Diverted domino reactivity in tertiary skipped diynes: A convenient access to polyfunctionalized cyclohexadienones and multivalent aromatic scaffolds

Article abstract of DOI:10.1002/chem.201101676

Diverting is the game! A new domino manifold has been implemented for the synthesis of cyclohexadienone-based scaffolds from tertiary skipped diynes and secondary amines. The manifold takes advantage of a new O-enolate-driven reactivity pattern discovered for these diynes. The scaffolds are conveniently transformed into the corresponding multivalent salicylate derivatives (see scheme).

Full text of DOI:10.1002/chem.201101676

COMMUNICATION
DOI: 10.1002/chem.201101676
Diverted Domino Reactivity in Tertiary Skipped Diynes: A Convenient
Access to Polyfunctionalized Cyclohexadienones and Multivalent Aromatic
Scaffolds
David Tejedor,*[a, b] Sara Lꢀpez-Tosco,[a, b] Javier Gonzꢁlez-Platas,[c] and
Fernando Garcꢂa-Tellado*[a, b]
Domino reactions[1] constitute single-operation, multi-step
processes able to generate two or more bonds under a con-
stant set of reaction conditions. Usually, they transform
simple starting materials into more complex chemical enti-
ties utilizing networks of construction reactions.[2] This prop-
erty makes them excellent synthetic tools to carry out mo-
lecular construction with atom-,[3] redox-[4] and step-econo-
my.[5] The sequential order by which these multi-step pro-
cesses are performed (the reaction manifold) ultimately de-
termines the chemical outcome of the process and therefore,
the topology of the final product (the skeletal connectivity).
In the last years, we have focused our efforts in the use of
small, readily-accessible, densely functionalized platforms
for the diversity-oriented domino generation of privileged
structural motifs with biological relevance.[6] Skipped diynes
1[7] constitute an example of such platforms (Scheme 1).
They are conveniently synthesized in one step and on a mul-
tigram scale from alkyl propiolates and acid chlorides by a
triethylamine-assisted multicomponent A2BB’4CR.[8] This
modular origin ensures a convenient grade of functional di-
versity on the tertiary sp3-center (diversity domain). The re-
activity profile of the platform is defined by the two alky-
noate units and the propargyl ester function (reactivity
domain). Recent reports from our group[9] have shown how
these C7 units can be selectively transformed into polysubsti-
tuted pyrroles 4,[9a] 1,4-diazepane derivatives 5,[9b] or pyra-
Scheme 1. Synthesis and properties of skipped diynes 1.
zoles 6,[9b] when they are made to react with primary
amines,
1,2-diamines,
and
hydrazines,
respectively
(Scheme 2). These heterocycles are generated by N-cycliza-
tion of the corresponding enamine intermediates 2 (Nu=
2
3
À
PgNH, HNCH(R )CH(R )NH2, and PgNH NH, respective-
ly). Although the reactivity profile of enamine 2 can be
characterized by the two canonical representations 2 (neu-
tral) and 3 (zwitterionic), the N-cyclization controls the
main domino reactivity pattern of this molecule (Nu-driven
domino processes). We envisioned that an alternative O-
[a] Dr. D. Tejedor, Dr. S. Lꢀpez-Tosco, Dr. F. Garcꢁa-Tellado
Instituto de Productos Naturales y Agrobiologꢁa
Departamento de Quꢁmica Biolꢀgica y Biotecnologꢁa
Consejo Superior de Investigaciones Cientꢁficas
Astrofꢁsico Francisco Sꢂnchez 3
38206 La Laguna, Tenerife (Spain)
Fax : (+34)922260135
E-mail: fgarcia@ipna.csic.es
dtejedor@ipna.csic.es
[b] Dr. D. Tejedor, Dr. S. Lꢀpez-Tosco, Dr. F. Garcꢁa-Tellado
Instituto Canario de Investigaciꢀn del Cꢂncer (Spain)
[c] Dr. J. Gonzꢂlez-Platas
Crystallographer, Servicio de Difracciꢀn de Rayos X
Departamento de Fꢁsica Fundamental II
Universidad de La Laguna, Avda. Astrofꢁsico Francisco Sꢂnchez 2
38204 La Laguna, Tenerife (Spain)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101676.
Scheme 2. Diverted domino reactivity of tertiary skipped diynes 1.
Chem. Eur. J. 2011, 17, 9571 – 9575
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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enolate-driven domino reactivity pattern biased by the
mesomeric form 3 could take place if this N-cyclization
could be blocked. Under these conditions, the O-cyclization
reaction of the enamine 2 would provide the cyclic oxonium
ion 7, which could be conveniently transformed into differ-
ent products. This new scenario would enable the develop-
ment of new domino processes and therefore, it would in-
crease the synthetic power of these C7 platforms. The chemi-
cal accomplishment of this goal requires: 1) disfavoring the
N-cyclization; 2) favoring the shift of the electronic density
from the nitrogen to the oxygen atom; 3) stabilizing the
cyclic oxonium ion 7 by a redistribution of the electronic de-
ficiency through the canonical form 8 and 4) a polar and
protic medium to favor the separation of charges produced
going from 2 (neutral) to 3 (zwitterionic) and to assist in the
acid–base quenching of the O-cyclization reaction. Whereas
secondary amines could meet the first three requirements
through the interconversion between their corresponding
iminium and enamine forms,[10] alcohols would guarantee
the fourth condition. In this communication we report the
feasibility of this conceptual approach and we show how it
can be implemented for the diversity-oriented synthesis of
polysubstituted cyclohexadienones and multivalent aromatic
scaffolds, which possess a survey of valuable functionalities
decorating the ring.
work studying the reaction of diyne 1a (1 equiv) and pyrro-
lidine (9a; 1 equiv) in dichloromethane. After several
assays, it was found that the reaction at room temperature
for 16 h afforded the mixture of cyclohexadienones deriva-
tives 10aa and 11aa although in low yield (Table 1, entry 1).
When the amount of pyrrolidine was doubled (to adjust the
stoichiometry to the formation of 11aa), the reaction exclu-
sively generated the compound 11aa in 67% yield (Table 1,
entry 2). The structures of these two products,[12] which were
unexpected, constituted experimental evidence of a reactivi-
ty shift in the diynic platform, and they established the
chemical outcome for the novel domino reaction pathway
elicited from these platforms. According to our initial hy-
pothesis, alcohols would be beneficial solvents for this
domino reaction. It was gratifying to find that the use of
MeOH or EtOH as a solvent allowed the diamine derivative
11aa to be obtained in nearly quantitative yield (Table 1,
entries 3–4). On the other hand, the reaction of diyne 1a
with dibenzylamine (9b) was shown to be solvent depen-
dent. Whereas the reaction in EtOH generated the mixture
of monoamines 10ab (5%) and 12ab (5%) together with
the diamine 11ab (86%, Table 1, entry 5), the reaction in
MeOH afforded the monoamine 10ab (39%) and diamime
11ab (53%, Table 1, entry 6).
With these results at hand, it soon became evident that
strong nucleophilic amines and/or less nucleophilic alcoholic
solvents favored the formation of diamine derivatives 11,
whereas low nucleophilic amines and a stronger nucleophilic
alcoholic solvent favored the formation of monoamine de-
rivatives 10.
The hypothesis was assessed using the reaction of diyne
1a with different secondary amines under different reaction
conditions. Table 1 summarizes the main experimental re-
sults,[11] using two representative secondary amines: pyrroli-
dine (9a), as a representative example of cyclic and highly
nucleophilic secondary amines, and dibenzylamine (9b) as a
representative example of acyclic, sterically demanding sec-
ondary amines with reduced nucleophilicity. We began this
When dibenzylamine was used, the presence of product
12ab with an ethoxy group, revealed the participation of the
solvent (EtOH), which was further confirmed by crossover
experiments. Moreover, it was also confirmed that 10 and 12
did not interconvert under these reaction conditions (see
the Supporting Information for details). Interestingly, the di-
lution of the methanolic reaction increased the formation of
the monoamine 10ab up to 79% yield (entry 7). Further ex-
periments with the dibenzylamine derivatives 9b–d, which
share a similar steric environment at the nitrogen center but
feature different electronic properties,[13] showed a clear re-
lationship between the nucleophilicity of the amine and the
ratio of monoamine 10/diamine 11 in the reaction mixtures
(Table 1, entries 7–9). The reaction with amine 9d, the worst
nucleophile, was very slow and it afforded monoamine 10ad
in 47% yield (50% of conversion) after 7 days at room tem-
perature. We did not observe other chemical entities differ-
ent to the products and starting materials in the crude reac-
tion mixture. This fact seems to point to an early rate limit-
ing step in this domino reaction.
Table 1. Domino reaction of diyne 1a and secondary amines 9a–d.[a]
Entry
Solvent
Amine
10
11
[%]
[%]
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
MeOH
EtOH
C4H8NH[b]
C4H8NH
C4H8NH
C4H8NH
Bn2NH
9a
9a
9a
9a
9b
9b
9b
9c
9d
30
9
67
>99
>99
86
53
21
33
7
n.d.[c]
n.d.
n.d.
10[e]
39
EtOH
MeOH
MeOH[d]
MeOH[d]
MeOH[d]
Bn2NH
Bn2NH
79
The chemical efficiency and the complexity generation
power of this reaction exceeded all our expectations. The re-
PMDBA[f]
PNDBA[g]
67
93[h]
À
À
action generated up to four new bonds (2C N, 1 C C, 1C=
O) and one ring with excellent atom economy and an opera-
tionally simple protocol.
[a] Reaction conditions: diyne (0.10 mmol), amine (0.22 mmol), solvent
(2 mL). [b] 0.11 mmol. [c] n.d. =none detected. [d] 0.01m. [e] Roughly
equimolecular mixture of monoamides 11ab and 12ab. [f] PMDBA=
The set of experimental data can be rationalized through
the O-enolate-driven domino manifold outlined in
bis(4-methoxyphenyl)methanamine.
[g] PNDBA=bis(4-nitrophenyl)-
ACHTUNGTRENNUNG
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Diverted Domino Reactivity in Tertiary Skipped Diynes
COMMUNICATION
Scheme 3. The scenario comprises two reaction pathways (a
and b) diverging from a common intermediate IV. Pathway
a is launched by the addition of a second amine unit on the
tion conditions, dibenzylamine (9b) can react following
either of the two pathways, and the chemical outcome of the
reaction will be determined by the stoichiometry, solvent,
concentration, and temperature. Because tertiary dibenzyla-
mines could be considered masked forms of primary amines
(hydrogenolysis renders the free primary amine), the instal-
lation of these motifs into the cyclohexadienones 10 and 11
would increase their synthetic value. With this idea in mind,
we next undertook the selective transformation of diyne 1a
into cyclohexadienones 10ab and 11ab.
After some experimental work, we found that the reac-
tion of diyne 1a with one equivalent of dibenzylamine (9b)
could be selectively funneled toward route b (MeOH
(0.01m), 658C, 16 h) to afford monoamine 10ab in 95%
yield (method A, Table 2, entry 1). The scope of this domino
reaction was explored using the set of skipped diynes shown
in Table 2. The reaction was tolerant with different function-
alities decorating the diynes 1b–i, rendering the correspond-
ing monoamine derivatives 10bb–ib in excellent yields. Al-
though the tertiary sp3 center on the skipped diyne does not
participate directly in the reaction, it exerts steric hindrance
on the alkynoate moiety. This steric effect resulted in a low-
Table 2. Domino reaction of diyne 1 and dibenzyl amine (9b).
Entry
R
Method
10
11
[%][a]
[%][a]
Scheme 3. O-enolate driven domino mechanistic proposal.
1
2
3
4
5
6
7
8
Ph
1a
A[b]
B[c]
B[d]
A
B
A
B
A
B
A
A[e]
B
A
B
A
B
A
B
95
94
91
cyclic oxonium ion IV to give the orthoaminal V, which re-
arranges to aminal VII through the formation of the immo-
nium-enolate VI. The elimination of R2OH from VII deliv-
ers the diamino derivative 11. The much less favored elimi-
nation of R2NH would generate the monoamine derivative
10. The pathway b is triggered by the addition of the solvent
on IV to give the corresponding orthoester derivative (not
shown), which rearranges to the mixed ketal VIII, which in
turn eliminates alcohol to give the statistical mixture of
monoamines 10 and 12. Thus, whereas pathway a affords di-
amine 11 as the main compound, route b only delivers
monoamine 10 (or 12 if methanol is not used as the alcohol-
ic solvent). The pathway a is triggered by a bimolecular re-
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-FC6H4
1b
1c
1d
1e
84
93
92
74
86
86
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
95
94
88
80
87
85
81
4-BiPh
1 f
1g
1h
1i
93
96
93
94
4-MeC6H4
3-MeOC6H4
3,5-diMeOC6H3
action (rate=ka [IV]ACTHNUTRGNE[NUG amine]) and consequently, it would be
A
B
A
A
B
benefited by high nucleophilic amines, high concentration,
low nucleophilic solvents and low temperatures. On the
other hand, route b is launched by a pseudo-first-order reac-
tion (rate=kap [IV], kap =kb [solvent]) and it would be bene-
fited by low nucleophilic amines, dilution, nucleophilic sol-
vents, and a higher temperature. Whereas pyrrolidine (9a)
meets the requirements of route a and it exclusively affords
diamine derivative 11aa[14] with independence of the reac-
iPr
C6H11
1j
1k
85[f]
84[f]
40[g]
[a] Yields of isolated products. [b] Method A: diyne (0.10 mmol), diben-
zylamine (0.11 mmol), MeOH (0.01m), 658C, 16 h. [c] Method B: diyne
(0.10 mmol), dibenzylamine (0.22 mmol), CH2Cl2/EtOH/H2O (4:4:1),
(0.0.5m), RT, 16 h. [d] 15 mmol scale.[e] 7.5 mmol scale. [f] 3 days. [g] 1
week.
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F. Garcꢁa-Tellado, D. Tejedor et al.
Table 3. Synthesis of multivalent aromatic platforms 13 and 14.[a]
ering of the reactivity of aliphatic diynes 1j and 1k, which
needed more forcing conditions (3 days) to be efficiently
converted into their corresponding monoamine derivatives
10jb and 10kb (Table 2, entries 21 and 22).
With the monoamine derivatives 10ab–kb at hand, we ex-
plored the selective formation of the corresponding diamine
derivatives 11ab–kb. Preliminary experiments had shown
that the reaction of dibenzylamine (9b) and diyne 1a in
EtOH generated the diamine 11ab in good yield (86%),
however it was contaminated with significant amounts of
monoamine derivatives 10–12ab (10%, Table 1, entry 5).
According to Scheme 3, it was apparent that if the nucleo-
philicity of the EtOH could be lowered then route b could
be diminished and the yield of diamine 11 would be in-
creased.[15] Water was envisioned as a convenient co-solvent
because it was expected that it would lower the nucleophi-
licity of EtOH through coordination, whereas it would in-
crease the polarity of the reaction medium. After several ex-
perimental trials, we found that the mixture of EtOH/H2O
(4:1) was optimal for the selectivity of the reaction, but un-
fortunately, the low solubility of the lipophilic diynes 1b–k
in this aqueous media compromised the reaction efficiency.
Fortunately, it was found that the addition of CH2Cl2 to the
aqueous solvent cocktail brought the diynes 1a–k into solu-
tion increasing the reaction efficiency without eroding the
selectivity of the reaction. (Method B, Table 2). Under these
conditions, aromatic diynes 1a–i uniformly reacted with two
equivalents of dibenzylamine to give the corresponding di-
Entry
Starting
material
R
Product
Yield
[%][b]
1
2
3
4
5
6
7
8
10ab
10eb
10hb
10ib
10kb
11ab
11eb
11 fb
11gb
11hb
11ib
Ph
4-FC6H4
3-MeOC6H4
3,5-diMeOC6H3
C6H11
Ph
4-FC6H4
4-BiPh
13a
13e
13h
13i
13k
14a
14e
14 f
14g
14h
14i
75
68[c]
62
75
48
76
74
50
75
63
77
9
10
11
4-MeC6H4
3-MeOC6H4
3,5-diMeOC6H3
[a] See the Experimental Section. [b] Yield of isolated product.
[c] 7.0 mmol scale.
dered the corresponding amine-free aromatic scaffolds 13
and 14 in excellent yields. Gratifyingly, this two-step process
could be efficiently performed without isolation of the
phenol intermediate with a good overall efficiency for both
platforms (Table 3). In addition, the whole transformation
could be performed at multigram scale (Table 3, entry 2).
It is important to note that the substitution pattern deco-
rating structures 13 and 14 is not directly accessible by the
established methodologies in the construction of biaryl[19]
and salicylate-based structures[20] using simple and ready
available precursors. In addition, the metal-free installation
of two aromatic unprotected amine groups, which are rele-
vant functional motifs in pharmacological and new materials
research, is an appealing value of this methodology when
compared with described metal-catalyzed aminations.[21]
In summary, we have shown that tertiary skipped diynes 1
can be efficiently and selectively transformed into polysub-
stituted cyclohexadienones 10 and 11 by a divergent O-eno-
late-driven domino process. The manifold uses benzylamine
as the secondary amine to generate up to four new bonds
ACHTUNGTRENNUNGamine derivatives 11ab–ib in good to excellent yields
(Table 2). Aliphatic substituted diynes were not convenient
substrates for this reaction. The steric hindrance exerted by
the tertiary sp3 center on the alkynoate moiety comprised a
kinetic barrier difficult to overcome. Under these conditions,
diyne 1k needed a week at room temperature to deliver the
diamine 11ak in only 40% yield (Table 2, entry 23).
It is important to highlight that these reactions can be per-
formed at multigram scales without significant erosion in
the reaction efficiency (Table 2, entries 3 and 11).
Cyclohexadienones 10 and 11 represent densely function-
alized building (synthetic) blocks with a polyvalent reactivi-
ty profile. Among the wide set of imaginable transforma-
tions that could be addressed on these platforms, we show
herein their direct transformation into multivalent aromatic
platforms 13 and 14 (Table 3), which constitute valuable ex-
amples of salicylate derivatives[16] with a privileged biaryl[17]
motif (R=Ar) and one (compound 13) or two (compound
14) amine groups in their structures. This transformation
takes advantage of the presence of the tertiary aryloate
group that is positioned a to the non-enolizable carbonyl
group. Reduction of this ketone to the corresponding alco-
hol would provide the corresponding phenol derivative by
the concomitant elimination of the aroylate group. The re-
duction of this hindered ketone was problematic but it was
conveniently achieved using an excess of Mg in EtOH and
heated to reflux to afford the corresponding phenol deriva-
tive in moderated to good yields (Table 3).[18] The amine de-
À
À
(2C N, 1 C C, 1C=O) and one ring with excellent atom
economy and an operationally simple protocol. Moreover,
we have shown how these polysubstituted cyclohexadie-
nones are suitable platforms for the access to multivalent ar-
omatic scaffolds decorated with a rich functional pattern
comprising a biaryl (Ar, Ar), a salicylate (1,2-OH, COOH),
an arylphenol (1,2-OH, Ar), a biarylamine (1,2-NH, Ar),
and an anthranilate (1,2-NH,COOH). This substitution pat-
tern is well suited for the generation of natural-product-like
libraries throughout functional pairing strategies;[22] such
study is ongoing in our laboratory.
À
protection under standard conditions (H2 Pd(OH)2) ren-
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Diverted Domino Reactivity in Tertiary Skipped Diynes
COMMUNICATION
11, 3502–3510; f) D. Tejedor, D. Gonzꢂlez-Cruz, F. Garcꢁa-Tellado,
J. J. Marrero-Tellado, M. L. Rodrꢁguez, J. Am. Chem. Soc. 2004, 126,
8390–8391; g) D. Tejedor, F. Garcꢁa-Tellado, J. J. Marrero-Tellado, P.
de Armas, Chem. Eur. J. 2003, 9, 3122–3131.
Experimental Section
General procedure for the synthesis of monoamines 10: (Table 2, Method
A). Dibenzylamine (0.55 mmol) was added to a solution of diyne 1a
(188 mg, 0.50 mmol) in MeOH (50 mL) and the reaction mixture was
stirred overnight at reflux. After removing the solvent under reduced
pressure the products were purified by flash column chromatography
(silica gel, EtOAc/CH2Cl2) to yield 10ab. In certain cases it is useful to
recrystallize the final product to remove small amounts of unreacted di-
benzylamine (CH2Cl2 and 1.5% EtOAc/Hexane). Alternatively, chroma-
tography can be avoided if the amount of subproduct cyclohexadienones
11 is not significant. Recrystallization typically affords the final product
with yields similar to the reported ones in Table 2.
[7] D. Tejedor, S. Lꢀpez-Tosco, J. Gonzꢂlez-Platas, F. Garcꢁa-Tellado, J.
Org. Chem. 2007, 72, 5454–5456.
[8] A2BB’4CRs refers to a four-component reaction that utilizes two
different components (A and B) to give a product that incorporates
into its structure two identical units of component A and two
chemo-differentiated units of component B (B and B’). For full de-
tails and more examples of this type of multicomponent reactions,
see: D. Tejedor, F. Garcꢁa-Tellado, Chem. Soc. Rev. 2007, 36, 484–
491.
[9] a) D. Tejedor, S. Lꢀpez-Tosco, J. Gonzꢂlez-Platas, F. Garcꢁa-Tellado,
Chem. Eur. J. 2009, 15, 838–842; b) D. Tejedor, S. Lꢀpez-Tosco, J.
Gonzꢂlez-Platas, F. Garcꢁa-Tellado, Chem. Eur. J. 2010, 16, 3276–
3280.
General procedure for the synthesis of monoamines 11: (Table 2, Method
B). Dibenzylamine (1.05 mmol) was added to a solution of diyne 1a
(188 mg, 0.50 mmol) in a mixture of EtOH/CH2Cl2/H2O (4 mL/4 mL/
1 mL) at room temperature. The reaction mixture was stirred overnight.
After removing the solvent under reduced pressure the products were
purified by flash column chromatography (silica gel, EtOAc/CH2Cl2) to
yield 11ab.
[10] For selected reviews, see: a) C. Grondal, M. Jeanty, D. Enders, Nat.
Chem. 2010, 2, 167–178; b) D. Enders, C. Grondal, M. R. M. Hꢅtl,
Angew. Chem. 2007, 119, 1590–1601; Angew. Chem. Int. Ed. 2007,
46, 1570–1581.
General procedure for the synthesis of salicylates 13 and 14: Cyclohexa-
dienone 11ab (738 mg, 1.00 mmol) was dissolved in MeOH (100 mL). Mg
turnings (70 mmol) were added and the mixture was heated overnight at
658C. After the reaction mixture was cooled to 08C, HCl (6m) was
added slowly. Once the methanol was evaporated under reduced pres-
sure, the aqueous phase was extracted twice with CH2Cl2. After removing
the solvent at reduced pressure, the crude products were dissolved in
MeOH/CH2Cl2 (1:1, 100 mL). Pd(OH)2/C (20%, 90 mg) was then added
and the reaction mixture was hydrogenated with H2 (1 atm) at room tem-
perature for 16 h. After filtration with celite and removal of the solvent
under reduced pressure, the products were purified by flash column chro-
matography (silica gel, EtOAc/hexane) to afford 14a.
[11] From the large number of experimental results obtained from the
reaction of diyne 1a with different secondary amines under different
reaction conditions, we have collected (in Table 1) the most relevant
and illustrating results related to this work.
[12] The structures of these compounds were unambiguously assigned by
single-crystal X-ray diffraction analysis. CCDC-820434 and 820435
contain the supplementary crystallographic data for the structures
10aa and 11aa respectively. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[13] pKa (Bn2NH)=8.76; pKa (PMDBA, 9c)=9.55; pKa (PNDBA,
9d)=6.98 (Calculated using the ACD/pKa dB program).
[14] The reaction of pyrrolidine and related secondary amines with skip-
ped diynes 1 in EtOH (or MeOH) presented a general scope with
regard to the diyne. In all the assayed cases, the reactions afforded
the corresponding diamine derivatives 11 in good to excellent yields.
These results are not included in this work.
[15] Although iPrOH (a less nucleophilic solvent) was selective in the
formation of 11ab (no 10ab was detected), it was less efficient since
only 47% of the desired product was isolated after 16 h.
[16] Salicylates constitute core structures of pharmacologically important
natural products. S. Brꢆse, A. Encinas, J. Keck, C. F. Nising, Chem.
Rev. 2009, 109, 3903–3990.
Acknowledgements
This research was supported by the Spanish MICINN and the European
RDF (CTQ2008–06806-C02–02), the Spanish MSC ISCIII (RETICS
RD06/0020/1046), FUNCIS (PI 43/09). S. L.-T. thanks the Spanish MEC
for a FPU grant. The authors thank technician Ms. Anna Jurado Varona
for her experimental assistance.
[17] D. A. Horton, G. T. Bourne, M. L. Smythe, Chem. Rev. 2003, 103,
893–930.
[18] Cl substituents at the aromatic ring were not tolerated. Mg/EtOH
Keywords: cyclization
reactions · multicomponent reactions · skipped diynes
·
cyclohexadienone
·
domino
2
2
À
À
reduced the sp C Cl to the corresponding sp C H.
[19] For selected reviews, see: a) J. A. Ashenhurst, Chem. Soc. Rev. 2010,
39, 540–548; b) R. Martin, S. L. Buchwald, Acc. Chem. Res. 2008,
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Received: June 1, 2011
Published online: July 26, 2011
Chem. Eur. J. 2011, 17, 9571 – 9575
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9575