Radical Carbonylation under Low CO Pressure: Synthesis of Esters from Activated Alkylamines at Transition Metal-Free Conditions

Article abstract of DOI:10.1002/cjoc.202000624

High CO pressure (> 40 bar) is usually needed in radical carbonylation reactions in the absence of metal catalyst. In this communication, we developed a transition-metal-free radical carbonylation of activated alkylamines with phenols and alcohols under low CO pressure (1—6 bar). Various esters were obtained in moderate to excellent yields under simple reaction conditions with good functional group compatibility.

Full text of DOI:10.1002/cjoc.202000624

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Radical Carbonylation Under Low CO Pressure: Synthesis of Esters from
Activated Alkylamines at Transition Metal-Free Conditions
Authors: Fengqian Zhao, Han-Jun Ai, and Xiao-Feng Wu*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2020, 38, 10.1002/cjoc.202000624.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.202000624.
ISSN 1001-604X • CN 31-1547/O6
mc.manuscriptcentral.com/cjoc
www.cjc.wiley-vch.de

For submission: https://mc.manuscriptcentral.com/cjoc
Report
CJC
For published articles: https://onlinelibrary.wiley.com/journal/16147065
中
国 化 学 - An International Journal
Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Radical Carbonylation Under Low CO Pressure: Synthesis of Es-
ters from Activated Alkylamines at Transition Metal-Free Condi-
tions
Fengqian Zhao,a Han-Jun Ai,a and Xiao-Feng Wu*a,b
a
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany, E-mail:
Xiao-Feng.Wu@catalysis.de
b Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning,
116023, China, E-mail: xwu2020@dicp.ac.cn
Keywords
Carbonylation | Radical | Ester | Alkylamine | Katritzky salt
Main observation and conclusion
High CO pressure (> 40 bar) usually needed in radical carbonylation reactions in the absence of metal catalyst. In this communication,
we developed a transition-metal-free radical carbonylation of activated alkylamines with phenols and alcohols under low CO pressure
(1-6 bar). Various esters were obtained in moderate to excellent yields under simple reaction conditions with good functional group
compatibility.
Comprehensive Graphic Content
Ph
Ph
=
R
benzyl,
allyl
alkyl,
examples
O
phenyl,
base
R
+
+
ROH
CO
1-6 bar
N
BF4
O
61
(
)
to 94%
Ph
up
yield
and
as
alcohols
Phenols
Low CO
pressure
coupling partner
tolerance
Good functional
Transition-metal-free
group
*E-mail:
View HTML Article
Supporting Information
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202000624
This article is protected by copyright. All rights reserved.

First author et al.
Report
absence of transition-metal catalysts.
Background and Originality Content
Carbonyl-containing compounds (esters, amides, aldehydes,
ketones) are widely found in pharmaceuticals, functional materials,
and biologically active molecules. Carbonyl structures are also
important building blocks in organic transformations.[1] Hence the
synthesis of carbonyl-containing compounds is an attractive sub-
ject. Since the first example of the highly efficient trapping of CO
by radicals was reported by Ryu et al. in 1990,[2] radical carbonyla-
tion with CO as a cheap carbonyl source has gained considerable
attention. Nowadays, this strategy represents one of the most
powerful tools, and has been widely used in the construction of
carbonyl skeleton in both academia and industry.[3] Various novel
methods, including transition-metal catalyzed, oxidant-induced
and photoinitiated carbonylation, have been developed to obtain
value-added carbonylated products.[4]
In general, there are two accepted pathways for the radical
carbonylative transformations: 1) One is trapping the radical by
(noble)metal center to form an organometallic intermediate and
then followed by CO insertion (Scheme 1a, path a).[5] However,
this process is usually limited by the slow oxidative addition
and/or rapid β-hydride elimination.[6] 2) The other pathway is
capture the CO by radicals to generate acyl radicals directly
(Scheme 1a, path b). This acyl radical generation process is re-
versible (the reversed decarbonylation step is even more favored),
thus require high CO pressure (> 40 bar)[7] or metal catalyst[8] to
stabilize the acyl radical intermediates. Therefore, there is still an
unmet need for low CO pressure strategy that can be applied in
transition-metal-free radical carbonylation. Notably, Ryu and
co-workers reported their achievement on black-light-induced
radical carbonylation of alkyl iodides in 2010. The reaction pro-
ceeds under 1 bar of CO in the presence of tetrabutylammonium
borohydride, the corresponding hydroxymethylated products were
formed in moderate to good yields.[7f]
Results and Discussion
Our initial research started with deaminative carbonylation of
Katritzky salts 1a and 4-methoxyphenol 2a in the presence of DBU
under CO pressure, 5% yield of alkylphenol ester 3 was detected
(Table 1, entry 1). The yield of 3 was greatly improved when
Cs2CO3 was added to the reaction (Table 1, entry 2). DBU was
proved to be indispensable through control experiment (Table 1,
entry 3). Subsequently, other promoters, such as DBN, TBD, and
DABCO were used to replace DBU, and DBN gave the best result
and two equivalents of it is necessary (Table 1, entries 4-5, see the
Supporting Information for more details). Various bases were
submitted to the transformation and K3PO4 gave a significant im-
provement in the yield (Table 1, entries 6-10, see the Supporting
Information for more details). In addition, other solvents were also
used, and DMAc led to a great increase in the reaction efficiency
(Table 1, entries 11-12, see the Supporting Information for more
details). It is worthy to mention that good yield can be still ob-
tained when 6 bar of CO was used. Notably, this transformation
can also be achieved under 1 bar CO with 54% yield of 3 was ob-
tained (Table 1, entry 13). Furthermore, the yield was improved
slightly by increasing the reaction concentration (Table 1, entry 14).
Decreasing the temperature led to reduced yield of ester (Table 1,
entry 15).
Table 1 Optimization of the reaction conditionsa
Ph
Ph
OMe
Promoter
Base
equiv)
OMe
(2.0
equiv)
O
(1.0
+
N
BF4
Cy
O
HO
CO Solvent, 80 °C, 15 h
,
Ph
1a
2a
3
Entry
1
Promoter
DBU
Base
Solvent
THF
CO (bar) Yield (%)b
Scheme 1 The strategies for radical carbonylation
strategies
radical
General
for
/
20
20
20
20
20
20
20
20
20
20
20
6
5
25
a)
carbonylation
O
[M]
CO
2
3
DBU
/
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Na2CO3
K3PO4
t-BuOK
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
THF
THF
R-[M]
a
R
path
[M]
trace
47
or
hv
[M], [O]
4
DBN
TBD
DBN
DBN
DBN
DBN
DBN
DBN
DBN
DBN
DBN
DBN
THF
RX
R
O
O
NuH
[O]
[M]
5
THF
14
=
=
aryl
R
X
R
alkyl,
I,
R
Nu
Limitation:
CO
Br, N BF etc.
,
2
4
O
R
CO
6
THF
32
b
path
pressure
metal catalyst
O
High
or
7
THF
32
R
[M]
8
THF
72
work
this
pressure
(
Transition-metal-free radical
under low CO
O
R1
b)
carbonylation
)
9
THF
20
O
Ph
R1
Ph
R3
OH
R1
CO bar)
(6
R1
R3
DBU
10
11
12
13
14c
15c,d
MeCN
DMAc
DMAc
DMAc
DMAc
DMAc
42
O
N
DBU
BF4
R2
R2
benzyl,
R2
R2 Ph
R3
=
allyl
87
aryl,
alkyl,
Low CO
as
base
pressure
promotor
scope
Organic
Broad substrates
90
Transition-metal-free
1
54
6
92 (91)e
As an effective strategy for the formation of alkyl radicals,
deamination of Katritzky salts, which are easily obtained from
amines, has been used in various transformations[9] as well as in
carbonylation reactions.[10] However, as above discussed, high
pressure of CO and/or metal catalyst was still required in deamina-
tive carbonylation of Katritzky salts. In order to solve these chal-
lenges, and also as our continuing interest in deaminative car-
bonylation of Katritzky salts, we herein developed a radical car-
bonylative coupling of activated amines and phenols. This new
transformation proceeds under low CO pressure (1-6 bar) in the
6
60
a Reaction conditions: 1a (0.12 mmol, 1.2 equiv), 2a (0.1 mmol, 1.0 equiv),
promoter (0.2 mmol, 2.0 equiv), base (0.1 mmol, 1.0 equiv), solvent (2.0
mL), CO, 80 C, 15 h. b Determined by GC using hexadecane as the internal
o
c
d
e
standard.
1,5-Diazabicyclo[4.3.0]non-5-ene.
1,8-Diazabicyclo[5.4.0]undec-7-ene.
DMAc (1.5 mL).
60 oC.
Isolated yield. DBN
DBU
TBD
=
=
=
1,3,4,6,7,8-Hexahydro-2H-pyrimido [1,2-a] pyrimidine.
Scheme 2 Scope of radical carbonylation
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Ph
R1
Ph
DBN
K3PO
equiv)
(2.0
O
equiv)
4 (1.0
R1
R3
O
+
HO R3
N
O
BF4
CO bar), DMAc
(6 (3.0
80 °C, 15 h
Katritzky salts
mL)
R2
R2 Ph
OMe
OMe
O
OMe
OMe
OMe
OMe
O
O
O
O
O
O
O
O
O
O
t-Bu
:
7
,
3
4
,
8
,
91%
85%
O
5
,
=
62%
56%
O
,
81%
6
, 60%,
cis trans 1:4.4
OMe
OMe
OMe
OMe
OMe
O
O
O
O
O
O
O
O
O
N
Et
O
9
,
10
,
11
12
,
13
,
53%
92%
90%
and
84%
75%
O
,
O
alcohols
phenols
Et
t-Bu
Ph
O
O
O
O
O
O
O
O
O
O
N
O
N
O
N
O
N
O
N
Et
Et
Et
Et
Et
14
15
16
17
18
52%
61%
O
70%
70%
53%
,
,
,
,
,
,
,
O
O
O
O
O
H
N
O
Ph
O
N
O
O
O
O
O
O
O
N
O
O
O
N
Et
OMe
Et
O
19
,
20
21
22
23
67%
O
94%
O
70%
72%
82%
90%
O
,
,
,
,
,
,
,
F
O
O
OMe
O
O
O
O
O
O
O
,
O
N
O
O
Br
N
O
N
Et
O
Et
51%
42%
61%
50%
O
74%a
O
O
24
25
26
27
28
,
O
O
O
O
O
O
O
O
O
O
,
N
O
N
O
t-Bu
O
N
Ph
O
O
Et
Et
Et
O
O
O
29
30
31
32
,
33
88%
61%
73%
84%
,
Ph
O
O
benzyl alcohols
N
O
O
O
O
O
O
N
H
O
O
O
O
N
Ph
Et
O
N
O
37
38
82%
72%
O
36
62%a
86%
O
,
,
,
72%b
34
35
,
,
,
,
O
O
O
O
O
O
O
O
O
O
O
O
N
O
O
N
N
Et
Ph
Et
Et
Br
N
H
O
O
O
O
39
,
40
41
,
42
,
43
87%
Si
91%
O
69%
O
86%
O
82%
O
CF3
O
O
OMe
O
O
O
N
O
N
O
N
O
Et
Et
Et
O
O
O
44
,
45
,
46
47
48
,
71%
O
66%
45%
77%
56%
O
,
,
O
O
alkyl alcohols
O
O
O
O
S
S
O
O
O
N
N
N
O
O
O
O
N
Et
Et
Et
Et
N
O
O
O
49
,
50
,
51
52
,
53
51%
,
85%
O
87%
50%
59%
,
O
O
O
O
O
O
Cl
O
O
O
O
O
O
N
O
N
O
N
O
N
O
N
O
N
Et
Et
Et
Et
Et
O
Et
64%
50%
55%
70%c
57%c
39%d
59
,
O
O
O
O
O
O
54
,
55
,
56
57
,
58
,
,
bioactive molecules
O
H
H
H
O
O
O
O
H
H
H
H
H
H
O
O
O
O
H
41%
O
N
O
N
Et
60
61
,
62
63
40%
,
83%
64%
,
Et
,
O
Estrone
Cholestanol
Nerol
from
from
from
from
O
Epiandrosterone
Reaction conditions: Katritzky salts (0.24 mmol, 1.2 equiv), phenols or alcohols (0.2 mmol, 1.0 equiv), DBN (0.4 mmol, 2.0 equiv), K3PO4 (0.2 mmol, 1.0
equiv), DMAc (3.0 mL), CO (6 bar), 80 oC, 15 h, isolated yield. a 2.0 equiv of Katritzky salts were uesd. b 0.1 mmol 2,2'-biphenol was uesd. c 5.0 equiv of al-
cohols and 0.2 mmol Katritzky salts were uesd. d 10.0 equiv of alcohols and 0.2 mmol Katritzky salts were uesd.
With the optimized reaction conditions in hand, the substrate
scope of this transformation was examined. A variety of Katritzky
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
salts derived from amines were tested firstly and led to the corre-
sponding esters in moderate to excellent yields (Scheme 2, 3-13).
Cyclic, chain, and phenyl-containing amine derivatives were
well-tolerated in this transformation (3-11). When the derivative
of indan-2-amine was used, moderate yield was obtained because
of the fast β-hydride elimination of the alkyl radical intermediate
(8). Remarkably, N- and O-heterocyclic amines were successfully
converted into the corresponding esters in good yields (12-13). It
is important to mention that primary alkyl Katritzky salts can not
be activated in the current reaction system.
Subsequently, the scope with respect to phenols were exam-
ined. Various phenols were all tolerated and delivered the desired
esters smoothly (Scheme 2, 14-34). Versatile functional groups
appended to the phenols, such as alkyl (15-17, 19), phenyl (18),
alkoxy (20), allyl (21), dimethylamino (22), amide (23), fluorine
(24), ketone (28), and pyrrolyl (30) were all efficiently transformed
into the desired products in moderate to excellent yields. Re-
markably, the corresponding esters also can be obtained in mod-
system under the standard conditions, the reaction was inhibited
completely, meanwhile the adduct of radical with TEMPO 64 was
detected by GC-MS (See the Supporting Information for GC-MS).
In contrast, when the reaction was carried out in the absence of
DBN or at room temperature, neither 3 nor 64 was detected. Sub-
sequently, the product was obtained in 24% yield when BHT (bu-
tylated hydroxytoluene) was added to the reaction. We also de-
tected the cyclohexyl radicals through EPR spectra (See the Sup-
porting Information for more details). And the addition of
1,1-diphenylethylene lead to 18% yield of 3 and 35% yield of 65.
These results suggest that the alkyl radical and acyl radical were
probably generated in this transformation and the key to promote
the formation of alkyl radicals is DBN and heat. Finally, when
PO , the corresponding ester was
PhONa replaced PhOH and K3
4
isolated in 36% yield (52% yield, when PhOH and K3PO4 were
used). It proven that phenols were deprotonated to form PhO- in
the presence of bases.
erate yields with electron-withdrawing groups substituted phenols, Scheme 3 Mechanistic experiments
a)
including bromine (25), ester (26), and acetyl (27). Meanwhile, the
OMe
+
Ph
Ph
O
2a
equiv)
(1.0
standard conditions
influence of steric hindrance was tested as well, 2-tert-butyl (31),
2-phenyl (32), 2,6-dimethyl (33), and 2,6-diphenyl (34) were all
well-tolerated, the yields of the wished esters had no decrease or
even got better. When 2-hydroxycarbazol was used, the desired
ester was obtained in good yield, and no amide was detected (35).
The reaction occurs selectively at the -OH site when benzene rings
contain both -OH and -NH. Additionally, 2,2'-biphenol can be
transformed into the corresponding diester in good yield (36). In
addition to phenols, 3-hydroxypyridine was also applied in this
transformation smoothly and the corresponding ester was ob-
tained in moderate yield (37). To expand the scope of substrates,
benzyl alcohols were also tested. As shown in Scheme 2, the cor-
responding esters were obtained smoothly when various benzyl
alcohols were tested instead of phenols (38-50). Methoxy (38-39)
and phenyl (40) substituted benzyl alcohols gave the desired es-
ters in excellent yields. Other synthetically valuable groups, such
as dimethylamino (41), amide (42), halogen (43), trifluoromethyl
(45), and cyclopropyl (46) were also well-tolerated in this trans-
formation, the presence of benzylic substituent had no obvious
effect on the reaction. In addition to this, 1-indanol (47),
1-(1-naphthyl) ethanol (48), thienyl (49), and pyridyl methanol (50)
able to give the corresponding products in good yields as well.
Alkyl alcohols can also be used in this transformation. Both
primary and secondary alcohols can deliver the desired esters
successfully (51-59), but tertiary alcohols were not applicable un-
der our conditions. Unsaturated alcohols were also able to be
transformed in moderate to good yields and the triple bond (57)
or double bond (58) were retained in products. Meanwhile,
2-chloroethanol was well-tolerated (59). These functional groups
provide the possibility for subsequent transformations and utiliza-
tions. Remarkably, compared with phenols, most alkyl alcohols
provided their esters in moderated yields, this might due to the
decreased acidity of the -OH group.
N
BF4
N
O
O
TEMPO
equiv)
(2.0
Ph
equiv)
,
1a
64
3
0%
(1.2
GC-MS)
(detected by
no
at
:
not
detected
detected
DBN
r.t.
: not
OMe
Ph
Ph
O
2a
equiv)
(1.0
standard conditions
N
BF4
O
,
BHT
equiv)
(2.0
Ph
equiv)
1a
3 24
%
(1.2
N
(GC yield)
OMe
+
Ph
Ph
O
,
Ph
O
O
2a
equiv)
(1.0
standard conditions
Ph
BF4
1,1-Diphenylethylene
Ph
equiv)
equiv)
(1.0
,
1a
3
18%
65
35%
(1.2
(GC yield)
(GC yield)
b)
Ph
Ph
O
standard conditions
PhONa
N
O
BF4
equiv)
(1.0
instead of PhOH
and
O
N
O
N
Ph
Et
Et
K3PO4
O
O
,
14
36
%
1k
equiv)
(1.2
and
were uesd:
52%
when PhOH
K3PO4
On the basis of above results and previous literatures,[10,11]
a
possible mechanism was proposed (Scheme 4). Firstly, radical I
was formed from 1 through a SET process with DBN, and DBN
radical was produced at the same time. Then, CO trapped by the
alkyl radical I form an acyl radical II which will be oxidized by the
DBN radical to give the corresponding acyl cation III. Finally, the
terminal ester product IV will be formed after reacting with alco-
hols in the presence of base.
Scheme 4 Proposed mechanism
To prove the application values of our transformation, bioac-
tive molecules were also tested. Estrone, which was usually used
as pharmaceutical intermediates and common raw materials, pro-
vided the corresponding ester in 83% yield (Scheme 2, 60). Natu-
rally occurring steroids, such as epiandrosterone (61) and choles-
tanol (62), could be easily transformed and provided the target
esters in 41% and 64% yields, respectively. Nerol with multiple
unsaturated bonds delivered the desired ester smoothly as well
(63). These results proved the application potential of this transi-
tion-metal-free transformation in the synthesis and modification
of pharmaceutical molecules.
Ph
R1
Ph DBN DBN
DBN DBN
O
O
R1
CO
R1
R1
N
BF4
SET
-Tppy
SET
R2
R2
II
R2
III
R3OH
base
R2 Ph
1
I
O
R1
R3
O
R2
IV
To gain some insight into the mechanism of this reaction,
mechanistic experiments were performed (Scheme 3). When
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) was added into the
Conclusions
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
In conclusion, under low CO pressure (1-6 bar), a transi-
W.; Liu, T.; Wu, J. Light-Promoted Organic Transformations Utilizing
Carbon-Based Gas Molecules as Feedstocks. Angew. Chem. Int. Ed.
2021, 10.1002/anie.202010710.
tion-metal-free radical carbonylation of activated alkylamines with
phenols and alcohols has been developed. Various target esters
were obtained in moderate to excellent yields under modest reac-
tion conditions. The involvement of radical intermediates was
proven by our preliminary mechanistic studies. From synthetic
point of view, this transformation can be more meaningful in the
pharmaceutical fields which need to avoid the use of metals.
For selected recent examples on transition-metal, oxidant-induced
and photoinitiated radical carbonylation, see: (a) Peng, J.-B.; Geng,
H.-Q.; Wu, X.-F. The Chemistry of CO: Carbonylation. Chem. 2019, 5,
526-552; (b) Zhao, S.; Mankad, N. P. Metal-Catalysed Radical Car-
bonylation Reactions. Catal. Sci. Technol. 2019, 9, 3603-3613; (c)
Yang, L.; Shi, L.; Xing, Q.; Huang, K.-W.; Xia, C.; Li, F. Enabling CO In-
sertion into o-Nitrostyrenes beyond Reduction for Selective Access to
Indolin-2-one and Dihydroquinolin-2-one Derivatives. ACS Catal. 2018,
8, 10340-10348; (d) Zhang, W.; Zhao, M.-N.; Chen, M.; Ren, Z.-H.;
Guan, Z. Palladium-Catalyzed Regioselective Cyclocarbonylation of
N-(3-Phenylprop-2-ynyl)anilines with Carbon Monoxide and Alcohols
for the Synthesis of Quinoline-3-carboxylic Esters. Asian J. Org. Chem.
2018, 7, 1605-1608; (e) Cheng, J.; Qi, X.; Li, M.; Chen, P.; Liu, G. Palla-
dium-Catalyzed Intermolecular Aminocarbonylation of Alkenes: Effi-
cient Access of β-Amino Acid Derivatives. J. Am. Chem. Soc. 2015, 137,
2480-2483; (f) Qi, X.; Yu, F.; Chen, P.; Liu, G. Intermolecular Palladi-
um-Catalyzed Oxidative Fluorocarbonylation of Unactivated Alkenes:
Efficient Access to β-Fluorocarboxylic Esters. Angew. Chem. Int. Ed.
2017, 56, 12692-12696; (g) Hu, Y.; Shen, Z.; Huang, H. Palladi-
um-Catalyzed Intramolecular Hydroaminocarbonylation to Lactams:
Additive-Free Protocol Initiated by Palladium Hydride. ACS Catal.
2016, 6, 6785-6789; (h) Yu, H.; Zhang, G.; Huang, H. Palladi-
um-catalyzed Dearomative Cyclocarbonylation by C-N Bond Activa-
tion. Angew. Chem. Int. Ed. 2015, 54, 10912-10916; (i) Zhang, G.; Gao,
B.; Huang, H. Palladium-Catalyzed Hydroaminocarbonylation of Al-
kenes with Amines: A Strategy to Overcome the Basicity Barrier Im-
parted by Aliphatic Amines. Angew. Chem. Int. Ed. 2015, 54,
7657-7661; (j) Lu, Y.; Leow, D.; Wang, X.; Engle, K. M.; Yu, J.-Q. Hy-
droxyl-Directed C–H Carbonylation Enabled by mono-N-Protected
Amino Acidligands: An Expedient Route to 1-Isochromanones. Chem.
Sci. 2011, 2, 967-971; (k) Zeng, L.; Li, H.; Hu, J.; Zhang, D.; Hu, J.; Peng,
P.; Wang, S.; Shi, R.; Peng, J.; Pao, C.-W.; Chen, J.-L.; Lee, J.-F.; Zhang,
H.; Chen, Y.-H.; Lei, A. Electrochemical Oxidative Aminocarbonylation
of Terminal Alkynes. Nat. Catal. 2020, 3, 438-445; (l) Zhang, H.; Shi, R.;
Ding, A.; Lu, L.; Chen, B.; Lei, A. Transition-Metal-Free Alkoxycar-
bonylation of Aryl Halides. Angew. Chem. Int. Ed. 2012, 51,
12542-12545; (m) Guo, W.; Lu, L. Q.; Wang, Y.; Wang, Y. N.; Chen, J.
R.; Xiao, W.-J. Metal-Free, Room-Temperature, Radical Alkoxycar-
bonylation of Aryldiazonium Salts through Visible-Light Photoredox
Catalysis. Angew. Chem. Int. Ed. 2015, 54, 2265-2269; (n) Lu, B.;
Cheng, Y.; Chen, L.-Y.; Chen, J.-R.; Xiao, W.-J. Photoinduced Cop-
per-Catalyzed Radical Aminocarbonylation of Cycloketone Oxime Es-
ters. ACS Catal. 2019, 9, 8159-8164.
For selected recent examples on radical carbonylation involving the
formation of metal alkyl intermediates, see: (a) Yin, H.; Kumke, J. J.;
Domino, K.; Skrydstrup, T. Palladium Catalyzed Carbonylative Cou-
pling of Alkyl Boron Reagents with Bromodifluoroacetamides. ACS
Catal. 2018, 8, 3853-3858; (b) Sargent, B. T.; Alexanian, E. J. Palladi-
um-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl
Bromides at Low Pressure. J. Am. Chem. Soc. 2016, 138, 7520-7523;
(c) Xie, P.; Xie, Y.; Qian, B.; Zhou, H.; Xia, C.; Huang, H. Palladi-
um-Catalyzed Oxidative of Benzylic C-H Bonds via Nondirected
C(sp3)-H Activation. J. Am. Chem. Soc. 2012, 134, 9902-9905; (d) Ai, H.
J.; Wang, H.; Li, C. L.; Wu, X.-F. Rhodium-Catalyzed Carbonylative
Coupling of Alkyl Halides with Phenols under Low CO Pressure. ACS
Catal. 2020, 10, 5147-5152.
(a) Zanti, G.; Peeters, D. DFT Study of Small Palladium Clusters Pdn
and Their Interaction with a CO Ligand (n = 1-9). Eur. J. Inorg. Chem.
2009, 26, 3904-3911; (b) Bissember, A. C.; Levina, A.; Fu, G. C. A Mild,
Palladium-Catalyzed Method for the Dehydrohalogenation of Alkyl
Bromides: Synthetic and Mechanistic Studies. J. Am. Chem. Soc. 2012,
134, 14232-14237.
Experimental
A 4 mL screw-cap vial was charged with Katritzky salts (0.24
mmol), phenols or alcohols (if solid, 0.2 mmol, 1.0 equiv), K3PO4
(0.2 mmol, 1.0 equiv) and an oven-dried stirring bar. The vial was
closed by Teflon septum and phenolic cap and connected with
atmosphere with a needle. After flashed the vials with argon and
vacuum three times, DBN (0.4 mmol, 2.0 equiv), phenols or alco-
hols (if liquid, 0.2 mmol, 1.0 equiv) and dry DMAc (3.0 mL) were
injected by syringe. The vial was fixed in an alloy plate and put into
Parr 4560 series autoclave (500 mL) under argon atmosphere. At
room temperature, the autoclave was flushed with carbon mon-
oxide for three times and 6 bar of carbon monoxide was charged.
The autoclave was reacted at 80 °C for 15 h. Afterwards, the auto-
clave was cooled to room temperature and the pressure was
carefully released. The mixture was diluted with water (15 mL) and
extracted with EtOAc (3 × 5 mL). The combined organic layer was
removed under reduced pressure and the residue was purified by
silica gel chromatography (n-Pentane/EtOAc) to afford the corre-
sponding esters.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement
The authors thank the Chinese Scholarship Council (CSC) for
financial support. We also thank the analytical team of LIKAT for
their excellent analytic support.
References
(a) Goossen, L. J.; Rodriguez, N.; Goossen, K. Carboxylic Acids as Sub-
strates in Homogeneous Catalysis. Angew. Chem. Int. Ed. 2008, 47,
3100-3120; (b) Otera, J. Esterification: Methods, Reactions, and Ap-
plications; Wiley-VCH: Weinheim, Germany, 2003; pp. 1−303.
Ryu, I.; Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. Free Radical
Carbonylation. Efficient Trapping of Carbon Monoxide by Carbon
Radicals. J. Am. Chem. Soc. 1990, 112, 1295-1297.
(a) Ryu, I.; Sonoda, N. Free-Radical Carbonylations: Then and Now.
Angew. Chem. Int. Ed. 1996, 35, 1050-1066; (b) Matsubara, H.; Ka-
wamoto, T.; Fukuyama, T.; Ryu, I. Applications of Radical Carbonyla-
tion and Amine Addition Chemistry: 1,4-Hydrogen Transfer of
1-Hydroxylallyl Radicals. Acc. Chem. Res. 2018, 51, 2023-2035; (c)
Lang, R.; Xia, C.; Li, F. Carbonylative Diversification of Unactivated
Heteroaromatic Compounds. New J. Chem. 2014, 38, 2732-2738; (d)
Liu, Q.; Zhang, H.; Lei, A. Oxidative Carbonylation Reactions: Organ-
ometallic Compounds (R-M) or Hydrocarbons (R-H) as Nucleophiles.
Angew. Chem. Int. Ed. 2011, 50, 10788-10799; (e) Hu, X. Q.; Liu, Z. K.;
Xiao, W. J. Radical Carbonylative Synthesis of Heterocycles by Visible
Light Photoredox Catalysis. Catalysts 2020, 10, 1054; (f) Zhu, C.; Liu, J.;
Li, M.-B.; Bäckvall, J.-E. Palladium-catalyzed oxidative dehydrogena-
tive carbonylation reactions using carbon monoxide and mechanistic
overviews. Chem. Soc. Rev., 2020, 49, 341-353; (g) Cai, B.; Cheo, H.
For selected recent examples on radical carbonylation involving acyl
radicals directly attacked by nucleophiles, see: (a) Cartier, A.; Lever-
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
nier, E.; Corcé, V.; Fukuyama, T.; Dhimane, A.-L.; Ollivier, C.; Ryu, I.;
droxymethylation of Unactivated Alkyl Iodides with CO to Provide
One-Carbon-Extended Alcohols. Angew. Chem. Int. Ed. 2018, 57,
5867-5870.
Fensterbank, L. Carbonylation of Alkyl Radicals Derived from Organo-
silicates through Visible-Light Photoredox Catalysis. Angew. Chem. Int.
Ed. 2019, 58, 1789-1793; (b) Cartier, A.; Levernier, E.; Dhimane, A. L.;
Fukuyama, T.; Ollivier, C.; Ryu, I.; Fensterbank, L. Synthesis of Ali-
phatic Amides through a Photoredox Catalyzed Radical Carbonylation
Involving Organosilicates as Alkyl Radical Precursors. Adv. Synth.
Catal. 2020, 362, 2254-2259; (c) Lu, L.; Cheng, D.; Zhan, Y.; Shi, R.;
Chiang, C.-W.; Lei, A. Metal-Free Radical Oxidative Alkoxycarbonyla-
tion and Imidation of Alkanes. Chem. Commun. 2017, 53, 6852-6855;
(d) Ryu, I.; Tani, A.; Fukuyama, T.; Ravelli, D.; Fagnoni, M.; Albini, A.
Atom-Economical Synthesis of Unsymmetrical Ketones through Pho-
tocatalyzed C-H Activation of Alkanes and Coupling with CO and Elec-
trophilic Alkenes. Angew. Chem. Int. Ed. 2011, 50, 1869-1872; (e)
Majek, M.; Jacobi von Wangelin, A. Metal-Free Carbonylations by
Photoredox Catalysis. Angew. Chem. Int. Ed. 2015, 54, 2270-2274. (f)
Kobayashi, S.; Kawamoto, T.; Uehara, S.; Fukuyama, T.; Ryu, I.
Black-Light-Induced Radical/Ionic Hydroxymethylation of Alkyl Io-
dides with Atmospheric CO in the Presence of Tetrabutylammonium
Borohydride. Org. Lett. 2010, 12, 1548-1551; (g) Zhou, Q.-Q.; Guo, W.;
Ding, W.; Wu, X.; Chen, X.; Lu, L.-Q.; Xiao, W.-J. Decarboxylative Al-
kynylation and Carbonylative Alkynylation of Carboxylic Acids Ena-
bled by Visible-Light Photoredox Catalysis. Angew. Chem. Int. Ed.
2015, 54, 11196-11199.
For selected recent reviews on deaminative transformations of Kat-
ritzky salts, see: (a) Rössler, S. L.; Jelier, B. J.; Magnier, E.; Dagousset,
G.; Carreira, E. M.; Togni, A. Pyridinium Salts as Redox-Active Func-
tional Group Transfer Reagents. Angew. Chem. Int. Ed. 2020, 59,
9264-9280; (b) He, F.-S.; Ye, S.; Wu, J. Recent Advances in Pyridinium
Salts as Radical Reservoirs in Organic Synthesis. ACS Catal. 2020, 9,
8943-8960; (c) Kong, D.; Moon, P. J.; Lundgren, R. J. Radical Coupling
from Alkyl Amines. Nat. Catal. 2019, 2, 473-476; (d) Pang, Y.; Moser,
D.; Cornella, J. Pyrylium Salts: Selective Reagents for the Activation of
Primary Amino Groups in Organic Synthesis. Synthesis, 2020, 52,
489-503.
For selected recent examples on deaminative carbonylation of Kat-
ritzky salts, see: (a) Zhao, F.; Li, C.-L.; Wu, X.-F. Deaminative Car-
bonylative Coupling of Alkylamines with Styrenes under Transi-
tion-Metal-Free Conditions. Chem. Commun. 2020, 56, 9182-9185; (b)
Li, C.-L.; Jiang, X.; Lu, L.-Q.; Xiao, W.-J.; Wu, X.-F. Cobalt(II)-Catalyzed
Alkoxycarbonylation of Aliphatic Amines via C-N Bond Activation. Org.
Lett. 2019, 21, 6919-6923; (c) Jiang, X.; Zhang, M.-M.; Xiong, W.; Lu,
L.-Q.; Xiao, W.-J. Deaminative (Carbonylative) Alkyl-Heck-type Reac-
tions Enabled by Photocatalytic C-N Bond Activation. Angew. Chem.
Int. Ed. 2019, 58, 2402-2406.
For selected recent examples on radical carbonylation involving acyl
radicals react with metals, see: (a) Sumino, S.; Fusano, A.; Fukuyama,
T.; Ryu, I. Carbonylation Reactions of Alkyl Iodides through the Inter-
play of Carbon Radicals and Pd Catalysts. Acc. Chem. Res. 2014, 47,
1563-1574; (b) Cheng, L.-J.; Mankad, N. P. Copper-Catalyzed Boro-
carbonylative Coupling of Internal Alkynes with Unactivated Alkyl
Halides: Modular Synthesis of Tetrasubstituted β-Borylenones. An-
gew. Chem. Int. Ed. 2018, 57, 10328-10332; (c) Cheng, L.-J.; Islam, S.
M.; Mankad, N. P. Synthesis of Allylic Alcohols via Cu-Catalyzed Hy-
drocarbonylative of Alkynes with Alkyl Halides. J. Am. Chem. Soc.
2018, 140, 1159-1164; (d) Zhao, S.; Mankad, N. P. Cu-Catalyzed Hy-
Hu, J.; Cheng, B.; Yang, X.; Loh, T.-P. Transition-Metal-Free Deamina-
tive Vinylation of Alkylamines. Adv. Synth. Catal. 2019, 361,
4902-4908.
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
Manuscript accepted: XXXX, 2021
Accepted manuscript online: XXXX, 2021
Version of record online: XXXX, 2021
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Entry for the Table of Contents
Radical Carbonylation Under Low CO Pressure: Synthesis of Esters from Activated Alkylamines at Transition Metal-Free Conditions
Fengqian Zhao, Han-Jun Ai, and Xiao-Feng Wu*
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Ph
Ph
=
R
benzyl,
allyl
alkyl,
examples
O
phenyl,
base
R
+
+
ROH
CO
1-6 bar
N
BF4
O
61
(
)
to 94%
Ph
up
yield
and
as
alcohols
Phenols
Low CO
pressure
coupling partner
tolerance
Good functional
Transition-metal-free
group
Transition-metal-free radical carbonylation of activated alkylamines with phenols and alcohols has been successful developed. This radical carbonyla-
tive strategy can be carried out under low CO pressure (1-6 bar). Esters with various functional groups were obtained in moderate to good yields.
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de