Alkaline-Earth Metal Catalyzed Dehydrative Allylic Alkylation

Article abstract of DOI:10.1021/acs.orglett.9b03730

An alkaline-earth metal catalytic system for environmentally benign allylic alkylation was developed. Allylic alcohols can be utilized directly at room temperature in this transition-metal-free process, producing water as the only byproduct. A variety of

Full text of DOI:10.1021/acs.orglett.9b03730

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Alkaline-Earth Metal Catalyzed Dehydrative Allylic Alkylation
Peizhong Xie,*,† Shuangshuang Li,† Yanan Liu,† Xinying Cai,† Jinyu Wang,† Xiaobo Yang,†
and Teck-Peng Loh*,†,§
†School of Chemistry and Molecular Engineering, Institute of Advanced Synthesis, Nanjing Tech University, Nanjing 211816, P.R.
China
§Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371
S
* Supporting Information
ABSTRACT: An alkaline-earth metal catalytic system for
environmentally benign allylic alkylation was developed. Allylic
alcohols can be utilized directly at room temperature in this
transition-metal-free process, producing water as the only
byproduct. A variety of allylic compounds, including the ones
containing all-carbonyl quaternary centers, can be obtained
with high yields.
he development of organic transformations that utilize
inexpensive, innocuous, transition-metal-free, and readily
available feedstock to reduce the economic and environmental
impact continues to be one of the major goals in organic
synthesis.1 In recent decades, the palladium-catalyzed allylic
alkylation of carbon nucleophiles with allylic halides or their
equivalents2 (Scheme 1, 1) has been widely used by the
advances, the dehydrative cross-coupling reaction still needs
to be optimized to overcome the dependence on transition
metals and limited nucleophile/allylic alcohol copartners.
In light of our interest in the development of greener and
more practical organic transformations,12 we turned our
attention to the dehydrative cross-coupling of allylic alcohols
with 1,3-dicarbonyl compounds under transition-metal-free
conditions. The alkaline-earth metals exhibited robust catalytic
activity13,14 for hydrogenation,14a hydroamination,14b and
Friedel−Crafts-related cationic cycloaddition15 and proved to
be promising reagents for the C−OH bond activation. We
envisioned that the interaction between calcium salts and
allylic alcohols might enable the C−OH bond dissociation
supplying calcium hydroxide, which might then function as a
base, promoting the cross-coupling process. This approach
would be one of the most efficient and environmentally
friendly ways to achieve allylic alkylation of nucleophiles by
using allylic alcohols (Scheme 1, 3).
T
Scheme 1. Metal-Promoted Allylic Alkylation
Initially, the allylic alcohol 1a (methyl 2-(hydroxy(phenyl)-
methyl)acrylate) and the 1,3-dicarbonyl compound 2a (ethyl
2-oxocyclopentane-1-carboxylate) were selected as the model
substrates to investigate the dehydrative cross-coupling process
in the presence of alkaline-earth metal catalysts (Table 1). The
calcium salt Ca(NTf2)2 alone was inefficient at promoting this
transformation at room temperature (Table 1, entry 1). A trace
amount of (or no) desired product 3a (ethyl (E)-1-(2-
(methoxycarbonyl)-3-phenylallyl)-2-oxocyclopentane-1-car-
boxylate) was detected when the Lewis acidity of calcium was
increased by introducing additives such as KPF6, Et4NPF6,
Et4NBF4, and Bu4NPF6 (Table 1, entries 2−5). To our delight,
the desired product 3a was isolated in 75% yield when
Ca(NTf2)2 and PPh3 were combined (Table 1, entry 6).
synthetic community.3 Taking waste minimization and
sustainability into account, the direct substitution of allylic
alcohols via dehydrative cross-coupling is highly sought-after
and represents a much greener, atom- and step-economical
approach (Scheme 1, 2).4 However, it is challenging to break
the inherently strong C−O bond of C−OH by using
palladium.4,5 Until now, transition metals (Pd,6 Au,7 Ir,8 Ru,9
Ni,10 etc.11), external activators, such as Brønsted or Lewis
acids, and even high temperature were required to promote the
allylation of specific substrates. Despite these important
Received: October 22, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03730
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
this reaction effectively (Table 1, entries 1, 28). In the tested
case, the Brønsted acid such as TsOH, TfOH or HNTf2 was
also inefficient (Table 1, entries 29−31).
Next, the scope of this transformation was investigated
under the optimized conditions. As shown in Scheme 2,
Table 1. Screening Reaction Conditions
d
a
entry
cat.
add.(mol %)
solvent
yield of 3a (%)
Scheme 2. Dehydrative Cross-Coupling of Allylic Alcohols
1
2
3
4
5
6
7
8
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(OTf)2
CaCl2
Ba(NTf2)2
Cu(OTf)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
toluene
EtOH
0
9
0
0
0
KPF6 (30)
Bu4NPF6 (30)
Et4NPF6 (30)
Et4NBF4 (30)
PPh3 (30)
DABCO (30)
DMAP (30)
NEt3 (30)
Na2CO3 (30)
K2CO3 (30)
NEt3 (30)
NEt3 (30)
NEt3 (30)
NEt3 (30)
NEt3 (20)
NEt3 (20)
NEt3 (20)
NEt3 (20)
NEt3 (20)
NEt3 (20)
NEt3 (20)
NEt3 (10)
NEt3 (20)
NEt3 (10)
NEt3 (20)
NEt3 (10)
NEt3 (20)
75
80
74
90
trace
38
81
38
70
complex
95
81
trace
trace
0
9
10
11
12
13
14
15
b
16
b
17
b
18
b
19
H2O
DMA
b
e
20
b
21
DCE
64
20
88
82
81
88
82
0
b
22
dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
b
23
c
24
c
25
b
26
b
27
28
29
30
31
TsOH
TfOH
HNTf2
0
0
0
a
Experimental conditions: 1 (0.30 mmol), 2 (1.2 equiv, 0.36 mmol),
Ca(NTf2)2 (20 mol %, 0.06 mmol), and Et3N (20 mol %, 0.06 mmol)
were dissolved in CH3CN (2.0 mL) and then stirred at 30 °C for 27−
72 h. Isolated yields. 2 (1.5 equiv, 0.45 mmol) was used at 80 °C for
a
Allyl alcohols 1 (0.3 mmol) and 2 (0.36 mmol) were dissolved in
solvent (2.0 mL) in a Schlenk tube (10 mL); catalyst (30 mol %) and
additive were then added subsequently. The reaction was stirred at 30
b
b
c
°C for 48 h. Catalyst (20 mol %) was used. Catalyst (10 mol %) was
24 h.
d
e
used. Isolated yields. DMA = MeCONMe2.
various Morita−Baylis−Hillman (MBH) alcohols were com-
patible with these reaction conditions and delivered the
corresponding allylic compounds in good to excellent yield.
The electronic properties of the phenyl ring on the allylic
alcohols were also studied. Both electron-withdrawing (3a−3f)
and electron-donating groups (3g, 3h) on the phenyl ring were
tolerated. For instance, even the trifluoromethyl (3d), nitro
(3e), and cyano (3f) groups were amenable to this protocol.
The sterically demanding MBH alcohols also afforded 3h in
excellent yield. The substituent position (ortho, para or meta)
had limited effect on the yield. The multisubstituted
compounds were also able to undergo this transformation.
MBH alcohols with a fused-aromatic ring (3n), and a furan-2-
yl group (3o) reacted with 2a to deliver the corresponding
products in high yields. In addition, a 1,3-diene skeleton (3p)
could be easily obtained by selecting ethyl (E)-3-hydroxy-2-
methylene-5-phenylpent-4-enoate as the starting material. In
addition to the aromatic substituted compounds, both cyclic
and straight-chain alkyl-substituted MBH alcohols were
suitable substrates, affording 3q−3s in high yields. Allylic
Screening other cocatalysts revealed that NEt3 was better than
DABCO or DMAP (Table 1, entries 7−9). Interestingly, a
much lower yield was obtained when NEt3 was replaced by an
inorganic base, such as Na2CO3 or K2CO3 (Table 1, entries 10
and 11). In addition to Ca(NTf2)2, other alkaline-earth metal
catalysts, such as CaCl2, Ca(OTf)2, and Ba(NTf2)2, can
promote this transformation, albeit with a lower yield (Table 1,
entries 12−14). However, the traditional strong Lewis acid
Cu(OTf)2 was not a suitable catalyst for this reaction under
identical conditions (Table 1, entry 15). The reaction was
solvent-sensitive, disfavoring protic solvents such as alcohols or
water (Table 1, entries 16−18). Other solvents, such as
toluene or DCE, promoted the formation of 3a in moderate to
high yield (Table 1, entries 19 and 20). The desired product
was obtained in a notably low yield when 1,4-dioxane or
DMSO was used (Table 1, entries 21 and 22). Decreasing the
catalyst load to 10 mol % had a limited effect on this
transformation (Table 1, entries 16, 23−27). In the control
experiments, neither calcium nor Et3N alone could promote
B
DOI: 10.1021/acs.orglett.9b03730
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
alcohols with β-cyano substituents did not work well, which
indicated that the ester group on the MBH alcohol skeleton
was important for this process (3t). In addition to the MBH
alcohols, other allylic alcohols, such as (E)-1,3-diarylprop-2-en-
1-ol, with either electron-withdrawing or electron-donating aryl
substituents, were screened (3u−3w); these compounds were
also able to undergo this transformation, although higher
temperature was required. In this case, the reaction was
sensitive to steric hindrance (3u and 3v) and electronic
properties of the aryl group (3u and 3w). For 3u−3w, mixtures
of two diastereomers (the ratio of syn/anti isomers is about 1/
1) were generated. Under the identity conditions, 1,1-
diphenylprop-2-en-1-ol and (E)-3-phenylprop-2-en-1-ol only
can delivered a trace amount of the desired product (3x and
3y). Remarkably, the anticonvulsant drug stiripentol (diac-
omit; ME-2080) could also be easily modified using this
method (3z). In all of the tested case, the final products 3a−
3w, 3z were detected only with E-configuration.
allylic alkylation process. It should be noted that the
trifluoromethyl group could also be incorporated into the
corresponding product by selecting 4,4,4-trifluorobutan-2-one
as the nucleophile source, although 3al was isolated in lower
yield.
Calcium-catalyzed allylic alkylation could be performed on a
10 mmol scale and deliver the desired product 3a in 93% yield
(3.1 g). Remarkably, estrone derivatives could readily react with
allylic alcohols (4). For allylic alcohols with adjacent C−H
bonds, the competitive self-dehydration process that delivered
1,3-dienes presented a very challenging organic synthesis task.
A citronellal derivative could also react with 2a to afford the
corresponding product 5 in good yield. Our results revealed
that this novel dehydrative allylic alkylation methodology can
enhance organic transformations and pharmaceutical molecule
modifications (Scheme 4).
Scheme 4. Gram-Scale Reaction and Preliminary Protocol
Applicationsa
Further experiments were conducted to explore the nature
of the nucleophiles that can be used under the optimized
conditions (Scheme 3). A large variety of cyclic and acyclic β-
Scheme 3. Dehydrative Cross-Coupling with Carbonic
a
Nucleophiles (NuH)
The detailed reaction mechanism still remained unclear.
Based on the solvent effect observations (Table 1, entries 16−
22), we preliminarily came to the conclusion that hydrogen
bonding and coordination might be important for this
transformation. Based on the essential role of the cooperative
catalytic system, we propose the following mechanism (Figure
1). The reaction may proceed via a dual activation model, in
a
Experimental conditions: 1 (0.30 mmol), 2 (1.2 equiv, 0.36 mmol),
Ca(NTf2)2 (20 mol %, 0.06 mmol), and Et3N (20 mol %, 0.06 mmol)
were dissolved in CH3CN (2.0 mL) and then stirred at 30 °C for 24−
b
c
48 h. Isolated yields. At 80 °C. At 60 °C.
Figure 1. Proposed allylic alkylation mechanism.
ketoesters were found to be suitable substrates for this protocol
(3aa−3ad). Thus, all-carbon quaternary centers with various
substituents could be constructed effectively. The reaction with
ethyl 2-cyanopropanoate also proceeded smoothly to deliver
the corresponding product (3ae) in moderate yield. These
results revealed that the carbonyl group of 2 was not crucial for
this transformation. Notably, malonate ester derivatives were
also excellent substrates for this transformation (3af, 3ag). In
addition to ethyl 2-oxocyclopentane-1-carboxylate 2a, a variety
of β-ketoesters, bearing both aryl (3ah) and alkyl (3ai−3ak)
substituents, were proved to be valuable substrates for this
which both the 1,3-dicarbonyl compound and allylic alcohol
form coordination complexes with calcium and generate
intermediates A and B, respectively. In intermediate A, the
participation of both calcium and the amine could help
stabilize formation of the enol tautomer of the nucleophiles. In
the presence of a protic solvent, the hydrogen bond that forms
between the protic solvent hydrogen and the amine prevents
the generation of A. On the other hand, the sluggish C−OH
bond of allylic alcohol is activated by calcium through
coordination (intermediate B), which facilitates the subse-
quent allylic nucleophilic substitution, affording the final
C
DOI: 10.1021/acs.orglett.9b03730
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
He, W.-M. ACS Sustainable Chem. Eng. 2019, 7, 8798. (h) Chu, X.-Q.;
Ge, D.-H.; Shen, Z.-L.; Loh, T.-P. ACS Catal. 2018, 8, 258.
(2) For some selected reviews, see: (a) Helmchen, G. J. Organomet.
Chem. 1999, 576, 203. (b) Tenaglia, A.; Heumann, A. Angew. Chem.,
Int. Ed. 1999, 38, 2180. (c) Trost, B. M. Chem. Pharm. Bull. 2002, 50,
1. (d) Kazmaier, U. Curr. Org. Chem. 2003, 7, 317. (e) Trost, B. M. J.
Org. Chem. 2004, 69, 5813. (f) Jensen, T.; Fristrup, P. Chem. - Eur. J.
2009, 15, 9632. (g) Milhau, L.; Guiry, P. J. Top. Organomet. Chem.
2011, 38, 95.
(3) (a) Trost, B. M.; Schultz, J. E. Synthesis 2019, 51, 1. (b) You, S.
L.; Dai, L. Angew. Chem., Int. Ed. 2006, 45, 5246. (c) Braun, M.;
Meier, T. Angew. Chem., Int. Ed. 2006, 45, 6952. (d) Yorimitsu, H.;
Oshima, K. Angew. Chem., Int. Ed. 2005, 44, 4435.
product 3a with water as the only byproduct. In contrast, the
oxygen atom of the solvent (1,4-dioxane or DMSO) fully
coordinates to calcium and might result in catalyst
deactivation. In addition, the carbocation process, especially
for the 1,3-diaryl alcohols, can not be completely ruled out. For
instance, the regioselectivity is poor and four isomers (α,γ-
selectivity and syn/anti isomers) can be detected by H NMR
when (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-ol was se-
lected as the substrate.
In summary, we have developed a dehydrative cross-
coupling transition-metal- and halogen-free allylic alkylation
protocol. The developed calcium catalytic system can directly
and reliably incorporate allylic alcohols at room temperature,
thus enabling this reaction to proceed in an environmentally
benign manner while producing only water as a byproduct.
The all-carbon quaternary centers with different allylic
substituents can be isolated in good to excellent yields, and a
wide-spectrum of functional groups is tolerated. This
investigation also sheds light on alkaline-earth metal catalysis
with respect to the dehydrative cross-coupling process,
although at this stage, only the MBH alcohols and some
activated versions can be used.
1
(4) (a) Kumar, R.; Van der Eycken, E. V. Chem. Soc. Rev. 2013, 42,
1121. (b) Sundararaju, B.; Achard, M.; Bruneau, C. Chem. Soc. Rev.
2012, 41, 4467. (c) Butt, N. A.; Zhang, W. Chem. Soc. Rev. 2015, 44,
7929.
(5) (a) van Gemmeren, M. V.; Borjesson, M.; Tortajada, A.; Sun, S.
Z.; Okura, K.; Martin, R. Angew. Chem., Int. Ed. 2017, 56, 6558.
(b) Mao, J.; Zhang, J.; Jiang, H.; Bellomo, A.; Zhang, M.; Gao, Z.;
Dreher, S. D.; Walsh, P. J. Angew. Chem., Int. Ed. 2016, 55, 2526.
(6) For some selected examples, see: (a) Tao, Z. L.; Zhang, W. Q.;
Chen, D. F.; Adele, A.; Gong, L. Z. J. Am. Chem. Soc. 2013, 135, 9255.
(b) Jiang, G. X.; List, B. Angew. Chem., Int. Ed. 2011, 50, 9471.
(c) Jiang, G.; List, B. Adv. Synth. Catal. 2011, 353, 1667. (d) Lu, X.;
Lu, L.; Sun, J. J. Mol. Catal. 1987, 41, 245. (e) Mukai, R.; Horino, Y.;
Tanaka, S.; Tamaru, Y.; Kimura, M. J. Am. Chem. Soc. 2004, 126,
11138. (f) Kimura, M.; Shimizu, M.; Shibata, K.; Tazoe, M.; Tamaru,
Y. Angew. Chem., Int. Ed. 2003, 42, 3392. (g) Kimura, M.; Futamata,
M.; Shibata, K.; Tamaru, Y. Chem. Commun. 2003, 234. (h) Kimura,
M.; Futamata, M.; Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127,
4592. (i) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128,
6314. (j) Goodenough, K. M.; Raubo, P.; Harrity, J. P. A. Org. Lett.
2005, 7, 2993. (k) Li, Y. X.; Xuan, Q. Q.; Liu, L.; Wang, D.; Chen, Y.
J.; Li, C. J. J. Am. Chem. Soc. 2013, 135, 12536.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b03730.
Experimental procedures, screening reaction conditions,
analytical data for all new compounds, and NMR spectra
of products (PDF)
́
(7) (a) Xia, Z.; Corce, V.; Zhao, F.; Przybylski, C.; Espagne, A.;
AUTHOR INFORMATION
Corresponding Authors
■
̀
Jullien, L.; Le Saux, T.; Gimbert, Y.; Dossmann, H.; Mouries-Mansuy,
V.; Ollivier, C.; Fensterbank, L. Nat. Chem. 2019, 11, 797.
(b) Kothandaraman, P.; Rao, W.; Zhang, X.; Chan, P. W. H.
Tetrahedron 2009, 65, 1833.
*E-mail: peizhongxie@njtech.edu.cn.
*E-mail: teckpeng@ntu.edu.sg.
(8) (a) Helmchen, G.; Dahnz, A.; Dubon, P.; Schelwies, M.;
̈
ORCID
Weihofen, R. Chem. Commun. 2007, 675. (b) Takeuchi, R.; Kashio,
M. J. Am. Chem. Soc. 1998, 120, 8647. (c) Yamashita, Y.;
Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129,
7508. (d) Roggen, M.; Carreira, E. M. J. Am. Chem. Soc. 2010, 132,
11917. (e) Lafrance, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2012,
51, 3470. (f) Roggen, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2011,
50, 5568. (g) Roggen, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2012,
51, 8652. (h) Hamilton, J. Y.; Sarlah, D.; Carreira, E. M. J. Am. Chem.
Soc. 2013, 135, 994.
(9) Lee, D.-H.; Kwon, K.-H.; Yi, C. S. Science 2011, 333, 1613.
(10) (a) Kita, Y.; Kavthe, R. D.; Oda, H.; Mashima, K. Angew. Chem.,
Int. Ed. 2016, 55, 1098. (b) Bernhard, Y.; Thomson, B.; Ferey, V.;
Sauthier, M. Angew. Chem., Int. Ed. 2017, 56, 7460.
Peizhong Xie: 0000-0002-6777-0443
Teck-Peng Loh: 0000-0002-2936-337X
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (21702108),
the Natural Science Foundation of Jiangsu Province, China
(BK20160977), the Six Talent Peaks Project in Jiangsu
Province (YY-033), the grant from Ministry of Education of
Singapore MOE2016-T1-002-043 (RG111/16), and Nanjing
Tech University (39837101).
(11) (a) Shibuya, R.; Lin, L.; Nakahara, Y.; Mashima, K.; Ohshima,
T. Angew. Chem., Int. Ed. 2014, 53, 4377. (b) Das, K.; Shibuya, R.;
Nakahara, Y.; Germain, N.; Ohshima, T.; Mashima, K. Angew. Chem.,
Int. Ed. 2012, 51, 150. (c) Mora, G.; Piechaczyk, O.; Houdard, R.;
REFERENCES
́
Mezailles, N.; Le goff, X. F.; Le Floch, P. Chem. - Eur. J. 2008, 14,
■
10047.
(1) For some selected examples, see: (a) Pronin, S. V.; Reiher, C. A.;
Shenvi, R. A. Nature 2013, 501, 195. (b) Jin, J.; MacMillan, D. W. C.
Nature 2015, 525, 87. (c) Wu, L.; Moteki, T.; Gokhale, A. A.;
Flaherty, D. W.; Toste, F. D. Chem. 2016, 1, 32. (d) Liu, Y.; Han, S.-
J.; Liu, W.-B.; Stoltz, B. M. Acc. Chem. Res. 2015, 48, 740. (e) Xie, P.;
Wang, J.; Liu, Y.; Fan, J.; Wo, X.; Fu, W.; Sun, Z.; Loh, T.-P. Nat.
Commun. 2018, 9, 1321. (f) Beddoe, R. H.; Andrews, K. G.; Magne,
V.; Cuthbertson, J. D.; Saska, J.; Shannon-Little, A. L.; Shanahan, S.
E.; Sneddon, H. F.; Denton, R. M. Science 2019, 365, 910. (g) Wu, C.;
Hong, L.; Shu, H.; Zhou, Q.-H.; Wang, Y.; Sun, M.; Jiang, S.; Cao, Z.;
(12) (a) Zhao, K.; Shen, L.; Shen, Z.-L.; Loh, T.-P. Chem. Soc. Rev.
2017, 46, 586. (b) Xie, P.; Wang, J.; Fan, J.; Liu, Y.; Wo, X.; Fu, W.;
Loh, T.-P. Green Chem. 2017, 19, 2135. (c) Liu, Y.; Xie, P.; Sun, Z.;
Wo, X.; Gao, C.; Fu, W.; Loh, T.-P. Org. Lett. 2018, 20, 5353. (d) Xie,
P.; Fan, J.; Liu, Y.; Wo, X.; Fu, W.; Loh, T.-P. Org. Lett. 2018, 20,
3341. (e) Wo, X.; Xie, P.; Fu, W.; Gao, C.; Liu, Y.; Sun, Z.; Loh, T.-P.
Chem. Commun. 2018, 54, 11132. (f) Xie, P.; Fu, W.; Cai, X.; Sun, Z.;
Wu, Y.; Li, S.; Gao, C.; Yang, X.; Loh, T.-P. Org. Lett. 2019, 21, 7055.
(g) Xie, P.; Fu, W.; Wu, Y.; Cai, X.; Sun, Z.; Li, S.; Gao, C.; Yang, X.;
D
DOI: 10.1021/acs.orglett.9b03730
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Loh, T.-P. Org. Lett. 2019, 21, 4168−4172. (h) Xie, P.; Wo, X.; Yang,
X.; Cai, X.; Li, S.; Gao, C.; Yang, X.; Loh, T.-P. Green Chem. 2019, 21,
5207.
(13) Wu, X.; Zhao, L.; Jin, J.; Pan, S.; Li, W.; Jin, X.; Wang, G.;
Zhou, M.; Frenking, G. Science 2018, 361, 912.
̈
(14) (a) Bauer, H.; Alonso, M.; Farber, C.; Elsen, H.; Pahl, J.;
Causero, A.; Ballmann, G.; De Proft, F.; Harder, S. Nat. Catal. 2018,
1, 40. (b) Crimmin, M. R.; Casely, I. J.; Hill, M. S. J. Am. Chem. Soc.
2005, 127, 2042.
(15) (a) Stopka, T.; Niggemann, M. Chem. Commun. 2016, 52,
5761. (b) Rauser, M.; Schroeder, S.; Niggemann, M. Chem. - Eur. J.
2015, 21, 15929. (c) Fu, L.; Niggemann, M. Chem. - Eur. J. 2015, 21,
6367. (d) Gao, S.; Stopka, T.; Niggemann, M. Org. Lett. 2015, 17,
5080. (e) Stopka, T.; Niggemann, M. Org. Lett. 2015, 17, 1437.
(f) Begouin, J.-M.; Capitta, F.; Wu, X.; Niggemann, M. Org. Lett.
2013, 15, 1370. (g) Haven, T.; Kubik, G.; Haubenreisser, S.;
Niggemann, M. Angew. Chem., Int. Ed. 2013, 52, 4016. (h) Meyer, V.
J.; Niggemann, M. Chem. - Eur. J. 2012, 18, 4687. (i) Niggemann, M.;
Meel, M. J. Angew. Chem., Int. Ed. 2010, 49, 3684. (j) Morcillo, S. P.;
Leboeuf, D.; Bour, C.; Gandon, V. Chem. - Eur. J. 2016, 22, 16974.
(k) Morcillo, S. P.; Presset, M.; Floquet, S.; Coeffard, V.; Greck, C.;
Bour, C.; Gandon, V. Eur. J. Org. Chem. 2016, 2016, 2688.
(l) Leboeuf, D.; Schulz, E.; Gandon, V. Org. Lett. 2014, 16, 6464.
(m) Sandridge, M. J.; France, S. Org. Lett. 2016, 18, 4218. (n) Davies,
J.; Leonori, D. Chem. Commun. 2014, 50, 15171.
E
DOI: 10.1021/acs.orglett.9b03730
Org. Lett. XXXX, XXX, XXX−XXX