Ruthenium-catalyzed hydrocarbamoylative cyclization of 1,6-diynes with formamides

Article abstract of DOI:10.1246/cl.160961

The ruthenium-catalyzed hydrocarbamoylative cyclization of 1,6-diynes with formamides afforded exocyclic-diene-type α,β,γ,δ-unsaturated amides with 100% stereoselectivity. A plausible mechanism involving ruthenium hydride species is proposed to explain the experimental results. Some control experiments, performed using DMF-d₇ and/or D₂O, corroborate the proposed mechanism.

Full text of DOI:10.1246/cl.160961

Advance Publication Cover Page
Ruthenium-Catalyzed Hydrocarbamoylative Cyclization of 1,6-Diynes with Formamides
Shota Mori, Masatoshi Shibuya, and Yoshihiko Yamamoto*
Advance Publication on the web November 26, 2016
doi:10.1246/cl.160961
© 2016 The Chemical Society of Japan
Advance Publication is a service for online publication of manuscripts prior to releasing fully edited, printed versions. Entire
manuscripts and a portion of the graphical abstract can be released on the web as soon as the submission is accepted. Note that the
Chemical Society of Japan bears no responsibility for issues resulting from the use of information taken from unedited, Advance
Publication manuscripts.

1
Ruthenium-Catalyzed Hydrocarbamoylative Cyclization of 1,6-Diynes with Formamides
Shota Mori, 1 Masatoshi Shibuya, 1 and Yoshihiko Yamamoto*1
1Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa, Nagoya 464-8601
E-mail: yamamoto-yoshi@ps.nagoya-u.ac.jp
with high atom efficiency (Scheme 1b).7b However, the
drawbacks of this method is that it requires moisture-sensitive
isocyanates and stereoselectivity is imperfect owing to the
isomerization of the acrylamide moiety under catalytic
conditions.
During our study on the ruthenium-catalyzed
hydrofunctionalization/cyclization of ,-diynes,8 we
discovered that in the presence of a ruthenium catalyst,
hydrocarbamoylative cyclization of 1,6-diynes proceeded in
DMF to afford similar cyclic ,-unsaturated amides
(Scheme 1c). The advantage of this method is that the
carbamoyl group can be directly introduced from readily
available and bench-top stable formamides with the formal
cleavage of a formyl C–H bond, and the exocyclic diene
moiety is constructed with complete stereoselectivity. Herein,
we report the preliminary results of our study on the
ruthenium-catalyzed hydrocarbamoylative cyclization of 1,6-
diynes using formamides.
In order to optimize the reaction conditions, the
hydrocarbamoylative cyclization of a representative diyne
substrate (2a) was investigated using DMF (3a) as a solvent
(Scheme 2 and Table 1). In the presence of 10 mol % cationic
ruthenium complex [CpRu(MeCN)3]PF6 (1a, Cp = 5-C5H5),
2a was heated in DMF at 100 °C under Ar. The reaction
completed in 1 h, affording amide 4aa in 57% yield (Table 1,
entry 1). Notably, the stereochemistry of both alkylidene
moieties was completely controlled (vide infra).
The
ruthenium-catalyzed
hydrocarbamoylative
cyclization of 1,6-diynes with formamides afforded exocyclic-
diene-type ,,,-unsaturated amides with complete
stereoselectivity. A plausible mechanism involving ruthenium
hydride species is proposed to explain experimental results.
Some control experiments performed using DMF-d7 and/or
D2O corroborate the proposed mechanism.
Acrylamide is an important raw material that is used for
the industrial production of polyacrylamides.1 Although the
parent acrylamide is manufactured by the catalytic hydration
of acrylonitrile at an industrial scale,2 an efficient and
selective access to multi-substituted acrylamides has been
sought in laboratory settings.3 One of the most atom-efficient
approaches is the hydrocarbamoylation of substituted alkynes.
To this aim, the stoichiometric and catalytic carbonylative
coupling of alkynes with amines has been developed,
although such coupling requires harmful carbon monoxide.3,4
To avoid the use of carbon monoxide, the transition-metal-
catalyzed hydrocarbamoylation of alkynes with formamides
has been recently developed to produce cyclic and acyclic
,-unsaturated amides (Scheme 1a).5 Despite these
breakthroughs, a relevant hydrocarbamoylative coupling of
formamides with two molecules of alkynes that yields
,-unsaturated amides has not yet been realized.
R1
R2
O
(a)
Rh, Ni, Pd cat.
R1
R2
+
H
+
NR3
2
Ph
H
CONR3
2
cat. (x mol %)
Ph
CONMe2
H
CONHR2
R1
R1
(b)
O
O
O
C
N
X
Y
Ni cat.
Ph
DMF (3a, 1 mL), T, t
H
X
Y
2a (0.3 mmol)
Ph
R2
4aa
R
X
Ar
(c) Ths work
X
Me
Me
X
R
O
TsN
Ar
Ru cat.
R
CONR2
H
5a X = O, R = Ph
+
X
R
H
NR2
5b X = NTs, R = Me
6
Ar
Ar
Scheme 2 Hydrocarbamoylative cyclization of diyne 2a in DMF.
Scheme 1 (a) Hydrocarbamoylation of alkynes with formamides,
(b) cyclocoupling of ,-enynes with isocyanates, and (c)
hydrocarbamoylative cyclization of 1,6-diynes (This work).
When more electron-rich catalyst [Cp*Ru(MeCN)3]PF6
(1b, Cp* = 5-Me5C5) was used, the reaction completed in a
shorter reaction time (20 min) and the yield of 4aa increased
to 72% (entry 2). On the other hand, the neutral catalyst
Further, ,-unsaturated amides are important
synthetic targets as they are found in various natural products,
showing significant biological activities.6 Nevertheless, the
atom-efficient synthesis of ,-unsaturated amides is still
scarce.7 Notably, D’Souza and Louie reported that the nickel-
catalyzed cyclocoupling of ,-enynes with isocyanates
produced exocyclic-diene-type ,-unsaturated amides
Cp*RuCl(cod) (1c, cod
= 1,5-cyclooctadiene) proved
ineffective owing to the yield of an undesired dimerization
product 5a (entry 3). When the reaction was repeated at a
lower temperature of 70 °C, 4aa was obtained in a
comparable yield, albeit with a longer reaction time of 2 h
(entry 4). However, a further reduction in the reaction

2
temperature (50 °C) diminished the yield of 4aa (entry 5). At
a decreased loading of 1b (5 mol %), the reaction did not
complete even after stirring at 120 °C for 12 h (entry 6).
Therefore, the conditions of entry 2 are optimal. In striking
contrast, diyne 6 bearing methyl terminals was treated with 1b
(10 mol %) in DMF at 100 °C for 11 h, affording 5b in 31%
yield. Therefore, terminal aryl groups are essential for this
reaction. The use of n-propyl formate istead of DMF did not
produce the corresponding hydrocarboxylative cyclization
product.
regioselectivity. As a result, amide 4la and 4la’ were formed
in 63% combined yield with a ratio of 4la/4la’ = 2:1. This
result suggests that carbamoylation preferably occurs at the
more electron-rich terminal.
Ar
1b (10 mol %)
Ar
Ar
CONMe2
H
O
O
DMF (3a, 1 mL)
2
100 °C
4
Ar
R1, R3 = H, R = Me, 20 min: 4ba 71%
R1, R3 = H, R = Cl, 20 min: 4ca 79%
R1, R3 = H, R = F, 20 min: 4da 86%
R1, R3 = H, R = CO2Et, 6.5 h: 4ea 64%
R1, R3 = H, R = Ac, 6.5 h: 4fa 64%
R1, R3 = H, R = CHO, 20 h: 4ga 15% (2g 6%)
R1, R3 = H, R2 = OMe, 20 h: 4ha 27% (2h 16%)
R1–R2 = OCH2O, R3 = H, 5.5 h: 4ia 47%
R1, R3 = OMe, R2 = H, 3 h: 4ja 74%
R1, R2, R3 = OMe, 40 min: 4ka 73%
Table 1. Optimization of reaction conditions using DMF solvent.
a
R1
Entry
Cat. (x)
1a (10)
1b (10)
1c (10)
1b (10)
1b (10)
1b (5)
T (°C)
100
100
100
70
t (h)
1
Yield (%)
57 (59)
72 (76)
1
2
3
4
5
6
R2
Ar =
1/3
6
R3
b
—
2
72 (76)
c
50
20
(42)
Ar1
Ar1
c
120
12
(48)
aIsolated yields. The yields determined by the NMR analysis of crude
Ar1 = p-MeOC6H4
Ar2 = p-FC6H4
CONMe2
H
H
+
O
O
b
materials are indicated in parentheses. Dimer 5a was obtained in 21%
CONMe2
c
yield (NMR) along with unreacted 2a (28% NMR). Unreacted 2a was
20 min, 63%, 2:1
Ar2
Ar2
4la
4la'
observed for entries 5 (8% NMR) and 6 (4% NMR).
Figure 1 Reactions of diynes 2b–l in DMF.
The scope of diyne substrates in terms of terminal aryl
groups was investigated under optimized conditions (Fig. 1).
The reaction of diyne 2b with p-tolyl terminals afforded a
result similar to that obtained with the reaction of 2a.
Similarly, diynes 2c and 2d, possessing p-chlorophenyl and p-
fluorophenyl terminals, afforded the corresponding amides
4ca and 4da in higher yields (79% and 86%, respectively). To
investigate electronic influence of the aryl terminals, diyne
substrates possessing electron-withdrawing or electron-
donating substituents on the aryl terminals were subjected to
the reaction. The reaction of p-ethoxycarbonyl and p-acetyl-
substituted diyne 2e and 2f completed in 6.5 h, affording 4ea
and 4fa in 64% yields. In contrast, diyne 2g with p-
formylphenyl terminals gave the corresponding product 4ga
in a low yield (15%) due to side reaction(s).9
When the reaction of diyne 2h with p-methoxyphenyl
terminals was carried out at 100 °C for 20 h, 4ha was
obtained in a low yield (27%) along with the recovered
substrate (16%). Therefore, electron-donating aryl terminals
are detrimental to hydrocarbamoylative cyclization.
Nevertheless, diyne 2i with 1,3-benzodioxol-5-yl terminals
was allowed to react with DMF at 100 °C for 5.5 h, affording
amide 4ia in a moderate yield (47%). Moreover, diynes 2j and
2k with 3,5-dimethoxyphenyl or 3,4,5-trimethoxyphenyl
terminal groups were converted to the corresponding amides
4ja and 4ka, respectively, over a shorter period, and their
yields were higher (74% and 73%, respectively). In these
cases, polyoxygenated aryl terminals are presumably less
electron-donating, because the resonance of the ether-oxygen
lone pairs with the -system of the terminal phenyl rings is
inefficient owing to the restricted conformations. Then, the
reaction of unsymmetrical diyne 2l, possessing both p-
methoxyphenyl and p-fluorophenyl terminals, was carried out
to investigate the influence of the terminal groups on
Furthermore, the impact of the tether moiety was
investigated as shown in Fig. 2. The reaction of tosylamide-
derived diyne 2m efficiently underwent hydrocarbamoylative
cyclization under optimized conditions to afford amide 4ma
in 75% yield. Because a single crystal with good quality was
obtained, the structure of 4ma was unambiguously confirmed
by X-ray diffraction analysis (Fig. S2). In contrast, the
reaction of malonate-derived diyne 2n was sluggish at 100 °C,
and, thus, the reaction was carried out at a higher temperature
(140 °C). However, the yield of 4na (33%) was much lower
than the yields of 4aa and 4ma. The inefficiency of 2n can be
ascribed to the sterically demanding malonate moiety.
Accordingly, diynes 2o, 2p and 2q possessing less-hindered
tertiary carbon centers in the tethers, were subjected to
hydrocarbamoylative cyclization at 140 °C for 20 h. As a
result, the conversions of these substrates improved, and the
corresponding products 4oa, 4pa and 4qa were obtained in
40–50% yields. Thus, ester, ketone and acetoxy groups were
well tolerated. Although diyne 2r with an all-methylene tether
was completely consumed at 140 °C, an inseparable mixture
of the desired product 4ra and unidentified by-products was
formed. Nevertheless, 4ra was isolated in 43% yield along
with the intact 2r (20%) when the same reaction was carried
out at 100 °C for 20 h. In contrast, no corresponding product
was observed for the reaction of 1,7-diyne 2s. Moreover,
neither
hydrocarbamoylative
cyclization
nor
hydrocarbamoylation occurred from 1,6-enyne 7 or (3-
methoxyprop-1-ynyl)benzene (8). These results show that a
1,6-diyne moiety is imperative for the present
hydrocarbamoylative cyclization.

3
Ph
Ph
Ph
1b (10 mol %)
1b (10 mol %)
Ph
Ph
Ph
Ph
O
CONMe2
H
CONR2
H
X
X
O
+
O
H
NR2
DMF (3a, 1 mL)
H2O (0.3 equiv)
dioxane, 100 °C
3
(3 equiv)
2a
2
100–140 °C
4
4
Ph
Ph
Ph
Ph
Ph
Ph
NR2
N
( )n
MeO2C
MeO2C
CONMe2
H
CONMe2
H
TsN
O
O
O
O
Ph
Ph
Ph
n = 1, 1 h: 4ac 73%
100 °C, 30 min: 4ma 75%
140 °C, 20 h: 4na 33%
R = Me, 6 h: 4aa 65%
R = Et, 6 h: 4ab 45%
n = 2, 2.5 h: 4ad 55%
n = 0, 20 h: 4ae 37%
Ph
R = CO2Et, 140 °C, 20 h: 4oa 50%
R = Ac, 140 °C, 20 h: 4pa 44% (9%)a
R = OAc, 140 °C, 20 h: 4qa 40% (24%)a
R = H, 100 °C, 20 h: 4ra 43% (20%)a
R = Et, 2 h: 4ab 59% (10 equiv 3b
)
R
CONMe2
O
Ph
H
NMe
H
H
O
Ph
CON(Me)allyl
Ph
Ph
H
N
O
O
H
Ph
Ph
3f (10 equiv), 3.5 h
Ph
TsN
MeO
Ph
H
8
4af
Ph
9
48%
7
2s
Figure 3 Reactions of 2a with formamides 3a–f in dioxane.
Figure 2 Reactions of diynes 2m–s and enyne 7 in DMF. aYields
of unreacted 2 were shown in parenthesis.
To gain insights into the reaction mechanism, we carried
out several control experiments. The reaction of diyne 2a with
3 equiv of DMF was carried out in the presence of 1 equiv of
D2O in dioxane at 100 °C for 3 h, affording 4aa-d1 in 55%
yield with a 44% D content at the vinylic position. Therefore,
the vinylic proton is derived from both D2O and DMF. The
reaction of 2a with 3 equiv of DMF-d7 was also carried out in
the presence of 1 equiv of H2O in dioxane at 100 °C for 3 h,
affording 4aa-d7 in 65% yield. In this case, the D labels of the
N-methyl substituents were completely preserved, although
the D content of vinylic proton was only 17%. These results
indicate that the ruthenium hydride species involved in the
catalytic cycle caused H–D exchange, and the vinylic proton
was derived from the formyl proton as well as added H2O.
Ph
In order to reduce the amount of formamides, we
screened several reaction parameters and found that in the
presence of 1b (10 mol %), 2a was heated with DMF (3a, 3
equiv) and H2O (0.3 equiv) in dioxane at 100 °C for 6 h to
afford 4aa in 65% yield. Although the use of THF as a solvent
(70 °C, 8 h) afforded a similar result, other solvents such as
chlorobenzene, N,N-dimethylacetamide, acetonitrile, and 1,2-
dichloroethane proved ineffective. The reaction was sluggish
in the absence of H2O; however, its increased loading resulted
in a negative impact on the yield of 4aa because undesired
hydrative cyclization proceeded.10 The reactions of diyne 2a
with other formamides were investigated under the conditions
referred above (Fig. 3). N,N-Diethylformamide (3b) afforded
the corresponding amide 4ab in a lower yield (45%). The
same reaction was repeated with an increased loading of 3b
(10 equiv) in a shorter reaction time (2 h), affording 4ab in an
improved yield (59%). These results show that relatively
bulky formamide reduced the reaction efficiency. In fact, the
reaction of N-formylpyrrolidine 3c afforded amide 4ac in a
good yield of 73%, whereas the yield of the corresponding
piperidine derivative 4ad was moderate (55%). However, the
reaction was sluggish using much smaller N-formylazetidine
3e and 4ae was obtained in a lower yield (37%). Moreover,
the reaction of diyne 2a with N-allylformamide 3f (10 equiv),
was also examined as a synthetic application. Interestingly,
the expected hydrocarbamoylative cyclization product 4af
underwent exo-selective intramolecular Diels–Alder reaction
(IMDA) to afford tricyclic lactam 9 as a single stereoisomer
in 48% yield. The relative stereochemistry of 9 was elucidated
by NOE measurements (Fig. S1). The density functional
theory calculations suggest that the second IMDA step is a
thermally feasible process, which proceeds with an activation
energy of G‡ = +28.5 kcal/mol and is exergonic by G =
25.4 kcal/mol (Fig. S3).
1b (10 mol %)
Ph
CONMe2
O
O
O
O
O
O
D
44%D
Ph
DMF (3 equiv)
D2O (1 equiv)
2a
2a
2a
Ph
4aa-d1 55%
dioxane, 100 °C, 3 h
Ph
100%D
CON(CD3
1b (10 mol %)
Ph
Ph
)
2
D
17%D
DMF-d7 (3 equiv)
H2O (1 equiv)
Ph
dioxane, 100 °C, 3 h
4aa-d7 65%
Ph
53%D
CON(CD3
1b (10 mol %)
Ph
Ph
)
2
D
54%D
DMF (1.5 equiv)
DMF-d7 (1.5 equiv)
D2O (1 equiv)
Ph
4aa-d7 59%
dioxane, 100 °C, 3 h
Scheme 3 Control experiments.

4
Furthermore, the same reaction was also repeated with
DMF/DMF-d7 (each 1.5 equiv) in dioxane at 100 °C for 3 h,
affording 4aa-d7 with the D contents of 53% and 54% at the
N-methyl and vinylic protons, respectively. This result
indicates that no KIE was observed (kDMF/kDMF-d7 ≃ 1) and,
thus, the formyl C–H cleavage is not involved in the rate-
determining step. Moreover, N-formylpiperidine (3d) was
treated with 20 mol % 1b in the presence of D2O (1 equiv) in
dioxane at 100 °C for 8 h; however, the incorporation of
deuterium into the formyl proton was negligible. Therefore,
the direct cleavage of the formyl C–H bond via oxidative
addition can be ruled out.
dioxane. Under these conditions, we could obtain various
amides from the combination of 1,6-diynes and formamides.
As an synthetic application, tandem hydrocarbamoylative
cyclization/intramolecular
Diels–Alder
reaction
was
achieaved to obtain a fused lactam as a single stereoisomer.
This research is partially supported by the Platform
Project for Supporting in Drug Discovery and Life Science
Research from AMED, and JSPS KAKENHI Grand Number
JP 16KT0051. We also thank Profs. T. Fukuyama & S.
Yokoshima (Nagoya Univ.) and Mr. H. Sato (Rigaku) for X-
ray analysis.
Tsuji and co-workers previously proposed that the
hydrocarbamoylation of internal alkynes was catalyzed by
Supporting
Information
is
available
on
hydropalladium
species,
which
undergo
initial
http://dx.doi.org/10.1246/cl.******.
hydropalladation of an internal alkyne.5c Similarly, it can be
envisaged that ruthenium hydride species [Cp*RuH]
undergoes sequential hydroruthenation of a diyne.11 However,
this mechanism is less likely to occur because the present
reaction is strictly limited to 1,6-diynes with aryl terminals
(Fig. 2). Thus, the involvement of ruthenacycle intermediates
was inferred from the necessity of a 1,6-diyne moiety. On the
basis of the above results, a plausible mechanism is proposed
as outlined in Scheme 4. The initial oxidative cyclization of
diyne 2 with [Cp*RuH(DMF)] generates ruthenacycle 10,12
which undergoes subsequent reductive elimination to generate
dienylruthenium intermediate 11. Next, the insertion of the
ligated DMF into the Csp2–Ru bond produces
alkoxyruthenium intermediate 12, which finally undergoes -
H elimination to afford amide 4 with the concomitant
restoration of [Cp*RuH].13 Because this pathway involves
ruthenium hydride species, the observed deuterium
incorporation from D2O can be explained by the H–D
exchange of the hydride ligands.
References and Notes
1
2
3
4
a) T. Siyam, Des. Monomers Polym. 2001, 4, 107; b) M. J.
Caulfield, G. G. Qiao, D. H. Solomon, Chem. Rev. 2002, 102, 3067.
H. Yamada, M. Kobayashi, Biosci. Biotech. Biochem. 1996, 60,
1391.
J. H. Park, S. Y. Kim, S. M. Kim, Y. K. Chung, Org. Lett. 2007, 9,
2465, and cited references.
a) T. Sugihara, Y. Okada, M. Yamaguchi, M. Nishizawa, Synlett
1999, 768; b) B. E. Ali, J. Tijani, A. M. El-Ghanam, J. Mol. Catal.
A: Chem. 2002, 187, 17; c) B. E. Ali, J. Tijani, Appl. Organomet.
Chem. 2003, 17, 921; d) Y. Li, H. Alper, Z. Yu, Org. Lett. 2006, 8,
5199.
5
6
a) Y. Kobayashi, H. Kamisaki, K. Yanada, R. Yanada, Y.
Takemoto, Tetrahedron Lett. 2005, 46, 7549; b) Y. Nakao, H. Idei,
K. S. Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 5070; c)
T. Fujihara, Y. Katafuchi, T. Iwai, J. Terao, Y. Tsuji, J. Am. Chem.
Soc. 2010, 132, 2094.
a) F. Babudri, V. Fiandanese, F. Naso, A. Punzi, Tetrahedron Lett.
1994, 35, 2067, and cited references; b) K. L. Erickson, J. A.
Beutler, J. H. Cardellina II, M. R. Boyd, J. Org. Chem. 1997, 62,
8188; c) J. Tanaka, T. Higa, Tetrahedron Lett. 1996, 37, 5535; d) R.
Jansen, B. Kunze, H. Reichenbach, G. Höfle, Eur. J. Org. Chem.
2000, 913; e) Y. Feng, J. Liu, Y. P. Carrasco, J. B. MacMillan, J. K.
De Brabander, J. Am. Chem. Soc. 2016, 138, 7130, and cited
references.
Ar
Cp*RuH(DMF)
Ar
Ar
DMF
X
X
RuCp*
7
Recent examples, see: a) C. Wang, J. Lu, G. Mao, Z. Xi, J. Org.
Chem. 2005, 70, 5150; b) B. R. D’Souza, J. Louie, Org. Lett. 2009,
11, 4168; c) T. H. Babu, S. Pawar, D. Muralidharan, P. T. Perumal,
Synlett 2010, 2125; d) X.-W. Wang, P. Li, H. Xiao, S.-Z. Zhu, G.
Zhao, Tetrahedron 2011, 67, 7618; e) R. Ding, Y. Li, C. Tao, B.
Cheng, H. Zhai, Org. Lett. 2015, 17, 3994.
oxidative
H
2
cyclization
Ar
10
NMe2
Ar
O
H
RuCp*
X
8
9
a) Y. Yamamoto, K. Fukatsu, H. Nishiyama, Chem. Commun. 2012,
48, 7985; b) Y. Yamamoto, S. Mori, M. Shibuya, Chem. Eur. J.
2013, 19, 12034; c) Y. Yamamoto, S. Mori, M. Shibuya, Chem.
Eur. J. 2015, 21, 9093.
It is assumed that the formyl group on the aryl terminals underwent
cycloaddition with the diyne moiety, because polymeric by-
products were formed. The rhodium-catalyzed cycloaddition of
diynes with aldehydes was reported, see: Y. Otake, R. Tanaka, K.
Tanaka, Eur. J. Org. Chem. 2009, 2737.
H
reductive
insertion
elimination
Ar
11
Ar
Ar
Ar
NMe2
NMe2
– Cp*Ru
H
X
X
H
O
O

-H
RuCp*
10
a) B. M. Trost, M. T. Rudd, J. Am. Chem. Soc. 2003, 125, 11516;
b) Y. Yamamoto, K. Yamashita, H. Nishiyama, Chem. Commun.
2011, 47, 1556.
elimination
Ar
4
12
Scheme 4 Proposed mechanism for hydrocarbamoylative
11
12
J. Le Paih, D. C. Rodríguez, S. Dérien, P. H. Dixneuf, Synlett 2000,
95.
Oxidative cyclization of rhodium hydride species with a 1,6-diyne
was proposed, see: H.-Y. Jang, M. J. Krische, J. Am. Chem. Soc.
2004, 126, 7875.
cyclization.
In conclusion, we discovered that the ruthenium-
catalyzed hydrocarbamoylative cyclization of 1,6-diynes
proceeded in DMF to afford exocyclic-diene-type -
unsaturated amides with complete stereoselectivity.
Furthermore, we also found that the same reaction proceeded
with 3–10 equiv of formamides by adding H2O (0.3 equiv) in
13
Because oxidative cyclization occurs at room temperature (Y.
Yamamoto, T. Arakawa, R. Ogawa, K. Itoh, J. Am. Chem. Soc.
2003, 125, 12143), either DMF insertion or -H elimination is
assumed to be the rate determining step.