Allenols versus Allenones: Rhodium-Catalyzed Regiodivergent and Tunable Allene Reactivity with Triazoles

Article abstract of DOI:10.1002/chem.201702468

2-Pyrrolines and 6-oxo-hexa-2,4-dienals have been prepared through the divergent reactions of 1-benzenesulfonyl-4-aryl-1,2,3-triazoles with functionalized allenes. The rhodium-catalyzed reactions between allenols and 1-benzenesulfonyl-4-aryl-1,2,3-triazoles yielded 2-pyrrolines. This transformation is compatible with the presence of aliphatic, aromatic, heterocyclic, amide, and halogen functional groups. Interestingly, a reactivity switch took place when the allene-tethered alcohol substrate was replaced by its ketone counterpart. When the rhodium-catalyzed reaction of 1-benzenesulfonyl-4-phenyl-1,2,3-triazole was performed with allenones, acyclic 6-oxo-hexa-2,4-dienals were stereoselectively formed as (2Z,4E) isomers.

Full text of DOI:10.1002/chem.201702468

A Journal of
Accepted Article
Title: Allenols versus Allenones: Rhodium-Catalyzed Regiodivergent
and Tunable Allene Reactivity with Triazoles
Authors: Pedro Almendros, Benito Alcaide, Sara Cembellín, Teresa
Martínez del Campo, and Guillermo Palop
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
█ Synthetic Methods
Allenols versus Allenones: Rhodium-Catalyzed Regiodivergent and
Tunable Allene Reactivity with Triazoles
Benito Alcaide,*[a] Pedro Almendros,*[b] Sara Cembellín,[a] Teresa Martínez del Campo,[a] and
Guillermo Palop[a]
Dedication ((optional))
Abstract: 2-Pyrrolines and 6-oxo-hexa-2,4-dienals have halogen functional groups. Interestingly, a reactivity switch
been prepared through the divergent reactions of 1- took place when the allene-tethered alcohol substrate was
benzenesulfonyl-4-aryl-1,2,3-triazoles with functionalized replaced by its ketone counterpart. When the rhodium-
allenes. The rhodium-catalyzed reactions between allenols catalyzed reaction of 1-benzenesulfonyl-4-phenyl-1,2,3-
and 1-benzenesulfonyl-4-aryl-1,2,3-triazoles yielded 2- triazole was performed with allenones, acyclic 6-oxo-hexa-
pyrrolines. This transformation is compatible with the 2,4-dienals were stereoselectively formed as (2Z,4E)
presence of aliphatic, aromatic, heterocyclic, amide, and
isomers.
Introduction
Although catalytic triazole transannulation with 1,2-dienes bearing
an additional nucleophilic center is attractive, it may be
troublesome due to additional selectivity problems. Herein, we
describe the rhodium-catalyzed reactions of 1-benzenesulfonyl-4-
aryl-1,2,3-triazoles with allene-tethered alcohols or ketones, which
provide a divergent synthetic protocol for the construction of 2-
pyrrolines or 6-oxo-hexa-2,4-dienals through controllable α-imino
metal carbene related processes.
N-Sulfonyl-1,2,3-triazoles are important synthetic intermediates,
which have been used as latent α-imino metal carbenes for the
preparation of a vast array of functionalized organic compounds.[1]
On the other hand, despite regioselectivity issues, the allene
moiety has attracted much attention due to its chamaleonic
reactivity, which results in a variety of synthetically useful
transformations.[2] Numerous examples on the metal-catalyzed
transannulation reactions of N-sulfonyl-1,2,3-triazoles with
different functional groups have been described. However, to the
best of our knowledge there is just three reports on the reactivity of
this heterocycle with the allene scaffold (Scheme 1a).[3] Taking into
account that the intermolecular transannulation reaction reported
by Miura and Murakami is limited to simple monosubstituted
allenes,[3b] we decide to test the reactivity of more functionalized
allenes, namely, α-allenols and α-allenones (Scheme 1b).
[a]
Prof. Dr. Benito Alcaide, Dr. Sara Cembellín, Dr. Teresa Martínez
del Campo, Guillermo Palop
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de
Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química
Universidad Complutense de Madrid
28040 Madrid (Spain)
Fax: (+34) 91-3944103
E-mail: alcaideb@quim.ucm.es
[b]
Prof. Dr. Pedro Almendros
Instituto de Química Orgánica General
Consejo Superior de Investigaciones Científicas, IQOG-CSIC
Juan de la Cierva 3, 28006 Madrid (Spain)
Fax: (+34) 91-5644853
E-mail: Palmendros@iqog.csic.es
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
1
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
R
•
unidentified products (Scheme 3). Probably, the highly
encumbered indolone-tethered allenol 1j did not afford the 2-
pyrroline 4ja because of steric reasons, due to the presence of the
tertiary stereocenter proximal to the reactive side. Interestingly, the
reactions of allenols 1k–m derived from aliphatic aldehydes with
triazole 3a afforded the required 2-pyrrolines 4ka–ma with a very
high selectivity -by our detection method through NMR the other
diastereomer could not be detected-, but in moderate yields
(Scheme 3). The rhodium-catalyzed reaction between 1-phenyl-1-
methyl-1,2-propadiene, a 1,1-disubstituted allene which lacks the
hydoxy group, and triazole 3a was not very competent and led to a
complicated mixture (Scheme 3). In order to know the influence of
the hydroxyl group, the allenyl ether 1b-Me derived from protection
of the OH in allenol 1b was employed (Scheme 3). The absence of
the free alcohol has a negative impact in the reactivity because no
pyrroline 4ba-Me was detected when allene 1b-Me was treated
with N-sulfonyl-1,2,3-triazole 3a in presence of Rh2(oct)4. Starting
allene 1b-Me remained unreactive after 2 hours (the required time
for completion of the reaction of allenol 1b), and under prolonged
heating the only products observed were derived from
decomposition of triazole 3a. Tentatively, the failure of the OMe-
allene 1b-Me should be attributed to the absence of a beneficial
coordinative interaction between the rhodium and the OH group
which is present in allenols such as 1b, presumably in the transient
species formed after the attack of the allene moiety to the
rhodacarbene. Unfavorable steric reasons may also be operative.
5 mol% Rh
(II)
R
N
∆
,
microwave
N
N
ref. 3a
Ts
Ts
N
(a)
previous
Ts
work
10 mol% Ni
i)
10 mol%
(0)
R1
Me
R1
phosphine
ii)
H
•
+
N
N
N
N
Ts
Ts
R2
N
N
ref. 3b
R2
NTs
H
R1
1 mol% Rh
R1
(II)
∆
,
molecular sieves
•
+
N
Me
R2
ref. 3c
R2
R1
OH
R2
Ar
Ar
R2
Ts
mol%
1
R1
O
+
N
N
X
X
N
N
•
Ts
Ts
Ts
N
N
Rh
(II)
Ar
OH
R2
R1
R2
(b)
work
this
O
O
Ar
Ar
R2
R1
R1
mol%
1
+
N
•
N
Ts
N
Rh
(II)
R1
R2
H
Ar
O
O
Scheme 1. Transannulation reactions of N-sulfonyl-1,2,3-triazoles with allenes.
Results and Discussion
Starting allenols 1a–i were easily prepared from the appropriate
aldehyde and a conveniently substituted 1-bromo-2-propyne
through indium-promoted reaction under Barbier conditions.[4]
Allenones 2 were readily obtained by oxidation of allenols 1 with
Dess–Martin periodinane.[5] Initially, we surveyed whether allenol
1a was a competent substrate to be engaged in the metal-
catalyzed reaction with N-sulfonyl-1,2,3-triazole 3a. This
assumption exhibits some troubles and displays an obstacle
because of the competitive and well-known O–C cyclization of
allenols in the presence of metals.[6] Happily, the Rh2(oct)4-
catalyzed reaction proceeded smoothly in toluene at reflux
temperature to afford the 2-pyrroline derivative 4aa (Scheme 2) as
a separable mixture (80:20) of diastereomers. The aromatization
was blocked by the methyl group at the newly generated
quaternary streocenter. Different solvents such as CHCl3 or 1,4-
dioxane were not as effective as toluene. Poor performance was
achieved with the use of different promoters such as Cu(OTf)2 or
AgNTf2. When the loading of rhodium salt was augmented from 1
mol% to 5 mol%, it resulted in a negligible yield increasement. Our
next ain was to investigate the generality of the 2-pyrroline
formation reaction by variation of the allenol substitution pattern. In
the event, a variety of allenols were probed to give the non-
aromatic heterocyclic products 4aa–ai in reasonable yields
(Scheme 2). The stereoselectivities of the reactions of allenols 1a–
i derived from aromatic aldehydes with triazoles 3a,b were found
to be modest, and the best result was obtained (selectivity ca.
85:15) from the reactions between allenol-tethered indoles 1h and
1i with N-sulfonyl-1,2,3-triazole 3a (Scheme 2). The rhodium-
catalyzed reaction of tertiary allenol 1j with N-sulfonyl-1,2,3-
triazole 3a was troublesome, and give a complicated mixtures of
2
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
Ar
Ph
•
•
Ar
Ph
Rh
mol%)
Rh
mol%)
2(oct)4 (1
2(oct)4 (1
N
OH
N
OH
Ts
+
Ts
N
N
+
R2
N
N
R2
Ts
Ts
OH
Ph
N
toluene, reflux
OH
Ph
N
toluene, reflux, 5 h
R2
R1
R1
R2
R1
R1
3a,b
1a–i
3a
1j–m
4aa–ia
4ja–ma
Ph
Ph
Ph
Ph
Ph
Ph
N
N
N
N
Ts
Ts
Ts
Ts
N
N
N
N
Ts
Ts
Ts
Ts
OH
OH
OH
OH
OH
Me
Me
Ph
Me
OH
OH
OH
Me
Me
Ph
Me
O
Ph
[a]
=
N
80:20)
3
(d.r.
4aa
O
Ph
100:0)
(37%)
Ph
Me
h)[b]
O
=
(62%,
=
=
100:0)
(d.r.
4ka
(d.r.
4la
Me
=
Me
Cl
=
4
ja
(0%)
•
(48%)
[a]
[a]
[a]
=
70:30)
2
67:33)
3
75:25)
3
100:0)
(41%)
(d.r.
(d.r.
h)[b] 4ca
(d.r.
h)[b] 4da
(d.r.
ma
4ba
h)[b]
4
(69%,
(60%,
(73%,
Ph
Ph
Ph
PMP
Ph
Rh
mol%)
2(oct)4 (1
complicated
mixture
+
N
N
N
N
N
N
Me
Ph
Ts
Ts
Ts
Ts
Ts
N
toluene, reflux, 5 h
OH
OH
OH
OH
Ph
Me
Me
Me
1-phenyl-1-methyl-
1,2-propadiene
3a
OMe
OMe
Ph
•
Cl
Cl
N
Rh
Ts
2(oct)4 (1
OMe
[a]
[a]
[a]
[a]
=
=
=
=
70:30)
70:30)
+
55:45)
55:45)
3a
(d.r.
4fb
(d.r.
4ga
(d.r.
4fa
Me
OMe
(d.r.
4ea
mol%) X
Me
2 h)[b]
2 h)[b]
toluene, reflux, 2 h
2 h)[b]
10
h)[b]
(49%,
(38%,
(36%,
(55%,
PMP
OH
Ph
Ph
Ph
N
N
N
N
Me
Me
4ba-Me
Ts
Ts
Ts
Ts
OH
OH
OMe
1b–Me
Me
Me
Me
I
Me
N Me
N Me
Scheme 3. Rhodium-catalyzed reaction of allenols 1j–m (R1 = alkyl) with triazole
3a. Controlled synthesis of 2-pyrrolines 4ja–ma.
Cl
Me
[a]
=
70:30)
4ba-Me
(0%)
[a]
[a]
(d.r.
4gb
=
=
85:15)
85:15)
(d.r.
4ha
(d.r.
4ia
2 h)[b]
10 h)[b]
3 h)[b]
(62%,
(31%,
(40%,
Having found a reliable method for the synthesis of 2-
pyrrolines 4 through the coupling of allenols 1 with N-sulfonyl-1,2,3-
triazoles 3, we decide to undertake the study of a different type of
allenes, namely, allenones 2. However, allenones can react under
rhodium-, silver-, gold-, and palladium-catalyzed conditions to form
new O–C bonds through traditional cycloisomerization paths,
resulting in furans.[5],[7] Given this established reactivity, we face a
potential problem in the form of a rival cyclization reaction. Taking
into account the high affinity of rhodium salts toward N-sulfonyl-
1,2,3-triazoles, we envisioned that the reaction of the
azaheterocycle 3 with the metallic catalyst should take place first;
thus making feasible our synthetic design. Under the optimized
reaction conditions for allenols 1, complete consumption of the
starting allenone 2a in presence of N-sulfonyl-1,2,3-triazole 3a was
observed. Noteworthy, lack of formation of the cyclic product of
type 4 was observed under Rh2(oct)4 catalysis. In the event, the
1,6-dicarbonyl derivative 5a was formed instead as single isomer
but in a low 25% yield. Consequently, a notable effect on the
outcome of the reaction was evidenced due to the different
electronic character of the allene precursor. This initial experiment
settled the viability of a substrate-controlled divergent allene
reactivity, but the low yield of the final product is a serious limitation
for its synthetic utility. Fortunately, the efficiency of the reaction was
improved with the modification of the solvent (chloroform rather
than toluene). Scheme 4 outlines the preparation of several 6-oxo-
hexa-2,4-dienals 5. The imine functionality in 5m-imin survived the
Scheme 2. Rhodium-catalyzed reaction of allenols 1a–i (R1 = Ar) with triazoles
3. Controlled synthesis of 2-pyrrolines 4aa–ia. PMP = 4MeOC6H4. [a] The
mixture of diastereomers was separated by column chromatography. [b] Major
diastereomer shown. Yields refers to major isomer, isolated as pure product with
correct analytical and spectroscopic data. Minor isomer could not be isolated as
pure material.
3
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
reaction conditions and the chromatographic purification, but the
final iminoketone adduct was isaolated in diminished yield.
Cycloisomerization adducts, namely, furans were detected in all
cases as minor side products (ca. 5%) by TLC and 1HNMR
analyses of the crude reaction mixtures. Unlike allenols 1, which
undergo triazole transannulation reactions, allenones 2 displayed
a different type of reactivity, enabling the synthesis of 1,6-
Rh2(oct)4 catalyst with the appropriate N-sulfonyl-1,2,3-triazole 3,
which is in equilibrium with its α-imino tautomer 6, results in the
formation of an α-imino Rh(II)-carbene 7 after extrusion of
dinitrogen. Nucleophilic addition of the internal double bond of the
cumullene moiety in allenols 1 to rhodacarbenes 7 formed
zwitterions 8. Species 8 suffer a regioselective azacyclization
reaction through attack of the imine moiety towards the positively
charged allylic carbon atom to give 2-pyrrolines 4 with concurrent
regeneration of the rhodium(II) catalyst.[10]
dicarbonyls 5.[8] Adducts
5
were obtained in
a
totally
stereoselective fashion as single (2Z,4E) isomers. The structure
and stereochemistry of 6-oxo-hexa-2,4-dienal 5d was
unambiguously assigned through its X-ray crystallographic
analysis (Figure 1).[9]
Ar
N
N
Ts
Ts
N
O
3
O
R2
Ph
R2
R1
R1
Rh
mol%)
2(oct)4 (1
Ar
N2
+
•
N
N
Ts
h
N
CHCl3 reflux, 12
,
Ar
N
H
Rh(II)
Ph
n
6
3a
2a–
−
Y
N
Ts
N2
5a–m-imin
OH
R2
Ar
R1
O
O
O
4
Ph
Me
Me
N
Rh
Ts
Ph
7
azacyclization
Rh
Me
Cl
Ar
nucleophilic
addition
H
H
H
Ph
Ph
Ph
N
Ts
O
O
O
OH
R2
a
c
5
5
5d
(47%)
O
R1
(72%)
Ph
(45%)
OH
R2
8
R1
O
O
•
Ph
Me
Ph
O
O
1
Cl
H
H
H
Ph
Ph
Ph
Scheme 5. Mechanistic explanation for the formation of 2-pyrrolines 4.
NTs
5m-imin
O
O
e
5
n
5
(58%)
(38%)
(48%)
A tentative mechanistic proposal for the generation of 6-oxo-
hexa-2,4-dienals 5 from allenones 2 and N-sulfonyl-1,2,3-triazole
3a under Rh2(oct)4 catalysis is summarized in Scheme 6. The
required formation of the α-imino Rh(II)-carbene 7 occurs in the
same way that above. However, replacing the allenol by an
allenone resulted in a switch of the reactivity. A positional
selectivity reversal should occur by attack of the terminal double
bond of the allenone 2 to the electrophilic center of the
rhodacarbene 7. In this way, it may be formed zwitterionic species
9, which suffer a 1,2-hydride shift to its isomeric zwitterion 10,
which rapidly evolves to the 1,6-dicarbonyl derivative 5 after
release of the metal catalyst. The unforeseen isolation of imine 5m-
imin from allenone 2m may reforce the pathway depicted in
Scheme 6. An alternative mechanistic possibility to the attack of
the electrophilic carbon of compound 7 to the end of the allene,
which should be contemplated, is an initial cyclopropanation of the
terminal double bond of the allene.[11]
Scheme 4. Rhodium-catalyzed reaction of allenones
Controlled synthesis of 1,6-dicarbonyl derivatives 5.
2
with triazole 3a.
Figure 1. ORTEP drawing of (2Z,4E)-6-(4-chlorophenyl)-5-methyl-6-oxo-2-
phenylhexa-2,4-dienal 5d. Thermal ellipsoids shown at 50% probability.
A plausible mechanistic proposal for the rhodium-catalyzed
formation of 2-pyrrolines 4 from allenols 1 and N-sulfonyl-1,2,3-
triazoles 3 is depicted in Scheme 5. Initially, reaction of the
4
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
Ph
the concentration (c) is expressed in g per 100 mL. All commercially available
compounds were used without further purification.
N
N
Ts
Ts
N
O
3a
General procedure for the synthesis of 2-pyrrolines 4. Rh2(Oct)4 (0.001
mmol) and the appropriate triazole 3 (0.10 mmol) were added to a stirred solution
of the corresponding allenol 1 (0.11 mmol) in toluene (1.0 mL) under argon. The
resulting mixture was stirred under argon atmosphere at reflux temperature until
disappearance of the starting material (TLC). After filtration through a pad of
Celite, the mixture was extracted with ethyl acetate (3 x 3 mL), and the combined
extracts were washed twice with brine. The organic layer was dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the residue eluting
with hexanes/ethyl acetate mixtures gave analytically pure compounds.
Spectroscopic and analytical data for 2-pyrrolines 4 follow.[12]
R2
R1
Ph
N2
N
H
Rh(II)
Ph
O
6
Y
5
R2
R1
Ph
Rh
H
N
Ts
Rh
Ph
7
10
Ts
2-Pyrroline 4ba. From 51 mg (0.30 mmol) of allenol 1b, and after flash
chromatography of the residue using hexanes/ethyl acetate (6:1) as eluent gave
compound 4ba (92 mg, 69%) as a colorless oil; 1H NMR (300 MHz, C6D6, 25 oC):
δ = 7.77 (m, 4H, Ar), 7.33 (s, 1H, =CH), 7.22 (d, 1H, J = 8.1 Hz, Ar), 7.00 (d, 2H,
J = 8.2 Hz, Ar), 6.90 (m, 3H, Ar), 6.61 (d, 2H, J = 8.0 Hz, Ar), 6.13 (br s, 1H, OCH),
5.02 (s, 1H, =CHH), 4.93 (s, 1H, =CHH), 2.12 (s, 3H, Me), 1.81 (s, 3H, Me), 1.76
(s, 3H, Me); 13C NMR (75 MHz, C6D6, 25 oC): δ = 195.5, 146.1, 142.9, 138.5,
136.8, 135.2, 135.1, 134.0, 133.4 (=CH), 129.9 (Ar, 2CH), 129.5 (Ar, 2CH), 129.2
(Ar, 2CH), 128.7 (Ar, 2CH), 128.6 (Ar, CH), 128.3 (Ar, 2CH), 127.8 (Ar, 2CH),
117.7 (=CH2), 59.9 (OCH), 21.2 (Me), 21.0 (Me), 16.2 (Me); IR (CHCl3): ν = 3279,
1684, 1594 cm–1; HRMS (ES): calcd for C27H27NO3S [M + H]+: 446.1790; found:
446.1773.
N
nucleophilic
addition
O
R2
R1
1,2-hydride
shift
O
H
R2
R1
Rh
Ph
•
N
2
Ts
9
Scheme 6. Mechanistic explanation for the formation of 6-oxo-hexa-2,4-dienals
5.
2-Pyrroline 4ca. From 67 mg (0.28 mmol) of allenol 1c, and after flash
chromatography of the residue using hexanes/ethyl acetate (6:1) as eluent gave
compound 4ca (85 mg, 60%) as a colorless oil; 1H NMR (300 MHz, C6D6, 25 oC):
δ = 7.56 (d, 2H, J = 8.3 Hz, Ar), 7.41 (d, 2H, J = 8.0 Hz, Ar), 7.35 (dd, 1H, J = 8.3,
1.2 Hz, Ar), 7.23 (m, 1H, Ar), 7.10 (m, 2H, Ar), 7.02 (d, 3H, J = 8.0 Hz, Ar), 6.94
(m, 3H, Ar), 6.75 (t, 2H, J = 7.9 Hz, Ar), 6.53 (s, 1H, =CH), 6.47 (d, 2H, J = 8.0
Hz, Ar), 5.80 (s, 1H, OCH), 5.61 (s, 1H, =CHH), 5.25 (s, 1H, =CHH), 2.11 (s, 3H,
Me), 1.65 (s, 3H, Me); 13C NMR (75 MHz, C6D6, 25 oC): δ = 197.5, 142.9, 142.4,
141.4, 139.4, 138.0, 137.6, 135.8, 134.2, 133.4 (=CH), 131.3 (Ar, CH), 129.6 (Ar,
2CH), 129.5 (Ar, 2CH), 129.1 (Ar, 2CH), 128.9 (Ar, 2CH), 128.6 (Ar, 2CH), 128.4
(Ar, 2CH), 128.2 (Ar, CH), 127.9 (Ar, 2CH), 127.7 (Ar, 2CH), 121.3 (=CH2), 59.6
(OCH), 21.2 (Me), 20.9 (Me); IR (CHCl3): ν = 3280, 1685, 1595 cm–1; HRMS
(ES): calcd for C32H29NO3S [M + H]+: 508.1946; found: 508.1940.
Conclusion
In conclusion, we report that the divergent reaction of 1-
benzenesulfonyl-4-aryl-1,2,3-triazoles with functionalized allenes
has selectively afforded 2-pyrrolines and 6-oxo-hexa-2,4-dienals.
The rhodium-catalyzed reactions between allenols and 1-
benzenesulfonyl-4-aryl-1,2,3-triazoles yielded 2-pyrrolines, while a
reactivity switch took place when the allene-tethered alcohol
substrate was replaced by its ketone counterpart. Thus, acyclic 6-
oxo-hexa-2,4-dienals were stereoselectively formed as (2Z,4E)
isomers when the rhodium-catalyzed reaction of 1-
benzenesulfonyl-4-phenyl-1,2,3-triazole was performed with
allenones. Items for future study of this reactivity switch comprise
the analysis of additional factors which influence the reaction
outcome, election of different allene substrates, and mechanistic
details.
2-Pyrroline 4la. From 95 mg (0.40 mmol) of allenol 1l, and after flash
chromatography of the residue using hexanes/ethyl acetate (8:1) as eluent gave
compound 4la (99 mg, 48%) as a colorless oil; 1H NMR (300 MHz, C6D6, 25 oC):
δ = 7.68 (t, 4H, J = 8.2 Hz, Ar), 7.05 (m, 10H, Ar), 6.91 (m, 3H, Ar), 6.60 (d, 2H,
J = 7.9 Hz, Ar), 6.06 (d, 1H, J = 8.5 Hz, =CH), 5.96 (d, 1H, J = 8.5 Hz, OCH), 4.98
(s, 1H, =CHH), 4.75 (s, 1H, =CHH), 3.22 (m, 2H, =CH2), 1.78 (s, 3H, Me); 13C
NMR (75 MHz, C6D6, 25 oC): δ = 195.2, 145.6, 142.8, 140.7, 140.5, 138.6, 138.5,
135.0, 133.5 (=CH), 130.0 (Ar, 2CH), 129.9 (Ar, 2CH), 129.6 (Ar, 2CH), 129.5 (Ar,
2CH), 128.8 (Ar, 2CH), 128.7 (Ar, 2CH), 128.6 (Ar, 2CH), 128.5 (Ar, 2CH), 127.6
(Ar, 2CH), 126.4 (Ar, CH), 120.9 (=CH2), 60.0 (OCH), 36.1 (CH2), 21.0 (Me); IR
(CHCl3): ν = 3279, 1686, 1595 cm–1; HRMS (ES): calcd for C32H30NO3S [M +
H]+: 508.1941; found: 508.1949.
Experimental Section
General methods: 1H NMR and 13C NMR spectra were recorded on a Bruker
Avance-300 or Varian VRX-300S. NMR spectra were recorded in CDCl3 or C6D6
solutions, except otherwise stated. Chemical shifts are given in ppm relative to
TMS (1H, 0.0 ppm), or CDCl3 (1H, 7.27 ppm; 13C, 76.9 ppm), or C6D6 (1H, 7.16
ppm; 13C, 128.0 ppm). Low and high resolution mass spectra were taken on an
AGILENT 6520 Accurate-Mass QTOF LC/MS spectrometer using the electronic
impact (EI) or electrospray modes (ES) unless otherwise stated. IR spectra were
recorded on a Bruker Tensor 27 spectrometer. X-Ray crystallographic data were
collected on a Bruker Smart CCD difractomer using graphite-monochromated
Mo-Kα radiation (λ = 0.71073 Å) operating at 50 Kv and 35 mA with an exposure
of 30.18 s in ω. Specific rotation [α]D is given in 10–1 deg cm2 g–1 at 20 °C, and
2-Pyrroline 4ma. From 100 mg (0.54 mmol) of allenol 1m, and after flash
chromatography of the residue using hexanes/ethyl acetate (3:1) as eluent gave
compound 4ma (100 mg, 41%) as a colorless oil; [α]D20 = +16.7 (c 0.3 in CHCl3);
1H NMR (300 MHz, C6D6, 25 oC): δ = 7.76 (d, 2H, J = 8.3 Hz, Ar), 7.72 (d, 2H, J
= 7.1 Hz, Ar), 6.93 (m, 3H, Ar), 6.68 (d, 2H, J = 8.5 Hz, Ar), 6.16 (d, 1H, J = 8.8
5
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
Angew. Chem. Int. Ed. 2013, 52, 1371; f) B. Chattopadhyay, V. Gevorgyan,
Angew. Chem. 2012, 124, 886; Angew. Chem. Int. Ed. 2012, 51, 862.
Hz, OH), 6.02 (d, 1H, J = 7.3 Hz, =CH), 5.91 (d, 1H, J = 8.6 Hz, OCH), 4.92 (s,
1H, =CHH), 4.90 (s, 1H, =CHH), 4.67 (q, 1H, J = 7.5 Hz, OCH), 3.88 (t, 1H, J =
7.7 Hz, CHH), 3.50 (t, 1H, J = 7.7 Hz, CHH), 1.80 (s, 3H, Me), 1.52 (s, 3H, Me),
1.47 (s, 3H, Me), 1.38 (s, 3H, Me); 13C NMR (75 MHz, C6D6, 25 oC): δ = 195.4,
145.7, 142.9, 138.6, 137.0, 135.0, 133.5 (=CH), 129.3 (Ar, 2CH), 128.5 (Ar, 2CH),
128.4 (Ar, 2CH), 128.0 (Ar, CH), 127.5 (Ar, 2CH), 118.1 (=CH2), 109.4, 73.4
(OCH), 69.6 (OCH2), 60.2 (OCH), 27.0 (Me), 26.3 (Me), 21.0 (Me), 15.4 (Me); IR
(CHCl3): ν = 3281, 1685, 1593 cm–1; HRMS (ES): calcd for C25H33N2O5S [M +
NH4]+: 473.2105; found: 473.2114.
[2]
For selected reviews, see: a) W. Yang, A. S. K. Hashmi, Chem. Soc. Rev.
2014, 43, 2941; b) S. Kitagaki, F. Inagaki, C. Mukai, Chem. Soc. Rev. 2014,
43, 2956; c) T. Cañeque, F. M. Truscott, R. Rodríguez, G. Maestri, M.
Malacria, Chem. Soc. Rev. 2014, 43, 2916; d) T. Lechel, F. Pfrengle, H.-
U. Reissig, R. Zimmer, ChemCatChem 2013, 5, 2100; e) S. Yu, S. Ma,
Angew. Chem. 2012, 124, 3128; Angew. Chem. Int. Ed. 2012, 51, 3074;
f) N. Krause, C. Winter, Chem. Rev. 2011, 111, 1994; g) B. Alcaide, P.
Almendros, Adv. Synth. Catal. 2011, 353, 2561; h) S. Ma, Chem. Rev.
2005, 105, 2829; i) A. S. K. Hashmi, Angew. Chem. 2000, 112, 3737;
Angew. Chem. Int. Ed. 2000, 39, 3590; j) Y. Yu, W. Yang, F. Rominger, A.
S. K. Hashmi, Angew. Chem. 2013, 125, 7735; Angew. Chem. Int. Ed.
2013, 52, 7586; k) R. L. Melen, L. C. Wilkins, B. M. Kariuki, H.
Wadepohl, L. H. Gade, A. S. K. Hashmi, D. W. Stephan, M. M. Hansmann,
Organometallics, 2015, 34, 4127.
General procedure for the synthesis of 6-oxo-hexa-2,4-dienals 5. Rh2(Oct)4
(0.001 mmol) and the appropriate triazole 3 (0.10 mmol) were added to a stirred
solution of the corresponding allenone 2 (0.11 mmol) in choroform (1.0 mL) under
argon. The resulting mixture was stirred under argon atmosphere at reflux
temperature until disappearance of the starting material (TLC). After filtration
through a pad of Celite, the mixture was extracted with ethyl acetate (3 x 3 mL),
and the combined extracts were washed twice with brine. The organic layer was
dried (MgSO4) and concentrated under reduced pressure. Chromatography of
the residue eluting with hexanes/ethyl acetate mixtures gave analytically pure
compounds. Spectroscopic and analytical data 6-oxo-hexa-2,4-dienals 5 follow.
[3]
a) Intramolecular version: E. E. Schultz, R. Sarpong, J. Am. Chem. Soc.
2013, 135, 4696; b) Intermolecular version: T. Miura, K. Hiraga,
T. Biyajima, T. Nakamuro, M. Murakami, Org. Lett. 2013, 15, 3298; c)
Rearrangement: T. Miura, T. Nakamuro, T. Biyajima, M. Murakami, Chem.
Lett. 2015, 44, 700.
[4]
[5]
[6]
B. Alcaide, P. Almendros, T. Martínez del Campo, E. Soriano, J. L. Marco-
Contelles, Chem. Eur. J. 2009, 15, 1901.
B. Alcaide, P. Almendros, T. Martínez del Campo, Eur. J. Org.
Chem. 2007, 2844.
6-Oxo-hexa-2,4-dienal 5a. From 40 mg (0.25 mmol) of allenone 1a, and after
flash chromatography of the residue using hexanes/ethyl acetate (10:1) as eluent
gave compound 5a (33 mg, 47%) as a colorless oil; 1H NMR (300 MHz, C6D6,
25 oC): δ = 8.93 (s, 1H, CHO), 7.84 (d, 2H, J = 8.4 Hz, Ar), 7.19 (m, 3H, Ar), 7.08
(m, 5H, Ar), 6.74 (d, 1H, J = 12.0 Hz, =CH), 6.45 (dd, 1H, J = 12.0, 1.5 Hz, =CH),
1.60 (d, 3H, J = 1.3 Hz, Me); 13C NMR (75 MHz, C6D6, 25 oC): δ = 197.9 (CO),
192.0 (CHO), 148.0, 143.0 (=CH), 142.7, 136.3, 133.9 (Ar, CH), 132.8, 130.5 (Ar,
2CH), 129.6 (Ar, 2CH), 129.2 (Ar, 2CH), 128.5 (Ar, 2CH), 128.4 (Ar, CH), 126.4
(=CH), 21.8 (Me); IR (CHCl3): ν = 1704, 1689, 1655, 1619 cm–1; HRMS (ES):
calcd for C19H16O2 [M + H]+: 277.1223; found: 277.1221.
For selected reviews, see: a) J. Le Bras, J. Muzart, Chem. Soc. Rev. 2014,
43, 3003; b) M. P. Muñoz, Chem. Soc. Rev. 2014, 43, 3164. For a selected
contribution, see: c) A. S. K. Hashmi, M. C. Blanco, D. Fischer, J. W. Bats,
Eur. J. Org. Chem. 2006, 1387.
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a) J. A. Marshall, E. D. Robinson, J. Org. Chem. 1990, 55, 3450; b) J. A.
Marshall, G. S. Bartley, J. Org. Chem. 1994, 59, 7169; c) J. A. Marshall,
E. M. Wallace, J. Org. Chem. 1995, 60, 796; d) A. S. K. Hashmi, Angew.
Chem. 1995, 107, 1749; Angew. Chem. Int. Ed. Engl. 1995, 34, 1581; e)
A. S. K. Hashmi, T. L. Ruppert, T. Knöfel, J. W. Bats, J. Org. Chem. 1997,
62, 7295; f) A. S. K. Hashmi, J.-H. Choi, J. W. Bats, J. Prakt. Chem. 1999,
341, 342; g) A. S. K. Hashmi, L. Schwarz, J. W. Bats, J. Prakt. Chem. 2000,
342, 40; h) A. S. K. Hashmi, L. Schwarz, J. H. Choi, T. M. Frost, Angew.
Chem. 2000, 112, 2382; Angew. Chem. Int. Ed. 2000, 39, 2285; i) A. S. K.
Hashmi, L. Schwarz, M. Bolte, Eur. J. Org. Chem. 2004, 1923; j) C.-Y.
Zhou, P. W. H. Chan, C.-M. Che, Org. Lett. 2006, 8, 325; k) A. S. K.
Hashmi, L. Schwarz, Chem. Ber./Recueil 1997, 130, 1449; also other
carbonyl groups lead to cyclization: l) A. S. K. Hashmi, A. M. Schuster, S.
Litters, F. Rominger, M. Pernpointner, Chem. Eur. J. 2011, 17, 5661.
6-Oxo-hexa-2,4-dienal 5c. From 33 mg (0.14 mmol) of allenone 1c, and after
flash chromatography of the residue using hexanes/ethyl acetate (10:1) as eluent
gave compound 5c (37 mg, 72%) as a colorless oil; 1H NMR (300 MHz, C6D6,
25 oC): δ = 9.02 (s, 1H, CHO), 7.98 (d, 2H, J = 8.2 Hz, Ar), 7.22 (m, 4H, Ar), 7.21
(d, 1H, J = 12.0 Hz, =CH), 7.12 (m, 4H, Ar), 7.05 (d, 1H, J = 12.0 Hz, =CH), 6.86
(m, 2H, Ar), 6.84 (t, 2H, J = 7.9 Hz, Ar), 1.91 (s, 3H, Me); 13C NMR (75 MHz,
C6D6, 25 oC): δ = 196.4 (CO), 191.9 (CHO), 150.1, 145.2, 144.0, 143.0 (=CH),
136.5, 134.8, 132.7, 130.7 (Ar, 2CH), 130.2 (Ar, 2CH), 130.0 (Ar, 2CH), 129.5
(Ar, CH), 129.3 (Ar, 2CH), 128.5 (Ar, 2CH), 128.4 (Ar, CH), 126.9 (Ar, 2CH), 124.3
(=CH), 21.4 (Me); IR (CHCl3): ν = 1712, 1684, 1652, 1612 cm–1; HRMS (ES):
calcd for C25H20O2 [M + H]+: 353.1536; found: 353.1543.
[8]
[9]
The carbonyl moiety is an important functionality present in several
bioactive compounds, which have been widely used in synthetic organic
chemistry based on its chameleonic reactivity. Several methodologies for
the preparation of 1,3-, 1,4- and 1,5-dicarbonyl derivatives have been
developed; but, the preparation of the 1,6-dicarbonyl counterpart is more
troublesome. For a recent strategy for 1,6-dicarbonyl synthesis, see: X.
Chen, X. Liu, J. T. Mohr, J. Am. Chem. Soc. 2016, 138, 6364.
CCDC 1413458 contains the supplementary crystallographic data for
Acknowledgements
compound 5d in this paper (www.ccdc.cam.ac.uk/data_request/cif).
[10] If this mechanistic picture is operative, cyclization of intermediates 8 could
also occur at another terminus of the allyl cation moiety leading to pyrroles.
However, we did not observe the formation of pyrroles. Final products, 2-
pyrrolines 4, are stable under the reaction conditions, despite that the
undetected pyrroles seem thermodynamically more stable.
Financial support from the MINECO and FEDER (Projects
CTQ2015-65060-C2-1-P
and
CTQ2015-65060-C2-2-P)
is
gratefully acknowledged. S. C. thanks MEC for a predoctoral
contract. We thank Dr. M. R. Torres for X-ray analysis.
[11] According
to
reference
[3c],
it
is
expected
to
afford
methylenecyclopropane intermediates. However, we were not able to
detect the formation of these species as byproducts.
Keywords: allenes • enones • heterocycles • regioselectivity •
synthetic methods
[12] Experimental procedures as well as full spectroscopic and analytical data
for compounds not included in this Experimental Section are described in
the Supporting Information. It contains compound characterization data,
experimental procedures, and copies of NMR spectra for all new
compounds.
[1]
For selected recent reviews, see: a) Y. Jiang, R. Sun, X.-Y. Tang, M. Shi,
Chem. Eur. J. 2016, 22, 17910; b) Y. Wang, X. Lei, Y. Tang, Synlett 2015,
26, 2051; c) H. M. L. Davies, J. S. Alford, Chem. Soc. Rev. 2014, 43, 5151;
d)
e)
P. Anbarasan, D. Yadagiri, S. Rajasekar, Synthesis 2014, 46, 3004;
A. V. Gulevich, V. Gevorgyan, Angew. Chem. 2013, 125, 1411;
6
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Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
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7
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10.1002/chem.201702468
Chemistry - A European Journal
DOI: 10.1002/chem.201xxxxxx
Entry for the Table of Contents
FULL PAPER
The rhodium-catalyzed reaction of 1-
benzenesulfonyl-4-aryl-1,2,3-triazoles
with functionalized allenes, namely
allenols and allenones, has selectively
afforded in a divergent way, 2-
Synthetic Methods
Benito Alcaide,* Pedro Almendros,*
Sara Cembellín, Teresa Martínez del
Campo, and Guillermo Palop
pyrrolines and 6-oxo-hexa-2,4-dienals.
O
OH
R2
R2
R1
R1
•
•
Ar
■■ – ■■
N
N
Ts
mol%
1
mol%
1
N
Rh2
Rh2
(oct)
(oct)
4
4
Ar
Allenols versus Allenones: Rhodium-
Catalyzed Regiodivergent and
Tunable Allene Reactivity with
Triazoles
O
H
R2
R1
N
Ts
OH
R2
R1
Ar
examples
14
O
to 73%
up
yield
examples
6
to 72%
up
yield
8
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