Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of Unactivated Alkyl Iodides with Balloon CO

Article abstract of DOI:10.1021/acs.orglett.9b01573

This work emphasizes the synthesis of alkyl esters via Cu-catalyzed and In-mediated alkoxycarbonylation of unactivated alkyl iodides in the presence of In or InI. The reactions were suitable for the preparation of primary, secondary, and even tertiary alkyl esters, representing an exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.

Full text of DOI:10.1021/acs.orglett.9b01573

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of
Unactivated Alkyl Iodides with Balloon CO
Yanchi Chen, Lei Su, and Hegui Gong*
School of Materials Science and Engineering, Center for Supramolecular Chemistry and Catalysis and Department of Chemistry,
Shanghai University, 99 Shang-Da Road, Shanghai 200444, China
S
* Supporting Information
ABSTRACT: This work emphasizes the synthesis of alkyl
esters via Cu-catalyzed and In-mediated alkoxycarbonylation
of unactivated alkyl iodides in the presence of In or InI. The
reactions were suitable for the preparation of primary,
secondary, and even tertiary alkyl esters, representing an
exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic
studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.
type carbonylation of alkyl tosylates.7 To avoid use of precious
arbonylation of unactivated alkyl electrophiles with
Ccarbon monoxide (CO) is the subject of growing interest transition metals, Mankand and Wu focused on copper-
catalyzed carbonylation of alkyl radicals.8,9 The reactions use
in synthetic chemistry, which has shown great promise in
carbonyl introduction.1 A challenge of these reactions often
low to high pressure of CO (3 to 20 atm) to intercept the alkyl
radials and generate alkyl carbonyl radicals for further
manipulations, e.g., hydroxymethylation,8 and alkenylation
with alkynes and alkenes.9 The hydroxymethylation of primary,
secondary, and tertiary alkyl iodides is performed under 3 atm
of CO by silane reduction of the acyl iodides formed from
iodine transfer to acyl radicals (Scheme 1). However,
preparation of esters through alkoxycarbonylation of unac-
tivated tertiary alkyl substrates appears to be elusive wherein
only special substrates such as adamantyl halides and t-Bu-I
have been used for ester formation under high CO pressure or
UV irradiation.3,10 Moreover, to the best of our knowledge, the
use of copper to mediate alkoxycarbonylation of alkyl halides
has not been revealed.
Herein, we report a Cu-catalyzed alkoxycarbonylation of
unactivated primary, secondary, and tertiary alkyl iodides that
effectively generates alkyl esters under mild reaction conditions
under 1 atm of CO. The use of indium powder or indium(I)
iodides is indispensable for the reaction, wherein formation of
alkyl-indium was excluded.4,11 This work represents an
exceptionally rare carbonylation method for the formation of
esters by creating acylated all carbon quaternary centers using
balloon CO, which may find applications in the synthesis of
structurally more complex scaffolds containing ester moieties.
We commenced our studies with the reaction of a secondary
alkyl iodide 1 in the presence of balloon CO and 5 equiv of
MeOH. After extensive screening of the reaction conditions, an
optimal 70% yield for the ester 2 was identified using a
combination of CuOTf/In/MgCO3 in 1,4-dioxane (method A,
Table 1, entry 1). The major side reactions were composed of
hydrodehalogenation (14%) and hydroxylation (5%) of the
relies on the capture of in situ generated alkyl radicals by high
pressure CO under relatively forcing conditions, e.g., UV light
irradiation in the presence of Pd, Rh catalysts.1 In this context,
numerous elegant transformations have been developed.2
Recently, manipulation of the carbonylative alkylation under
low CO pressure has received prominent progress.3−9
Alexanian has exploited elegant Pd-catalyzed carbonylation of
alkyl bromides by judicious selection of carbene ligands.5 The
remarkably mild reaction conditions using a Pd(IPr) catalyst
allow expeditious alkoxycarbonylation of secondary alkyl
bromides under low CO pressure (2 atm, Scheme 1). The
same group also disclosed Mn-catalyzed intramolecular
carbonylative cyclization of alkene-tethered alkyl iodides
under 10 atm of CO atmosphere6 and Co-catalyzed SN2
Scheme 1. Selected Examples of Carbonylation of Alkyl
Halides with Low Pressure CO
Received: May 5, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01573
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Optimization for the Methoxycarbonylation of 1
under 1 atm of CO
a
b
entry
variation from the standard conditions
yield (%)
c
1
2
3
none
w/o In
w/o CuOTf
78 (70)
d
ND
d
ND
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
w/o MgCO3
69
70
66
74
ND
ND
ND
61
ND
76
CuCl instead of CuOTf
CuBr instead of CuOTf
CuI instead of CuOTf
CuCl2 instead of CuOTf
CuSO4 instead of CuOTf
Cu(OTf)2 instead of CuOTf
InI instead of In
InCl3 instead of In
K2CO3 instead of MgCO3
Et3N instead of MgCO3
2.0 atm of CO
d
d
d
d
<10
68
68
4.0 atm of CO
Zn instead of In
trace
d
Mn instead of In
ND
e
c
none
63
a
b
Standard conditions: see Table 1, entry 1. NMR yield using 2,5-
c
d
dimethylfuran as the internal reference. Isolated yield. Not detected.
e
The reaction was scaled up to 2 mmol.
alkyl iodide.12 Both Cu salt and In proved to be necessary.
Without either of them, no reaction occurred (entries 2−3).
The reaction furnished 2 in 69% yield in the absence of
MgCO3 (entry 4). Examination of other copper salts indicated
that CuI salts were generally effective (entries 5−7), whereas
no reactions occurred when CuII salts were employed (entries
8−10). Interestingly, use of InI furnished 2 in 61% yield,
whereas InCl3 was ineffective (entries 11−12),13 which differs
from the previously reported Co/InCl3/UV conditions.3
Variation of the base additives, the pressure of CO, and
reductants did not lead to improved yields (entries 13−18).
Other alcohols such as ethanol give the ester in moderate
yields.12 Finally, the reaction was performed on a 2 mmol scale,
and the yield for 2 was obtained in 63% (entry 19).
A survey of the substrate compatibility was executed next.
We first examined a set of cyclic alkyl iodides; moderate to
good yields for the esters 3−9 (Figure 1) were obtained. Of
note is the effectiveness of the sterically more hindered esters 5
and 6 which contain a bridge carbon and a scaffold derived
from cholestane. The substrates containing free amide protons
were also suitable, as evidenced in the products 8a and 8b. The
cyclododecanecarboxylic acid methyl ester 9 was also attained
in 74% yield. For open-chain alkyl electrophiles, the secondary
iodides were generally more effective than the primary ones as
verified by the examples of 10−21. For 12 and 13, CO at 4
atm was used, possibly due to chelation of the furyl and thienyl
with Cu that eroded the coupling yields. For the secondary
iodide adjacent to an admantanyl group, the ester 17 was
obtained in 43% yield. The reaction was not limited to 2-iodo
substrates. Conversion of 9-iodo-heptadecane to 18 was
successful. The reaction conditions were tolerant of a wide
Figure 1. Methoxycarbonylation of primary and secondary alkyl
iodides. (a) Standard reaction conditions as in Table 1, entry 1.
Isolated yield. (b) Without MgCO3. (c) 1.5 equiv of In. (d) 4 atm of
CO.
range of functional groups. These included Boc, Ts, acetal,
ester, OTs, and silyl ether.
Encouraged by the results observed for the sterically
hindered secondary alkyl iodides, we questioned whether the
more challenging tertiary alkyl iodides were competent with
the present ester formation method. Such a reaction is
intriguing, since alkoxycarbonylation of tertiary alkyl electro-
philes remains an extraordinary challenge in the carbonylative
ester forming process.10 With method A, the yield for the
desired product 22 was observed in 5% yield. However, by
replacement of 1.2 equiv of indium powder with 1 equiv of InI,
the yield was boosted to 60%. Thus, with the modified method
(method B, Figure 2) we examined the scope and limitations
of tertiary alkyl iodides. Similar to 22 that bears an ester
moiety, benzofuryl- and phosphoryl-decorated esters 23 and
24 were obtained in moderate yields, although 4 atm of CO
were needed for 23. The tertiary alkyl iodides adjacent to
benzylic groups were effective to give 25−27 in moderate
yields, wherein the benzyl moieties contained phenyl,
trimethoxy, and dichloro substituents. The iodides vicinal to
phenylethyl and (6-bromo)hexyl produced 28−29 in 45% and
48% yields, respectively. The bromo group in the latter
B
DOI: 10.1021/acs.orglett.9b01573
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
recovery of 1 (eq 4), further confirming that formation and
involvement of alkyl−In reagents is less likely in the ester
forming process. It also indicates that generation of alkyl
radicals by reaction of alkyl iodides with In and CuI is less
plausible under the present reaction conditions.13−16
We also examined the reactions in a stepwise fashion. Thus,
treatment of a mixture of In and CuI with a balloon of CO in
1,4-dioxane for 1 h followed by addition of 1 and MeOH
furnished 2 in 55% yield (eq 5). However, exposure of either
In or CuI to CO prior to the addition of the remaining
reaction components failed to generate 2 in appreciable yields
(eqs 6−7). These observations suggest that In(Cu)x(CO)y
complexes may form which is crucial for this esterification
process.16,17 The consumption of alkyl iodide 1 was only
observed when CO (balloon) was present by exposure of 1 to
a mixture of CuI and In (eq 5). Thus, formation of an alkyl
radical can be realized through one-electron reduction or
iodine abstraction by In(Cu)x(CO)y to afford In(Cu)m(CO)nI
(Scheme 2). The low pressure radical carbonylation of the
Figure 2. Methoxycarbonylation of tertiary alkyl iodides. (a) Reaction
conditions: method B. Isolated yield. (b) 4 atm of CO. (c) CsCO3
instead of K2CO3. (d) 1.5 equiv of InI.
product offers opportunities for further manipulation. Finally,
the tertiary alkyl iodides presented in cyclic rings furnished the
products 30−36 in moderate to good yields, wherein the four-,
five-, and six-membered rings were all effective. The formation
of ester 31 on the fused bicyclic ring is noted. A low yield was
obtained due to a competitive ring-opening deamination
process.
Scheme 2. Proposed Catalytic Cycle
To gain insight into the reaction, we first confirmed that
alkyl radicals were involved in this carbonylation method by
ring cyclization of 6-iodohept-1-ene and ring opening of
(iodomethyl)cyclopropane to afford the esterification products
37 and 38 in 33% and 22% yields, respectively (eqs 1−2).
alkyl radical may involve reaction of alkyl radicals with
In(Cu)x(CO)y or In(Cu)m(CO)nI to give acyl−In(Cu)
intermediates. Upon metholysis, the ester can be produced
and Cu(I) maybe regenerated (Scheme 2).
In summary, we have disclosed that, under Cu-catalyzed and
In-mediated reductive conditions, effective alkoxycarbonyla-
tion of unactivated alkyl iodides has proven to be viable. The
construction of quaternary carbon centers upon formation of
esters from tertiary alkyl iodides represents the first examples
of formation of tertiary alkyl esters using carbon monoxide as
the carbonylation source. The transformations were performed
using balloon CO, which is rare in the concurrent carbon-
ylation of alkyl radicals. Thus, the mild reaction conditions
Next, subjection of preformed alkyl−InX2 to the standard
method A with or without In did not lead to the ester product,
suggesting that involvement of in situ formation of an alkyl−In
intermediate followed by carbonylation is less likely (eq 3).11,12
Exposure of 1 under the standard reaction conditions in the
absence of CO (with or without MeOH) resulted in >90%
C
DOI: 10.1021/acs.orglett.9b01573
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Ed. 2012, 51, 12542−12545. (c) Liu, J.; Liang, B.; Shu, D.; Yang, Z.;
Lei, A. Alkoxycarbonylation of aryl iodides catalyzed by Pd with a
thiourea type ligand under balloon pressure of CO. Tetrahedron 2008,
64, 9581−9584.
developed in the present work may find useful applications in
the late-stage installation of ester functionalities, which also
serves a complement to the known methods.
(5) Sargent, B. T.; Alexanian, E. J. Palladium-Catalyzed Alkox-
ycarbonylation of Unactivated Secondary Alkyl Bromides at Low
Pressure. J. Am. Chem. Soc. 2016, 138, 7520−7523.
ASSOCIATED CONTENT
* Supporting Information
■
S
(6) McMahon, C. M.; Renn, M. S.; Alexanian, E. J. Manganese-
Catalyzed Carboacylations of Alkenes with Alkyl Iodides. Org. Lett.
2016, 18, 4148−4150.
(7) Sargent, B. T.; Alexanian, E. J. Cobalt-Catalyzed Carbonylative
Cross-Coupling of Alkyl Tosylates and Dienes: Stereospecific
Synthesis of Dienones at Low Pressure. J. Am. Chem. Soc. 2017,
139, 12438−12440.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01573.
Detailed experimental procedures and characterization
of new compounds (PDF)
(8) (a) Cheng, L.-J.; Mankad, N. P. Cu-Catalyzed Hydro-
carbonylative C−C Coupling of Terminal Alkynes with Alkyl Iodides.
J. Am. Chem. Soc. 2017, 139, 10200−10203. (b) Cheng, L.-J.; Islam, S.
M.; Mankad, N. P. Synthesis of Allylic Alcohols via Cu-Catalyzed
Hydrocarbonylative Coupling of Alkynes with Alkyl Halides. J. Am.
Chem. Soc. 2018, 140, 1159−1164. (c) Cheng, L.-J.; Mankad, N. P.
Copper-Catalyzed Borocarbonylative Coupling of Internal Alkynes
with Unactivated Alkyl Halides: Modular Synthesis of Tetrasub-
stituted β-Borylenones. Angew. Chem., Int. Ed. 2018, 57, 10328−
10332. (d) Pye, D. R.; Cheng, L.-J.; Mankad, N. P. Cu/Mn Bimetallic
Catalysis Enables Carbonylative Suzuki−Miyaura Coupling with
Unactivated Alkyl Electrophiles. Chem. Sci. 2017, 8, 4750−4755.
(e) Zhao, S.; Mankad, N. P. Cu-Catalyzed Hydroxymethylation of
Unactivated Alkyl Iodides with CO to Provide One-Carbon-Extended
Alcohols. Angew. Chem., Int. Ed. 2018, 57, 5867−5972.
(9) (a) Li, Y.; Dong, K.; Zhu, F.; Wang, Z.; Wu, X.-F. Copper-
Catalyzed Carbonylative Coupling of Cycloalkanes and Amides.
Angew. Chem., Int. Ed. 2016, 55, 7227−7230. (b) Li, Y.; Wang, C.;
Zhu, F.; Wang, Z.; Dixneuf, P. H.; Wu, X.-F. Copper-Catalyzed
Alkoxycarbonylation of Alkanes with Alcohols. ChemSusChem 2017,
10, 1341−1345.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hegui_gong@shu.edu.cn.
ORCID
Hegui Gong: 0000-0001-6534-5569
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support was provided by the Chinese NSF (Nos.
21871173 and 21572127).
■
REFERENCES
■
(1) Selected reviews on carbonylation reaction of alkyl halide:
(a) Ryu, I.; Sonoda, N.; Curran, D. P. Tandem Radical Reactions of
Carbon Monoxide, Isonitriles, and Other Reagent Equivalents of the
Geminal Radical Acceptor/Radical Precursor Synthon. Chem. Rev.
1996, 96, 177−194. (b) Ryu, I.; Sonoda, N. Free-Radical Carbon-
ylations: Then and Now. Angew. Chem., Int. Ed. Engl. 1996, 35, 1050−
1066. (c) Ryu, I. Radical Carboxylations of Iodoalkanes and Saturated
Alcohols Using Carbon Monoxide. Chem. Soc. Rev. 2001, 30, 16−25.
(d) Frisch, A. C.; Beller, M. Catalysts for Cross-Coupling Reactions
with Non-activated Alkyl Halides. Angew. Chem., Int. Ed. 2005, 44,
674−688. (e) Wu, L.; Fang, X.; Liu, Q.; Jackstell, R.; Beller, M.; Wu,
X.-F. Palladium-Catalyzed Carbonylative Transformation of C(sp3)−
X Bonds. ACS Catal. 2014, 4, 2977−2989. (f) 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. (g) Li, Y.; Hu, Y.; Wu, X.-F. Non-noble
Metal-catalysed Carbonylative Transformations. Chem. Soc. Rev. 2018,
47, 172−194.
(2) (a) Kondo, T.; Tsuji, Y.; Watanabe, Y. Photochemical
Carbonylation of Alkyl Iodides in the Presence of Various Metal
Carbonyls. Tetrahedron Lett. 1988, 29, 3833−3836. (b) 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.
(c) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.; Sonoda,
N. New Strategies in Carbonylation Chemistry: The Synthesis of δ-
Lactones from Saturated Alcohols and CO. J. Am. Chem. Soc. 1998,
120, 8692−8701.
(10) Xe-irradiation−carbonylation at 45 atm: Fukuyama, T.;
Nishitani, S.; Inouye, T.; Morimoto, K.; Ryu, I. Effective Acceleration
of Atom Transfer Carbonylation of Alkyl Iodides by Metal
Complexes. Application to the Synthesis of the Hinokinin Precursor
and Dihydrocapsaicin. Org. Lett. 2006, 8, 1383−1386.
(11) Formation of alkyl-InX2 under Cu-mediated conditions: Kim,
S.; Kim, C.-E.; Seo, B.; Lee, P. H. In Situ Generation of Phosphoryl
Alkylindiums and Their Synthetic Application to Arylalkyl Phospho-
nates via Palladium-Catalyzed Cross-Coupling Reactions. Org. Lett.
2014, 16, 5552−5555.
(12) See the Supporting Information for details.
(13) The reaction may involve possible reduction of Cu(I) to Cu(0)
red
red
(E1/2 = + 0.52 V vs SCE in water) by In(I) (E1/2 = −0.41 V vs
red
SCE in water) or In(0) (E1/2 = −0.14 V vs SEC in water), which
may account for the incompetence of In(III).
(14) In-induced alkyl radical formation often requires water as the
solvent. For reviews, see: (a) Miyabe, H.; Naito, T. The Utility of
Indium in Aqueous Medium Radical Reactions. Org. Biomol. Chem.
2004, 2, 1267−1270. (b) Loh, T.-P.; Chua, G.-L. Discovery of Indium
Complexes as Water-Tolerant Lewis acids. Chem. Commun. 2006,
́
2739−2749. (c) Auge, J.; Lubin-Germain, N.; Uziel, J. Recent
Advances in Indium-Promoted Organic Reactions. Synthesis 2007,
2007, 1739.
(15) (a) Miyabe, H.; Ueda, M.; Nishimura, A.; Naito, T. Indium-
Mediated Intermolecular Alkyl Radical Addition to Electron-Deficient
C = N Bond and C = C Bond in Wate. Org. Lett. 2002, 4, 131−134.
(b) Yanada, R.; Nishimori, N.; Matsumura, A.; Fujii, N.; Takemoto,
Y. Indium-Mediated Atom-Transfer Cyclizations and Reductive
Cyclizations. Tetrahedron Lett. 2002, 43, 4585−4588. (c) Bhatti, N.
H.; Salter, M. M. A Novel Atom-Transfer Cyclisation Catalysed by
Indium Metal in Halogenated Solvents. Tetrahedron Lett. 2004, 45,
8379−8382. (d) Cao, L.; Shen, M.; Li, C. Indium-Mediated Alkyl
Radical Addition to (η6-Arene) tricarbonylmanganese Complexes in
Aqueous Media. Organometallics 2005, 24, 5983−5988. (e) Shen, Z.-
(3) Adamantyl bromide as the only viable example of tertiary alkyl
halides ester formation has been reported using Co-catalysis,
mediated by InCl3 mediated at 1 atm of CO under UV irradiation;
see: Cash, D.; Combs, A.; Dragojlovic, V. Cobalt-catalyzed Photolytic
Methoxycarbonylation of Bromoalkanes in the Presence of a Lewis
Acid. Tetrahedron Lett. 2004, 45, 1143−1145.
(4) (a) Zhao, Y.; Jin, L.; Li, P.; Lei, A. Palladium-Catalyzed
Oxidative Carbonylation of Alkyl and Aryl Indium Reagents with CO
under Mild Conditions. J. Am. Chem. Soc. 2008, 130, 9429−9433.
(b) Zhang, H.; Shi, R.; Ding, A.; Lu, L.; Chen, B.; Lei, A. Transition-
Metal-Free Alkoxycarbonylation of Aryl Halides. Angew. Chem., Int.
D
DOI: 10.1021/acs.orglett.9b01573
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
L.; Loh, T.-P. Indium-Copper-Mediated Barbier-Grignard-Type
Alkylation Reaction of Imines in Aqueous Media. Org. Lett. 2007,
9, 5413−5416. (f) Shen, Z.-L.; Goh, K. K. K.; Yang, Y.-S.; Lai, Y.-C.;
Wong, C. H. A.; Cheong, H.-L.; Loh, T.-P. Direct Synthesis of Water-
Tolerant Alkyl Indium Reagents and Their Application in Palladium-
Catalyzed Couplings with Aryl Halides. Angew. Chem., Int. Ed. 2011,
50, 511−514. (g) Chen, B.-Z.; Zhi, M.-L.; Wang, C.-X.; Chu, X.-Q.;
Shen, Z.-L.; Loh, T.-P. Synthesis of Alkyl Indium Reagents by Using
Unactivated Alkyl Chlorides and Their Applications in Palladium-
Catalyzed Cross-Coupling Reactions with Aryl Halides. Org. Lett.
2018, 20, 1902−1905. (h) Friestad, G. K.; Qin, J. Intermolecular
Alkyl Radical Addition to Chiral N-Acylhydrazones Mediated by
Manganese Carbonyl. J. Am. Chem. Soc. 2001, 123, 9922−9923.
(16) Formation of an In(Cu) complex has been proposed for
initiation of alkyl radicals from alkyl iodides: Shen, Z.-L.; Yeo, Y.-L.;
Loh, T.-P. Indium-Copper and Indium-Silver Mediated Barbier-
Grignard-Type Alkylation Reaction of Aldehydes Using Unactivated
Alkyl Halides in Water. J. Org. Chem. 2008, 73, 3922−3922.
(17) (a) Himmel, H.-J.; Downs, A. J.; Green, J. C.; Greene, T. M.
Thermal and Photolytic Reactions of Gallium and Indium Atoms (M)
and Their Dimers M2 with Carbon Monoxide in Low-Temperature
Matrices: Formation of Terminal, Bridged, and Ionic Carbonyl
Derivatives. J. Phys. Chem. A 2000, 104, 3642−3654. (b) Hatton, W.
G.; Hacker, N. P.; Kasai, P. H. Indium Dicarbonyl: Matrix Isolation
ESR and IR Study. J. Phys. Chem. 1989, 93, 1328−1332.
E
DOI: 10.1021/acs.orglett.9b01573
Org. Lett. XXXX, XXX, XXX−XXX