Understanding the Mechanism of the Divergent Reactivity of Non-Heteroatom-Stabilized Chromium Carbene Complexes with Furfural Imines: Formation of Benzofurans and Azetines

Article abstract of DOI:10.1021/acs.joc.5b02729

(Chemical Equation Presented) The mechanisms of the reaction between non-heteroatom-stabilized alkynyl chromium carbene complexes prepared in situ and furfural imines to yield benzofurans and/or azetines have been explored by means of density functional theory method calculations. The reaction proceeds through a complex cascade of steps triggered by a nucleophilic addition of the imine nitrogen atom. The formation of two benzofuran regioisomers has been explained in terms of competitive nucleophilic attacks to different positions of the carbene complex. Each of these regioisomers can be obtained as the major product depending on the starting materials. The overall sequence could be controlled to yield benzofurans or azetines by adjusting the substituents present in the initial carbene complex. This mechanistic information allowed for the preparation of new benzofurans and azetinylcarbenes in good yields.

Full text of DOI:10.1021/acs.joc.5b02729

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Article
Understanding the Mechanism of the Divergent Reactivity of
Non-Heteroatom-Stabilized Chromium Carbene Complexes
with Furfural Imines: Formation of Benzofurans and Azetines
Ignacio Funes-Ardoiz, Jairo González, Javier Santamaría, and Diego Sampedro
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02729 • Publication Date (Web): 22 Jan 2016
Downloaded from http://pubs.acs.org on January 23, 2016
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Understanding the Mechanism of the Divergent
Reactivity of NonꢀHeteroatomꢀStabilized Chromium
Carbene Complexes with Furfural Imines: Formation of
Benzofurans and Azetines
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†
‡
‡
†
Ignacio Funes-Ardoiz , Jairo González , Javier Santamaría* , Diego Sampedro*
†
Departamento de Química, Universidad de La Rioja,
Centro de Investigación en Síntesis Química (CISQ), Madre de Dios, 53, 26006 Logroño, Spain.
‡ Departamento de Química Orgánica e Inorgánica e Instituto Universitario de Química
Organometálica "Enrique Moles", Unidad Asociada al C.S.I.C. Universidad de Oviedo, C/ Julián
Clavería, 8, 33006 Oviedo, Spain
diego.sampedro@unirioja.es; jsv@uniovi.es
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
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Abstract
The mechanisms of the reaction between nonꢀheteroatomꢀstabilized alkynyl chromium carbene
complexes prepared in situ and furfural imines to yield benzofurans and/or azetines have been explored
by means of density functional theory method calculations. The reaction proceeds through a complex
cascade of steps triggered by a nucleophilic addition of the imine nitrogen atom. The formation of two
benzofuran regioisomers has been explained in terms of competitive nucleophilic attacks to different
positions of the carbene complex. Each of these regioisomers can be obtained as the major product
depending on the starting materials. The overall sequence could be controlled to yield benzofurans or
azetines by adjusting the substituents present in the initial carbene complex. This mechanistic
information allowed for the preparation of new benzofurans and azetinylcarbenes in good yields.
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Introduction
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Since their discovery in 1964 and especially during the last decades, group 6 Fischer carbene
2ꢀ8
complexes have demonstrated a high versatility as a powerful synthetic tool.
However, nonꢀ
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heteroatomꢀstabilized carbene complexes, first reported by Casey in 1973, did not emerged as an
alternative reagent until recently, due to their low stability. Among them, nonꢀheteroatomꢀstabilized
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alkynylcarbenes, smoothly in situ synthesized from the corresponding Fischerꢀtype alkoxycarbenes,
resulted synthetically useful and experienced significant differences in terms of reactivity with their
alkoxycarbene analogs. Accordingly, these compounds are able to form open chain policonjugated
1
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compounds as endiynes or linear dienynes or diendiynes and also to participate in different
cyclizations with the formation of three to sevenꢀmembered rings. Thus, nonꢀheteroatomꢀstabilized
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alkynylcarbenes react with olefins to form cyclopropanes, or with imines to access stable
1
4
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azetinylcarbenes or benzoazepines through formal [2+2] and [4+3] heterocyclizations, respectively.
1
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Finally, also a formal [3+3] benzofuran synthesis from furylimines has been reported. This particular
reaction focused our attention as imine nitrogen does not belong to the final structure of the molecule,
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unlike the heterocyclizations previously reported. In addition, the coupling of furan moieties with
alkynes has been demonstrated to be an effective route to complex organic molecules in organic
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synthesis.
On the other hand, some of the benzofurans were obtained as a mixture of regioisomers
indicating two different reaction pathways. In Table 1, benzofurans 5 obtained from alkynylcarbenes 3
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and 2ꢀfuraldehyde imine 4 are shown. When the R and R groups are interchanged (see for instance
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d/5e in Table 1 and ref. 16) the main regioisomer is different. A direct relationship between these
ratios and the operating mechanisms is difficult to obtain with the methodology employed here (at both
the experimental and computational levels) and only general trends will be considered (see below).
Table 1. [3+3] Benzofuran synthesis from, in situ synthesized, nonꢀheteroatomꢀstabilized carbene
complexes 3 (Ref: 16)
1
2
a
Compound
R
R
Yield (%)
5
a
Ph
Ph
Ph
Ph
Ph
p-Tol
Bu
81
b
5b
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d
c-C H
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e
c-C H
Ph
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5
5
f
Ph
PhꢀC≡C
74%
a Overall yield from the corresponding alkoxycarbene 1
b Performed at ꢀ75ºC. Regioisomeric ratio (>10:1)
c Regioisomeric ratio (>20:1)
d Performed at ꢀ80ºC. Regioisomeric ratio (>8:1)
Herein we present a deep computational study for the reported formal [3+3] carbocyclization between
chromium nonꢀheteroatomꢀstabilized alkynylcarbene complexes 3 and furfural imine 4 in order to give a
rational explanation for the formation of the corresponding benzofurans 5 and their regioisomers. Also,
the formation of azetinylcarbenes from a related mechanism is described. Finally, to give an extra
experimental support for the theoretical results, several additional experiments have been performed.
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Results and Discussion
A first mechanistic proposal for the formation of benzofurans 5 was outlined in the original paper.
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It was suggested that a nucleophilic addition of the furan Cꢀ3 in 4 to the carbene carbon in the nonꢀ
heteroatomꢀstabilized carbene 3 may initiate the reaction sequence. A subsequent cascade of
transformations may eventually lead to the final products 5. An initial assessment of this first reaction
step pointed out that this may not be the case as the attack of the Cꢀ3 in the furan moiety to the carbene
carbon led to a high energy intermediate (40.3 kcal/mol above the reactants, see Figure S1). This is in
contrast with the mild reaction conditions experimentally used. An inspection of the chemical structures
of the furan reagent reveals two different reaction points that may be involved in a nucleophilic attack,
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namely the Cꢀ3 position and the imine nitrogen atom. Also, it is wellꢀknown that alkynylcarbene
complexes can suffer nucleophilic attacks in both the carbene and the alkyne Cꢀ2 carbon atoms. Thus,
four different possibilities may arise as combination of these two elements (see Figure 1).
Figure 1. Electrophilic positions in 3 and nucleophilic positions in 4.
After computing all possibilities, the attack of the imine nitrogen atom to the alkyne Cꢀ2 carbon
resulted in the most favorable pathway. A TS 20.1 kcal/mol above the reagents (2ꢀfuraldehyde imine 4
and nonꢀheteroatomꢀstabilized carbene complex 3b) was found for this step at the M06/ 6ꢀ311+G(d,p)
/
LanL2TZ(f)//M06/ 6ꢀ31+G(d)/LanL2DZ level (see computational details). The intermediate I resulting
from this attack is 8.6 kcal/mol more stable than the reagents. The stability of this intermediate (28.7
kcal/mol more stable than the TS) may be due to the extended conjugation present in the molecule. A
competitive attack of the imine nitrogen to the carbene atom is slightly higher in energy (23.4 kcal/mol)
but the resulting intermediate IX is 12.3 kcal/mol above the reagents (Figure 2).
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TS-IX
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Figure 2. Competitive nucleophilic attacks of 4 to 3. Free energies in kcal/mol relative to 3b + 4.
From intermediate I, the reaction cascade progress by a cyclization to afford a sevenꢀmembered ring
by attack of the furan Cꢀ3 to the carbene carbon with simultaneous 1,2 migration of the metal
pentacarbonyl moiety. An energy barrier of 20.1 kcal/mol was found for this step and II is located 8.4
kcal/mol below the initial reactants (see Figure 3). This type of cyclization is related to similar processes
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recently reported.
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Figure 3. Computed mechanism for the formation of 5.
Next, a [1,5] hydrogen atom migration allows recovering the aromaticity of the furan moiety and
yields III as a stable intermediate 14.5 kcal/mol below the reactants. Following the mechanistic
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proposal of Echavarren and coꢀworkers in a similar reaction of the coupling between alkynes and
furfural derivatives, we also explored the possibility of a hydrogen [1,3] migration from intermediate II.
This new species could undergo an electrocyclization processes to obtain the final aromatic compound.
In spite of our efforts, we were unable to find this new intermediate. Instead, the transition state leading
to a [1,2] hydrogen migration was found very high in energy (34.9 kcal/mol) (see Figure S2 in the
Supporting Information). Thus, this pathway seems not competitive. In addition, starting from
intermediate III, a sequence of [1,5] hydrogen migrations could lead to the protonation of the metalꢀ
carbon bond but this pathways is also disfavored (16.4 kcal/mol, figure S2) with respect to the reversible
reaction. In contrast, the positive charge located in the quaternized nitrogen atom allows for a charge
distribution and fragmentation of the carbonꢀnitrogen single bond to yield IV via a TS which is 5.3
kcal/mol above the reactants. In this new intermediate, a reactive aldimine is formed next to the metal
center. A preparative step transforms IV in V by a single bond rotation. The barrier height of 3.3
kcal/mol leads to the slightly more stable compound V in which the iminic hydrogen atom is in the right
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position for the next steps. A hydrogen atom migration now takes place surmounting a barrier of 25.1
kcal/mol to yield VI. A geometrical modification (from sꢀtrans to sꢀcis in VII) provides the molecule
with the right conformation to allow the electrocyclization to yield VIII. Finally, an imineꢀenamine
tautomerization yields the final product. These last steps are driven by the high stability of the final
benzofurans.
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As reported before, when the nonꢀheteroatomꢀstabilized carbene complex is not symmetric, two
regioisomeric benzofurans can arise in different ratios. In all cases, a major isomer is obtained but a
minor isomer could also be found when the substituents in the carbene and conjugated carbon atoms are
different. This is not a drawback for the preparation of specific benzofurans as both regioisomers can be
conveniently obtained as major compounds from the adequate selection of alkoxycarbene complex 1
and alkyne 2 to provide the desired product. However, the formation of the minor product is relevant
from the mechanistic point of view. Thus, we explored different possibilities to explain the formation of
these regioisomers. Some alternatives include cyclizations and different migrations. However, it is not
evident the formation of the minor regioisomers from any of these reaction paths. The right explanation
may come from the different nucleophilic attacks discussed in Figure 1. While the attack of imine to
alkyne Cꢀ2 carbon is favored and explains the major isomer, the attack to the carbene carbon is also
available and may be competitive in the experimental conditions. Thus, we explored the fate of the
intermediate IX (see Figure 4).
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Figure 4. Computed mechanism for the formation of the regioisomeric benzofurans.
After the nucleophilic attack and formation of IX, the system evolves through a 1,3ꢀmetal
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migration to yield X. A very small barrier (1.1 kcal/mol) and the increased stability of X imply that
after the formation of IX this step should take place very fast. Also, as X and I are quite stable (6.2 and
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.6 kcal/mol below the reactants) these two species won’t equilibrate and the ratio of the regioisomers
will be governed by the initial nucleophilic attacks. The next step comprises a cyclization together with
a 1,2ꢀmetal migration to form XI in a similar fashion as the previously described formation of II (see
Figure 3). Once the sevenꢀmembered cycle is formed (XI or II), the regiochemistry of the final products
is fixed. The final steps are then equivalent to those reported in Figure 3.
Once it has been computationally found a reasonable explanation for the formation of the minor
regioisomer from carbene 3b, it can be inferred that the formation of the major isomer is controlled by
the difference between the energy of the transition states TS-I and TS-IX (see Figure 2). In order to
give experimental support for these computational results, we decided to perform a single experiment to
discard a major influence of the nature of the substituents of the carbene. Thus, in situ synthesized nonꢀ
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2
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2
heteroatomꢀstabilized carbene complex 3g (R = p-Tol; R = Ph), isomer of 3b (R = Ph; R = pꢀTol), was
reacted with imine 4. After 4h of reaction at ꢀ75ºC, benzofuran 5g was obtained as the major
regioisomer (5g:5b; ca. 6:1; 64% overall yield). This result indicates a prevalence of the choice between
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the two electrophilic positions of the carbene 3 to be attacked by the imine, over the nature of the
substituents (Ph or p-Tol).
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Once determined the mechanisms leading to both regioisomeric benzofurans, we aimed for a related
reaction of nonꢀheteroatomꢀstabilized carbene complexes with a furfural imine. In a previously reported
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yielded azetinyl carbene 6h in good yield (see Scheme 1). This azetine could be later used in a
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subsequent reaction to form complex oxazines. Intrigued by this different behavior when only a
substituent is changed, we explored the mechanism of the azetine formation in order to try to control the
formation of the different products.
Fc
O
Bu
O
N
N
Bu
THF, -80ºC
(
CO)5Cr
+
and warm up
pTol
(CO) Cr
Fc
H
5
pTol
3
h
4
6h
6
4%
Fc = Ferrocenyl
Scheme 1. Formation of azetinylcarbene 6h (see ref.14).
The alternative mechanism leading to the formation of the azetine should be relevant in the early
stages of the reaction. Once the cyclization process (to yield II) has taken place, it seems very
improbable that a complex fragmentation and rearrangement process could lead to 6. The results
obtained are shown in Figure 5.
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Figure 5. Computed mechanism for the formation of 6b.
Once the intermediate I is formed, a cyclization process could allow the formation of 6b. A similar
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transformation has been previously reported. The transition structure leading to this transformation is
7.7 kcal/mol above the reactants, clearly above the 11.5 kcal/mol energy barrier leading to the
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formation of the benzofurans (see Figure 3). This energy difference of 6.2 kcal/mol should be enough to
drive the reaction to the exclusive formation of benzofurans. However, the resulting azetine 6b is very
stable (15.9 kcal/mol below the reactants, compared with the value of ꢀ8.4 kcal/mol of II). Thus, it
seems plausible to alter the reaction outcome by modifying the relative energy of these two TSs through
directed structural modification. In this sense, an electron donating group as a ferrocenyl should
contribute to increase the nucleophilicity at Cꢀ2 carbon in intermediate I, favoring the pathway leading
to the azetinylcarbene 6h formation.
To test this hypothesis, we decided to study the reactivity of the imine 4 with other nonꢀheteroatomꢀ
stabilized carbene complexes wearing electronꢀdonating groups, and compare the results with the model
16
14
compounds 3b and 3h (Table 2). For that purpose, we selected first alkynylcarbene 3i wearing a pꢀ
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methoxyphenyl group at the alkyne position. Thus, in situ synthesized nonꢀheteroatomꢀstabilized
carbene complex 3i reacted with imine 4 allowing the reaction to warm up until ꢀ20ºC, yielding a
mixture of benzofuran 5i and azetine 6i in 22% and 49%, respectively overall yield, from the
corresponding alkoxycarbene 1. In both cases, benzofuran 5i and azetine 6i are obtained as a mixture of
regioisomers. The formation of both types of heterocycles and their isomers is in agreement with a
connection between both pathways, and indicates a similar energy for both transition states TS-aze and
TS-II. On the other hand, placing a second pꢀmethoxyphenyl group at the carbene carbon (complex 3j)
resulted, under the same reaction conditions, in the formation of the azetinylcarbene 6j in high yield and
as a sole compound. In this case, both substituents contributed to increase the mentioned nucleophilicity
at Cꢀ2 in intermediate I.
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Table 2. Synthesis of benzofurans 5 or azetinylcarbenes 6.
1
2
a
Carbene
3b
R
R
Yield (%)
b
Ph
p-Tol
Ph
pꢀTol
5b, 61
ꢀ
3
h
Fc
ꢀ
6h, 64
c
d
3
i
p-MeOC H
5i, 22
6i, 49
6
4
3
j
p-MeOC H
p-MeOC H
ꢀ
6j, 74
6
4
6
4
a Overall yield from the corresponding alkoxycarbene 1
b Performed at ꢀ75ºC. Regioisomeric ratio (>10:1)
c Regioisomeric ratio (ca.4:1)
d Regioisomeric ratio (ca.2:1)
Conclusions
We have shown here a complete computational exploration of the different mechanisms operating for
the reaction of nonꢀheteroatomꢀstabilized chromium carbene complexes with the furfural imine using
density functional method calculations. Complex reaction cascades were found to operate in the
preparation of regioisomeric benzofurans and the related synthesis of azetines. The different
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nucleophilic attacks to the alkyne C2 and carbene positions were found to control the formation of the
regioisomers. Thus, small differences in these key transition structures influence the reaction outcome
to yield the diverse regioisomers experimentally found. Also, the computed mechanisms provide an
explanation for the formation of azetinylcarbene complexes also found in the reaction mixture. In
addition, the directed structural modifications of these selected transitions structures allowed to control
the main product of the reaction. Therefore, the collected mechanistic information was used to tune the
reaction outcome by selection of the substituents present in the starting material. Thus, the possibility to
obtain both types of valuable compounds, benzofurans or azetines, using a similar methodology confers
an added value to the use of nonꢀheteroatomꢀstabilized chromium carbene complexes.
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Experimental Section
General Experimental Methods. All operations were carried out under argon atmosphere using
conventional Schlenck techniques. All common reagents were obtained from commercial suppliers and
used without further purification unless otherwise indicated. Tetrahydrofuran (THF) was distilled from
sodiumꢀbenzophenone, prior to use. Hexane and ethyl acetate were used from commercial suppliers.
TLC was performed on aluminiumꢀbacked plates coated with silica gel 60, with F254 indicator or
neutral aluminium oxide. Flash chromatographic columns were carried out on silica gel 60, (230ꢀ400
mesh). Highꢀresolution mass spectra were determined by electronic impact using mass spectrometer
with a triple sector analyzer. NMR spectra were run on a 300 or 400 MHz spectrometer using CDCl or
3
C D as solvents.
6
6
General experimental procedure for the preparation of the new benzofurans 5g,5i and
azetinylcarbenes 6i-j: To a freshly prepared solution, under argon atmosphere at ꢀ80ºC, of 0.95 mmol
of lithium acetilyde 2 (0.95 mmol of acetylene, 0.95 mmol of butyllithium (1.6 M in hexane)) in 20 mL
of tetrahydrofuran, 0.5 mmol of chromium alkoxycarbene 1 were added. The mixture was stirred for 15
min at that temperature and 0.19 mL (1.1 mmol) of trimethylsilyl trifluoromethanesulfonate (TMSOTf)
were added to form the nonꢀheteroatomꢀstabilized metal carbenes 3 (blue solution). At this point, 1
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mmol of 2ꢀfuraldehyde imine 4 was added and the mixture kept at ꢀ75ºC for 5g or allowed to warm up,
until colour change was observed. Removal of the solvents under reduced pressure followed by a
chromatographic column through silica gel of the residue, yielded the corresponding benzofurans 5 and
1
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9
1
1
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22
azetinylcarbenes 6.
1
N-butyl-6-phenyl-4-p-tolylbenzofuran-7-amine (5g). H NMR (300 MHz, CDCl , 25 ºC, TMS):
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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9
0
3
Colourless oil; 114 mg (64% yield) (mixture of regioisomers 5g:5b; ca. 6:1); Rf = 0.49 (Hexane/Ethyl
1
acetate 20:1); H NMR (300 MHz, CDCl , 25ºC, TMS): (Major isomer) δ = 7.69 (d, J = 2.0 Hz, 1H),
3
7.64 (d, J = 8.0 Hz, 2H), 7.58 – 7.24 (m, 7H), 7.15 (s, 1H), 6.98 (d, J = 4.0 Hz, 1H), 4.00 (m, 1H), 3.56
13
(
t, J = 8.0 Hz, 2H), 2.46 (s, 3H), 1.54 (m, 2H), 1.35 (m, 2H), 0.92 (t, J = 8.0 Hz, 3H). C NMR (CDCl ,
3
75 MHz, 25 ºC): (Major isomer) δ = 145.3 (C), 144.8 (CH), 140.4 (C), 136.9 (C), 136.7 (C), 131.4 (C),
1
1
29.7 (2 x CH), 129.6 (2 x CH), 128.6 (2 x CH), 128.1 (2 x CH), 126.5 (C), 126.4 (CH), 125.5 (CH),
25.3 (C), 124.6 (C), 106.2 (CH), 46.4 (CH ), 33.1 (CH ), 21.3 (CH ), 20.1 (CH ), 13.9 (CH ). HRMS
2
2
3
2
3
+
(EI) for C H NO [M] : 355.1936; found 355.1940.
2
5
25
N-butyl-4-phenyl-6-(4-methoxyphenyl)benzofuran-7-amine (5i): Colourless oil; 41 mg (22%
1
yield) (mixture of regioisomers ca. 4:1); Rf = 0.25 (Hexane/Ethyl acetate 20:1); H NMR (300 MHz,
CDCl , 25ºC, TMS): (Major isomer) δ = 7.69 (d, J = 2.2 Hz, 1H), 7.56 (d, J = 8.7 Hz, 2H), 7.53ꢀ7.47
3
(m, 5H), 7.14 (s, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 2.2 Hz, 1H), 4.06ꢀ3.78 (bm, 1H), 3.88 (s,
13
3H), 3.52 (t, J = 7.1 Hz, 2H), 1.61 – 1.44 (m, 2H), 1.33 (m, 2H), 0.91, (t, J = 7.3 Hz, 3H). C NMR (75
MHz, CDCl , 25ºC): (Major isomer) δ = 158.4 (C), 145.5 (C), 144.7 (CH), 139.8 (C), 132.9 (C), 130.9
3
(C), 129.7 (2 x CH), 129.1 (2 x CH), 128.8 (2 x CH), 127.1 (CH), 126.4 (C), 125.4 (C), 125.1 (CH),
124.5 (C), 114.0 (2 x CH), 106.2 (CH), 55.3 (CH ), 46.5 (CH ), 33.0 (CH ), 20.0 (CH ), 13.9 (CH ).
3
2
2
2
3
HRMS (EI) for C H NO [M]: Calc: 371.1885; found: 371.1870.
2
5
25
2
Pentacarbonyl[(1-butyl-2-furyl-4-(4-methoxyphenyl)-1,2-dihydroazet-3-
yl)benzylidene]chromium(0) (6i) Red oil; 136 mg (49% yield) (mixture of regioisomers ca. 2:1); Rf =
1
0
1
.41 (Hexane/Ethyl acetate 3:1); H NMR (400 MHz, C D , 25ºC, TMS): (Mayor isomer) δ = 7.31 (s,
6
6
H), 7.35 – 6.70 (m, 8H), 6.30 (m, 2H), 6.46 (d, J = 8.8 Hz, 2H), 3.35 (s, 3H), 3.05 – 2.75 (m, 2H), 1.15
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1
3
–
0.75 (m, 4H), 0.60 (t, J = 7.2 Hz, 3H). C NMR (100 MHz, C D , 25ºC): (Mayor isomer) δ = 253.2
6 6
1
2
3
4
5
6
7
8
9
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1
1
1
1
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1
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(
C), 227.5 (C), 220.6 (4 x C), 166.9 (C), 158.4 (C), 151.3 (C), 146.5 (C), 144.5 (CH), 131.4 (2 x CH),
128.7 (2 x CH), 128.6 (2 x CH), 128.5 (CH), 115.1 (CH), 114.4 (2 x CH), 113.4 (CH), 111.9 (CH), 72.8
CH), 55.1 (CH ), 45.4 (CH2), 30.2 (CH ), 20.3 (CH ), 13.7 (CH ).
(
3
2
2
3
Pentacarbonyl[(1-butyl-2-furyl-4-(4-methoxyphenyl)-1,2-dihydroazet-3-yl)4-
0
1
2
3
4
5
6
7
8
9
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methoxybenzylidene]chromium(0) (6j): Red oil; 220 mg (74% yield); Rf = 0.22 (Hexane/Ethyl acetate
1
3
:1); H NMR (300 MHz, C D , 25ºC, TMS): δ = 7.30 (s, 1H), 7.05 – 6.95 (m, 1H), 6.85 (d, J = 3.1 Hz,
6
6
1H), 6.79 (d, J = 8.8 Hz, 2H), 6.7 – 6.51 (m, 3H), 6.48 (d, J = 8.8 Hz, 2H), 6.33 – 6.26 (m, 2H), 3.34 (s,
13
3
H), 3.20 (s, 3H), 3.10 – 2.78 (m, 2H), 1.17 – 0.93 (m, 2H), 0.85 (m, 2H), 0.63 (t, J = 7.2 Hz, 3H); C
NMR (75 MHz, C D , 25ºC): δ = 250.9 (C), 227.4 (C), 220.7 (4 x C), 166.5 (C), 162.7 (C), 158.2 (C),
6
6
151.7 (C), 146.9 (C), 144.5 (CH), 139.1 (C), 131.2 (2 x CH), 128.7 (2 x CH), 118.9 (C), 115.1 (CH),
14.3 (2 x CH), 113.7 (2 x CH), 111.9 (CH), 72.6 (CH), 55.3 (CH ), 55.2 (CH ), 45.5 (CH ), 30.3
1
3
3
2
(CH ), 20.4 (CH ), 13.7 (CH ).
2 2 3
2
3
Computational Details: All calculations were carried out using the Gaussian09 program package
24
and the Density Functional Theory (DFT) method. We used the hybrid metaꢀGGA M06 functional
with two different basis sets. This functional has been recently reported to give good results with other
25
26
group VI metal as Mo and W. The standard basis set 6ꢀ31+G(d) was used for C, N, O and H and
27
LanL2DZ with the associated pseudopotential for Cr were used for the optimizations and frequencies
2
8
ꢀ29ꢀ30
calculations, while the 6ꢀ311+G(d,p) basis set for C, N, O, H and LanL2TZ(f) for Cr
(with the
LANL2DZ pseudopotential) were used to refine the potential energies in order to reduce the basis set
superposition error. All points were characterized as minima (no imaginary frequency) or TS (one
imaginary frequency, IRC was done when it was necessary). In addition, all the structures were
31
optimized using the SMD as implicit solvation model with tetrahydrofuran as solvent (ε = 7.4257). All
the energies in the presented profiles are Gibbs Free energies in solution and in kcal/mol referred to the
separated reactants. These energies have been calculated by adding the free energy correction calculated
with the smaller basis set, plus the SCF energy calculated with the larger basis set.
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Acknowledgment. This research was supported by the Spanish MINECO/FEDER (CTQ2014ꢀ59650ꢀ
P and CTQ2013ꢀ41511ꢀP) and Principality of Asturias (Spain, GRUPIN14ꢀ013). We are grateful to the
Supercomputing Center of Galicia (CESGA) for CPU time allocation.
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Supporting Information Available. Figure S1, Figure S2, Computed energies, Cartesian coordinates
for computed compounds, NMR spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
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References
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(2)
3)
Springer, New York, 2004; Vol. 13.
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(
22) Azetinylcarbene 6i and specially 6j resulted to be compounds of low stability and we
1
2
were not able to measure a mass spectrum. During measurement of NMR spectra some new signals
corresponding to decomposition products come out. However, color and significant NMR signals are in
complete agreement with the already reported analogs. See ref 14
3
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