Branch-selective allylic C-H carboxylation of terminal alkenes by pd/sox catalyst

Article abstract of DOI:10.1021/ol5019135

A ligand-controlled branch-selective allylic C-H carboxylation through Pd catalysis is described. The developed catalytic system, which consists of Pd(OAc)₂, sulfoxide-oxazoline (sox) as a ligand and benzoquinone as an oxidant, couples terminal alkenes and carboxylic acids to furnish the corresponding branched allylic esters with high regioselectivity.

Full text of DOI:10.1021/ol5019135

Letter
pubs.acs.org/OrgLett
Branch-Selective Allylic C−H Carboxylation of Terminal Alkenes by
Pd/sox Catalyst
Hiroki Kondo,† Feng Yu,‡ Junichiro Yamaguchi,† Guosheng Liu,*,‡ and Kenichiro Itami*,†,§,∥
†Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
§Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan
∥JST ERATO, Itami Molecular Nanocarbon Project, Nagoya University, Chikusa, Nagoya 464-8602, Japan
S
* Supporting Information
ABSTRACT: A ligand-controlled branch-selective allylic C−
H carboxylation through Pd catalysis is described. The
developed catalytic system, which consists of Pd(OAc)2,
sulfoxide−oxazoline (sox) as a ligand and benzoquinone as
an oxidant, couples terminal alkenes and carboxylic acids to
furnish the corresponding branched allylic esters with high
regioselectivity.
llylic C−H oxidation of alkenes has received much
ligands such as dimethyl sulfoxide (DMSO) and benzoquinone
as an oxidant.6 Additionally, it has been reported that the use of
vinyl sulfoxide or bis-sulfoxide ligands is essential to give
branched products (Scheme 1). It should also be emphasized
that a ligand-controlled, enantioselective, allylic C−H oxidation
has not been developed; White’s chiral Lewis acid cocatalyst
strategy is the sole example inducing enantioselectivity.4c Thus,
the development of a new class of ligand system potentially
inducing enantioselectivity is of great importance in the field.
In 2013, as a part of our campaign exploring ligand-enabled
catalysis for C−H coupling,7 we discovered a C−H/C−B
coupling of sterically hindered heteroarenes employing
arylboronic acids and using catalytic amounts of Pd(OAc)2,
sulfoxide−oxazoline (sox) as the ligand, and iron phthalocya-
nine (FePc) as the cocatalyst under air (Scheme 2, eq 1).8 For
example, 2,3-dimethylthiophene can be coupled with (2-
methylnaphthalen-1-yl)boronic acid in the presence of a Pd
catalyst to give the corresponding coupling product in 92%
yield using sulfoxide−oxazoline (sox) L1 as the ligand, whereas
DMSO and White’s bis-sulfoxide resulted in low yields. We
hypothesized that the Pd/sox catalyst might also be effective for
allylic C−H oxidation. Moreover, due to the stronger bonding
of the nitrogen than that of sulfur,8 the trans-effect and the
bulky steric hindrance of oxazoline substituent R provide a
chance to tune the regioselectivity to afford the branch product
(Scheme 2, eq 2). Thus, we set out to investigate the effect of
sox ligands for allylic C−H oxidation, and herein we report a
highly regioselective allylic C−H carboxylation of terminal
alkenes by the Pd/sox catalyst.
A
attention from the organic chemistry community because
it can form allylic alcohol and amine derivatives that are useful
in the synthesis of pharmaceuticals and complex natural
products.1 Palladium catalysis has proven particularly effective
for such alkene C−H oxidations, and various procedures for
cyclic alkene substrates have been developed.2 Recently,
regioselective C−H oxidation of terminal alkenes using Pd
catalysts has been reported (Scheme 1). Efforts to control the
regioselectivity of C−H oxidation of terminal alkenes have
mostly resulted in a preferential reaction at the less hindered
position to give linear products (L).3 Only a few catalytic
systems are known to be effective in producing branched
products (B) as exemplified by the pioneering works reported
by the group of White.4,5 Most of these reactions use sulfoxide
Scheme 1. Pd-Catalyzed Regioselective C−H Oxidation of
Terminal Alkenes
Received: July 2, 2014
Published: July 28, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
Scheme 2. C−H/C−B Coupling of Heteroarenes with
Hindered Arylboronic Acids Using a Pd/sox Catalyst (eq 1)
and Our Hypothesis for a Branch-Selective Allylic C−H
Carboxylation Using the Pd/sox Catalyst (eq 2)
Table 1. Ligand Screening for the Pd-Catalyzed Allylic C−H
a
Carboxylation
b
c
entry
ligand
yield of 2a/%
(B)/(L)
1
2
3
4
5
6
7
8
9
L1
58
56
60
57
47
−
85:15
99:1
96:4
90:10
84:16
−
87:13
95:5
99:1
97:3
97:3
98:2
96:4
98:2
>99:1
97:3
L2
L3
L4
L5
L6
L7
7
L8
14
3
L9
d
10
L3
66
74
86
74
84
74
74
d
11
L10
L11
L12
L13
L14
L15
d
12
d
13
d
14
d
15
d
16
a
Reaction conditions: 1a (0.2 mmol), Pd(OAc)2 (0.02 mmol), ligand
(0.02 mmol), benzoquinone (0.4 mmol), AcOH (0.8 mmol) in 1,4-
b
Using oct-1-ene (1a) as a model substrate for terminal
alkenes, allylic C−H carboxylation was conducted using various
sox ligands, following the standard procedure of White and co-
workers: 10 mol % Pd(OAc)2,4b 10 mol % ligand, 2.0 equiv of
benzoquinone, and 4.0 equiv of AcOH in 1,4-dioxane for 48 h
at 45 °C under air (Table 1).9 When iPr-sox L1 was used as the
ligand, allylic C−H acetoxylation of 1a proceeded to give the
corresponding product 2a(B) (B: branch) and 2a(L) (L:
linear) in a combined 58% yield with 85:15 (B/L)-selectivity
(Table 1, entry 1). Ligand t-Bu-sox L2 gave a better branch-
selectivity ratio of 99:1 (Table 1, entry 2). Surprisingly, t-Bu-sox
L3, a diastereomer of t-Bu-sox L2, gave a slightly better yield
(60% yield) whereas the B/L ratio was slightly decreased (96:4,
Table 1, entry 3). When the t-Bu-sox L3 was changed to Me-
sox L4 and H-sox L5, the branch selectivity became gradually
worse (Table 1, entries 4 and 5). These results indicate that the
substituent on the oxazoline might be more important in
controlling the branch selectivity. Compared to the sox ligand,
the bis-oxazoline ligands such as L6 are ineffective for this
transformation (Table 1, entry 6), which clearly indicate the
importance of a sulfoxide moiety in ligand structure. Phenyl
sulfoxide ligand L7 and L8 without the oxazoline moiety were
not effective (Table 1, entries 7 and 8). A sox ligand L9 with an
oxazoline at the meta-position was also ineffective (Table 1,
entry 9). Interestingly, when the loading of t-Bu-sox L3 was
lowered to 5 mol %, the yield and regioselectivity of 2a were
maintained (Table 1, entry 10).10 Next, based on the t-Bu-sox
L3, some modified ligands (L10−L15) bearing both electron-
deficient and -donating substituents on the phenyl group were
investigated (Table 1, entries 13−16). As a result, L11 (4-
fluoro) and L13 (4,5-difluoro) were found to be the best
ligands and afforded the branched product 2a(B) in 86% and
84% yields, respectively with 98% branch selectivity (Table 1,
entries 12 and 14).11,12 It should be noted that, unfortunately,
the enantiomeric excess of the branched product 2a(B) was less
than 5%. These results clearly show that the chiral environment
created by the current sox system needs to be significantly
dioxane (1.2 mL), 45 °C, 48 h, under air. The yield of 2a was
c
determined by GC analysis. The ratio of 2a(B) and 2a(L) was
d
determined by GC analysis. 5 mol % ligand and 10 mol % Pd(OAc)2
were employed.
modified to achieve an enantioselective allylic C−H oxidation
process.
Previously we have shown in the C−H/C−B biaryl coupling
chemistry that a chiral sox ligand L1 coordinates to
palladium(II) in a bidentate fashion.7 Since the optimal ligand
structure in the present C−H oxidation turned out to be the
diastereomer (L3, L11, and L13, for example), we questioned
whether these new ligands also coordinate to palladium(II) in a
S−N bidentate fashion. Thus, L3 was treated with PdCl2 in
CH2Cl2 at room temperature to give the PdCl2(L3) complex
(3) (see the Supporting Information for details). The X-ray
crystal structure analysis of 3 revealed that the S atom of the
sulfoxide coordinates to the Pd center as well as the N atom of
the oxazoline unit (Figure 1).
Next, we examined the scope of this reaction using several
carboxylic acids and terminal alkenes using the Pd(OAc)2/L11
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Letter
In summary, we have developed a highly branch-selective
allylic C−H carboxylation of terminal alkenes using a Pd
catalyst with a sulfoxide−oxazoline (sox) ligand. The developed
Pd/sox catalyst is responsible for the increase in both yield and
regioselectivity. The development of related dual-functionalized
catalysts and the application to other C−H functionalization
reactions are ongoing in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, characterization data for all new
compounds, and details of computational study. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
Figure 1. X-ray crystal structure of PdCl2(L3) complex 3. Selected
bond lengths (Å): Pd1−N1 = 2.039(2), Pd1−S1 = 2.2402(8), Pd1−
Cl1 = 2.2905(8), Pd1−Cl2 = 2.3048(8).
S
catalyst (Figure 2). When acetic acid was changed to other
carboxylic acids such as cinnamic acid and their derivatives, the
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: gliu@mail.sioc.ac.cn (G.S.L.).
*E-mail: itami@chem.nagoya-u.ac.jp (K.I.).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Dr. Yasutomo Segawa (Nagoya Univ.) for assistance
in X-ray crystal structure analysis and Dr. Keiko Kuwata
(Nagoya Univ.) for assistance in mass spectroscopy. This work
was supported by the Funding Program for Next Generation
World-Leading Researchers from JSPS (K.I.), a Grant-in-Aid
for Scientific Research on Innovative Areas “Molecular
Activation Directed toward Straightforward Synthesis”
(25105720 to J.Y.), and KAKENHI (25708005 to J.Y.) from
MEXT. ITbM is supported by the World Premier International
Research Center (WPI) Initiative, Japan. F.Y. and GS.L. thank
the National Science Foundation of China (No. 21222510) for
the financial support.
REFERENCES
■
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(9) Initially, we conducted the allylic C−H oxidation of 1a using 5
mol % FePc instead of benzoquinone in the presence of 10 mol % Pd/
L1 catalyst, which is exactly the same procedure as that in ref 8.
However, the reaction gave 2a only in 2% yield.
(10) 5 mol % Pd(II) source is enough for efficient promotion of this
reaction. The excess amount of ligand might stabilize the active species
within the catalytic cycle.
(11) The product yields (B/L ratio) after 12 and 24 h under the
optimized conditions using L11 are as follows: 29% yield (B/L = 99:1)
after 12 h; 53% yield (B/L = 99:1) after 24 h.
(12) When White’s Pd/bis-sulfoxide catalyst was used for the
reaction of 1a, 2a was formed in 83% yield with 98% branch selectivity.
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