Combined Experimental and Computational Study on Ruthenium(II)-Catalyzed Reactions of Diynes with Aldehydes and N,N-Dimethylformamide

Article abstract of DOI:10.1021/acs.joc.7b01229

Cycloaddition reactions of 1,6-diynes bearing methyl terminal groups with p-anisaldehyde were conducted using a cationic ruthenium catalyst with a η⁵-pentamethylcyclopentadienyl ligand in THF at room temperature to afford dienyl ketones via ring opening of the initially formed fused pyrans. (Z)-Stereoisomers of dienyl ketones were selectively obtained using the ruthenium catalyst, whereas previously reported rhodium catalysts produced (E)-isomers. These (E)- and (Z)-selectivities are kinetically controlled as the control experiments showed that the E/Z-isomerization of (E)-dienylketone occurs at 70 °C for 10 h to afford an E/Z-ratio of almost 1:1. The origin of this characteristic stereoselectivity for the ruthenium catalyst was attributed to the direct ring opening of the CpRu⁺-coordinated pyran complex intermediates on the basis of theoretical calculations [PCM (THF) M06L/SDD-6-311++G(d,p)//B3LYP/LanL2DZ-6-31G(d)] and control experiments. The (Z)-selectivity increased when the bulkiness of the diyne terminal substituents increased. Notably, the reaction of 1,6-diynes bearing tert-butyl terminal groups with various α,β-unsaturated aldehydes exclusively afforded (Z)-dienyl ketones even at 70 °C when a cationic ruthenium complex with a smaller η⁵-cyclopentadienyl (Cp) ligand was used as the catalyst. The same Cp complex was found to be also efficient for the hydrocarbamoylative cyclization of sterically demanding 1,6-diynes bearing tertiary or quaternary carbon tethers with N,N-dimethylformamide.

Full text of DOI:10.1021/acs.joc.7b01229

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Article
Combined Experimental and Computational Study on Ruthenium(II)-
Catalyzed Reactions of Diynes with Aldehydes and N,N-Dimethylformamide
Yoshihiko Yamamoto, Yuta Okude, Shota Mori, and Masatoshi Shibuya
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01229 • Publication Date (Web): 06 Jul 2017
Downloaded from http://pubs.acs.org on July 7, 2017
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Combined
Experimental
and
Computational
Study
on
Ruthenium(II)-Catalyzed Reactions of Diynes with Aldehydes and
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N,N-Dimethylformamide
Yoshihiko Yamamoto,* Yuta Okude, Shota Mori, and Masatoshi Shibuya
Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences,
Nagoya University, Chikusa, Nagoya 464-8601, Japan
*yamamoto-yoshi@ps.nagoya-u.ac.jp
In memory of Prof. Takao Ikariya.
tBu
tBu
Ru
CpRu
Direct ring opening
tBu
tBu
O
O
X
X
+
RCHO
X
tBu
H
[2+2+2]
(Z)-Selective
Z
R
DFT & Experiments
tBu
R
H
Abstract: Cycloaddition reactions of 1,6-diynes bearing methyl terminal groups with
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p-anisaldehyde were conducted using a cationic ruthenium catalyst with a
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η -pentamethylcyclopentadienyl ligand in THF at room temperature to afford dienyl
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ketones via ring opening of the initially formed fused pyrans. (Z)-Stereoisomers of
dienyl ketones were selectively obtained using the ruthenium catalyst, whereas
previously reported rhodium catalysts produced (E)-isomers. These (E)- and
(
Z)-selectivities are kinetically controlled as the control experiments showed that the
E/Z-isomerization of (E)-dienylketone occurs at 70 °C for 10 h to afford an E/Z ratio of
almost 1:1. The origin of this characteristic stereoselectivity for the ruthenium catalyst
+
was attributed to the direct ring opening of the CpRu -coordinated pyran complex
intermediates on the basis of theoretical calculations [PCM (THF) M06L/SDD–
6-31++G(d,p)//B3LYP/LanL2DZ–6-31G(d)]
and
control
experiments.
The
(
Z)-selectivity increased when the bulkiness of the diyne terminal substituents increased.
Notably, the reaction of 1,6-diynes bearing tert-butyl terminal groups with various
α,β-unsaturated aldehydes exclusively afforded (Z)-dienyl ketones even at 70 °C when
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a cationic ruthenium complex with a smaller η -cyclopentadienyl (Cp) ligand was used
as the catalyst. The same Cp complex was found to be also efficient for the
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hydrocarbamoylative cyclization of sterically demanding 1,6-diynes bearing tertiary or
quaternary carbon tethers with N,N-dimethylformamide.
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Introduction
The transition-metal-catalyzed [2 + 2 + 2] cycloaddition of alkynes has been
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known as a powerful tool for single-step assembly of highly substituted benzenes.
Similarly, the [2 + 2 + 2] cocycloadditions of alkynes with nitriles or isocyanates
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produce valuable nitrogen heterocycles such as pyridines and pyridones. In contrast,
relevant cycloadditions of alkynes with carbonyl compounds have been significantly
less developed owing to the weak coordination ability of carbonyl groups compared to
that of soft nitrogen compounds such as nitriles or isocyanates. For example, Tsuda,
Saegusa, and coworkers pioneered nickel-catalyzed cycloadditions of α,ω-diynes with
3
a
aldehydes, leading to fused pyrans and their ring-opened derivatives. Later, Tekevac
and Louie expanded the scope of this reaction in terms of the carbonyl partner to
3b
ketones using an N-heterocyclic carbene ligand. Although several stoichiometric
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reactions using cobalt and zirconium complexes were also reported, catalytic protocols
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have long been limited to nickel catalysts. Recently, the Shibata and Tanaka laboratories
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have independently developed rhodium-catalyzed methods. In particular, Tanaka and
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coworkers expanded the scope of carbonyl compounds: in addition to simple aldehydes
and ketones, the authors successfully employed dicarbonyl compounds and
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b
acylphosphonates as the cycloaddition partners.
Our group reported
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ruthenium-catalyzed cycloadditions of 1,6-diynes with electron-deficient ketones. In
this previous study, however, only tricarbonyl compounds functioned as the carbonyl
components in the presence of a neutral ruthenium catalyst, Cp*RuCl(cod) (Cp* =
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η -C
5
Me
5
, cod = 1,5-cyclooctadiene).
We recently discovered that hydrocarbamoylative cyclization of 1,6-diynes
bearing phenyl terminal groups with N,N-dimethylformamide (DMF) proceeds in the
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presence of a cationic ruthenium catalyst, [Cp*Ru(MeCN) ]PF (1a) (Scheme 1a). This
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reaction mode is different from those of previous [2 + 2 + 2] cycloaddition reactions of
diynes with aldehydes and ketones because the formyl C–H bond is cleaved. To extend
this work further, we screened formyl compounds such as formate esters and aldehydes,
and found that reaction of diyne 2a with p-anisaldehyde (3a) produces 4aa as a result of
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normal [2 + 2 + 2] cycloaddition/electrocyclic ring opening (Scheme 1b). Although the
yield was good (79%), the stereochemistry of the resultant 1,2-diarylalkene moiety was
not controlled (E/Z = 1:1.1). This lack of stereoselectivity is in striking contrast to those
typically reported for rhodium-catalyzed cycloadditions of similar diynes, bearing alkyl
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terminal groups, with aldehydes. Therefore, we reasoned that the stereoselectivity
might depend on the substrate structure and/or reaction conditions. Herein, we report
the results of our combined experimental and computational study on the
ruthenium-catalyzed reaction of diynes, equipped with alkyl terminal groups, with
aldehydes, in which stereoselectivity differed markedly from that observed in
previously reported rhodium-catalyzed reactions. In addition, hydrocarbamoylative
cyclization of previously challenging 1,6-diyne substrates was revisited using a different
catalyst.
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Scheme 1. Ruthenium-catalyzed reactions of diyne 2a with (a) DMF and (b) aldehyde
(
2a).
Results and Discussion
Initial experimental results and a proposed mechanism for the reaction of
1,6-diynes with aldehydes. As mentioned above, the reaction of 2a with 3a afforded
dienyl ketone 4aa in a good yield but without stereoselectivity. In addition, the reaction
was found to be limited to 1,6-diynes as the 1,7-diyne with phenyl terminal groups and
two malonate moieties in the tether was completely unreactive (Scheme 1b). Thus, we
turned our attention to 1,6-diynes with alkyl terminal groups as substrates. At the outset,
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the reaction of malonate-derived diyne 2b, bearing methyl terminal groups, with 3a was
performed and the stereoselectivity of the obtained product 4ba was compared with that
reported previously (Scheme 2). Tanaka and coworkers reported that the reaction of 2b
with 3a proceeded at room temperature in the presence of 5 mol % [Rh(cod) ]BF and
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2
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H -BINAP ligand to afford (E)-4ba as the major stereoisomer in an excellent yield
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5b
(
Scheme 2b). In contrast, when the same reaction was conducted using 10 mol % 1a
as the catalyst in THF at 70 °C for 15 min, 4ba was produced in 78% yield with the
opposite stereoselectivity (E/Z = 1:8) (Scheme 2a). Furthermore, an improved yield
(88%) and stereoselectivity (E/Z = 1:28) were observed, when the same reaction was
performed at room temperature, albeit for a longer time of 1.5 h. Thus, these results
suggest that the stereoselectivity in the formation of the ring-opened product depends on
both substrate structure (Schemes 1b vs. 2a) and reaction conditions (Schemes 2a vs.
2b).
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Scheme 2. (a) Ruthenium- and (b) rhodium-catalyzed reactions of diyne 2b with
aldehyde 3a, and (c) 6π electrocyclic ring opening of the initially formed bicyclic pyran
5
. X = C(CO Me) , Ar = p-MeOC H . *E/Z ratio for crude products.
2 2 6 4
4
,5,7
As previously reported,
it is believed that the initial product of the [2 + 2 + 2]
cycloaddition of diyne 2b with aldehyde 3a is bicyclic pyran 5, which undergoes
thermal electrocyclic ring opening to produce dienyl ketone 4ba (Scheme 2c).
According to this mechanism, the stereoselectivity in the formation of 4ba is
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determined during the pyran ring-opening step: the stereochemistry of 4ba can be
controlled by the kinetic preference for one of the two rotatory directions of the aryl
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group (torquoselectivity) and/or the thermodynamic stability of (E)- and (Z)-4ba. Thus,
density functional theory (DFT) calculations were performed at the PCM (THF)
M06L/SDD–6-31++G(d,p)//B3LYP/LanL2DZ–6-31G(d) level of theory to inspect the
electrocyclic ring opening of a model pyran (Figure 1). For computational efficiency,
tetrahydrofuran-fused pyran A was selected as the model compound. The starting pyran
A can adapt two conformations: the phenyl substituent can occupy an equatorial
position (eq-A) or axial position (ax-A). The former is slightly (0.7 kcal/mol) less stable
than the latter owing to the steric repulsion between methyl and phenyl substituents.
The transition states (TSs) for the outward and inward rotations were located higher in
energy by 11.8 and 13.5 kcal/mol, respectively, than ax-A. In contrast, the dienyl ketone
(Z)-B was estimated to be 2.2 kcal/mol more stable than (E)-B. Accordingly, the
outward-rotation product (E)-B is kinetically favored with the estimated E/Z ratio of
1
8:1. On the other hand, the inward-rotation product (Z)-B is thermodynamically
favored and the calculated equilibrium E/Z ratio is 1:42. Calculations for the ring
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opening of the real compound 5 also afforded a similar energy profile as shown in
Figure 1.
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Figure 1. Calculated energy surface for the electrocyclic ring opening of a model pyran
A and malonate derivative 5 (X = C(CO Me) , R = OMe) with relative Gibbs free
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energies in THF at 298 K,
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atm [PCM (THF) M06L/SDD–
6-31++G(d,p)//B3LYP/LanL2DZ–6-31G(d)].
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Taking into consideration the above computational data, the results shown in
Scheme 2 can be interpreted as follows: the rhodium-catalyzed reaction proceeds at
room temperature to generate the kinetically more favored (E)-4ba as the major
stereoisomer, while the ruthenium-catalyzed reaction affords the thermodynamically
more favored (Z)-4ba as the major stereoisomer. However, the E/Z ratio (1:28 at rt) for
the ruthenium catalyzed reaction is much higher than that expected according to the
above calculations. The E/Z ratio was lower (1:8) at 70 °C and further lowered after a
longer reaction time for 1 h (Scheme 2a, shown in parentheses). These facts show that
the initially formed product (Z)-4ba is gradually converted into (E)-4ba at 70 °C. To
check thermal E/Z isomerization, 4ba, which was obtained by the
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5a
rhodium/BINAP-catalyzed reaction with an E/Z ratio of 8:1, was heated in THF at
70 °C for 10 h (Scheme 3). As a result, the E/Z ratio of the recovered 4ba decreased to
1:1.3. Therefore, the formation of 4ba from pyran 5 is reversible and the equilibrium
E/Z ratio is 1:1.3 at 70 °C.
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Scheme 3. Synthesis of (E)-4b and its thermal isomerization to (Z)-4b.
Computational study on the ruthenium-catalyzed [2 + 2 + 2] cycloaddition of
a model diyne with benzaldehyde. It has been suggested that ruthenium-catalyzed [2 +
2
+ 2] alkyne cyclotrimerization and the relevant cocycloadditions involving other
unsaturated molecules proceed via the oxidative coupling of alkynes with [Cp’RuCl]
fragments and subsequent [2
+
2] cycloaddition of the resultant
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ruthenacyclopentatrienes with the third reaction component. In order to gain insights
into the (Z)-selectivity observed in the ruthenium catalysis, the reaction of model
ruthenium diyne complex C ligated by benzaldehyde was analyzed by DFT calculations
(Figure 2 and Figure S1 in Supporting Information). The initial oxidative cyclocoupling
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+
of the diyne ligand with the CpRu fragment proceeded with an activation energy of
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12.7 kcal/mol, generating ruthenacyclopentadiene D. Ruthenacycle D underwent facile
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isomerization to ruthenacyclopentatrienes exo-E via TSDE with a small activation
energy of +6.9 kcal/mol. Due to its delocalized structure, exo-E is 13 kcal/mol more
stable than D.
There are two major stereochemical courses available for the subsequent [2 + 2]
cycloaddition. The first is an endo mode, where the aldehyde phenyl substituent is
oriented towards the ruthenacycle moiety, and the other is the exo mode with the
opposite phenyl orientation. The activation energy was found to be 1.9 kcal/mol lower
for the endo transition state (endo-TS ) than for exo-TS . The formation of
EF
EF
ruthenatricycle intermediates with long Ru–Cα distances (2.248 and 2.319 Å,
respectively) was more endergonic for exo-F than for endo-F. Therefore, the initial [2 +
2] cycloaddition step is more feasible for the endo mode than for the exo mode. Notably,
exo/endo-F have distorted three-legged piano-stool geometry with the Cα’–O*
distances of ca. 3.12 Å and therefore, subsequent Cα’–O* bond-forming reductive
4
elimination facilely occurred to produce η -pyran complexes exo/endo-G. The
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activation energy was found to be 1.7 kcal/mol lower for endo-TSFG than for exo-TSFG.
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The formations of endo/exo-G were largely exergonic owing to the stability of η -diene
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complexes. More importantly, the DFT calculations showed that both pyran complexes
can evolve into ring-opened products (E)/(Z)-H with smaller activation energies than
those associated with the ring opening of the corresponding free pyran A (Figure 1).
Notably, upon coordination, the C*–O* bonds were elongated by 0.066 Å for
endo-G/ax-A and 0.068 Å for exo-G/eq-A, thereby facilitating the ring opening step.
Therefore, it can be qualitatively assumed that the kinetically more favored endo
pathway directly delivered the (Z)-dienyl ketone as the kinetic product under the
ruthenium-catalyzed conditions. The most highest energy barrier estimated for the
initial oxidative cyclocoupling process from C is lower than 20 kcal/mol and the
production of the final dienyl ketone complexes H from C is ca. 50 kcal/mol exergonic.
Thus, the overall catalytic process should be feasible at room temperature.
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Figure 2. Calculated energy surface for the reaction of model complex C leading to (E)-
and (Z)-dienyl ketone complexes H with relative Gibbs free energies in THF at 298 K, 1
atm [PCM (THF) M06L/SDD–6-31++G(d,p)//B3LYP/LanL2DZ–6-31G(d), endo-mode,
blue; exo-mode, red].
Scope and limitations of the ruthenium-catalyzed reaction of 1,6-diynes with
aldehydes. In the next step, we investigated the influence of the diyne terminal alkyl
groups. For ease of separation, tosylamide-derived diynes bearing methyl, n-propyl,
isopropyl, and tert-butyl terminal groups were selected as substrates (Scheme 4). The
reaction of diyne 2c bearing methyl substituents with aldehyde 3a was completed within
1
1
h using 10 mol % 1a in THF at room temperature, affording 4ca in 77% yield. The H
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NMR analysis of crude 4ca revealed that the E/Z ratio (1:5) was lower than that for 4ba
(1:28). Therefore, the stereoselectivity depends on the tether groups. The reactions of
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other diyne substrates bearing bulkier terminal substituents required elevated reaction
temperatures, due to sluggish reactions. When the reaction of diyne 2d bearing n-propyl
substituents with aldehyde 3a was conducted at 70 °C for 1 h, 4da was obtained in 86%
yield with an E/Z ratio of 1:3. Further increase in the bulkiness of the diyne terminal
substituents provided a positive effect on the stereoselectivity. Namely the use of diyne
2e bearing isopropyl substituents led to the formation of 4ea in 82% yield with a
significantly improved E/Z ratio of 1:15, even though a longer reaction time of 6 h was
required for the reaction to reach completion. Furthermore, only the (Z)-isomer was
produced when diyne 2f bearing tert-butyl substituents was examined. However, in this
case, the reaction was not complete even after 10 h and 16% of 2f remained unreacted.
In striking contrast, no reaction occurred when diyne 2g bearing trimethylsilyl (TMS)
terminal groups was used as the substrate. The stereochemistry of 4fa was confirmed by
nuclear Overhauser effect (nOe) observed between the tert-butyl group and vinylic
proton on the alkene moiety.
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Scheme 4. Reactions of diynes 2c–g with aldehyde 3a.
The above results imply that dienyl ketone (Z)-4fa, bearing tert-butyl substituents,
was irreversibly produced and the isomerization to give the (E)-isomer was completely
suppressed. To examine this behavior further, DFT calculations were repeated for the
ring opening reaction of model pyran I (Figure 3). Among the two possible conformers,
eq-I was found to be 7.8 kcal/mol less favored than ax-I owing to the severe steric
repulsion between the tert-butyl and phenyl groups. The transition state for the outward
rotation and the product (E)-J were located 1.3 and 4.4 kcal/mol higher than the
transition state for the inward rotation and (Z)-J, respectively. Therefore, the formation
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of the (Z)-isomer is both kinetically and thermodynamically favored. Moreover, the
activation energy of the ring closing of (Z)-J was estimated to be 26.3 kcal/mol. This
value is higher than that calculated for the ring closing of (Z)-B (22.6 kcal/mol).
Accordingly, the E/Z isomerization is effectively suppressed.
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Figure 3. Calculated energy surface for the electrocyclic ring opening of a model pyran
I with relative Gibbs free energies in THF at 298 K, 1 atm [PCM (THF) M06L/SDD–
6-31++G(d,p)//B3LYP/LanL2DZ–6-31G(d)].
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Next, the influence of the tether moiety was investigated using diynes bearing
tert-butyl terminal groups (Scheme 5). Previous experiments showed that the reaction of
bulky diyne 2f was not complete even within 10 h and therefore, we employed a
cationic ruthenium complex bearing a smaller Cp ligand, [CpRu(MeCN) ]PF (1b, Cp =
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3
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η -C
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H
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), as the catalyst. Thus, in the presence of 10 mol % 1b, the reaction of 2f with
3a in THF at 70 °C was complete within 10 h, affording 4fa in 85% yield. Similarly,
ether-tethered diyne 2h underwent cycloaddition with 3a in a shorter reaction time of 5
h, affording 4ha in 85% yield. These new conditions were found to be effective also for
diynes bearing a quaternary carbon center: 4ia and 4ja were obtained in 81% and 80%
yields, respectively, from the reactions of malonate- or acetylacetone-derived diynes 2i
and 2j within 10 h. Moreover, the reaction of malononitrile-derived diyne 2k afforded
4ka in 58% yield, although the reaction did not reach completion even after 20 h.
Accordingly, the formyl group of 3a exclusively reacted in the presence of esters,
ketones, and nitriles under the reaction conditions employing the cationic ruthenium
catalyst (see below). The known unsymmetrical diyne 2l bearing methyl and tert-butyl
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terminal groups was also used as a substrate to investigate regioselectivity. The
reaction of 2l with 3a was sluggish with only 83% conversion of 2l even after heating
for 24 h and a modest yield of 4la (43%). Nevertheless, 4la was obtained as an
exclusive regio- and stereoisomer as confirmed by nOe measurements.
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Scheme 5. Reactions of diynes 2f,h–l with aldehyde 3a.
Finally, the scope of the carbonyl components was investigated for the reaction
with diyne 2f (Scheme 6). The reaction with o-anisaldehyde (3b) was slower than that
with p-anisaldehyde (3a), most likely as a result of the steric effect. When
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p-tolualdehyde (3c) was used, the corresponding adduct 4fc was obtained in 82% yield.
Benzaldehydes 3d–f, bearing F, Cl, and Br substituents at the para-position, were also
used to obtain the corresponding products in good yields. In striking contrast,
p-(trifluoromethyl)benzaldehyde (3g) and p-formylacetophenone (3h) showed
extremely low conversions, affording hardly any of the corresponding adducts, and
therefore evidencing the inefficiency of electron-deficient formyl groups. It is assumed
that an electron-deficient formyl group has weak coordination ability, resulting in an
inefficient conversion. In contrast, the reaction of 2-formylthiophene (3i) reached
completion within 5 h, affording the corresponding product 4fi in 69% yield. In addition
to (hetero)arylaldehydes, p-methoxycinnamaldehyde (3j) also participated in the
reaction, producing 4fj in 81% yield. However, no reaction occurred when
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3-phenylpropanal, p-methoxyacetophenone, or ethyl pyruvate were used. Thus, we
confirmed that α,β-unsaturated aldehydes are essential as carbonyl components.
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Scheme 6. Reactions of diyne 2f with various aldehydes and ketones.
Hydrocarbamoylative cyclization of 1,6-diynes bearing tertiary or
quaternary carbon tethers with DMF. In our previous study, hydrocarbamoylative
cyclization of diyne 2m bearing a malonate tether with DMF was very sluggish, even at
8
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40 °C, and the yield of 6m was as low as 30% (Scheme 7a). Based on the follow-up
computational study, it is assumed that hydrocarbamoylative cyclization proceeds via
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(
1) oxidative coupling of diyne 2m with Cp*RuH species, which is assumed to be
+
generated from Cp*Ru with Me NH, and subsequent reductive elimination from the
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resultant ruthenacycle 7, (2) insertion of DMF into the Ru–C bond of 8, and (3) β-H
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elimination from alkoxoruthenium 9 (Scheme 7b). In this proposed mechanism, the
final step was considered to be the most problematic owing to the steric repulsion
between the bulky Cp* ligand and the methoxycarbonyl substituent in TS9–6m. Our
investigation examining the reactions of 1,6-diynes with aldehydes showed that
complex 1b with a smaller Cp ligand is superior to the bulkier Cp* complex 1a when
bulky diynes equipped with tert-butyl terminal groups were used as substrates. For this
reason, it was presumed that the smaller catalyst 1b is more suitable than 1a for the
challenging hydrocarbamoylative cyclization of bulky diynes.
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Scheme 7. (a) Previous hydrocarbamoylative cyclization of diyne 2m with DMF and
(b) a proposed mechanism for this process.
Thus, the reactions of diynes bearing tertiary or quaternary carbon tethers with
DMF were briefly revisited using catalyst 1b (Scheme 8). Gratifyingly, the reaction of
diyne 2m was completed within 30 min in the presence of 10 mol % 1b at 140 °C,
affording 6m in 70% yield. Similarly, acetylacetone derivative 6n and
cyclohexane-1,3-dione derivative 6o were obtained in 78% and 75% yields, respectively.
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The reaction of 2p without a carbonyl group also afforded 6p in 68% yield, even though
a longer reaction time of 3 h was required. Moreover, diynes 2q and 2r bearing tertiary
carbon tethers were converted into the corresponding products in 70% yield. These new
results are markedly superior to those previously obtained with the bulkier catalyst 1a.
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Scheme 8. Hydrocarbamoylative cyclization of diynes 2m–r using catalyst 1b.
Conclusion
We have demonstrated that the ruthenium-catalyzed reaction of diynes bearing
alkyl terminal groups with arylaldehydes afforded dienyl ketones with a
stereoselectivity that was significantly different from that of the previously reported
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rhodium-catalyzed reactions. The results of DFT calculations suggest that this
characteristic stereoselectivity could be attributed to the direct ring opening of the
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initially formed ruthenium η -pyran complex. Although the dienyl ketone products
could undergo isomerization under the reaction conditions, thereby decreasing the
stereoselectivity, the reactions of diynes bearing bulky tert-butyl terminal groups using
[
CpRu(MeCN) ]PF as the catalyst produced the (Z)-products as the exclusive
3 6
stereoisomer. A variety of arylaldehydes with alkyl, alkoxy, and halogen substituents,
2-thienylaldehyde, as well as cinnamaldehyde successfully reacted. Nevertheless, strong
electron-withdrawing groups on arylaldehydes were found to be detrimental to the
reaction. Likewise, no reaction occurred when saturated aldehyde and ketones were
employed, thus demonstrating that α,β-unsaturated aldehydes are key reaction
components. Challenging hydrocarbamoylative cyclization of diynes bearing tertiary or
quaternary carbon tethers was also successful when smaller [CpRu(MeCN) ]PF was
3
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employed as the catalyst.
Experimental Section
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General. Column chromatography was performed on silica gel (Cica silica gel
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0N) with solvents specified below. H and C NMR spectra were obtained for samples
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in CDCl solutions at 25 °C. H NMR chemical shifts are reported in terms of chemical
3
shift (δ, ppm) relative to the singlet at δN7.26 ppm for chloroform. Splitting patterns are
designated as follows: s, singlet; d, doublet; t, triplet; q, quartet; quint, quintet; sext,
13
sextet; sept, septet; m, multiplet. Coupling constants are reported in Hz. C NMR
spectra were fully decoupled and are reported in terms of chemical shift (δ, ppm)
3
relative to the triplet at δ 77.0 ppm for CDCl . High resolution mass spectra (HRMS)
were obtained on a ESI- or DART-TOF mass spectrometer. Aldehydes, ketones, and dry
solvents were purchased and used as received. 1,6-Diynes 2a, 2b, 2c, 2g, 2i, and 2l–r
8,11,13
were known compounds.
to the literature procedures.
Ruthenium catalysts 1a and 1b were prepared according
14
Preparation of 1,6-Diynes
General procedure for N,N-Dipropargylsulfonamides – Synthesis of
N,N-bis(4,4-dimethylpent-2-ynyl)-4-methylbenzenesulfonamide (2f): To a solution
of TsNH (172.2 mg, 1.01 mmol) in DMF (2 mL) was added NaH (ca. 60 wt% in
2
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mineral oil, 90.0 mg, 2.25 mmol) at 0 °C. The mixture was stirred at 0 °C for 15 min
and at room temperature for 1 h. To this mixture was added a preformed solution of
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4,4-dimethylpent-2-ynyl methanesulfonate (433.9 mg, 2.28 mmol) in dry DMF (4 mL)
at room temperature. The reaction mixture was stirred at room temperature for 2 h. The
reaction was quenched with sat. NH Cl (5 mL). The aqueous phase was extracted with
4
AcOEt/hexane (5:1, 3 × 5 mL). The combined organic layer was washed with brine (3
×
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10 mL), and dried over MgSO . After concentration in vacuo, the obtained crude
product was purified by silica gel chromatography (hexane/AcOEt = 10:1) to afford
1
diyne 2f (182.1 mg, 50% yield) as a white solid (mp 105.9–107.3 °C); H NMR (400
3
MHz, CDCl , 25 °C) δ 1.06 (s, 18 H), 2.41 (s, 3 H), 4.10 (s, 4 H), 7.28 (d, J = 8.0 Hz, 2
13
H), 7.70 (d, J = 8.0 Hz, 2 H);
3
C NMR (100 MHz, CDCl , 25 °C) δ 21.4, 27.2, 30.7,
36.5, 70.8, 94.3, 127.8, 129.5, 135.7, 143.4;
HRMS (ESI) m/z calcd for
+
C H NO S•Na 382.1817, found 382.1817 [M+Na] .
21
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2
Analytical data for N,N-di(hex-2-ynyl)-4-methylbenzenesulfonamide (2d):
1
1
46.9 mg, 38%; yellow oil; H NMR (400 MHz, CDCl
3
, 25 °C) δ 0.86 (t, J = 7.2 Hz,
6
H), 1.36 (sext, J = 7.2 Hz, 4 H), 1.98 (tt, J = 7.2, 2.2 Hz, 4 H), 2.40 (s, 3 H), 4.10 (t, J
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
3
=
2.2 Hz, 4 H), 7.26 (d, J = 8.4 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H);
C NMR (100
MHz, CDCl , 25 °C) δ 13.3, 20.5, 21.4, 21.8, 36.6, 72.5, 86.0, 127.9, 129.2, 135.6,
3
10
11
12
13
14
15
16
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19
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25
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59
60
1
43.3; HRMS (ESI) m/z calcd for C H NO S•Na 354.1504, found 354.1509
19 25
2
+
[M+Na] .
Analytical
data
for
4-methyl-N,N-bis(4-methylpent-2-ynyl)benzenesulfonamide (2e): 58.1 mg, 19%;
1
white solid (mp 97.1–98.6 °C); H NMR (400 MHz, CDCl
3
, 25 °C) δ 1.10 (d, J = 7.2
Hz, 12 H), 2.34–2.42 (m, 2 H), 2.40 (s, 3 H), 4.10 (d, J = 2.0 Hz, 4 H), 7.28 (d, J = 8.0
13
Hz, 2 H), 7.71 (d, J = 8.0 Hz, 2 H);
3
C NMR (100 MHz, CDCl , 25 °C) δ 20.3, 21.4,
22.6, 36.5, 71.6, 91.5, 127.9, 129.4, 135.8, 143.4; HRMS (ESI) m/z calcd for
+
C H NO S•Na 354.1504, found 354.1502 [M+Na] .
19
25
2
Synthesis of 1-(4,4-dimethylpent-2-ynyloxy)-4,4-dimethylpent-2-yne (2h):
To a suspension of NaH (ca. 60 wt% in mineral oil, 68.0 mg, 1.6 mmol) in dry MeCN (6
mL) was added a 4,4-dimethylpent-2-yn-1-ol (113.8 mg, 1.01 mmol) at 0 °C and the
mixture was stirred at room temperature for 1 h. To this mixture was added a preformed
solution of 4,4-dimethylpent-2-ynyl methanesulfonate (231.8 mg, 1.22 mmol). The
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