Visible-Light-Mediated Ru-Catalyzed Synthesis of 3-(Arylsulfonyl)but-3-enals via Coupling of α-Allenols with Diazonium Salts and Sulfur Dioxide

Article abstract of DOI:10.1021/acs.orglett.0c03482

The first coupling of α-allenols, sulfur dioxide, and arenediazonium salts is presented. The three-component reaction which is promoted by visible light can be easily accomplished using DABSO as a sulfur dioxide surrogate in the presence of a photoredox catalyst. In this manner, a broad range of electron-rich and electron-deficient aryl substituents are well accommodated in the sulfonylation-rearrangement cascade to afford the 2,2-disubstituted 3-(arylsulfonyl)but-3-enals in reasonable yields. Based on control experiments, a radical mechanism which does imply 1,2-aryl migration has been proposed.

Full text of DOI:10.1021/acs.orglett.0c03482

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Letter
Visible-Light-Mediated Ru-Catalyzed Synthesis of
3‑(Arylsulfonyl)but-3-enals via Coupling of α‑Allenols with
Diazonium Salts and Sulfur Dioxide
Fernando Herrera, Amparo Luna,* and Pedro Almendros*
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ABSTRACT: The first coupling of α-allenols, sulfur dioxide, and
arenediazonium salts is presented. The three-component reaction
which is promoted by visible light can be easily accomplished using
DABSO as a sulfur dioxide surrogate in the presence of a photoredox
catalyst. In this manner, a broad range of electron-rich and electron-
deficient aryl substituents are well accommodated in the sulfonyla-
tion−rearrangement cascade to afford the 2,2-disubstituted 3-
(arylsulfonyl)but-3-enals in reasonable yields. Based on control
experiments, a radical mechanism which does imply 1,2-aryl migration has been proposed.
he sulfone moiety is among the most outstanding and
the photoredox catalyst of choice (Table 1, entries 1−3) while
Tchameleonic functional groups. Sulfones are versatile acetonitrile was found to be the optimal solvent (Table 1,
synthetic intermediates,1 exhibit pharmacological properties,2
and are also used in material science.3 Vinylsulfones are a
particular subclass of sulfones which display significant
biological activity.4 Sulfur dioxide is a toxic and difficult to
handle gas, which precludes its use in daily organic synthesis.
The seminal work of the Willis group employing a bench-stable
source of sulfur dioxide,5 namely DABSO [DABCO·(SO2)2],
did allow the widespread use of sulfonylative coupling
chemistry. Advances in sulfur dioxide insertion chemistry
using DABSO have allowed the preparation of a variety of
sulfonyl compounds under mild conditions.6,7 On the other
hand, the allene moiety is a versatile building block which
provides efficient synthetic routes to a great variety of cyclic
and acyclic molecules.8 To the best of our knowledge, previous
efforts in the preparation of sulfones from allenes has been
limited to the reactions of allenes with sulfonyl halides, sulfinic
acids, or tosyl cyanide (Scheme 1a)9 and sulfonyl hydrazides
(Scheme 1b and 1c).10 Aiming to surmount this weakness, we
planned to include the combined use of allenes, DABSO, and
diazonium salts. Arenediazonium salts are convenient arylation
reagents because they bear a weak C−N bond which gives
benign N2 as the byproduct. In this context, Wu reported the
copper-catalyzed intramolecular oxysulfonylation of allenoic
acids (Scheme 1d).11 Herein, we present a convenient method
for the synthesis of 2,2-disubstituted 3-(arylsulfonyl)but-3-
enals through the three-component coupling of α-allenols, the
sulfur dioxide surrogate DABSO, and arenediazonium salts,
which is promoted by visible light12 (Scheme 1e).
entries 2, 4−6). The effect of the amounts of DABSO and aryl
diazonium tetrafluoroborate salt was also screened. The use of
2 equiv of DABSO together with 1.5 equiv of diazonium salt
was found to be sufficiently efficient. Diminished yields were
obtained when less excess was used (Table 1, entries 7, 8). The
reaction did not progress in the absence of either the
photocatalyst or irradiation (Table 1, entries 9, 10). However,
3-(arylsulfonyl)but-3-enal 3a was obtained in a low 9% yield
when the reaction was promoted by solar light (Table 1, entry
11). Gratifyingly, the ruthenium-catalyzed (2 mol %) treat-
ment of allenol 1a with 1.5 equiv of diazonium salt 2a and 2
equiv of DABSO under visible light irradiation (LED light
bulb) in acetonitrile (30 mL/mmol 1a) gave rise to product 3a
in moderate yield (59%). The formation of 2-(4-bromophen-
yl)-3-[(4-bromophenyl)sulfonyl]-2-methylbut-3-enal 3a
should be explained invoking a sulfonylation−rearrangement
cascade. The lack of formation of furan-type cyclized adducts
was observed. Noteworthy, the carbon−bromide bonds of
reagents 1a and 2a were transferred unaltered to the final
polyfunctionalized product 3a, which may result in a further
orthogonal functionalization using conventional cross-coupling
chemistry.
Having the optimal conditions in hand, we moved toward
surveying the scope of the above transformation by the
Received: October 19, 2020
In order to optimize the reaction conditions, allenol 1a and
arenediazonium salt 2a were selected as model substrates.
Results depicted in Table 1 revealed that Ru(bpy3)(PF6)2 is
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© XXXX American Chemical Society
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A

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reaction of various allenols 1 with diazonium salt 2a (Scheme
2). The reactions progressed well for allenols 1a−k, bearing
Scheme 1. Synthesis of Sulfones from Allenes: Previous and
Current Proposal
Scheme 2. Sulfonylation-Rearrangement Cascade of
Allenols 1a−k under Photocatalysis; Controlled Synthesis
of 2,2-Disubstituted 3-(Arylsulfonyl)but-3-enals 3a−k
substituents of varying electronic demand at the various
positions of the benzene ring. Thus, both electron-withdrawing
groups (CO2Me) and electron-donating groups (OMe and
Me) and Br were compatible with the sulfonylation−
rearrangement cascade, providing the required products 3a−
k in reasonable yields (49−72%; complete conversion).
Reaction monitoring to make sure that the reaction is
conveniently progressing was carried out using TLC until
total consumption of the starting allenol. Interestingly, ortho-,
meta-, and para-substitution on the benzene ring was well-
tolerated. Besides, a heteroaromatic nucleus worked well as it is
evidenced by the success of the process in products 3j and 3k,
bearing a 2-thienyl and a 3-thienyl ring, respectively.
Additionally, the scope of the sulfonylation−rearrangement
cascade was assessed by the reaction of allenol 1c with
diazonium tetrafluoroborate salts 2b−i having a variety of
substituents at the aryl nucleus (Scheme 3). Precursors 2
displaying no substitution as well as both electron-reach and
electron-withdrawing groups including methoxy, halogens (Cl,
Br and F), nitro, and carboxyethyl all exhibited high reactivities
(complete conversion) in the sequence smoothly providing the
desired 2,2-disubstituted 3-(arylsulfonyl)but-3-enals 3l−r.
Remarkably, products 3 prepared in Schemes 2 and 3 possess
a newly created all-carbon quaternary center, the formation of
which is challenging in organic synthesis.13,14
Table 1. Sulfonylation-Rearrangement Cascade of Allenol
1a with Arenediazonium Salt 2a under Modified Photoredox
Conditions
a
b
c
entry
photocatalyst
solvent
time (h)
yield 3a (%)
1
2
3
4
5
6
7
8
[Ir]
MeCN
MeCN
MeCN
DCE
16
20
16
20
20
20
18
18
20
20
10
10
48
59
21
0
0
0
31
35
0
0
[Ru]
Eosin Y
[Ru]
[Ru]
[Ru]
[Ru]
[Ru]
−
THF
MeOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
d
e
9
f
10
11
12
[Ru]
[Ru]
[Ru]
g
9
30
h
a
b
[Ir] = [Ir(ppy)2(dtbbpy)](PF6)2]. [Ru] = [Ru(bpy)3](PF6)2]. The
Surprisingly, oxindole-tethered quaternary allenol 4a can
smoothly be converted into homodimeric derivatives 5a and
5b under otherwise identical conditions; the structure of (E,E)-
5b was assigned by single-crystal X-ray diffraction analysis
(Supplementary Scheme S1).15 Next, different experiments
were conducted using allenols 1a-Ar and 1b-Ar having C-aryl
substituents at the internal allene position. Noteworthy,
despite the considerable steric hindrance in the final products,
the aryl moiety is well tolerated and 2,2-diaryl-3-(arylsulfonyl)-
but-3-enals 6a−e were obtained after complete conversion in
moderate yields (Scheme 3). In one case, the nonexpected
reactions were carried out under an argon atmosphere using 1a (0.2
mmol), 2a (0.3 mmol), and DABSO (0.4 mmol). Reaction progress
c
was followed by TLC. Yield of pure, isolated product with correct
d
analytical and spectral data. The reaction was carried out using 1a
e
(0.2 mmol), 2a (0.3 mmol), and DABSO (0.2 mmol). The reaction
was carried out using 1a (0.2 mmol), 2a (0.2 mmol), and DABSO
f
g
(0.4 mmol). The reaction was carried out in the darkness. The
h
reaction was carried out using daylight on a sunny day. The reaction
was carried out in the presence of air instead of under argon.
B
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Scheme 3. Photocatalyzed Sulfonylation−-Rearrangement
Cascade of Allenols 1c and 1a,b-Ar with Arenediazonium
Salts 2a−i; Controlled Synthesis of 2,2-Disubstituted 3-
(Arylsulfonyl)but-3-enals 3l−r and 6a−e
Scheme 4. Tentative Mechanistic Explanation for the
Multicomponent Reaction between DABSO, Diazonium
Salts, and α-Allenols
3-enals bearing both electron-rich and electron-deficient aryl
substituents are accessible using DABSO as a sulfur dioxide
surrogate, visible light, and a ruthenium catalyst. Control and
radical inhibition experiments indicate that a radical mecha-
nism is possible for the sulfonylation−rearrangement cascade.
ASSOCIATED CONTENT
* Supporting Information
■
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c03482.
rearranged aldehyde 7a was obtained as a chromatographically
separable minor product.
Experimental procedures, characterization data of new
compounds, and copies of NMR spectra (PDF)
In order to shed light on the reaction mechanism, various
control experiments were performed (Supplementary Scheme
S2). No sulfonyl-butenals were formed in the absence of the
photocatalyst or when the reaction was carried out in darkness.
The above results suggest the formation of arylsulfonyl radicals
under photoredox catalytic conditions, with the crucial role of
both the ruthenium photosensitizer and visible light. Besides,
the construction of the sulfonyl-butenal scaffold was sup-
pressed with the presence in the reaction medium of TEMPO
(Supplementary Scheme S2), a well-known radical inhibitor.
All these experiments together point to the radical nature of
the sulfonylation−rearrangement cascade and participation of
arylsulfonyl radicals.
A pathway for the formation of 3-(arylsulfonyl)but-3-enals 3
is outlined in Scheme 4.1617 Initially, participation of the
DABSO results in the generation of the 1,4-diazabicyclo-
[2.2.2]octanyl cation radical I and the arylsulfonyl radical II.
This crucial reactive species is ready to react with the α-allenol
1 to form allylic radicals III, which after oxidation would
evolve to allylic cations IV. This oxidation step which implies a
single electron transfer (SET) is mediated by visible light,
catalyzed by the ruthenium salt (photoredox catalyst), and
promoted by the cation radical I. Next, 1,2-aryl migration
allows the formation of cationic homoallylic alcohols V, which
rapidly evolve to protonated β,γ-unsaturated aldehydes VI.
Final products, 2,2-disubstituted-3-(arylsulfonyl)but-3-enals 3,
are obtained after spontaneous deprotonation of intermediates
VI.
Accession Codes
CCDC 1900824 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Amparo Luna − Grupo de Lactamas y Heterociclos Bioactivos,
Departamento de Química Orgánica, Unidad Asociada al
CSIC, Facultad de Química, Universidad Complutense de
Madrid, 28040 Madrid, Spain; Email: alunac@
quim.ucm.es
Pedro Almendros − Instituto de Química Orgánica General,
IQOG, CSIC, 28006 Madrid, Spain; orcid.org/0000-
0001-6564-2758; Email: palmendros@iqog.csic.es
Author
Fernando Herrera − Grupo de Lactamas y Heterociclos
Bioactivos, Departamento de Química Orgánica, Unidad
Asociada al CSIC, Facultad de Química, Universidad
Complutense de Madrid, 28040 Madrid, Spain
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c03482
In conclusion, the three-component coupling of α-allenols,
sulfur dioxide, and arenediazonium salts18 has been uncovered.
The reactions were conducted in mild conditions at room
temperature. In this way, 2,2-disubstituted 3-(arylsulfonyl)but-
Notes
The authors declare no competing financial interest.
C
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ACKNOWLEDGMENTS
■
This work was supported in part by the Spanish Agencia
́
Estatal de Investigacion and European Regional Development
Fund (Project PGC2018-095025-B-I00).
DEDICATION
■
́
́
́
In memory of Prof. Jose. L. Gomez-Skarmeta (1966−2020), a
reputed biochemist and friend.
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E
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