Highly Stereoselective Synthesis of 1,2-Disubstituted Indanes by Pd-Catalyzed Heck/Suzuki Sequence of Diarylmethyl Carbonates

Article abstract of DOI:10.1021/acs.orglett.0c00945

A palladium-catalyzed Mizoroki-Heck-type cyclization/Suzuki-Miyaura cross-coupling cascade of diarylmethyl carbonates with arylboronic acid derivatives has been developed to deliver the corresponding 1,2-disubstituted indanes in good yields with high dias

Full text of DOI:10.1021/acs.orglett.0c00945

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Letter
Highly Stereoselective Synthesis of 1,2-Disubstituted Indanes by Pd-
Catalyzed Heck/Suzuki Sequence of Diarylmethyl Carbonates
Akihiro Matsude, Koji Hirano,* and Masahiro Miura*
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sı Supporting Information
ABSTRACT: A palladium-catalyzed Mizoroki−Heck-type cyclization/Suzuki−Miyaura cross-coupling cascade of diarylmethyl
carbonates with arylboronic acid derivatives has been developed to deliver the corresponding 1,2-disubstituted indanes in good
yields with high diastereoselectivity (trans/cis > 20:1). The key to achieve the high chemoselectivity and stereoselectivity is the use of
the tris[3,5-di(tert-butyl)-4-methoxyphenyl]phosphine (DTBMP) ligand of remote steric hindrance. Moreover, the asymmetric
synthesis is possible by the enantiospecific, stereoinvertive reaction of the optically active starting substrates to form the chiral
indanes with high stereochemical fidelity (>98% es).
he Mizoroki−Heck-type reaction is one of the most
tion/Suzuki−Miyaura coupling sequence of diarylmethyl
carbonates with arylboronic acid derivatives to furnish the
corresponding 1,2-disubstituted indanes with high trans-
selectivity (trans/cis > 20:1). Furthermore, the asymmetric
synthesis is also possible by the enantiospecific, stereoinvertive
cascade reaction of the readily available optically active starting
substrates with high stereochemical fidelity (>98% es). The
related nickel-catalyzed enantiospecific Mizoroki−Heck-type
cyclization of secondary benzyl ethers was developed by Jarvo,
but application to the sequential bond-forming process is still a
T
powerful and reliable catalytic carbon−carbon bond
1
forming reactions in modern organic synthetic chemistry. In
particular, the intramolecular versions (Mizoroki−Heck
cyclization) are often applied to the construction of unique
ring structures. Among them, the Mizoroki−Heck cyclization/
cross-coupling sequence can readily provide multiply sub-
stituted cyclic frameworks, which are of prevalence in bioactive
molecules and natural products. To date, synthetic chemists
have developed various protocols for the palladium-catalyzed
2
6
domino cyclization/cross-coupling of sp C-hybridized aryl
formidable challenge.
We have recently developed the palladium-catalyzed intra-
halides bearing the tethered alkene moiety with external
nucleophiles to form versatile ring systems, which often
molecular Mizoroki−Heck-type reaction of diarylmethyl tert-
2
7
includes the asymmetric synthesis. On the other hand, the use
butyl carbonates. In our continuing interest in this chemistry,
3
of sp C-hybridized alkyl electrophiles in such sequential
we envisioned our blueprint for the sequential coupling in
conjunction with the arylboronic acid external nucleophiles.
Our working hypothesis is illustrated in Scheme 1. The initial
transformations still remains underdeveloped while the simple
Mizoroki−Heck-type reaction of alkyl halides is known to be
3
promoted by several transition metal catalysts. As a limited
oxidative addition of diarylmethyl tert-butyl carbonate 1 to
successful example, Oshima, Yorimitsu, and co-workers
reported the cobalt-catalyzed tandem Mizoroki−Heck-type
cyclization/cross-coupling of alkyl halides to afford the highly
0
Pd L A forms the corresponding σ-benzylpalladium B, which
n
8
is in equilibrium with the π-benzylpalladium B′. The
subsequent migratory insertion of the pendant alkene moiety
4
substituted five-membered cyclic systems. However, the
affords the alkylpalladium intermediate C. The interception
highly reactive Grignard reagents are necessary as the external
carbon nucleophiles. Moreover, the cyclization event occurs via
carbon-centered free radical species; therefore, the stereo-
chemistry in the ring closure step is generally difficult to
control. Thus, further development of such a cascade reaction,
particularly, stereocontrolled process with the alkyl electro-
Received: March 16, 2020
5
philes is highly appealing. Herein, we report a palladium-
catalyzed highly diastereoselective Mizoroki−Heck cycliza-
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c00945
A
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Scheme 1. Working Hypothesis of Pd-Catalyzed Mizoroki−
Heck Cyclization/Suzuki−Miyaura Sequence and
Conceivable Challenges
Table 1. Optimization Studies for Pd-Catalyzed Mizoroki−
Heck/Suzuki−Miyaura Sequence of Diarylmethyl
a
Carbonate 1a with Arylboronic acid 2a
b
yield (%)
c
entry
2
ligand
XPhos
P(t-Bu)3
3aa, trans/cis
4aa
5a
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
48, 1:1.2
0, −
13
0
0
0
0
7
39
0
0
0
31
15
40
16
19
10
0
30
15
0
PCy3
52, 1:1.8
74, 1.6:1
79, 1:1.3
82, 1:1.3
0, −
69, 2.6:1
80, 2.8:1
83, 13:1
81, 4.6:1
82, >20:1
79, >20:1
(94), >20:1
PCy Ph
2
PCyPh2
with the arylboronic acid 2 (transmetalation; C to D) followed
PPh3
by the reductive elimination furnishes the targeted 1,2-
0
P(4-CF C H )
disubstituted indane 3 and the starting Pd L A to complete
3
6
4
n
P(4-MeOC H )
the catalytic cycle. However, there are several challenges
associated with the aforementioned reaction design. First one
is the chemoselectivity issue: the benzylpalladium B or B′
could directly undergo the Suzuki−Miyaura cross-coupling
reaction with the boronic acid 2 through transmetalation and
6
4
DMMP
DTBMP
DTBP
DTBMP
DTBMP
DTBMP
10
11
12
13
14
0
0
0
0
6
3
0
2
2a-Bpin
2a-Bneo
2a-Bneo
reductive elimination to deliver the undesired triarylmethane
d
9
4
. Similarly, the alkylpalladiums C and D are prone to β-
a
3
hydride elimination, giving the simple Mizoroki−Heck-type
Conditions: 1a (0.20 mmol), 2 (0.30 mmol), [PdCl(η -C
3
H
)]
5
2
10
(
0.0050 mmol), ligand (0.022 mmol), K CO (0.60 mmol), t-
2 3
b
cyclization byproduct 5. Second is the control of relative
stereochemistry (trans or cis) of the adjacent chiral carbon
centers in the insertion step (B to C). Finally, the
configuration at the point chirality of the starting diarylmethyl
carbonate 1 (inversion, retention, or racemization) should be
mentioned when the optically active substrate is employed.
On the basis of the above scenario, we began optimization
studies with the diarylmethyl tert-butyl carbonate 1a, 4-
̊
1
AmOH/H O (2.0/0.1 mL), 100 C, 2 h, N . Estimated by H NMR
2
2
with 1-methylnaphthalene as the internal standard. Isolated yield is in
parentheses. Determined by H NMR of crude material. With 2a-
Bneo (0.21 mmol) and K PO (0.20 mmol).
c
1
d
3
4
3
methoxyphenylboronic acid (2a), [PdCl(η -C H )] catalyst,
3
5
2
K CO base, and t-AmOH (2-methyl-2-butanol)/H O mixed
2
3
2
solvent system to identify the appropriate ligand (Table 1). An
initial attempt with the XPhos ligand, which was the optimal
ligand in our previous work, resulted in the formation of the
that the reaction of 1a proceeded more efficiently and
stereoselectively with the corresponding neopentylglycol ester
2a-Bneo and K PO base to afford 3aa in 94% isolated yield
7
desired 3aa albeit with moderate yield (48%), trans/cis
selectivity (1:1.2), and chemoselectivity (4aa, 13%; 5a, 31%;
entry 1). To suppress the β-hydride elimination en route to 5a,
we next investigated some electron-rich, bulky alkylphosphine
3
4
with >20:1 trans/cis selectivity (entry 14). Some additional
observations are to be noted: bidentate ligands generally
produced a mixture of 3aa, 4aa, and 5a; other Pd sources such
as Pd(OAc) , PdCl , and Pd (dba) totally shut down the
11
ligands (entries 2−5). Although the yield of 3aa increased, a
2
2
2
3
significant amount of the Mizoroki−Heck-type product 5a was
reaction; the external base was not necessary but increased the
product yield (see the Supporting Information for more
detailed optimization studies).
still formed. On the other hand, unexpectedly, the simple PPh
3
also promoted the reaction to afford 3aa in 82% yield (entry
6
). Inspired by this intriguing outcome, we moved our
With the optimal conditions in hand (Table 1, entry 14), we
first examined the scope of the diarylmethyl carbonates 1
(Scheme 2). Both electron-donating and -withdrawing groups
on the benzene ring were well tolerated to form the
corresponding substituted indanes 3ba−3da in high yields
(91−>99%). The 2-naphthalene substituent could also be
replaced with methoxy-substituted naphthalene, 1-naphtha-
lene, and higher fused phenanthrene moieties (3ea−3ga; 81−
90%). Additionally, the heteroaromatic substrates such as
dibenzothiophene, benzothiophene, and benzofuran could also
be employed (3ha−3ja; 63−82%). Particularly notable is the
successful transformation of conceivably more challenging
attention to triarylphosphine ligands. Whereas the electron-
withdrawing ligand was ineffective (entry 7), electron-donating
P(4-MeOC H ) , DMMP, and DTBMP produced 3aa,
particularly with DTBMP chemoselectively providing 3aa
with high trans/cis selectivity (13:1; entry 10). The control
experiment with the DTBP ligand maintained the high
chemoselectivity but lowered the stereoselectivity (entry 11),
thus suggesting that the tBu groups at the meta positions
mainly suppress the β-hydride elimination and both tBu and
MeO groups affect the stereoselectivity in the insertion step (B
6
4 3
12
to C in Scheme 1). Subsequent fine-tuning finally revealed
B
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Scheme 2. Products of Pd-Catalyzed Mizoroki−Heck Cyclization/Suzuki−Miyaura Coupling Sequence of Various
c
Diarylmethyl Carbonates 1 and Arylboronates 2-Bneo
a
b
c
3
On a 1.0 mmol scale with 1.01 equiv of 2a-Bneo. For 16 h. Conditions: 1 (0.20 mmol), 2-Bneo (0.21 mmol), [PdCl(η -C H )] (0.0050
3
5
2
mmol), DTBMP (0.022 mmol), K PO (0.20 mmol), tAmOH/H O (2.0/0.1 mL), 100 °C, 2 h, N .
3
4
2
2
1
3
monocyclic substrates: thiophene-substituted, biphenyl-sub-
stituted, and even simple phenyl-substituted diarylmethyl
carbonates smoothly underwent the reaction to deliver the
corresponding 1,2-disubstituted indanes 3ka−3ma in accept-
able yields. In addition to the indane structure, the cyclo-
pentanaphthalene framework 3na could also be readily
prepared with high chemo- and stereoselectivity. The scope
of arylboronates 2-Bneo is also substantially broad. The
arylboronates bearing electron-withdrawing trifluoromethyl
and chloro groups were amenable without any difficulty (3ab
and 3ac). The carbonyl functions including aldehyde, ketone,
and ester were equally compatible under the standard reaction
conditions (3ad−3af). The sterically demanding 1-naphthyl-
boronate was also reactive to afford 3ag in a high yield.
Furthermore, a range of heteroarylboronates was successfully
coupled with 1a, and free NH-indole, pyridine, and thiophene
substituents were thus readily introduced to the indane scaffold
(3ah−3aj). In all cases, the high diastereoselectivity was
observed (trans/cis > 20:1). The trans stereochemistry of 3ea
and 3na was unambiguously confirmed by X-ray analysis
(CCDC 1981987 and 1981988). The reaction was also
scalable and easily conducted on a 1.0 mmol scale without
any erosion of yield and stereoselectivity, thus indicating the
14
good reproducibility and reliability (3aa).
We finally focused on the enantiospecificity of the reaction
(Scheme 3). Pleasingly, the readily prepared optically active
15
(S)-1a was converted with inversion of configuration to the
enantioenriched (R,R)-3aa in high enantiospecificity (97:3 er,
>99% es). The steric and electronic nature of diarylmethyl
carbonates 1 (chloro, methoxy, and biphenyl substituents) and
C
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Scheme 3. Optically Active Products by Enantiospecific,
Accession Codes
Stereoinvertive Pd-Catalyzed Mizoroki−Heck Cyclization/
CCDC 1981987, 1981988, 1984967, and 1984968 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
Suzuki−Miyaura Coupling Sequence of Chiral Diarylmethyl
a
Carbonates (S)-1 and Arylboronates 2-Bneo
1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Koji Hirano − Department of Applied Chemistry, Graduate
School of Engineering, Osaka University, Suita, Osaka 565-
0
871, Japan; orcid.org/0000-0001-9752-1985;
Email: k_hirano@chem.eng.osaka-u.ac.jp
Masahiro Miura − Department of Applied Chemistry, Graduate
School of Engineering, Osaka University, Suita, Osaka 565-
0
871, Japan; orcid.org/0000-0001-8288-6439;
Email: miura@chem.eng.osaka-u.ac.jp
Author
Akihiro Matsude − Department of Applied Chemistry,
Graduate School of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan
a
%
es = (% ee of product 3/% ee of starting substrate 1) × 100.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00945
Notes
arylboronates 2 (methoxy, chloro, formyl, and NH-indolyl
functions) did not affect the enantiospecificity, and the
corresponding chiral 1,2-disubstituted indanes were obtained
with high stereochemical fidelity (98 to >99% es). The
absolute configurations of (R,R)-3da and (R,R)-3ec were
determined by single X-ray crystallographic analysis (CCDC
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI Grant Nos. JP
8K19078 (Grant-in-Aid for Challenging Research (Explor-
■
1
atory)) to K.H. and JP 17H06092 (Grant-in-Aid for Specially
Promoted Research) to M.M. We thank Dr. Yuji Nishii (Osaka
University) for his assistance with X-ray analysis.
1
984967 and 1984968), which suggests the S 2-type oxidative
N
addition with inversion of configuration (A to B in Scheme
16
1
).
In conclusion, we have developed a Pd/DTBMP-catalyzed
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1
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(
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4
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2
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limitations.
(
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(
17) Given the steric bulkiness of DTBMP, one possibility is the
formation of a low-coordinating Pd species. Actually, the reaction with
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the direct Suzuki−Miyaura coupling byproduct 4aa was still
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E
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