Synthesis of Benzofurans and Benzoxazoles through a [3,3]-Sigmatropic Rearrangement: O-NHAc as a Multitasking Functional Group

Article abstract of DOI:10.1021/acs.oprd.9b00002

The synthesis of heterocycles relies heavily on diverse sigmatropic rearrangements triggered by the cleavage of X-Y (X, Y = C, O, N, S, I) bonds. However, a unified rearrangement approach for constructing heterocyclic libraries is highly desirable. Encouraged by computational analysis of [3,3]-sigmatropic rearrangements, we can now rapidly synthesize oxa-heterocycles by treating N-phenoxyacetamides (Ph-ONHAc) with compounds containing an sp-hybridized carbon. The generality of the process is illustrated by the late-stage diversification of natural products, including estrone and an approved drug. A combination of experimental and computational studies revealed that the reactions proceed through a facile Claisen-like [3,3]-sigmatropic rearrangement/annulation process.

Full text of DOI:10.1021/acs.oprd.9b00002

Communication
pubs.acs.org/OPRD
Cite This: Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Synthesis of Benzofurans and Benzoxazoles through a [3,3]-
Sigmatropic Rearrangement: O−NHAc as a Multitasking Functional
Group
Dingyuan Yan,†,‡ Heming Jiang,§ Wenxue Sun,‡ Wei Wei,‡ Jing Zhao,*,†,∥ Xinhao Zhang,*,§
and Yun-Dong Wu§
†State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and
Chemical Engineering, Nanjing University, Nanjing 210093, China
‡State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
§Lab of Computational Chemistry and Drug Design, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen
Graduate School, Shenzhen 518055, China
∥Shenzhen Research Institute of Nanjing University, Shenzhen 518000, China
S
* Supporting Information
mild manner was discovered by Yorimitsu and co-workers.6
ABSTRACT: The synthesis of heterocycles relies heavily
on diverse sigmatropic rearrangements triggered by the
cleavage of X−Y (X, Y = C, O, N, S, I) bonds. However, a
unified rearrangement approach for constructing hetero-
cyclic libraries is highly desirable. Encouraged by
computational analysis of [3,3]-sigmatropic rearrange-
ments, we can now rapidly synthesize oxa-heterocycles by
treating N-phenoxyacetamides (Ph−ONHAc) with com-
pounds containing an sp-hybridized carbon. The general-
ity of the process is illustrated by the late-stage
diversification of natural products, including estrone and
an approved drug. A combination of experimental and
computational studies revealed that the reactions proceed
through a facile Claisen-like [3,3]-sigmatropic rearrange-
ment/annulation process.
The same strategy was used by Procter and co-workers to
construct C3 functionalization of benzothiophenes.7 Peng and
co-workers subsequently reported an ingenious design to form
α-arylated nitriles by an accelerated [3,3]-rearrangement,
releasing steric congestion associated with the formation of
an active S/I−ketenimine species.8
An intrinsically weak and highly polar O−N bond was found
to promote sigmatropic rearrangements.9 Substantial progress
has been made in O−N-cleavage-assisted rearrangements by
Tomkinson10 and Ioffe11 in the past several decades. Notably,
Ngai12 and Nakamura13 recently reported the [1,3] rearrange-
ment of OCF3/OMe groups of N-aryl-N-hydroxylamine
derivatives to afford various ortho-functionalized aniline
derivatives, respectively. Very recently, an efficient synthesis
of multisubstituted o-anisidines via N-heterocyclic carbene
(NHC) Cu-catalyzed [1,3]/[1,2] domino rearrangement of N-
methoxyanilines was developed by Nakamura (Figure 1a).14
Although high efficiency has been achieved in the synthesis
of indoles15 as well as benzofurans16 under mild reaction
conditions via cleavage of O−N bonds, a unified approach to
access diverse oxa-heterocycles is highly desirable. The
introduction of an O−N bond may encompass the elevated
temperature accompanied by the classical Claisen [3,3]-
sigmatropic rearrangement.1b,2a,17 The other challenge is that
the annulation/aromatization may not occur readily after the
rearrangement step18 (Figure 1b). Following our continued
interest in the O−N bond,19 we hypothesized that a facile
[3,3]-sigmatropic rearrangement might be envisioned by
installing an sp-hybridized carbon on the nitrogen in the
oxyacetamide moiety (O−NHAc) to facilitate the subsequent
annulation.20 To confirm this hypothesis, density functional
theory (DFT) calculations were first performed.21 The free
energy profiles of the [3,3]-sigmatropic rearrangement and the
bond dissociation energies (BDEs) of the O−Y bonds (Y = C,
KEYWORDS: sigmatropic rearrangements,
oxa-heterocycles, O−N bond cleavage
INTRODUCTION
■
One century after their discovery, [3,3]-sigmatropic rearrange-
ments occupy an irreplaceable role in the synthesis of complex
organic molecules and continue to be intensively investigated.1
Although a wealth of protocols to obtain biologically active
heterocycles have been reported,2 many of them require harsh
conditions3 (such as high temperature, long reaction timed,
and the need for strong oxidants). As an alternative, [3,3]-
sigmatropic rearrangement reactions triggered by the cleavage
of X−Y (X, Y = C, O, N, S, I) bonds have attracted much
attention for the synthesis of those skeletons under relatively
mild conditions. For example, the Fischer indole rearrange-
ment, which is based on cleavage of the N−N bond in
phenylhydrazines, remains among the most widely used
approaches to indoles.4 Recently, Maulide and co-workers
made pivotal progress in Pummerer-type rearrangements to
use the sulfoxide as an arylation/directing group through
cleavage of the O−S bond.5 Significantly, an extension of the
Pummerer reaction to produce benzofurans in a practical and
Special Issue: 25th Anniversary of the Buchwald-Hartwig Amination
Received: January 1, 2019
© XXXX American Chemical Society
A
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Figure 1. Protocol to construct heterocycles via [3,3]-sigmatropic rearrangement. (a) Recent works on the rearrangement of N-arylhydroxylamine
derivatives. (b) Challenges to obtain diverse oxa-heterocycles via a [3,3]-sigmatropic rearrangement. (c) DFT calculations on the synthesis of
heterocycles via a [3,3]-sigmatropic rearrangement by incorporation of an O−NHAc group. Relative free energies and energies are in kcal/mol. (d)
Our approaches toward oxa-heterocycles by treating PhONHAc with compounds containing an sp-hybridized carbon.
N) in several model substrates are listed in Figure 1c. Aryl
vinyl ether (INT1a) is regarded as the standard reference of a
classical Claisen rearrangement. The barrier for O−N bond
cleavage is indeed significantly lower than that for O−C bond
cleavage, and this is well-correlated with the calculated BDEs.
Furthermore, pericyclic processes with O−N bond cleavage
become highly exergonic. Notably, incorporation of an sp-
hybridized carbon in the migrating moiety indeed promotes
the rearrangement (TS1c vs TS1d and TS1e vs TS1f). The
N−Csp bonds in TS1d and TS1f are much shorter than the
diminished yields, whereas DBU and DABCO provided no
product. Subsequently, different solvents were screened, and
the results indicated that 1,2-dimethoxyethane (DME) is
efficient with a 94% yield, whereas other solvents, such as 1,2-
dichloroethane, acetone, and tetrahydrofuran, afforded inferior
yields (Supplementary Table 1, entries 12−22). Ultimately, the
t
optimal reaction conditions employed 1.5 equiv of BuONa in
DME at room temperature for 20 min.
The scope of N-phenoxyacetamides was examined under
standard reaction conditions (Table 1). Many N-phenoxyace-
tamides bearing electron-rich and electron-poor groups worked
well, giving moderate to excellent yields (3a−l, 56−92% yield).
Notably, when meta-substituted N-phenoxyacetamides 1k and
1l were used, the annulation occurred at the two ortho
positions, and the yields of the products annulated at the less-
hindered site were much higher (3k′ and 3l). We also
examined substituents on the nitrogen atom of the N-
phenoxyamide. Compounds 1n−r afforded the desired
products in 53−93% yield. Unfortunately, substrates bearing
strongly electron-deficient groups such as −CCl3, −CF3, and
−C6F5 as R2 could not be used under the same reaction
conditions, possibly because of the reduced nucleophilicity of
the nitrogen in such compounds. After the acetamide in 1a was
changed to a sulfonamide, the desired product 3s was formed
in 80% yield. Suitable alkynyl electron-withdrawing groups
included ketone (3t), sulfonamide (3u), and phosphonate
(3v). Finally, we performed the synthesis of multisubstituted
2
N−Csp bonds in TS1c and TS1d, suggesting that the lower
barriers of TS1d and TS1f could be attributed to the
delocalization resonance involving an sp-hybridized carbon
(see Supplementary Figure 2 for details). Herein we report a
unified rearrangement to synthesize oxa-heterocycles by
treatment of N-phenoxyacetamides (Ph−ONHAc) with
compounds containing an sp-hybridized carbon (Figure 1d).
RESULTS AND DISCUSSION
■
As the first attempt, a solution of N-phenoxyacetamide (1a)
and 2.0 equiv of ethyl 3-bromopropiolate (2a) in ethyl acetate
was treated with 1.5 equiv of NaOH at ambient temperature
over a period of 20 min. We were pleased to observe that ethyl
2-acetamidobenzofuran-3-carboxylate (3a) was obtained in
46% NMR yield (Supplementary Table 1, entry 1). Following
this encouraging result, we screened a variety of other bases
(Supplementary Table 1, entries 2−11). Sodium tert-butoxide
was the best, and potassium methoxide gave slightly
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a
a
Table 1. Substrate Scope of Type I Reaction
Table 2. Substrate Scope of Type II Reaction
a
Standard conditions: A mixture of 4 (0.6 mmol) and 2-iodopyridine
(1.2 mmol) in MeCN (1.0 mL) was treated with Tf2O (0.6 mmol)
under N2. The mixture was stirred at 0 °C for 15 min and then added
to a solution of 1 (0.2 mmol) and tBuONa (0.3 mmol) in MeCN (1.0
mL) at 0 °C. The reaction mixture was allowed to warm to room
temperature for 3 h.
substituted N-phenoxyacetamides (Table 3). N-Phenoxyaceta-
mides with electron-donating groups on the aryl moiety
a
Table 3. Substrate Scope of Type III Reaction
a
Standard conditions: 1 (0.2 mmol), 2 (0.4 mmol), and tBuONa (0.3
mmol) in DME (2 mL) at ambient temperature for 20 min. EWG =
b
electron-withdrawing group; N.R.= no reaction. 0.1 mmol of 1, 0.1
t
mmol of 2, and 0.15 mmol BuONa were used.
difuran product 3w when a dibromoalkyne substrate was
subjected to our reaction conditions.
Keteniminium salts have exhibited great power in organic
synthesis.22 Recently, Maulide and co-workers have exploited
this strategy extensively for the functionalization of amides.5b,23
Inspired by those pioneering works, we thought that the
electrophilic keteniminium generated from an amide might be
used to trigger rearrangement of the O−N bond to construct
benzofurans. To our delight, after screening the reaction
conditions carefully, we obtained a 76% yield of N-
(benzofuran-2-yl)acetamide (5a) when 1a was treated with
N,N-diethylacetamide (see Supplementary Table 2 for the
optimization of the conditions). N-Phenoxyacetamides and
N,N-disubstituted amides with different substituents were
effectively converted to products in acceptable yields (Table 2,
5b-5e, 53−64%).
a
t
Standard conditions: 1 (0.2 mmol), BrCN (0.4 mmol), and BuOK
(0.3 mmol) in DME (2.0 mL) at ambient temperature for 30 min.
Encouraged by the successful synthesis of benzofurans from
N-phenoxyacetamides, we then tried to extend this trans-
formation to obtain benzoxazoles. When 1a and cyanogen
bromide (BrCN) were subjected to the standard conditions,
benzoxazole 6a was successfully obtained in 79% NMR yield.
When potassium tert-butoxide was used as the base and DME
as the solvent, 6a was formed in 89% NMR yield and 87%
isolated yield within 30 min (for details, see Supplementary
Table 3). With the optimized reaction conditions established,
we next examined the versatility of the reaction with diversely
reacted smoothly with BrCN, and the corresponding products
(6a−g) were isolated in 73−91% yield. This annulation
reaction can tolerate reactive functional groups such as fluoro
(6h) and chloro (6i and 6j), which are useful for further
synthetic transformations. When meta-substituted N-phenox-
yacetamides were used, the annulation took place at two ortho
sites. Therefore, for substrates 1k and 1l, two regioisomers
with a ratio of almost 1:1 were obtained. Replacing the acetyl
C
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group with other groups such as propionyl or isobutyryl led to
smooth reactions, affording the desired products 6m and 6n in
86% and 95% yield, respectively. The N-phenoxyamide with a
Boc-substituent on the nitrogen afforded the corresponding
product 6o in 63% yield. Moreover, the same reaction
conditions could be used when the acetamide was replaced
by a sulfonamide (6p).
Late-stage functionalization of natural products and
synthetic drugs is important in the synthesis of bioactive
compounds.24 Hence, we were pleased to find that the
outstanding versatility of our newly developed strategy
provides a unique approach to the modification of complex
molecules into oxyheterocyclic derivatives. N-Aryloxyamides
derived from tyrosine, triclosan, and estrone were prepared and
subjected to the optimized conditions (Table 4). The [3,3]-
Figure 2. Further synthetic application of our strategy. (a) Rapid
synthesis of an inhibitor of hFBPase-1. Type III reaction conditions: 1
(0.2 mmol), BrCN (0.4 mmol), and BuOK (0.3 mmol) in solvent
(2.0 mL) at ambient temperature for 30 min. (b) Modification of
tyrosine in aqueous buffer. Reaction conditions: 1 (0.2 mmol), 3a
(0.4 mmol), and K2CO3 (0.3 mmol) in PBS (2.0 mL) at 37 °C for 2
h.
t
Table 4. Late-Stage Manipulation of Complex Natural
a
Products and an Approved Drug
suggests that it is potentially a novel click reaction
(Supplementary Figure 1).
Given the unique versatility of these annulation reactions, we
delineated the mechanism of the reaction, and further
experiments were conducted to investigate the mechanistic
details. When the O−N bond was replaced by a N−N or S−N
bond in either reaction type I or reaction type III, none of the
desired products were detected. The calculated BDEs of the
corresponding N−N or S−N bond in INT1, ranging from 35.7
to 44.1 kcal/mol, are as high as those of INT1a and INT1b,
which are unreactive (Figure 1c). Furthermore, the free energy
barrier for the [3,3]-sigmatropic rearrangement (TS1) was
calculated to be at least 10.1 kcal/mol higher than that of
TS1d, suggesting poor reactivity. The above experimental and
computational results illustrated the indispensable role of the
O−N bond (Figure 3a). For reaction type I, the protocol was
found to be general for electron-withdrawing groups as
substituents in 2, but electron-donating substituents (−nBu,
−TIPS, −Ph) were not beneficial in this transformation
(Figure 3b). An intermolecular competition reaction between
1b and 1i under type I reaction conditions revealed that the
aryl moiety with higher electron density facilitated the
annulation (Figure 3c).
a
Reaction conditions: type I reaction conditions: 1 (0.2 mmol), 2a
(0.4 mmol), and tBuONa (0.3 mmol) in DME (2.0 mL) for 20 min at
ambient temperature; type III reaction conditions: 1 (0.2 mmol),
BrCN (0.4 mmol), and BuOK (0.3 mmol) in DME (2 mL) for 30
min at ambient temperature.
t
DFT calculations were performed to investigate the detailed
free energy profiles for the reactions. Figure 4 shows the critical
rearrangement steps for reaction type I leading to 3a from 1a.
Other reaction types and the details of the overall profile are
shown in Supplementary Figures 3−6. First, the amide (NH)
of substrate 1a was deprotonated19c in the presence of the base
sodium tert-butoxide, forming intermediate INT0. Next,
nucleophilic substitution of ethyl 3-bromopropiolate by
INT0 led to the formation of intermediate INT1 via TS0.
The computational results indicated that this step is the rate-
determining step with a free energy barrier of 8.3 kcal/mol.
The computations of the control experiment and competitive
experiment in Figure 3b,c were consistent with the
experimental observations and revealed that TS0 is indeed
the rate-determining step (see Supplementary Figures 3 and 5
for details). The subsequent [3,3]-sigmatropic rearrangement
occurs through TS1 to form INT2. Dearomatization takes
place in this step, which is associated with a free energy barrier
of 6.0 kcal/mol. Then the facile process of aromatization and
cyclization leads to the final product 3a (see Supplementary
Figure 4 for details). This reaction is intensely exergonic with
an overall reaction free energy of −133.1 kcal/mol. The type
sigmatropic rearrangement took place smoothly, affording the
corresponding 2-aminobenzofurans (3x−y′) and 2-amino-
benzoxazoles (6q and 6r) in acceptable yields. The structure
of 3y was unambiguously established by single-crystal X-ray
diffraction.
Benzoxazole benzenesulfonamides have been identified as
inhibitors of human fructose-1,6-bisphosphatase (hFBPase-
1).25 However, the reported approach to obtain such
compounds requires high temperatures with the aid of
microwave radiation. Here, benzoxazole benzenesulfonamides
(6s and 6t) were synthesized successfully under mild reaction
conditions (Figure 2a). With a modification of the newly
developed reaction type I, we also achieved the functionaliza-
tion of tyrosine in phosphate-buffered saline (PBS) (Figure
2b). In order to further understand this reaction, we studied its
kinetics. N-Phenoxyacetamide (1a) (0.5 mmol), ethyl 3-
t
bromopropiolate (2a) (2.0 equiv), and BuONa (1.5 equiv)
were mixed in DME (5.0 mL) at 25 °C, and the reaction was
1
monitored by H NMR spectroscopy. We obtained a second-
order rate constant of (4.4 0.065) × 10−2 M−1 s−1, which
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and computational studies suggests that the rearrangement/
annulation process is intensely exothermic and that the O−N
bond is indispensable. We are currently exploring more
sigmatropic rearrangement reactions based on the O−N
bond cleavage.
EXPERIMENTAL SECTION
■
General. Commercially available chemicals were obtained
from Adamas, Energy, TCI, and Bide and used as received
unless otherwise stated. Reactions were monitored with
1
analytical thin-layer chromatography (TLC) on silica. H and
13C NMR data were recorded on Bruker NMR spectrometers
(300, 400, and 500 MHz) unless otherwise specified. Chemical
shifts (δ) are given in parts per million relative to TMS. The
residual solvent signals were used as references, and the
chemical shifts were converted to the TMS scale (CDCl3, δH =
7.26 ppm and δC = 77.16 ppm; CD2Cl2, δH = 5.32 ppm and δC
= 54.00 ppm; DMSO-d6, δH = 2.50 ppm and δC = 39.52 ppm;
MeOH-d4, δH = 3.31 ppm and δC = 49.00 ppm; acetone-d6, δH
= 2.05 ppm and δC = 29.84 and 206.26 ppm). HRMS (ESI)
analysis was performed by The Analytical Instrumentation
Center at Peking University, Shenzhen Graduate School, and
the HRMS data are reported with ion mass/charge (m/z)
ratios as values in atomic mass units.
For NMR spectra of compounds in this Communication, see
Supplementary Figures 13−74. For the crystallographic data
for compounds 3l, 3y, 5b, 5d, and 6o, see Supplementary
Figures 6−10 and Supplementary Tables 4−36. For the
representative experimental procedures and analytic data of
compounds synthesized, see Supplementary Methods.
Figure 3. Mechanistic study. (a) Irreplaceability of the O−N bond.
(b) Control experiments. (c) Competition experiment. Type I
t
reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), and BuONa
(0.3 mmol) in DME (2 mL) for 20 min at ambient temperature. Type
III reaction conditions: 1 (0.2 mmol), BrCN (0.4 mmol), and tBuOK
(0.3 mmol) in DME (2.0 mL) for 30 min at ambient temperature.
EDG = electron-donating group; N.R. = no reaction.
Standard Reaction Conditions of Reaction Type I. N-
Phenoxyacetamide (1a) (30 mg, 0.20 mmol), 2a (70.8 mg,
0.40 mmol), and DME (2.0 mL) were weighed into a 10 mL
t
pressure tube, to which BuONa (28.8 mg, 0.30 mmol) was
added. The reaction vessel was stirred at room temperature for
20 min. Then the mixture was concentrated under vacuum,
and the residue was purified by column chromatography on
silica gel with a gradient eluent of petroleum ether and ethyl
acetate to afford the product ethyl 2-acetamidobenzofuran-3-
1
carboxylate (3a) (45.4 mg, 92% yield) as a white solid. H
NMR (400 MHz, CDCl3): δ 9.86 (s, 1H), 7.71 (d, J = 7.4 Hz,
1H), 7.44 (d, J = 8.0 Hz, 1H), 7.29−7.14 (m, 2H), 4.36 (q, J =
7.1 Hz, 2H), 2.33 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR
(101 MHz, CDCl3): δ 166.80, 165.61, 156.09, 150.37, 124.55,
123.99, 123.66, 120.61, 111.11, 91.35, 60.70, 24.70, 14.35.
HRMS (ESI): calcd for C13H13NNaO4 [M + Na]+, 270.0737;
found, 270.0736.
Figure 4. Free energy profile for the synthesis of 3a from 1a in
solution, showing a plausible mechanism for the formation of 3a via
[3,3]-sigmatropic rearrangements.
Standard Reaction Conditions of Reaction Type II. To
a mixture of N,N-diethylacetamide (65 μL, 0.6 mmol) and 2-
iodopyridine (60 μL, 1.2 mmol) in MeCN was added triflic
anhydride (40 μL, 0.6 mmol) dropwise at 0 °C under N2. This
mixture was stirred for 15 min and then added to a solution of
1a (30 mg, 0.20 mmol) and tBuONa (28.8 mg, 0.3 mmol) at 0
°C, and the mixture was allowed to warm to room
temperature. After 3 h, the reaction mixture was concentrated
under reduced pressure, and the residue was purified by flash
chromatography on silica gel to afford N-(benzofuran-2-
III reaction proceeds by a process similar to that for type I (see
Supplementary Figure 6 for details). For these reactions, the
cleavage of the weak O−N bond and the reconstruction of
aromaticity provide the driving force for the reaction.
CONCLUSION
■
1
yl)acetamide (5a) (26.6 mg, 76% yield) as a white solid. H
We have reported that O−NHAc acts as a diverse functional
group for the unified synthesis of benzofurans and benzox-
azoles. This strategy was successfully applied to the late-stage
modification of natural products as well as the rapid
construction of hFBPase-1. A combination of experimental
NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 7.46 (d, J = 6.9 Hz,
1H), 7.31 (d, J = 7.0 Hz, 1H), 7.19 (d, J = 12.5 Hz, 2H), 6.76
(s, 1H), 2.24 (s, 3H). 13C NMR (101 MHz, DMSO): δ
166.82, 149.56, 147.59, 129.48, 123.26, 122.83, 120.40, 110.18,
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Standard Reaction Conditions of Reaction Type III. 1a
(30 mg, 0.20 mmol), BrCN (42 mg, 0.40 mmol), and DME
(2.0 mL) were weighed into a 10 mL pressure tube, to which
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1998, 63 (21), 7547−7551.
11.10 (s, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.9 Hz,
1H), 7.37−7.25 (m, 2H), 2.52 (s, 3H). 13C NMR (101 MHz,
DMSO): δ 168.82, 155.63, 147.96, 141.05, 124.94, 123.94,
118.56, 110.38, 24.29. HRMS (ESI): calcd for C9H8N2NaO2
[M + Na]+, 199.0477; found, 199.0477.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.oprd.9b00002.
■
S
1H NMR spectra, 13C NMR spectra, and high-resolution
mass spectra for selected compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: jingzhao@nju.edu.cn.
*E-mail: zhangxh@pkusz.edu.cn.
■
ORCID
Jing Zhao: 0000-0001-5177-5699
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
Financial support was provided by the National Natural
Science Foundation of China (21622103, 21571098,
21671099, and 91753121), the Natural Science Foundation
of Jiangsu Province (BK20160022), the Fundamental Research
Funds for the Central Universities (020514380139), the
S h e n z h e n B a s i c R e s e a r c h P r o g r a m
(JCYJ20170413150538897), the Shenzhen STIC
(JCYJ20170412150343516), and the Shenzhen San-Ming
Project (SZSM201809085).
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(b) Peng, B.; Geerdink, D.; Fares, C.; Maulide, N. Chemoselective
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