Photoinduced Aminocarbonylation of Aryl Iodides

Article abstract of DOI:10.1002/chem.201503164

Transition metal-catalyzed aminocarbonylation of aryl halides with CO and amines, pioneered by Heck and co-workers in the 1970s, is among the most commonly employed reactions to make aromatic amides. A catalyst-free aminocarbonylation of aryl iodides with CO and amines, which simply uses photoirradiation conditions by Xe-lamp, has now been developed. This methodology shows broad functional-group tolerance, including that of heteroaromatic amides. A hybrid radical/ionic chain mechanism, involving electron transfer from zwitterionic radical intermediates generated by nucleophilic attack of amines to aroyl radicals, is proposed.

Full text of DOI:10.1002/chem.201503164

DOI: 10.1002/chem.201503164
Communication
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Photochemistry |Hot Paper|
Photoinduced Aminocarbonylation of Aryl Iodides
Takuji Kawamoto, Aoi Sato, and Ilhyong Ryu*[a]
success of the metal-catalyst-free system of Eq. (2) depends on
how to deliver an efficient chain in the absence of a radical
mediator. Consequently, we proposed the electron transfer-
based aminocarbonylation pathway of aryl iodides outlined in
Scheme 2. Thus, photoinduced cleavage of an aryl iodide
would yield an aryl radical,[9] which would then react with CO
to give the corresponding acyl radical. This species then reacts
with an amine by nucleophilic addition to give a zwitterionic
radical intermediate.[8,10] Electron transfer to the aryl iodide
would give phenyl radical and complete the cycle and a radical
chain reaction, in which formally the electron acts as the cata-
lyst.
Abstract: Transition metal-catalyzed aminocarbonylation
of aryl halides with CO and amines, pioneered by Heck
and co-workers in the 1970s, is among the most common-
ly employed reactions to make aromatic amides. A cata-
lyst-free aminocarbonylation of aryl iodides with CO and
amines, which simply uses photoirradiation conditions by
Xe-lamp, has now been developed. This methodology
shows broad functional-group tolerance, including that of
heteroaromatic amides. A hybrid radical/ionic chain mech-
anism, involving electron transfer from zwitterionic radical
intermediates generated by nucleophilic attack of amines
to aroyl radicals, is proposed.
We initiated our examination of the proposed metal-free
aminocarbonylation reaction using 4-iodoacetophenone (1a)
and morpholine (2a) as model substrates (Table 1). When
a benzotrifluoride (BTF) solution of 1a and 2a was irradiated
The aminocarbonylation of aryl halides, pioneered by Heck
and co-workers in the 1970s,[1] is among the most commonly
employed carbonylation reactions for the synthesis of a variety
of aromatic amides.[2,3] The reaction relies on transition metal
catalysts, such as Pd [Scheme 1, Eq. (1)]. Encouraged by the
Scheme 1. Metal-catalyzed and metal-catalyst-free aminocarbonylation of ar-
omatic halides.
Scheme 2. Proposed mechanism of aminocarbonylation of iodoarenes by
electron as catalyst.
potential of aryl radical carbonylation,[4] we envisioned that
aminocarbonylation of iodoarenes could be carried out by
a novel photochemical reaction system that does not use any
transition metal catalyst [Scheme 1, Eq. (2)]. Herein we report
the first achievement of this transformation, based on the con-
cept that the electron acts as a catalyst.[5,6]
Table 1. Optimization of reaction conditions.
Since aryl radicals add to CO to form the corresponding aro-
matic acyl radicals,[7] and acyl radicals can be trapped by
amines under tin hydride-mediated conditions,[8] key to the
Entry
Solvent (mL)
Conv. [%][a]
Yield [%][a]
1
2
3
4[c]
5[d]
BTF (10)
63
93
100
76
50
79
88 (81)[b]
72
BTF (10)/H2O (1)
MeCN (10)
MeCN (10)
MeCN (10)
[a] Dr. T. Kawamoto, A. Sato, Prof. Dr. I. Ryu
Department of Chemistry, Graduate School of Science
Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan)
Fax: (+81)72-254-9695
95
51
[a] Determined by GC; [b] yield of product isolated by silica-gel column
chromatography; [c] Pyrex tube was used; [d] reaction was performed
under 10 atm of CO.
E-mail: ryu@c.s.osakafu-u.ac.jp
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201503164.
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Table 2. Photoinduced aminocarbonylation with various amines and aryl
Table 2. (Continued)
iodides.
Entry
1
2
3
Yield
[%][a]
Entry
1
2
3
Yield
[%][a]
31
15
3q
17
2a
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
morpholine (2a)
piperidine (2b)
diethylamine (2c)
n-butylamine (2d)
tert-butylamine (2e)
aniline (2 f)
3a
3b
3c
3d
3e
3 f
81
74
72
68
82
38
1l
4
[a] Yield of product isolated by silica-gel column chromatography; [b] t=
24 h; [c] t=70 h; [d] morpholine (4 equiv) was used.
7[b]
2a
80
with a 500 W Xe lamp through a quartz tube for 14 h under
70 atm pressure of CO, the envisaged 1-[4-(morpholine-4-car-
bonyl)phenyl]ethanone (3a) was obtained in 50% yield
(Table 1, entry 1). Since the morpholine·HI salt is not soluble in
BTF, water was added to the reaction system, which improved
the yield of 3a to as high as 79% (Table 1, entry 2). The use of
acetonitrile as a solvent gave an 88% yield of 3a (Table 1,
entry 3). The use of a Pyrex tube was also effective, giving the
desired product in good yield (Table 1, entry 4). Since heated
conditions (1008C, 14 h) without light did not cause the car-
bonylation reaction, we think that photoirradiation contributed
to the initiation process to generate aryl radicals by homolysis
of ArÀI bond.[8] Regarding CO pressure, only 10 atm of CO
gave a very low yield (Table 1, entry 5).
1b
3g
8[b]
2a
2a
2a
2a
52
50
74
82
63
60
89
77
61
1c
3h
3i
9[b]
1d
10[b]
11[b]
12
1e
1 f
1g
3j
3k
3l
With the optimized conditions (Table 1, entry 3) in hand, we
next examined the substrate scope of the aminocarbonylation
using various amines and iodoarenes (Table 2). The reaction of
secondary amines such as piperidine (2b) and diethylamine
(2c) with 1a gave the corresponding amides 3b and 3c in
74% and 72% yields, respectively (Table 2, entries 2 and 3).
The primary amines n-butylamine (2d) and tert-butylamine
(2e) were also tested, both of which worked well (Table 2, en-
tries 4 and 5). The reaction with aniline afforded the desired
amide in a modest yield (Table 2, entry 6). A variety of aryl io-
dides 1b–k were also shown to participate in the amide syn-
thesis (Table 2, entries 7–16). For example, the reactions of
ethyl 4-iodobenzoate (1b), 4-iodobenzotrifluoride (1c), iodo-
benzene (1d), 4-iodotoluene (1e), and 4-iodoanisole (1 f) gave
good yields of 3g, 3h, 3i, 3j, and 3k, respectively (Table 2, en-
tries 7–11). The reactions of 4-chloroiodobenzene (1g) and 4-
fluoroiodobenzene (1h) proceeded chemoselectively at the
aryl-iodine bond to give the corresponding chlorine- and fluo-
rine-containing products 3l and 3m, respectively (Table 2, en-
tries 12 and 13). Heterocyclic iodides such as 2-iodopyridine
(1i), 3-iodopyridine (1j), and 4-iodopyridine (1k) were also ex-
amined, which gave the corresponding amides 3n, 3o, and 3p
in good yields (Table 2, entries 14–16). We also examined the
2a
2a
13[b]
14[c,d]
15[c]
16[c,d]
1h
1i
3m
3n
2a
2a
2a
1j
3o
3p
1k
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aminocarbonylation of 2-iodoallyloxybenzene (1l), in order to
test for the presence of aryl radicals under the employed con-
ditions. Cyclized amide 3q was formed in 31% yield, as expect-
ed. However it was accompanied by the unexpected double
carbonylation product a-ketoamide 4 in 15% yield (Table 2,
entry 17).[11] Judging from the fact that the reaction at higher
pressure of CO (150 atm) did not increase the yield of 4, a reac-
tion mechanism involving the second carbonylation of an acyl
radical is highly unlikely and we are now pursuing the reaction
mechanism to give 4.[12]
The behavior of 1-bromo-4-iodobenzene (1m) in the amino-
carbonylation reaction with CO was intriguing, since the less
reactive bromoarene portion was also carbonylated
(Scheme 3). Thus, exposure of 1m to standard reaction condi-
tions afforded mono- and bis-aminocarbonylation products 3r
and 5 in 13% and 51% yields, respectively [Scheme 3, Eq. (3)].
However, the separate reaction of isolated 3r gave virtually
none of the bis-amide 5 [Scheme 3, Eq. (4)].
These results are consistent with the scenario that A, derived
from acyl radical and amine 2a, is a key intermediate in the
preparation of 5 (Scheme 4).[13] Species A, after deprotonation,
has two possible ways it can fragment: One is an intermolecu-
lar electron transfer (ET) to give 3r (path a); the other is an in-
tramolecular ET to cleave the CÀBr bond[14] yielding aryl radical
B, which then reacts with CO and morpholine to yield 5
(path b). Accordingly, that the 1,4-biscarbonylated product 5 is
the major product provides strong support for the intramolec-
ular ET path b. A possibile intermolecular ET path from iodo-
benzene (1d) to 3r was also examined by adding iodobenzene
(20 mol%) to the reaction of 3r and 2a. However, aminocarbo-
nylation of 1d only took place to afford 3i.
The aminocarbonylation of organic halides has long been
taken for granted as requiring a transition metal catalyst. Our
new methodology, having a broad scope with regard to both
aryl iodides and amines, has demonstrated that the aminocar-
bonylation process does not require any metal catalyst or or-
ganocatalyst. The concept reported herein is quite simple but
may provide inspiration for the design of even more transition
metal-free carbonylation reactions.
Experimental Section
A magnetic stirring bar, MeCN (10 mL), 4-iodoacetophenone (1a,
121 mg, 0.5 mmol), and morpholine (2a, 86 mg, 1 mmol) were
placed in a stainless steel autoclave for photoreaction equipped
with an inserted quartz glass liner. The autoclave was closed,
purged three times with carbon monoxide, pressurized with CO
(70 atm) and then irradiated by xenon arc lamp (500 W) with stir-
ring for 14 h. After the reaction, excess CO was discharged at room
temperature. The solvent was removed under reduced pressure.
The residue was purified by flash chromatography on silica gel
(hexane/AcOEt=1:1) to give 3a (93 mg, 81%).
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search (A). We thank Prof. Cathleen M. Crudden for helpful dis-
cussions.
Keywords: amides
· carbonylation · electron transfer ·
photochemistry · radical reactions
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Received: August 11, 2015
Published online on September 1, 2015
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