Copper-Catalyzed C(sp)-C(sp3) Coupling of Terminal Alkynes with Alkylsilyl Peroxides via a Radical Mechanism

Article abstract of DOI:10.1021/acs.orglett.8b00173

A copper-catalyzed C(sp)-C(sp³) coupling reaction between terminal alkynes and alkylsilyl peroxides is reported. In the presence of a copper catalyst and 4-dimethylaminopyridine, the reaction smoothly affords a variety of internal alkynes by co

Full text of DOI:10.1021/acs.orglett.8b00173

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Copper-Catalyzed C(sp)−C(sp3) Coupling of Terminal Alkynes with
Alkylsilyl Peroxides via a Radical Mechanism
Ryu Sakamoto,† Terumasa Kato,† Shunya Sakurai,† and Keiji Maruoka*,†,‡
†Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
‡School of Chemical Engineering and Light Industry, Guangdong University of Technology, No. 100, West Waihuan Road, HEMC, 4
Panyu District, Guangzhou 510006, China
S
* Supporting Information
ABSTRACT: A copper-catalyzed C(sp)−C(sp3) coupling reaction
between terminal alkynes and alkylsilyl peroxides is reported. In the
presence of a copper catalyst and 4-dimethylaminopyridine, the reaction
smoothly affords a variety of internal alkynes by coupling alkylsilyl
peroxides and terminal alkynes. Mechanistic studies suggest that the
reaction proceeds via a radical mechanism, whereby the alkyl radicals are generated from the alkylsilyl peroxides. The present
transformation represents a rare example of a radical-mediated C(sp)−C(sp3) coupling reaction of terminal alkynes.
Scheme 1. Reactions of Alkynes and Their Derivatives with
Alkyl Radicals
lkynes are structurally important in natural products,
Abiologically active molecules, and functional materials,
and they also represent versatile synthetic intermediates.1
Therefore, considerable research efforts have been devoted in
recent decades to the development of novel synthetic methods to
generate substituted alkynes.2 The Sonogashira coupling of
terminal alkynes and aryl/vinyl halides or triflates is one of the
most reliable ways for the formation of C(sp)−C(sp2) bonds for
the synthesis of internal alkynes.3 On the other hand, the
Sonogashira coupling of terminal alkynes with alkyl halides, i.e.,
the formation of C(sp)−C(sp3) bonds, still remains a
challenging topic in current organic synthesis.4 Thus, the
development of alternative approaches to the formation of
C(sp)−C(sp3) bonds involving terminal alkynes is a very
promising research target.
Recently, radical alkynylations using electrophilic alkyne
reagents such as alkynyl sulfones or alkynyl benziodoxolones
have emerged as a particularly useful approach for the formation
of C(sp)−C(sp3) bonds.5−7 Given the recent focus on atom-
economic and sustainable chemistry, the direct use of terminal
alkynes for the synthesis of internal alkynes should be preferable
from a practical perspective. However, examples for the direct
C(sp)−C(sp3) coupling between terminal alkynes and alkyl
radicals to obtain internal alkynes remain elusive, as the reaction
between terminal alkynes and alkyl radicals usually leads to the
difunctionalization or reductive alkylation of alkynes, resulting in
the formation of internal alkenes (Scheme 1a).8−10 Therefore,
the development of novel radical strategies for the direct
formation of C(sp)−C(sp3) bonds for the synthesis of internal
alkynes from terminal alkynes is highly desirable.
benziodoxolones via β-fragmentation of alkoxy radicals (Scheme
1b).6h While this approach allows the synthesis of versatile
internal alkynes under mild reaction conditions, the reaction still
requires alkynyl benziodoxolone reagents. In this context, we
report herein the copper-catalyzed direct C(sp)−C(sp3)
coupling reaction of terminal alkynes with alkylsilyl peroxides
via a radical mechanism (Scheme 1c). This approach enables the
generation of alkyl radicals by β-fragmentation of less strained
cyclic and linear alkoxy radicals, thus resulting in the formation of
a variety of internal alkynes.
The β-fragmentation reaction of alkoxy radicals has been
recently recognized as a useful strategy for the generation of alkyl
radicals and successfully been applied in a variety of radical
reactions.11 In 2016, Chen and co-workers reported the visible-
light-induced radical alkynylation of strained cycloalkanols (i.e.,
cyclobutanol and cyclopropanol) and linear alcohols with alkynyl
Received: January 17, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00173
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
As part of our efforts on the development of radical-mediated
reactions, we have recently reported a novel approach to the
generation of alkyl radicals using alkylsilyl peroxides (1), i.e., the
copper-catalyzed selective mono-N-alkylation of primary amides
and arylamines.12 These peroxides are readily prepared by the
reactions of corresponding alcohols with hydrogen peroxide in
the presence of sulfonic acid, followed by the protection with
trialkylsilyl groups. They also easily generate a variety of alkyl
radicals via β-fragmentation of alkoxy radicals under mild
conditions depending on their structure. To demonstrate the
further utility of 1, we became interested in the development of a
direct C(sp)−C(sp3) coupling reaction between terminal
alkynes and alkylsilyl peroxides.
Initially, we examined the reaction between 1-ethynyl-4-
methylbenzene and cyclic alkylsilyl peroxide 1a as an alkyl radical
source, which afforded δ-alkynyl ketone 2a (for optimization
details, see Supporting Information). After extensive screening of
conditions, we finally discovered that the reaction of the alkyne
with 1a (1.4 equiv) in the presence of CuI (5 mol %) and 4-
dimetylaminopyridine (DMAP) (1.0 equiv) at 80 °C furnished
2a in excellent yield (Table 1, entry 1). With the optimized
conditions in hand, we subsequently examined the scope of this
reaction with respect to the alkylsilyl peroxides (1). The use of
six- (1b) and seven-membered cyclic peroxides (1c) furnished
the corresponding products (2b and 2c) in moderate to good
yields (entries 2 and 3). Different substituents on the aryl moiety
of the peroxides (1d−f) were well tolerated, affording the
respective products (2d−f) in high yield (entries 4−6). The
reaction with 1g, which bears an ether moiety, afforded 2g in
moderate yield (entry 7). When ethyl-substituted cyclopentyl
peroxide 1h was used, the ring opening of the cyclopentyl moiety
occurred selectively to furnish δ-alkynyl ketone 2h in good yield
(entry 8). In the case of bicyclic peroxide 1i, which is a
norcamphor derivative, 2i was obtained as a diastereomeric
mixture via the selective cleavage of the C(1)−C(2) bond of the
norbornane moiety (entry 9). Acyclic alkylsilyl peroxides 3a and
3b were also applicable to introduce cyclohexyl or tetrahy-
dropyranyl moieties, affording 4a and 4b in good yield (Scheme
2).
a
Scheme 2. Alkynylation Using Acyclic Alkylsilyl Peroxides 3
a
The yield was determined by 1H NMR spectroscopy using CH3NO2
as an internal standard; the isolated yield is given in parentheses.
Subsequently, the suitability of different alkynes for this
transformation was examined (Scheme 3). The reaction of
Table 1. Alkynylation Reaction Using Cyclic Alkylsilyl
Peroxides 1 with 1-Ethynyl-4-methylbenzene
a b
,
a
Scheme 3. Scope of Alkynes
a
The yield was determined by 1H NMR spectroscopy using CH3NO2
as an internal standard; the isolated yield is given in parentheses.
phenylacetylene with 1a proceeded smoothly to afford 5a in high
yield. A methyl substituent at the ortho position of the aryl moiety
did not affect the reaction, and 5b was obtained in excellent yield.
A variety of aryl groups containing electron-withdrawing or
-donating substituents successfully furnished the corresponding
products (5c−g) in moderate to good yields. The use of an
alkenyl-substituted alkyne also afforded the corresponding
product (5h) in 53% yield. In the case of alkyl-substituted
alkynes, the desired products (5i and 5j) were obtained in low
yield. The reactions using silyl or phthalimide (Phth)
substituents on the alkyne provided the corresponding alkynes
(5k and 5l) in moderate yield.
a
Unless otherwise specified, reactions were carried out in the presence
of 1 (1.4 equiv), alkyne (0.2 mmol), CuI (5 mol %), and DMAP (1.0
equiv) in benzene (0.2 M) at 80 °C under an atmosphere of argon.
b
The yield was determined by 1H NMR spectroscopy using CH3NO2
as an internal standard; the isolated yield is given in parentheses.
c
Temp = 50 °C.
B
DOI: 10.1021/acs.orglett.8b00173
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
The synthetic utility of the δ-alkynyl ketones thus obtained is
illustrated in Scheme 4. δ-Alkynyl ketone 2a (R = Ph) was
Scheme 6. Effect of Different Pyridines on the Copper-
Catalyzed C(sp)−C(sp3) Coupling between Terminal
Alkynes and Alkylsilyl Peroxides
Scheme 4. Subsequent Transformations of Products
converted into the corresponding alcohol (6) by treatment with
sodium borohydrate, followed by palladium-catalyzed intra-
molecular cyclization to give a 2,6-disubstituted tetrahydropyran
(7).14 Additionally, 2h (R = Et) was readily converted into α−β-
unsaturated ketone 8 in 80% yield upon carrying out an acid-
catalyzed intramolecular cyclization.15
In order to better understand the underlying reaction
mechanism, a series of control experiments were carried out.
Initially, in order to rule out the potential involvement of alkyl
hydroperoxides formed from the alkylsilyl peroxides as a possible
source of alkyl radicals, the same reaction was carried out using 1-
ethynyl-4-methylbenzene and hydroperoxide 9 instead of 1a.16
The reaction with hydroperoxide 9 provided a complex mixture,
including a small amount of 2a (Scheme 5a). This result revealed
2,6-lutidine, 4-cyanopyridine, or methyl isonicotinate was not
effective. The use of an N-methyl DMAP salt was also not
successful. These observations suggest that electronic and steric
effects of the pyridine nitrogen atom significantly affect the
decomposition of the peroxide.
Scheme 7 shows our proposed catalytic cycle for the C(sp)−
C(sp3) coupling of terminal alkynes and alkylsilyl peroxides.
Scheme 7. Plausible Reaction Mechanism
Scheme 5. Control Experiments
Alkylsilyl peroxides 1 should decompose in the presence of
nitrogen-coordinated copper species, which would lead to the
generation of alkoxy radicals (12) and copper−silanoxide
complexes (13).19 A subsequent β-fragmentation of 12 would
generate the corresponding alkyl radicals 14. After a ligand
exchange on the copper center between an alkyne and a
silanoxide, the coupling of the alkyl radicals and copper−alkynyl
complexes (15) could finally afford the desired products.
In conclusion, a copper-catalyzed C(sp)−C(sp3) coupling
reaction between terminal alkynes and alkylsilyl peroxides has
been developed. We discovered that the use of 4-dimethyl-
aminopyridine (DMAP) is critical for the efficient formation of a
C−C bond between the terminal alkynes and alkyl radicals. The
reaction provides access to versatile internal alkynes by coupling
terminal alkynes and alkylsilyl peroxides, and it offers a synthetic
approach to internal alkynes that complements Sonogashira-type
reactions. Further investigation into the applications of such
alkylsilyl peroxides and the details of the reaction mechanism is
currently in progress in our laboratory.
the importance of the silyl group for the efficient cleavage of the
O−O bond to generate the alkoxy radicals. Next, we carried out
radical-trapping experiments. A reaction using alkynyl sulfone 10
instead of a terminal alkyne as the alkyl radical acceptor provided
2a in 53% yield (Scheme 5b).5,17 The addition of the radical
scavenger 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radi-
cal under standard conditions inhibited the reaction, thus
affording radical adduct 11 (Scheme 5c). These results suggest
that the reaction probably involves a free-radical mechanism
involving alkyl radicals.
Upon screening several pyridines, we tentatively concluded
that DMAP should work as a base as well as a ligand for the
copper catalyst, promoting the degradation of the peroxides
(Scheme 6).18 While pyridine and electron-rich pyridines such as
DMAP, 4-(pyrrolidin-1-yl)pyridine, or 4-methoxypyridine facili-
tated the decomposition of the peroxide and thus the formation
of 2a, the addition of bulky or electron-deficient pyridines such as
C
DOI: 10.1021/acs.orglett.8b00173
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Shi, L.; Zhang, X.-Z.; Chen, S.-Y.; Yu, X.-Q. Org. Lett. 2016, 18, 4024.
(j) Cheng, Z.-F.; Feng, Y.-S.; Rong, C.; Xu, T.; Wang, P.-F.; Xu, J.; Dai,
J.-J.; Xu, H.-J. Green Chem. 2016, 18, 4185. (k) Yang, C.; Yang, J.-D.; Li,
Y.-H.; Li, X.; Cheng, J.-P. J. Org. Chem. 2016, 81, 12357. (l) Le Vaillant,
F.; Wodrich, M. D.; Waser, J. Chem. Sci. 2017, 8, 1790.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b00173.
■
S
(7) Feng, Y.-S.; Xu, Z.-Q.; Mao, L.; Zhang, F.-F.; Xu, H.-J. Org. Lett.
2013, 15, 1472.
Experimental procedures and characterization data for all
compounds (PDF)
(8) (a) Geraghty, N. W. A.; Hannan, J. J. Tetrahedron Lett. 2001, 42,
3211. (b) Doohan, R. A.; Geraghty, N. W. A. Green Chem. 2005, 7, 91.
(c) Oka, R.; Nakayama, M.; Sakaguchi, S.; Ishii, Y. Chem. Lett. 2006, 35,
1104. (d) Tusun, X.; Lu, C.-D. Synlett 2013, 24, 1693. (e) Li, J.; Zhang,
J.; Tan, H.; Wang, D. Z. Org. Lett. 2015, 17, 2522. (f) Cheung, C. W.;
Zhurkin, F. E.; Hu, X. J. Am. Chem. Soc. 2015, 137, 4932. (g) Li, Y.; Ge,
L.; Qian, B.; Babu, K. R.; Bao, H. Tetrahedron Lett. 2016, 57, 5677.
(9) (a) Ichinose, Y.; Matsunaga, S.; Fugami, K.; Oshima, K.; Utimoto,
K. Tetrahedron Lett. 1989, 30, 3155. (b) Han, L.-B.; Ishihara, K.; Kambe,
N.; Ogawa, A.; Ryu, I.; Sonoda, N. J. Am. Chem. Soc. 1992, 114, 7591.
(10) (a) Liu, W.; Li, L.; Li, C.-J. Nat. Commun. 2015, 6, 6526. (b) Tang,
S.; Wang, P.; Li, H.; Lei, A. Nat. Commun. 2016, 7, 11676.
(11) For selected examples, see: (a) Jiao, J.; Nguyen, L. X.; Patterson,
D. R.; Flowers, R. A., II Org. Lett. 2007, 9, 1323. (b) Wang, Y.-F.; Chiba,
S. J. Am. Chem. Soc. 2009, 131, 12570. (c) Wang, Y.-F.; Toh, K. K.; Ng, E.
P. J.; Chiba, S. J. Am. Chem. Soc. 2011, 133, 6411. (d) Ilangovan, A.;
Saravanakumar, S.; Malayappasamy, S. Org. Lett. 2013, 15, 4968.
(e) Bloom, S.; Bume, D. D.; Pitts, C. R.; Lectka, T. Chem. - Eur. J. 2015,
21, 8060. (f) Ren, S.; Feng, C.; Loh, T.-P. Org. Biomol. Chem. 2015, 13,
5105. (g) Zhao, H.; Fan, X.; Yu, J.; Zhu, C. J. Am. Chem. Soc. 2015, 137,
3490. (h) Yu, J.; Zhao, S.; Liang, S.; Bao, X.; Zhu, C. Org. Biomol. Chem.
2015, 13, 7924. (i) Ren, R.; Zhao, H.; Huan, L.; Zhu, C. Angew. Chem.,
Int. Ed. 2015, 54, 12692. See also, refs 5g, 6d, and i.
(12) Sakamoto, R.; Sakurai, S.; Maruoka, K. Chem. - Eur. J. 2017, 23,
9030.
(13) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed.
2000, 39, 2632.
(14) Kadota, I.; Lutete, L. M.; Shibuya, A.; Yamamoto, Y. Tetrahedron
Lett. 2001, 42, 6207.
(15) (a) Jin, T.; Yamamoto, Y. Org. Lett. 2007, 9, 5259. (b) Jin, T.;
Yamamoto, Y. Org. Lett. 2008, 10, 3137. (c) Jin, T.; Yang, F.; Liu, C.;
Yamamoto, Y. Chem. Commun. 2009, 3533.
(16) (a) Masuyama, A.; Sugawara, T.; Nojima, M.; McCullough, K. J.
Tetrahedron 2003, 59, 353. (b) Johansson, S. G. H.; Emilsson, K.; Grøtli,
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: maruoka@kuchem.kyoto-u.ac.jp.
ORCID
Keiji Maruoka: 0000-0002-0044-6411
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was partially supported by a Grant-in-Aid for Scientific
Research from the MEXT (Japan).
■
REFERENCES
■
(1) (a) Liu, J.; Lam, J. W. Y.; Tang, B. Z. Chem. Rev. 2009, 109, 5799.
(b) Bisoyi, H. K.; Kumar, S. Chem. Soc. Rev. 2010, 39, 264. (c) Patai, S.,
Ed. Chemistry of Triple-Bonded Functional Groups; Wiley: New York,
1994. (d) Stang, P. J., Diederich, F., Eds. Modern Acetylene Chemistry;
VCH: Weinheim, Germany, 1995. (e) Liu, J.; Lam, J. W. Y.; Tang, B. Z.
Chem. Rev. 2009, 109, 5799.
(2) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979.
(3) (a) Negishi, E., Ed. Handbook of Organopalladium Chemistry for
Organic Synthesis; Wiley-Interscience: New York, 2002; p 493.
(b) Chinchilla, R.; Naj
(4) (a) Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642.
́
era, C. Chem. Rev. 2007, 107, 874.
(b) Altenhoff, G.; Wurtz, S.; Glorius, F. Tetrahedron Lett. 2006, 47, 2925.
̈
(c) Vechorkin, O.; Barmaz, D.; Proust, V.; Hu, X. J. Am. Chem. Soc. 2009,
131, 12078. (d) de Carne-
́
Carnavalet, B.; Archambeau, A.; Meyer, C.;
Cossy, J.; Folleas, B.; Brayer, J.-L.; Demoute, J.-P. Org. Lett. 2011, 13,
́
956. (e) Vechorkin, O.; Godinat, A.; Scopelliti, R.; Hu, X. Angew. Chem.,
Int. Ed. 2011, 50, 11777. (f) Yi, J.; Lu, X.; Sun, Y.-Y.; Xiao, B.; Liu, L.
Angew. Chem., Int. Ed. 2013, 52, 12409. (g) García, P. M. P.; Ren, P.;
Scopelliti, R.; Hu, X. ACS Catal. 2015, 5, 1164. (h) Jin, L.; Hao, W.; Xu,
J.; Sun, N.; Hu, B.; Shen, Z.; Mo, W.; Hu, X. Chem. Commun. 2017, 53,
4124.
M.; Borje, A. Chem. Res. Toxicol. 2010, 23, 677. (c) Kundu, R.; Ball, Z. T.
̈
Org. Lett. 2010, 12, 2460. (d) Too, P. C.; Tnay, Y. L.; Chiba, S. Beilstein J.
Org. Chem. 2013, 9, 1217. (e) Fan, J.-H.; Zhou, M.-B.; Liu, Y.; Wei, W.-
T.; Ouyang, X.-H.; Song, R.-J.; Li, J.-H. Synlett 2014, 25, 657.
(17) When an alkynyl benziodoxolone was used as the radical acceptor,
2a was obtained in only 10% yield. For further details, see the
Supporting Information.
(5) (a) Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 4486.
(b) Xiang, J.; Jiang, W.; Fuchs, P. L. Tetrahedron Lett. 1997, 38, 6635.
(c) Xiang, J.; Fuchs, P. L. Tetrahedron Lett. 1998, 39, 8597. (d) Schaffner,
A.-P.; Darmency, V.; Renaud, P. Angew. Chem., Int. Ed. 2006, 45, 5847.
(e) Hoshikawa, T.; Kamijo, S.; Inoue, M. Org. Biomol. Chem. 2013, 11,
164. (f) Yang, J.; Zhang, J.; Qi, L.; Hu, C.; Chen, Y. Chem. Commun.
2015, 51, 5275. (g) Ren, R.; Wu, Z.; Xu, Y.; Zhu, C. Angew. Chem., Int.
Ed. 2016, 55, 2866. (h) Gao, C.; Li, J.; Yu, J.; Yang, H.; Fu, H. Chem.
Commun. 2016, 52, 7292. (i) Li, J.; Tian, H.; Jiang, M.; Yang, H.; Zhao,
Y.; Fu, H. Chem. Commun. 2016, 52, 8862. (j) Zhou, S.; Song, T.; Chen,
H.; Liu, Z.; Shen, H.; Li, C. Org. Lett. 2017, 19, 698. (k) Paul, S.; Guin, J.
Green Chem. 2017, 19, 2530. (l) Jiang, H.; He, Y.; Cheng, Y.; Yu, S. Org.
Lett. 2017, 19, 1240.
(6) (a) Liu, X.; Wang, Z.; Cheng, X.; Li, C. J. Am. Chem. Soc. 2012, 134,
14330. (b) Huang, H.; Zhang, G.; Gong, L.; Zhang, S.; Chen, Y. J. Am.
Chem. Soc. 2014, 136, 2280. (c) Zhang, R.-Y.; Xi, L.-Y.; Zhang, L.; Liang,
S.; Chen, S.-Y.; Yu, X.-Q. RSC Adv. 2014, 4, 54349. (d) Wang, S.; Guo,
L.-N.; Wang, H.; Duan, X.-H. Org. Lett. 2015, 17, 4798. (e) Zhou, Q.-Q.;
Guo, W.; Ding, W.; Wu, X.; Chen, X.; Lu, L.-Q.; Xiao, W.-J. Angew.
Chem., Int. Ed. 2015, 54, 11196. (f) Le Vaillant, F.; Courant, T.; Waser, J.
Angew. Chem., Int. Ed. 2015, 54, 11200. (g) Wang, C.-Y.; Song, R.-J.; Xie,
Y.-X.; Li, J.-H. Synthesis 2016, 48, 223. (h) Jia, K.; Zhang, F.; Huang, H.;
Chen, Y. J. Am. Chem. Soc. 2016, 138, 1514. (i) Zhang, R.-Y.; Xi, L.-Y.;
(18) For references on complexes of Cu(I) and pyridine derivatives,
see: (a) Dembo, M. D.; Dunaway, L. E.; Jones, J. S.; Lepekhina, E. A.;
McCullough, S. M.; Ming, J. L.; Li, X.; Baril-Robert, F.; Patterson, H. H.;
Bayse, C. A.; Pike, R. D. Inorg. Chim. Acta 2010, 364, 102. (b) Ley, A. N.;
Dunaway, L. E.; Brewster, T. P.; Dembo, M. D.; Harris, T. D.; Baril-
Robert, F.; Li, X.; Patterson, H. H.; Pike, R. D. Chem. Commun. 2010, 46,
4565. (c) Wang, J.-H.; Li, M.; Zheng, J.; Huang, X.-C.; Li, D. Chem.
Commun. 2014, 50, 9115.
(19) At this time, we cannot exclude the possibility that a copper−
acetylide complex is involved in the degradation of the alkylsilyl
peroxides, as the reaction of 1a and 1-ethynyl-4-methylbenzene in the
presence of DMAP and (4-methylphenylethynyl)copper afforded 2a in
a lower yield (49%). For further details, see the Supporting Information.
D
DOI: 10.1021/acs.orglett.8b00173
Org. Lett. XXXX, XXX, XXX−XXX