Pd-Catalyzed Negishi Cross-Coupling of Vinyl Bromides with Diborylmethylzinc Chloride

Full text of DOI:10.1002/bkcs.12212

Communication
DOI: 10.1002/bkcs.12212
BULLETIN OF THE
M. Kim et al.
KOREAN CHEMICAL SOCIETY
Pd-Catalyzed Negishi Cross-Coupling of Vinyl Bromides
with Diborylmethylzinc Chloride
†,
Minjae Kim,† Jun Hee Lee,‡, and Seung Hwan Cho
*
*
†Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673,
Republic of Korea. *E-mail: seunghwan@postech.ac.kr
‡Department of Advanced Materials Chemistry, Dongguk University Gyeongju Campus, Gyeongju 38066,
Republic of Korea. *E-mail: leejunhee@dongguk.ac.kr
Received December 9, 2020, Accepted December 23, 2020, Published online January 4, 2021
Keywords: Palladium, Negishi coupling, Allylboronate ester, gem-diborylalkane, Cross-coupling
Allylboron compounds are valuable synthetic precursors dur-
ing the synthesis of a variety of pharmaceuticals and biologi-
cally active compounds.1 In particular, α-boryl-substituted
allylic boronate esters have been considered promising
reagents because they can chemoselectively react with alde-
hydes or aldimines to produce homoallylic alcohols or
homoallylic amines that contain a vinyl boron unit.2 Thus,
the discovery of an efficient methodology that provides
access to diverse α-boryl-substituted allylic boronate esters
is desirable in organic synthesis.
In prior studies, such compounds have been prepared
by the transition-metal-free insertion of B2pin2 into N-
tosylhydrazone,3b by the metal–catalyzed alkene isomeriza-
tion of gem-diborylalkanes containing an alkene moiety in
the alkyl substituents,4 or 1,4-diboration of dienylboronate
ester.2c More recently, transition-metal-catalyzed cross-
coupling approaches have also been disclosed (Scheme 1(a)).
For example, our group reported Cu-catalyzed cross-coupling
of diborylmethylzinc halides with various vinyl iodonium sal-
ts.5a Meek and co-workers developed Pd-catalyzed coupling
of diborylmethyllithium with 2,2-disubstituted vinyl halides.6
However, the former method required extra steps for the
preparation of iodonium salts, and the latter approach typi-
cally showed low yields probably due to high reactivity of
diborylmethyllithium.
In our continuing interest in the development of
chemoselective transformations of gem-diborylalkanes,7,8 we
recently demonstrated that diborylmethylzinc halides served
as useful multi-organometallic reagents in Pd-catalyzed,
chemoselective cross-coupling with aryl (pseudo)halides.5b,9
Based on this achievement, we envisaged that Pd-catalyzed
coupling of diborylmethylzinc halides with vinyl halides
would offer an attractive route for the preparation of
α-boryl-substituted allylic boronate esters (Scheme 1(b)).
We commenced our study by employing 1-bromo-
2-methylprop-1-ene (2a) as an electrophile and
diborylmethylzinc bromide 1-ZnBr as a nucleophile in the
presence of Pd2(dba)3 (1.0 mol%) as a catalyst and P(o-
tolyl)3 (2.0 mol%) as a ligand in THF at 60 ꢀC (Table 1).
However, we obtained the desired coupled product 3a in a
low yield of 24% (Table 1, entry 1). Further evaluation rev-
ealed that the halide source of diborylmethylzinc halides
strongly affected the reaction efficiency. Pleasingly, we
obtained product 3a in a good yield of 83% using
diborylmethylzinc chloride 1-ZnCl (entry 2). Unfortunately,
no reaction took place when diborylmethylzinc iodide 1-ZnI
was employed as a nucleophile (entry 3). Noteworthy is that
the choice of a ligand is also critical to the success of the
cross-coupling reaction in high efficiency. When a mono-
phosphine such as P(m-tolyl)3 or P(p-tolyl)3 was used
instead of P(o-tolyl)3, the yield of the reactions decreased
(entries 4 and 5). Interestingly, the employment of bidentate
ligand such as 1,10-bis(diphenylphosphino)ferrocene (dppf)
as a ligand resulted in a negligible conversion (entry 6).
Having determined the optimal conditions, we investi-
gated the substrate scope of vinyl bromides in Pd-catalyzed
coupling with 1-ZnCl. As depicted in Scheme 2, the cou-
pling reactions of (E)-vinyl bromides bearing various alkyl
substituents at the β-position proceeded without difficulties,
giving α-boryl-substituted allylic boronate esters 3a–3e
in good-to-moderate yields. Reactions performed with
(bromomethylene)cyclohexane and cycloheptane efficiently
produced 3f and 3g, respectively, in good yields. When the
monosubstituted vinyl bromides, such as (E)-(2-bromovinyl)
trimethylsilane and (2-bromovinyl)trimethylsilane, were
exposed to 1-ZnCl at an elevated temperature of 80 ꢀC in
the presence of Pd2(dba)3 (2.0 mol%) and P(o-tolyl)3
(4.0 mol%), we obtained the corresponding cross-coupling
products 3h and 3i in moderate yields. We were pleased to
find that a 1,2,2-trisubstituted vinyl bromide such as
2-bromo-3-methylbut-2-ene also underwent the coupling
reaction to afford 3j in good yield. Furthermore, the
cross-couplings of the cyclic vinyl bromides, such as
3-bromo-1,2-dihydronaphthalene and 3-bromo-3-fluoro-1,2-
dihydronaphthalene, with 1-ZnCl also proceeded smoothly
to yield the corresponding α-boryl-substituted allylic
boronate esters 3k and 3l in 90% and 65% yields, respec-
tively. Pleasingly, we found that a rather complicated vinyl
bromide derived from estrone,10,11 a female sex hormone,
Bull. Korean Chem. Soc. 2021, Vol. 42, 499–501
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Scheme 1. Approaches for synthesizing α-boryl-substituted allylic
boronate esters.
can also be successfully used in this cross-coupling reaction
to afford 3m in 40% yield.
Next, we sought to demonstrate the synthetic utility of
α-boryl-substituted allylic boronates via their further trans-
formations. To this end, as summarized in Scheme 3, the
treatment of 3m with lithium 2,2,6,6-tetramethylpiperidide
(LiTMP) generated the allylic (diboryl)lithium species in
situ, which was then captured by CH2I2 to give the vinyl
boronate ester 4 in 41% yield.12 Subsequent oxidation of
Scheme 2. Scope of vinyl bromides. The reaction was conducted
using Pd2(dba)3 (1.0 mol%), P(o-tolyl)3 (2.0 mol%), vinyl bro-
mide (0.20 mmol), 1-ZnCl (1.5 equiv), and THF (1.0 mL) at
60 ꢀC for 5 h. [a]Pd2(dba)3 (2.0 mol%) and P(o-tolyl)3 (4.0 mol%).
[b]Runs at 80 ꢀC. In all cases, isolated yields were indicated.
1-ZnX. The halide source of 1-ZnX and the choice of a
monophosphine ligand are critical to the success of the
cross-coupling reactions. Hence, the coupling process pro-
ceeds efficiently by using diborylmethylzinc chloride
1-ZnCl in the presence of Pd2(dba)3 as the catalyst along
with P(o-tolyl)3 as the ligand, providing various α-boryl-
substituted allylboronate esters in good-to-moderate yields.
Furthermore, we have also demonstrated that the obtained
α-boryl-substituted allylboronate ester can be used as a syn-
thetically useful synthon for the preparation of advanced
derivatives.
4
with basic hydrogen peroxide provided the
α,β-unsaturated ketone 5 in 77% yield.
In conclusion, we have reported the Pd-catalyzed cross-
coupling of vinyl bromides with diborylmethylzinc halides
Table 1. Optimization study.
Entry
[M]X
Ligand]
Yield (%)[a]
1
2
3
4
5
6
ZnBrꢁLiBr (1-ZnBr)
ZnClꢁLiCl (1-ZnCl)
ZnIꢁLiI (1-ZnI)
P(o-tolyl)3
P(o-tolyl)3
P(o-tolyl)3
P(m-tolyl)3
P(p-tolyl)3
dppf
24
83
<1
44
17
<1
ZnClꢁLiCl (1-ZnCl)
ZnClꢁLiCl (1-ZnCl)
ZnClꢁLiCl (1-ZnCl)
[a] The reaction was conducted using Pd2(dba)3 (1.0 mol%), ligand
(2.0 mol%), 2a (0.20 mmol), 1-ZnX (1.5 equiv), and THF (1.0 mL) at
60 ꢀC for 5 h. 1H-NMR was determined using 1,1,2,2-
tetrachloroethane as an internal standard.
Scheme 3. Further transformations of α-boryl-substituted allylic
boronate ester 3m.
Bull. Korean Chem. Soc. 2021, Vol. 42, 499–501
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Acknowledgments.
This work was supported by
the National Research Foundation of Korea (NRF-
2019R1A2C2004925). J.H.L. is grateful for the Dongguk
University Research Fund of 2020.
Supporting Information. Additional supporting informa-
tion may be found online in the Supporting Information
section at the end of the article.
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Bull. Korean Chem. Soc. 2021, Vol. 42, 499–501
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