Dirhodium(ii)/P(t-Bu)3 catalyzed tandem reaction of α,β-unsaturated aldehydes with arylboronic acids

Article abstract of DOI:10.1039/c8ob01997e

Phosphine ligated dirhodium(ii) acetate is advocated as a catalyst for the synthesis of aryl alkyl ketones by the tandem reaction of α,β-unsaturated aromatic or aliphatic aldehydes with arylboronic acids. This tandem procedure included arylation followed by the isomerization reaction. This method exhibits good functional group tolerance and has a broad substrate scope. With the conjugated aldehydes, the one-step synthesis of γ,δ-unsaturated ketones was realized through this reaction. It is noteworthy that the length of the Rh-P bond is an important factor affecting catalytic reactions. The comparative analysis of the crystal structures of axially alkylphosphane and arylphosphane ligated dirhodium(ii) acetate revealed that the shorter Rh-P bond length favors the isomerization process as compared to the longer one. In addition, the dirhodium(ii) compound can be recovered after the completion of the reaction.

Full text of DOI:10.1039/c8ob01997e

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Takeharu Haino et al.
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DOI: 10.1039/C8OB01997E
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ARTICLE
Dirhodium(II)/P(t‐Bu)3 Catalyzed Tandem Reaction of ,‐
Unsaturated Aldehyde with Arylboronic Acids
Ziling Ma and Yuanhua Wang*
Received 00th January 20xx,
Accepted 00th January 20xx
The phosphine ligated dirhodium(II) acetate is advocated as a catalyst for the synthesis of aryl alkyl ketones by the tandem
reaction of‐unsaturated aromatic or aliphatic aldehydes with arylboronic acids. This tandem procedure included
arylation followed by isomerization reaction. This method exhibits good functional group tolerance and has a broad
substrate scope. With the conjugated aldehydes, the one‐step synthesis of ‐unsaturated ketones was realized through
this reaction. It is noteworthy that the length of Rh‐P bond is an important factor affecting catalytic reactions. The
comparative analysis of the crystal structures of axially alkylphosphane and arylphosphane ligated dirhodium(II) acetate
revealed that the shorter Rh‐P bond length favors the isomerization process as compared to the longer one. In addition,
dirhodium(II) compound can be recovered after completion of the reaction.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
affected across the Rh‐Rh bond (Fig 1).4 We previously reported the
efficient preparation of axially ligated Rh2(OAc)4(P(t‐Bu)3)2
A high degree of potential cooperativity and electronic
communication between the metal‐metal covalent bonds lead to the
evidence that multi‐metallic synergism contributes to the design of
new catalysts for their potential use in organic syntheses. To
comprehend the functional approach of these catalysts, it is
important to understand the multinuclear reaction pathways and to
develop the well‐defined multinuclear platforms. Dirhodium(II)
complexes (Rh2(II)) possess a dimeric “paddlewheel” structure
surrounded by Rh‐Rh single bond with four bridging ligands and two
axial ligands and hence act as an efficient catalyst for the generation
of carbene and nitrene species.1,2 Although this high symmetrical
structure of Rh2(II) provides two equivalent axial sites as the
catalytically active sites, only one of the two rhodium atoms acts as
an efficient catalytic site at a time during the reaction.1,3 Based on
this observation, the simple and efficient strategy to enhance the
rate and/or selectivity of Rh2(II)‐catalyzed reactions was developed.
complexes with unusually long Rh‐P‐bond length and achieved
their excellent catalytic performance in arylation reactions using
arylboronic acids and isatin derivatives.5 As part of our ongoing
studies on a combined approach of alkyl phosphine ligands (PR3) and
Rh2(II) along with their applicative aspects, the present paper
describes the one‐pot tandem reaction of ,‐unsaturated aldehyde
with arylboronic acids to easily prepare the aryl alkyl ketones in good
yields. The resulting aryl‐alkyl products are the versatile building
blocks for the synthesis of bioactive scaffolds, drugs and natural
products.6 General methods for the synthesis of aryl alkyl ketones
include Friedel‐Crafts acylation reaction,7 benzylic oxidation of
alkylbenzenes,8 and the addition of organometallic reagents to
benzaldehyde.9
However, all these methods suffer various
disadvantages such as relatively harsh reaction conditions, low yields,
limited substrate scope, lack of atomic economy, and complicated
workup and purification procedure. Zou et al. previously reported
the synthesis of aryl alkyl ketones using cinnamaldehyde derivatives
with arylboronic acids catalyzed by rhodium complex.10 In their
procedure, only seven examples were reported and the substrates
were limited to the use of cinnamaldehyde derivatives only. Herein,
we developed the catalytic system that worked very well not only
with‐unsaturated aromatic but also with the‐unsaturated
aliphatic aldehydes. The scope of the reaction was much enlarged as
other conjugated aldehydes like 2,4‐hexadienal was also used. With
the conjugated aldehydes, the one‐step synthesis of‐unsaturated
ketones were realized. As a key intermediate used in the preparation
of heterocyclic compounds, it may take multiple steps to synthesize
in the previous reports.11 In addition, the noble Rh2(OAc)4 was
recovered efficiently after the completion of the reaction.
Fig 1. Structure of dirhodium(
Ⅱ) carboxylate catalysts.
By introducing a ‐donating ligand coordinated axially to one of the
Rh atoms, the electrophilicity of the other Rh atom was found
College of Chemistry, Sichuan University, Chengdu, 610064, P. R. China
E‐mail: yhwang@scu.edu.cn
†Electronic Supplementary Information (ESI) available. See DOI: 10.1039/
x0xx00000x
Results and discussion
Our studies began with the arylation reaction between
cinnamaldehyde 1a and arylboronic acid 2a. Gois and coworkers
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reported the use of Rh2(II)/N‐heterocyclic carbene (NHC) complexes electron‐rich and electron‐poor aryl‐substituted cinnamaldehydes
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to catalyze the reaction of 1a with 2a to obtain the secondary 1a‐1j could be successfully converted to theDdOesI:ir1e0d.10p3r9o/dCu8cOtsB0319w9i7thE
alcohols.12 Instead of producing secondary alcohols, we found that high yields. A variety of functional groups including nitro, methoxy,
the reaction between 1a and 2a catalyzed by Rh2(OAc)4(PR3)2 in halogen group were well tolerated. The steric hindrance of aryl
toluene/H2O under the previously reported conditions gave the 1,3‐ substitution of
1 did not affect the reaction, as both 2‐
diphenylpropan‐1‐one 3aa as the final product. This result drew our methoxycinnamic aldehyde 1b and 2‐nitrocinnamic aldehyde 1d
attention and stimulated us to investigate the reaction inside. gave ketone products 3ba and 3da in 87% and 84% yields,
Various PR3 ligands were screened in the reaction including selected respectively. When more substituted ‐unsaturated aromatic
Buchwald ligands (Ruphos, Breetphos). The bulky alkyl P(t‐Bu)3 aldehydes were applied in this reaction, the secondary
ligand was proved to be the best ligand, resulting in the better yields alcoholswere obtained as major products and only a very small
of 3aa in shorter time (Table 1, entry 8).
amounts of aryl alkyl ketones products were detected.
Under optimal reaction conditions, extending the model reaction
to other aldehyde substrates (Table 2), it was observed that both
Table 1. Evaluation of various PR3 ligand a
entry
1
ligand
No Ligand
yield/%
Trace
2
3
4
Johnphos
PCy3HBF4
PCy2Ph
15
8
5
5
6
7
PCyPh2
PPh3
42
49
24
Ruphos
8
Brettphos
Trace
88
9 b
[(t‐Bu)3PH]BF4
a Unless otherwise noted, all reactions were performed by using 1a (0.50 mmol), 2a (0.55 mmol), Rh2(OAc)4 (1 mol %), Ligand (2.5 mol %) and K2CO3 (10 mol %) in 2 mL
of toluene/H2O (v/v = 3/1) at 90 ℃ for 4 h under N2. Yield of 1H NMR. b Yield of isolated product.
2 | J. Name., 2012, 00, 1‐3
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Table 2. The scope of α, β‐unsaturated aromatic aldehydes 1 with arylboronic acids 2a
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DOI: 10.1039/C8OB01997E
entry
1
R1
2‐OMe (1b)
2‐Cl (1c)
2‐NO2 (1d)
4‐OMe (1e)
4‐Me (1f)
4‐Br (1g)
4‐Cl (1h)
4‐F (1i)
4‐NO2 (1j)
H (1a)
R2
H (2a)
product
3ba
3ca
3da
3ea
3fa
yield/%
87
85
84
85
89
88
84
82
80
86
89
82
87
65
85
86
84
84
89
87
85
87
87
67
2
H (2a)
3
H (2a)
4
H (2a)
5
H (2a)
6
H (2a)
3ga
3ha
3ia
7
H (2a)
8
H (2a)
9
H (2a)
3ja
10b,c
11
12
13
14b
15
16
17
18b
19
20
21b
22d
23
24b
2‐OMe (2b)
2‐Me (2c)
3‐OMe (2d)
3‐Me (2e)
3‐NO2 (2f)
4‐OMe (2g)
4‐t‐Bu (2h)
4‐Me (2i)
4‐Ph (2j)
4‐Cl (2k)
4‐F (2l)
3ab
3ac
3ad
3ae
3af
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
3ag
3ah
3ai
H (1a)
H (1a)
H (1a)
3aj
H (1a)
3ak
3al
H (1a)
H (1a)
4‐CF3 (2m)
1‐naphthyl(2n)
3,5‐Me (2o)
3,5‐F (2p)
3am
3an
3ao
3ap
H (1a)
H (1a)
H (1a)
a Unless otherwise noted, all reactions were performed by using ‐unsaturated aromatic aldehydes 1 (0.50 mmol), arylboronic acids 2 (0.55 mmol), Rh2(OAc)4 (1 mol %),
[(t‐Bu)3PH]BF4 (2.5 mol %) and K2CO3 (10 mol %) in 2 mL of toluene/H2O (v/v = 3/1) at 90 ℃ for 4 h under N2. Yield of isolated product. b The reactions were performed
in 2 mL of 1/1(v/v) DME/H2O. c The reaction was performed by using 2b (0.65 mmol) d The reaction was performed at 90 ℃ for 8 h under N2.
The substrate scope of arylboronic acids 2 was also examined in reactions but gave no products, which indicated the alkenylboronic
this reaction. It was noticed that both electron‐rich and electron‐ acids or alkylboronic acids were not suitable substrates for this
poor aryl substituents of the 2 reacted smoothly with 1a to afford the reaction.
corresponding ketone products 3ab‐3ap (Table 2). It was observed
Further studies showed that the aliphatic unsaturated aldehydes
that several arylboronic acids substrates such as 2b, 2f, 2j, 2m gave were also reacted with 2 to afford the desired products in moderate
fewer yields of the ketone products in toluene/H2O biphasic solvents. yields. As shown in Table 3, crotonaldehyde derivatives 1k‐1o
However, when DME/H2O was used instead of toluene/H2O, the reacted smoothly with different aryl substituted boronic acids 2a‐2m.
ketone products (3ab, 3af, 3aj, 3am) were obtained in good yields. The electron rich arylboronic acids produced better yields as
This could be explained as the solubility of the aforementioned compared to their electron‐deficient analogs. It is worth noting that
arylboronic acids were not good in toluene/H2O solvent. Sterically the ‐unsaturated ketones 3na‐3oa were obtained easily when
bulkier arylboronic acids such as 1‐naphthyphenyl boronic acids 2n conjugated alkene such as compound 1n (2E,4E/2E,4Z = 86/14) and
reacted with 1a to yield the ketones 3an in 87% yield, albeit in a 1o (2E,4E/2E,4Z = 91/9) were used as substrates in this reaction. The
longer time (8 h). The electron‐deficient arylboronic acids such as ‐unsaturated ketones act as key substrates for the synthesis of
3,5‐difluorophenylboronic acid 2p gave the moderate yield of heterocyclic compounds such as N‐sulfonyl substituted pyrrolidines,
product 3ap in the DME/H2O solvent. The boronic acids such as (E)‐ polysubstituted tetrahydrofurans, and highly biologically active
styrylboronic acid, cyclopropylboronic acid et al were also tried in the pyrethridine skeletons.11 However, several steps or harsh conditions
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formed in small amounts and then transformed to diketone 6. These
DOI: 10.1039/C8OB01997E
results indicated that the two catalytic cycles were prevailed in this
reaction: firstly, the 1,2‐addition of arylboronic acid to aldehyde,
followed by isomerization of resulting allylic alcohol intermediate to
afford the ketone product.
were required for the synthesis of‐unsaturated ketones as shown
in previous reports.11b,13 Compared to the reported methods, this
streamlined procedure provides a convenient approach to use the
readily available material to synthesis these useful molecules.
During the course of our study, we observed accompanying three
compounds formed that were believed to be intermediates.
Therefore, to elucidate the reaction pathway, we stopped the
reaction in the middle that was performed between 1a and 2a under
optimized conditions. All the intermediates were isolated and
characterized using spectroscopic techniques. As shown in scheme 1,
the three intermediates are inferred as secondary allylic alcohol 4,
allylic alcohol 5 obtained via aldol reaction from 3aa with 1a, and
diketone 6. Considering that the intermediates varied significantly
during the reaction, we used 1H NMR to monitor the reaction.
As shown in Scheme 1, we observed the very quick consumption
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of aldehyde 1a with concomitant formation of secondary allylic
alcohol 4. After 10 min, the conversion of the compound 4 already
achieved 90%. This result was found consistent with our previous
study.5 The aryl reaction was very fast due to longer Rh‐P bond
distance in the Rh2(OAc)4(P(t‐Bu)3)2, which facilitated the substitution
of one of the P(t‐Bu)3 ligands by the arylboronic acid 2a. It was
interesting to observe that the compound 4 was slowly transformed
into ketone product 3aa. Meanwhile, the aldol products 5 was
Scheme 1. Reaction profile of tandem reaction catalyzed by Rh2(OAc)4(P(t‐Bu)3)2
Since the mechanism of arylation catalyzed by Rh2(OAc)4(P(t‐Bu)3)2
complex was already investigated in our previous study,5 herein, we
focused on the procedure of isomerization of an allylic alcohol.
Table 3. The scope of ‐unsaturated aliphatic aldehydes with 2a
Rh2(OAc)4 (1 mol %)
[(t‐Bu)3PH]BF4 (2.5 mol %)
OH
B
O
O
R1
OH
+
R1
K2CO3 (10 mol %)
toluene/H2O= 3/1 or DME/H2O= 1/1
90 oC , 6 h , N2
H
R2
R2
3ka‐3oa
2a‐2m
R1
1k‐1o
entry
1
2
3
4
5
6
7
8
R2
product
yield/%
58
57
50
46
57
56
41
38
30
54
61
65
70
69
53
72
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Me (1k)
Et (1l)
H (2a)
3ka
3kc
3kd
3ke
3kg
3ki
3kk
3kl
3km
2‐Me (2c)
3‐OMe (2d)
3‐Me (2e)
4‐OMe (2g)
4‐Me (2i)
4‐Cl (2k)
4‐F (2l)
4‐CF3 (2m)
H (2a)
H (2a)
H (2a)
2‐Me (2c)
3‐Me (2e)
4‐OMe (2g)
4‐Me (2i)
4‐Cl (2k)
4‐F (2l)
9
10
11
12
13
14
15b
16
17
18
19
3la
3ma
n‐Pr (1m)
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
CH3CH=CH (1n) E/Z=86/14
C2H5CH=CH (1o) E/Z =91/9
3na E/Z=78/22
3nc E/Z =82/18
3ne E/Z =79/21
3ng E/Z =84/16
3ni E/Z =79/21
3nk E/Z =83/17
3nl E/Z =87/13
3oa E/Z =88/12
63
61
62
H (2a)
a Unless otherwise noted, all reactions were performed by using‐unsaturated aliphatic aldehydes 1 (1.00 mmol), arylboronic acids 2 (1.10 mmol), Rh2(OAc)4 (1 mol %),
[(t‐Bu)3PH]BF4 (2.5 mol %) and K2CO3 (10 mol %) in 4 mL of 3/1(v/v) toluene/H2O at 90 ℃ for 4 h under N2. Yield of isolated product. The E/Z ratios of commercially
b
available substrates 1n and 1o were determined by 1H‐NMR spectra. The E/Z ratio of products 3na‐oa were determined by 1H‐NMR spectra of the isolated products.
The reactions were performed in 4 mL of 1/1(v/v) DME/H2O
.
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Although, the isomerization of allylic alcohol is a well known Rh2(OAc)4(PPh3)2>Rh2(OAc)4(PCyPh2)2>Rh2(OAc)4(PCy2Ph)2>Rh2(OAc)
procedure, especially catalyzed by the Rh, Ru or Ir metal,14 but it has 4(PCy3)2.
never been reported by the dinuclear metal to the best of our
To understand the catalytic performances of these different
knowledge. In this regard, we attempt to understand how the complexes towards the isomerization of the allylic alcohol, we
Rh2(OAc)4(P(t‐Bu)3)2 complex catalyzed the isomerization of allyl prepared the crystals of Rh2(OAc)4(PCyPh2)2 and Rh2(OAc)4(PCy2Ph)2
alcohol along with the effects of axial phosphane ligands on the complexes according to our previous method. Selected data of
Rh2(OAc)4. Therefore, we used the intermediate 4 as starting crystal structures are provided in Fig 2 to compare with other
material to study the isomerization. Unexpectedly, the bulky ligands reported structures. From the data, it is obvious that the length of
ligated Rh2(OAc)4(P(t‐Bu)3)2‐catalyzed isomerization reaction was Rh‐P bond of Rh2(OAc)4(PPh3)2 complex (2.477Å) was shorter than
slow and the reaction was completed in almost 8 h. To our surprise, other complexes, and the situation was same with the Rh‐O bond
the aryl ligands PPh3 combined with Rh2(OAc)4 were clearly shown (2.045 Å) (Table 4). As previous research reported,5 the length of the
superior to the Rh2(OAc)4(P(t‐Bu)3)2, catalyzing the isomerization Rh‐P bond was determined by the ability of σ‐donating and the steric
reaction to produce the product 3aa in only 2 h without any base profile of PR3 ligands, the short Rh−P bond in Rh2(OAc)4(PPh3)2
added. However, the Rh2(OAc)4(PPh3)2 complex was proved to be complex is the result of strong  back‐bonding between Rh and P. As
incompetent to catalyze the arylation in our previous work.5,15 This opposed to the previous report that longer Rh−P bond favors the
result suggested that the axial ligands need to be carefully selected arylation reaction, this structural analysis indicated that the short Rh‐
when applied in the different reactions. Based on these results, we P bond facilitated the isomerization reaction.
continued to investigate the performance of different
Rh2(OAc)4(PR3)2 complexes such as PCyPh2, PCy2Ph and PCy3 in the
isomerization reaction to clarify which ligands are optimal.
Fig 2. ORTEP crystal structure of Rh2(OAc)4(PCyPh2)2 and Rh2(OAc)4(PCy2Ph)2. The
molecular structures are depicted in an ellipsoid style at the 50% probability level.
However, it is inferred from the data shown in Table 1 from the
previous studies that the tandem reaction catalyzed by
Rh2(OAc)4(PPh3)2 complex gave the product 3aa in 49% yield only.
The studies of the reaction catalyzed by Rh2(OAc)4(PPh3)2 showed
that the starting material 1a was only partial converted to
intermediate 4 after 1 h (see ESI), indicating that the arylation
catalyzed by the Rh2(OAc)4(PPh3)2 complex was slow.
The
deboronate reaction occurred under the basic aqueous condition
may account for the moderate yield of final product 3aa.17 Taken
into full consideration, the Rh2(OAc)4(P(t‐Bu)3)2 complex
demonstrated its competence to catalyze the two sequential
catalytic cycles regardless of catalyzing the isomerization slowly.
Scheme 2. Reaction profile of the isomerization of allyl alcohol
Rh2(OAc)(PR3)2
4 catalyzed by
As shown in the Scheme 2, the rate of isomerization reaction kept
on increasing with the increased aryl portion in the ligands.
Compared with the reaction catalyzed by PCy2Ph with only 1%
conversion, the conversion of 3aa reached to 75% conversion after
1h in the reaction catalyzed by Rh2(OAc)4(PPh3)2 complex. According
to scheme 2, the sequence of efficient catalysts catalyzed the
isomerization reaction are as follows:
Table 4. Selected bond distances from crystal structure data of selected axially
ligated dirhodium(II) complexes
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entry
Rh2(OAc)2(PR3)2
Rh‐Rh
(Å)
Rh‐O
(Å)
Rh‐P
(Å)
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DOI: 10.1039/C8OB01997E
5
1
2
3
4
5
Rh2(OAc)4(P(t‐Bu)3)2
2.454
2.457
2.454
2.451
2.451
2.046
2.055
2.050
2.050
2.045
2.663
2.509
2.499
2.492
2.477
5
Rh2(OAc)2(PCy3)2
Rh2(OAc)2(PCy2Ph)2
Rh2(OAc)2(PCyPh2)2
16
Rh2(OAc)2(PPh3)2
Further, on the basis of the structure information, some
experiments were conducted to unravel the mechanism of
isomerization. The UV‐vis spectral analysis was applied to validate
the stability of Rh2(II) complex as the presence of axial ligands may
cause the Rh‐Rh bond to undergo oxidative cleavage.2,18 The mixture
was allowed to rest at room temperature after the reaction between
1a and 2a was finished, and two layers were separated (toluene and
water, respectively). The toluene layer was found to be reddish
purple and the UV‐vis spectrum showed an absorption peak at 557
nm, indicating the existence of Rh2(OAc)4(P(t‐Bu)3)2 complex (Fig 3).
Meanwhile, the light green water layer with absorption peaks at 444
and 587 nm in Uv‐vis spectrum indicated the existence of free ligated
Rh2(OAc)4. The absorbance spectral studies confirmed that the Rh‐
Rh bond still remained intact during this tandem procedure.19
According to our previously reported method,5 we successfully
recovered the catalyst with 45% recovery rate (see ESI).
Scheme 3. Isotopic labeling studies and crossover experiment
Based on the above information, the mechanism of the two‐step
catalytic cycle was proposed. The arylation mechanism is similar to
that reported in our previous work,5 as the substrate aldehyde 1 and
phenylboronic acid 2 reacted with Rh2(II) catalyst to form a six‐
membered ring transition state leading to the arylation reaction.
Based on isomerization results and deuterium labeling experiments,
we proposed that the mechanism of isomerization was consistent
with that of metal alkoxide21 (Scheme 4). The presence of trans‐
effect4,22 was found to exist in the Rh2(OAc)4(PR3)2 complex which
demonstrated that only one Rh atom out of two Rh atoms of
Rh2(OAc)4 complex serves as the reaction center. First, the oxygen
atom of allylic alcohols coordinated axially with the Rh atom,
dissociated by the phosphine ligand to form C. The hydrogen atom
on the hydroxyl of allylic alcohol and the oxygen atom in the bridging
ligand of Rh2(OAc)4 formed hydrogen bond which resulted in a four‐
membered ring transition state D. Further, the Rh‐O bond in the D
was broken to generate E. 23 Followed by the ‐H elimination, the
intermediacy ‐rhodium hydride ketone complex F was generated
which underwent 1,4‐addition of the hydride to afford G. Then, the
dissociated acetoxy ligand coordinated with the rhodium atom to
regenerate the Rh2(OAc)4, accompanying the formation of axially
coordinated enols. The enols were decomplexed from the Rh2(OAc)4
during tautomerism to give the saturated ketones product. During
the whole catalytic cycle, the axial ligand PR3 attached with one of
the two rhodium atoms, fine‐tuned the electrophilicity of the
catalytic rhodium atom across the Rh‐Rh bond. The detailed
explanation of the superiority of PPh3 as axial ligand compared to the
alkyl phosphane ligands require further study.
Fig 3. UV‐vis spectral analysis of the toluene phase and the water phase. (A)
Rh2(OAc)4(P(t‐Bu)3)2 (3 mg) in toluene (2.5 mL) (λmax = 557 nm). (B) The toluene phase
(λmax = 557 nm) of the reaction. (C) The water phase (λmax = 444 nm & 587 nm) of the
reaction. (D) Rh2(OAc)4(H2O)2 (3 mg) in water (2.5 mL) (λmax = 444 nm & 587 nm).
Essentially, three different mechanisms14b,20 have been proposed
for the isomerization of allylic alcohols catalyzed by metal catalyst,
which involve either
a metal hydride addition‐elimination
mechanism, a‐allyl metal hydride mechanism, or a mechanism
involving a metal alkoxide. Next, to gain further insights into the
mechanism, deuterium labeling and crossover experiments were
conducted (Scheme 3). The essential role of H2O in the mixed solvent
of the reaction was probed by performing labeling experiments using
D2O. The reaction in toluene/D2O resulted in the formation
of monodeuterated product (Scheme 3, 3aa‐d2). Another two
reactions with selectively‐labeled substrates 4‐d1 were then
conducted. The formation of 1,3‐deuterium shift ketone product
3aa‐d3 was detected, whereas the result of the crossover experiment
demonstrated that this 1,3‐deuterium shift process was
intramolecular since there was no transfer of deuterium between the
compounds 4‐d1 and 7.
6 | J. Name., 2012, 00, 1‐3
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Journal Name
ARTICLE
94, 1091−1160. (c) M. P. Doyle, R. Duffy, M. RVaitenwikAortivcleaOnndlinLe.
Zhou, Chem. Rev. 2010, 110, 704−724.D(OdI): 1H0..1M03.9L/.CD8aOvBi0e1s9a9n7dE
D. Morton, Chem. Soc. Rev. 2011, 40, 1857−1869.
D. J. Timmons, M. P. Doyle, F. A. Cotton, C. A. Murillo and R. A.
Walton, Multiple Bonds between Metal Atoms; Springer
Science and Business Media: New York, 2005.
(a) M. C. Pirrung, H. Liu and A. T. Morehead, J. Am. Chem. Soc.
2002, 124, 1014−1023. (b) M. C. Pirrung and A. T. Morehead,
J. Am. Chem. Soc. 1996, 118, 8162−8163.
2
3
4
5
6
7
A. F. Trindade, J. A. S. Coelho, C. A. M. Afonso, L. F. Veiros and
P. M. P. Gois, ACS Catal. 2012, 2, 370−383.
J. T. Tan, Y. Kuang, Y. Wang, Q. F. Huang, J. Zhu and Y. H. Wang,
Organometallics, 2016, 35, 3139−3147.
N. Krause, Modern Organocopper Chemistry; Wiley‐VCH:
Weinheim, 2002.
(a) J. K. Groves, Chem. Soc. Rev. 1972, 1, 73–79. (b) A. Fürstner,
D. Voigtländer, W. Schrader, D. Giebel and M. T. Reetz, Org.
Lett. 2001, 3, 417‐420. (c) J. Ross and J. L. Xiao, Green Chem.
2002, 4, 129–133.
8
9
(a) S. Lai and D. G. Lee, Tetrahedron, 2002, 58, 9879–9887. (b)
B. Akhlaghinia, H. Ebrahimabadi, E. K. Goharshadi, S. Samiee
and S. Rezazadeh, J. Mol. Catal. A: Chem. 2012, 357, 67–72.
(a) J. J. Crawford, K. W. Henderson and W. J. Kerr, Org. Lett.
2006, 8, 5073−5076. (b) P. S. Sagara, R. Chebolu, A. Bahuguna
and P. C. Ravikumar, RSC Adv. 2014, 4, 15011–15013.
10 Z. Y. Wang, G. Zou and J. Tang, Chem. Commun. 2004,
1192−1193.
11 (a) M. B. Hay and J. P. Wolfe, Tetrahedron Lett. 2006, 47, 2793–
2796. (b) I. R. Hazelden, X. F. Ma, T. Langer and J. F. Bower,
Angew. Chem. Int. Ed. 2016, 55, 11198–11202. (c) H. Jiang and
A. Studer, Angew. Chem. Int. Ed. 2017, 56, 12273 –12276.
12 (a) A. F. Trindade, P. M. P. Gois, L. F.Veiros, V. André, M. T.
Duarte, C. A. M. Afonso, S. Caddick and F. G. N. Cloke, J. Org.
Chem. 2008, 73, 4076−4086. (b) A. F. Trindade, V. André, M. T.
Duarte, L. F. Veiros, P. M. P. Gois and C. A. M. Afonso,
Tetrahedron. 2010, 66, 8494−8502.
13 S. Giboulot, F. Liron, G. Prestat, B. Wahl, M. Sauthier, Y.
Castanet, A. Mortreux and G. Poli, Chem. Commun. 2012, 48,
5889−5891.
14 (a) N. Ahlsten, A. Bartoszewicz and B. Martín‐Matute, Dalton
Trans. 2012, 41, 1660−1670. (b) S. Manzini, A. Poater, D. J.
Nelson, L. Cavallo and S. P. Nolan, Chem. Sci. 2014, 5, 180−188.
15 Y. Kuang and Y. H. Wang, Eur. J. Org. Chem. 2014, 1163−1166.
16 G. G. Christoph, J. Halpern, G. P. Khare, Y. B. Koh and C.
Romanowski, Inorg. Chem. 1981, 20, 3029−3037.
Scheme 4. Possible mechanism
Conclusions
In conclusion, a strong ‐donating ligand, tert‐butylphosphine,
coordinated to the axial position of Rh2(OAc)4 acted as an efficient
combined catalyst in the tandem reaction of‐unsaturated
aromatic or aliphatic aldehydes with arylboronic acids to produce
various functional ketone derivatives in high yields. The tandem
procedure occurred in two steps including arylation and
isomerization reactions. This protocol was well tolerated by
variously substituted aromatic rings and other functional groups.
Especially, the ‐unsaturated ketones were synthesized in a one‐
pot reaction with great ease using this strategy. The recovery of
metal catalyst Rh2(OAc)4 after the completion of reaction also
supports the potential application of this catalyst in organic
syntheses. The further investigation will be focused on the detailed
explanation of effect of fine tuning of axial PR3 ligands.
17 (a) D. G. Hall, In Boronic Acids; Wiley‐VCH, 2011. (b) S. W. Reilly,
H. K. Box, G. R. Kuchenbeiser, R. J. Rubio, C. S. Letko, K. D.
Cousineau and T. K. Hollis, Tetrahedron. Lett. 2014, 55,
6738−6742.
18 R. D. Adams and F. A. Eds. Cotton, Catalysis by Di‐ and
Polynuclear Metal Cluster Complexes; Wiley‐VCH: New York,
1998.
19 (a) V. M. Miskowski, W. P. Schaefer, B. Sadeghi, B. D.
Santarsiero and H. B. Gray, Inorg. Chem. 1984, 23, 1154−1162.
(b) J. W. Jr. Trexler, A. F. Schreiner and F. A. Cotton, Inorg. Chem.
1988, 27, 3265−3269. (c) F. A. Cotton, E. A. Hillard and C. A.
Murillo, J. Am. Chem. Soc. 2002, 124, 5658−5660.
Conflicts of interest
There are no conflicts to declare.
20 (a) V. Cadierno, S. E. García‐Garrido, J. Gimeno, A. Varela‐
Álvarez and J. A. Sordo, J. Am. Chem. Soc. 2006, 128,
Acknowledgements
1360−1370.
(b) D. V. McGrath and R. H. Grubbs,
We are grateful for the financial support provided by the National
Natural Science Foundation of China (21272102).
Organometallics, 1994, 13, 224−235. (c) V. Branchadell, C.
Crévisy and R. Grée, Chem. Eur. J. 2003, 9, 2062−2067. (d) B.
M. Trost and R. J. Kulawiec, J. Am. Chem. Soc. 1993, 115,
2027−2036.
21 (a) B. Martín‐Matute, K. Bogár, M. Edin, F. B. Kaynak and J‐E.
Bäckvall, Chem. Eur. J. 2005, 11, 5832−5842. (b) N. Ahlsten, H.
Lundberg and B. Martín‐Matute, Green Chem. 2010, 12,
1628−1633.
Notes and references
1
(a) M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley:
New York, 1998. (b) T. Ye and M. A. McKervey, Chem. Rev. 1994,
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Journal Name
22 X. Xu and M. P. Doyle, Inorg. Chem. 2011, 50, 7610−7617.
23 (a) A. Dobson and S. D. Robinson, Inorg Chem, 1977, 16,
137−142. (b) J. J. Cheng, M. J. Zhu, C. Wang, J. J. Li, X. Jia(nPge,nYt.
W. Wei, W. J. Tang, D. Xue and J. L. Xiao, Chem. Sci. 2016, 7,
View Article Online
4428−4434.
DOI: 10.1039/C8OB01997E
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