Diaryliodonium salts as efficient Lewis acid catalysts for direct three component Mannich reactions

Article abstract of DOI:10.1039/c5ra00209e

Diaryliodonium(iii) salts, as highly active and versatile Lewis acid catalysts for the direct three component Mannich reaction under solvent free conditions, have been investigated. The Mannich products were isolated in good to excellent yields in a very clean manner. Additionally, the catalyst could be recycled without significant loss of its catalytic activity. This journal is

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Diaryliodonium Salts as Efficient Lewis Acid Catalysts for Direct Three
Component Mannich Reactions
Yanxia Zhang,a,b Jianwei Han*b and Zhen-Jiang Liu*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Diaryliodonium(III) salts (8, Figure 1) have been extensively
used in organic synthesis. As one of the most versatile
hypervalent iodine compounds, diaryliodonium(III) salts were
40 employed as electrophilic arylating agents in a wide range of
reactions and the interest in iodine(III)ꢀmediated reaction has
recently increased considerably due to their structural properties.8
Iodine(III) compounds are electrophilic at iodine, because of the
node in the nonꢀbonding orbital of the hypervalent bond. With
45 this consideration, cationic iodine, which has a lowꢀlying LUMO
that can accept an electron pair, was able to form adducts with
electroꢀnegative atoms in the substrate, such as oxygen, nitrogen,
sulfur and halogens. This interaction has partial charge transfer
character thus activating the substrates towards nucleophilic
50 attack for catalysis. Moreover, diaryliodonium salts are airꢀ and
moistureꢀstable compounds, whose chemical properties are
similar to transition metals derivatives of Hg, Pb and Pd
complexes, but without the toxicity and environmental
problems associated with these heavy metals.8 Herein, we
55 would like to describe our results on the evaluation of
diaryliodonium(III) salts as catalysts in three component Mannich
reactions. To the best of our knowledge, there is no report
concerning diaryliodonium salts as Lewis acid catalysts in
organic synthesis.
Diaryliodonium(III) salts, as highly active and versatile Lewis
acid catalysts for the direct three component Mannich
reaction under solvent free conditions have been investigated.
The Mannich products were isolated in good to excellent
10 yields in a very clean manner. Additionally, the catalyst could
be recycled without significant loss of its catalytic activity.
In the vital part of green chemistry, catalysis has been identified
to be one of the most valuable contributors to improve the
synthetic efficiency while minimizing the chemical wastes.1 As a
15 result, the recent decades witnessed an explosive growth in this
field with the development of various novel catalysts.2 Lewis
acids are considered to be the most popular catalytic species in a
broad variety of transformations.3 Apart from a numbers of
metalꢀbased Lewis acid catalysts, many organic ionic salts
20 bearing cationic center as electron pair acceptor have shown
highly catalytic activity in the name of ionic liquids and ionꢀpair
catalysts.4 So far, several major classes of cations including
ammonium, imidazolium, pyridinium, phosphonium, sulfonium,
silylium and carbeniums were well documented (1ꢀ7, Figure 1).5
25 However, the hypervalent halogen cations received much less
attention for exploring their Lewis acid catalytic activity although
oxidations of various alcohols and phenols, αꢀfunctionalizations
of carbonyl compounds, cyclizations, and rearrangements
catalyzed by hypervalent iodines were well documented.6 In
30 2012, we reported a cationic bromonium, which generated from
Nꢀhalosuccinimide with triphenylphosphine oxide, as an efficient
Lewis acid catalyst for Nazarov cycization of dihydropyran
derivatives.7
60
Figure 2. The photographs for comparison of Mannich reaction
with/without iodonium catalysis. Tube 1: without catalyst; Tube 2: 10 mol%
diphenyliodonium triflate as the catalyst.
65
Although a number of Mannichꢀtype reactions have been
reported,9 the reaction of acetophenone (9a), benzaldehyde (10a)
35 Figure 1. Major ionic salts with various cations as Lewis acid catalysts in
organic reactions.
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DOI: 10.1039/C5RA00209E
and aniline (11a) still remains as a good model to evaluate newly
developed Lewis acid catalysts due to the easy availability of
starting materials.10 Initially, we explored the diphenyliodonium
triflate as a catalyst in this reaction for probing the potential
catalytic activity. To our delight, the desired product of 12a was
isolated in 83% yield with a 10 mol% catalyst loading by using
chloroform as solvent at ambient temperature. To establish the
optimal reaction conditions, various solvents were screened (see
with recycled catalyst. d the loading of acids was used in one equivalent. e
conc. HCl was used in an excess amounts.
35
Next, we investigated the influence of the counteranions of the
diphenyliodonium salts on the catalytic activity, as shown in
5
ꢀ
ꢀ
Table 1, BF4 , TsOꢀ and PF4 as anions gave a comparative yield,
respectively (entries 6ꢀ9, Table 1), however, Brꢀ as anion gave a
lower yield of 55% (entry 9, Table 1). Subsequently, we
Supporting Information), it was found that solvent free conditions 40 examined the structural diversity of various diaryliodonium salts
10 give the best yield of 86%. The model reaction could be
monitored by phase transition phenomena as shown in Figure 2,
the reaction mixture was totally solidified after 24 hours in the
presence of 10 mol% diphenyliodonium triflate as catalyst. As a
as Lewis acid catalysts. The functional groups including halogen,
tertꢀbutyl, and methoxyl on paraꢀposition of aromatic ring were
evaluated in the model reaction. Generally, catalysts of 8f-j can
afford the products in good yields (entries 10ꢀ14, Table 1).
comparison, the reaction did not occur checked by thin layer 45 Electronꢀdonating group of methoxyl gave lower yield of 56%
15 chromatography (TLC) if no catalyst was employed. In order to
compare the activity with common acid catalysts, several
Brønsted acids such as trifluoromethanesulfonic acid (TfOH),
hydrochloric acid (conc. HCl), camphorsulfonic acid (CSA) and
(entry 14, Table 1). Iodonium bromide 8k of [(3ꢀNO2C6H4)2I]Br
as catalysts was also applied in the reaction, only 54% yield of
12a were achieved. Unsymmetrical iodonium salts were also
employed as the catalysts; it was pleasing to find that 8l-n can
Lewis acid of calcium chloride were tried in Mannich reaction 50 catalyze the reaction more efficiently than 8a. Alkynylꢀ
20 under the standard solvent free conditions, noteworthy is that the
acids as promoters were used in one equivalent for improving
efficiency. TfOH and HCl can also provide an excellent yield of
91% and 92% while the rest of acids gave the moderate to good
yields of 57ꢀ85% (entries 2ꢀ5, Table 1).
mesitylioodonium triflate 8m also afford the desired product in a
good yield of 87%. To our surprise, the yield could be improved
to 93% with the use of 8n which bearing a pentafluorobenzene
ring in the catalyst structure. Furthermore, in general, the
55 iodonium salts are of excellent solubility in water. The catalyst of
8n was recycled by water extraction and evaporation. A yield of
83% was achieved by using the recycled iodonium salts under the
standard conditions; this result can meet the requirements of
green chemistry without obvious loss of activity.
25
Table 1 Optimization of catalysts for Mannich reaction under solvent free
conditionsa
60
With 8n as the optimized catalyst in hand, we explored the
scope of the three component Mannich reaction with a range of
substrates of various aldehydes, ketones and amines. In all cases,
the three component Mannich reaction proceeded in the presence
of 10 mol% of iodonium salts smoothly to give the corresponding
Entry
1
2d
3d
4e
Cat.
8a
Ar1(Ar2) of 8
(Ph)2
X
OTf
ꢀꢀ
% Yieldb
86
65 products in good to excellent yields at room temperature (Table
2). It is noted that acetophenones, benzaldehydes and anilines
carrying either electronꢀdonating or electronꢀwithdrawing
substituents reacted well. Substrates with various substituents on
the orthoꢀ, metaꢀ, and paraꢀpositions of aromatic ring were well
70 tolerated in this catalytic protocol. However, steric factors
affected the reactivity, for example, the products of 12k were
obtained in moderate yield of 69% (Table 2). Interestingly, 4ꢀ
bromoꢀ2ꢀnitrobenzaldehyde gave 12p in a good yield of 83%.
Pentafluorobenzaldehyde was employed as aldehyde component
75 for checking the fluorous interactions with fluoroꢀcontaining
catalyst 8n, however, only 45% yield of 12n was achieved with
standard procedure. For the both aldehyde and aniline derivatives,
substrates with electronꢀdonating methoxyl group afford better
results. For example, 4ꢀmethoxyaniline as reactants furnished
80 product 12u in an excellent yield of 90%. As expected,
cyclohexanone as a more reactive partner gave the desired
product 12e in a quantitative yield. The results of this study on
the various substrates were summarized in Table 2. Overall, it can
be seen that the scope and generality of the present method has
85 been shown with respect to various aldehydes and anilines.
TfOH
TsOH
HCl
CaCl2
8b
ꢀꢀ
91
ꢀꢀ
ꢀꢀ
85
ꢀꢀ
ꢀꢀ
92
5d
ꢀꢀ
ꢀꢀ
57
6
(Ph)2
Br
55
7
8c
(Ph)2
BF4
OTs
PF6
OTf
OTf
OTf
OTf
OTf
Br
65
8
8d
(Ph)2
80
9
8e
(Ph)2
71
10
11
12
13
14
15
8f
(4ꢀFC6H4)2
(4ꢀClC6H4)2
(4ꢀBrC6H4)2
(4ꢀtBuC6H4)2
(4ꢀMeOC6H4)2
(3ꢀNO2C6H4)2
85
8g
81
8h
77
8i
77
8j
56
8k
54
4ꢀMeOC6H4(4ꢀ
NO2C6H4)
16
8l
OTs
89
17
18
8m
8n
C6H4C≡C(Ph)
OTf
87
C6F5(Mesityl)
OTs
93 (83)c
a
Unless otherwise specified, reaction conditions: 9a (1 mmol), 10a (1
30 mmol), 11a (1 mmol) in the presence of catalyst (0.1 mmol) at room
temperature for 24 hours. b Isolated yield. c Yield in bracket was obtained
2
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The mechanism of classic Mannich reaction had been
described;11 an enolized carbonyl species was realized from the
active hydrogen compounds with the catalysis of an acid, the
15 resulting enol attacked the iminium ion which formed from the
amine and aldehyde to yield Mannich base. However, a subject of
considerable discussion is the possibility of the formation of
chalcones from an enolized carbonyl species with benzaldehydes,
chalcone could then react with aniline to afford the desired
20 Mannich bases. In this connection, two control experiments were
carried out with this catalytic protocol. The reaction of anline
with chalcone gives Mannich base 12a in 79% yield [(Scheme 1,
Eq. (1)]. Another reaction between acetophenone and imine 14
was attempted; the product 12a was also obtained in a slight
25 lower yield of 60% [(Scheme 1, Eq. (2)]. Of note, the formation
of chalcone in this case was also observed in this procedure
[(Scheme 1, Eq. (2)]. Therefore, thus far, no single mechanism
which could be accounted for all the experimental facts has been
suggested.
5
Table 2 Scope of Mannich reactions under solvent free conditionsa, b
Ar1
O
O
Ar2
8n (10 mol%)
1
+ Ar CHO Ar2NH2
R1
N
R2
+
R1
conditions
H
R2
12
9
10
11
O
O
O
N
N
H
N
H
H
OMe
12d, 85%
N
Br
12c, 90%
12b, 83%
NO2
NO2
O
Ph
O
O
8n
(10 mol%)
O
NH
O
(1)
(2)
PhNH2
N
+
N
H
Ph
+
Ph
N
H
solvent free, r.t.,
24 h.
H
Ph
Ph
11a
13
12a, 79% yield
12g, 76%
12e, 99%
12f, 67%
Ph
Br
Cl
O
Ph
OMe
O
NH
8n
(10 mol%)
N
Ph
Me
solvent free, r.t.,
24 h.
Ph
Ph
O
Ph
O
O
9a
12a, 60% yield
14
N
H
N
N
30
H
H
Scheme 1. Control experiments for reaction pathways in yielding
Mannich products.
12j, 88%
12i, 96%
12h, 96%
Me
Cl
The asymmetric version of catalytic Mannich reaction is a
35 useful method for the preparation of enantioenriched αꢀ
aminocarbonyl molecules which possess favourable
Br
O
O
O
N
H
N
H
N
H
pharmacological properties.12 Diaryliodonium salts with a chiral
anion were reported for asymmetric inductions.13 Hence, the
asymmetric variations of Mannich reaction were investigated as
40 depicted in Scheme 2. Dꢀcamphorsulfonate and (S)ꢀBINOLꢀ
phosphate as chiral anions were employed for the iodonium
catalysts in the title reaction. Unfortunately, 8o afforded the
desired product 12a in 45% yield without enantioselectivity.
Enantiomeric excess value of 7% was obtained with 8p as the
45 catalysts although the yield of 12a in 89% is satisfactory (Scheme
2).
12m, 87%
12l, 94%
12k, 69%
Br
Br
F
NO2
O
O
O
N
H
N
H
N
H
N
12n, 45%
12p, 83%
12o, 94%
CF3
Cl
Cl
O
O
O
N
H
N
H
N
H
12r, 89%
12s, 76%
12q, 86%
Br
OMe
O
O
N
H
N
H
12u,90%
12t, 98%
a
Unless otherwise specified, reaction conditions: 9 (1 mmol), 10 (1
Scheme 2. Attempts on asymmetric Mannich reactions with catalysis by
50 8o and 8p .
mmol), 11 (1 mmol) in the presence of iodonium salt 8n (0.1 mmol) at
10 room temperature for 24 hours. b Isolated yield.
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DOI: 10.1039/C5RA00209E
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In summary, we have firstly demonstrated that
diaryliodonium(III) salts are highly active and versatile Lewis
acid catalysts for the direct three component Mannich reaction.
The products are isolated in good to quantitative yields in a very
clean manner. The high yields and recyclable catalyst for this
reaction show potential for using hypervalent iodine species as
Lewis acid catalysts in the development of novel sustainable
processes, both in industry and academia. Furthermore, the
catalytic activity could be tuned by the changing the aromatic
10 groups around the iodocation. It is anticipated to discover chiral
version of catalysis by using chiral hypervalent iodine(III)
compounds or the strategy of asymmetric counteranionꢀdirected
catalysis as described above. Therefore, we are continuing to
explore the scope and limitation of iodocation catalysis by tuning
15 the Lewis acidity to gain more understanding of reactivity and to
further extend the reaction scope. These results will be reported
in due course.
65
70
75
5
Acknowledgment. This work was supported by the National
20 Nature Science Foundation of China (NSFC, Nos. 21472213,
21202186, 21102093), The Chinese Academy of Sciences–
Croucher Funding Scheme for Joint Laboratories and the
Innovation Program of Shanghai Municipal Education
Commission (No. 14YZ144).
25 Notes and references
a School of Chemical and Environmental Engineering, Shanghai Institute
of Technology,100 Haiquan Road, Shanghai 201418, P. R. China. Fax:
(+86)-21- 60877231; Tel: (+86)-21- 60877227; E-mail: zjliu@sit.edu.cn
b Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai
30 Institute of Organic Chemistry, The Chinese Academy of Sciences, 345
Ling Ling Road, Shanghai 200237, P. R. China. Fax: (+86)-21-
54925383; Tel: (+86)-21- 54925551; E-mail: jianweihan@sioc.ac.cn
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
35 DOI: 10.1039/b000000x/
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