Synthesis of Quaternary α-Fluorinated α-Amino Acid Derivatives via Coordinating Cu(II) Catalytic α-C(sp3)-H Direct Fluorination

Article abstract of DOI:10.1021/acs.orglett.8b03044

A coordinating, copper-catalyzed direct α-C(sp³)-H fluorination method has been developed to prepare vital quaternary α-fluorinated α-amino acid derivatives. A Cu(II) catalytic SET oxidative addition mechanism is proposed, involving a key fluoride-coupled Cu(II) charge transfer complex. The protocol can tolerate a rich variety of α-amino acids, for which the auxiliary group is removed in high yield and substituted for the direct preparation of dipeptide derivatives with detachable, single absolute configurations of the target compounds.

Full text of DOI:10.1021/acs.orglett.8b03044

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis of Quaternary α‑Fluorinated α‑Amino Acid Derivatives via
Coordinating Cu(II) Catalytic α‑C(sp3)−H Direct Fluorination
Qiang Wei,∥,† Yao Ma,∥,§ Li Li,§ Qingfei Liu,‡ Zijie Liu,§ and Gang Liu*,†,‡
†Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
‡School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
§Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
S
* Supporting Information
ABSTRACT: A coordinating, copper-catalyzed direct α-
C(sp3)−H fluorination method has been developed to
prepare vital quaternary α-fluorinated α-amino acid deriva-
tives. A Cu(II) catalytic SET oxidative addition mechanism is
proposed, involving a key fluoride-coupled Cu(II) charge
transfer complex. The protocol can tolerate a rich variety of α-amino acids, for which the auxiliary group is removed in high
yield and substituted for the direct preparation of dipeptide derivatives with detachable, single absolute configurations of the
target compounds.
ith the rapid development of peptide-based drugs1 and
2
Wproteomic investigations
in recent years, more
innovative and efficient methods are urgently needed to
modify natural α-amino acids (α-AAs). Fluorine-containing α-
AAs have found a variety of applications in peptide or protein
modifications, including enhanced hydrolytic stability, re-
stricted conformation, and even tagging for imaging.3
However, to date, the introduced fluorine has been limited
to the side chains of the α-AAs,3i although a fluorine on the α-
site could more effectively improve the peptide or protein’s
physicochemical or even pharmacological properties, such as
tolerating the hydrolytic ability of peptide bonds to proteinase,
increasing the optical stability of α-stereocenter, but with
minimal impact on the native activity of the α-AA.4
α-Fluorinated glycines are generally prepared by a Gabriel
reaction, which form the bonds between α-halogenated
carboxyl acid ester and amines.5 α-Fluorinated quaternary
AAs, including α-fluorinated α-aryl glycines and 3′-fluorotha-
Figure 1. Transition-metal-catalyzed α-C(sp3)−H functionalization
lidomide, can be prepared by the direct fluorination of α-
carbanions or enolates (deprotonation of α-AAs with excess
strong base, such as LiHMDS/KHMDS, at extremely low
temperature)6 that lack functional group tolerance or
regiospecificity. Li’s group recently developed the α-fluorinated
α-aryl glycine derivatives by the direct N−F bond insertion of
diazocarbonyl compounds.7 Transition-metal-catalyzed C−H
direct functionalization to form new C−C, C−N, C−O, and
C−X bonds has been widely applied to the site-specific
modification of α-AAs, addressing the involved multiple steps,
harsh conditions, and the use of stoichiometric and/or toxic
reagents in traditional methods.8 However, its C(α)−H
modifications of α-AAs were limited to C(α)−C bonds via a
pivotal reductive elimination mechanism of enolate-Pd(II) and
C(α)-Pd(II) intermediates (Figure 1A)9 Hartwig’s group
prepared α-arylation glycine derivatives utilizing Pd-catalysis.
To achieve the quaternary α-arylation AAs, they had to
methods of α-AA derivatives.
previously fuse the tertiary C(α)−H in azlactones (an AA
derivative with more acidic α-protons and less hindrance due
to their cyclic structures, Figure 1A).10 Trost’s group
developed asymmetric Pd-catalyzed alkylation based on
azlactones to form chiral quaternary α-AAs.11 As an improve-
ment, recently, You’s group has successfully realized a
coordinating Fe-catalyzed or Ni-catalyzed radical oxidative
cross-dehydrogenative-coupling reaction with a picolinamide
auxiliary to prepare quaternary α-AA esters, which substituted
the role of azlactones to activate the C(α)−H with a broader
Received: September 24, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03044
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
scope and milder conditions (Figure 1B).12 Inspired by this
progress, we investigated the first α-C(sp3)−H direct
fluorination of α-AAs (Figure 1C) via a coordinating metal-
catalyzed strategy.13
byproduct 2ai′ (42%, Table 1, entry 1). Other copper salts did
not give better results (entries 2−8). Considering the role of a
ligand in promoting metal-catalyzed activity and inhibiting β-H
elimination,15 we further tested many N-hetero ligands (Table
S3, SI). We found that quinuclidine (L1) increased the yield of
2ai to 49%, but 2ai′ (42%) still occurred (Table 1, entry 9).
Other quinuclidine ligands were then screened (entries 10−
13), and amazingly we found that (R)-3-hydroxy quinuclidine
(L5, entry 13) significantly decreased 2ai′ which consequently
resulted in an increased yield of desired 2ai (78%). Further
increasing or decreasing the L5 amount did not improve the
yield of 2ai (entry 14 or 16). Finally, an 81% isolated yield was
achieved when optimal L5 (20%, entry 15) was used.
To resolve the kinetically disfavored C(sp3)−Metal−F
reductive elimination,14 an appropriate auxiliary group (AG)
should be introduced first to assist with the transformation
(Figure 1C, INTx). Initially, we tested various AGs containing
N- or O-atoms by the designed reaction using Pd(OAc)2,
fluorinating agent Selectfluor, and phthaloyl(Phth)-amino-
protected phenylglycine derivatives 1bx (Table 1A), and
Table 1. Design and Optimization of α-C(sp3)−H
Fluorination
The reaction scope was next examined with the gained
optimal conditions. For the aliphatic methyne α-C(sp3)−H
bonds, branched and unbranched alkanes (Scheme 1, 2aa−
Scheme 1. Fluorination of Aliphatic Methyne C(sp3)−H
a b
,
Bonds
e
e
e
entry
Cu Salt
ligand
2ai (%)
1ai (%)
2ai′ (%)
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OTf)2
CuCl
CuI
CuF2
Cu(acac)2
Cu(eaa)2
Cu2O
−
−
−
−
−
−
−
−
39
30
26
10
10
49
42
28
11
no conversion
no conversion
0
21
30
40
53
24
no conversion
9
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
L1 (40%)
L2 (40%)
L3 (40%)
L4 (40%)
L5 (40%)
L5 (80%)
L5 (20%)
L5 (10%)
49
43
62
50
78
59
81
56
0
42
19
9
11
trace
trace
10
a
10
11
12
13
14
15
16
27
18
28
12
24
trace
23
Conditions: 1a (0.1 mmol), selectfluor (0.15 mmol), Cu(OAc)2 (40
mol %), Ag2CO3 (0.2 mmol), L5 (20 mol %), and MeCN (1.5 mL) at
b
c
115 °C under Ar for 8 h. Isolated yield. Cu(OAc)2 (80 mol %), 10
h.
2ae), cycloalkanes (2af), olefins (2ag), aromatics (2ah−2ak),
amides (2al and 2ao), esters (2am−2an), and ethers (2ap)
were compatible with this fluorination protocol in moderate to
high yields (42−91%). The steric hindrance next to the α-
C(sp3)−H (2ab and 2ad) and the highly active β-C(sp3)−H
(2af, 2ag, 2am, and 2ao) were the main reason for the
variation in yield. For the benzylic methyne α-C(sp3)−H
bonds, whether electron-donating or -withdrawing substituents
were used, a higher yield (65−91%, Scheme 2) and efficiency
(80 °C, 2 h) were attained than those in the former Pd
catalytic system (23%, 115 °C, 16 h, Table 1A).
13
a
Conditions: 1ba (0.1 mmol), selectfluor (0.15 mmol), Pd(OAc)2
(10 mol %), Ag2CO3 (0.2 mmol), and 1,4-dioxane (1.5 mL) at 115
b
c
°C under Ar for 16 h. 2-Picoline (10 mol %). Yield was determined
d
by 1H NMR using internal standard DEM. 1ai (0.1 mmol),
selectfluor (0.15 mmol), Cu salt (40 mol %), Ag2CO3 (0.2 mmol),
Ligand X (x mol %), and MeCN (1.5 mL) at 115 °C under Ar for 8 h.
e
Isolated yield.
To explore the application of such α-fluorinated α-AAs, it
was necessary to find mild conditions for effective removal of
the AG. Unfortunately, over many trials, the literature
methods16 did not convert the amide to a corresponding
carboxyl group or its derivatives without affecting the newly
introduced C(α)−F bond. Triflic anhydride (Tf2O) is known
as an excellent activating agent for the amide bond with
exceptional functional group tolerance.17 Therefore, Tf2O and
found that the desired C(α)-fluorinated product 2ba was
formed in 23% yield only when a pyridine was used as the AG.
Then, a 91% yield was obtained by adding 10% of a 2-picoline
ligand (Table S1, Supporting Information (SI)). Unfortu-
nately, this condition did not work completely for the
phenylalanine derivative 1ai with the more inert aliphatic
tertiary α-C(sp3)−H bond (Table 1B). Further attempts using
many other metal salts undertaken for 1ai (Table S2, SI).
Fortunately, Cu(OAc)2 successfully gave the anticipated
product 2ai (39%), accompanied by the β-H elimination
18
catalytic amounts of CoCl2 were tested, and the carboxylic
acid 3ai (65%) and ester 4ai (70%) were herein acquired in
high yield (Scheme 3). Importantly, dipeptides (5ai, 6ai, 7ai)
could be directly prepared by using L-amino acid esters with
B
DOI: 10.1021/acs.orglett.8b03044
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Fluorination of Benzylic Methyne C(sp3)−H
pyridine. Thus, two possible pathways to reach 2ai exist:
pathway A is the direct nucleophilic reaction of the generated
enolate-Cu(II) intermediate INT2, and B is the oxidation
addition of the formed α-C(sp3)−Cu(II) intermediate INT3
by highly oxidative selectfluor (Figure 2, pathway A and B).
a b
,
Bonds
a
Conditions: 1b (0.1 mmol), selectfluor (0.15 mmol), Cu(OAc)2 (40
mol %), Ag2CO3 (0.2 mmol), and MeCN (1.5 mL) at 80 °C under Ar
b
c
for 2 h. Isolated yield. Cu(OAc)2 (20 mol %) at 60 °C for 2 h.
Figure 2. Proposed mechanism.
Scheme 3. Conversion of AG
However, the concomitant β-H elimination byproduct 2ai′
indicates the presence of INT3, which supports the pathway B.
Interestingly, 1ai was nearly converted into 2ai′ in the absence
of selectfluor (Table 2, entry 2), confirming a competitive
reaction between fluorination and β-H elimination mediated
by INT3 (Figure 2, INT3 to 2ai′). The radical trapping
reagents TEMPO and BHT could markedly suppress the
fluorination of 1ai (Table 2, entries 3−5), suggesting the
presence of free radicals in the reaction,19 which almost rule
out pathway A. Recent literature reported that selectfluor can
fluorinate the benzyl C(sp3)−H adjacent to N-heterocycles by
a charge-transfer complex mediated SET route.20 Ritter’s group
also developed an aromatic C−H fluorination via a SET from a
fluoride-coupled Pd(III) electron transfer to a Pd(II)
complex.21 We observed that the radical trapping significantly
increased 2ai′ (Table 2, entries 3 and 4) leading to the
speculation that a SET oxidative addition from the INT3 to α-
C(sp3)−Cu(III) intermediate INT4 occurred in our fluorina-
tion which involved the key complexes C1 and C2 (Figure 2,
INT3-4). Another control experiment showed that the N-
methylated amide bond of the AG (Table 2, entry 6) did not
proceed in the reaction, implying the participation of its H-
atom in the fluorination (Figure 2, C2 to INT4) and further
excluding pathway A. Additionally, the observed silver mirror
in reaction (SI) also explains the involved oxidation of Ag2CO3
in the reaction (Figure 2, AgI2CO3 to Ag0).
a
Conditions: 2ai (0.1 mmol), Tf2O (0.15 mmol), DIPEA (0.5
b
mmol), DCM (1.5 mL) at −10 °C under Ar for 2 h. LiOH (0.2
mmol)/H2O (1 mL) was added at rt for 18 h. CoCl2 (10 mol
%)/EtOH (1 mL) was added at rt for 18 h. CoCl2 (10 mol %)/AA
methyl esters (0.25 mmol) were added at rt for 18 h. Isolated yield.
c
d
e
relatively high yields (63−83%), and a pair of diastereoisomers
of the α-fluorinated dipeptide derivatives (6ai-1, 6ai-2; 7ai-1,
7ai-2) were easily separated and optical isomers were
indisputably identified by circular dichroism (Scheme 3 and
Figures S1−S10, SI).
To illuminate the mechanism, several studies were
performed in Table 2. A blank experiment without an auxiliary
N-atom (entry 1) was first investigated. As expected, 1aq could
not be fluorinated, which indicated the coordinating role of
a
Table 2. Mechanistic Studies
A primary kinetic isotope effect (21% yield) was gained (kH/
kD ≈ 4.0) in the intermolecular competition experiments
(Figure S11, SI), evidencing that our Cu(II) catalyzed α-
C(sp3)−H activation process was the rate-limiting step, which
is distinguished from the more sluggish Pd(IV)−F reductive
elimination.14 The signal of the Cu(II) complex was not visible
or appeared as a small broad peak in the NMR spectrum due
to the paramagnetism of Cu(II) (Figures S13−S14, SI);
therefore, we monitored the reaction intermediates by 19F
NMR in CD3CN. The blank experiment without 1ai showed
the Cu(OAc)2 noncoordinated 19F NMR signal of selectfluor
(δ −150.95). When 1ai was added into the reaction at rt and
80 °C for 1 h respectively, an extra broad peak appeared at δ
−150.75 that in all probability indicated the formed fluoride-
coupled Cu(II) electron transfer complex C1 with a weak
coordinated 19F NMR signal (Table 2, entry 9; Figure S12 in
SI for details).
b
entry
conditions
results
1
2
3
4
5
6
7
8
X = CH, Y = H (1aq)
1ai, no selectfluor
no conv
2ai: 0%, 2ai′: 70%
2ai: 11%, 2ai′: 62%
2ai: 0%, 2ai′: 71%
no conv
1ai + TEMPO (2 equiv)
1ai + TEMPO (5 equiv)
1ai + BHT (2 equiv)
X = N, Y = Me (1ar)
no 1ai, CD3CN, rt, 1 h
1ai, CD3CN, rt or 80 °C, 1 h
no conv
δ −150.95
δ −150.75, −150.95
a
Conditions: 1ax (0.1 mmol), selectfluor (0.15 mmol), Cu(OAc)2
(40 mol %), Ag2CO3 (0.15 mmol), and MeCN (1.5 mL) at 115 °C
b
under Ar for 8 h. Isolated yield or δ value of 19F NMR.
C
DOI: 10.1021/acs.orglett.8b03044
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(3) (a) Buer, B. C.; Marsh, E. N. Protein Sci. 2012, 21, 453.
(b) Hunter, L.; Butler, S.; Ludbrook, S. B. Org. Biomol. Chem. 2012,
10, 8911. (c) Jackel, C.; Koksch, B. Eur. J. Org. Chem. 2005, 2005,
4483. (d) Kokhan, S. O.; Tymtsunik, A. V.; Grage, S. L.; Afonin, S.;
Babii, O.; Berditsch, M.; Strizhak, A. V.; Bandak, D.; Platonov, M. O.;
Komarov, I. V.; Ulrich, A. S.; Mykhailiuk, P. K. Angew. Chem., Int. Ed.
2016, 55, 14788. (e) Jackel, C.; Salwiczek, M.; Koksch, B. Angew.
Chem., Int. Ed. 2006, 45, 4198. (f) Berger, A. A.; Voller, J. S.; Budisa,
N.; Koksch, B. Acc. Chem. Res. 2017, 50, 2093. (g) Gillis, E. P.;
Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med.
Chem. 2015, 58, 8315. (h) Salwiczek, M.; Nyakatura, E. K.; Gerling,
U. I.; Ye, S.; Koksch, B. Chem. Soc. Rev. 2012, 41, 2135. (i) Robalo, J.
R.; Huhmann, S.; Koksch, B.; Vila Verde, A. Chem. 2017, 3, 881.
(4) Wu, Y.; Li, Y. H.; Li, X.; Zou, Y.; Liao, H. L.; Liu, L.; Chen, Y.
G.; Bierer, D.; Hu, H. G. Chem. Sci. 2017, 8, 7368.
(5) (a) Annedi, S. C.; Li, W.; Samson, S.; Kotra, L. P. J. Org. Chem.
2003, 68, 1043. (b) Takeuchi, Y.; Kirihara, K.; Shibata, N.; Kirk, K. L.
Chem. Commun. 2000, 785. (c) Hu, L.; Che, C.; Tan, Z.; Zhu, G.
Chem. Commun. 2015, 51, 16641.
(6) (a) Mohar, B.; Baudoux, M.; Plaquevent, J. C.; Cahard, D.
Angew. Chem., Int. Ed. 2001, 40, 4214. (b) Yamamoto, T.; Suzuki, Y.;
Ito, E.; Tokunaga, E.; Shibata, N. Org. Lett. 2011, 13, 470. (c) Mohar,
B.; Sterk, D.; Ferron, L.; Cahard, D. Tetrahedron Lett. 2005, 46, 5029.
(7) Chen, G.; Song, J.; Yu, Y.; Luo, X.; Li, C.; Huang, X. Chem. Sci.
2016, 7, 1786.
Based on the above collected data, along with the previously
proposed mechanisms in Figure 1A9 and recent fluoride-
coupled SET reactions,20−22 a catalytic cycle for this reaction is
described in Figure 2. The coordination of Cu(II) and the
alkalinity of Ag2CO3 promote the generation of INT1 and its
enolate intermediate INT2. Highly nucleophilic INT3 existing
in equilibrium with its tautomer INT29 promotes the
production of C1 using selectfluor. Then, a SET oxidative
addition generates the Cu(III) complex C2.20,21 A H-ion
transfer of C2 then generates more stable INT4, following the
reductive elimination which afforded the product 2ai. The
associated Cu(I) is reoxidized to Cu(II) by excessive Ag2CO3.
Meanwhile, the β-H elimination of INT3 is inhibited by L5,
which may occur by occupying the empty metal orbital used to
break C(β)−H.15
In summary, the first direct α-C(sp3)−H fluorination of the
α-AA derivatives has been realized by our coordinating Cu(II)
catalytic method, which provides a wide range of α-AA
substrates, including aliphatic and benzylic methyne α-
C(sp3)−H with rich substituents. Mechanism studies revealed
a Cu(II) catalytic SET oxidative addition process, in which a
key fluoride-coupled Cu(II) charge transfer complex C1 is
detected by 19F NMR. The β-H elimination byproduct is
effectively inhibited by the (R)-3-hydroxy quinuclidine ligand.
Mild conditions for efficient removal of the AG are disclosed
without affecting newly introduced C(α)−F, which allows us
to directly synthesize and separate the α-fluorinated dipeptide
derivatives with a single configuration. This work should
potentially feature in forming corresponding peptides and
proteins.
(8) Noisier, A. F.; Brimble, M. A. Chem. Rev. 2014, 114, 8775.
(9) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082.
(10) (a) Lee, S.; Beare, N. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001,
123, 8410. (b) Liu, X. X.; Hartwig, J. F. Org. Lett. 2003, 5, 1915.
(11) (a) Trost, B. M.; Czabaniuk, L. C. J. Am. Chem. Soc. 2012, 134,
5778. (b) Trost, B. M.; Dogra, K. J. Am. Chem. Soc. 2002, 124, 7256.
(12) (a) Li, K.; Tan, G.; Huang, J.; Song, F.; You, J. Angew. Chem.,
Int. Ed. 2013, 52, 12942. (b) Li, K.; Wu, Q.; Lan, J.; You, J. Nat.
Commun. 2015, 6, 8404.
(13) He, G.; Wang, B.; Nack, W. A.; Chen, G. Acc. Chem. Res. 2016,
49, 635.
(14) Park, H.; Verma, P.; Hong, K.; Yu, J. Nat. Chem. 2018, 10, 755.
(15) (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119,
12382. (b) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
11108.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03044.
■
S
(16) (a) Shendage, D. M.; Frohlich, R.; Haufe, G. Org. Lett. 2004, 6,
3675. (b) Talbot, E. P.; Fernandes, T. d. A.; McKenna, J. M.; Toste,
F. D. J. Am. Chem. Soc. 2014, 136, 4101. (c) Liu, Y. J.; Liu, Y. H.;
Zhang, Z. Z.; Yan, S. Y.; Chen, K.; Shi, B. F. Angew. Chem., Int. Ed.
2016, 55, 13859. (d) van der Heijden, G.; Jong, J. A.; Ruijter, E.;
Orru, R. V. Org. Lett. 2016, 18, 984.
(17) Bechara, W. S.; Pelletier, G.; Charette, A. B. Nat. Chem. 2012,
4, 228.
(18) Zhang, Q.; Yin, X. S.; Chen, K.; Zhang, S. Q.; Shi, B. F. J. Am.
Chem. Soc. 2015, 137, 8219.
(19) (a) Lv, Y.; Wang, X.; Cui, H.; Sun, K.; Pu, W.; Li, G.; Wu, Y.;
He, J.; Ren, X. RSC Adv. 2016, 6, 74917. (b) Wu, S. W.; Liu, F. Org.
Lett. 2016, 18, 3642. (c) Wang, C.; Cai, J.; Zhang, M.; Zhao, X. J. Org.
Chem. 2017, 82, 1260.
(20) Danahy, K. E.; Cooper, J. C.; Van Humbeck, J. Angew. Chem.,
Int. Ed. 2018, 57, 5134.
(21) Yamamoto, K.; Li, J.; Garber, J. A. O.; Rolfes, J. D.; Boursalian,
G. B.; Borghs, J. C.; Genicot, C.; Jacq, J.; van Gastel, M.; Neese, F.;
Ritter, T. Nature 2018, 554, 511.
Experimental procedures, spectroscopic data, and copies
of NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gangliu27@tsinghua.edu.cn.
ORCID
Gang Liu: 0000-0001-5549-5686
Author Contributions
∥Q.W. and Y.M. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the funding support of grants from
the National Natural Science Foundation of China (Nos.
81573289, 81773575, and 81773114) and the National Key
R&D Program of China (2016YFE0113700).
(22) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
REFERENCES
■
(1) Henninot, A.; Collins, J. C.; Nuss, J. M. J. Med. Chem. 2018, 61,
1382.
(2) Zhao, L.; Basle, O.; Li, C. J. Proc. Natl. Acad. Sci. U. S. A. 2009,
106, 4106.
D
DOI: 10.1021/acs.orglett.8b03044
Org. Lett. XXXX, XXX, XXX−XXX