Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Free Carboxylic Acids

Article abstract of DOI:10.1021/jacs.8b03509

A monoprotected aminoethyl amine chiral ligand based on an ethylenediamine backbone was developed to achieve Pd-catalyzed enantioselective C(sp³)-H arylation of cyclopropanecarboxylic and 2-aminoisobutyric acids without using exogenous directing groups. This new chiral catalyst affords new disconnection for preparing diverse chiral carboxylic acids from simple starting materials that are complementary to the various ring forming approaches.

Full text of DOI:10.1021/jacs.8b03509

Subscriber access provided by Kaohsiung Medical University
Communication
Pd(II)-Catalyzed Enantioselective C(sp3)–H Arylation of Free Carboxylic Acids
Peng-Xiang Shen, Liang Hu, Qian Shao, Kai Hong, and Jin-Quan Yu
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 09 May 2018
Downloaded from http://pubs.acs.org on May 9, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
Pd(II)-Catalyzed Enantioselective C(sp3)–H Arylation of Free Carboxylic Acids
8
9
Peng-Xiang Shen, Liang Hu, Qian Shao, Kai Hong and Jin-Quan Yu*
†Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
RECEIVED DATE (automatically inserted by publisher); yu200@scripps.edu
ligand that enables enantioselective C–H arylation of a broad
Abstract: A mono-protected aminoethyl amine (MPAAM)
range of cyclopropanecarboxylic acid, as well as the 2-
chiral ligand based on an ethylenediamine backbone was
aminoisobutyric acid.
developed to achieve Pd-catalyzed enantioselective C(sp3)–H
arylation of cyclopropanecarboxylic and 2-aminoisobutyric
acids without using exogenous directing groups. This new chiral
catalyst affords new disconnection for preparing diverse chiral
carboxylic acids from simple starting materials that are
complementary to the various ring forming approaches.
The development of asymmetric syntheses of chiral
cyclopropanes8 continues to attract attention because of their
prevalence in biologically active natural products and
pharmaceuticals.9
We,
therefore
selected
cyclopropanecarboxylic acid as a model substrate for our ligand
development. Notably, our previous enantioselective C–H
coupling of cyclopropanecarboxamides with Ar-Bpin required
the presence of α-quaternary carbon centers (Scheme 1).2a,2c,10
Desymmetrization through C–H activation holds the
potential to become a broadly useful chiral technology due to
the widespread presence of symmetric prochiral C(sp3)–H bonds
in the majority of organic molecules.1 Pd(II)-catalyzed
enantioselective intermolecular C(sp3)–H activation was
recently made possible by the combination of a weakly
coordinating directing group and a chiral bidentate ligand.2-5
This strategy was firstly demonstrated by the development of N-
perfluoroaryl amide-directed enantioselective C–H cross-
coupling of α-quaternary cyclopropanecarboxamides using
mono-N-protected amino acids (MPAA) as the chiral ligands.2a
Recently, chiral bidentate quinoline ligands were developed to
realize enantioselective functionalization of methylene C(sp3)–
H bond of acyclic N-perfluoroaryl carboxamides to construct β-
chiral centers,2c while bidentate oxazoline ligands enabled
enantioselective C(sp3)–H functionalization of gem-dimethyl of
N-perfluoroaryl or methoxy carboxamides for the construction
of α-chiral centers.2d However, substrates in these reactions
require pre-installed directing groups which need to be removed
after C–H functionalization (Scheme 1). Following the same
notion of achieving protecting group free synthesis,6 we
embarked on the development of enantioselective C–H
activation of carboxylic acids without using exogenous directing
groups.
Scheme 1. Bidentate Ligands Developed for Enantioselective
C(sp3)–H Functionalization of Carboxylic Acids
Directed functionalization of C(sp3)–H bonds of carboxylic
acids without installing an external directing group remains a
significant challenge despite recent advances using
pyridine/quinoline and MPAA ligands.7 These difficulties
escalate in the development of enantioselective C–H activation
reactions. First, C(sp3)–H activation reactions of free carboxylic
acids suffer from low reactivity due to the weak directing ability
of the carboxyl groups. Second, the conformation of the metal-
carboxylate complex is more flexible than that of the metal-
amide directing group complex, which could cause problems for
stereocontrol. Indeed, our previously developed bidentate
acetyl-protected aminoethyl quinoline ligand only had limited
success with a single special substrate, phthalyl-protected 1-
aminocyclopropanecarboxylic acid.2c Therefore, we set out to
develop a new type of ligand that could achieve more effective
control of enantioselectivity with free carboxylic acids. Herein
we report the development of ethylenediamine derived chiral
Based on our previous chiral bidentate MPAA, quinoline, and
oxazoline ligands, it is known that the acetyl-protected amino
group (NHAc) is a privileged moiety of chiral ligands for
promoting C–H cleavage.2b-2d We, therefore, decided to keep this
motif intact while replacing the carboxyl, quinoline, or
oxazoline with another σ-donor for chelation; Tertiary amines
were chosen as the other σ-donor, because of its distinct
stereochemical implication compared with quinoline and
oxazoline, as well as the more diffuse lone pair of sp3 nitrogen
than sp2 nitrogen. Consequently, we synthesized a series of
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
mono-protected aminoethyl amine (MPAAM) ligands to
group (L16) also reduced the reactivity and selectivity. Hence,
we focused on the modification of the benzyl group. Introducing
substituents to the para or ortho positions on the phenyl group,
as well as replacing phenyl with a naphthalenyl group lowered
the yield (L17-L21). Finally, our previous three classes of chiral
ligands all gave modest/poor yields or enantioselectivity (L22-
L23).
achieve enantioselective C(sp3)–H functionalization of
1
2
3
4
5
6
Table 1. Ligand Screening for Enantioselective Arylation of
Cyclopropanecarboxylic Acida,b
7
8
Table 2. The Scope of Aryl Iodides for Enantioselective Arylation
of Cyclopropanecarboxylic Acida,b
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a Conditions: 1 (0.2 mmol), 2a (2.0 equiv), Pd(OAc)
Ag CO (1.5 equiv), Na CO
(1.5 equiv), HFIP (0.25 mL), 80 °C, air, 16 h. b 1H NMR
yields, using CH Br as an internal standard. The er values were determined by SFC
2
(10 mol%), ligand (20 mol%),
2
3
2
3
2
2
analysis on a chiral stationary phase.
free carboxylic acids (Table 1). First, various N-alkyl tertiary
amine ligands were tested. Despite a moderate background
reaction in the absence of ligands (Table 1), effective binding of
the ligands and possible ligand acceleration afforded significant
enantioselectivity. The comparison of the results from L1 to L4
indicates that steric hindrance on the tertiary amines reduces the
reactivity. For example, the diisopropylamine ligand only
provided 8% yield of the product with almost no
enantioselectivity. Cyclic amine ligands L5 and L6 were inferior
in both reactivity and enantioselectivity. Notably, replacing
acetyl with other protecting groups led to a complete loss of
reactivity (L7-L10). Ligands with different side chains were also
examined. Among different substituents, a benzyl group (L1)
gave the best yield of 82% and highest er of 97:3, while,
isopropyl (L11), sec-butyl (L12), tert-butyl (L13), and isobutyl
groups (L14) gave slightly lower yields and enantioselectivities.
Surprisingly, phenyl group substitution (L15) provided only 20%
yield and low enantioselectivity. The less hindered homobenzyl
a Conditions 1 (0.2 mmol), 2 (2.0 equiv), Pd(OAc)2 (10 mol%), L1 (20 mol%), Ag2CO3
b
(1.5 equiv), Na2CO3 (1.5 equiv), HFIP (0.25 mL), 80 °C, air, 16 h. Isolated yields.
c
The er values were determined by SFC analysis on a chiral stationary phase.
Conditions 2a (0.2 mmol), 1 (2.0 equiv), Pd(OAc)2 (10 mol%), L1 (20 mol%), Ag2CO3
(1.0 equiv), Na2CO3 (1.5 equiv), HFIP (0.25 mL), 80 °C, air, 16 h. d Using Pd (5 mol%)
e
and L1 (10 mol%). Using AgOAc (3.0 equiv) instead of Ag2CO3 (1.5 equiv),
NaHCO3 (1.5 equiv) instead of Na2CO3 (1.5 equiv). f Using 2 (1.5 equiv).
With the high-yielding and highly selective conditions in hand,
we examined the scope of aryl iodides (Table 2). The majority of the
aryl iodides containing electron-withdrawing and electron-
donating groups afforded the desired products in good yields and
high enantioselectivities (up to 98:2 er). Aryl iodides bearing
electron-withdrawing groups such as para-methoxycarbonyl (3a),
para-acetyl (3b), para-trifluoromethyl (3d), meta-trifluoromethyl
(3k) and ortho-methoxycarbonyl (3t) gave slightly higher yields
than other aryl iodides. However, aryl iodide with a nitro group (3c)
gave 53% yield of the product with 90:10 er. Iodobenzonitrile (3e)
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
also afforded a lower yield but with high enantioselectivity. Note
cyclopropanecarboxylic acids are also suitable substrates for this
reaction. Arylation of α-ethyl (5e), butyl (5f), and chloropentyl
(5h) cyclopropanecarboxylic acids under 60 °C afforded the
mono-arylated products in good yields and er. Surprisingly, α-
phenylpropyl substitution reduced the yield to 58% (5g).
Although α-benzyl containing substrates (5i and 5j) decomposed
under these conditions, replacement of Ag2CO3 with AgOAc
provided desired products in moderate yields and high
enantioselectivities. Benzyl-protected 1-hydroxymethyl (5k)
and phthalyl-protected 1-aminomethyl cyclopropanecarboxylic
acids (5l) provided good yields and excellent enantioselectivities.
These β-hydroxyl and β-amino-cyclopropanecarboxylic acid
motifs are recurrent structures in bioactive molecules.12
1
2
3
4
5
6
7
8
that aryl iodides containing bromo (3h), phosphonate (3j), and
aldehyde (3m) afforded the desired products in high yields and
good enantioselectivities. In addition to substituted phenyl
iodides, heteroaryl iodides such as 2-acetyl-5-iodothiophene (3u)
and 5-iodo-2-furaldehyde (3v) could also be tolerated in this
reaction, providing moderate yields and high er. The reaction
with 4-iodo-2-(trifluoromethyl)pyridine gave the arylated
product in 61% yield with 88:12 er (see Supporting Information).
The absolute configurations of the arylated compound were
confirmed by optical rotation mesurements (see Supporting
Information). The reaction with 5 mol% of Pd(OAc)2 provided a
slightly lower yield of product (3a) with the same
enantioselectivity (Table 2). The use of 1.2 equiv of aryl iodide
gave the arylated product in lower yield (61%) with 97:3 er (see
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4. Enantioselective Arylation of 2-Aminoisobutyric
Acida,b
Supporting Information).
The reaction using methyl
iodobenzoate as the limiting reagent and a lower loading of silver
salt also afforded a higher yield and similar enantioselectivity
(3a).
Table 3.
Enantioselective Arylation of
Substituted
Cyclopropanecarboxylic Acids a,b
a
Conditions: 1 (0.1 mmol), 7 (2.5 equiv), Pd(OAc)2 (10 mol%), L1 (20 mol%),
AgOAc (3.0 equiv), NaHCO3 (1.5 equiv), HFIP, 80 °C, air, 24 h. b Isolated yields. The
er values were determined by SFC analysis on a chiral stationary phase. c Isolated as
the corresponding methyl ester.
The performance of this new chiral ligand was further
evaluated in the desymmetrization of geminal dimethyl groups
for the enantioselective arylation of phthalyl-protected 2-
aminoisobutyric acid (Table 4). Such reactions could provide a
simple avenue for the synthesis of diverse chiral α-amino acids.
While aryl iodides bearing different substituents gave similar
yields of products, the enantioselectivities varied. Electron-
neutral
group-substituted
aryl
iodides
gave
good
enantioselectivities, aryl iodides containing electron-
withdrawing groups (7a, 7b, and 7g) provided lower er. Since
aryl iodides are not involved in the enantio-determining C–H
activation step, it is possible that one of the chiral palladacycle
intermediates from this particular substrate is less reactive in the
oxidative addition step with the aryl iodide, thereby
contributing to the enantioselectivity partially. A further
extensive mechanistic study will be conducted to rationalize this
observation. The absolute configuration of the product was
confirmed by X-ray crystallographic analysis (see Supporting
Information).
a
Conditions 4 (0.2 mmol), 2a (2.0 equiv), Pd(OAc)2 (10 mol%), L1 (20 mol%),
Ag2CO3 (1.5 equiv), Na2CO3 (1.5 equiv), HFIP (0.25 mL), 80 °C, air, 16 h. b Isolated
c
yields. The er values were determined by SFC analysis on a chiral stationary phase.
60 °C. d Using AgOAc (3.0 equiv) instead of Ag2CO3 (1.5 equiv), NaHCO3 (1.5 equiv)
instead of Na2CO3 (1.5 equiv), 60 °C.
A wide range of α-substituted cyclopropanecarboxylic acids
were also tested using methyl iodobenzoate as the coupling
partner (Table 3). 1-Aryl-1-cyclopropanecarboxylic acids (5a-d),
which are an important motif in pharmaceutical chemistry,11
were arylated to give the desired products in excellent yields and
enantioselectivities. Interestingly, C(sp2)–H arylation of the α-
phenyl groups did not occur. Chloro (5b), bromo (5c) and
trifluoromethyl (5d) substituents on the phenyl group of
substrates were all well tolerated in this reaction. α-Alkyl
To further demonstrate the utility of this new methodology, a
late-stage C–H functionalization of a promising drug candidate
for neurological disorders, Itanapraced,13 was performed. The
reaction proceeded smoothly, and the modified molecule was
obtained in high yield and with excellent enantioselectivity (eq
1).
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides;
Wiley: New York, 1998. (b) Doyle, M. P.; Protopopova, M. N. Tetrahedron
1998, 54, 7919. (c) Denmark, S. E.; Beutner, G. In Cycloaddition Reactions
in Organic Synthesis; Kobayashi, S., Jørgensen, K. A., Eds.; Wiley-VCH:
Weinheim, Germany, 2002; pp 85ff. (d) Lebel, H.; Marcoux, J.-F.; Molinaro,
C.; Charette, A. B. Chem. Rev. 2003, 103, 977. (e) Lou, Y.; Horikawa, M.;
Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126,
8916. (f) Goudreau, S. R.; Charette, A., B. J. Am. Chem. Soc. 2009, 131,
15633. (g) Zhu, S.; Cui, X.; Zhang, X. P. Eur. J. Inorg. Chem. 2012, 430.
(h) Wang, Y.; Wen, X.; Cui, X.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc.
2017, 139, 1049.
1
2
3
4
5
6
7
8
In summary, we have developed a new class of chiral mono-
protected aminoethyl amine ligands which enable the
enantioselective C–H activation of free carboxylic acids without
using exogenous directing groups. Enantioselective C–H
arylation of simple cyclopropanecarboxylic acid and phthalyl-
protected 2-aminoisobutyric acid provides a new synthetic
disconnection for the asymmetric synthesis of diverse chiral
carboxylic acids. The successful design of this new ligand to
match the weakly coordinating carboxylic acid for stereocontrol
offers a framework for understanding the chiral induction in
C(sp3)–H activation.
(9) Talele, T. T. J. Med. Chem. 2016, 59, 8712.
(10)For Pd(0) and Rh(I)-catalyzed intramolecular enantioselective C–H
functionalization of cyclopropanes, see (a) Saget, T.; Cramer, N. Angew.
Chem., Int. Ed. 2012, 51, 12842. (b) Pedroni, Saget, T.; Donets, P. A.;
Cramer, N. Chem. Sci. 2015, 6, 5164; (c) Pedroni, J.; Cramer, N. Angew.
Chem. Int. Ed. 2015, 54, 11826; (d) Lee, T.; Hartwig, J. F. Angsew. Chem.,
Int. Ed. 2016, 55, 8723; (e) Ladd, C. L.; Charette, A. B. Org. Lett. 2016, 18,
6046. (f) Pedroni, J.; Cramer, N. J. Am. Chem. Soc. 2017, 139, 12398.
(11)Peretto, I.; Radaelli, S.; Parini, C.: Zandi, M.; Raveglia, L. F.; Dondio, G.;
Fontanella, L.; Misiano, P.; Bigogno, C.; Rizz, A.; Riccardi, B.; Biscaioli,
M.; Marchetti, S.; Puccini, P.; Catinella, S.; Rondelli, I.; Cenacchi, V.;
Bolzoni, P. T.; Caruso, P.; Villetti, G.; Facchinetti, F.; Del Giudice, E.;
Moretto, N.; Imbimbo, B.P. J. Med. Chem. 2005, 48, 5705.
(12)(a) MITSUBISHI TANABE PHARMA CORPORATION; Sakurai, O.;
Saruta, K; Hayashi, N.; Goi, T; Morokuma, K.; Tsujishima, H.; Sawatomo,
H.; Shitama, H.; Imashiro, R. WO Patent 2012/81736, 2012. (b) Edgar, D.
M.; Hangauer, D. G.; Shiosaki, K.; Solomon, M.; White, J. F. US Patent
2006/63755, 2006.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Acknowledgments. We gratefully acknowledge The Scripps
Research Institute, the NIH (NIGMS 2R01 GM084019) and
Shanghai RAAS Blood Products Co. Ltd. for financial support.
We thank Dr. Jason Chen from Automated Synthesis Facility,
The Scripps Research Institute for his assistance with 2D
HPLC/SFC analysis. This communication is dedicated to
Professor Elias J. Corey on the occasion of his 90th birthday.
(13)CHIESI FARMACEUTICI S.P.A. WO Patent 2004/74232, 2004.
Supporting Information Available: Experimental procedures
and spectral data for all new compounds (PDF). Crystallographic
data (CIF). These materials are available free of charge via the
Internet at http://pubs.acs.org.
References
(1) For selected reviews of enantioselective C–H Functionalization: (a) Giri, R.;
Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem. Soc. Rev. 2009, 38,
3242. (b) Newton, C. G.; Wang, S.-G.; Oliveira, C. C.; Cramer, N. Chem.
Rev. 2017, 117, 8908. (c) Saint-Denis, T. G.; Zhu, R.-Y.; Chen, G.; Wu, Q.-
F.; Yu, J.-Q. Science 2018, 359, 759.
(2) (a) Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu, J.-Q. J. Am. Chem.
Soc. 2011, 133, 19598. (b) Xiao, K.-J.; Lin, D. W.; Miura, M.; Zhu, R.-Y.;
Gong, W.; Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 8138. (c) Chan,
K. S. L.; Fu, H.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 2042. (d) Chen,
G.; Gong, W.; Zhuang, Z.; Andra, M. S.; Chen, Y.-Q.; Hong, X.; Yang, Y.-
F.; Liu, T.; Houk, K. N.; Yu, J.-Q. Science 2016, 353, 1023. (e) Wu, Q.-F.;
Shen, P.-X.; He, J.; Wang, X.-B.; Zhang, F.; Shao, Q.; Zhu, R.-Y.; Mapelli,
C.; Qiao, J. X.; Poss, M. A.; Yu, J.-Q. Science 2017, 355, 499.
(3) For the preliminary result of enantioselective C(sp3)–H functionalization
using mono-N-protected amino acid ligands (MPAA) and pyridine directing
group: Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q. Angew. Chem., Int.
Ed. 2008, 47, 4882.
(4) For selected Pd(0)-catalyzed intramolecular enantioselective C–H
functionalization see: (a) Nakanishi, M.; Katayev, D.; Besnard, C.; Kꢀndig,
E. P. Angew. Chem., Int. Ed. 2011, 50, 7438. (b) Anas, S.; Cordi, A.; Kagan,
H. B. Chem. Commun. 2011, 47, 11483. (c) Saget, T.; Lémouzy, N.; Cramer,
N. Angew. Chem., Int. Ed. 2012, 51, 2238. (d) Martin, N.; Pierre, C.; Davi,
M.; Jazzar, R.; Baudoin, O. Chem. Eur. J. 2012, 18, 4480. (e) Zhu, C.; Wang,
D.; Zhao, Y.; Sun, W.-Y.; Shi, Z. J. Am. Chem. Soc. 2017, 139, 16486.
(5) For Pd (II)-catalyzed enantioselective C–H functionalization using
phosphoric acids/amides ligands (a) Yan, S.-B.; Zhang, S.; Duan, W.- L.
Org. Lett. 2015, 17, 2458. (b) Wang, H.; Tong, H.-R.; He, G.; Chen, G.
Angew. Chem., Int. Ed. 2016, 55, 15387. (c) Jain, P.; Verma, P.; Xia, G.; Yu,
J.-Q. Nat. Chem. 2016, 353, 1023.
(6) Young, I. S.; Baran, P. S. Nat. Chem. 2009, 1, 193.
(7) (a) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunder,
L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510. (b) Chen, G.; Zhuang,
Z.; Li, G.-C.; Saint-Denis, T. G.; Xiao, Y.; Joe, C. L.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2017, 56, 1506. (c) Zhu, Y.; Chen, X.; Yuan, C.; Li, G.;
Zhang, J.; Zhao, Y. Nat. Commun. 2017, 8, 14904. (d) Ghosh, K. K.; van
Gemmeren, Manual. Chem. Eur. J. 2017, 23, 17697.
(8) For selected reviews and reactions of asymmetric cyclopropanation, see: (a)
Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment