Rhodium(iii) vs. cobalt(iii): a mechanistically distinct three-component C-H bond addition cascade using a Cp*RhIII catalyst

Article abstract of DOI:10.1039/c8cc08792j

Three-component C-H bond additions across two different coupling partners remain underdeveloped. Herein, we report the first three-component Rh^III-catalyzed C-H bond additions to a wide range of dienes and aldehydes. Our method constitutes a complementary access with Ellman's Co^III-catalytic system to homoallylic alcohols.

Full text of DOI:10.1039/c8cc08792j

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Rhodium(III) vs. cobalt(III): a mechanistically
distinct three-component C–H bond addition
cascade using a Cp*Rh catalyst†
Cite this: Chem. Commun., 2019,
5, 695
III
5
Received 4th November 2018,
Accepted 7th December 2018
Ruirui Li, Cheng-Wei Ju and Dongbing Zhao
*
DOI: 10.1039/c8cc08792j
rsc.li/chemcomm
Three-component C–H bond additions across two different coupling generate a nucleophilic allyl-M species, which may further undergo
partners remain underdeveloped. Herein, we report the first three- an addition to an aldehyde. During the preparation of this manu-
III
III
component Rh -catalyzed C–H bond additions to a wide range of script, Ellman et al. reported three-component Co -catalyzed C–H
10
dienes and aldehydes. Our method constitutes a complementary bond addition to dienes and aldehydes (Fig. 1a). However, their
III
access with Ellman’s Co -catalytic system to homoallylic alcohols.
method still suffers from limitations: (1) the use of 1-aryl-1,3-
butadienes did not provide the three-component coupling product
Transition metal-catalyzed directed C–H bond functionaliza- and (2) the unconjugated dienes have never been investigated.
III
tion with unsaturated p-bonds has become an attractive alter- Herein, we report the first three-component Rh -catalyzed C–H
1
native to assemble keystone building blocks. Of the many bond additions to dienes (Fig. 1b). Our further study indicates that
III
III
transition-metal catalysts that facilitate this process, Cp*Rh
the Rh -catalytic system in this reaction involved a different rate-
III
catalysts have been demonstrated to be among the most determining step and catalytic cycle from Ellman’s Co -catalytic
useful. Very recently, some studies demonstrated that the system with a different scope of substrates.
Cp*Co catalyst could promote the reactions already established
with Cp*Rh catalysts to access identical products. More inter- 2-phenyl pyridine, 1-phenyl-1,3-butadiene and ethyl glyoxylate.
estingly, further research proved that the Cp*Co catalyst and After an extensive survey, the optimized conditions were identified
Cp*Rh catalyst would also show different reactivities and sub- to be: [RhCp*(CH
2
III
We sought to identify the reactivity with the reaction between
III
3,4
III
III
3
CN)
3
](SbF
6
)
2
as the catalyst (10 mol%) and a
strate scopes, which provide the opportunity to build up comple- mixture of acetonitrile and hexafluoroisopropanol (HFIP) as the
5
mentary access to important organic transformation.
solvent (4 : 1; 0.5 mL), wherein product 4a was afforded in 68%
Sequential multicomponent reactions have long been recog-
nized as a powerful tool to enable the rapid generation of
6
complex molecular scaffolds. However, despite the growing
number of publications describing transition metal-catalyzed
1
,7
directed C–H bond addition,
three-component C–H bond
additions across two different coupling partners remain under-
developed. In 2016, Ellman described the first three-component
III
8
C–H addition cascade by Rh -catalysis. Later on, Ellman proved
that the three-component C–H addition cascade can be signifi-
III
9
cantly improved by employment of a Cp*Co -catalytic system.
III
III
However, at that stage, both Rh and Co -systems were only
efficient with a,b-unsaturated ketones. Inspired by Ellman’s work,
we rationalized that a switch of the a,b-unsaturated ketone to a
simple diene in three-component C–H bond addition would
State Key Laboratory and Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin, 300071, China.
E-mail: dongbing.chem@nankai.edu.cn
†
Electronic supplementary information (ESI) available. CCDC 1864795 and
864796. For ESI and crystallographic data in CIF or other electronic format
1
Fig. 1 Rhodium(III) vs. cobalt(III) in three-component C–H bond addition
see DOI: 10.1039/c8cc08792j
to dienes and aldehydes.
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a
Table 1 Control experiments for the screening of reaction conditions
III
b
Entry
M
-catalyst
Solvent
Yield [%] (d.r.)
1
2
3
4
5
6
[RhCp*(CH
3
CN)
/AgSbF
3
](SbF
6
6
)
2
CH
CH
CH
CH
CH
3
3
3
3
3
CN/HFIP
CN/HFIP
CN/HFIP
CN/HFIP
CN
68 (90 : 10)
55 (94 : 6)
N.R.
N.R.
65 (85 : 15)
N.R.
[Cp*RhCl
2
]
2
[Cp*Co(CO)I
[Cp*Co(CO)I
2
]/AgSbF
]/AgNTf
6
2
2
[RhCp*(CH
[RhCp*(CH
[RhCp*(CH
—
3
3
3
CN)
CN)
CN)
3
3
3
](SbF
](SbF
](SbF
6
6
6
)
)
)
2
2
2
HFIP
c
7
8
CH
CH
3
CN/HFIP
CN/HFIP
64 (86 : 14)
N.R.
3
a
III
Reactions were carried out using M catalyst (10 mol%), 1a (0.2 mmol),
2
0
a (0.4 mmol), and 3a (0.24 mmol) in a CH
2
.4 mL : 0.1 mL) for 24 h at 100 1C under an N atmosphere. Isolated
1 c
3
CN/HFIP mixture (0.5 mL,
b
yields; the diastereoselectivities were checked by H NMR. Reaction
time: 48 h.
yield with 90 : 10 diastereoselectivity at 100 1C (Table 1, entry 1).
Control experiments were subsequently conducted to understand
the role of each component. Switching of [RhCp*(CH
3 3 6 2
CN) ](SbF )
to the precatalyst [Cp*RhCl with AgSbF led to a decrease in the
2
]
2
6
III
III
yield (Table 1, entry 2). Changing the Rh catalyst to Co species
dramatically reduced the yield of this three component C–H
addition cascade (Table 1, entries 3 and 4). The effect of
each component of the mixed solvents was also investigated
1
0
(
entries 5 and 6). It has been proved that both the solvents are
important for achieving both high reactivity and good diastereo- Fig. 2 The substrate scope of dienes. If we didn’t point out the diastereo-
selectivity, it means only a single diastereoisomer was observed for this
selectivity. Extending the reaction time is not advantageous
(
III
substrate in the reaction.
Table 1, entry 7). Finally, we proved that the Rh catalyst is
essential for this three component C–H addition cascade
Table 1, entry 8).
Having optimized the reaction conditions, we first investi- (Fig. 2, 2w to 4n; 2x and 2y to 4q), which indicated an iterative
(
gated the substrate scope of dienes using 1a as the C–H bond protodemetalation/allylic activation process of the CQC bond
substrate and 3a as the aldehyde (Fig. 2). The terminal conjugated during this reaction for these substrates.
dienes bearing an aryl group at the a-position (Fig. 2, 2b–l), which
Subsequently, we examined the scope of C–H bond sub-
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are incompatible with Ellman’s Co -catalytic system, were first strates in this three-component C–H activation/chain walking/
tested under the optimized conditions. In general, with electron- addition cascade. As shown in Fig. 3, a series of three-component
neutral, electron-withdrawing or electron-rich substituents at the coupling products bearing substituents at the 4-, 5-, and/or
ortho, meta-, or para-position of the phenyl ring, the reaction 6-positions of the phenyl ring were synthesized in good yields
proceeded smoothly, with comparable yields and diastereo- and high diastereoselectivities (Fig. 3, 5a–t). It is important to
selectivities (Fig. 2, 4b–l). Additionally, 1-heteroaryl substituted stress that the reactions were preferred at the more sterically
1,3-butadiene 2m was also a capable substrate. Furthermore, accessible position when a meta-substituent was attached to the
we proved that the a-alkyl substituted 1,3-butadienes 2n–r also phenyl ring of the C–H bond compounds (Fig. 3, 5n–r). This
underwent the reaction smoothly and the yields and diastereo- method was remarkably compatible with important functional
selectivities were comparable to those of the 1-aryl substituted groups such as halogens and OTf, ester, ketone, vinyl, hydroxy,
1
,3-butadiene 2b–l (Fig. 2, 4n–r). The sterically congested and trifluoromethoxy groups, which could be subjected to
a,a-disubstituted 1,3-butadienes 2s and t are also reactive further synthetic transformations. Our method is suitable for
Fig. 2, 4s and t). Furthermore, some of the 2-substituted not only diverse 2-aryl pyridines, but also the other C–H
,3-butadienes could also be converted into the corresponding substrates bearing different directing groups such as pyrimidines
products with decreased yields (Fig. 2, 4u and v). In addition, and pyrazoles (Fig. 3, 5u and 5v).
(
1
the skipped dienes 2w and x and isolated diene 2y were also
Furthermore, we wondered if aryl aldehydes are also suitable
explored to expand the range of diene substrates. Interestingly, as the coupling substrates. The reaction between 1a, 2a and
all of the skipped dienes and isolated diene gave identical benzaldehyde was examined. Unfortunately, only trace amounts
products with their corresponding conjugated 1,3-dienes of the desired product were obtained. After an extensive screening,
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Fig. 3 The scope of C–H bond substrates. If we didn’t point out the
diastereoselectivity, it means only a single diastereoisomer was observed
for this substrate in the reaction.
we found that the reaction occurred smoothly with good yields
with the assistance of stoichiometric amounts of Zn(OAc) and
2
pentafluorobenzoic acid A1 under neat conditions upon switching
the benzaldehyde to aryl aldehyde bearing an electron-withdrawing
group at the para- or meta-position (Fig. 4, 6a–e). This result clearly
highlights the difference and the complementarity between
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III
Co and Rh catalysis for this three-component C–H bond
addition cascade.
Fig. 5 A series of mechanistically insightful reactions.
The structures and the relative stereochemistry for all the
products were assigned from analogy to the crystal structures 4s
between 2-phenyl pyridine derived-diene 8 and 3a as well as the
reaction between 1s, diene 8 and 3a (Fig. 5e and f). Both of the
reactions only gave around 10% yield of product 4a. In addition, it
was observed that the reaction between 2-phenyl pyridine derived-
alkene 10 and 3a is incapable of forming the desired product 4a
11
and 5d (Fig. S1, ESI†). Then, a series of mechanistically insightful
reactions were conducted. First, the value of k /k = 1.0 as well as
the value of KIE = 1.3 indicated that the C–H bond cleavage
H
D
12
process is not rate-determining (Fig. 5a). Additionally, we proved
III
3
that by using 10 mol% Rh catalyst 7 in CH CN/HFIP (4 : 1), the
(Fig. 5g). These observations imply that (1) the synergistic reactivity
reaction between 1s, 2a and 3a works efficiently (Fig. 5b), suggest-
ing the plausible intermediacy of cyclometalated complex 7 in the
catalytic cycle. Furthermore, a series of control experiments were
carried out. First, we separately subjected diene 2a and aldehyde
of the diene and aldehyde might be crucial; (2) a stepwise pathway
involving free intermediates such as 8 or 10 is rather unlikely;
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and (3) the internal hydride transfer involving Rh -H species is
unlikely. Instead, a pathway in which the hydroarylated product
between 2-phenyl pyridine 1a and diene 2a stays coordinated to
the rhodium center until the addition to aldehyde 3a step is
complete seems more likely. When the reaction was performed
with 4,4-di-deuterated diene, H/D scrambling in the product
3a to the standard conditions with 1a (Fig. 5c and d). Diene 2a
resulted in only a 10% yield of diene 8. Attempted coupling of 1a
with aldehyde 3a only resulted in a trace amount of 9 with more
than 95% recovery of 1a. Furthermore, we conducted the reaction
0
has never been observed and mono-deuterated product 4a is
exclusively formed in 60% yield (Fig. 5h). It reveals that the
intramolecular H-migration during the reaction seems not to
occur and the irreversible allylic C–H bond activation is
more likely to be involved, which is different from Ellman’s
III
Co -catalytic system. Additionally, when the reaction was
performed in CH CN/MeOD, deuterium incorporation was
3
observed at the 4-position of 4a (Fig. 5i), implying that proto-
demetalation of C–Rh species might occur.
On the basis of our mechanistic experiments, we propose a
directed C–H bond cleavage to form intermediate 7 as the first
Fig. 4 The scope of aldehyde substrates. Only single diastereoisomers
were detected for these substrates in the reaction.
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Notes and references
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Fig. 6 Proposed catalytic cycle for the Rh -catalyzed C–H addition
cascade.
2
018, 8, 242; (e) T. Piou and T. Rovis, Acc. Chem. Res., 2018, 51, 170.
III
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3
III
step in the presence of Rh catalyst, which is followed by
alkene coordination and insertion, thus affording the Z - or
Z -Rh -allyl species 11 (Fig. 6). The formation of resulting
Rh -allyl species 11 presumably involves protodemetalation
with the H-source (ROH) to form intermediate 12, which might
further undergo allylic C–H bond activation to afford Rh -allyl
species 13 with the assistance of the directing group. The
nucleophilic addition of an aldehyde 3 with the Rh -allyl
species 13 and subsequent protonolysis would provide the desired
homoallylic alcohols 4–6 and regenerate the Rh catalyst. For
nonconjugated dienes, the reaction would involve a sequential
elimination/reinsertion process of the double bond to access the
thermodynamically favored Rh -allyl species 11.
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3
III
III
3
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2
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III
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III
III
5
6
III
III
In conclusion, we have developed the first Rh -catalyzed
(c) Y. Suzuki, B. Sun, K. Sakata, T. Yoshino, S. Matsunaga and M. Kanai,
directing group-assisted three-component C–H addition cascade
across dienes and aldehydes. Our method is suitable for a wide
range of conjugated and nonconjugated dienes, and constitutes
a complementary access with Ellman’s Co(III) catalytic system.
Mechanistic experiments indicated a directed aryl C–H bond
activation/directed allylic C–H bond activation/addition cascade,
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(
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III
7 Some latest examples of Rh -catalyzed two-component CꢀH bond
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III
which is different from Ellman’s proposal in the Co catalytic
system.
We are grateful for the financial support from the National
Natural Science Foundation of China (21871146, 21602115), the
(e) T. Piou, F. Romanov-Michailidis, M. A. Ashley, M. Romanova-
1
000-Talent Youth Program, the Natural Science Foundation of
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8
9
Tianjin (18JCYBJC20400), the Fundamental Research Funds for
the Central Universities and Nankai University.
2016, 55, 12650.
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0 J. A. Boerth, S. Maity, S. K. Williams, B. Q. Mercado and J. A. Ellman,
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1
1
1 CCDC 1864795 (4s) and 1864796 (5d)†.
2 (a) E. M. Simmons and J. F. Hartwig, Angew. Chem., Int. Ed., 2012,
Conflicts of interest
51, 3066; (b) J. Atzrodt, V. Derdau, W. J. Kerr and M. Reid, Angew.
There are no conflicts to declare.
Chem., Int. Ed., 2018, 57, 3022.
698 | Chem. Commun., 2019, 55, 695--698
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