Enantioselective Copper-Catalyzed Trifluoromethylation of Benzylic Radicals via Ring Opening of Cyclopropanols

Full text of DOI:10.1016/j.chempr.2020.07.003

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Article
Enantioselective Copper-Catalyzed
Trifluoromethylation of Benzylic Radicals via
Ring Opening of Cyclopropanols
Chao Jiang, Lei Wang,
Honggang Zhang, Pinhong
Chen, Yin-Long Guo, Guosheng
Liu
gliu@mail.sioc.ac.cn
HIGHLIGHTS
Asymmetric catalytic radical
trifluoromethylation
Novel quinolinyl-containing
bisoxazoline ligand
Electrophilic CF3 reagent is crucial
to the reaction
External CF3 anion remarkably
diminished enantioselectivity
The asymmetric trifluoromethylation of aryl-substituted cyclopropanols via a
radical ring-opening pathway is reported herein, which provides an easy and
straightforward access to structurally diverse b-CF3 ketones in good yields and
excellent enantioselectivities under very mild conditions. Critical to the success of
the copper-catalyzed radical relay is that a benzylic radical intermediate can be
enantioselectively trapped by reactive (L*)CuIICF3. In addition, a novel quinolinyl-
containing bisoxazoline ligand plays a significant role in the asymmetric
trifluoromethylation.
Jiang et al., Chem 6, 1–13
September 10, 2020 ª 2020 Elsevier Inc.
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Enantioselective Copper-Catalyzed
Trifluoromethylation of Benzylic Radicals
via Ring Opening of Cyclopropanols
Chao Jiang,1 Lei Wang,1 Honggang Zhang,1 Pinhong Chen,1 Yin-Long Guo,1 and Guosheng Liu1,2,3,
*
SUMMARY
The Bigger Picture
The incorporation of
The asymmetric trifluoromethylation of aryl-substituted cyclopropa-
nols via a radical ring-opening pathway is reported herein, which
provides an easy and straightforward access to structurally diverse
b-CF3 ketones in good yields and excellent enantioselectivities un-
der very mild conditions. Critical to the success of the copper-cata-
lyzed radical relay is that a benzylic radical intermediate can be
enantioselectively trapped by reactive (L*)CuIICF3. In addition, a
novel quinolinyl-containing bisoxazoline ligand plays a significant
role in the asymmetric trifluoromethylation.
trifluoromethyl (CF3) groups into
biologically active molecules has a
significant effect on their physical
and biological properties, and
optically pure CF3-containing
organic molecules broadly exist in
pharmaceuticals and agricultural
chemicals. Thus, exploration of
efficient asymmetric
trifluoromethylation methods is
sought after. Recently, radical
trifluoromethylation coupling
emerged as one of most efficient
methods for the synthesis of CF3-
containing molecules, but
INTRODUCTION
The incorporation of trifluoromethyl (CF3) groups into biologically active molecules
has a significant effect on their physical and biological properties, such as lipophilic-
ity, metabolic stability, and bioavailability.1,2 Particularly, optically pure CF3-con-
taining organic compounds have been broadly utilized as pharmaceuticals and
agrochemicals.3 Therefore, considerable effort has been devoted to the develop-
ment of asymmetric trifluoromethylations during the last decade.4–7 Despite
advances, the asymmetric trifluoromethylation mainly relied on asymmetric nucleo-
philic and electrophilic trifluoromethylations, which are limited to the synthesis of
enantiomerically enriched CF3-substituted alcohols and ketones, respectively.8–10
In contrast, the asymmetric trifluoromethylation of carbon-centered radicals is
extremely difficult owing to highly reactive radical species. So far, there are no re-
ports of asymmetric radical trifluoromethylations to date.
asymmetric variants remain a
formidable challenge. In this
article, a copper-catalyzed
asymmetric trifluoromethylation
of cyclopropanols via a radical
relay process is disclosed using a
chiral ligand Bn-BoxQu. The
reaction enables the synthesis of
diverse, optically pure b-CF3
ketones efficiently, which can
serve as versatile building blocks
for the synthesis of an (R)–CF3-
modified analog of the drug
cinacalcet.
Distinct from the extensive studies on CF3 radical addition to alkenes,11–13 an alter-
native method for the trifluoromethylation of the carbon-centered radicals has
recently received much attention and serves as an attractive tool to introduce the
CF3 group into organic molecules. For instance, as shown in Scheme 1A, Li and
co-workers reported a series of Cu-mediated radical trifluoromethylation reactions
by using a stoichiometric amount of Cu(III) species [(Bpy)Cu(CF3)3].14,15 Copper-
mediated C–H bond trifluoromethylation reactions with the same (Bpy)Cu(CF3)3 re-
agent were also developed by the groups of Liu16 an Cook17 independently. Addi-
tionally, copper-catalyzed radical trifluoromethylation reactions were demonstrated
by using (L)Zn(CF3)2 (L = Bpy or DMPU) (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyr-
imidinone) as effective nucleophilic CF3 reagents.18–20
As our ongoing research interest in asymmetric radical transformations (ATRs), we
have recently developed a copper-catalyzed radical relay strategy for the enantiose-
lective cyanation21–23 and arylation,24,25 where the benzylic radical was enantiose-
lectively trapped by (Box)Cu(CN)2 or (Box)Cu-Ar species.26–29 Inspired by the recent
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Scheme 1. Copper-Mediated or -Catalyzed Radical Trifluoromethylation
Qu, quinolinyl.
progress on the radical trifluoromethylation,14–20 we envisioned that the asymmetric
trifluoromethylation of secondary alkyl radicals forging chiral C–CF3 bonds might be
possible by introducing chiral ligands.
Initially, we investigated the asymmetric trifluoromethylations of benzylic C–H bonds
and styrenes using a nucleophilic CF3 reagent (e.g., TMSCF3) instead of TMSCN (tri-
methylsilyl cyanide) under our previously reported conditions.21 Unfortunately,
these reactions failed to give the desired products in an enantioselective manner.
Recently, the mechanistic studies from the Liu group30 revealed that ligands readily
dissociated from a copper center in the reactions of (L)nCu(CF3)3 (L, Bpy or Py) with
alkylzinc reagents. Subsequently, the resulting RCu(CF3)3 underwent direct reduc-
1State Key Laboratory of Organometallic
Chemistry and Shanghai Hongkong Joint
Laboratory in Chemical Synthesis, Center for
tive elimination to form R–CF3 bonds. On the contrary, the CF3 anion is extremely
difficult to disassociate from the copper center,30,31 indicating that the CF3 anion ex-
Excellence in Molecular Synthesis, Shanghai
hibited a stronger binding to the copper center (Scheme 1A, bottom), which is
Institute of Organic Chemistry, University of
similar to the effect of cyanides on the asymmetric cyanation of benzylic radicals.21
Chinese Academy of Sciences, Chinese Academy
of Sciences, 345 Lingling Road, Shanghai 200032,
Therefore, the excess amount of CF3 anion could potentially promote the ligand
China
dissociation from the copper center, making the asymmetric radical trifluoromethy-
2Chang-Kung Chuang Institute, East China
lation extremely difficult.
Normal University, 3663 North Zhongshan Road,
Shanghai 200062, China
3Lead Contact
In order to avoid the detrimental effect of excessive CF3 anions, we turned our atten-
tion to surveying electrophilic trifluoromethylating reagents.32,33 Over the last
*Correspondence: gliu@mail.sioc.ac.cn
https://doi.org/10.1016/j.chempr.2020.07.003
decade, the ring opening of cyclopropanols proceeding through a radical process
2
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to generate a key carbon-centered radical intermediate has been well-established,
especially in the presence of high-valent metal species.34–40 With this model reac-
tion, we communicate herein the asymmetric radical trifluoromethylation reaction,
where the benzylic radical was generated by the copper-catalyzed radical ring open-
+
ing of aryl-substituted cyclopropanols.41–43 Notably, the Togni-I CF3 reagent was
employed as an electrophilic CF3 source, avoiding the presence of excess amounts
of CF3 anion. In addition, a novel bisoxazoline (Box) ligand bearing two quinolinyl
moieties plays a key role in both the reaction efficiency and enantioselectivity
(Scheme 1B).
RESULTS AND DISCUSSION
To test the possibility of the asymmetric radical trifluoromethylation, the radical ring
opening of cyclopropanols was used as a model reaction. We examined the reaction
of cyclopropanol 1a with Togni-I reagent in MeOH at 0ꢀC for 12 h, in the presence of
10 mol % Cu(MeCN)4PF6 and 12 mol % bisoxazoline (Box) L1 as the catalyst. To our
delight, the reaction provided the desired trifluoromethylation product 2a in 36%
yield, albeit with a very low enantioselectivity (7% ee). Encouraged by this result, a
series of different Box ligands were then investigated as shown in Scheme 2A
(Table S1). The ligand L2, bearing gem-methyl and benzyl groups, yielded the prod-
uct 2a with 22% ee; replacing the methyl group with an ethyl group (L3) led to
remarkably increased enantioselectivity (60% ee). The ligand L4, with gem-ethyl
and pyridyl methylene (PyCH2) groups, gave the product 2a in a better yield (40%)
but with a lower enantioselectivity (26% ee); in comparison, introducing a quinolinyl
methylene (QuCH2) group into the ligand L5 resulted in a much better enantioselec-
tivity (64% ee).
Moreover, the enantioselectivity could be further improved to 81% ee by intro-
ducing gem-diQuCH2 groups into the ligand L6. Solvent screening revealed that,
in a mixture of MeOH and CHCl3, the reaction gave the product 2a in slightly better
enantioselectivity (86% ee). In addition, performing the reaction at À10ꢀC could
further increase the enantioselectivity (up to 91% ee). While all the above-mentioned
reactions gave the product 2a in only low to moderate yields, increasing the loading
of catalyst was highly beneficial to the reaction efficiency; the reaction using 20 mol
% Cu(I) and 24 mol % Box L6 delivered the product 2a in 68% yield with 93% ee, and
even better yields (74%) and higher enantioselectivity (95% ee) were obtained using
30 mol % Cu(I) and 36 mol % L6.
In order to elucidate the roles of the quinolinyl moiety in L6, we prepared the ligand
L7 bearing QuCH2 and NpCH2 groups and L8 bearing gem-diNpCH2 groups. The
reaction using L7 afforded product 2a in a 50% yield with 92% ee, while L8 resulted
in a significantly diminished yield (16%) with very low enantioselectivity (5% ee).
These control experiments suggested that the QuCH2 group plays an important
role in the enantioselective trifluoromethylation reaction.
Inspired by our previous studies, a (L*)CuII-CF3 complex was proposed to act as a key
intermediate for the radical coupling reactions (Scheme 1B). Thus, we assumed that
analyzing the structures of (L*)CuBr2 (L* = L6 or L8) complexes should provide more
information for the enantioselective control. However, we failed to get any crystals of
these complexes; instead, complexes (L9)CuBr2 and (L10)CuBr2 (L9 and L10 are
derived from 1-amino-2-indanol) were unambiguously identified as a twisted square
planar geometry by X-ray crystallography. The general trend in enantioselectivity of
the reactions using L9 and L10 is similar to that of the reactions using L6 and L8
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Scheme 2. Optimization of the Reaction Conditions
aReaction was run on a 0.1 mmol scale.b19F-NMR yield with CF3-DMAc as an internal standard.cThe
ee values were determined by HPLC on a chiral stationary phase.dCHCl3/CH3OH
(v/v = 7:3).eReaction at À10ꢀC.fCu(I) catalyst (20 mol %) and ligand (24 mol %).gCu(I) catalyst (30 mol
%) and ligand (36 mol %).hCu(CH3CN)4PF6 (30 mol %) and L9 or L10 (36 mol %) in CHCl3/CH3OH
(v/v = 7:3) at À10ꢀC.
(Scheme 2B, top). Notably, the binding geometry of quinolinyl with Cu in (L9)CuBr2 is
remarkably different than that of naphthyl with Cu in (L10)CuBr2, in that a weak inter-
action between quinoline and the copper center makes a more crowded geometry
4
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Scheme 3. The Effect of CF3 Anion
around the copper center in (L9)CuBr2 than (L10)CuBr2, accounting for higher enan-
tioselectivities in the benzylic radical-trapping step (Scheme 2B, bottom).
To clarify the effect of excess CF3 anions on the enantioselectivity, external nucleo-
philic CF3 reagents, such as (DMPU)2Zn(CF3)2, TMSCF3/CsF were added to the stan-
dard reaction conditions. In comparison to the standard conditions, shown in
Scheme 3 (Table S5), the enantiomeric excess of 2a dramatically decreased, whereas
À
the higher concentration of free CF3 from TMSCF3 gave an even lower ee value
than that of (DMPU)2Zn(CF3)2. This observation is consistent with our hypothesis
that excess CF3 anions exhibit a negative effect on the asymmetric trifluoromethyla-
tion, owing to the competitive coordination to the copper center and the resulting
dissociation of L6.
With the optimized reaction conditions in hand, we then explored the substrate
scope of the asymmetric trifluoromethylation reaction (Scheme 4A). The reaction
tolerated a wide array of functional groups with different electronic nature on the
benzene ring of substrate 1. For example, introducing different groups, such as alkyl,
aryl, halogen, CF3, SCF3, OCF3, and ether at the C4 or C3 position on the benzene
ring furnished the corresponding b-CF3 ketones 2a–2r in good yields (53%–70%)
with excellent enantioselectivities (87%–94% ee). However, ortho-substituted sub-
strates yielded the desired products 2s and 2t in good yields with moderate to
good enantioselectivities (86% ee for 2s and 59% ee for 2t). In addition, the aryl
framework was extended to a naphthalene-derived system (2u, 49% yield and
91% ee). Moreover, substituents adjacent to the hydroxyl group in aryl-substituted
cyclopropanols 1 can be various alkyl and aryl groups, and all these substrates
gave the desired products 2v–3g in moderate to good yields (42%–77%) with
good to excellent enantioselectivity (80%–94% ee). In addition, various functional
groups, such as a halogen, thioether, or thiophene on the alkyl chain were tolerated
under our current conditions. The absolute configuration of (S)-3e was determined
by X-ray. More importantly, the reaction of a substrate derived from lithocholic
acid also proceeded smoothly to afford the desired product 3h in a 70% yield with
excellent diastereoselectivity (91% de). To demonstrate the scalability of our
method, the asymmetric trifluoromethylation was performed on a gram scale to
give 1.22 g of the product 2g without loss of reaction yields and enantioselectivity
(59% yield, 93% ee). Moreover, when the catalyst loading decreased to 20 mol %
or 15 mol %, the reaction also proceeded smoothly to give the desired products
(2d, 2g, 2i, 2n, and 2p) with the same or slightly diminished yields and/or selectivities
(Scheme 4B). Unfortunately, reactions of 2-alkylcyclopropanols provided the desired
trifluoromethylation products with poor enantioselectivity, presumably owing to the
involvement of unstable transient alkyl-substituted carbon-centered radicals, which
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Scheme 4. Substrate Scope
aReaction conditions: 1 (0.2 mmol), Togni-I (0.3 mmol), Cu(CH3CN)4PF6 (30 mol %), L6 (36 mol %) in
2.0 mL CHCl3/MeOH (v/v = 7:3) at À10ꢀC.bIsolated yield and enantiomeric excess (ee) were
determined by HPLC on a chiral stationary phase.c6.0 mmol scale (2g 1.22 g).dCu(CH3CN)4PF6
(20 mol %), L6 (24 mol %).eCu(CH3CN)4PF6 (15 mol %), L6 (18 mol %).
is unable to be trapped enantioselectively by the chiral copper(II) intermediate at the
moment.
Finally, the compatibility of functional groups and heteroarenes was surveyed by sub-
jecting various additives into the standard reaction conditions of 1a. As shown in
Scheme 5, excellent functional group compatibility was observed. For instance,
various functional groups, such as ester A1, phenol A2, aldehyde A3, pyridine-N-ox-
ide A4, amine A5, nitrile A6, and amides A7 and A8, were well tolerated, which nearly
had no effect on both reactivity and enantioselectivity of the standard reaction. More-
over, these additives were remained in the catalytic system with good to excellent
levels of mass balance. In addition, similar results were also observed in the cases
6
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Scheme 5. Functional-Group Tolerance
aReaction was run on a 0.1 mmol scale.b19F-NMR yield with CF3-DMAc as an internal standard and the ee values were determined by HPLC on a chiral
stationary phase.cGC yield.
recv, recovered additives.
of indoles A9 and A10, quinoline A11, benzofuran A13, thiophenes A14 and A15, and
benzoxazole A16, and all of additives were survived very well except for free indole
A9. However, pyridine A12 proved to have a detrimental effect on the reaction.
Transformation and Application
To showcase the synthetic utility of our method, further transformations of the enan-
tiomerically enriched b-CF3 ketones were surveyed (Scheme 6). For example, 2g
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Scheme 6. Synthetic Applications
Reaction conditions:
(A) PhNHNH2, HOAc.
(B) Propylphosphonic anhydride, 2-amino-acetophenone in DMF.
(C) cat. (S)-CBS, BH3.SMe2.
(D) cat. Pd(PPh3)4, 3-Pyridylboronic acid, K2CO3 in dioxane/H2O.
(E) (1) TFA, m-CPBA in DCM; (2) Pd/C, H2 in THF.
(F) (1) (COCl)2, (R)-1-(1-naphthyl)ethylamine in DCM; (2) BH3 in THF.
could be readily converted into indole 4 in a 72% yield with 91% ee and quinoline 5 in
a 45% yield with 92% ee. The ketone moiety was reduced to give an optically pure
b-CF3 alcohol 6 in a 88% yield with a 5.3:1 dr ratio by using (S)-CBS as the catalyst,
and two isomers were separated by silica column. In addition, 2g was converted into
7 via a cross-coupling reaction. Furthermore, our present asymmetric trifluorome-
thylation reaction was applied to the synthesis of an (R)-CF3-modified analog of ci-
nacalcet, a drug for the treatment of secondary hyperparathyroidism in patients
with chronic kidney disease and hypocalcemia.44 The trifluoromethylation product
3i (91% ee) underwent sequential Baeyer-Villiger oxidation and hydrogenation to
yield b-CF3 acid 8 in a 88% yield without the loss of optical purity. Compound 8
was further converted into CF3-modified cinacalcet 9 through a condensation and
reduction sequence in a 52% overall yield with a 96% de, providing an opportunity
to survey the fluorine effects on the biologically active cinacalcet.
To provide more insight into the possible radical reaction mechanism, several con-
trol experiments were conducted. When a,b-unsaturated ketone 10 was subjected
to the reaction of 1v under the standard conditions, only the ring-opened product
2v was obtained in a 53% yield with 93% ee, ruling out the possible asymmetric
8
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Scheme 7. Mechanistic Studies
Michael addition pathway (Schemes 7A and S1). By adding 2 equiv of CBrCl3 as a
radical scavenger to the model reaction, the bromination product 11 was produced
in 25% yield (Schemes 7B and S2). In addition, reactions of two opposite enantio-
mers, (+)-1a and (À)-1a, delivered the same enantiomer 2a in similar yields with
the same enantioselectivity (93% ee) (Schemes 7C and S3). These observations sug-
gested that the benzylic radical was involved in the asymmetric trifluoromethylation
reaction. In fact, the benzylic radical was also trapped by DMPO (5,5-dimethyl-1-pyr-
roline N-oxide), and the resulting more stable radical 12 was detected by EPR (elec-
tron paramagnetic resonance) and high resolution mass spectrometry, which also
demonstrated the involvement of the benzylic radical (Schemes 7D and S4; Fig-
ure S1). Moreover, when 1 equiv of styrene was subjected to the reaction of 1s under
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Figure 1. Reaction of 1s Monitored by Mass Spectrometry In Situ
Qu, quinolinyl; CF, chemical formula.
the standard conditions, besides the ring-opening trifluoromethylation product 2s,
the radical addition product 14 and the benzylic radical self- and cross-coupling
products 13 and 15 were also observed (Schemes 7E and S5). We reasoned that
the initial oxidation of L*Cu(I) with Tongi-I led to the formation of a (L*)CuIIICF3 spe-
cies. Then, homolytic cleavage of CuIII-CF3 bonds occurred to generate a CF3
radical, followed by radical addition to the styrene, leading to the formation of
13–15 (right). However, in the absence of styrene, the (L*)CuIIICF3 complex reacted
with 1s to generate a benzylic radical int-I via a radical ring-opening pathway, result-
ing in the formation of trifluoromethylated product 2s (left).
We also analyzed a crude mixture of the reaction of 1s by mass spectrometry in situ
(Figures 1 and S3). A peak of 679.40 (m/z), assigned to (L6)Cu(I), was observed as the
predominant species in the solution, indicating that the oxidation of (L6)Cu(I) with
Togni-I might be the rate-determining step (Figure 1A). Moreover, the 19F NMR (nu-
clear magnetic resonance) spectrum of the reaction mixture showed a signal at À25
ppm, which is consistent with the data of CuICF3 reported in the literature (see Fig-
ure S4).45 Furthermore, there are two peaks of 817.10 (m/z) and 913.24 (m/z) (Fig-
ure 1B) obtained in the mixture, which could be derived from the same key (L6)Cu(III)
species C bearing two CF3 and cyclopropanoxide after losing a CF3 anion (G) and
propropanoxide (H), respectively (Scheme 8). Finally, a peak of 981.20 (m/z) (Fig-
ure 1B) assigned to (L6)Cu(II) species D generated from the (L*)Cu(III) species B by
losing CF3 radical (Scheme 8) was also observed. Moreover, the MS spectrum
showed a much stronger signal at 679.40 (m/z) and very weak signals at 817.10
(m/z), 913.24 (m/z), and 981.20 (m/z) (Figure 1A), indicating that the concentration
of CuICF3 species A is much higher than those of Cu(III) species B and C. This obser-
vation revealed that the oxidation of Cu(I) species A to Cu(III) species B possibly con-
tributes to the rate-determining step. This conclusion is also supported by additional
kinetic studies: the reaction exhibited a first order dependence on the concentration
of the copper catalyst [Cu(I)/L6 = 1:1.2] and the saturated dependence on both
Togni-I and cyclopropanol substrate (for details, see Figures S7–S9).
Based on these studies, a proposed mechanism is described in Scheme 8. Initially, the
oxidation of CuI with Togni-I-containing complex I as the rate-determining step (for
details, see Figures S5 and S10) yielded a Cu(III) intermediate B, which subsequently
reacted with cyclopropanols 1 to give a complex C. Homolytic cleavage of CuIII–O
10
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Scheme 8. Proposed Mechanism
bonds in complex C led to the formation of a (L*)CuII(CF3)2 species F and an alkoxide
radical E. Fast radical ring opening of the alkoxide radical E formed a benzylic radical,
which was enantioselectively trapped by the (L*)CuII(CF3)2 species F via a possible
Cu(III) intermediate, affording the final enantioenriched trifluoromethylation.
Conclusion
In conclusion, we have developed a copper-catalyzed enantioselective oxidative
trifluoromethylation of aryl-substituted cyclopropanols via copper-catalyzed
radical relay, which provides an efficient and straightforward access to b-CF3 ke-
tones in good yields with good to excellent enantioselectivity. Further mechanistic
studies and new asymmetric radical trifluoromethylations are ongoing in our
laboratory.
EXPERIMENTAL PROCEDURES
Resource Availability
Lead Contact
Further information and requests for resources should be directed to and will be ful-
filled by the Lead Contact, Guosheng Liu (gliu@mail.sioc.ac.cn).
Materials Availability
This study did not generate new unique reagents.
Data and Code Availability
The crystallography data have been deposited at the Cambridge Crystallographic
Data Center (CCDC) as CCDC: 1956334 (3e), 1956335 [(L9)CuBr2], and 1956336
[(L10)CuBr2] and can be obtained free of charge from www.ccdc.cam.ac.uk/
getstructures.
Full experimental procedures are provided in the Supplemental Information.
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SUPPLEMENTAL INFORMATION
Supplemental Information can be found online at https://doi.org/10.1016/j.chempr.
2020.07.003.
ACKNOWLEDGMENTS
We are grateful for financial support from the National Natural Science Foundation of
China (NFSC, nos. 21532009, 21790330, 91956202, 21821002, and 21761142010),
the Science and Technology Commission of Shanghai Municipality (nos.
17JC1401200 and 19590750400), the Strategic Priority Research Program (no.
XDB20000000), the Key Research Program of Frontier Science (QYZDJSSWSLH055),
and the International Partnership Program (121731KYSB20190016) of the Chinese
Academy of Sciences.
AUTHOR CONTRIBUTIONS
C.J. and H.Z. conducted the experiments. L.W. and Y.-L.G. conducted the MS spec-
trum experiments. C.J. and G.L. designed the experiments and analyzed the data.
G.L. and P.C. wrote the paper.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: October 9, 2019
Revised: February 24, 2020
Accepted: July 3, 2020
Published: July 30, 2020
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Cyclopropanols, Chem (2020), https://doi.org/10.1016/j.chempr.2020.07.003
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