
N-Benzylformamide
N-Methylformamide
Formanilide
N-Benzylformamide
Formamide
N-Methylformanilide
N,N-Dibutylformamide
43
99
22
48
99
58
96
0
90/10
85/17
86/14
—
97/3
90/10
89/11
79/21
—
1
10
10
10
10
10
10
9
10
11
12
3
2
0
0
—
—
10 N-Methylformanilide
11 N,N-Dibutylformamide
3
0
—
A Reaction conditions: 1.6 mmol amide, 4.8 mmol 2-norbornene,
0.023 mmol Ru3(CO)12, 1 mL toluene, 24 h reaction time, 180◦C.
B Calculated based on formamides by GC with internal standard
(cyclododecane).
A Reaction conditions: 1.6 mmol amide, 4.8 mmol styrene, 0.023 mmol
Ru3(CO)12, 1 mL toluene, 24 h reaction time, 180◦C.
B Calculated based on formamides by GC with internal standard
(cyclododecane).

220
D. C. D. Nath et al.
and N-methylformanilide as well as unsubstituted for-
mamides, hydroamidation did not occur (Table 1, entries 11
and 12). Kondo and coworkers have previously reported no
reaction of formamide or DMF with this catalyst, which they
attributed to low solubility of these species in alkenes.[27]
The results of hydroamidations of styrene with formamide
and N-substituted formamides (Scheme 2) are shown below
(Table 2).
In the absence of CO, no addition of N-methylformamide
and styrene was observed (Table 2, entry 1). At one atmo-
sphere pressure of CO the catalyst showed activity, irrespec-
tive of the N-formamide substituent (Table 2, entries 2–4),
along with a major product arising from anti-Markovnikov
addition. The ratio of anti-Markovnikov to Markovnikov
addition products was about 9:1, and was highest for the
bulkiest N-substituents. A tendency towards a high percent-
age of anti-Markovnikov addition in styrene with pyridyl
formamide has previously been reported by Chang and
coworkers.[5,26]
When the pressure of CO increased from one atmosphere
to 10 kg cm−2, the amount of formamide reacted, and the
yield of reacted formamide converted into addition prod-
uct, both dramatically increased without significant changes
in exo-selectivity. A similar order of activity to that seen
for 2-norbornene was observed, depending on the nature
of the N-formamide substituent: CH3 (32–91% conversion,
69–91% selectivity) > Ph (15–65% conversion, 80–91%
selectivity) > PhCH2 (58–54% conversion, 83–91% selectiv-
ity). The dependence of yield on substituent bulk was much
less pronounced than observed for the bulky 2-norbornene
substrate. The other significant difference between the two
alkenes is the high effectiveness of the catalyst in the addition
of simple formamide to styrene, at 10 kg cm−2 CO pres-
sure, in contrast to the absence of adduct formation between
2-norbornene and formamide under identical conditions, and
at 1 kg cm−2 pressure.
A range of other alkenes were also examined under one
atmosphere of CO at 180◦C for 24 h with the highly reac-
tiveN-methylformamide:thesewerecyclohexene, hex-1-ene,
dodec-1-ene, 3,3-dimethylbut-1-ene, and vinyltrimethyl-
silane.Ayieldof16%wasobtainedinthecaseofcyclohexene
and no reaction was observed for the terminal alkenes.This is
consistent with the previous findings of Chang and cowork-
ers, who could successfully carry out hydroamidation of
terminal alkenes only with chelating formamides.[26] Kondo
and coworkers, on the other hand, could readily hydroamidate
hex-1-ene with N-benzylformamide and N-octylformamide
at 180–200◦C under 20 kg cm−2 ethylene with Ru3(CO)12
by employing a higher alkene/formamide ratio (8/1, cf. 3/1
in this work).[27] At a 2:1 alkene to formamide ratio, Kondo
and coworkers reported that hydroamidation under argon at
170◦C with the catalyst [PPN][Ru3H(CO)11] was successful
only with ethylene and cyclohexene, without listing the other
alkenes attempted.[32]
The ionic liquids 1-butyl-3-methylimidazolium tetrafluo-
roborate [bmim][BF4], 1-hexyl-3-methylimidazolium bis-
(trifluoromethylsulfonyl)imide [hmp][NTf2], and 1-butyl-
3-methylimidazolium
bis(trifluoromethylsulfonyl)imide
[bmim][NTf2] were used as solvents under 20 kg cm−2 pres-
sure of CO at 180◦C in the reaction of formanilide and
2-norbornene (Table 3, entries 1–4). Yields of the adducts
formed from formanilide and 2-norbornene were 86–91%
from conversions of 70–79%, and were accompanied by
91–94% exo-selectivity. N-Methylformamide showed a yield
of 99 and 100% conversion with 97% exo-selectivity in
addition to 2-norbornene in [bmim][NTf2] under 10 or
20 kg cm−2 pressure of CO at 180◦C. Even under an atmos-
pheric pressure of CO, a conversion of 91% to give 93%
N-methylformamide/2-norbornene addition product was
achieved in [bmim][NTf2] without changing exo-selectivity.
On the other hand, no reaction was observed when the
temperature was reduced to 100◦C. In the absence of CO
Table 3. Hydroamidation reaction of N-substituted formamide and 2-norbornene with Ru3(CO)12
catalytic system in ionic liquidA
Run
Amide
Solvent
PCO
[kg cm−2
Conv.B
[%]
YieldB
[%]
exo/
endoB
]
1
2
3
4
5
6
7
8
Formanilide
Formanilide
Formanilide
FormanilideC
N-Methylformamide
N-Methylformamide
N-Methylformamide
N-MethylformamideD
N-Methylformamide
N-Benzylformamide
N-Benzylformamide
N-Methylformanilide
N,N-Dibutylformamide
[bmim][BF4]
[hmp][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
[bmim][NTf2]
20
20
20
20
20
10
1
20
0
0
70
78
79
24
100
100
91
2
19
7
53
47
45
60
71
72
12
99
99
85
0
10
2
48
0
94/6
93/7
91/9
91/9
97/3
97/3
97/3
—
—
—
94/6
—
—
9
10
11
12
13
20
20
20
0
A Reaction conditions: 1.6 mmol amide, 4.8 mmol 2-norbornene, 0.023 mmol Ru3(CO)12, 1 mL ionic liquid,
24 h reaction time, 180◦C.
B Calculated based on formamides by GC with internal standard (cyclododecane).
C Formanilide/norbornene 1/1.
D At 100◦C.

Hydroamidation of Alkenes with N-Substituted Formamides
221
Table 4. Hydroamidation reaction of formamides and styrene with
Ru3(CO)12 catalytic system in [bmim][NTf2]A
Table 5. Hydroamidation of 2-norbornene with formanilide in the
presence of phosphinesA
Run Formamide
CO
[kg cm−2
Conv.B YieldB
[%]
Linear/
[%] branchedB
Run
Phosphorous ligand
Ionic liquid
Conv.B
[%]
YieldB
[%]
]
1
2
3
4
5
6
7
8
9
10
PCy3
Ph2P(CH2)PPh2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][PF6]
[bmim][NTf2]
[bmim][OTf]
[bmim][Cl]
[bmim][ONf]
[mbp][BF4]
[Oct3MeN][Cl]
11
3
8
5
33
7
5
9
8
5
4
0
5
2
27
4
1
6
5
1
1
2
3
N-Methylformamide
Formamide
N-Benzylformamide
20
10
10
72
100
48
26
84
0
85/15
83/17
—
A Reaction conditions: 1.6 mmol amide, 4.8 mmol styrene, 0.023 mmol
Ru3(CO)12, 1 mL [bmim]Tf2N, 24 h reaction time, 180◦C.
B Conversion and yield were calculated based on formamides by GC
with internal standard (cyclododecane).
PPh3
A Reaction conditions: 1.6 mmol amide, 4.8 mmol 2-norbornene,
0.023 mmol Ru3(CO)12, 0.133 mmol phosphine, 1 mL ionic liquid, 15 h
reaction time, 180◦C.
atmosphere, a 55% yield of the addition product was
obtained from 19% conversion at 180◦C, and black metal-
lic Ru particles were deposited. This result suggests that a
CO atmosphere is necessary to stabilize the active species
for the hydroamidation reaction, even in ionic media.[33]
For reactions attempted with disubstituted formamides,
such as N-methylformanilide and N,N-dibutylformamide in
[bmim][NTf2], no norbornene adduct was found even at
trace levels. Most ionic liquid work was carried out with
[bmim][NTf2] because it had the lowest viscosity of the ionic
liquids readily available.
The hydroamidation of styrene in [bmim][NTf2] was also
attempted (Table 4). Formamide was added to styrene to
give 84% overall yield of the addition products, with a
4.9:1 ratio of the linear anti-Markovnikov product to the
branched Markovnikov product, whereas for the more substi-
tuted amides, N-methylformamide gave much less addition
product and N-benzylformamide gave no addition product.
Note that the majority of reactions in ionic liquids were car-
riedoutatgreaterCOpressuresthanreactionswithequivalent
substrates in toluene. At equivalent CO pressures, reactions
carried out in ionic liquids gave lower conversion of for-
mamides, a lower proportion of conversion to the desired
addition products, but higher exo-selectivity. This may possi-
bly be attributed to a reduced rate of diffusion of the reactants
to the active sites.
The catalytic activity of Ru3(CO)12 in combination with
phosphines as ligands was next examined using a series of
ionic liquids at 180◦C for 15 h under an N2 atmosphere
(Table 5).
In [bmim][BF4], phosphines were not suitable as ligands
and conversions were no more than 11%, with 0 to 63% selec-
tivity for the desired adduct (Table 5, entries 1–4). This is in
contrast to the fact that the same catalytic system in conjunc-
tion with tricylcohexylphosphine gives 48% overall yield in
the reaction of formanilide and 2-norbornene in toluene as
solvent.[15] The bulkiest phosphine, Ph2P(CH2)PPH2, gave
none of the desired adduct.
B By GC.
nonafluorobutanesulfonate [bmim][NfO], and 1-butyl-3-
methylimidazolium trifluoromethanesulfonate [bmim][TfO]
were screened (Table 5, entries 4–10). In this series only
[bmim][NTf2] showed a significant yield of addition product,
with a conversion of 33% comprising 82% addition product.
These results suggest that the bulky phosphine ligands steri-
cally hinder the active site of the catalyst. It is significant that
this effect is marked in the ionic liquids, which are highly
viscous, and is least for [bmim][NTf2], which is one of the
less-viscous ionic liquids.[8,34] The incorporation of the phos-
phine ligand, while reducing conversion, did not remove the
desired activity except in the case of Ph2P(CH2)PPH2. In all
other cases the proportion of the reacted formanilide con-
verted into the addition products was at least as great as that
obtained under N2 in toluene (Table 1, entry 2).
In the absence of both Ph3P and CO (Table 3, entry 10),
only a trace amount of the addition product was seen using
ionic liquid as solvent. Thus, both phosphine ligands and CO
stabilizetheactivespecies, aspreviouslyreported, butinionic
liquids a relatively low pressure of CO is more effective than
0.133 M phosphines.
Several observations requiring further elaboration have
been made in the course of this study. For monosubstituted
formamides, the conversion and the selectivity for the desired
product both decrease with increasing bulk of the substituent.
No addition reactions on disubstituted formamides were
observed, and addition to simple formamide was observed
only for styrene. Variations in the formamide had a greater
impact on yield and conversion for 2-norbornene than for
cyclohexene.
Hydroamidation could only be carried out with
2-norbornene, cyclohexene, and styrene, while no addition
products were observed in a series of other terminal alkenes.
Two slightly different schemes for hydroamidation have
been proposed by Chang and coworkers[26] and by Kondo
and coworkers,[32] differing only in whether insertion of an
alkene into a Ru–H bond occurs before or after binding of
the formamide to ruthenium (Scheme 3).
With Ph3P as a ligand, a series of ionic liquids, 1-butyl-
3-methylimidazolium hexafluorophosphate [bmim][PF6],
[bmim][BF4],
[bmim][Cl], 3-methyl-N-butylpyridinium tetrafluoroborate
[mbp][BF4], methyl trioctylammonium chloride
[Oct3MeN][Cl], [bmim][NTf2], 1-butyl-3-methylimidazolium
1-butyl-3-methylimidazolium
chloride
In these mechanisms, the substituents at the formamide
nitrogen remain distant from the active site, so it is not clear

222
D. C. D. Nath et al.
O
(a)
why there should be the strong dependence on the degree
of substitution at nitrogen seen in this work. Is it possi-
ble that there is a more significant interaction between Ru
and the amide nitrogen than has previously been suggested?
The mechanism of hydroamination of alkynes by Ru3(CO)12
apparently involves the intermediate formation of an M–H
bond from an N–H bond, rather than a C(O)–H bond.[24,35]
As both kinds of bonds are present in the monosubstituted
amides, the possibility that insertion into the N–H bond may
occur is a possibility.
It has been observed in many systems that insertion of an
alkene into metal–hydride bonds is rapid and reversible, and
hence this is unlikely to be the rate controlling step in the
reaction.[36] Variations in initial coordination of alkenes to
Ru, however, maybesignificant, andthiswillbefavouredbya
lack of electron-withdrawing substituents on the alkene, lack
of steric hindrance impeding access to the bonding π-orbital,
and a symmetrical distribution of charge in this π-orbital, as
seen in the substrates that were found to react effectively with
the bulky catalyst of Kondo et al.[32]
O
H
N
H
R
N
H
R
RЈ
[Ru]
H
O
O
H
[Ru]
[Ru]
N
H
R
N
H
R
RЈ
H
RЈ
RЈ
O
(b)
N
H
R
RЈ
[Ru]
H
H
The following mechanism of hydroamidation is proposed
as a possible explanation for the absence of any hydroami-
dation adducts from N,N-disubstituted formamides and for
the significant effect of the magnitude of the R group on the
yield of the reaction (Scheme 4).
H
O
[Ru]
(1) Insertion of Ru into the N–H bond of a monosubsti-
tuted or unsubstituted formamide, with loss of carbon
monoxide ligands. Several syntheses showed a high con-
version of monosubstituted formamide substrate into
products other than the desired one, which is why this
step is suggested to precede the second. Such an inser-
tion has been previously suggested for the addition of
aryl formamides to alkynes.[35] Hydroamidation could
be carried out only at high CO pressures with unsubsti-
tuted formamide. At low carbon monoxide pressures, an
adjoining Ru in Ru3(CO)12 could conceivably insert into
[Ru]
N
H
R
RЈ
RЈ
H
H
O
H
N
H
R
Scheme3. (a)MechanismofChangandcoworkers.[26] (b)Mechanism
of Kondo and coworkers.[32]
O
O
N
H
R
R
Ј
H
N
H
R
H
[Ru]
O
H
O
N
R
[Ru]
H
R
Ј
[Ru]
N
R
H
O
C
H
H
R
Ј
RЈ
H
[Ru]
H
N
O
R
R
Ј
[Ru]
N
R
H
H
O
[Ru]
N
R
H
R
Ј
Scheme 4. Possible mechanism.

Hydroamidation of Alkenes with N-Substituted Formamides
223
the second N–H bond, giving a bridged structure unsuit-
able for further reaction. However, the dramatic change
in formamide behaviour between 1 and 10 kg cm−2 CO
(Table 2, entries 5 and 9) requires further investigation.
(2) Complexation of Ru with the alkene. The stability of
alkene complexes with Ru3(CO)12 has been investigated
by Leadbeater with ethene and alkenes bearing electron-
withdrawing groups giving more stable complexes and
those with electron-donating substituents giving less
stable complexes: styrene complexes could be observed
only below −20◦C.[37] This suggests that variations in
the suitability of alkene substrates for complexation are
insufficient to explain the trends in yield.
catalyst. The way excess CO could do this is clear, but it is
not apparent how a phosphine ligand which is never dissoci-
ated from Ru could effect this. It is possible that a mechanism
involving more than one Ru centre is necessary, and also that
there is not a straightforward single-step transition from the
Ru–N–C to the Ru–N–H species.
Conclusions
A series of hydroamidation reactions of alkenes by for-
mamides are carried out using Ru3(CO)12 catalyst in toluene
and in a series of ionic liquids. The key factors in achiev-
ing significant conversion into the desired products appears
to be use of an alkene that is a good ligand for Ru and a
monosubstituted formamide. Yield and conversion fall with
increasing steric bulk of the formamide subsitituent. All
disubstituted formamides are found to be inactive, for which
reason a speculative mechanism involving initial insertion of
Ru into the N–H bond has been proposed. Additional pres-
sure of CO greatly improves conversion and yield, and under
equivalent pressures of CO no significant improvement in
conversion or yield is obtained by using ionic solvents rather
than toluene: the least viscous ionic liquid, [bmim][NTf2]
is most effective as a solvent for the hydroamidation. The
greater viscosity of the ionic liquids in comparison to toluene
is also reflected in an indication of greater exo-selectivity in
addition to norbornene.
(3) Insertion of the alkene into the Ru–H bond. This con-
certed process is unlikely to be rate determining and
requires a planar transition state: steric hindrance around
the Ru centre will suffice to give the high selectivity for
exo/anti-Markovnikov addition.
(4) Insertion of the alkene is suggested to occurs after initial
insertion of Ru into the N–H bond and before further
rearrangement. Insertion will lead to a more crowded
environment around the metal centre, where H will have
been replaced by a bulky group.A bond-forming reaction
between the nucleophilic carbon on Ru and the carbonyl
carbon with concomitant formation of an Ru–H bond
can proceed smoothly through a cyclic Ru–C–N inter-
mediate or transition state arising from insertion of Ru
into the adjacent C–H bond, which results in a relief
of steric hindrance around Ru. This step of the sug-
gested mechanism is susceptible to experimental test
by the use of selectively deuterated formamides, as it
predicts the hydrogen on the nitrogen of the initial for-
mamide should be transferred to the carbonyl carbon
in the adduct. This experimental test has not yet been
carried out. This rearrangement would be expected to
be more rapid for 1,2-disubstituted alkenes, and to pro-
ceed more slowly where there is a larger R group on
the formamide, or where rearrangement is more entrop-
ically unfavourable in terms of rearrangements of other
ligands (e.g., larger phosphines) or giving rise to more
unfavourable solvent–substrate interactions (e.g., with
the ionic liquids). This rearrangement appears to be the
only plausible rate-determining step in this mechanism,
when reported complexation trends are considered.
(5) Finally, the insertion of Ru into the N–H bond can
be reversed to give the hydroamidation product and
regenerate the catalyst. In order to prevent the cata-
lyst from degradation through the formation of larger
and larger ruthenium clusters, it is presumably neces-
sary for all complexation sites not involved directly in
the mechanism above to remain occupied by CO or
phosphine.
Experimental
Materials
The reagents N-methylformamide, styrene, Ru3(CO)12, triphenylphos-
phine, methylenebis(diphenylphosphine), tricylcohexyl phosphine
(all six Aldrich), formanilide, N-methylformanilide (N-formyl-N-
methylaniline), 2-norbornene (bicyclo[2.2.1]hept-2-ene) (all threeTCI),
hex-1-ene (Wako), cyclohexene (Kanto), and N-benzylformamide (Alfa
Aesar) were all used as supplied without further purification. The
ionic liquids [bmim][PF6], [bmim][BF4], [bmim][Cl], [mbp][BF4], and
[Oct3MeN][Cl] (Solvent Innovation) were all used as received, while
[bmim][NTf2], [bmim][NfO], and [bmim][TfO] were synthesized as
reported previously.[38]
Typical Reaction Procedure
For each hydroamidation reaction, the reagents were added in the
sequence N-formamide, alkene, and Ru3(CO)12 under N2 to a stirred
25 mL stainless steel autoclave, followed by addition of toluene or ionic
liquid as solvent. The N2 was exchanged with CO several times at room
temperature, and the vessel was pressurized with additional CO if nec-
essary. The autoclave was then heated in an oil bath at 180◦C for 24 h.
After reaction, the autoclave was cooled and the product was analyzed
by gas/liquid chromatography (GLC) with an internal standard (cyclo-
dodecane) and gas chromatography–mass spectrometry (GC-MS). For
reactions carried out in ionic liquids, the product was extracted in diethyl
ether. The residual ionic liquid was dried under vacuum at 70◦C for 5 h
and reused.
Analytical Procedures
Two problems with this mechanism should be noted.
Firstly, styrene has an anomalously high reactivity for a
weakly complexing substrate that is not 1,2-disubstituted.
Secondly, it is clear that excess CO or phosphine must be
present in order to avoid the irreversible reduction of the
Productswereisolatedbymedium-pressureliquidchromatography(LC)
in a silica gel column with 1/1 hexane/ethyl acetate as eluent, fol-
lowed by recycling preparative high-pressure LC (JAI LC-908-G30),
and then crystallization from diethyl ether and hexane at −20◦C. Fol-
lowing isolation, the products were analyzed on a Shimadzu GC-17A

224
D. C. D. Nath et al.
gas chromatograph equipped with ultra alloy: FFAP (P/N: UAFFAP-
30M-0.25F) and on a Shimadzu QP-5000 GC-MS. 1H and 13C NMR
spectra were recorded on a JEOL JNM-LA500 FT NMR system.
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bridge-H (C7)), 1.43 (1H, dd, J 9.48, 9.13, exo-H (C3)), 1.49–1.54 (2H,
m, endo-H (C5,6)), 1.60 (1H, d, J 11.57, bridge-H (C7)), 1.83–1.87
(1H, m, endo-H (C3)), 1.96 (1H, s, bridge-H (C4)), 2.11 (1H, d, J 5.49,
endo-H (C2)), 2.28 (1H, s, bridge-H (C1)), 2.79 (3H, d, J 4.9, CH3),
5.65 (1H, s, NH). δC (500 MHz, CDCl3, Me4Si), 26.4, 28.7, 29. 9, 34.5,
36.0, 36.6, 41.5, 48.1, 176.6.
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