Palladium-Catalyzed Highly Regioselective Aromatic Substitution of Benzylic Ammonium Salts with Amines

Article abstract of DOI:10.1021/acs.orglett.9b02820

An unprecedented aromatic substitution reaction of benzylic ammonium salts has been developed through palladium-catalyzed C-N bond cleavage. A range of primary and secondary amines participated in a palladium-catalyzed aromatic substitution reaction of benzylic ammonium salts, delivering sterically hindered aromatic amines in moderate to excellent yields with extremely high regioselectivity. Preliminary mechanistic studies permitted successful identification of Π-benzylpalladium complexes and Γ-vinyl allylic amines as key intermediates. This study paves the way for the use of benzylic ammonium salts in the aromatic substitution reactions.

Full text of DOI:10.1021/acs.orglett.9b02820

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium-Catalyzed Highly Regioselective Aromatic Substitution of
Benzylic Ammonium Salts with Amines
Ya-Nan Xu,† Meng-Zeng Zhu,† Yu-Kun Lin,† and Shi-Kai Tian*,†,‡
†Hefei National Laboratory for Physical Sciences at the Microscale, Center for Excellence in Molecular Synthesis, and Department of
Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
‡Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: An unprecedented aromatic substitution reaction of
benzylic ammonium salts has been developed through palladium-
catalyzed C−N bond cleavage. A range of primary and secondary
amines participated in a palladium-catalyzed aromatic substitution
reaction of benzylic ammonium salts, delivering sterically hindered
aromatic amines in moderate to excellent yields with extremely high
regioselectivity. Preliminary mechanistic studies permitted successful
identification of π-benzylpalladium complexes and γ-vinyl allylic amines as key intermediates. This study paves the way for the
use of benzylic ammonium salts in the aromatic substitution reactions.
benzylic ammonium salts serve as effective benzylating agents
to couple with alkenes,6a aromatics,6b,k,m aldehydes,6p CO2,6f,p,r
CO,6l organoborons,4h,k,6b−e,g−j,q and sulfur nucleophiles,6n,o
offering a functional group handle orthogonal to benzylic
halides and alcohol derivatives. Herein, we report for the first
time an aromatic substitution reaction of benzylic ammonium
salts through palladium-catalyzed C−N bond cleavage
(Scheme 1b).
uaternary ammonium salts are readily accessible and
Q have been widely employed in promoting aqueous
solubility or in interacting with anionic partners.1 While the
C−N bond cleavage of quaternary ammonium salts has been
frequently demonstrated in a few well-known reactions such as
the Hofmann elimination2 and the Stevens rearrangement,3 it
is less often utilized in bond formation reactions with other
molecules. Despite the huge challenge in the discrimination of
different C−N bonds, significant progress has been made in
the intermolecular bond formation reactions of quaternary
aryl,4 benzylic,4h,k,5,6 allylic,6p,7 and propargylic8 ammonium
salts, releasing electronically neutral tertiary amines as leaving
groups. Although benzylic ammonium salts can be directly
substituted by nucleophiles at the benzylic position,5 the use of
transition metal catalysts significantly broadens the scope of
their coupling partners (Scheme 1a). In the presence of
palladium, rhodium, iridium, nickel, and copper catalysts,
In the course of exploring new C−N bond cleavage reactions
of quaternary ammonium salts,5l,m,9 we unexpectedly found
that the PdCl2/PPh3-catalyzed reaction of benzylic ammonium
salt 1a with dialkylamine 2a afforded tertiary aromatic amine
3a, instead of the corresponding tertiary benzylic amine, in
70% yield (Table 1, entry 1). This reaction represents the first
example of an aromatic substitution reaction of benzylic
ammonium salts via C−N bond cleavage, offers a functional
group handle orthogonal to the corresponding benzylic
chlorides10 and alcohol derivatives,11 and provides a
convenient method for the synthesis of sterically hindered
aromatic amines with high regioselectivity. Therefore, we
decided to optimize the reaction conditions to achieve higher
yields. We first surveyed a number of palladium sources (5 mol
%) in the model reaction of benzylic ammonium salt 1a with
dialkylamine 2a in the presence of PPh3 (10 mol %) and
NaOtBu (3 equiv) in tetrahydrofuran at 70 °C for 5 h (entries
2−9). Gratifyingly, the use of inexpensive Pd(OAc)2 afforded
tertiary aromatic amine 3a in the highest yield, 86% (entry 6).
Importantly, the corresponding benzylic substitution product,
4-(naphthalen-1-ylmethyl)morpholine, was not observed at all.
Increasing the scale from 0.2 to 5 mmol gave a slightly lower
Scheme 1. C−N Bond Cleavage Reactions of Benzylic
Ammonium Salts
Received: August 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02820
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization of the Reaction Conditions
Scheme 2. Scope of Benzylic Ammonium Salts
yield
b
entry
[Pd]
PdCl2
L
base
solvent
(%)
1
2
3
4
5
6
7
8
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
none
PPh3
none
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
LiOtBu
KOtBu
NaOEt
NaOH
NaH
K3PO4
Cs2CO3
DBU
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
MTBE
dioxane
toluene
hexane
THF
THF
70
86
25
78
75
86
80
81
85
0
Pd(PPh3)2Cl2
[Pd(allyl)Cl]2
Pd(PhCN)Cl2
Pd(COD)Cl2
Pd(OAc)2
Pd(OCOCF3)2
Pd(dba)2
9
Pd(PPh3)4
none
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
0
( )-BINAP
dppf
trace
46
84
64
69
trace
84
0
0
82
0
0
0
46
0
45
26
79
60
dppb
dppp
PCy3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
a
Reaction conditions: 1 (0.20 mmol), 2a (0.20 mmol), Pd(OAc)2 (5
mol %), PPh3 (10 mol %), NaOtBu (3 equiv), THF (1.0 mL), 70 °C,
5 h. Isolated yields are given. For the synthesis of 3r, N,N,N-trimethyl-
1-(thiophen-2-yl)methanaminium triflate (1r) was prepared in situ
from N,N-dimethyl-1-(naphthalen-1-yl)-1-(thiophen-2-yl)-
methanamine and MeOTf.
c
29
d
30
a
Reaction conditions: 1a (0.20 mmol), 2a (0.20 mmol), [Pd] (5 mol
%), L (10 mol %), base (3 equiv), solvent (1.0 mL), 70 °C, 5 h.
high regioselectivity (3a−h). The aromatic substitution
reaction was successfully extended to a range of branched
benzylic and dibenzylic ammonium triflates, in which only the
naphthalene ring was substituted by dialkylamine 2a at the
para position (3i−r).13 In all the above cases, the benzylic
substitution products were not detected. Aromatic amine 3i
was obtained in a low yield simply because competing
Hofmann elimination of the benzylic ammonium triflate
occurred to afford 1-vinylnaphthalene in 22% yield. Moreover,
this method provides orthogonal reactivity to aryl halides (3c
and 3o−q), which are amenable to further synthetic
elaboration.
We then surveyed the substrate scope for the amine partners
in the aromatic substitution reaction of benzylic ammonium
salt 1a (Scheme 3). The reaction proceeded well with both
cyclic and acyclic secondary dialkylamines as well as N-
methylaniline under the standard conditions (3s−x). Notably,
these reaction conditions selectively activate the benzylic C−N
bond in the presence of benzylic C−O bonds (3v),
highlighting the complementarity of benzylic ammonium
salts to benzylic ethers. We next examined a number of
primary amines. While the use of benzylamine as a nitrogen
nucleophile led to the formation of secondary aromatic amine
b
c
Isolated yield. 1a was replaced with N,N,N-trimethyl-1-(naphthalen-
d
1-yl)methanaminium chloride (1aa). 1a was replaced with N,N,N-
trimethyl-1-(naphthalen-1-yl)methanaminium iodide (1ab).
yield (81%). The reaction failed to occur in the absence of
either a palladium source or a phosphine ligand (entries 10 and
11). Next, we examined some other readily available phosphine
ligands, bases,12 and solvents and failed to enhance the yield
(entries 12−28). Finally, we investigated the counterion effect
of the benzylic ammonium salt and obtained lower yields when
replacing the triflate anion with a chloride anion or an iodide
anion (entries 29 and 30).
Under the optimized conditions (Table 1, entry 6), we
observed a broad substrate scope for the benzylic ammonium
triflates in the aromatic substitution reaction using dialkyl-
amine 2a as a nitrogen nucleophile (Scheme 2). In addition to
various substituted (naphthalen-1-yl)methylammonium tri-
flates, (anthracen-9-yl)methyl and (phenanthren-1-yl)methyl-
ammonium triflates served as suitable substrates in the reaction
to afford the corresponding sterically hindered tertiary
aromatic amines in moderate to good yields with extremely
B
DOI: 10.1021/acs.orglett.9b02820
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 3. Scope of Secondary and Primary Amines
Scheme 4. Mechanistic Studies
a
Reaction conditions: 1a (0.20 mmol), 2 (0.20 mmol), Pd(OAc)2 (5
mol %), PPh3 (10 mol %), NaOtBu (3 equiv), THF (1.0 mL), 70 °C,
5 h. Isolated yields are given. For the synthesis of 3w, NHMe2·HCl
and NaOtBu (5 equiv) were used. The synthesis of 3y was run at 80
°C with Pd(PPh3)2Cl2 and o-phenylphenyl diphenylphosphane
instead of Pd(OAc)2 and PPh3.
respectively. The structure of complex 5aaa was unambigu-
ously confirmed by X-ray crystallography (CCDC 1907865),
providing substantial evidence, for the first time, of the
oxidative addition of a benzylic ammonium salt to a Pd(0)
species through C−N bond cleavage. Both complexes 5aaa and
5aab participated in the coupling reaction with dialkylamine 2a
to afford tertiary aromatic amine 3a albeit in unsatisfactory
yields. Moreover, both of them were found to serve as effective
catalysts in promoting the reaction between benzylic
ammonium salt 1a and dialkylamine 2a. These results
substantially support the intermediacy of π-benzylpalladium
complexes in the aromatic substitution reaction of benzylic
ammonium salts with amines.
On the basis of the above experimental results and previous
relevant reports,6g,q,10,15 we propose the following reaction
pathway for the aromatic substitution reaction of benzylic
ammonium salt 1a with dialkylamine 2a (Scheme 5). Oxidative
addition of benzylic ammonium salt 1a to palladium(0)
(PdLn), generated in situ from Pd(OAc)2 through reduction
with the phosphine ligand or the amine substrate, affords
trimethylamine and π-benzylpalladium complex 5a.6g Ligand
substitution of complex 5a with dialkylamine 2a in the
presence of a strong base affords π-benzylpalladium complex
3y in a low yield,14 the reaction with 1-adamantylamine, a very
bulky primary aliphatic amine, gave a good yield (3z). In
contrast, higher yields were achieved from the reaction with a
range of primary aromatic amines, in which substitution was
well tolerated at the para, meta, and ortho positions of the
aromatic ring (3aa−ai).
To gain insights into the reaction mechanism, we carried out
several experiments to identify the intermediates generated in
the aromatic substitution reaction of benzylic ammonium salts
with amines (Scheme 4). After the reaction of benzylic
ammonium salt 1k with dialkylamine 2a was performed under
the standard conditions for 0.5 h, we quenched the reaction
mixture and subsequently isolated γ-vinyl allylic amine 4k in
32% yield. Isomerization of this intermediate required the
presence of NaOtBu and afforded aromatic amine 3k in 78%
yield. Treatment of benzylic ammonium salt 1aa with a
stoichiometric amount of Pd(PPh3)4 in tetrahydrofuran at
room temperature permitted us to isolate two π-benzylpalla-
dium complexes, 5aaa (having one phosphine ligand) and
5aab (having two phosphine ligands), in 38% and 32% yields,
C
DOI: 10.1021/acs.orglett.9b02820
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ORCID
Scheme 5. Proposed Reaction Mechanism (L = PPh3, n =
1−4)
Shi-Kai Tian: 0000-0002-2938-7013
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the financial support from the National
Natural Science Foundation of China (21772182), the
Strategic Priority Research Program of the Chinese Academy
of Sciences (XDB20000000), and the Fundamental Research
Funds for the Central Universities.
REFERENCES
■
(1) (a) Hashimoto, T.; Maruoka, K. Chem. Rev. 2007, 107, 5656−
̀
5682. (b) Briere, J.-F.; Oudeyer, S.; Dalla, V.; Levacher, V. Chem. Soc.
Rev. 2012, 41, 1696−1707. (c) Zhang, C.; Cui, F.; Zeng, G.-M.; Jiang,
M.; Yang, Z.-Z.; Yu, Z.-G.; Zhu, M.-Y.; Shen, L.-Q. Sci. Total Environ.
2015, 518−519, 352−362. (d) Qian, D.; Sun, J. Chem. - Eur. J. 2019,
25, 3740−3751.
(2) Cope, A. C.; Trumbull, E. R. Org. React. 1960, 11, 317−388.
6a.15 Then, complex 6a undergoes reductive elimination to
afford γ-vinyl allylic amine 4a in a highly regioselective manner
via intramolecular C−N bond coupling between the para
carbon atom of the η3-exo-(1-naphthyl)methyl ligand and the
nitrogen atom of the amide ligand (as shown in transition state
7a), and concurrently regenerates palladium(0) to continue
the catalytic cycle.15 Finally, γ-vinyl allylic amine 4a
participates in aromatization via isomerization under basic
conditions to afford tertiary aromatic amine 3a.10
In summary, we have developed for the first time an
aromatic substitution reaction of benzylic ammonium salts
through palladium-catalyzed C−N bond cleavage. In the
presence of 5 mol % Pd(OAc)2, 10 mol % PPh3, and 3
equiv of NaOtBu, a range of primary and secondary amines
participated in the aromatic substitution reaction of benzylic
ammonium salts to afford sterically hindered aromatic amines
in moderate to excellent yields with extremely high
regioselectivity. A plausible reaction mechanism was proposed
according to the successful identification of π-benzylpalladium
complexes and γ-vinyl allylic amines as key intermediates. This
study paves the way for the use of benzylic ammonium salts in
the aromatic substitution reactions.
́
(3) (a) Marko, I. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3; pp 913−974.
(b) BachAuthor Vitae, R.; HarthongAuthor Vitae, S.; Lacour, J. In
Comprehensive Organic Synthesis II, 2nd ed.; Knochel, P., Molander, G.
A., Eds.; Elsevier: Oxford, 2014; Vol. 3; pp 992−1037.
(4) (a) Wenkert, E.; Han, A.-L.; Jenny, C.-J. J. Chem. Soc., Chem.
Commun. 1988, 975−976. (b) Blakey, S. B.; MacMillan, D. W. C. J.
Am. Chem. Soc. 2003, 125, 6046−6047. (c) Reeves, J. T.; Fandrick, D.
R.; Tan, Z. L.; Song, J. J.; Lee, H.; Yee, N. K.; Senanayake, C. H. Org.
Lett. 2010, 12, 4388−4391. (d) Xie, L.-G.; Wang, Z.-X. Angew. Chem.,
Int. Ed. 2011, 50, 4901−4904. (e) Zhang, X.-Q.; Wang, Z.-X. J. Org.
Chem. 2012, 77, 3658−3663. (f) Guo, W.-J.; Wang, Z.-X. Tetrahedron
2013, 69, 9580−9585. (g) Zhang, X.-Q.; Wang, Z.-X. Org. Biomol.
Chem. 2014, 12, 1448−1453. (h) Zhang, H.; Hagihara, S.; Itami, K.
Chem. - Eur. J. 2015, 21, 16796−16800. (i) Zhu, F.; Tao, J.-L.; Wang,
Z.-X. Org. Lett. 2015, 17, 4926−4929. (j) Wu, D.; Tao, J.-L.; Wang,
Z.-X. Org. Chem. Front. 2015, 2, 265−273. (k) Hu, J.; Sun, H.; Cai,
W.; Pu, X.; Zhang, Y.; Shi, Z. J. Org. Chem. 2016, 81, 14−24.
(l) Wang, D.-Y.; Kawahata, M.; Yang, Z.-K.; Miyamoto, K.;
Komagawa, S.; Yamaguchi, K.; Wang, C.; Uchiyama, M. S. Nat.
Commun. 2016, 7, 12937. (m) Yi, Y.-Q.-Q.; Yang, W.-C.; Zhai, D.-D.;
Zhang, X.-Y.; Li, S.-Q.; Guan, B.-T. Chem. Commun. 2016, 52,
10894−10897. (n) Ogawa, H.; Yang, Z.-K.; Minami, H.; Kojima, K.;
Saito, T.; Wang, C.; Uchiyama, M. ACS Catal. 2017, 7, 3988−3994.
(o) He, F.; Wang, Z.-X. Tetrahedron 2017, 73, 4450−4457.
(5) (a) Snyder, H. R.; Eliel, E. L.; Charnahan, R. E. J. Am. Chem. Soc.
1951, 73, 970−973. (b) Brasen, W. R.; Hauser, C. R. J. Org. Chem.
1953, 18, 806−809. (c) Kellner, K.; Rothe, S.; Steyer, E. M.;
Tzschach, A. Phosphorus Sulfur Relat. Elem. 1980, 8, 269−274.
(d) Barton, D. H. R.; Fekih, A.; Lusinchi, X. Tetrahedron Lett. 1985,
26, 6197−6200. (e) Bordwell, F. G.; Hughes, D. L. J. Am. Chem. Soc.
1986, 108, 7300−7309. (f) Crozet, M. P.; Jentzer, O.; Vanelle, P.
Tetrahedron Lett. 1987, 28, 5531−5534. (g) Kornblum, N.;
Ackermann, P.; Manthey, J. W.; Musser, M. T.; Pinnick, H. W.;
Singaram, S.; Wade, P. A. J. Org. Chem. 1988, 53, 1475−1481.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02820.
■
S
Experimental procedures, characterization data, X-ray
crystallographic data, and copies of NMR spectra (PDF)
Accession Codes
́
́
(h) Stara, I. G.; Stary, I.; Zavada, J. J. Org. Chem. 1992, 57, 6966−
6969. (i) Axelsson, O.; Peters, D. J. Heterocycl. Chem. 1997, 34, 461−
463. (j) Khalafi-Nezhad, A.; Zare, A.; Parhami, A.; Hasaninejad, A.;
CCDC 1907865 contains 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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
̌
Moosavi Zare, A. R. J. Iran. Chem. Soc. 2008, 5, S40−S46. (k) Maras,
̌
N.; Polanc, S.; Kocevar, M. Org. Biomol. Chem. 2012, 10, 1300−1310.
(l) Gui, Y.; Tian, S.-K. Org. Lett. 2017, 19, 1554−1557. (m) Chen, Z.;
Han, L.; Tian, S.-K. Org. Lett. 2017, 19, 5852−5855.
(6) (a) Yi, P.; Zhuangyu, Z.; Hongwen, H. Synthesis 1995, 1995,
́
́
̈
, A. G. Org. Lett.
245−247. (b) de la Herran, G.; Segura, A.; Csaky
AUTHOR INFORMATION
Corresponding Author
■
2007, 9, 961−964. (c) Maity, P.; Shacklady-McAtee, D. M.; Yap, G.
P. A.; Sirianni, E. R.; Watson, M. P. J. Am. Chem. Soc. 2013, 135, 280−
285. (d) Shacklady-McAtee, D. M.; Roberts, K. M.; Basch, C. H.;
*E-mail: tiansk@ustc.edu.cn.
D
DOI: 10.1021/acs.orglett.9b02820
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Song, Y.-G.; Watson, M. P. Tetrahedron 2014, 70, 4257−4263.
(e) Basch, C. H.; Cobb, K. M.; Watson, M. P. Org. Lett. 2016, 18,
136−139. (f) Moragas, T.; Gaydou, M.; Martin, R. Angew. Chem., Int.
Ed. 2016, 55, 5053−5057. (g) Wang, T.; Yang, S.; Xu, S.; Han, C.;
Guo, G.; Zhao, J. RSC Adv. 2017, 7, 15805−15808. (h) Liu, X.-Y.;
Zhu, H.-B.; Shen, Y.-J.; Jiang, J.; Tu, T. Chin. Chem. Lett. 2017, 28,
350−353. (i) Turtscher, P. L.; Davis, H. J.; Phipps, R. J. Synthesis
̈
2018, 50, 793−802. (j) Zhang, Z.; Wang, H.; Qiu, N.; Kong, Y.; Zeng,
W.; Zhang, Y.; Zhao, J. J. Org. Chem. 2018, 83, 8710−8715.
(k) Sasagawa, A.; Yamaguchi, M.; Ano, Y.; Chatani, N. Isr. J. Chem.
2017, 57, 964−967. (l) Yu, W.; Yang, S.; Xiong, F.; Fan, T.; Feng, Y.;
Huang, Y.; Fu, J.; Wang, T. Org. Biomol. Chem. 2018, 16, 3099−3103.
(m) Li, J.; Zheng, Z.; Xiao, T.; Xu, P.-F.; Wei, H. Asian J. Org. Chem.
2018, 7, 133−136. (n) Lu, F.; Chen, Z.; Li, Z.; Wang, X.; Peng, X.; Li,
C.; Li, R.; Pei, H.; Wang, H.; Gao, M. Asian J. Org. Chem. 2018, 7,
141−144. (o) Jiang, W.; Li, N.; Zhou, L.; Zeng, Q. ACS Catal. 2018,
8, 9899−9906. (p) Liao, L.-L.; Cao, G.-M.; Ye, J.-H.; Sun, G.-Q.;
Zhou, W.-J.; Gui, Y.-Y.; Yan, S.-S.; Shen, G.; Yu, D.-G. J. Am. Chem.
Soc. 2018, 140, 17338−17342. (q) Wang, T.; Guo, J.; Wang, X.; Guo,
H.; Jia, D.; Wang, H.; Liu, L. RSC Adv. 2019, 9, 5738−5741. (r) Yang,
D.-T.; Zhu, M.; Schiffer, Z. J.; Williams, K.; Song, X.; Liu, X.;
Manthiram, K. ACS Catal. 2019, 9, 4699−4705.
(7) (a) Dressaire, G.; Langlois, Y. Tetrahedron Lett. 1980, 21, 67−70.
(b) Langlois, Y.; Van Bac, N.; Fall, Y. Tetrahedron Lett. 1985, 26,
1009−1012. (c) Van Bac, N.; Fall, Y.; Langlois, Y. Tetrahedron Lett.
1986, 27, 841−844. (d) Hosomi, A.; Hoashi, K.; Tominaga, Y. J. J.
Org. Chem. 1987, 52, 2947−2948. (e) Gupton, J. T.; Layman, W. J. J.
Org. Chem. 1987, 52, 3683−3686. (f) Hosomi, A.; Hoashi, K.; Kohra,
S.; Tominaga, Y.; Otaka, K.; Sakurai, H. J. Chem. Soc., Chem. Commun.
1987, 570−571. (g) Doi, T.; Yanagisawa, A.; Miyazawa, M.;
Yamamoto, K. Tetrahedron: Asymmetry 1995, 6, 389−392. (h) Raska-
̈
tov, J. A.; Jakel, M.; Straub, B. F.; Rominger, F.; Helmchen, G. Chem. -
Eur. J. 2012, 18, 14314−14328.
(8) (a) Iwai, I.; Hiraoka, T. Chem. Pharm. Bull. 1962, 10, 81−86.
(b) Murai, T.; Fukushima, K.; Mutoh, Y. Org. Lett. 2007, 9, 5295−
́
5298. (c) Guisan-Ceinos, M.; Martín-Heras, V.; Tortosa, M. J. Am.
Chem. Soc. 2017, 139, 8448−8451. (d) Ma, S.; Liu, Q.; Tang, X.; Cai,
́
Y. Asian J. Org. Chem. 2017, 6, 1209−1212. (e) Guisan-Ceinos, M.;
́
Martín-Heras, V.; Soler-Yanes, R.; Cardenas, D. J.; Tortosa, M. Chem.
Commun. 2018, 54, 8343−8346. (f) Zhang, L.; Zhang, Z.-J.; Xiao, J.-
Y.; Song, J. Org. Lett. 2018, 20, 5519−5522.
(9) (a) Zhang, J.; Chen, Z.-X.; Du, T.; Li, B.; Gu, Y.; Tian, S.-K. Org.
Lett. 2016, 18, 4872−4875. (b) Zhou, M.-G.; Dai, R.-H.; Tian, S.-K.
Chem. Commun. 2018, 54, 6036−6039. (c) Xu, Y.-N.; Tian, S.-K.
Tetrahedron 2019, 75, 1632−1638. (d) Jin, Y.-X.; Yu, B.-K.; Qin, S.-
P.; Tian, S.-K. Chem. - Eur. J. 2019, 25, 5169−5172.
(10) (a) Bao, M.; Nakamura, H.; Yamamoto, Y. J. Am. Chem. Soc.
2001, 123, 759−760. (b) Peng, B.; Feng, X.; Zhang, X.; Ji, L.; Bao, M.
Tetrahedron 2010, 66, 6013−6018. (c) Zhang, S.; Wang, Y.; Feng, X.;
Bao, M. J. Am. Chem. Soc. 2012, 134, 5492−5495. (d) Zhang, S.; Yu,
X.; Feng, X.; Yamamoto, Y.; Bao, M. Chem. Commun. 2015, 51,
3842−3845. (e) Zhang, S.; Cai, J.; Yamamoto, Y.; Bao, M. J. Org.
Chem. 2017, 82, 5974−5980. (f) Zhang, S.; Ullah, A.; Yamamoto, Y.;
Bao, M. Adv. Synth. Catal. 2017, 359, 2723−2728.
(11) (a) Ueno, S.; Komiya, S.; Tanaka, T.; Kuwano, R. Org. Lett.
2012, 14, 338−341. (b) Komatsuda, M.; Muto, K.; Yamaguchi, J. Org.
Lett. 2018, 20, 4354−4357.
(12) A small amount of the benzylic substitution product, 4-
(naphthalen-1-ylmethyl)morpholine, was observed when using the
bases shown in Table 1 except NaOtBu, KOtBu, and NaH.
(13) The aromatic substitution reaction was not observed with the
phenyl ring (3k and 3q) and the thiophenyl ring (3r). Moreover, we
did not observe the reaction of PhCH2NMe3OTf (1s) with
dialkylamine 2a under the standard conditions.
(14) Under the standard conditions amine 3y was obtained in 22%
yield and 1-methylnaphthalene was isolated as an undesired product
in 53% yield.
(15) For density functional theory calculations, see: Xie, H.; Zhang,
H.; Lin, Z. Organometallics 2013, 32, 2336−2343.
E
DOI: 10.1021/acs.orglett.9b02820
Org. Lett. XXXX, XXX, XXX−XXX