De Novo Synthesis of α-Hydroxy Ketones by Gallic Acid-Promoted Aerobic Coupling of Terminal Alkynes with Diazonium Salts

Article abstract of DOI:10.1002/chem.201705106

An unprecedented metal-free direct preparation of unprotected α-hydroxy ketones from terminal alkynes under mild conditions with diazonium salts as the arene source and without the requirement of irradiation is described. The process is general and fully compatible with a wide variety of substitution in both reactants. Experimental and computational evidence strongly suggest the involvement of radical species in the transformation.

Full text of DOI:10.1002/chem.201705106

A Journal of
Accepted Article
Title: De Novo Synthesis of α-Hydroxy Ketones via Gallic Acid-
Promoted Aerobic Coupling of Terminal Alkynes with Diazonium
Salts
Authors: Pedro Almendros, Benito Alcaide, Israel Fernández,
Fernando Herrera, and Amparo Luna
This manuscript has been accepted after peer review and appears as an
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To be cited as: Chem. Eur. J. 10.1002/chem.201705106
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Supported by

10.1002/chem.201705106
Chemistry - A European Journal
COMMUNICATION
De Novo Synthesis of α-Hydroxy Ketones via Gallic Acid-Promoted
Aerobic Coupling of Terminal Alkynes with Diazonium Salts
Benito Alcaide,*[a] Pedro Almendros,*[b] Israel Fernández,[c] Fernando Herrera,[a] and Amparo Luna[a]
Abstract: An unprecedented metal-free direct preparation of
Ar3PAuCl
ArN2BF4
+
unprotected α-hydroxy ketones from terminal alkynes under mild
conditions with diazonium salts as the arene source and without the
requirement of irradiation is described. The process is general and
fully compatible with a wide variety of substitution in both reactants.
Experimental and computational evidences strongly suggest the
involvement of radical species in the transformation.
(1)
[(Ph3P)AuNTf2]
photocatalyst
or
R
Z
Z
R
Ar
work
literature
RT, visible
base,
ligand
light
Ref.
[6e,f,g]
=
or
TMS
H
H5 3PAuCl]
)
ArN2BF4
+
[(C6
O
C6H4 3PAuCl]
[(4CF3
)
photocatalyst
(2)
literature
R1
R1
R2
or
R2
work
work
RT,
+
LEDs
RT, blue LEDs
green
Ref.
Ar
[6a]
The occurrence of the α-hydroxy ketone framework in natural
products and biologically relevant molecules,[1] coupled to the use
of this moiety as a versatile building block in organic synthesis,[2]
have led to research efforts on the preparation of α-hydroxy
ketones.[3] Usually, reported synthetic methods are tedious and
present several drawbacks such as harsh conditions, low atom
economy, the use of harmful reagents or transition metals, and
the formation of environmentally unfriendly by-products. Aiming to
surmount these shortcomings, we decided to implement a benign
method for the facile preparation of functionalized α-hydroxy
ketones (typical cross benzoin products).
H5 3PAuCl]
)
[(C6
R2
O
OH
photocatalyst
R2
R1
(3)
literature
ArN2BF4
ArN2BF4
R3
R1
RT, visible
light
R3
Ref.
Ar
[6b,c,d]
OH
acid
gallic
(4)
current work
+
R
R
Ar
acetone-H
2O
O
O2 RT
,
Scheme 1. Reactions of alkynes with diazonium salts.
The oxidation of organic molecules mediated by O2 is a recent
and green methodology that can be carried out at room
temperature.[4] The use of arenediazonium salts as the
The cytotoxicity of transition metal impurities prevents
samples prepared via metal catalysis to enter biological assays.
Therefore, the development of efficient metal-free strategies for
the synthesis of molecules of biological interest is a growing
concern these days. Inspired by previous efforts on the
organomediated generation of aryl radicals from arenediazonium
salts,[7] we decided to perform a non-photochemical metal-free
coupling between arenediazonium salts and alkynes solely
promoted by an organic molecule. We initiated our study using
phenylacetylene 1a as the starting alkyne and phenyldiazonium
salt 2a as the arylation partner. Ascorbic acid I, gallic acid II, and
benzene-1,2,3-triol III were selected as cheap organic promoters
for the generation of radicals from arenediazonium salts by
dinitrogen extrusion. After extensive solvent screening, we
selected an acetone/water mixture (3:1) as the solvent of choice
(Table 1, entry 2 and entries 7–10). Rather unexpectedly, the
obtained product was the α-hydroxy ketone 3aa, whose formation
required the participation of both water in the solvent and oxygen
from the air. The yield of benzoin 3aa increased with the inclusion
of an O2 balloon (Table 1, entries 2 and 6). The use of excess (3
equiv) of diazonium salt was not benefitial due to the formation of
diazo-derived side products (Table 1, entry 4). The inclusion of
excess (3 equiv) of alkyne increased the cleanliness and the
reaction efficiency to afford the desired product 3aa in 59% yield
(Table 1, entry 2). The use of a 1a:2a ratio of 1:1 was less effective
in this transformation (Table 1, entry 5). The optimal amount of
promoters was established at 100 mol% (Table 1, entry 2). Lower
loadings of I, II, or III resulted in diminished final yields of 2-
hydroxy-1,2-diphenylethan-1-one 3aa (Table 1, entries 11–13).
Promoters I and III were found to be less effective that gallic acid
(Table 1, entries 2 and 3).
functionalization source may represent
a
non-toxic and
convenient strategy, because these aryl transfer reagents release
N2 as the only waste by-product.[5] Moreover, arenediazonium
tetrafluoroborates are readily available from low-cost anilines.
Although remarkable progress has been achieved in the arylation
of alkynes through the use of arenediazonium salts [Scheme 1,
Eq. (1), Eq. (2), and Eq. (3)],[6] there is absence of reports on the
synthesis of α-hydroxy ketones. Herein, we describe an
unprecedented metal-free direct preparation of unprotected α-
hydroxy ketones from terminal alkynes under mild conditions with
diazonium salts as the arene source and without the requirement
of irradiation [Scheme 1, Eq. (4)].
[a]
Prof. Dr. B. Alcaide, F. Herrera, Dr. T. Luna
Grupo de Lactamas y Heterociclos Bioactivos, Unidad Asociada al
CSIC, Departamento de Química Orgánica I, Facultad de Ciencias
Químicas
Universidad Complutense de Madrid, E-28040 Madrid (Spain)
E-mail: alcaideb@quim.ucm.es
[b]
[c]
Prof. Dr. P. Almendros
Instituto de Química Orgánica General, IQOG
Consejo Superior de Investigaciones Científicas, CSIC,
Juan de la Cierva 3, 28006 Madrid (Spain)
E-mail: Palmendros@iqog.csic.es
Dr. I. Fernández
Departamento de Química Orgánica I and Centro de Innovación en
Química Avanzada, Facultad de Ciencias Químicas
Universidad Complutense de Madrid, E-28040 Madrid (Spain)
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/chem.201705106
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COMMUNICATION
Table 1. Screening of reaction conditions for α-hydroxy ketone formation by
organopromoted arylation of alkyne 1a.[a]
serve as reactive handle for further cross-coupling reactions,
survived under the above radical conditions. Interestingly, the
reaction of 4-ethynylbenzenediazonium salt 2i allows the
formation of α-hydroxy ketone 3ai, which bears an alkyne moiety.
On the basis of the results in Scheme 2, both the electronic nature
and the bulk of the substituent on the diazonium salt were
established as not essential (except for NO2) for the reaction to
occur.
COOH
HO
H
OH
O
HO
O
HO
gallic
HO
OH
OH
HO
OH
OH
III
-ascorbic
II
I
acid
( )
acid
OH
L
benzene-1,2,3-triol
(
)
( )
acid
gallic
+
Ph
ArN2BF4
Ph
Ar
O
2 (balloon)
acetone/water
OH
1a
2a–j
O
RT
,
mol%)
(3:1)
organopromoter
(X
+
3aa–ai
Ph
PhN2BF4
Ph
Ph
3aa
acetone/water
(3:1)
1a
2a
Br
OH
Ph
OH
OH
OH
O
RT
O2
,
Ph
3aa
Ph
Ph
Ph
Br
Ph
O
O
O
O
Entry
1
Promoter (X mol%)
I (100)
t (h)
1a:2a Ratio
3:1
Yield (%)[b]
Br
1 h)
3ab
2 h)
3ac
2 h)
OH
3ad
2 h)
(50%,
(59%,
(52%,
(53%,
2
2
45
59
46
33
41
48
1
OH
OH
OH
2
II (100)
III (100)
II (100)
II (100)
II (100)
II (100)
II (100)
II (100)
II (100)
II (50)
3:1
Ph
Ph
Ph
O
3
2
3:1
O
O
O
F
OMe
CO2Et
CF3
4
2
1:3
3ae
Ph
2 h)
3af
4 h)
3ag
1 h)
3ah
2 h)
(45%,
(49%,
(44%,
(61%,
5
2
1:1
OH
OH
3:1[c]
3:1[d]
3:1[e]
3:1[f]
3:1[g]
3:1
Ph
6
2
O
O
7
48
2
NO2
3ai
4 h)
3aj
48
h)
(43%,
(0%,
8
1
9
24
24
2
12
1
Scheme 2. Gallic acid-promoted reaction of alkyne 1a with arenediazonium
salts 2a–j. Controlled synthesis of α-hydroxy ketones 3aa–ai.
10
11
12
13
26
25
21
II (25)
2
3:1
Next, the scope of this coupling was further evaluated by the
reaction of diazonium salt 2b with a series of alkynes having
different substitution pattern (Scheme 3). The protocol was found
to be general and good results were obtained in most of the cases.
The reaction was found to be amenable to heterocyclic-tethered
alkynes such as thiophene derivatives 1i and 1k. Substitution of
the benzene nucleus by a naphthalene core in the alkyne was well
tolerated, and the corresponding α-hydroxy ketone 1i was
achieved in 68% yield. The reaction of diyne systems 1i and 1k
containing two alkynes tethered by an aromatic or heterocyclic
ring gave in a controlled manner the mono-functionalized
products 3ib and 3kb. This result is of potential interest because
the remaining alkyne can be further elaborated. However, the
dialkyne-tethered BODIPY 3l was unreactive under the reaction
conditions. Aliphatic terminal alkynes such as hex-1-yne as well
as non-terminal alkynes such as 1,2-diphenylethyne were both
ineffective for this transformation. Arylalkynes with a strong
acceptor group at the aryl moiety (e.g., 1-ethynyl-4-nitrobenzene)
did not react either under our conditions.
II (10)
2
3:1
[a] Unless otherwise noted, all reactions were carried out in acetone/water (3:1)
in the presence of an oxygen balloon at room temperature. [b] Yield of pure,
isolated product with correct analytical and spectral data. [c] Open air reaction.
It was carried out without the oxygen balloon. [d] The reaction was carried out
in DMF. [e] The reaction was carried out in acetone. [f] The reaction was carried
out in DMF/water (3:1). [g] The reaction was carried out in acetone/MeOH (3:1).
We were curious to check whether this facile generation of 2-
hydroxy-1,2-diphenylethan-1-one 3a could be a general method
for the preparation of α-hydroxy ketones. With the optimized
reaction conditions in hand, we explored the scope and limitations
of this transformation. The combination of alkyne 1a with a variety
of diazonium salts 2a–j smoothly yielded α-hydroxy ketones 3aa–
ai. The results are summarized in Scheme 2. It was found that
arenediazonium salts bearing either electron-withdrawing groups
(CO2Et and CF3) or electron-donating groups such as MeO
resulted in reaction success. The carboxylate derivative 3ag was
obtained in 61% isolated yield as pure product, but adducts 3af
and 3ah were produced in diminished yields. However, the highly
electron-poor nitro derivative 2j did not afford the α-hydroxy
ketone 3aj. The steric effect was studied through the reactions of
1a with arenediazonium salts 2b–d bearing a Br group at ortho-,
meta-, and para-positions. Unnoticeable differences were
observed with these different substitutions in the aromatic ring.
Interestingly, the C–Br bond in products 3ab–ad, which could
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10.1002/chem.201705106
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COMMUNICATION
OH
acid
gallic
= –46.7 kcal/mol) which constitutes the driving force of the
transformation.
+
R
Br
N2BF4
2b
R
O
2 (balloon)
1b–l
O
acetone/water
RT
,
(3:1)
Br
3bb–kb
R1
OH
OH
OH
MeO
O
O
O
Br
Br
Br
1 h)
3hb
S
2 h)
3gb
(51%,
(59%,
3bb R1
3cb R1
1 h)
=
=
Me
(65%,
OMe
1 h)
(39%,
3db R1 Br
1 h)
=
(58%,
MeO
3eb R1
3fb R1
=
OH
CF
6
h)
3 (52%,
OH
=
F
3 h)
(41%,
O
Br
S
O
OH
Br
1.5 h)
3jb
(68%,
3kb
24 h)
(71%,
O
Ph
Br
Me
Me
3ib
2.5 h)
(70%,
Figure 1. Computed reaction profile for the reaction between phenylacetylene
and phenyl radical in the presence of oxygen. Relative enthalpies and bond
lengths are given in kcal/mol and angstroms, respectively. All data have been
computed at the PCM(acetone)-B3LYP-D3/6-311+G**//PCM(acetone)-B3LYP-
D3/6-31+G** level.
N
N
B
F
F
Me
Me
24 h)
3lb
(0%,
Scheme 3. Gallic acid-promoted reaction of alkynes 1b–l with arenediazonium
salt 2b. Controlled synthesis of α-hydroxy ketones 3bb–kb.
According to the computed spin densities, INT5 is better
described as a C-radical rather than an O–radical (due to the
conjugation, see Figure 2). This species is able to react with a
water molecule to produce the radical diol INT6 in a single
reaction step via TS3, a saddle point associated with the
simultaneous formation of the C–OH and O–H bonds. However,
the computed relatively high activation barrier of 31.6 kcal/mol for
this reaction makes the transformation not fully compatible with a
process occurring at room temperature. Fortunately, we found
that another water molecule can be involved in the transformation
serving as a proton-shuttle which leads to the formation of INT6
with a much lower activation energy (∆H≠ = 16.7 kcal/mol, via
TS3’).[9] Finally, the transformation ends up with an intermolecular
hydrogen atom transfer (HAT) mechanism involving INT6 and the
gallic radical (GalO•), initially produced in the aryl radical
generation from PhN2BF4 mediated by gallic acid (GalOH). This
highly exothermic (∆HR = –44.3 kcal/mol) HAT process leads
therefore to the formation of the experimentally observed α-
hydroxyketone 3aa with the concomitant regeneration of gallic
acid, which can enter in a new catalytic cycle.
In order to gain insight regarding the mechanism of this
transformation, a catalytic amount of hydroquinone was added to
the reaction mixture of alkyne 1a and diazonium salt 2a under
otherwise optimized conditions. In the event, the yield of product
3a was considerably lower. The above result suggests that the
present reaction might involve a radical process. To get some
information about the origin of the oxygen atoms at the α-hydroxy
ketones 3, an isotopic labelling study with H218O was carried out.
Unexpectedly, the reaction of 1a with 2b in presence of H218O
yielded nearly unlabeled 18O-labelled product at the hydroxylic
moiety 18O-3ab. This may be attributed to the fact that unwanted
unlabeled residual water in the reaction medium reacts faster than
H218O, avoiding high 18O atom incorporation.
Density Functional Theory calculations were carried out to
gain more insight into the reaction mechanism involved in the
formation of α-hydroxyketones.[8] To this end, the reaction
between phenylacetylene (1a) and phenyl radical (Ph•), initially
formed upon reaction of PhN2BF4 and gallic acid,[7] was explored.
Our calculations indicate that the process begins with the
formation of a van der Waals reaction complex (INT1) which
evolves into radical INT2 in a highly exothermic process (∆HR = –
46.7 kcal/mol). This step proceeds via the transition state TS1,
which is associated with the formation of the new C–C bond, with
a very low activation barrier of 0.1 kcal/mol. According to the data
in Figure 1, the alternative radical addition leading to the isomer
INT2’ (via TS1’) is both kinetically and thermodynamically
unfavored. Next, molecular oxygen enters into the reaction
sequence and leads to the formation of the peroxy radical INT3 in
a barrierless, highly exothermic process (∆HR = –34.1 kcal/mol).
Reaction of the peroxy radical INT3 with a new molecule of C-
radical INT2 leads to the extremely labile peroxyde INT4 which
rapidly evolves into radicals INT5 by homolytic breakage of the
corresponding O–O bond in a strongly exothermic process (∆HR
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10.1002/chem.201705106
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COMMUNICATION
Figure 2. Computed reaction profile for the formation of α-hydroxyketone 3aa.
Relative enthalpies and bond lengths are given in kcal/mol and angstroms,
respectively. All data have been computed at the PCM(acetone)-B3LYP-D3/6-
311+G**//PCM(acetone)-B3LYP-D3/6-31+G** level.
Soc. 2014, 136, 7539; g) X. Linghu, J. S. Johnson, Angew.
Chem. 2003, 115, 2638; Angew. Chem. Int. Ed. 2003, 42, 2534.
[4]
For recent reviews, see: a) G. Urgoitia, R. SanMartin, M. T. Herrero, E.
Domínguez, ACS Catal. 2017, 7, 3050; b) A. Axelsson, L. Ta, H. Sundén,
Synlett 2017, 28, 873. For selected contributions, see: c) A. Ragupathi,
V. P. Charpe, A. Sagadevan, K. C. Hwang, Adv. Synth. Catal. 2017, 359,
1138; d) S. D. McCann, S. S. Stahl, Acc. Chem. Res. 2015, 48, 1756; e)
Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3381; f)
A. N. Campbell, S. S. Stahl, Acc. Chem. Res. 2012, 45, 851; g) S. S.
In conclusion, a metal-free direct preparation of unprotected
α-hydroxy ketones from terminal alkynes under mild conditions
with diazonium salts as the arene source and without the
requirement of irradiation has been successfully achieved. This
transformation involves the initial generation of an aryl radical
which reacts with the alkyne to produce a new radical species
able to react with oxygen and water to afford the observed α-
hydroxyketones. With the help of DFT calculations, a proton
shuttle mechanism mediated by water is suggested to be key in
the formation of intermediate radical diols. Study of this reactivity
in more complex molecules is planned for the future.
Stahl, Angew.
Chem. 2004, 116, 3480;
Angew.
Chem.
Int.
Ed. 2004, 43, 3400. For a Cluster, see: h) Catalytic Aerobic Oxidations
(Eds.: T. Rovis, S. S. Stahl), Synlett 2017, 353, 28, 1546–1585.
a) I. Ghosh, L. Marzo, A. Das, R. Shaikh, B. König, Acc. Chem.
Res. 2016, 49, 1566; b) N. Oger, F.-X. Felpin, ChemCatChem 2016, 8,
1998; c) F. Mo, G. Dong, Y. Zhang, J. Wang, Org. Biomol. Chem. 2013,
11, 1582; d) H. Bonin, E. Fouquet, F.-X. Felpin, Adv. Synth. Catal. 2011,
353, 3063; e) J. M. R. Narayanam, C. R. J. Stephenson, Chem. Soc. Rev.
2011, 40, 102; f) M. R. Heinrich, Chem. Eur. J. 2009, 15, 820; g) B. Dong,
H. Peng, S. E. Motika, X. Shi, Chem. Eur. J. 2017, 23, 11093.
a) L. Huang, M. Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem.
2016, 128, 4888; Angew. Chem. Int. Ed. 2016, 55, 4808; b) A. Tlahuext-
Aca, M. N. Hopkinson, R. A. Garza-Sánchez, F. Glorius, Chem. Eur. J.
2016, 22, 5909; c) J. Um, H. Yun, S. Shin, Org. Lett. 2016, 18, 484; d) B.
Alcaide, P. Almendros, E. Busto, A. Luna, Adv. Synth. Catal. 2016, 358,
1526; e) S. Kim, J. Martín-Rojas, F. D. Toste, Chem. Sci. 2016, 7, 85; f)
A. Tlahuext-Aca, M. N. Hopkinson, B. Sahoo, F. Glorius, Chem.
Sci. 2016, 7, 89; g) R. Cai, M. Lu, E. Y. Aguilera, Y. Xi, N. G. Akhmedov,
J. L. Petersen, H. Chen, X. Shi, Angew. Chem. 2015, 127, 8896; Angew.
Chem. Int. Ed. 2015, 54, 8772.
[5]
[6]
Acknowledgements
Support for this work by the MINECO and FEDER (Projects
CTQ2014-51912-REDC, CTQ2015-65060-C2-1-P, CTQ2015-
65060-C2-2-P, CTQ2016-78205-P) is gratefully acknowledged. F.
H. thanks UCM for a predoctoral contract.
[7]
For selected reports, see: a) D. Felipe-Blanco, F. Alonso, J. C. Gonzalez-
Gomez, Adv. Synth. Catal. 2017, 359, 2857; b) M. D. Perretti, D. M.
Monzón, F. P. Crisóstomo, V. S. Martín, R. Carrillo, Chem. Commun.
2016, 52, 9036; c) F. P. Crisóstomo, T. Martín, R. Carrillo, Angew. Chem.
2014, 126, 2213; Angew. Chem. Int. Ed. 2014, 53, 2181; d) A. Studer, D.
P. Curran, Angew. Chem. 2011, 123, 5122; Angew. Chem. Int. Ed. 2011,
50, 5018; e) S. Losada-Barreiro, V. Sánchez-Paz, C. Bravo-Díaz, Helv.
Chim. Acta 2007, 90, 1559; f) J. F. Bunnett, Acc. Chem. Res. 1978, 11,
413.
Keywords: alkynes • α-hydroxy ketones • metal-free
reactions • selectivity • synthetic methods
[1]
[2]
a) J. Zhu, A. J. H. Klunder, B. Zwanenburg, Tetrahedron
Lett. 1994, 35, 2787; b) A. G. M. Barrett, J. Head, M. L. Smith, N. S.
Stock, J. Org. Chem. 1999, 64, 6005; c) K. D. Wellington, R. C.
Cambie, P. S. Rutledge, P. R. Bergquist, J. Nat. Prod. 2000, 63, 79.
a) S. Bhattacharya, R. Rahaman, S. Chatterjee, T. K. Paine, Chem. Eur.
J. 2017, 23, 3815; b) F. Cui, L. Dou, Q. Yang, Y. Yu, Z. Niu, Y. Sun, H.
Liu, A. Dehestani, K. Schierle-Arndt, P. Yang, J. Am. Chem.
Soc. 2017, 139, 3027; c) J. Christoffers, T. Werner, W. Frey, A.
Baro, Chem. Eur. J. 2004, 10, 1042; d) F. A. Davis, B. C. Chen, Chem.
Rev. 1992, 92, 919.
[8]
[9]
All calculations were carried out at the PCM(acetone)-B3LYP-D3/6-
311+G**//PCM(acetone)-B3LYP-D3/6-31+G** level. See computational
details in the Supporting Information.
For a related proton-shuttle mechanism in the hydroamination of alkynes
which also decreases the corresponding activation barrier, see: G.
Kóvacs, A. Lledós, G. Ujaque, Angew. Chem. 2011, 123, 11343; Angew.
Chem. Int. Ed. 2011, 50, 11147.
[3]
a) W. Liu, C. Chen, P. Zhou, J. Org. Chem. 2017, 82, 2219; b) L. M.
Zhang, L. L. Zhu, J. Yang, J. S. Luo, R. Hong, J. Org. Chem. 2016, 81,
3890; c) J. Yu, J. Cui, C. Zhang, Eur. J. Org. Chem. 2010, 7020; d) C.
Chen, X. Feng, G. Zhang, Q. Zhao, G. Huang, Synthesis 2008, 3205; e)
W. S. Ide, J. S. Buck, The Synthesis of Benzoins, in Organic Reactions,
John Wiley & Sons, 2004, vol. 4, 269–304. For cross benzoin synthesis,
see: f) S. M. Langdon, M. M. D. Wilde, K. Thai, M. Gravel, J. Am. Chem.
[10] For a recent review on HAT processes, see: M. Nechab, S. Mondal, M.
P. Bertrand, Chem. Eur. J. 2014, 20, 16034.
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10.1002/chem.201705106
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Benito Alcaide,* Pedro Almendros,*
Israel Fernández, Fernando Herrera,
and Amparo Luna
COOH
HO
OH
OH
OH
-
+
R
ArN2BF4
R
Ar
Page No. – Page No.
acetone H2O
O
O
2, RT
metal-free
examples
19
no
no
heating
irradiaton
De Novo Synthesis of α-Hydroxy
Ketones via Gallic Acid-Promoted
Aerobic Coupling of Terminal
Alkynes with Diazonium Salts
to 71%
up
yield
An organopromoted preparation of unprotected α-hydroxy ketones from terminal
alkynes under mild aerobic conditions with diazonium salts as the arene source and
without the requirement of irradiation has been achieved.
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