A Cu/Pd Cooperative Catalysis for Enantioselective Allylboration of Alkenes

Article abstract of DOI:10.1021/jacs.5b09146

A cooperative Cu/Pd-catalyzed asymmetric three-component reaction of styrenes, B₂(pin)₂, and allyl carbonates was reported. This reaction, in the presence of chiral CuOAc/SOP and achiral Pd(dppf)Cl₂ catalysts, occurs smoothly with high enantioselectivities (up to 97% ee). The allylboration products, which contain alkene (or diene) unite and alkylboron group, are easily functionalized. The utility of this protocol was demonstrated through the synthesis of an antipsychotic drug, ()-preclamol.

Full text of DOI:10.1021/jacs.5b09146

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Communication
A Cu/Pd Cooperative Catalysis for Enantioselective Allylboration of Alkenes
Tao Jia, Peng Cao, Bing Wang, Yazhou Lou, Xuemei Yin, Min Wang, and Jian Liao
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b09146 • Publication Date (Web): 12 Oct 2015
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A Cu/Pd Cooperative Catalysis for Enantioselective Allylbora-
tion of Alkenes
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Tao Jia, Peng Cao, Bing Wang, Yazhou Lou, Xuemei Yin, Min Wang and Jian Liao*
Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041,
China.
Supporting Information Placeholder
reagent.1a,12 We believe that the stereospecific transmetal-
lation of alkylcopper with XPd(L)R’ in the proposed
ABSTRACT: A cooperative Cu/Pd-catalyzed asymmetric
three-component reaction of styrenes, B2(pin)2 and allyl
carbonates was reported. This reaction, in the presence of
mechanism, and the compatibility of the chiral L*Cu(I)-
complex with the achiral Pd(0)- or Pd(II)-complex would
chiral CuOAc/SOP and achiral Pd(dppf)Cl2 catalysts, oc-
be the key issues. In our previous work,13 a sterespecific
curs smoothly with high enantioselectivities (up to 97%
copper-tin transfer was observed in Cu(I)-catalyzed enan-
ee) . The allylboration products, which contain alkene (or
tioselective alkene stannylboration when using chiral sul-
diene) unite and alkylboron group, are easily functional-
foxide-(P-aryl)phosphine (SOP) ligand. In this work, we
ized. The utility of this protocol was demonstrated
found that P-alkyl sulfoxide-phosphine ligands14 can ef-
through the synthesis of an antipsychotic drug, (-)-
fectively promote the aforementioned Cu-Pd transmetal-
lation and realize a highly enantioselective allylboration
of alkenes.
preclamol.
Multifunctional and enantioenriched organoboranes
are useful building blocks in the synthesis of natural
products and bioactive compounds.1 Transition metal-
catalyzed asymmetric carboboration reaction is an effi-
cient and straightforward approach to access chiral multi-
substituted alkyl- or alkenylboranes.2 For instance, Ito
and coworkers developed a successful copper-catalyzed
Scheme 1. Strategy of Catalytic Asymmetric Intermo-
lecular Carboboration of Alkenes
borylative cyclization to prepare optically pure β-aryl or
silylated cyclopropylboronates.3 The related asymmetric
carboboration of allenes, alkynes and 1,3-enynes are also
applied in the synthesis of chiral di-, tri- and tetra-
substituted alkenylboron esters by Hoveyda1c,4 and Lin.5
However, up to date, enantioselective carboboration of
alkenes for the construction of enantioenriched and muti-
functional alkylborons are less developed. Sporadic ex-
amples were reported and limited to Cu-catalyzed boryla-
tive aldol carboboration6 and Pd-catalyzed 1,1-
arylboration.7
To test the feasibility, the three-component reaction
of styrene (1a), B2(pin)2 and allylic electrophiles was per-
formed in the presence of (SOP)CuCl catalyst precursor
and Pd(dppf)Cl2 co-catalyst. After screening a series of
allyl substrates with different leaving groups (e.g. halides,
esters and carbonates), t-butyl allyl carbonate 2a was con-
firmed as the best electrophile in terms of the reactivity
and selectivity. (see supporting information for details) In
the presence of chiral ligand A, three-component assem-
bling 3aa was afforded in 39% NMR yield with 90% ee,
albeit low conversion and unavoidable generation of side
products 4 and 5. (Table 1, entry 1) Systematic survey to
palladium complex, copper salt, base and solvent revealed
that the use of CuOAc, KOH and t-BuOMe enabled im-
Very recently, Semba, Nakao8 and Brown9 independent-
ly reported a remarkable three-component carboboration
of alkenes with bis(pinacolato)diboron (B2(pin)2) and aryl
or vinyl halides by a Cu/Pd cooperative catalysis. We en-
visioned using this combination catalysis10 as a platform
to develop enantioselective carboboration of simple al-
kenes. The proposed procedure involves two cooperative
catalytic cycles (Scheme 1), a Cu-catalyzed enantioselec-
tive generation of β-borylalkylcopper11 and a Pd-catalyzed
cross-coupling transformation of this enantioenriched
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provements of the catalytic efficiency (Table 1, entry 4, for
asymmetric allylboration. (Table 2) When 2a was used as
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4
5
6
7
8
9
details see supporting information). However, the hy-
droboration and β-H elimination products still cannot be
avoided and severely erode yields of desired reaction (4+5>
20% yield). Other P-diphenyl sulfoxide-phosphines or
commercially available chiral phophine ligands, (i.e. B, C
and D) were also evaluated but no better results were
yielded. (entries 5-7 and see supporting informations) To
our delight, P-dialkyl sulfoxide-phosphine ligands (E-H)
effectively improve yields of 3aa, concomitant formation
of trace 4 and 5 (<5%). (entries 8-11) Accordingly, the P-
diisopropyl ligand H provided 3aa in 80% yield with 92%
ee. (Table 1, entry 11) In the presence of optimal copper
and palladium catalysts, the reaction was performed at
0oC and gave 3aa in 80% isolated yield with 95% ee. (Ta-
ble 1, entry 12)
the electrophilic coupling partner, a wide range of vinyl
arenes could be effectively converted into the correspond-
ing three-component products with generally excellent
enantioselectivities. The reaction is compatible with vari-
ous functional groups such as alkyl, aryl, OBz, halogen
bound to benzene ring. Particularly, most of halogens (i.e.
F, Cl or Br), which (Cl and Br) are not tolerant of
(NHC)CuBpin-catalyzed carboboration,8,9,15 can be in-
stalled at o-, m- or p-site of styrene substrates and have
little effects on this transformation. Styrenes with p-CF3
(product 3la, 51% yield, 82% ee) or m-OMe (product 3oa,
78% yield, 96% ee) were also reactive. The product 3oa
was assigned to (S)-configuration, and this stereochemi-
cal outcome is consistent with that of Cu(I)/SOP-
catalyzed boryl stannaylation when using the same ligand
A.13 Therefore, the transmetallation from Cu to Pd should
proceed in stereochemically retentive manner, the same
with Cu-Sn transferring process. Notably, 4-vinyl indole
and 2-vinyl naphthalene are appropriate to provide 3pa
and 3qa in good yields and ees. Although the attempted
allylboration of 1,2-substituted styrene derivatives (i.e. β-
methyl styrene), methyl crotonate (hydroboration prod-
uct was observed) and alkyl-substituted alkenes were fu-
tile, that of bicyclo[2.2.1]hepta-2,5-diene proceeded
smoothly and highly diastereoselective exo-3rb was af-
forded in good yield with moderate enantioselectivity.
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Table 1. Asymmetric Allylboration of the Styrenea
Table 2. Substrate Scope of Three-Component
Coupling Reactiona
copper
salt
CuCl
yield(%)b
(3aa/4+5)
39/19
25/14
65/21
62/27
63/7
53/28
30/59
81/4
eec
(%)
90
88
84
89
-20
-77
68
84
85
entry
base
1
2
3
4
5
A
A
A
A
B
C
D
E
NaOtBu
NaOtBu
NaOtBu
KOH
KOH
KOH
KOH
KOH
KOH
KOH
CuBr
†
b
c
3ba
R= o-Me( ); 91% , 97% ee
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
R= o-Cl (3ca); 82%, 96% ee
R= o-Br (3da); 68%, 94% ee
Bpin
Bpin
R
3ea
R= p-Me(
); 53%, 91% ee
R= p-tBu(3fa); 54%, 96% ee
R= p-Ph(3ga); 76%, 94% ee
6
7
3ha
R= p-OBz( );62%, 96% ee
R= p-F (3ia); 80%, 96% ee
R
(3ea-3la)
(3ba-3da)
8
9
10
11
12d
3ja
R= p-Cl
(
); 61%, 96% ee
F
78/8
75/4
3ka
R= p-Br (
); 43%, 96% ee
R= p-CF3 (3la); 51%, 82% ee
G
H
H
90
92
95
Bpin
Bpin
Bpin
KOH
KOH
80/3
81(80)e/5
MeO
Cl
Br
aReaction was performed with 1a (0.2 mmol), 2a (0.3
mmol), B2(pin)2 (0.3 mmol), Pd(dppf)Cl2 (5 mol %), the
copper salt (10 mol %), L (12 mol %), the base (0.2 mmol)
in BuOMe (4 mL) at 20 C for 12h Determined by H
NMR spectroscopy. Determined by HPLC analysis and
3ma
73%, 94% ee
3oa
78%, 96% ee
3na
56%, 94% ee
t
o
b
1
Bpin
Bpin
c
Bpin
BocN
the absolute configuration was assigned to (S) by compar-
ing the optical rotation of (S)-11 with literature (see
scheme 2). dThe reaction was performed at 0 oC. eThe data
in the parenthesis was isolated yield of 3aa.
3qa
81%, 97% ee
3pa
77%, 94% ee
3rb
71%, 67% ee
Ph
aReactions conditions: 1 (0.2 mmol), 2a (0.3 mmol),
B2(pin)2 (0.3 mmol), Pd(dppf)Cl2 (5 mol %), CuOAc (10
With these optimized conditions in hand, we next
investigated the substrate scope of this Cu/Pd-catalyzed
mol %), H (12 mol %), KOH (0.2 mmol) in t-BuOMe (4
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mL) at 0oC for 12h. bIsolated yields. cDetermined by HPLC
analysis.
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50
40
38
96
(2f)
4
(3bf)
(3bg)
(3bg’)
5
This Cu/Pd catalysis is not only applicable to the un-
6
7
8
9
substituted symmetric allyl electrophile, but also compat-
ible with mono- and disubstituted allyl systems. More
complex and unsymmetrically substituted allylic electro-
philes would make the reaction more complicated since
regio- and/or diastereoisomeric products in the “allyl
fragment” can be formed. When we examined the cross
coupling of alkyl- and aryl-substituted allyl complexes
with the in situ generated alkylcopper from 1b, both
branched (b) and linear (l) allyllic carbonates were used.
(Table 3) Both phenyl-substituted l-2b and b-2b gave the
only linear allylation product 3bb in high yield with excel-
lent ee.16 (entry 1) Interestingly, for the coupling of alkyl-
substituted substrates, b-2c was preferable to the corre-
sponding l-2c allylic carbonate in terms of the reactivity
and enantioselectivity, probably due to the “memory ef-
fect”.17 (entry 2) Other branched allyl electrophiles such as
n-Pr (2d), Cy (2e) and vinyl-substituted (2f) carbonates
are also established with high level of enantiopuri-
ties.(entries 3-5) When chiral 2g was used in the asym-
metric reaction, 3bg or 3bg’ was provided by (R)-H or (S)-
H ligand with the newly generated stereogenic center
totally reversed. (95/5 vs 3/97 dr, entries 6-7) The current
catalytic system also demonstrates excellent ability to
control the diastereoselectivity when racemic cyclic allylic
carbonates were applied. For instance, asymmetric alkyla-
tion of 2h and 2i afforded 3bh and 3bi bearing two adja-
cent and stereodefined C-centers. (entries 8-9) The prod-
uct 3bh is assigned to the trans-isomer by NOE analysis
of the derivative 6. (see supporting information) Notably,
the enantioselective arylboration8,9 can occur smoothly
when using PhI (2j) as electrophile. (entry 10)
6
95:5d
(2g)
3:97d
96
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7
(2g)
47
(>20/1)
8
(2h)
(2i)
(3bh)
70
(12/1)
9
94
90
(3bi)
(3bj)
10
PhI ( 2j)
54
aThe reaction was performed with 1 (0.2 mmol), 2 (0.3
mmol), B2(pin)2 (0.3 mmol), Pd(dppf)Cl2 (5 mol %), the
copper salt (10 mol %), H (12 mol %), the base (0.2 mmol)
t
o
b
c
in BuOMe (4 mL) at 0 C for 12h Isolated yields. Deter-
d
mined by HPLC analysis. The ratio of 3bg and 3bg’ was
checked by 1H NMR.
To illustrate the versatility and potential of this
methodology, site-selective transformations of enantioen-
riched β-allylboronic esters were implemented to con-
struct chiral hydrocarbon building blocks. (Scheme 2) For
instance, the ozonization18 of 3ba enables selective con-
version of C=C bond to C=O bond without interference of
C-B bond or loss of enantiopurity, whilst the oxidation by
NaBO3.4H2O11c selectively cleavages C-B bond. Thus ei-
ther γ-carbonyl boronate (7) or pent-4-en-1-ol (8) can be
obtained with high level of optical purities using different
oxidative reagents. Accordingly, B-oxidation/iodine ether-
ification19 of 3bh, provided bicyclic 6 with excellent dia-
stereo- and enantioselectivity. Other transformations
such as intramolecular Heck reaction20 of 3da to 9 and
Suzuki coupling13 of 3bb to 10 also proceeded well with
total retention of the stereocenter. The utility of this
asymmetric allylboration was also demonstrated through
the synthesis of (-)-preclamol,21 an antipsychotic drug,22
from the enantioenriched 3oa (96% ee). A sequential hy-
droboration/oxidation to (S)-11,21a followed by the ring
close amination and hydrolysis, gave just the (-)-
preclamol bearing (S)-stereocenter.
Table 3. The Scope of Allyl Boc Substratesa
yieldb
(%)
eec
(%)
entry
1
2
3
81
95
(lꢀ2b)
(3bb)
82
95
(bꢀ2b)
In summary, a cooperative Cu/Pd-catalyzed asym-
metric three-component reaction of styrenes, B2(pin)2
and allyl carbonates was developed. This work presents
the first example of catalytic asymmetric intermolecular
1,2-carboboration of alkenes, which contributes to the
development of new catalytic asymmetric protocols of
alkene difunctionalization.
76
86
91
97
(lꢀ2c)
2
(3bc)
(3bd)
(bꢀ2c)
3
51
37
93
91
(2d)
(2e)
4
Scheme 2. Products Transformations
(3be)
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ASSOCIATED CONTENT
Supporting Information
Procedures and full characterization of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* jliao@cib.ac.cn
Notes
The authors declare no competing financial interest.
(16) Direct borylation product (about 30% NMR yield) of l-2b
was observed. Although this side product can be significantly
minimized when reducing the amount of B2(pin)2(1.1 equiv.) and
the allyl carbonate(1.1 equiv.), the hydroboration and β-
elimination products (about 30% NMR yield) unavoidably
formed.
(17) (a) Lloyd-Jones, G. C. ; Stephen, S. C. Chem.-Eur. J. 1998, 4,
2539. (b) Trost, B. M. ; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70.
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6156.
ACKNOWLEDGMENT
We thank the NSFC (No. 21472184, 21572218, 21272226, and
21402186) and Western-Light Foundation of CAS for financial
support.
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5
ACS Paragon Plus Environment