Chromium(III)-Catalyzed C(sp2)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base

Article abstract of DOI:10.1021/jacs.0c00127

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp²)-H functionalization of an ortho-position of aromatic and α,β-unsaturated secondary amides using readily available AlMe₃ as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 °C, requires as low as 1-2 mol % of CrCl₃ or Cr(acac)₃ as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups. Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reactive intermediates bearing two molecules of the amide substrate on one chromium atom and also that one of these chromate(III) complexes takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism accounts for the effective suppression of methyl group delivery from AlMe₃ for ortho-C-H methylation.

Full text of DOI:10.1021/jacs.0c00127

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Article
Chromium(III)-catalyzed C(sp2)–H Alkynylation, Allylation, and
Naphthalenation of Secondary Amides with Trimethylaluminum as Base
Mengqing Chen, Takahiro Doba, Takenari Sato, Hlib
Razumkov, Laurean Ilies, Rui Shang, and Eiichi Nakamura
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c00127 • Publication Date (Web): 18 Feb 2020
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Journal of the American Chemical Society
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Chromium(III)-catalyzed C(sp2)–H Alkynylation, Allylation, and
Naphthalenation of Secondary Amides with Trimethylaluminum as
Base
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Mengqing Chen, Takahiro Doba, Takenari Sato, Hlib Razumkov, Laurean Ilies,† Rui Shang,* and Eiichi
Nakamura*
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
Supporting Information Placeholder
benefits of this mild base have been previously reported in the
ABSTRACT: Among base metals used for C–H activation
reactions, chromium(III) is rather unexplored despite its natural
context of base-metal-catalyzed C–H methylations.10
abundance and low toxicity. We report herein chromium(III)-
catalyzed C(sp2)–H functionalization of an ortho-position of
aromatic and ,-unsaturated secondary amides using readily
available AlMe3 as a base, and using bromoalkynes, allyl bromide,
and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This
redox-neutral reaction taking place at 70–90 °C requires as low as
1–2 mol% of CrCl3 or Cr(acac)3 as a catalyst without any added
ligand, and tolerates functional groups such as aryl iodide,
boronate, and thiophene groups. Stoichiometric and kinetics studies
as well as kinetic isotope effects suggest that the catalytic cycle
consists of a series of thermally stable but reactive intermediates
bearing two molecules of the amide substrate on one chromium
atom, and also that one of these chromate(III) complexs takes part
in the alkynylation, allylation, and naphthalenation reactions. The
proposed mechanism accounts for the effective suppression of
methyl group delivery from AlMe3 for ortho-C–H methylation.
INTRODUCTION
Base-metal-catalyzed deprotonative C–H activation1 is a
rapidly growing part of the modern C–H activation toolkit,2 where
an organometallic base deprotonates the C–H bond of the substrate
to generate a cyclometallated intermediate3 made of a high-valent
metal center (A, Figure 1a). This intermediate may then undergo
C–C bond formation either by intermolecular delivery of an R–
group to the metal center following reductive elimination,4 or by
reaction with an external electrophile without changing the
oxidation state of the metal.5 The latter manifold is more
synthetically attractive than the former because of the availability
of a broad structural variety of shelf-stable electrophiles, as
opposed to a limited variety of potentially unstable organometallics
for delivery of the R– group. However, the electrophilic trapping of
A is often plagued by competitive R– delivery from a coexisting
organometallic base, R–M,1a and to suppress this side reaction, the
reaction often requires an elaborate design of ligand6 and
organometallic base.7 In the present study, we propose a
combination of a carboxamide, a chromium(III) catalyst, and
mildly nucleophilic trimethylaluminum (AlMe3) to solve these
problems. Chromium(III) is a stable valence form of this naturally
abundant and low toxicity metal, whereas chromium(VI) is highly
toxic.8 Readily available and mildly reactive AlMe3 is the base of
choice, and undesired C–H methylation9 is suppressed. The unique
Figure 1. Deprotonative C–H functionalization reactions. (a)
Deprotonative C–H activation followed by reductive elimination or
electrophile trapping. (b) Chromium(III)-catalyzed C–H
functionalization via a reactive biscyclometallated Cr(III) ate
complex . The indicated amide coordination to Cr(III) on nitrogen
in B and C is tentative and requires further studies. (c)
Representative C–H functionalization products in this study.
We report herein C–H functionalization of aromatic and
,-unsaturated secondary amides with alkynyl-, allyl-, and aryl
electrophiles catalyzed by Cr(III) salts in the presence of a
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stoichiometric amount of AlMe3 (Figure 1b), which provides
access to variety of compounds including alkynylated
and 5. To secure full conversion of the amide substrate, we used
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2
3
4
5
6
7
8
a
two equivalents each of AlMe3 and 2. The reason for using excess
amount of AlMe3 and 2 might be ascribed to the undesired side
reaction between them. By contrast, the allylation reaction
discussed in Table 3 requires only one equivalent of AlMe3,
indicating that two of the three methyl groups potentially act as a
base to deprotonate C–H and N–H.
moclobemide, an antidepressant drug (Figure 1c). The reaction is
compatible with a variety of functional groups, including ether,
amine, ester, boronate, and halide, most notably, aryl iodide
functionalitie–a feature reflecting the advantages of this redox-
neutral chromium(III)-dominated reaction. The reaction takes
place with as little as 1 mol% of an inorganic chromium(III) salt
without using extraneous ligand. Stochiometric and kinetics studies
as well as kinetic isotope effects suggest that the catalytic cycle
consists of a series of thermally stable but reactive intermediates
bearing two molecules of the amide substrate on one metal atom
such as B (X = H or E), and also that one of these chromate(III)
complexes (C), a biscyclometallated intermediate,11 takes part in
the alkynylation, allylation, and naphthalenation reactions with
corresponding electrophiles. The proposed mechanism accounts
for effective suppression of methyl group delivery from AlMe3 for
ortho-C–H methylation. In light of the undervalued utility of
chromium among base metals in catalysis,12 the present result
suggests a new direction of research for its use in organic
synthesis.13
The use of THF as a cosolvent resulted in lower yield and in
the formation of the dimer 5 in 16% yield (Table 1, entry 2), while
THF was found to be the solvent of choice in the allylation reaction
discussed below. The ethereal solvent was found to be essential for
the reaction because the reaction did not proceed in toluene alone
(entry 3). Cr(acac)3 (70%) and CrBr3 (82%) also served as catalysts
(entries 4 and 5). For reasons unknown, however, Cr(acac)3 gave
approximately 10% higher yield than CrCl3 for the allylation
reactions discussed in the following paragraph. The reaction needs
heat and prolonged reaction time, because reducing the temperature
or reaction time caused lower conversion (entry 6 and see
Supporting Information Table S3 for details). Interestingly,
MeMgBr and ZnMe2 failed to give the desired alkynylation
product, probably because of the competitive reduction of Cr(III)
(entries 7 and 8). AlEt3 and AlMe2Cl also served as an effective
base, but resulted in a reduced yield of 3 (entries 9 and 10).
AlMe2Cl as effective base suggested that the sceond methyl from
AlMe3 also participates in the deprotonative C–H activation.
Reducing the amount of AlMe3 from 2.0 equiv to 1.5 equiv or 1.0
equiv resulted in a decreased yield of 3. Additionally, it is
worthwhile to mention FeCl3 and CoCl2 were totally ineffective in
replacement of CrCl3 under the optimized condition.
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RESULTS AND DISCUSSION
We first describe the alkynylation reaction and the key
parameters of this reaction, the allylation, and the naphthalenation,
followed by a mechanistic analysis that sheds light on the formation
of the biscyclometallated11, 14 chromium(III) ate complex C, and its
role in the catalytic cycle.
Alkynylation. The catalytic use of CrCl3 is first described for
C–H alkynylation15 using substituted ethynyl bromide as an
electrophile. In Figure 2, we illustrate a gram-scale reaction of N-
Table 1. Chromium(III)-catalyzed Synthesis of
3
by
Alkynylation of 1 with 2 under Diverse Catalytic Conditions
4-methoxybenzyl-3-methylbenzamide
(1,
PMB
=
4-
methoxybenzyl) using 1.0 mol% of CrCl3 as catalyst and 2.0 equiv
of AlMe3 to deliver the desired C–H alkynylation product 3 in 88%
1
isolated yield (1.38 g, 94% yield determined using H-NMR). A
full conversion of 1 was observed. We found neither a methylated
product10 4, nor a dimer16 5 in the crude reaction mixture.
aStandard condition is shown in Figure 2. The yield was determined using
GC with tridecane as an internal standard. bYield of isolated product.
cDimer 5 formed in 16% yield. dTHF as a solvent. eAlMe2Cl (3 equiv).
The scope of the C–H alkynylation reaction is illustrated in
Table 2. Besides N-PMB arene carboxamide (6, 7), N-benzyl (8)
and N-methyl (9) carboxamides also took part in the reaction. The
reaction showed exclusive monoselectivity on benzamide and
para-substituted benzamides, probably because the rigid alkyne
substituent on the ortho-position prohibits the formation of a
chromacycle on the other side (7, 11). Steric hindrance at the ortho-
position was not tolerated as shown for o-toluamide (17). Steric
hindrance on a meta-position (next to the ortho-position to be
functionalized) is partially tolerated, as shown with 3,5-
Figure 2. Cr(III)-catalyzed ortho-C–H alkynylation of benzamide.
Table 1 shows the key reaction parameters of the Cr(III)-
catalyzed C–H alkynylation of the PMB carboxamide 1 with a
silylethynyl bromide (see Tables S3 and S4 for other details).
Heating a mixture of 1 (1.0 equiv), 2 (2.0 equiv), CrCl3 (10 mol%),
and AlMe3 (2.0 equiv) in a mixed toluene and 1,2-DME solvent at
70 ºC under argon resulted in the formation of 3 in 83% isolated
yield (89% GC yield) (Table 1, entry 1). The product was free of 4
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dimethylbenzamide producing a C–H alkynylation product in 60%
iodide moiety is tolerated (16) without generating
1
2
3
4
5
6
yield (19). Such a sterically hindered C–H bond flanked by a
methyl group and a directing group was not smoothly cleaved
either under iron catalysis applying the bisphosphine ligand we
previously reported,4,5 or under many conditions using a precious-
metal catalyst.17 We ascribe this difference to the small size of the
chromium ion and the absence of a bulky ligand on the metal atom.
hydrodeiodonation byproduct – a side reaction that sometimes
plagues precious-metal catalysis. This iodide tolerance is in
agreement with the absence of a reduced chromium species in the
catalytic mechanism that we propose in this study.12f Thiophene-2-
carboxamide gave the desired product in moderate yield (21). The
reaction also applies to the alkynylation of alkene carboxamide to
generate an enyne structure (22). Comparison among
7
8
9
Table 2. Scope of Chromium(III)-catalyzed C–H Alkynylation
trimethylsilyl-
(23),
triethylsilyl-substituted
(3),
and
triisopropylsilyl (TIPS, 24) groups suggests a small steric effect.
tert-Butyl-substituted alkynyl bromides can be used (23), while
primary and secondary alkyl-substituted alkyne bromides (e.g., n-
hexyl- and cyclohexyl-) cannot, probably because of the presence
of the propargylic C–H bond. The reaction can be used for C–H
alkynylation of moclobemide (26), a drug for managing depression.
Aryl- and heteroaryl-substituted alkynyl bromides gave the desired
ortho-alkynylation products in moderate yields (27–32). 2-
(Bromoethynyl)-mesitylene gave the highest yield compared with
other aryl and heteroaryl-substituted alkynyl bromides, probably
because of the enhanced thermal stability of this bromoalkyne by
steric hindrance.
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N-8-Quinolinyl and N-2-picolyl groups that often serve as a
directing group for C–H activation inhibited the reaction, probably
because the basic nitrogen atoms on the bidentate directing group
interfere with the formation of the cyclometallated intermediates.
Tertiary benzamides and 2-phenylpyridine, both of which lack an
acidic NH group, failed to participate in the reaction.
Allylation. The allylation showed a reaction profile slightly
different from that of the alkynylation such as a preference for
Cr(acac)3 as catalyst (more soluble), and THF as solvent. Testing a
series of allylic electrophiles for ortho-C–H allylation5a,7b,18
showed allylic bromide to be the best allylic electrophile (Figure
3). Allylic chloride and allylic iodide gave lower yields than allylic
bromide. Allyl phenyl ether, an electrophile effective for iron-
catalyzed ortho-C–H allylation,5a,7b did not produce the desired C–
H allylation product. Allylic acetate did not participate in the
reaction, and an allyl phosphate did so in low yield.
Figure 3. Chromium(III)-catalyzed C–H allylation with different
allylic electrophiles
Unlike the C–H alkynylation, the allylation summarized in
Table 3 requires only one equivalent of AlMe3 to achieve good to
high yield. A small amount of diallylated product was observed for
the parent benzamide (33, 34). N-Isopropyl and N-aryl substituents
(37, 38) suppress the diallylation. C–H allylation proceeded well
with both electron-rich and electron-deficient amides (39, 40). Aryl
pinacol boronate (41) and aryl iodide (42), substituents useful for
further transformation, survived the reaction conditions. Alkenyl
carboxamide was allylated to deliver a 1,4-diene product (47). In
all cases examined, isomerization of C–H allylation products to
form styrenyl-type products was not observed under the Cr(III)-
catalyzed reaction condition.19 Substituted allylic bromides such as
2-methylallyl bromide, 3-methyl-2-butenyl bromide, and cinnamyl
bromide barely participated in the reaction, suggesting that
interaction of the olefinic part of the electrophile with a metal
center is crucial for the reaction.
aAll reactions were performed on a 0.4 mmol scale, and yields refer to the
b
isolated product. CrCl3 (1 mol%). Alkynyl chloride was used instead of
c
d
e
alkynyl bromide. CrCl3 (10 mol%). CrCl3 (2 mol%). Yield determined
using GC with tridecane as an internal standard. fReactions performed at 90
ºC. gTHF was used instead of DME at 80 ºC.
The reaction takes place effectively for both electron-rich (12,
18) and electron-deficient (13, 20) substrates, and is compatible
with a variety of functional groups, including ether (12), aryl
halides (13–16), amine (18), and ester (20). Interestingly, an aryl
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Table 3. Scope of Chromium(III)-catalyzed C–H Allylation
1
with Allylic Bromide
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Stochiometric Study of Reactive Cr(III) Intermediates:
The present reaction has several unique features among methods
for functionalization of unreactive C–H bonds. The reaction does
not require any extraneous ligand, taking place with only 1 mol%
of CrCl3, and the scope of the electrophile is rather unusual in that
only bromoalkynes, allyl bromides, and 1,4-dihydro-1,4-
epoxynaphthalene serve as effective electrophiles, whereas
common electrophiles such as alkyl halides, and simple and
electron-deficient olefins do not. We considered that the nature of
the reactive nucleophilic intermediate is worth being probed.
Correlation between the amount of CrCl3 and that of C–H
cleavage product (Figure 4) indicated that all of CrCl3 is converted
to a stable intermediate of 1:2 Cr/substrate stoichiometry (cf. C) in
the presence of excess amide substrate.
A
similar
biscyclometallated chromium(III) species has been reported
previously.14 Heating of the amide 1 and x mol% of CrCl3 in the
presence of one equivalent of AlMe3 at 90 °C for 24 h followed by
DCl/D2O quenching produced partially ortho-C–H deuterated 1 in
>95% recovery with deuteration ratio approximately equal to 2x
when x = 5, 10, 20, and 30. In these experiments (x = 5, 10, 20, and
30), neither a methylated product 4 nor an oxidative dimerization
product 5 was formed. The use of 50 mol % of CrCl3 resulted in
81% deuterium incorporation and produced 4 and 5 in 2% and 8%
yield (mol %), respectively, and the use of 100 mol % CrCl3
resulted in as much as 6% and 21% of 4 and 5, along with 92%
deuterium incorporation in recovered 1. The results of experiments
(x = 50, 100) suggested instability of the 1:2 chromacycle C in the
presence of an excess amount of CrCl3 to either undergo reductive
elimination or equilibrate to the 1:1 complex. Note that using CrCl2
did not give any deuterium incorporation and resulted in a full
recovery of 1.
aAll reactions were performed on a 0.4 mmol scale, and yields refer to the
isolated product. Cr(acac)3 used in 2.0 mol %. bCr(acac)3 used in 10 mol %
c
where lower catalyst loading afforded lower yield. Cr(acac)3 used in 1.0
mol %. dC–H methylation product was detected in 24% yield.
Naphthalenation.
We
found
that
1,4-dihydro-1,4-
epoxynaphthalene serves as a good electrophile to furnish ortho-
20
C–H naphthalenation product as shown in Table 4. Both N-
methylbenzamide and N-PMB-substituted benzamide reacted
smoothly and gave products in comparable yield (48 and 49), and
both electron-rich and electron-deficient benzamide were effective
substrates (56 and 57).
Table 4. Chromium(III)-catalyzed C–H Naphthalenation with
1,4-Dihydro-1,4-epoxynaphthalene
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O
H
CrCl3 (x mol %)
PMB AlMe3 (1.0 equiv)
DCl/D2O
Me
N
1
2
3
4
5
6
7
H
DME/toluene
(v/v = 1:1, 1.0 M)
90 °C, 24 h
Me
1
O
O
O
PMB
Me
PMB
NH
Me
PMB
N
H
N
HN
+
+
H
PMB
O
(H/D)
Me
1-D
5
4
Me
8
9
CrCl2: no reaction, no D incorporation
100
90
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90%
1
I
81% D
56% D
%D
III
5
4
II
0
20
40
CrCl3 (xmol %)
60
80
100
Figure 4. C–H activation/deuteration of 1 with x mol% of CrCl3 in
the presence of AlMe3
As shown in Figure 5a, the intermediate with a 1:2
Cr/substrate stoichiometry is reactive with bromoacetylene 2 under
the same thermal and solvent conditions as those used for the
catalytic reaction. The 1:2 complex formed at x = 50 reacted with
2 to give the C–H alkynylated product 3 in 42% yield based on the
amount of chromium (Figure 5a). A 1:1 Cr:substrate complex
formed at x = 100 was unreactive toward electrophiles as shown in
Figure 5b, c, while high ortho-deuteration ratio revealed cleavage
of the C–H bond . We surmise that the 1:1 complex formed after
C–H cleavage could be a neutral chromium(III) species. This
species would not play any significant role in catalysis, where a
large excess of the amide substrate converts it to the 1:2 complex
C. At this stage, we could obtain neither NMR data nor a single
crystal suitable for crystallographic analysis for the 1:2 and 1:1
complexes.
Figure 5. Stochiometric generation of 1:2 and 1:1 Cr(III)/amide
complexes.
The 1:2 complex C prepared in situ acts as a catalyst for the
C–H alkynylation reaction as shown in Figure 6. Deuterium
quenching experiments in Figure 4 show generation of a
biscyclometallated chromium (III) species upon heating a mixture
of CrCl3 (30 mol%), AlMe3 (1.0 equiv), and 1 at 90 ºC for 24 h. It
was observed that 10 mol% of C generated in situ from 0.40 mmol
of
1
effected the C–H coupling between N-PMB-p-
methoxybenzamide (0.40 mmol) and bromoalkyne 2 to give the
desired product 12 in 83% yield (0.33 mmol) together with the
product 3 derived from 1 in a small amount (0.016 mmol).
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Figure 6. Catalytic activity of biscyclometallated Cr(III)
intermediate C generated in situ.
Kinetics of the Catalytic Cycle: With the reactivity of
intermediates identified in stoichiometric reactions, we next
examined the kinetics of the catalytic reaction. Kinetic isotope
effect (KIE) experiments on two parallel reactions using a
benzamide and its d5-derivative showed a primary KIE of 2.9,
indicating that cleavage of the C–H bond is the turnover-limiting
step of the reaction (Eq. 1). CDH3 was generated from benzamide-
d5 (detected by 1H-NMR analysis), proving unambiguously that the
methyl group on AlMe3 deprotonated an ortho-C–H bond in the
amide. The reaction was not affected by the addition of a radical
Figure 7. Kinetics of the ortho-C–H alkynylation of amide 1 with
bromoacetylene 2 in the presence of AlMe3 and Cr(acac)3 in
DME/toluene (1:1) at 70 ºC. The initial rate (Δ[3]/Δt) was plotted
against the initial concentration of the reactant varied for the range
shown below. (a) Initial reaction rate against the initial
concentration of Cr(acac)3 [Cr(acac)3]0. Reaction conditions: 1
(0.50 M), 2 (1.0 M), Cr(acac)3 (2.5×10-3–4.0×10-2 M), AlMe3
(1.0 M), DME/toluene (1:1), 70 ºC, up to 4 h; (b) Initial reaction
rate against the initial concentration of amide [1]0. Reaction
conditions: 1 (0.063–0.50 M), 2 (1.0 M), Cr(acac)3 (0.010 M),
AlMe3 (1.0 M), DME/toluene (1:1), 70 ºC, up to 4 h; (c) Initial
reaction rate against the initial concentration of AlMe3 [AlMe3]0.
[Al*]0 = [AlMe3]0 – 0.5 M. Reaction conditions: 1 (0.50 M), 2 (1.0
M), Cr(acac)3 (0.010 M), AlMe3 (0.50–1.0 M), DME/toluene (1:1),
70 ºC, up to 4 h; (d) Initial reaction rate against the initial
concentration of alkyne [2]0. Reaction conditions: 1 (0.50 M), 2
(0.050–2.0 M), Cr(acac)3 (0.010 M), AlMe3 (1.0 M), DME/toluene
(1:1), 70 ºC, up to 4 h.
scavenger
such
as
1,1-diphenylethylene
and
9,10-
dihydroanthracene (see Supporting Information Fig. S6 for details),
eliminating the possibility of a free radical mechanism.
Based on the KIE and the kinetics data, we suggest a
catalytic cycle in Figure 8a. At the very beginning of the reaction,
an aluminum amide dimer reversibly dissociates into a monomer I
(top left) that quickly reacts with the inorganic chromium salt to
form the chromate(III) complex C (which may be the same as III
in the catalytic cycle). Once the cycle starts, I undergoes quick
ligand exchange with an alkynylated chromate(III) anion (VI) to
form the product VII and the first key Me–Cr(III) intermediate II
(i.e., B (X = H) in Figure 1b). The turn-over limiting C–H
activation within II may occur via a deprotonation mechanism
(TS1, Figure 8b), similarly to organoiron(III) ate species,1a to
produce the second key intermediate, the 1:2 complex III (i.e., C
The kinetic orders of the alkynylation of amide 1 with the
bromoalkyne 2, as determined for chromium, 1, AlMe3, and 3 using
Cr(acac)3 as a Cr(III) source soluble in DME/toluene (Figure 7), is
consistent with the KIE data (Eq. 1) in that the C–H activation is
the slowest step in the catalytic cycle. Details of the analysis are
shown in Supporting Information. The reaction was found to be
first order in Cr(acac)3 (Figure 7a) and half order in the amide 1
(Figure 7b). As shown in Figure 7c, the reaction occurs only at >1:1
stoichiometry between AlMe3 and 1. These findings agree well
with the results of crystallographic studies on the formation of a
stable dimeric complex from a secondary amide and AlMe3 (cf. Eq.
2),21 from which a reactive monomer reversibly forms and takes
part in the catalytic cycle. The reaction was found to be 0.38 order
in the bromoalkyne 2, suggesting reversible coordination of the
alkyne to a chromium species in the catalytic cycle.
in Figure 1b) that undergoes alkynylation via
a
chromate(III)/alkyne complex IV. The mechanism of the
alkynylation (TS2) on chromate species may resemble the
transition state of the alkenylation of R2Cu(I)Li that takes place via
a
cuprio(III)cyclopropane intermediate (Figure 8c).22
A
chromium(III) bromide V generated in this step quickly reacts with
AlMe3 to form VI (i.e., B (X = E) in Figure 1b), which generates
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the aluminum amide product VII upon transmetallation with I to
complete the catalytic cycle.
ASSOCIATED CONTENT
1
2
3
4
5
6
7
8
Supporting Information
In the catalytic cycle using 1–2 mol% Cr(III), we see a
Experimental procedures and physical properties of the
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
reason for the exclusive formation of the desired product, and the
absence of either C–H methylation (4) or the dimerization side
reactions (5); that is, the Cr(III) center always bears four anionic
ligands and the system remains in a reductive environment
throughout the cycle. We saw 4 and 5 only when we used an
unnecessary excess Cr(III) (refer to Figure 4).
AUTHOR INFORMATION
Corresponding Author
*rui@chem.s.u-tokyo.ac.jp; *nakamura@chem.s.u-tokyo.ac.jp
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ORCID
Rui Shang: 0000-0002-2513-2064
Eiichi Nakamura: 0000-0002-4192-1741
Present Addresses
†RIKEN Center for Sustainable Resource Science, Wako, Saitama,
Japan.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank MEXT for financial support (KAKENHI Grant-in-Aid
for Specially Promoted Research 19H05459 to E.N., and
KAKENHI Grant-in-Aid for Young Scientists JP19K15555 to
R.S.)
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41
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44
45
46
47
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50
51
52
53
54
55
56
57
58
59
60
10
ACS Paragon Plus Environment