Nickel(0)-Catalyzed Inert C-O Bond Functionalization: Organo Rare-Earth Metal Complex as the Coupling Partner

Article abstract of DOI:10.1021/acs.orglett.7b03753

An organo rare-earth metal complex has been employed as a highly efficient nucleophile in Ni(0)-catalyzed C-O bond functionalization. The optimized catalytic system which consists of Ni(cod)₂, PCy₃, and t-BuONa could smoothly convert 1 equiv of naphthyl ethers to alkylated naphthalene analogues with 0.4 equiv of Ln(CH₂SiMe₃)₃(THF)₂, delivering good to excellent yields. The reaction system could also activate the ArCH₂-O bond with mild base.

Full text of DOI:10.1021/acs.orglett.7b03753

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Nickel(0)-Catalyzed Inert C−O Bond Functionalization: Organo
Rare‑Earth Metal Complex as the Coupling Partner
Xiangqian Yan,† Fanzhi Yang,*,‡ Guilong Cai,† Qingwei Meng,† and Xiaofang Li*,†
†School of Chemistry and Chemical Engineering, Key Laboratory of Cluster Science of Ministry of Education, Beijing Institute of
Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
‡Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian
District, Beijing 100081, China
S
* Supporting Information
ABSTRACT: An organo rare-earth metal complex has been
employed as a highly efficient nucleophile in Ni(0)-catalyzed
C−O bond functionalization. The optimized catalytic system
which consists of Ni(cod)2, PCy3, and t-BuONa could
smoothly convert 1 equiv of naphthyl ethers to alkylated
naphthalene analogues with 0.4 equiv of Ln-
(CH2SiMe3)3(THF)2, delivering good to excellent yields.
The reaction system could also activate the ArCH2−O bond
with mild base.
Scheme 1. Application of Organo Rare-Earth Metal
Complexes in C−O Bond Activation
C−C bonds comprise the skeleton of organic molecules.
During the past decades, transition-metal-catalyzed cross-
couplings have been recognized as powerful tools for C−C
bond formations.1 Because of the abundance of phenol
derivatives in natural compounds, and because of the lower
toxicity of corresponding byproducts in comparison with aryl
halides, C−O bond functionalization has played an important
role in the category of sustainable cross-coupling chemistry.2
Despite the high dissociation energy of the C−O bond, the
activation of simple, stable, and easily available aryl ethers has
drawn increasing attention from chemists during the past
decade.3 Several organometallic reagents (including Grignard
reagent,4 organoboronic ester,5 organoaluminum,6 organo-
lithium,7 and organozinc8) have been employed as nucleo-
philes in transition-metal-catalyzed etheric cross-coupling
reactions (Scheme 1, eq 1). The metal core of organometallic
compound has been believed to coordinate with the oxygen
atom to form an alkoxide−Lewis acid adduct, which will
facilitate the subsequent C−O bond cleavage.6,9 Therefore, we
assume that other organo−metal complexes with strong Lewis
acidic metal cores (such as rare-earth metals) could be
promising nucleophiles in transition-metal-catalyzed inert C−
OR (R = Alk or Ar) bond functionalizations. On the other
hand, the widely used organolithium and Grignard reagents
with strong basicity could induce unwanted side reactions
(such as deprotonation), while the f-block element-cored
organometallic reagents might improve the chemoselectivity.
As a family of elements with unique properties in chemical
processes, rare-earth metals have proven efficacy in various
C−C bond formations, however, mostly as catalysts or
additives taking advantage of their strong Lewis acidity.10
Due to the instability of organo rare-earth metal complexes,
the employment of such compounds as coupling reagents in
transition-metal catalysis has been far less explored (Scheme
1, eq 2). As early as 1984, phenylytterbium iodide was
initiated into a transition-metal-catalyzed cross-coupling
reaction.11 After a quarter century, in situ generated
triaryllanthanum reagents were successfully utilized in
palladium-catalyzed arylation reactions.12 Very recently,
palladium-catalyzed alkylation and olefination were reported
using trialkyl rare-earth metals and aryl/vinyl bromides,13 of
which the reactive vinyl triflates were used as electrophiles in
coupling reactions.13b To the best of our knowledge,
unactivated electrophiles have remained unexplored in cross-
coupling reactions involving organo rare-earth metal com-
plexes.
Received: December 2, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03753
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Ni-Catalyzed C(sp2)−O Bond Functionalization
of 2-Naphthyl Ethers and 2a
As part of our interest in enriching the toolbox of nickel-
catalyzed cross-coupling reactions,3e,14 we herein report
nickel(0)-catalyzed inert C−O bond functionalization with
alkyl rare-earth metal complex as the nucleophile, introducing
the synthetically useful CH2SiMe3 group15 into various
naphthalene derivatives (Scheme 1, eq 3).
Considering the high reactivity of alkyl rare-earth metal
complexes, we initiated the optimization with 2-methoxynaph-
thalene (1a) and relatively stable Y(CH2SiMe3)3(THF)n (n =
2) (Table 1 and Table S1).16,17 Base has significant influence
a
Table 1. Optimization of Reaction Conditions
Ethyl- and isopropyl-substituted naphthols delivered lower
yield than 1a. The Np−O bond was selectively cleaved when
2-phenoxynaphthalene (1d) was used as the substrate. The
conversion of OPy group to a synthetically useful group has
been challenging for a long period.5e,h Taking advantage of
the present system, 3a was generated in moderate yield from
1e.
Subsequently, we evaluated the versatility of nickel-catalyzed
C(sp2)−O bond functionalization with 2a and methyl aryl
ethers bearing different substituents (Scheme 3). Functional
b
catalyst
ligand
yield
(%)
entry Ln
(5.0 mol %)
(10 mol %)
solvent
c
1
Y
Y
Ni(cod)2
Ni(cod)2
PCy3
PCy3
PCy3
PCy3
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
THF
31
78
95
94
72
56
80
56
58
16
95
75
0
2
3
Sc Ni(cod)2
4
Lu Ni(cod)2
5
Sc
Sc
Sc
Sc
Sc
Ni(cod)2
Ni(cod)2
Ni(cod)2
Ni(cod)2
Ni(cod)2
6
P(t-Bu)3
XPhos
SPhos
IPr·HCl
PCy3
7
8
9
Scheme 3. Ni-Catalyzed C(sp2)−O Bond Functionalization
of Methyl Aryl Ethers and 2a
10
11
12
Sc Ni(cod)2
Sc Ni(cod)2
PCy3
n-hexane
n-hexane
PhMe
PhMe
PhMe
PhMe
d
Sc Ni(cod)2
PCy3
13
14
15
16
Sc (Ph3P)2NiCl2
Sc (Ph2PCH2)2NiCl2
Sc Pd(Pt-Bu3)2
PCy3
PCy3
0
PCy3
0
Sc [Ru(p-cymene)
PCy3
0
Cl2]2
e
17
18


Ni(cod)2
Ni(cod)2
PCy3
PCy3
PhMe
PhMe
76
25
f
a
Reaction conditions: 1a (0.3 mmol), 2 (0.12 mmol), catalyst (5 mol
%), ligand (10 mol %), t-BuONa (0.3 mmol), solvent (2.0 mL). Yield
of isolated product. Without base. At room temperature;
LiCH2SiMe3 (0.3 mmol) was used as the coupling reagent;
b
c
d
e
f
ClMgCH2SiMe3 (0.3 mmol) was used as the coupling reagent.
on the reaction process. Without additional base, only 31% of
3a was obtained (Table 1, entry 1), while t-BuONa delivered
the best yield among all the tested bases (Table 1, entry 2,
and Table S1, entries 12−15). We then examined the
reactivity of another two rare-earth metalsSc and Lu from
periods 4 and 6, respectively, both delivering excellent yields
(Table 1, entries 3 and 4). The reaction without ligand
delivered a much lower yield of 72% (Table 1, entry 5).
Afterward, we tested different phosphine ligands and NHC
ligand; however, no better result was obtained (Table 1,
entries 6−9). Substrate 1a could deliver excellent yield in
hexane at 80 °C or at room temperature (Table 1, entries 11
and 12); however, this system is inapplicable to other
substrates, probably due to the poor solubility of hexane.
Nickel(II) catalysts and other transition metals like palladium
and ruthenium were inactive toward this reaction system
(Table 1, entries 13−16). The reactions using LiCH2SiMe3
and ClMgCH2SiMe3 as the coupling reagents delivered lower
yields of 76% and 25%, respectively.
groups including trimethylsilyl, 4-morpholino, and 1-pyrrolyl
groups are well tolerated. However, the catalytic system did
not work toward 1-methyl-2-methoxylnaphthalene, indicating
the electron-rich α-position plays an important role in forming
a stable transition state. Moreover, the reactions between
Sc(CH2SiMe3)3 and nonbenzannulated anisole could give very
few conversions.
An intramolecular competition experiment demonstrated
the priority of β-position in nickel-catalyzed C−O bond
activation/alkylation (Scheme 4).
With the optimized reaction conditions in hand, we first
studied the influence of different ether derivatives (Scheme 2).
Benzylalkyl ethers are generally too stable to be cleaved.18
We noticed that the ArCH2−O bond could be successfully
B
DOI: 10.1021/acs.orglett.7b03753
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 4. Ni-Catalyzed C(sp2)−O Bond Functionalization
of 1q and 2a
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.7b03753.
1
Experimental procedures, characterization data, and H
and 13C NMR spectra for new compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
activated using Na2CO3 as the base, delivering alkylated
products with good to excellent yields (Scheme 5).
*E-mail: yangfanzhi@bit.edu.cn.
*E-mail: xfli@bit.edu.cn.
ORCID
Scheme 5. Ni-Catalyzed ArCH2−O Bond Functionalization
of 4 and 2a
Fanzhi Yang: 0000-0002-5971-2032
Xiaofang Li: 0000-0003-3788-5431
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Generous support by the National Natural Science
Foundation of China (No. 21274012, 21322401), the 111
project (No. B07012), and Beijing Institute of Technology
(No. 1750012331710) is gratefully acknowledged.
A catalytic cycle was proposed as shown in Scheme 6: First,
1 will coordinate with [Ni]0 and organo rare-earth metal
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DOI: 10.1021/acs.orglett.7b03753
Org. Lett. XXXX, XXX, XXX−XXX