Rhenium-catalyzed acceptorless dehydrogenative coupling via dual activation of alcohols and carbonyl compounds

Article abstract of DOI:10.1021/cs400572q

The rhenium hetaphydride complex was found to be a versatile, homogeneous catalyst for dehydrogenative functionalization of alcohol. The dehydrogenative C-C coupling of alcohols and carbonyl compounds was carried out in the absence of base and hydrogen acceptors to afford a series of α,β-unsaturated carbonyl compounds. A possible dual activation pathway was proposed by mechanistic investigations.

Full text of DOI:10.1021/cs400572q

Research Article
pubs.acs.org/acscatalysis
Rhenium-Catalyzed Acceptorless Dehydrogenative Coupling via
Dual Activation of Alcohols and Carbonyl Compounds
Hongming Jin,† Jin Xie,† Changduo Pan,† Zhengbo Zhu,† Yixiang Cheng,† and Chengjian Zhu*,†,‡
†State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, People’s Republic of China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032,
People’s Republic of China
S
* Supporting Information
ABSTRACT: The rhenium hetaphydride complex was found
to be a versatile, homogeneous catalyst for dehydrogenative
functionalization of alcohol. The dehydrogenative C−C
coupling of alcohols and carbonyl compounds was carried
out in the absence of base and hydrogen acceptors to afford a
series of α,β-unsaturated carbonyl compounds. A possible dual
activation pathway was proposed by mechanistic investigations.
KEYWORDS: alcohol, dehydrogenation, rhenium, homogeneous catalysis, C−H activation
a
INTRODUCTION
Table 1. Screening for Optimal Reaction Conditions
■
Formulating sustainable, atom-economical strategies to con-
struct C−C bonds has emerged as a perennial topic in organic
chemistry.1 Alcohol as an inexpensive and green coupling
partner is much favored in terms of its ease of operation and
storage.2 In recent years, transition metal-catalyzed dehydro-
genative coupling of alcohol represents an efficient and general
method to construct intricate scaffolds.3,4 Despite significant
contributions to C−X bonds forming5,6 having been made by
dehydrogenative functionalization of alcohol, base and hydride
acceptors were usually required,3a,d,4c which was not environ-
mentally friendly. In this aspect, the development of base-free
and acceptorless dehydrogenative coupling for the formation of
C−C bonds is highly desirable. To meet the challenge, herein,
we disclose an unprecedented dehydrogenative C−C coupling
by rhenium complex-catalyzed dual activation of different
substrates.
entry
L
solvent
additive
yield
E/Z
3:1
1
2
3
PCy3
PPh3
P(tolyl)3
dppe
dppf
THF
64%
31%
37%
none
none
43%
trace
trace
71%
63%
none
75%
77%
71%
73%
THF
3:1
3:1
THF
b
4
THF
ND
ND
1:1
b
5
c
THF
6
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
THF
7
8
CHCl3
CH3CN
anisole
toluene
DMF
ND
ND
3:1
9
10
11
12
13
14
15
7:2
Recently, Klankermayer reported rhenium hydride com-
plexes as promising dehydrogenative catalysts that were applied
to dehydrogenative esterification and amidation.7 Moreover, a
rhenium hydride complex-catalyzed Thorpe−Ziegler reaction
ND
25:3
3:1
anisole
anisole
anisole
anisole
LiCl
nBu4NBr
KCl
3:1
4 Å MS
3:1
Scheme 1. Rhenium-Catalyzed Dehydrogenative C−C
Coupling via the Dual Activation Model
a
Reaction conditions: 1a (0.2 mmol), 2a (0.8 mmol), additive (0.4
mmol), ReH7L2 (5 mol %), and solvent (0.5 mL) under N2
atmosphere at 150 °C, isolated yield. ReH7L. 130 °C.
b
c
has been lately described by Takaya’s group, in which a Re−C
species, generated through direct C−H activation, was proposed
Received: July 17, 2013
Revised: August 13, 2013
© XXXX American Chemical Society
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Research Article
a,b
Table 2. Substrate Scope
a
Reaction conditions: 1 (0.2 mmol), 2 (0.8 mmol), LiCl (0.4 mmol), ReH7(PCy3)2 (5 mol %), and anisole (0.5 mL) under N2 atmosphere for 24−36 h at
b
c
d
150 °C, isolated yield. E/Z ratio ∼ 25:3. PMP = 4-methoxy phenyl. Additional ReH7(PPh3)2 (5 mol %) was added. Only the E isomer was obtained.
as the key intermediate.8 Inspired by these reports, we envisaged
a possible dehydrogenative coupling of alcohol to achieve
α-olefination of carbonyl compounds via a dual activation model
(Scheme 1). During our study, it was found that rhenium
hetpahydride complexes as versatile catalysts integrated separate
catalytic moieties into dehydrogenation coupling without a
traditional base and hydrogen acceptors. To the best of our
knowledge, there has been little success of the rhenium-catalyzed
dehydrogenative C−C coupling reaction, although rhenium-
catalyzed transformations have made outstanding achievements
in the past decades.7−11
to 130 °C, a lower yield was obtained (entry 3). Further
optimization showed that the yield could be increased to 71%
when anisole was used as a solvent. Unfortunately, the E/Z
selectivity was not significantly improved by altering the solvent
and temperature. Then, different additives were screened
(entries 9−12), and it was found that 3a could be isolated in
75% yield with a good E/Z selectivity by addition of anhydrous
LiCl (entry 9), which may form a more stable transition state
via Li+ chelation. The optimal reaction condition is catalyzed by
5 mol % ReH7(PCy3)2 under N2 atmosphere at 150 °C.
We next explored the scope of this transformation using the
optimized catalytic condition. The results are summarized in
Table 2. Gratifyingly, a series of oxindoles bearing different
substitutes (R = F, Me, Cl) furnished the desired 3-alkylene-
oxindoles in good yields. Other carbonyl compounds also
worked well and afforded only E isomers (3t−w). Subse-
quently, we screened a range of alcohols. The reaction of benzyl
alcohols bearing electron-donating groups (3a−e) proceeded
more smoothly than those bearing electron-withdrawing
RESULTS AND DISCUSSION
■
Initially, the reaction of N-phenyl oxindole 1a and benzyl
alcohol 2a was chosen as the model reaction to screen the
reaction conditions (Table 1). To our delight, 5 mol % of
ReH7(PCy3)2 gave 3a in a yield of 64% at 150 °C for 36 h,
whereas ReH7(PPh3)2 afforded the product in only 31% yield
(entries 1−2). When the reaction temperature was decreased
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Research Article
substitutes (3f−g) at the aromatic ring. A substrate bearing a
strong electron-withdrawing group, such as NO2, was not
engaged in this reaction.14 Aliphatic primary alcohols were also
used in this reaction. Surprisingly, a few of dehydrogenative
coupling products were isolated, while hydrogen autotransfer
products were obtained as major products (3x−y). We
therefore considered that the carbon−carbon double bonds
seem to be stabilized by the conjugated and steric effect of an
aromatic ring to avoid the following reduction reaction.
Scheme 2. Deuteration Experiments
To gain insight into the reaction mechanism, several
experiments were carried out. First, recatalyzed acceptorless
dehydrogenation of alcohols was tested (Table 3). It was found
Table 3. Recatalyzed Acceptorless Dehydrogenation of
a
Alcohols
mechanistic pathway (Scheme 2, eq 2). Compound 5 was
treated with 0.5 equiv of rhenium hydride complex at 150 °C
2
for 1 h. Detected by H NMR spectroscopy, the deuterium-
labeled substrate nearly vanished, and 6 was isolated in 95%
yield.13 Therefore, we speculated the H/D exchanging between
the carbonyl compounds and rhenium hydride complex
probably underwent Re−C intermediate forming or an enolate
type transition state. However, the definite intermediate was
still unclear. Moreover, the aldehyde hardly condensed with
carbonyl compounds in the absence of the rhenium complex.
The proposed mechanism is depicted in Scheme 3. Oxidative
Scheme 3. Proposed Mechanism
a
Reaction conditions: 2 (0.2 mmol), ReH7(PCy3)2 (5 mol %), and
anisole (0.5 mL) under N2 atmosphere at 150 °C, isolated yield.
addition of the rhenium complex to the α-C−H of carbonyl
compounds 1 could furnish Re−C species 7 or enolate
derivative 8. Aldehyde 4 generated in situ by alcohol 2
dehydrogenation inserts the Re−C bond, followed by reductive
elimination and dehydration to give the desired product 3.
that the dehydrogenation of 1-arylethanols under the standard
conditions proceeded successfully to give the corresponding
acetophenone derivatives in good yields (entries 1−3). Other
secondary alcohols, such as 1,2,3,4-tetrahydronaphthalen-2-ol,
also afforded 4o in 62% yield (entry 4); however, the
dehydrogenation of primary alcohols was less efficiently
catalyzed and was also impacted by the electronic effect on
the aromatic ring (entries 4−8).
Until now, there have been few reports on dehydrogenative
oxidation of alcohol for homogeneous rhenium complexes.12b
Thus, to disclose the detailed mechanism of this reaction, a
deuterium labeling study was proposed [Scheme 2, eq (1)].
The 1:1 mixture of α, α-d2-benzyl alcohol d-2a and 2b was
heated at 150 °C for 24 h. H/D scrambling was detected in
4-methoxy-benzaldehyde, suggesting that the alcohol dehydro-
genation step was reversible.6c,12,13 Upon our hypothesis for
catalytic C−H activation moiety, Re−C species as the key
intermediates have been proposed.8−11,15 In this view, a
deuterium experiment was devised to further substantiate our
SUMMARY
■
In summary, we have developed the first example of
homogeneous rhenium-catalyzed dehydrogenative C−C cou-
pling. The rhenium-catalyzed dual activation process may occur
in this transformation. The novel, acceptorless and base-free
catalytic system makes this reaction more benign and step-
economical. Moreover, it is a new development for rhenium
chemistry. Further studies on rhenium-catalyzed dehydrogen-
ation and the mechanistic details are under way in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and spectroscopic characterization
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
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Research Article
(13) For details, see the Supporting Information.
(14) For example:
AUTHOR INFORMATION
Corresponding Author
*E-mail: cjzhu@nju.edu.cn.
■
Notes
The authors declare no competing financial interest.
(15) (a) Zeiher, E. H. K.; DeWit, D. G.; Caulton, K. G. J. Am. Chem.
Soc. 1984, 106, 7006. (b) Moehring, G. A.; Williams, C. C.; Buford, J.;
Kaviani, M.; Sulko, J.; Fanwick, P. E. Inorg. Chem. 1998, 37, 3848.
(c) Jimenez, Y.; Strepka, A. M.; Borgohain, M. D.; Hinojosa, P. A.;
Moehring, G. A. Inorg. Chim. Acta 2009, 362, 3259.
ACKNOWLEDGMENTS
■
Dedicated to Professor Xiao-Zeng You for his 80th Birthday.
We gratefully acknowledge the National Natural Science
Foundation of China (21172106, 21074054), the National
Basic Research Program of China (2010CB923303), and the
Research Fund for the Doctoral Program of Higher Education
of China (20120091110010) for their financial support.
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