Copper-Catalyzed Asymmetric Borylallylation of Vinyl Arenes

Article abstract of DOI:10.1021/acs.orglett.7b03022

A copper-catalyzed, enantioselective method for the borylallylation of vinyl arenes is reported. The reaction produces enantioenriched and functionalized organoboron compounds by sequentially incorporating boryl and allyl groups onto the C - C bond of vinyl arenes. Copper-catalyzed borylative coupling of vinyl arenes with allyl phosphates successfully proceeds in a regio- and enantioselective manner in the absence of a palladium cocatalyst.

Full text of DOI:10.1021/acs.orglett.7b03022

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Copper-Catalyzed Asymmetric Borylallylation of Vinyl Arenes
Namhyeon Kim,† Jung Tae Han,† Do Hyun Ryu, and Jaesook Yun*
Department of Chemistry and Institute of Basic Science, Sungkyunkwan University, Suwon 440-746, Korea
S
* Supporting Information
ABSTRACT: A copper-catalyzed, enantioselective method
for the borylallylation of vinyl arenes is reported. The reaction
produces enantioenriched and functionalized organoboron
compounds by sequentially incorporating boryl and allyl
groups onto the CC bond of vinyl arenes. Copper-catalyzed
borylative coupling of vinyl arenes with allyl phosphates
successfully proceeds in a regio- and enantioselective manner
in the absence of a palladium cocatalyst.
in the allylation.7 In particular, copper-catalyzed allylic
he installation of different functional groups onto C−C
substitution8 could be a good candidate for a series of tandem
Tunsaturated bonds in a single process is a powerful
method for the preparation of complex organic molecules.1 In
reactions of in situ generated organocopper intermediates.
While a copper-catalyzed hydroallylation of styrenes has been
reported,9 copper-catalyzed borylative coupling of simple
styrenes with allylic electrophiles has not yet been reported
without cooperative palladium catalysis. To date, only copper-
catalyzed borylallylations of allenes, alkynes, and vinyl
boronates have been reported.10 Herein, we report an
enantioselective borylallylation of vinyl arenes catalyzed by a
chiral phosphine−copper catalyst that provides access to
functionalized alkylboranes.
recent years, organocopper intermediates generated by
borylcupration of unsaturated substrates with bis(pinacolato)-
diboron (B2pin2) have been discovered to be useful organo-
metallic reagents for the formation of various C−C bonds
through addition,2 substitution,3 and coupling reactions with
electrophiles.4 In these multicomponent reactions, borylated
organocopper intermediates were generated in situ from
alkenes, allenes, and alkynes in the presence of a copper
catalyst.
Our group recently reported the copper-catalyzed allylation
of enantioenriched α-boryl organocopper species (I).11 Given
the similar steric factors of α-boron organocopper species and
β-boryl organocopper species (II), we envisioned that catalytic
borylallylation could be achieved by copper catalysis in the
absence of palladium. Upon applying our previous reaction
conditions12 developed for α-boron organocopper species (I)
to simple styrene (1a) with allyl phosphate, however, the
desired product was obtained in poor NMR yield and ee (30%,
3% ee) along with the protonated side product. Therefore, we
screened a series of reaction conditions to optimize the
borylallylation of styrene (Table 1). After extensive inves-
tigation starting with a racemic ligand (dppbz, Figure 1), we
found that the desired product 3aa could be obtained in 84−
87% yield when CuBr or CuCl was used as precatalyst with
LiOMe as the base and allyl phosphate (2a) in dimethylace-
tamide (DMA) solvent. The use of other bases or solvents or
other allylic electrophiles resulted in low NMR yields or
substantial formation of side products resulting from C−H
borylation (3a′) and protoborylation (3a′′).13 Next, we
screened a variety of chiral ligands for their effectiveness
(entries 3−10). Among the screened ligands, Josiphos-type
ligands and QuinoxP ligand gave promising yields of the
desired product 3aa in good ee (entries 7−10). Finally, we
Recently, palladium and copper cooperative catalysis has
been applied to coupling reactions of such organocopper
intermediates with aryl halides.5 The dual catalysis was also
applied to the enantioselective allylboration of vinyl arenes by
Liao and co-workers using tert-butyl allyl carbonates as
electrophiles (Scheme 1, a).6 Transition-metal-catalyzed
allylation methods are considered valuable transformations
due to the versatility of the olefin functional group incorporated
Scheme 1. Catalytic Allylation Methods
Received: September 27, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03022
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
a
Table 1. Optimization
Scheme 2. Substrate Scope in Asymmetric Borylallylation
a
NMR yield (%)
a
b
conv
ee of
entry
[Cu]
ligand
(%)
3aa
3a′ + 3a′′ 3aa (%)
c
c
1
2
3
4
5
6
CuBr dppbz
94
92
87 (80)
84
<2
<2
CuCl dppbz
CuBr (R)-Segphos
CuBr Duanphos
CuBr (S,S)-BPE
90
50
3
75
77
100
43
98 (95)
43
<2
38
<2
56
CuBr (R,R)-
70
48
18 (S)
Walphos
7
CuBr (R,S)-t-Bu-
100
92
55
73
19
3
89
87
88
90
Josiphos
d
8
CuBr (R,S)-
Josiphos
d
c
c
9
CuBr (R,R)-
97
77 (73)
78 (74)
2
QuinoxP
d
10
CuCl (R,R)-
97
2
QuinoxP
a
Determined by 1H NMR analysis using DMF as an internal standard.
Determined by HPLC analysis on a chiral stationary phase. Isolated
b
c
yield of the corresponding hydroxy product via oxidation using
d
NaBO3. Reaction temperature was 40 °C instead of 60 °C.
Figure 1. Ligand structure.
chose CuCl/QuinoxP in DMA (entry 10) as an optimized set
of reaction conditions.
a
b
Isolated yield. Determined by HPLC analysis on a chiral stationary
Having identified optimized conditions, we next investigated
the substrate scope of the borylallylation (Scheme 2). Reactions
of styrene (1a) with different allylic electrophiles (2a−d)
proceeded to give good yields of borylallylated products with
good enantioselectivities. Substituted allylic electrophiles (2b−
d) provided improved yields of the products compared to allyl
phosphate 2a, presumably due to less competing side reaction
with the active Cu−Bpin catalyst. In particular, the use of Br-
substituted allylic phosphate (2d) led to the desired compound
containing a vinyl bromide, which could be further utilized in a
variety of other organic transformations.14 o-, m-, and p-methyl
and -methoxy-substituted styrenes were all reactive (1b−g), but
slightly decreased ee values were observed in the ortho- and
meta-substituted cases. Substrates (1e−j) with an electron-
donating- or electron-withdrawing substituent were suitable
substrates in the borylallylation. However, the vinyl arene (1h)
with an o-Cl exhibited relatively low enantioselectivity
compared to other ortho-substituted vinyl arenes. The reaction
phase.
of vinyl naphthalene and other heteroaromatic vinyl arenes gave
the desired products in good yields and ee. In particular, 3-vinyl
indole (1l) and vinyl ferrocene substrate (1n) afforded the
corresponding products 4lb and 4nb in 96% and 90% ee,
respectively. The reaction of a vinylsilane gave product 4oa in
40% yield and 80% ee. Finally, we found that internal alkene
substrates (1p and 1q) did not afford the desired coupled
products due to competitive reactions of the borylcopper
catalyst with allyl phosphate.
This three-component coupling was also effective with
secondary allylic phosphate 2e (Scheme 3, a), affording the
corresponding allylation products (E)- and (Z)-4ae in a 6:1
ratio in 86% ee. These results indicate the SN2′-substitution
occurs without much influence of the stereogenic center of the
allylic phosphate. However, 1,2-disubstituted internal allylic
B
DOI: 10.1021/acs.orglett.7b03022
Org. Lett. XXXX, XXX, XXX−XXX

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obtained by sequentially incorporating boryl and allyl groups
onto the CC bond of vinyl arenes in a regio- and
enantioselective manner. Efforts to develop more widely
applicable borylallylation protocols are underway.
Scheme 3. Borylallyation with Allyl Phosphate 2e and
Application of Product 3
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b03022.
Experimental procedures, characterization of products,
and NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jaesook@skku.edu.
ORCID
Do Hyun Ryu: 0000-0001-7615-4661
Jaesook Yun: 0000-0003-4380-7878
Author Contributions
†N.K. and J.T.H. contributed equally.
Notes
phosphates with increased steric demand at the terminal olefin
carbon were not efficient (see the Supporting Information for
details). In a brief application, the borylallylated product 3fa
was homologated15 without erosion of the ee to a known
intermediate in the synthesis of ramelteon16 (Scheme 3, b).
A proposed catalytic cycle for this reaction is shown in
Scheme 4. The active catalyst L*Cu−Bpin reacts with vinyl
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by National Research Foundation
of Korea (NRF) grants (NRF-2016R1A4A1011451 and NRF-
2016R1A2B4011719), funded by the Korean government
(MEST).
Scheme 4. Proposed Catalytic Cycle and Competitive
Reaction Pathways
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