α-Organylchalcogenation of aldehydes and ketones with diorganyl dichalcogenides promoted by K3PO4

Article abstract of DOI:10.1007/s00706-014-1188-7

A new catalytic method for direct α-organylchalcogenation of aldehydes and ketones has been developed. When various aldehydes and ketones were allowed to react with diorganyl dichalcogenides in the presence of K ₃PO₄, under mild reac

Full text of DOI:10.1007/s00706-014-1188-7

Monatsh Chem
DOI 10.1007/s00706-014-1188-7
ORIGINAL PAPER
a-Organylchalcogenation of aldehydes and ketones with diorganyl
dichalcogenides promoted by K3PO4
•
Barahman Movassagh Ali Yousefi
Received: 9 September 2013 / Accepted: 15 February 2014
Ó Springer-Verlag Wien 2014
Abstract A new catalytic method for direct a-organ-
ylchalcogenation of aldehydes and ketones has been
developed. When various aldehydes and ketones were
allowed to react with diorganyl dichalcogenides in the
presence of K3PO4, under mild reaction conditions, the
corresponding a-organylseleno and a-arylthio aldehydes
and ketones were obtained in good to high yields.
Several procedures have been developed for the prepa-
ration of a-phenylseleno aldehydes and ketones, including
(1) the reaction of electrophilic organoselenium reagents,
such as PhSeX (X = Br, Cl), N-(phenylseleno)phthalimide
(NPSP), PhSeX3, PhSeO2CCF3 with aldehydes, ketone
enolates, or enolate derivatives [18–23]; (2) the nucleo-
philic reaction of phenylselenolates with a-halo aldehydes
or ketones [24–26]; and (3) the insertion of elemental
selenium into zinc–carbon bonds [27]. The most common
method for a-sulfenylation of ketones involves the reaction
of enolates [28–33] with various sulfenylating reagents,
such as MeSSMe, PhSSPh, PhSCl, methylmethanthiosul-
fate (MeSSO2Me), N-phenylthiocaprolactam, or N-
(phenylthio)phthalimide. N-Chlorosuccinimide (NCS) has
also been introduced for a-sulfenylation of ketones with
aromatic thiols [34]. However, various drawbacks, such as
the employment of air- and moisture-sensitive and expen-
sive reagents or poisonous transition metal catalysts, the
use of very low temperature (-78 °C), low yields, labori-
ous manipulation, and multistep reactions encountered in
the reported methodologies, necessitate the development of
a more efficient and convenient method.
Keywords a-Organylchalcogenation Á
Diorganyl dichalcogenides Á Aldehydes Á Ketones Á
K3PO4
Introduction
Owing to the wide synthetic utility of a-organylseleno
carbonyl compounds [1–5] and a-sulfenyl ketones [6–9],
much effort has been devoted to their syntheses. For
example, a-phenylseleno aldehydes and ketones can be
converted into the corresponding synthetically useful a,b-
unsaturated carbonyl compounds through selenoxide
elimination reactions [10–12]. In addition, these com-
pounds can be transformed into other important organic
intermediates, such as amines [13], a-amino acids [14],
allylic alcohols [15], aziridines [16], and a-hydroxy esters
[17].
Recently, we reported a simple and very efficient pro-
cedure for a-phenylselenenylation of aldehydes and
ketones from the corresponding aldehydes or ketones and
diphenyl diselenide in the presence of KF/Al2O3 [35]. In
the same year, 2-phenylseleno aldehydes and ketones were
selectively obtained from diphenyl diselenide using KF/
Al2O3 and PEG-400 [36]. A similar reaction, utilizing
Cs2CO3 as catalyst, was reported by Nishiyama and co-
workers [37]; however, this catalyst was largely successful
on ketones, but complex reaction mixtures were observed
for aldehydes. Driven by our continuing interest in the
K3PO4-mediated reactions [38, 39] and with the aim to
expand its application, herein we present its utility in the
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-014-1188-7) contains supplementary
material, which is available to authorized users.
B. Movassagh (&) Á A. Yousefi
Department of Chemistry, K. N. Toosi University of
Technology, P.O. Box 16315-1618, Tehran, Iran
e-mail: bmovass1178@yahoo.com
123

B. Movassagh, A. Yousefi
synthesis of a-organylchalcogeno aldehydes and ketones
by the reaction of various aldehydes and ketones with
symmetrical diorganyl dichalcogenides. Symmetrical di-
chalcogenides (RXXR, X = Te, Se, S) are versatile
synthetic reagents [40, 41].
Table 1 Optimization of reaction conditions
Entry Solvent n-Heptanal/
mmol
K3PO4/
mmol
Conditions Yielda/
%
1
THF
3
3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2
40 °C/4 h NR
40 °C/4 h 70
40 °C/4 h 61
40 °C/4 h NR
40 °C/4 h 42
40 °C/4 h 78
40 °C/4 h 69
40 °C/4 h 63
40 °C/4 h 77
40 °C/4 h 46
40 °C/4 h 71
40 °C/4 h 69
40 °C/4 h 41
40 °C/4 h 32
25 °C/4 h 53
35 °C/4 h 64
50 °C/4 h 78
2
DMF
Tripotassium phosphate continues to attract much
attention from organic chemists because of its versatility in
synthetic chemistry: it is cheap, non-toxic, a strong inor-
ganic base (pKa = 12.32 for the conjugate acid), and it is
used as an alternative non-nucleophilic base in several
reactions [42–45].
3
CH3CN 3
4
EtOH
3
3
3
2
1
5
3
3
3
3
3
3
3
3
5
DME
6
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
7
8
9
10
11
12
13
14
15
16
17
Results and discussion
1
0.7
0.5
0.25
1.5
1.5
1.5
The model reaction of n-heptanal (1a) with diphenyl
diselenide was carried out under various reaction conditions
in an aerobic atmosphere in the presence of K3PO4
(Scheme 1). The results are listed in Table 1. The reaction
proceeded quantitatively with a molar ratio of diselenide/n-
heptanal/K3PO4 = 1:3:1.5 in dimethyl sulfoxide (DMSO)
at 40 °C (Table 1, entry 6). When diphenyl diselenide was
treated with 2, 1, and 5 equivalents of 1a at 40 °C for 4 h, 2a
was obtained in lower yields (Table 1, entries 7–9). It is
interesting to note that when higher (2 mmol) or lower (1,
0.7, 0.5, and 0.25 mmol) concentrations of K3PO4 were
used, the yields of 2a dropped (Table 1, entries 10–14). The
effect of the reaction temperature was also checked; lower
temperatures (25 and 35 °C) gave poorer results (Table 1,
entries 15 and 16) whereas higher temperature (50 °C) had
no effect on the isolated yield (Table 1, entry 17).
Reaction conditions: n-heptanal, diphenyl diselenide, K3PO4, 2 cm3
solvent, air atmosphere
DME 1,2-dimethoxyethane, NR no reaction
a
Isolated yields
Scheme 2
After optimization, a variety of other aldehydes and
ketones were shown to undergo the reaction smoothly,
giving the desired a-phenyl/alkylselenenylated product in
good to high yields (Scheme 2). The results are summa-
rized in Table 2.
corresponding mono a-phenyl/alkylselenyl ketones 4i–4q in
37–84 % yields (Table 2, entries 9–17).
All products were fully characterized by spectroscopic
methods (IR, 1H and 13C NMR) and compared with authentic
spectra. Interestingly, neither condensation adducts nor
double a-organylselenenylated products were detected in the
course of these reactions. The treatment of aldehydes with
diphenyl diselenide afforded the corresponding a-phe-
nylselenenylated products 4a–4h in 56–82 % yields
(Table 2, entries 1–8). When a-phenylselenenylation reac-
tions of various ketones with diorganyl diselenide were
examined, longer reaction times were observed, giving the
Encouraged by these results, we extended the scope of
this methodology to K3PO4-mediated reaction of carbonyl
compounds with diphenyl ditelluride and various disulfides
(Scheme 3; Table 3). As in the case of diorganyl disele-
nide, disulfides can also react smoothly with different
aldehydes and ketones under the same reaction conditions.
It was observed that ketones require longer reaction times
to afford the respective a-arylthio derivatives 6b–6g
(Table 3, entries 2–7). We also noted that the reaction
yields were slightly lower when a cyclic ketone, cyclo-
hexanone, was used. However, under the same reaction
conditions, the treatment of n-heptanal and 3-pentanone
with diphenyl ditelluride did not produce the expected a-
phenyltelluro derivatives even after 24 h.
Scheme 1
123

a-Organylchalcogenation of aldehydes and ketones
Table 2 K3PO4-mediated a-
organylselenation reactions of
aldehydes and ketones
Entry
Product
Time /h
3.5
Yielda /%
81
Ref.
[20]
SePh
CHO
SePh
1
4a
4b
4
2
3
6
3
61
82
[20]
[20]
CHO
SePh
4c
CHO
2
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
4
5
6
7
8
9
4d
4e
4f
4
5
64
72
62
56
73
82
[20]
[20]
[20]
[20]
[20]
[20]
3
5
6
6
4g
4h
4i
6
7
6
Ph
O
24
SePh
O
SePh
10
11
12
4j
4k
4l
20
20
20
84
82
80
[20]
[20]
[35]
O
O
SePh
SePh
Ph
Ph
O
13
14
4m
4n
28
24
64
62
[20]
[20]
SePh
SePh
O
O
N
SePh
15
4o
18
74
[20]
CH3
O
Se
Se
16
4p
4q
28
72
54
37
[46]
[47]
Ph
Reaction conditions: aldehyde
or ketone (3.0 mmol), diorganyl
dichalcogenide (1.0 mmol),
K3PO4 (1.5 mmol), in 2 cm3 dry
Ph
O
17
DMSO at 40 °C
a
Isolated yields
123

B. Movassagh, A. Yousefi
In conclusion, we have developed a new convenient and
efficient protocol for a-organylchalcogenation of aldehydes
and ketones with symmetrical diorganyl dichalcogenides in
the presence of K3PO4 under mild reaction conditions with
good to high yields. This process represents a suitable
alternative to existing methods.
layer chromatography (TLC) was carried out on precoated
plates (silica gel 60 F254). Preparative TLC was performed
on TLC glass plates (20 9 20 cm) using silica gel 60
PF254?366 as adsorbent.
General procedure
To a stirred solution of aldehyde or ketone (3.0 mmol) and
anhydrous K3PO4 (1.5 mmol) in 2 cm3 dry DMSO, dior-
ganyl dichalcogenide (1.0 mmol) was added. Stirring of
the resulting reaction mixture was continued at 40 °C for
an appropriate time (Tables 2, 3). After the reaction was
complete (monitored by TLC), the mixture was filtered and
the solid, K3PO4, was washed thoroughly with 25 cm3
EtOAc. The filtrate was washed with water (2 9 20 cm3)
and dried over anhydrous MgSO4. The solvent was evap-
orated to give the crude product which was purified by
preparative TLC (silica gel, eluent n-hexane/
EtOAc = 10:1). Excess diorganyl dichalcogenides were
recovered in high purity. All compounds were character-
Experimental
Chemicals were purchased from Merck chemical company.
1
Yields refer to the isolated products. H (300 MHz) and
13C (75 MHz) NMR spectra were recorded using a Bruker
AQS-300 Avance spectrometer. IR spectra were obtained
using an ABB FTLA 2000 instrument. Analytical thin-
Scheme 3
1
ized by IR, H and 13C NMR spectroscopy.
Table 3 K3PO4-mediated a-
arylthiolation of aldehydes and
ketones
Entry
Product
Time /h
3
Yielda /%
63
Ref.
[33]
SPh
H3C
1
6a
6b
CHO
3
O
CH3
H3C
2
3
20
18
86
85
[34]
[34]
SPh
O
CH3
H3C
6c
S
Br
O
CH3
H3C
4
6d
20
85
[34]
S
O
SPh
5
6
7
6e
6f
22
18
20
61
63
64
[34]
[34]
[34]
O
S
Reaction conditions: aldehyde
or ketone (3.0 mmol), diaryl
disulfide (1.0 mmol), K3PO4
(1.5 mmol), 2 cm3 dry DMSO at
40 °C
Cl
O
S
6g
Br
a
Isolated yields
123

a-Organylchalcogenation of aldehydes and ketones
Acknowledgments Acknowledgment is made to the K. N. Toosi
University of Technology Research Council for financial support of
this study. The authors express their gratitude to Dr. Sogand Nor-
oozizadeh for editing the English content of this manuscript.
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