Redox-Neutral β-C(sp3)-H Functionalization of Cyclic Amines via Intermolecular Hydride Transfer

Article abstract of DOI:10.1021/acs.orglett.9b03004

Herein, we report the first redox-neutral and transition-metal-free β-C(sp³)-H functionalization of cyclic amines via a consecutive intermolecular hydride transfer process. A series of N-aryl pyrrolidines and N-aryl 1,2,3,4-tetrahydropyridines decorated with CF₃ and carboxylic ester functionalities are directly accessed in good yields from pyrrolidines and piperidines. This work pushes forward the application of the intermolecular hydride transfer strategy in one-step assembly of molecular complexity.

Full text of DOI:10.1021/acs.orglett.9b03004

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Redox-Neutral β‑C(sp3)−H Functionalization of Cyclic Amines via
Intermolecular Hydride Transfer
Lan Zhou,† Yao-Bin Shen,† Xiao-De An,† Xian-Jiang Li,⊥ Shuai-Shuai Li,*,† Qing Liu,§
and Jian Xiao*,†,‡
†Shandong Province Key Laboratory of Applied Mycology, College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural
University, Qingdao, 266109, China
‡College of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China
§College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, China
⊥Shandong Kangqiao Biotechnology Co. Ltd., Binzhou, 256500, China
S
* Supporting Information
ABSTRACT: Herein, we report the first redox-neutral and
transition-metal-free β-C(sp3)−H functionalization of cyclic
amines via a consecutive intermolecular hydride transfer
process. A series of N-aryl pyrrolidines and N-aryl 1,2,3,4-
tetrahydropyridines decorated with CF3 and carboxylic ester
functionalities are directly accessed in good yields from
pyrrolidines and piperidines. This work pushes forward the
application of the intermolecular hydride transfer strategy in
one-step assembly of molecular complexity.
redox-neutral and transition-metal-free β-C(sp3)−H function-
unctionalized cyclic amines are prevalent in numerous
alization of cyclic amines is underdeveloped (Scheme 1d).
Fnatural products and pharmaceutical molecules, which are
increasingly momentous targets in drug discovery.1 Thus,
various synthetic methodologies are developed for elaborate
diversification of cyclic amines. Among the various methods
that enable the direct C(sp3)−H functionalization of amines,
the vast majority of them are devoted to studies regarding the
α-position of amines.2 However, the reports on direct
functionalization of challenging and poorly reactive β-
C(sp3)−H bonds of amines are relatively rare. In this context,
the transition-metal- and/or oxidant-based reagents have been
employed to achieve direct β-C(sp3)−H functionalization of
amines, such as the directing groups assisted and palladium-
catalyzed functionalization (Scheme 1a),3 transition-metal-
catalyzed hydrogen-borrowing reactions (Scheme 1b)4 and
stoichiometric amounts of oxidants promoted β-C(sp3)−H
functionalization (Scheme 1c).5 Despite these advances, the
Redox-neutral C−H functionalizations initiated by hydride
transfer (HT) enabled the rapid buildup of molecular
complexity with high atom and step economy.6 Recent
decades have witnessed the domination of intramolecular
hydride transfer triggered C−H functionalizations,7 and taking
advantage of the intermolecular hydride transfer to achieve the
diversity-oriented C−H functionalizations has been a long-
standing challenge.8−10 Very recently, the direct β-C(sp3)−H
functionalization of amines has been realized via intermolec-
ular hydride transfer by the Chang group9 and Ma group10
with B(C6F5)3 as a transient hydride acceptor. Nevertheless,
these sporadic examples only involve a single intermolecular
hydride transfer process and, to the best of our knowledge, the
transformation containing consecutive intermolecular hydride
transfer to tackle synthetic obstacles, such as β-C(sp3)−H
functionalization of amines, has never been reported.
Inspired by our research efforts on hydride transfer
reactions,11 we intend to design a new reaction cascade
initiated by intermolecular hydride transfer for β-C(sp3)−H
functionalization of amines. As shown in Scheme 2, we
envisage that an electrophile could trigger the first
intermolecular hydride transfer from amine 1 to generate
iminium I. The subsequent isomerization of I would afford
enamine II, which could trap another molecule of electrophile
to form the β-functionalized iminium ion III. Eventually, the
Scheme 1. β-C(sp3)−H Functionalization of Amines
Received: August 22, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03004
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Design of a New Reaction Cascade Involving
Consecutive Intermolecular Hydride Transfer
Table 1. Optimization of Direct β-C(sp3)−H
a
Functionalization of Cyclic Amines
b
entry
1
2
ratio (1a:2a)
catalyst
solvent
yield (%)
dr
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
TfOH
(−)-CSA
TsOH
PA
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
CHCl3
toluene
dioxane
THF
DMSO
DCE
DCE
DCE
90
84
82
53
87
77
83
80
80
90
93
75
94
89
84
92
1.5:1
2:1
c
3
4
1.9:1
1.5:1
2.3:1
1.9:1
1.8:1
1.9:1
2.0:1
2.0:1
2.1:1
1.9:1
2.3:1
2.5:1
2.3:1
2.3:1
1.6:1
2:1
d
5
6
7
8
TFA
Sc(OTf)3
Cu(OTf)2
Zn(OTf)2
In(OTf)3
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
−
9
2:1
10
11
12
1.5:1
1.2:1
1:1.5
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
second intermolecular hydride transfer from 1 to III would
furnish the β-functionalized amine 3 and regenerate iminium
ion I, thereby propagating the reaction. This transformation is
triggered by the first intermolecular hydride transfer and
terminated by the second intermolecular hydride transfer. The
key to the success of this transformation is to find a suitable
electrophile, which could not only start up the first hydride
transfer process but also react with enamine intermediate II
and undergo the whole catalytic cycle, thus accomplishing the
β-C(sp3)−H functionalization of cyclic amines. Eventually, we
found that ethyl trifluoropyruvate could serve as a good partner
to accomplish this formidable task (see Supporting Informa-
tion). Herein, we report the first consecutive intermolecular
hydride transfer reaction with amine as the hydride donor and
ethyl trifluoropyruvate as the hydride acceptor, which enables
the achievement of direct β-C(sp3)−H functionalization of
cyclic amines with ethyl trifluoropyruvate. To our knowledge,
this work also represents the first example of transition-metal-
free and redox-neutral β-C(sp3)−H functionalization of amines
via direct hydride transfer.
e
13
f
14
g
15
e
16
e
17
76
80
trace
trace
trace
82
e
18
e
19
−
−
−
2.3:1
2.1:1
2.1:1
e
20
e
21
h
22
i
23
89
58
j
24
a
The reactions were performed with 1a (0.2 mmol), 2a (0.1 mmol),
and 20 mol % of catalyst in 1.0 mL of solvent at 60 °C under air for 48
b
h. Isolated yield after column chromatography; dr was determined by
c
d
1H NMR. (−)-CSA = (−)-10-camphorsulfonic acid. PA = 1,1′-
e
binaphthyl-2,2′-diyl hydrogen phosphate. 10 mol % of TfOH was
f
g
h
used. 5 mol % of TfOH was used. 3 mol % of TfOH was used. 1a
i
At the outset, the feasibility of direct β-C(sp3)−H
functionalization of amines was investigated between 1-
(naphthalen-2-yl)pyrrolidine 1a and ethyl trifluoropyruvate
2a (Table 1). Initially, 20 mol % of Brønsted acids were
employed in 1,2-dichloroethane (DCE) at 60 °C to examine
this reaction. Encouragingly, the expected reaction occurred
smoothly in the presence of these catalysts, furnishing the β-
functionalized amine 3a embedded with CF3-substituted
tertiary alcohol in good yields, albeit with low diastereose-
lectivities (entries 1−5). The best result was obtained with
trifluoromethanesulfonic acid (TfOH), providing 3a in 90%
yield (entry 1). The structure of 3a has been unambiguously
confirmed by X-ray crystallographic analysis (see Supporting
Information). However, the employment of Lewis acid
catalysts failed to improve the reaction efficiency and
diastereoselectivity (entries 6−9). Afterward, the examination
of the ratio of starting materials and catalyst loadings showed
that the ratio of 1a and 2a being 1.2:1 with 10 mol % of TfOH
afforded the best efficiency with slightly higher diastereose-
lectivity (entries 10−15). The subsequent solvent screening
implied that other solvents were all ineffective in this reaction
(entries 16−21). Satisfyingly, the preparation of product 3a
(1.5 g) on a large scale proceeded smoothly, which
demonstrated the scalability of this protocol (entry 22, see
Supporting Information). When 1 equiv of TfOH was used,
(6.0 mmol), 2a (5.0 mmol) in 50 mL of DCE. 0.1 mmol of TfOH.
j
25 °C for 48 h.
this reaction still worked very well, affording 3a in 89% yield
(entry 23). However, the yield decreased dramatically in the
absence of TfOH and only a 58% yield was obtained (entry
24).
With the optimized reaction conditions in hand, the
generality of this protocol was investigated with a variety of
electronically and sterically diverse N-aryl pyrrolidines 1 and
keto esters 2 (Scheme 3). Remarkably, either electron-
donating or -withdrawing substituents on the naphthalene
ring had trivial impacts on this transformation, delivering the
corresponding β-functionalized 1-(naphthalen-2-yl)pyrrolidine
3a−l in moderate to good yields, albeit with unsatisfactory
diastereoselectivities. Intriguingly, the Friedel−Crafts-type
product was not observed, even when strong electron-donating
groups were employed, which illustrated the high chemo-
selectivity of this reaction. It was worth mentioning that a
broad range of functional groups, including halogens (3e, 3f,
3j), ester (3g), boronate (3h), and an acetyl group (3l), were
all well tolerated, demonstrating its robust compatibility for
preparing diversely functionalized target molecules. In addition
to ethyl trifluoropyruvate, methyl trifluoropyruvate and diethyl
2-oxomalonate were also good reaction partners for this
B
DOI: 10.1021/acs.orglett.9b03004
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
is of great importance for drug discovery.1a,13 When 1-(p-
tolyl)piperidine 4a was subjected to the optimal conditions, a
new spot was observed in comparatively lower yield.
Therefore, the careful screening was carried out and finally
the β-alkylated 1,2,3,4-tetrahydropyridine 5a decorated with
CF3 and carboxylic ester groups was obtained in 82% yield in
the presence of 20 mol % of InBr3 and 4 Å molecular sieves
(see Supporting Information). Because of the potential
biological application of β-functionalized 1,2,3,4-tetrahydro-
pyridine with CF3 and carboxylic ester moieties, N-aryl
piperidines were subjected to the established conditions to
investigate the generality (Scheme 4). Remarkably, the
Scheme 3. Substrate Scope for the Synthesis of 3a
a
Scheme 4. Substrate Scope for the Synthesis of 5
a
General conditions: The reactions were performed with 4 (0.1
mmol), 2 (0.2 mmol), InBr3 (20 mol %), and 50 mg of 4 Å MS in 1.0
mL of DCE at 80 °C; isolated yield.
benzene ring carrying electron-donating or -withdrawing
substituents almost had no influence on the reaction efficiency,
furnishing the corresponding products 5a−f in moderate to
good yields. In addition, multisubstituted benzene rings were
also tolerated, albeit furnishing the desired products 5g−i in
comparatively lower yields. Besides, the naphthalene sub-
stituents were also good candidates, obtaining the β-function-
alized enamines 5j−l in 65−84% yields.
To shed light on the reaction mechanism, the mechanistic
studies were conducted (Scheme 5). At first, the unaffected
efficiency of the standard reaction under a N2 atmosphere
excluded the possibility of O2 as an oxidant, which was
consistent with our assumption that ethyl trifluoropyruvate
would serve as an oxidant to oxidize amine to iminium (eq 1).
In order to further confirm the source of hydride donors, the
deuterium labeling experiment between deuterated substrate
[D]-1a and ethyl trifluoropyruvate was performed. The
observation of >99% deuterium at the α-position of [D]-3a
clearly illustrated the redox-neutral chain of this β-C(sp3)−H
functionalization (eq 2). Since there was a precedent that the
enamine intermediate could be in situ generated from N-aryl
pyrrolidin-2-one 6 with LiBHEt3 in several minutes,14
subsequently, ethyl trifluoropyruvate was subjected to the
solution of the enamine generated in situ to meticulously
a
General conditions: The reactions were performed with 1 (0.12
mmol), 2 (0.1 mmol), and TfOH (10 mol %) in 1.0 mL of DCE at 60
°C under air; isolated yield; dr was determined by 1H NMR
b
1
spectroscopy. Total yield determined by H NMR according to the
dr and the isolated yield of one isomer.
transformation, furnishing the desired products 3m and 3n in
76% and 67% yields, respectively. Moreover, the common
benzene rings instead of naphthalenes carrying pyrrolidines
were also fully compatible with this system, giving rise to the
corresponding β-functionalized N-Ph pyrrolidines 3o−u in
50−76% yields. As is well-known, generally, the biological
activities would be enhanced with the introduction of a
trifluoromethyl moiety;12 the current method provided an
efficient route to the β-trifluoromethyl substituted amines.
Unfortunately, it should be noted that when N-α-naphthalene
pyrrolidine and para-position-free N-phenylpyrrolidines were
used as reaction partners, only Friedel−Crafts-type products
were obtained.
In addition to pyrrolidine, we continue to check whether
other azacycles could be applied in this system. The piperidine
motif constitutes the most prevalent nitrogen ring system;
thus, the straightforward late-stage diversification of piperidine
C
DOI: 10.1021/acs.orglett.9b03004
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 5. Mechanistic Studies
Scheme 6. Proposed Mechanism
conformation difference between pyrrolidine and piperidine
rings. The formed vinylogous iminium intermediate V was
reduced immediately by another N-aryl piperidine, furnishing
the β-functionalized enamine 5 and iminium ion I, which
proceeded into the next catalytic cycle.
In conclusion, we have developed the first two consecutive
intermolecular hydride transfer process to realize the β-
C(sp3)−H functionalization of cyclic amines via a redox-
neutral chain process. A series of N-aryl pyrrolidines and N-aryl
1,2,3,4-tetrahydropyridines decorated with CF3 and carboxylic
ester functionalities were directly accessed in good yields from
pyrrolidines and piperidines, which possessed potential
biological activities. The compatibility with gram-scale reaction
further enhanced the synthetic practicality of this protocol. We
are optimistic that these reports will not only offer synthetic
chemists a distinctive toolbox for generation of diverse β-
functionalized amine libraries but also advance the application
of the intermolecular hydride transfer strategy in one-step
assembly of molecular complexity.
examine the reaction process. As expected, the β-functionalized
enamine 7 was isolated in 37% yield without any catalyst,
which certificated our presumption that an enamine was the
key intermediate for this transformation (eq 3). Eventually, the
formation of product [H/D]-3a by reaction of enamine 7 with
deuterated substrate [D]-1a under standard conditions fully
proved the hypothesis that another molecule of amine would
reduce the iminium ion to accomplish the redox-neutral chain
process (eq 4). Besides, the designed experiment to capture
the iminium ion intermediate was conducted with the
employment of substrate 8. To our delight, the α- and β-
position dual functionalized amine 9 was obtained in 81% yield
under the standared reaction conditions (eq 5), which
underwent a cascade [1,5]-hydride transfer/isomerization/
Prins-type reaction/dearomatization process.
On the basis of the experimental observation and literature
precedents, a plausible mechanism was proposed as shown in
Scheme 6. As our initial hypothesis, the amine 1 was oxidized
by ethyl trifluoropyruvate 2a to form iminium ion I and
alcohol 10, initiating the whole catalytic cycle. The existence of
compound 10 has been confirmed by the 19F spectrum (see
Supporting Information). After isomerization of I to II or II′,
the followed nucleophilic addition to ethyl trifluoropyruvate
afforded intermediate III or III′. The intermolecular hydride
transfer from the α-position of pyrrolidine to intermediate III
successively occurred, affording the corresponding β-function-
alized N-aryl pyrrolidine 3 and regenerating the iminium ion 1.
Different from the fate of III, the intermediate III′ suffered
from dehydration preferentially to give IV when N-aryl
piperidine was employed, which might be ascribed to the
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03004.
Experimental procedures and characterization data for
all the products (PDF)
Accession Codes
CCDC 1871940 and 1887048 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: flyshuaishuai@126.com.
*E-mail: chemjianxiao@163.com.
D
DOI: 10.1021/acs.orglett.9b03004
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
ORCID
Letter
2100−2103. (g) Gandamana, D. A.; Wang, B.; Tejo, C.; Bolte, B.;
Gagosz, F.; Chiba, S. Angew. Chem., Int. Ed. 2018, 57, 6181−6185.
(h) Mori, K.; Isogai, R.; Kamei, Y.; Yamanaka, M.; Akiyama, T. J. Am.
Jian Xiao: 0000-0003-4272-6865
Notes
́
Chem. Soc. 2018, 140, 6203−6207. (i) Idiris, F. I. M.; Majeste, C. E.;
Craven, G. B.; Jones, C. R. Chem. Sci. 2018, 9, 2873−2878.
The authors declare no competing financial interest.
̈
(j) Jurberg, I. D.; Peng, B.; Wostefeld, E.; Wasserloos, M.; Maulide,
N. Angew. Chem., Int. Ed. 2012, 51, 1950−1953.
(8) For α-C(sp3)−H functionalization of amines, see: (a) Chen, W.;
Ma, L.; Paul, A.; Seidel, D. Nat. Chem. 2018, 10, 165−169. (b) Shang,
M.; Chan, J. Z.; Cao, M.; Chang, Y.; Wang, Q.; Cook, B.; Torker, S.;
Wasa, M. J. Am. Chem. Soc. 2018, 140, 10593−10601. (c) Tian, J. J.;
Zeng, N. N.; Liu, N.; Tu, X. S.; Wang, X. C. ACS Catal. 2019, 9, 295−
300. (d) Maier, A. F. G.; Tussing, S.; Zhu, H.; Wicker, G.; Tzvetkova,
ACKNOWLEDGMENTS
■
We are grateful for the financial support from the NSFC
(21702117, 21878167). The Natural Science Foundation of
Shandong Province for Distinguished Young Scholars
(JQ201604) and General Project (ZR2017BB005) are also
gratefully acknowledged. The Key Research and Development
Program of Shandong Province (2017GSF218073) and
Qingdao Special Research Foundation of Science and
Technology (19-6-1-38 nsh) are also gratefully acknowledged.
We thank Dr. Fengying Dong and Central Laboratory of
Qingdao Agricultural University for NMR determination.
̈
P.; Florke, U.; Daniliuc, C. G.; Grimme, S.; Paradies, J. Chem. - Eur. J.
2018, 24, 16287−16291.
(9) Zhang, J.; Park, S.; Chang, S. J. Am. Chem. Soc. 2018, 140,
13209−13213.
(10) (c) Li, R.; Chen, Y.; Jiang, K.; Wang, F.; Lu, C.; Nie, J.; Chen,
Z.; Yang, G.; Chen, Y.-C.; Zhao, Y.; Ma, C. Chem. Commun. 2019, 55,
1217−1220.
(11) (a) Li, S.-S.; Lv, X.; Ren, D.; Shao, C.-L.; Liu, Q.; Xiao, J. Chem.
Sci. 2018, 9, 8253−8259. (b) Li, S.-S.; Zhou, L.; Wang, L.; Zhao, H.;
Yu, L.; Xiao, J. Org. Lett. 2018, 20, 138−141. (c) Wang, S.; An, X.-D.;
Li, S.-S.; Liu, X.; Liu, Q.; Xiao, J. Chem. Commun. 2018, 54, 13833−
13836. (d) Zhu, S.; Chen, C.; Xiao, M.; Yu, L.; Wang, L.; Xiao, J.
Green Chem. 2017, 19, 5653−5658. (e) Li, S.-S.; Zhu, S.; Chen, C.;
Duan, K.; Liu, Q.; Xiao, J. Org. Lett. 2019, 21, 1058−1062. (f) Lv, X.;
Hu, F.; Duan, K.; Li, S.-S.; Liu, Q.; Xiao, J. J. Org. Chem. 2019, 84,
1833−1844. (g) An, X.-D.; Duan, K.; Li, X.-J.; Yang, J.-M.; Lu, Y.-N.;
Liu, Q. J. Org. Chem. 2019, 84, 11839−11847. (h) Zhu, S.; Chen, C.;
Duan, K.; Sun, Y.-M.; Li, S.-S.; Liu, Q.; Xiao, J. J. Org. Chem. 2019, 84,
8440−8448. (i) Shen, Y.-B.; Li, L.-F.; Xiao, M.-Y.; Yang, J.-M.; Liu,
Q.; Xiao, J. J. Org. Chem. 2019, DOI: 10.1021/acs.joc.9b02110.
(12) (a) Young, S. D.; Britcher, S. F.; Tran, L. O.; Payne, L. S.;
Lumma, W. C.; Lyle, T. A.; Huff, J. R.; Anderson, P. S.; Olsen, D. B.;
Carroll, S. S.; Pettibone, D. J.; O’Brien, J. A.; Ball, R. G.; Balani, S. K.;
Lin, J. H.; Chen, I.-W.; Schleif, W. A.; Sardana, V. V.; Long, W. J.;
Byres, V. W.; Emini, E. A. Antimicrob. Agents Chemother. 1995, 39,
2602−2605. (b) Putman, D.; Hongenkamp, D.; Dasse, O.;
Whittemore, E. R.; Jensan, M. S. US Patent 20080039453A1, 2008.
(13) Petukhov, P. A.; Zhang, J.; Wang, C. Z.; Ye, Y. P.; Johnson, K.
M.; Kozikowski, A. P. J. Med. Chem. 2004, 47, 3009−3018.
(14) Xu, G.-Q.; Xu, J.-T.; Feng, Z.-T.; Liang, H.; Wang, Z.-Y.; Qin,
Y.; Xu, P. Angew. Chem., Int. Ed. 2018, 57, 5110−5114.
REFERENCES
■
(1) (a) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem.
2014, 57, 10257−10274. (b) Kittakoop, P.; Mahidol, C.; Ruchirawat,
S. Curr. Top. Med. Chem. 2013, 14, 239−252. (c) Cushnie, T. P. T.;
Cushnie, B.; Lamb, A. J. Int. J. Antimicrob. Agents 2014, 44, 377−386.
(2) For reviews, see: (a) Mahato, S.; Jana, C. K. Chem. Rec. 2016, 16,
1477−1488. (b) Seidel, D. Acc. Chem. Res. 2015, 48, 317−328.
(c) Mitchell, E. A.; Peschiulli, A.; Lefevre, N.; Meerpoel, L.; Maes, B.
U. W. Chem. - Eur. J. 2012, 18, 10092−10142. (d) Shi, L.; Xia, W.
Chem. Soc. Rev. 2012, 41, 7687−7697. (e) Campos, K. R. Chem. Soc.
Rev. 2007, 36, 1069−1084.
(3) (a) McNally, A.; Haffemayer, B.; Collins, B. S. L.; Gaunt, M. J.
Nature 2014, 510, 129−133. (b) Affron, D. P.; Davis, O. A.; Bull, J. A.
Org. Lett. 2014, 16, 4956−4959. (c) Calleja, J.; Pla, D.; Gorman, T.
W.; Domingo, V.; Haffemayer, B.; Gaunt, M. J. Nat. Chem. 2015, 7,
1009−1016. (d) Willcox, D.; Chappell, B. G. N.; Hogg, K. F.; Calleja,
J.; Smalley, A. P.; Gaunt, M. J. Science 2016, 354, 851−857. (e) Hogg,
K. F.; Trowbridge, A.; Alvarez-Perez, A.; Gaunt, M. J. Chem. Sci. 2017,
8, 8198−8203. (f) Antermite, D.; Affron, D. P.; Bull, J. A. Org. Lett.
2018, 20, 3948−3952.
(4) (a) Sundararaju, B.; Achard, M.; Sharma, G. V. M.; Bruneau, C.
J. Am. Chem. Soc. 2011, 133, 10340−10343. (b) Yuan, K.; Jiang, F.;
Sahli, Z.; Achard, M.; Roisnel, T.; Bruneau, C. Angew. Chem., Int. Ed.
2012, 51, 8876−8880. (c) Takasu, N.; Oisaki, K.; Kanai, M. Org. Lett.
2013, 15, 1918−1921.
(5) (a) Lai, J.; Chang, L.; Yuan, G. Org. Lett. 2016, 18, 3194−3197.
(b) Schultz, D. M.; Levesque, F.; DiRocco, D. A.; Reibarkh, M.; Ji, Y.;
Joyce, L. A.; Dropinski, J. F.; Sheng, H.; Sherry, B. D.; Davies, I. W.
Angew. Chem., Int. Ed. 2017, 56, 15274−15278. (c) Griffiths, R. J.;
Kong, W. C.; Richards, S. A.; Burley, G. A.; Willis, M. C.; Talbot, E. P.
A. Chem. Sci. 2018, 9, 2295−2300.
(6) For reviews, see: (a) Tobisu, M.; Chatani, N. Angew. Chem., Int.
Ed. 2006, 45, 1683−1684. (b) Peng, B.; Maulide, N. Chem. - Eur. J.
2013, 19, 13274−13287. (c) Wang, L.; Xiao, J. Adv. Synth. Catal.
2014, 356, 1137−1171. (d) Wang, L.; Xiao, J. Top. Curr. Chem. 2016,
374, 17. (e) Wang, L.; Xiao, J. Org. Chem. Front. 2016, 3, 635−638.
(f) Pan, S. C. Beilstein J. Org. Chem. 2012, 8, 1374−1384. (g) Haibach,
M. C.; Seidel, D. Angew. Chem., Int. Ed. 2014, 53, 5010−5036.
(h) Xiao, M.; Zhu, S.; Shen, Y.-B.; Wang, L.; Xiao, J. Youji Huaxue
2018, 38, 328−340. (i) Kwon, S. J.; Kim, D. Y. Chem. Rec. 2016, 16,
1191−1203.
(7) For representative examples, see: (a) Pastine, S. J.; McQuaid, K.
M.; Sames, D. J. Am. Chem. Soc. 2005, 127, 12180−12181.
(b) McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2009, 131, 402−
403. (c) Zhang, C. C.; De, K.; Mal, R.; Seidel, D. J. Am. Chem. Soc.
2008, 130, 416−417. (d) Mori, K.; Ehara, K.; Kurihara, K.; Akiyama,
T. J. Am. Chem. Soc. 2011, 133, 6166−6169. (e) Mori, K.; Sueoka, S.;
Akiyama, T. J. Am. Chem. Soc. 2011, 133, 2424−2426. (f) Haibach,
M. C.; Deb, I.; De, C. K.; Seidel, D. J. Am. Chem. Soc. 2011, 133,
E
DOI: 10.1021/acs.orglett.9b03004
Org. Lett. XXXX, XXX, XXX−XXX