Remote sp3 C–H Amination of Alkenes with Nitroarenes

Article abstract of DOI:10.1016/j.chempr.2018.04.008

Direct installation of a functional group at remote, unfunctionalized sites in an alkyl chain is a synthetically valuable but rarely reported process. The remote relay hydroarylamination of distal and proximal olefins, and of olefin isomeric mixtures, has been achieved through NiH-catalyzed alkene isomerization and sequential reductive hydroarylamination with nitroarenes. This provides an attractive approach to the direct installation of a distal arylamino group within alkyl chains. The single-step conversion of simple olefins and nitro(hetero)arenes to value-added arylamines is a practical strategy for amine synthesis as well as the remote activation of sp³ C–H bonds. The value of this transformation is further supported by the regioconvergent arylamination of isomeric mixtures of olefins. Modern organic synthesis requires more efficient strategies, such as C–H functionalization, with which to construct complex molecules from readily available chemicals. Undirected functionalization of remote aliphatic C–H bonds is a synthetically valuable but largely unknown process. Synergistic combination of metal-catalyzed chainwalking (migration of a double bond along the hydrocarbon chain, a process involving repeated migratory insertions and β-hydride eliminations) and cross-coupling chemistry offers a general approach to the remote functionalization of easily accessed unsaturated hydrocarbon substrates. In this paper, we demonstrate that direct installation of a distal arylamino group can be achieved from two common feedstock chemicals (olefins and nitroarenes) via nickel hydride chemistry. It is anticipated that the strategy could inspire the development of other remote functionalizations with different regioselectivity as well as asymmetric transformations. Zhu and colleagues describe the remote hydroamination of alkenes with nitro(hetero)arenes through nickel-catalyzed alkene isomerization and sequential reductive relay hydroamination process. Using two common feedstock chemicals, olefins and nitroaromatics, in an operationally simple procedure, this attractive protocol provides efficient and practical access to a wide range of arylamines under mild conditions.

Full text of DOI:10.1016/j.chempr.2018.04.008

Article
Remote sp3 C–H Amination of Alkenes with
Nitroarenes
Jichao Xiao, Yuli He, Feng Ye,
Shaolin Zhu
shaolinzhu@nju.edu.cn
HIGHLIGHTS
Direct remote hydroamination of
alkenes with nitroarenes
Nickel-catalyzed alkene
isomerization and sequential
reductive relay hydroamination
Readily available reactants and
catalysts, mild conditions, and
broad substrate scope
Practical, scalable, and
regioconvergent for arylamine
synthesis
Zhu and colleagues describe the remote hydroamination of alkenes with
nitro(hetero)arenes through nickel-catalyzed alkene isomerization and sequential
reductive relay hydroamination process. Using two common feedstock chemicals,
olefins and nitroaromatics, in an operationally simple procedure, this attractive
protocol provides efficient and practical access to a wide range of arylamines
under mild conditions.
Xiao et al., Chem 4, 1–13
July 12, 2018 ª 2018 Elsevier Inc.
https://doi.org/10.1016/j.chempr.2018.04.008

Please cite this article in press as: Xiao et al., Remote sp3 C–H Amination of Alkenes with Nitroarenes, Chem (2018), https://doi.org/10.1016/
j.chempr.2018.04.008
Article
Remote sp3 C–H Amination
of Alkenes with Nitroarenes
Jichao Xiao,1 Yuli He,1 Feng Ye,1 and Shaolin Zhu1,2,
*
SUMMARY
The Bigger Picture
Modern organic synthesis
Direct installation of a functional group at remote, unfunctionalized sites in an
alkyl chain is a synthetically valuable but rarely reported process. The remote
relay hydroarylamination of distal and proximal olefins, and of olefin isomeric
mixtures, has been achieved through NiH-catalyzed alkene isomerization and
sequential reductive hydroarylamination with nitroarenes. This provides an
attractive approach to the direct installation of a distal arylamino group within
alkyl chains. The single-step conversion of simple olefins and nitro(hetero)are-
nes to value-added arylamines is a practical strategy for amine synthesis as
well as the remote activation of sp3 C–H bonds. The value of this transformation
is further supported by the regioconvergent arylamination of isomeric mixtures
of olefins.
requires more efficient strategies,
such as C–H functionalization,
with which to construct complex
molecules from readily available
chemicals. Undirected
functionalization of remote
aliphatic C–H bonds is a
synthetically valuable but largely
unknown process. Synergistic
combination of metal-catalyzed
chainwalking (migration of a
double bond along the
INTRODUCTION
hydrocarbon chain, a process
involving repeated migratory
insertions and b-hydride
Arylamines are commonly encountered in pharmaceuticals, natural products, agro-
chemicals, and other chemicals.1–3 Classical methods for arylamine synthesis include
Buchwald-Hartwig amination,4–6 amine-carbonyl reductive amination,7 and nucleo-
philic substitution.8 Recently, direct amination of the ubiquitous sp3 C–H bond has
emerged as an attractive strategy for amine synthesis. However, to discriminate be-
tween the many structurally similar aliphatic C–H bonds in an alkyl chain and to
achieve high regio- and chemoselectivity, a local pre-installed polar directing
group is often required. This makes the strategy inefficient and limits its wide appli-
cation.9–11 Therefore, undirected strategies that allow C–H functionalization at
remote, unfunctionalized sites could be valuable for the synthesis of complex mole-
cules and will allow access to structures that would otherwise be difficult to synthe-
size.12,13 Given the abundance and availability of alkenes, olefin hydroamination has
in recent years been presented as a direct and attractive alternative with which to ac-
cess amines.14–29 However, this elegant approach has generally been restricted to
installation of an amino group at a C=C double bond. Remote functionalization of
olefins remains a formidable challenge in organic synthesis and in recent years has
attracted considerable interest from the chemistry community.30–52 More specif-
ically, the direct installation of an amino group by remote hydroamination of olefins
at an sp3 carbon distant from a double bond (Figure 1A) is a valuable but unexplored
process.53,54
eliminations) and cross-coupling
chemistry offers a general
approach to the remote
functionalization of easily
accessed unsaturated
hydrocarbon substrates. In this
paper, we demonstrate that direct
installation of a distal arylamino
group can be achieved from two
common feedstock chemicals
(olefins and nitroarenes) via nickel
hydride chemistry. It is anticipated
that the strategy could inspire the
development of other remote
functionalizations with different
regioselectivity as well as
asymmetric transformations.
Nitro(hetero)arenes are stable, inexpensive, and readily available starting materials.
They are also precursors of anilines, one of the most popular nitrogen sources, which
are usually prepared in advance by hydrogenation of the corresponding nitroarenes.
Because of these potential advantages, there is an impetus to discover chemical
transformations that directly utilize nitroarenes in synthetically valuable C–N
bond-forming reactions.55–65 Recently, Baran et al.26 developed a straightforward
Chem 4, 1–13, July 12, 2018 ª 2018 Elsevier Inc.
1

Please cite this article in press as: Xiao et al., Remote sp3 C–H Amination of Alkenes with Nitroarenes, Chem (2018), https://doi.org/10.1016/
j.chempr.2018.04.008
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Figure 1. Design Plan: Remote sp3 C–H arylamination Enabled by Alkene Isomerization and a
Sequential Reductive Hydroarylamination Relay Process
hydroamination approach to the construction of arylamines from nitroarenes by
combining a FeH-mediated radical reaction followed by a zinc reduction in a one-
pot fashion. A recent focus of our laboratory has been the development of NiH-cata-
lyzed olefin remote functionalization as a general strategy with which to achieve inert
sp3 C–H bond functionalization through NiH-catalyzed alkene isomerization and
subsequent cross-coupling.47,50,51 We recently sought to learn whether metal hy-
dride66–69-catalyzed chainwalking chemistry could be used to enable remote
aliphatic C–H amination through the direct use of nitroarenes as amination reagents.
Herein, we report the successful implementation of this strategy and demonstrate
the direct conversion of two simple feedstock chemicals, olefins and nitro(hetero)
arenes, to useful benzylic arylamines under mild conditions with high functional-
group tolerance (Figure 1B). In addition, some insights gleaned from preliminary
mechanistic studies are reported.
RESULTS
Reaction Optimization
Our initial investigation was focused on the remote hydroarylamination of 4-phenyl-1-
butene (1a) with 4-nitrotoluene (2a) (Figure 2; see also Tables S1 and S2). Investigation
of a variety of reaction parameters showed that high (99%) regioselectivity of the
benzylic arylamination product can be obtained in good yield at 50ꢀC with a combina-
tion of NiI2 and the C2-substituted bipyridine ligand L1 (6,60-dimethyl-2,20-bipyridine)
without extra base (Figure 2, entry 1). Control experiments revealed that the nickel cata-
lyst was necessary for the reaction to proceed, and substitution of NiI2 with another
nickel source (NiBr2) led to only a moderate yield and significant diminution in the regioi-
someric ratio (entry 2). Furthermore, replacement of the solvent, a mixture of 1,3-
dimethyl-3.4.5.6-tetrahydro-2(1H)-pyrimidinone (DMPU) and N,N-dimethylacetamide
(DMA) with another solvent (tetrahydrofuran) led to a substantial decrease in the yield,
and use of a single solvent was also less efficient (entries 3–5). Use of 1,1,1,3,5,5,5-hep-
tamethyltrisiloxane or polymethylhydrosiloxane results in decreased yield and regioiso-
meric ratio (rr), but trimethoxysilane is comparably effective (entries 6–8). Conducting
the reaction at room temperature also leads to a diminished yield (entry 9). Interestingly,
the desired migratory amination also proceeds in the absence of the ligand L1, although
the yield is very low (entry 10). In addition, absence of the methyl groups from L1 re-
duces the yield (entry 11), whereas a phosphine ligand, 20-(diphenylphosphino)-N,N0-
dimethyl-(1,10-biphenyl)-2-amine, is ineffective (entry 12).70–73 The use of lower catalyst
loading leads to a modest decrease in yield (entry 13) and finally, monitoring the
1State Key Laboratory of Coordination Chemistry,
Jiangsu Key Laboratory of Advanced Organic
Materials, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093,
China
2Lead Contact
*Correspondence: shaolinzhu@nju.edu.cn
https://doi.org/10.1016/j.chempr.2018.04.008
2
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j.chempr.2018.04.008
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Figure 2. Variation of Reaction Parameters
Yields were determined by GC with n-tetradecane as the internal standard. The yield in
parentheses is the isolated yield and is an average of two runs (0.2-mmol scale). rr refers to
regioisomeric ratio, representing the ratio of the major (benzylic amine) product to the sum of all
other isomers as determined by GC analysis (see Supplemental Information). DMPU, 1,3-dimethyl-
3,4,5,6-tetrahydro-2(1H)-pyrimidinone; DMA, N,N-dimethylacetamide; THF, tetrahydrofuran; Tol,
p-tolyl; PMHS, polymethylhydrosiloxane; PhDavePhos, 2-(diphenylphosphino)-N,N-dimethyl-(1,10-
biphenyl)-2-amine.
reaction by gas chromatography (GC) shows that the reaction rate is very fast in the first
20 min (entry 14). Notably, no extra reduction step26 is needed in this protocol to pro-
duce the final arylamine product.
Substrate Scope
We sought to define the scope of alkene coupling partners under the optimal con-
ditions. As illustrated in Figure 3A (see also Figures S36–S44 and S83–S102), termi-
nal aliphatic alkenes bearing a wide variety of substituents on the remote aryl ring
can undergo isomerization-hydroamination smoothly (1c–1g). Heteroaromatic sub-
strates, common scaffolds in medicinally relevant targets, such as those containing a
pyridine linked aryl ring (1g), a furan (1h), or a thiophene (1i; Figures S200 and S201),
in place of the aryl group are likewise suitable for this reaction.
Unactivated internal olefins are also suitable partners under these conditions (Fig-
ure 3B; see also Figures S45–S50 and S103–S118). Consistent with our expectations,
both E (1o and 1p) and Z (1n) alkenes, as well as E/Z mixtures (1j–1m) are accommo-
dated perfectly, yielding benzylic amines exclusively in comparable yields, regard-
less of the position of the C=C bond in the starting material. Notably, even with a
heteroatom substituent at the other terminus of the alkyl chain such as the Boc
carbamate in 1o or the ether in 1p (Figures S202 and S203), migration toward the
aryl group and subsequent benzylic amination are still preferred. Interestingly, a
trisubstituted internal alkene (1q; Figures S204 and S205), a challenging substrate
for transition-metal catalysis, also undergoes remote hydroamination, although
with diminished yield and rr.
Chem 4, 1–13, July 12, 2018
3

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j.chempr.2018.04.008
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Figure 3. Scope of Alkene Coupling Component
Isolated yields on 0.20-mmol scale (average of two runs). rr refers to regioisomeric ratio, representing the ratio of the major (benzylic amine) product to
the sum of all other isomers as determined by GC analysis. Ratios reported as >95:5 were determined by crude 1H NMR analysis. FG, functional group.
Perhaps less surprising, but equally useful, is the hydroamination of styrenes con-
taining various substituents to produce the desired benzylic amine exclusively (Fig-
ure 3C, 3r–3x; see also Figures S51–S55, S119–S132, S206, and S207). Although this
4
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Please cite this article in press as: Xiao et al., Remote sp3 C–H Amination of Alkenes with Nitroarenes, Chem (2018), https://doi.org/10.1016/
j.chempr.2018.04.008
4z
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Figure 4. Scope of Nitroarene Component
Yield and rr are as defined in Figure 3. y7.0 equiv silane. z24 hr.
is a reductive process, the sensitive ketone group in an estrone-derived styrene is
retained intact (3x). In contrast, the classical reductive amination of a carbonylamines
requires the protection of the ketone.
We next demonstrated the generality of this reaction with respect to the nitroarene
component (Figure 4; see also Figures S56–S82 and S133–S197). Substrates with
either electron-rich (2d–2g) or electron-deficient (2o–2y) substituents cross-couple
efficiently. Such mild and base-free reaction conditions potentially allow the use of
a range of nitroarene components with sensitive functional groups, including ethers
(2e and 2v), amines (2d and 2i), esters (2m and 2x), amides (2g and 2o), a sulfone (2k),
a thiolether (2f), and a nitrile (2n). Free phenol (2h), amine (2i), and alcohol (2j) are
well tolerated. Of particular interest are potential coupling motifs, including aryl ha-
lides (2o–2s), an aryltriflate (2t), and a boronic acid pinacol ester (2u), which are left
intact and utilizable for further cross-coupling transformations. A series of heterocy-
cles including benzofuran (2z), benzothiophene (2a0), indole (2b0), pyridine (2c0), and
benzooxazole (2d0), which are frequently found in medicinally active chemicals, were
also shown to be competent coupling partners.
Chem 4, 1–13, July 12, 2018
5

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j.chempr.2018.04.008
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Scheme 1. Large-Scale, Regioconvergent, and Expanded Alkene Scope Experiments
Applications
As a demonstration of the robustness and practicality of this protocol, we carried out
a 10-mmol-scale experiment and found that 3a could be isolated from the reaction in
80% yield without a decrease in the rr (Scheme 1A; see also Scheme S1). Moreover,
this process is also sufficiently effective to allow conversion of isomeric mixtures of
olefins into value-added arylamines in a regioconvergent fashion. This includes po-
sitional and geometrical isomers, which are generally much more readily available
and substantially cheaper than pure isomers. To provide proof of concept, we
used a mixture of equimolar amounts of three olefin isomers under the standard con-
ditions. Consistent with expectations amination was highly selective, occurring at
the benzylic position and producing only a single regioconvergent amination prod-
uct (Scheme 1B; see also Scheme S2). Additionally we extended this chemistry to
olefins with a remote ester group on the alkyl chain (Scheme 1C; see also Scheme
S3). Under slightly modified reaction conditions, migratory amination with excellent
selectivity at the carbon a to the ester is obtained, producing the N-aryl amino acid
derivative (6; Figures S2 and S3).
DISCUSSION
Proposed Catalytic Cycle
A detailed description of the proposed pathway is outlined in Figure 5. It was envi-
sioned that a nickel hydride species, LNiH (I) generated from silane, could be used to
initiate a rapid and reversible sequential b-hydride elimination and b-migratory rein-
sertion and iterative process from an olefin isomer (1a) to access a series of alkylnick-
el(I) intermediates (II, IV, etc.) along the alkyl chain. If nickel migration along the alkyl
chain is rapid and the reaction of benzylnickel(I) intermediate (IV) with the amination
reagent, the nitrosoarene (V) generated in situ from the nitroarene (2a), is favorable,
it will provide rapid access to the remote hydroxylamine intermediates (VI) rather
than hydroamination at the original C=C double bond. Further reduction of hydrox-
ylamine (VI) will provide the final hydroamination product (3a). The nickel hydride
species (I) is regenerated in situ by a stoichiometric amount of a hydrosilane to
achieve a net catalytic, remote hydroarylamination reaction.
6
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Please cite this article in press as: Xiao et al., Remote sp3 C–H Amination of Alkenes with Nitroarenes, Chem (2018), https://doi.org/10.1016/
j.chempr.2018.04.008
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Figure 5. Proposed Mechanism for Reductive Relay Hydroamination
Mechanistic Studies
A series of experiments were conducted to gain insight into the mechanism of the
reaction. The fact that olefin 1a itself, in the absence of nitroarene, can isomerize
to other positional isomers under standard conditions suggests that alkene isomer-
ization is unrelated to C–N bond formation, and also indicates that the nitroarene is
not involved in the chainwalking step (Scheme 2A; see also Table S3 and Figures
S208 and S209). Furthermore, no desired isomerization-hydroarylamination reaction
occurs when an oxygen atom or a gem-dimethyl spacer lacking a b-hydrogen is intro-
duced into the hydrocarbon chain between the benzylic position and double bond
(Scheme 2B; see also Scheme S4 and Figures S4 and S5). This is consistent with the
hypothesis that olefin isomerization occurs through rapid and reversible b-hydrogen
elimination and reinsertion steps.74–77 An isotope labeling experiment of a model
reaction was carried out with deuterodiphenylsilane. Deuterium scrambling and
deuterium incorporation at all the positions except the benzylic position along the
hydrocarbon chain were observed. As revealed by mass spectrometric analysis, a
mixture of undeuterated, monodeuterated, and polydeuterated products was ob-
tained. This supports a mechanism whereby chainwalking occurs with dissociation
and reassociation of free NiH/NiD from the NiH/NiD-olefin complex (Scheme 2C;
see also Scheme S5 and Figures S6–S8).50 Furthermore, when deuterium-labeled
olefin 1a-D is used in both standard and crossover reactions, deuterium scrambling
and deuterium incorporation at all the positions along the hydrocarbon chain are
also observed (Scheme 2C; see also Schemes S6 and S7 and Figures S9–S18). Deute-
rium incorporation in 3g-D further supports the dissociation and reassociation of
NiH/NiD from the olefin during the chainwalking process. Interestingly, no deute-
rium scrambling at the benzylic position in either 12 or 3g-D is observed, suggesting
that b-migratory insertion with a styrenic intermediate is highly regiospecific and
forms the benzylic nickel species. This hypothesis is further supported by experi-
ments using a styrene substrate (1a0) (Scheme 2D; see also Scheme S8). Only one
Chem 4, 1–13, July 12, 2018
7

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Scheme 2. Mechanistic Studies Concerning Chainwalking
8
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Scheme 3. Studies of the Mechanism of Reductive Hydroarylamination
regioisomer (3a0, Figures S19 and S20) is obtained and no isomerization of 1a0 is
observed during the partial conversion. To explore the chainwalking process further,
we evaluated an olefin substrate (S)-1b0 (Figures S210 and S211), with a pre-installed
stereogenic center (95% enantiomeric excess [ee]) in the alkyl chain, under the stan-
dard conditions (Scheme 2E; see also Scheme S9). In contrast to the preservation of
the chiral integrity in the PdH-catalyzed chainwalking process,33,37 in the corre-
sponding product (3b0, 1:1 diastereomeric ratio; Figures S21–S26), partial racemiza-
tion of this stereocenter is observed (the ee of this stereocenter drops from 95% to
65% and 95% to 62%). This again implies that NiH disengages during the chainwalk-
ing process.
Next, we set out to identify the active species of nitroarene. As shown in Scheme 3A
(see also Schemes S10 and S11), no reaction happens in the absence of nickel, and
nitrobenzene is easily reduced to aniline in the absence of olefin under standard con-
ditions. However, no desired hydroarylamination reaction occurs when aniline is
Chem 4, 1–13, July 12, 2018
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j.chempr.2018.04.008
resubjected to the standard conditions with the styrene (1c0), suggesting that aniline
is not involved in the hydroamination step (Scheme 3B; see also Scheme S12). Addi-
tionally, a series of potential intermediates were used directly in place of nitroben-
zene (Scheme 3C; see also Scheme S13 and Figures S27 and S28). Under standard
conditions, none of them give product 3d0 in any considerable yield. Considering
that the actual intermediate is generated in situ at low concentration under the stan-
dard reaction conditions, we next added these potential intermediates slowly over a
period of 1 hr. Indeed, the desired product 3d0 (Figures S29, S198, and S199) is ob-
tained in 22% GC yield in case of nitrosobenzene, suggesting that the nitrosoarene is
likely the actual intermediate. Due possibly to the relative high concentration of ni-
trosobenzene compared with the alkylnickel intermediate, low regioselectivity is
observed and aniline is the major side product. As suggested in our proposed mech-
anism, the final amination product presumably forms by reduction of hydroxylamine
intermediate (Figure 5). Indeed, hydroxylamine 15 (Figures S31–S34) and nitroso-
benzene 16 (Figures S30 and S35) could be monitored, isolated, and confirmed at
the early stage of the reaction (Scheme 3D; see also Scheme S14). As anticipated,
the final product 3a is obtained quantitatively from hydroxylamine 15 under stan-
dard conditions. Additional studies to fully elucidate the reaction pathway are
currently in progress.
Conclusion
We have developed a practical, operationally simple, and selective reductive
remote hydroamination process via a sequential NiH-catalyzed chainwalking-reduc-
tive hydroarylamination relay process. This mild and efficient protocol utilizes two
readily available reactants, inexpensive silane reductants, and earth-abundant nickel
salt catalysts. Excellent regio- and chemoselectivity are observed for a wide range of
both alkene and nitroarene coupling partners. The practical value of this process is
further highlighted by large-scale synthesis and regioconvergent amination of unre-
fined isomeric mixture of olefins. Studies toward a catalytic asymmetric version of
this transformation are continuing.78
EXPERIMENTAL PROCEDURES
Representative Procedure for NiH-Catalyzed Remote Hydroarylamination
6,60-Dimethyl-2,20-bipyridine (L1, 4.1 mg, 11 mol %) was added to an oven-dried
8-mL screw-cap vial (Figure S1) equipped with a magnetic stir bar. The vial was
introduced into a nitrogen-filled glovebox and NiI2 (6.3 mg, 10 mol %), anhydrous
DMPU (0.10 mL) and anhydrous DMA (0.10 mL) were added. The mixture was then
stirred for 10 min, at which time dimethoxymethylsilane (147 mL, 1.2 mmol, 6.0
equiv) was added and the stirring was continued for another 10 min at room tem-
perature before 4-phenyl-1-butene (60 mL, 0.40 mmol, 2.0 equiv) was added. The
tube was sealed with a Teflon-lined screw cap, removed from the glovebox and
stirred at 0ꢀC before a solution of 4-nitrotoluene (27.4 mg, 0.20 mmol, 1.0 equiv)
in anhydrous DMPU (0.10 mL) and anhydrous DMA (0.10 mL) was added dropwise
by syringe. The reaction mixture was then stirred at 25ꢀC for 10 min and stirred at
50ꢀC for up to 12 hr. After the reaction was complete, the reaction mixture was
immediately filtered through a short pad of silica gel (using EtOAc in hexanes) to
give the crude product. Tetradecane (20 mL) was added as an internal standard
for GC analysis. 1,1,2,2-Tetrachloroethane (10.5 mL, 0.10 mmol) was added as inter-
nal standard for 1H NMR analysis of the crude material. The product was purified by
chromatography on silica gel for each substrate. The yields reported are the
average of at least two experiments, unless otherwise indicated. See Supplemental
Information for more detailed Experimental Procedures and characterization data
for all products.
10
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SUPPLEMENTAL INFORMATION
Supplemental Information includes Supplemental Experimental Procedures, 211
figures, 3 tables, and 15 schemes and can be found with this article online at
https://doi.org/10.1016/j.chempr.2018.04.008.
ACKNOWLEDGMENTS
Support was provided by the 1000-Youth Talents Plan, the National Natural Science
Foundation of China (21772087 and 21702102), the Fundamental Research Funds
for the Central Universities (020514380095 and 020514380086), and the National
Science Foundation of Jiangsu Province (BK20160642). Y.H. thanks the Postgrad-
uate Research & Practice Innovation Program of Jiangsu Province (KYCX17_0021)
and the Nanjing University Innovation and Creative Program for PhD Candidates
(CXCY17-16) for support. We are grateful to Yun Du and Pei Hu for GC-MS analysis.
This paper is dedicated to Professor David W.C. MacMillan on the occasion of his
50th birthday.
AUTHOR CONTRIBUTIONS
Conceptualization, S.Z.; Methodology, J.X., Y.H., and S.Z.; Investigation, J.X., Y.H.,
and F.Y.; Writing – Original Draft, J.X.; Writing – Review & Editing, S.Z.; Supervision,
S.Z.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: December 4, 2017
Revised: February 11, 2018
Accepted: April 10, 2018
Published: May 17, 2018
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j.chempr.2018.04.008
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