Cobalt(II)-Catalyzed Alkoxycarbonylation of Aliphatic Amines via C-N Bond Activation

Article abstract of DOI:10.1021/acs.orglett.9b02534

The first cobalt-catalyzed deaminative alkoxycarbonylation reaction was described for the conversion of readily available primary alkyl amines to synthetically versatile esters with moderate to high yields. This transformation shows good functional group compatibility and can serve as a powerful tool for the modification of alkyl amine-containing complex natural products and drug molecules.

Full text of DOI:10.1021/acs.orglett.9b02534

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cobalt(II)-Catalyzed Alkoxycarbonylation of Aliphatic Amines via
C−N Bond Activation
Chong-Liang Li,†,‡,∇ Xuan Jiang,§,∇ Liang-Qiu Lu,*,§ Wen-Jing Xiao,§ and Xiao-Feng Wu*,†,‡
†Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
‡Leibniz-Institut fu
̈
r Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
̈
§Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
152 Luoyu Road, Wuhan, Hubei 430079, China
S
* Supporting Information
ABSTRACT: The first cobalt-catalyzed deaminative alkoxycar-
bonylation reaction was described for the conversion of readily
available primary alkyl amines to synthetically versatile esters
with moderate to high yields. This transformation shows good
functional group compatibility and can serve as a powerful tool
for the modification of alkyl amine-containing complex natural products and drug molecules.
lkyl amines are prevalent organic molecules in nature and
are important building blocks that are widely used in
salts with alkenes.5b Under blue-light irradiation and 80 bar of
CO pressure, good yields of the desired enones can be
obtained. In the above deaminative cross-coupling reactions,
the key alkyl radical species is mainly generated from
pyridinium salts by using transition-metal-catalyzed or photo-
induced single electron transfer (SET) pathways.
A
pharmaceutical synthetic chemistry (see Figure 1).1 Among
On the other hand, transition-metal-catalyzed carbonylation
has been widely used in organic chemistry for the preparation
of carbonyl-containing organic compounds over the past
decades.9 By using alcohol as the nucleophile, various esters
can be easily prepared through alkoxycarbonylation. In more
detail, arenes and aryl halides can be easily transformed to the
corresponding benzoates in good yields in the presence of
catalysts (Scheme 1, eq a). For the alkoxycarbonylation of
unactivated alkyl halides or alkanes, several catalytic systems
Figure 1. Examples of important primary alkyl amine pharmaceuticals.
Scheme 1. Alkoxycarbonylation Strategies
them, primary alkyl amines are readily available, inexpensive,
and abundant reagents. However, methods for their activation
are still very limited, especially in comparison with their
aromatic amine analogues and benzylic amines, which can be
activated by the formation of diazonium salts and π-
coordinated intermediate.
In 2017, a group of researchers led by Watson trailblazed the
use of pyridinium salts2 (“Katritzky salts”) that are derived
from primary alkyl amines as significant surrogates of alkyl
halides, carboxylic acids, sulfonates, oxalates, and organo-
metallics in nickel-catalyzed deaminative cross-coupling
reactions.3 Later, studies showed the great potential of
pyridinium salts in cross-coupling reactions, including C-
(sp3)−C(sp3),4 C(sp2)−C(sp3),5 and C(sp3)−C(sp)6 reactions.
Exploration of the formation of deaminative carbon−
heteroatom bonds, particularly C−X (X = N, O, S)7 and C−
B,8 have also been reported. Notably, some of us recently
developed a novel carbonylative Heck coupling of pyridinium
Received: July 20, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02534
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
also have been established (Scheme 1, eq b). However,
challenges that are due to the inherent presence of π-acidic CO
(which decreases the electron density on the metal center) and
fast subsequent β-hydride elimination still exist.10 For alcohols,
aromatic alcohols can be activated by triflate while aliphatic
alcohols can be transformed to the corresponding alkyl halides
and then easily carbonylated to give the desired esters (Scheme
1, eq c). However, carbonylation procedures that are able to
use alkyl amine as the electrophile are still very rarely reported.
In order to solve the challenges mentioned, and also as our
continuing efforts in developing new metal-catalyzed carbon-
ylation reactions,11 we herein describe a cobalt-catalyzed
deaminative carbonylation of activated primary amines with
alcohols, providing a versatile method for the transformation of
alkyl amino groups into ester products (Scheme 1, eq d).
We initiated our investigations by studying the alkoxycarbo-
nylation between phenethylpyridinium salt (1a) and CH3OH
(2a) in N,N-dimethylformamide (DMF). After screening
various reaction parameters, using a CoII(acac)2 catalyst with
the addition of 4,7-dihydroxy-1,10-phenanthroline (L5) and
2.0 equiv of potassium bicarbonate was found to be critical to
achieve excellent yields of the desired product (Table 1, entry
KH2PO4, and K2CO3, led to a significant decrease in the
reaction efficiency (Table 1, entries 10 and 11; see the
Supporting Information for more details). Notably, the
exclusion of DMF essentially shut down the reaction (Table
1, entry 12) and when DMF was substituted by THF or
CH3CN, this seemingly trivial change slightly diminished the
yield (Table 1, entries 13 and 14).
With the optimized conditions in hand, the scope of this
cobalt-catalyzed deaminative alkoxycarbonylation method-
ology was explored (see Figure 2). A variety of aryl-substituted
a
Table 1. Optimization of the Reaction Conditions
Figure 2. Scope of pyridinium salts for the alkoxycarbonylation.
Reaction conditions: 1a (0.25 mmol), 2a (10 mmol), Co(acac)2 (10
mol %), L5 (10 mol %), KHCO3 (2.0 equiv), CO (20 bar), DMF (1.1
mL), 100 °C, 12 h, isolated yield.
b
entry
deviation from standard conditions
yield [%]
c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
none
L1 instead of L5
L2 instead of L5
L3 instead of L5
L4 instead of L5
L6 instead of L5
L7 instead of L5
L8 instead of L5
91 [86]
0
0
0
10
23
trace
trace
20
trace
17
alkylpyridinium salts provided the corresponding esters in
moderate to excellent yields. Both 3- and 4-phenyl-substituted
pyridinium salts can deliver excellent yields of the correspond-
ing esters (3ba and 3ca). Versatile functional groups appended
to the aromatic ring, such as methyl, methoxy, fluoride,
chloride, and bromide, were well-tolerated (3fa to 3ja).
However, when electron-deficient functional groups substi-
tuted for other groups, such as the nitro and acetylamino
groups, the reactions in this chemistry failed (see the
Supporting Information for more details). Remarkably,
secondary alkyl amine substrate could also give the
corresponding ester product in 95% yield (3ka). Indole-
substituted alkyl amine gives a moderate yield as well (3la).
Furthermore, Alogliptin, which is a commercially available
antidiabetic drug,12 could be easily modified by this novel
transformation and give the desired product in 92% yield
(3ma). This fact supports the synthetic potential of natural or
drug molecule modification in the future.
L9 instead of L5
DABCO instead of KHCO3
K2CO3 instead of KHCO3
no DMF, CH3OH (1.5 mL)
THF instead of DMF
CH3CN instead of DMF
0
80
76
a
Reaction conditions: 1a (0.25 mmol), 2a (10 mmol), Co(acac)2 (10
mol %), L5 (10 mol %), KHCO3 (2.0 equiv), CO (20 bar), DMF (1.1
mL), 100 °C, 12 h. GC yields, using n-hexadecane as an internal
b
c
standard. Isolated yield.
1). Numerous N-ligands were screened and it was found that
the 1,10-phenanthroline-4,7-diol (L5), an electron-rich ar-
omatic diol ligand, providing the best outcomes (Table 1,
entries 2−9). Both steric and electron-deficient phenanthro-
line-ligands lowered the yield significantly (Table 1, entries 7−
9). Next, we found that other bases, such as DBU, DABCO,
Subsequently, the generality of this method, with respect to
the alcohol partner, was explored (Figure 3). Both ethanol and
methoxyethanol can deliver the desired esters smoothly, in
yields of 74% and 75%, respectively (4ab and 4ac). Here,
because of the low boiling point of the alcohols, 10 equiv of
alcohols are still needed. However, when 2-(phenylthio)-
B
DOI: 10.1021/acs.orglett.9b02534
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Mechanistic Experiments
Scheme 3. Proposed Mechanism
Figure 3. Scope of alcohols for the alkoxycarbonylation. Reaction
conditions: 1 (0.25 mmol), 2 (1.25 mmol), Co(acac)2 (10 mol %),
L5 (10 mol %), KHCO3 (2.0 equiv), CO (20 bar), DMF (1.5 mL),
100 °C, 12 h, isolated yield. For 4ab and 4ac, 2 (10 mmol) and DMF
(1.1 mL) were used.
ethanol was used as the nucleophile, only a 43% yield was
obtained (4ad). Notably, both allyl and propargyl alcohol can
deliver the corresponding products in 63% and 61%,
respectively (4ae, 4af). Then, electron-rich benzyl alcohols
(4aj to 4ai, 4ag) can give good yields of the target esters as
well, compared to the −CF3 group, which only gives 65% yield
(4aj to 4ai). Notably, our newly developed protocol could also
be readily extended to complex molecules derived from natural
product or pharmaceutical molecules. A highly efficient
intramolecular deaminative spirocyclization reaction was
performed; 81% yield of the target product (4ok) was
isolated.13 Moreover, 7-(2-hydroxyethyl)theophylline,14 could
be transformed to the corresponding product in 70% yield as
well (4al).
To investigate the reaction mechanism, a radical-clock
experiment was performed by using a cyclopropylpyridinium
salt 1p under standard reaction conditions (see Scheme 2).
Instead of normal carbonylative product 5pg, a ring-opened
product 5p′g was detected and isolated in 39% yield from the
reaction mixture. In addition, when this reaction was added
with a radical trapping reagent TEMPO (2,2,6,6-tetramethyl-1-
piperidinyloxy), this transformation was suppressed and no
desired carbonylative product (5pg) was detected. These
results suggest that deaminative alkoxycarbonylation follows a
radical-mediated pathway.
CoILn intermediate (B) to give alkyl-CoIILn species (C). The
coordination and insertion of CO to the alkyl-cobalt
intermediate (C) would form an (alkyl)acyl cobalt(II)
intermediate (IV). Finally, alcohol reacts with the acyl
cobalt(II) (D) and produces the desired esters via reductive
elimination. Catalytic active Co0Ln (A) is regenerated in this
step and used for the next cycle.
In summary, the first cobalt-catalyzed deaminative alkox-
ycarbonylation reaction for the conversion of readily available
primary alkyl amines to synthetically versatile esters has been
developed. This transformation shows good functional group
compatibility and efficiency and can serve as a powerful tool
for the modification of alkyl amine-containing complex natural
products and drug molecules. The involvement of alkyl radicals
in this process also has been supported.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02534.
General comments, general procedure, optimization
details, analytic data, and NMR spectra (PDF)
Based on these studies and literature, a plausible mechanism
of the deaminative carbonylation is proposed and shown in
Scheme 3. Initially, Katritzky salt 1 undergoes a single-electron
transfer (SET) pathway with a Co0Ln intermediate (A) to
deliver a pyridinyl radical 2. The pyridinyl radical 2 then
fragments and delivers alkyl radical 4, which recombines with
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: luliangqiu@mail.ccnu.edu.cn (L.-Q. Lu).
C
DOI: 10.1021/acs.orglett.9b02534
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) (a) Yue, H.; Zhu, C.; Shen, L.; Geng, Q.; Hock, K. J.; Yuan, T.;
Cavallo, L.; Rueping, M. Nickel-Catalyzed C−N Bond Activation:
Activated Primary Amines as Alkylating Reagents in Reductive Cross-
Coupling. Chem. Sci. 2019, 10, 4430−4435. (b) Jiang, X.; Zhang, M.
M.; Xiong, W.; Lu, L. Q.; Xiao, W. J. Deaminative (Carbonylative)
Alkyl-Heck-type Reactions Enabled by Photocatalytic C−N Bond
Activation. Angew. Chem., Int. Ed. 2019, 58, 2402−2406. (c) Guan,
W.; Liao, J.; Watson, M. P. Vinylation of Benzylic Amines via C-N
Bond Functionalization of Benzylic Pyridinium Salts. Synthesis 2018,
50, 3231−3237. (d) Fu, M.-C.; Shang, R.; Zhao, B.; Wang, B.; Fu, Y.
Photocatalytic Decarboxylative Alkylations Mediated by Triphenyl-
phosphine and Sodium Iodide. Science 2019, 363, 1429−1434.
(e) Klauck, F. J. R.; Yoon, H.; James, M. J.; Lautens, M.; Glorius, F.
Visible-Light-Mediated Deaminative Three-Component Dicarbofunc-
tionalization of Styrenes with Benzylic Radicals. ACS Catal. 2019, 9,
236−241. (f) Wu, J.; Grant, P. S.; Li, X.; Noble, A.; Aggarwal, V. K.
Catalyst-Free Deaminative Functionalizations of Primary Amines by
Photoinduced Single-Electron Transfer. Angew. Chem., Int. Ed. 2019,
58, 5697−5701. (g) Yang, Z.-K.; Xu, N.-X.; Wang, C.; Uchiyama, M.
Photoinduced C(sp3)-N Bond Cleavage Leading to the Stereo-
selective Syntheses of Alkenes. Chem. - Eur. J. 2019, 25, 5433−5439.
(6) (a) Ociepa, M.; Turkowska, J.; Gryko, D. Redox-Activated
Amines in C(sp3)−C(sp) and C(sp3)−C(sp2) Bond Formation
Enabled by Metal-Free Photoredox Catalysis. ACS Catal. 2018, 8,
11362−11367. (b) Ni, S.; Li, C.-X.; Mao, Y.; Han, J.; Wang, Y.; Yan,
H.; Pan, Y. Ni-Catalyzed Deaminative Cross-electrophile Coupling of
Katritzky Salts with Halides via C-N Bond Activation. Sci. Adv. 2019,
5, eaaw9516. (c) James, M. J.; Strieth-Kalthoff, F.; Sandfort, F.;
Klauck, F. J. R.; Wagener, F.; Glorius, F. Visible-Light-Mediated
Charge Transfer Enables C−C Bond Formation with Traceless
Acceptor Groups. Chem. - Eur. J. 2019, 25, 8240−8244. (d) Liao, J.;
Basch, C. H.; Hoerrner, M. E.; Talley, M. R.; Boscoe, B. P.; Tucker, J.
W.; Garnsey, M. R.; Watson, M. P. Deaminative Reductive Cross-
Electrophile Couplings of Alkylpyridinium Salts and Aryl Bromides.
Org. Lett. 2019, 21, 2941−2946. (e) Yi, J.; Badir, S. O.; Kammer, L.
M.; Ribagorda, M.; Molander, G. A. Deaminative Reductive Arylation
Enabled by Nickel/Photoredox Dual Catalysis. Org. Lett. 2019, 21,
3346−3351.
(7) (a) Moser, D.; Duan, Y.; Wang, F.; Ma, Y.; O’Neill, M. J.;
Cornella, J. Selective Functionalization of Aminoheterocycles by a
Pyrylium Salt. Angew. Chem., Int. Ed. 2018, 57, 11035−11039.
(b) Zhu, Z.-F.; Zhang, M.-M.; Liu, F. Radical Alkylation of
Isocyanides with Amino Acid-/Peptide-derived Katritzky salts via
Photoredox Catalysis. Org. Biomol. Chem. 2019, 17, 1531−1534.
(c) Zhu, Z.-F.; Zhang, M.-M.; Liu, F. Correction: Radical Alkylation
of Isocyanides with Amino Acid-/Peptide-derived Katritzky salts via
Photoredox Catalysis. Org. Biomol. Chem. 2019, 17, 3640−3640.
(8) (a) Hu, J.; Wang, G.; Li, S.; Shi, Z. Selective C-N Borylation of
Alkyl Amines Promoted by Lewis Base. Angew. Chem., Int. Ed. 2018,
57, 15227−15231. (b) Wu, J.; He, L.; Noble, A.; Aggarwal, V. K.
Photoinduced Deaminative Borylation of Alkylamines. J. Am. Chem.
Soc. 2018, 140, 10700−10704. (c) Sandfort, F.; Strieth-Kalthoff, F.;
Klauck, F. J. R.; James, M. J.; Glorius, F. Deaminative Borylation of
Aliphatic Amines Enabled by Visible Light Excitation of an Electron
Donor−Acceptor Complex. Chem. - Eur. J. 2018, 24, 17210−17214.
(9) (a) Brennfuehrer, A.; Neumann, H.; Beller, M. Palladium-
Catalyzed Carbonylation Reactions of Aryl Halides and Related
Compounds. Angew. Chem., Int. Ed. 2009, 48, 4114−4133. (b) Gadge,
S. T.; Gautam, P.; Bhanage, B. M. Transition Metal-Catalyzed
Carbonylative C-H Bond Functionalization of Arenes and C(sp3)-H
Bond of Alkanes. Chem. Rec. 2016, 16, 835−856. (c) Liu, B.; Hu, F.;
Shi, B.-F. Recent Advances on Ester Synthesis via Transition-Metal
Catalyzed C−H Functionalization. ACS Catal. 2015, 5, 1863−1881.
(d) Liu, Q.; Zhang, H.; Lei, A. Oxidative Carbonylation Reactions:
Organometallic Compounds (R-M) or Hydrocarbons (R-H) as
Nucleophiles. Angew. Chem., Int. Ed. 2011, 50, 10788−10799.
(e) Peng, J. B.; Wu, X. F. Ligand- and Solvent-Controlled Regio-
and Chemodivergent Carbonylative Reactions. Angew. Chem., Int. Ed.
2018, 57, 1152−1160. (f) Ryu, I. Radical Carboxylations of
*E-mail: xiao-feng.wu@catalysis.de (X.-F. Wu).
ORCID
Liang-Qiu Lu: 0000-0003-2177-4729
Wen-Jing Xiao: 0000-0002-9318-6021
Xiao-Feng Wu: 0000-0001-6622-3328
Author Contributions
∇These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Chinese Scholarship Council for financial
support. We also thank the Analytical Services Department of
Leibniz-Institute for Catalysis at the University of Rostock for
their excellent analytical service.
REFERENCES
■
(1) (a) Cheung, C. W.; Hu, X. Amine Synthesis via Iron-catalysed
Reductive Coupling of Nitroarenes with Alkyl Halides. Nat. Commun.
2016, 7, 12494. (b) Ruiz-Castillo, P.; Buchwald, S. L. Applications of
Palladium-Catalyzed C-N Cross-Coupling Reactions. Chem. Rev.
2016, 116, 12564−12649. (c) McGrath, N. A.; Brichacek, M.;
Njardarson, J. T. A Graphical Journey of Innovative Organic
Architectures That Have Improved Our Lives. J. Chem. Educ. 2010,
87, 1348−1349. (d) Vitaku, E.; Smith, D. T.; Njardarson, J. T.
Analysis of the Structural Diversity, Substitution Patterns, and
Frequency of Nitrogen Heterocycles among U.S. FDA Approved
Pharmaceuticals. J. Med. Chem. 2014, 57, 10257−10274. (e) Yang, Y.;
Shi, S. L.; Niu, D.; Liu, P.; Buchwald, S. L. Catalytic Asymmetric
Hydroamination of Unactivated Internal Olefins to Aliphatic Amines.
Science 2015, 349, 62−66.
(2) (a) Bapat, J. B.; Blade, R. J.; Boulton, A. J.; Epsztajn, J.; Katritzky,
A. R.; Lewis, J.; Molinabuendia, P.; Nie, P. L.; Ramsden, C. A.
Pyridines as Leaving Groups in Synthetic Transformations:
Nucleophilic Displacements of Amino Groups, and Novel Prepara-
tions of Nitriles and Isocyanates. Tetrahedron Lett. 1976, 17, 2691−
2694. (b) Katritzky, A. R.; Marson, C. M. Pyrylium Mediated
Transformations of Primary Amino Groups into Other Functional
Groups. New Synthetic Methods. Angew. Chem., Int. Ed. Engl. 1984,
23, 420−429. (c) Kong, D.; Moon, P. J.; Lundgren, R. J. Radical
Coupling from Alkyl Amines. Nature Catalysis 2019, 2, 473−476.
(d) Klauck, F. J. R.; James, M. J.; Glorius, F. Deaminative Strategy for
the Visible-Light-Mediated Generation of Alkyl Radicals. Angew.
Chem., Int. Ed. 2017, 56, 12336−12339.
(3) Basch, C. H.; Liao, J.; Xu, J.; Piane, J. J.; Watson, M. P.
Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross
Couplings via C−N Bond Activation. J. Am. Chem. Soc. 2017, 139,
5313−5316.
(4) (a) Plunkett, S.; Basch, C. H.; Santana, S. O.; Watson, M. P.
Harnessing Alkylpyridinium Salts as Electrophiles in Deaminative
Alkyl−Alkyl Cross-Couplings. J. Am. Chem. Soc. 2019, 141, 2257−
2262. (b) Liao, J.; Guan, W.; Boscoe, B. P.; Tucker, J. W.; Tomlin, J.
W.; Garnsey, M. R.; Watson, M. P. Transforming Benzylic Amines
into Diarylmethanes: Cross-Couplings of Benzylic Pyridinium Salts
via C−N Bond Activation. Org. Lett. 2018, 20, 3030−3033.
(c) Martin-Montero, R.; Yatham, V. R.; Yin, H.; Davies, J.; Martin,
R. Ni-catalyzed Reductive Deaminative Arylation at sp(3) Carbon
Centers. Org. Lett. 2019, 21, 2947−2951. (d) Klauck, F. J. R.; Yoon,
H.; James, M. J.; Lautens, M.; Glorius, F. Visible-Light-Mediated
Deaminative Three-Component Dicarbofunctionalization of Styrenes
with Benzylic Radicals. ACS Catal. 2019, 9, 236−241. (e) Zhang, M.-
M.; Liu, F. Visible-light-mediated Allylation of Alkyl Radicals with
Allylic Sulfones via A Deaminative Strategy. Org. Chem. Front. 2018,
5, 3443−3446.
D
DOI: 10.1021/acs.orglett.9b02534
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Iodoalkanes and Saturated Alcohols using Carbon Monoxide. Chem.
Soc. Rev. 2001, 30, 16−25. (g) Sumino, S.; Fusano, A.; Fukuyama, T.;
Ryu, I. Carbonylation Reactions of Alkyl Iodides through the
Interplay of Carbon Radicals and Pd Catalysts. Acc. Chem. Res.
2014, 47, 1563−1574. (h) Peng, J.-B.; Qi, X.; Wu, X.-F. Recent
Achievements in Carbonylation Reactions: A Personal Account.
Synlett 2017, 28, 175−194.
(10) (a) Hartwig, J. Organotransition Metal Chemistry: From Bonding
to Catalysis; University Science Books: Sausalito, CA, 2010; pp 301−
320. (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. (c) Nagahara, K.; Ryu, I.; Komatsu, M.; Sonoda, N.
Radical Carboxylation: Ester Synthesis from Alkyl Iodides, Carbon
Monoxide, and Alcohols under Irradiation Conditions. J. Am. Chem.
Soc. 1997, 119, 5465−5466.
(11) (a) Zhu, F. X.; Li, Y. H.; Wang, Z. C.; Wu, X. F. Iridium-
Catalyzed Carbonylative Synthesis of Chromenones from Simple
Phenols and Internal Alkynes at Atmospheric Pressure. Angew. Chem.,
Int. Ed. 2016, 55, 14151−14154. (b) Yin, Z. P.; Rabeah, J.; Bruckner,
A.; Wu, X. F. Gallic Acid-Promoted SET Process for Cyclobutanone
Oximes Activation and (Carbonylative-)Alkylation of Olefins. ACS
Catal. 2018, 8, 10926−10930. (c) Shen, C. R.; Spannenberg, A.; Wu,
X. F. Palladium-Catalyzed Carbonylative Four-Component Synthesis
of Thiochromenones: The Advantages of a Reagent Capsule. Angew.
Chem., Int. Ed. 2016, 55, 5067−5070. (d) Peng, J. B.; Wu, F. P.; Xu,
C.; Qi, X.; Ying, J.; Wu, X. F. Nickel-Catalyzed Carbonylative
Synthesis of Functionalized Alkyl Iodides. iScience 2018, 8, 175−182.
(e) Li, Y. H.; Dong, K. W.; Zhu, F. X.; Wang, Z. C.; Wu, X. F.
Copper-Catalyzed Carbonylative Coupling of Cycloalkanes and
Amides. Angew. Chem., Int. Ed. 2016, 55, 7227−7230.
(12) White, W. B.; Cannon, C. P.; Heller, S. R.; Nissen, S. E.;
Bergenstal, R. M.; Bakris, G. L.; Perez, A. T.; Fleck, P. R.; Mehta, C.
R.; Kupfer, S.; Wilson, C.; Cushman, W. C.; Zannad, F. Alogliptin
after Acute Coronary Syndrome in Patients with Type 2 Diabetes. N.
Engl. J. Med. 2013, 369, 1327−1335.
(13) Yardley, J. P.; Husbands, G. E. M.; Stack, G.; Butch, J.; Bicksler,
J.; Moyer, J. A.; Muth, E. A.; Andree, T.; Fletcher, H. 2-Phenyl-2-(1-
hydroxycycloalkyl)ethylamine Derivatives: Synthesis and Antidepres-
sant Activity. J. Med. Chem. 1990, 33, 2899−2905.
(14) Lentini, A.; Tabolacci, C.; Nardi, A.; Mattioli, P.; Provenzano,
B.; Beninati, S. Preclinical Evaluation of the Antineoplastic Efficacy of
7-(2-Hydroxyethyl)theophylline on Melanoma Cancer Cells. Melano-
ma Res. 2012, 22, 133−139.
E
DOI: 10.1021/acs.orglett.9b02534
Org. Lett. XXXX, XXX, XXX−XXX