BH3 ? Me2S: An Alternative Hydride Source for NiH-Catalyzed Reductive Migratory Hydroarylation and Hydroalkenylation of Alkenes

Article abstract of DOI:10.1002/ejoc.202100005

Borane dimethylsulfide (BMS) was found to be an efficient hydride source for nickel-hydride catalyzed reductive migratory hydrofunctionalization reactions. Catalytic reductive migratory hydroarylation and migratory hydroalkenylation were achieved with BMS in high yields and with excellent regioselectivity. A large-scale experiment employing as little as 0.5 equivalents of BH₃ ? Me₂S as the hydride source delivered the desired migratory hydroarylation product in high yield and selectivity.

Full text of DOI:10.1002/ejoc.202100005

Communications
doi.org/10.1002/ejoc.202100005
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BH3 ·Me2S: An Alternative Hydride Source for NiH-Catalyzed
Reductive Migratory Hydroarylation and Hydroalkenylation
of Alkenes
Jiandong Liu,[a] Hegui Gong,*[a] and Shaolin Zhu*[b]
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Borane dimethylsulfide (BMS) was found to be an efficient
hydride source for nickel-hydride catalyzed reductive migratory
hydrofunctionalization reactions. Catalytic reductive migratory
hydroarylation and migratory hydroalkenylation were achieved
with BMS in high yields and with excellent regioselectivity. A
large-scale experiment employing as little as 0.5 equivalents of
BH3 ·Me2S as the hydride source delivered the desired migratory
hydroarylation product in high yield and selectivity.
Starting from stable and easily available feedstock alkenes and
electrophilic cross-coupling partners, metal-hydride[1,2] catalyzed
reductive (migratory) hydrofunctionalization has been reported
recently to enable the synthesis of a range of structurally
complex molecules under mild conditions.[1–6] In these reactions,
a stoichiometric amount of hydrosilane is commonly used as an
efficient hydride source. For example, polymethylhydrosiloxane
(PMHS), a byproduct of the silicone industry is useful in this
context. Other silanes were shown to be optimal but are more
expensive than PMHS and hydrosilanes such as (MeO)3SiH and
(EtO)3SiH present a fire hazard.[7] Nickel hydride has enabled a
series of reductive migratory hydrofunctionalizations, including
arylation, alkylation, amination, and thiolation along the hydro-
carbon chain of alkenes (Figure 1a).[6] Owing to the low
molecular weight, fewer waste products, and low cost associ-
ated with borane (Figure 1b, 1 equivalent of BH3 is associated
with 3 equivalents of R3SiÀ H), we recently questioned whether
commercially available borane could be used as a mild,
inexpensive and safe hydride source in NiH chemistry. Here we
report the successful implementation of this possibility and
describe the use of borane dimethylsulfide (BMS) as a hydride
Figure 1. Borane dimethylsufide (BMS) as hydride source in nickel-hydride
catalyzed reductive migratory hydrofunctionalization reactions. FG=func-
tional group.
source in NiH-catalyzed reductive migratory hydroarylation and
migratory hydroalkenylation (Figure 1b).
The feasibility of using borane dimethylsulfide (BMS) as
hydride source was first examined with the migratory hydro-
arylation of 4-phenyl-1-butene (1a) with methyl 4-iodobenzoate
(2a) (Table 1).[6d] After extensive examination of the reaction
parameters, the desired migratory hydroarylation product (3a)
was found to be produced in 91% isolated yield as a single
°
benzylic isomer (>99:1 regioisomeric ratio) at À 19 C (Table 1,
entry 1). Other nickel catalysts such as NiCl2 ·dmbpy (dmbpy=
6,6’-dimethyl-2,2’-bipyridine) led to a lower yield (entry 2).
Reduction of the catalyst loading to 10 mol% also led to
diminished yield (entry 3). Inferior results were achieved with
other borane sources (entries 4–6). THF was found to be
unsuitable as the solvent (entry 7). An inferior result was
[a] J. Liu, Prof. H. Gong
School of Materials Science and Engineering, Center for Supramolecular
Chemistry and Catalysis, Department of Chemistry, Shanghai University,
Shanghai, 200444, China
E-mail: hegui_gong@shu.edu.cn
https://hgonggrp.shu.edu.cn/
°
obtained when the reaction was conducted at 0 C (entry 8).
Comparable results were obtained when 1 equiv. of the aryl
iodide (2a) was used (entry 9) or when 0.5 equiv. of BH3 ·Me2S
was used (entry 10), further highlighting the superiority of
BH3 ·Me2S as the hydride source. Replacement of aryl iodide
(2a) by the relatively less reactive aryl bromide led to
diminished yield (entry 11). The reaction proceeded fast and
was complete within 4 h (entry 12).
[b] Prof. S. Zhu
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of
Advanced Organic Materials,
Chemistry and Biomedicine Innovation Center (ChemBIC), School of
Chemistry and Chemical Engineering,
Nanjing University, Nanjing, 210093, China
E-mail: shaolinzhu@nju.edu.cn
Under the optimal reaction conditions, a fairly broad scope
of aryl iodides was suitable as coupling partners, delivering aryl
(3b–3l) or heteroaryl (3m–3p) products (Table 2). Both elec-
tron-withdrawing (3b–3e, 3g) and electron-rich (3f, 3j–3l) aryl
https://webplus.nju.edu.cn/slzhu/main.psp
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202100005
Part of the “YourJOC Talents” Special Collection.
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Table 1. Variation of reaction parameters.
Table 2. Scope of aryl iodide and alkenyl bromide coupling partners.[a]
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Entry
Variation from standard conditions
Yield [%][a]
rr[b]
1
2
3
4
5
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7
none
93 (91)
70
73
80
28
79
0
>99:1
99:1
98:2
>99:1
99:1
>99:1
–
NiCl2·dmbpy instead of NiBr2·dmbpy
10 mol% NiBr2·dmbpy
BH2·NiPr2 instead of BH3·Me2S
BH3·THF instead of BH3·Me2S
HBpin instead of BH3·Me2S
THF instead of DMA
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°
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0 C
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>99:1
>99:1
>99:1
>99:1
>99:1
1.0 equiv. 2a
0.5 equiv. BH3·Me2S
aryl bromide used
4 h
92
[a] Yields determined by crude 1H NMR using 2,5-dimethylfuran as the
internal standard. The yield in parentheses is the isolated yield. [b]
Regioselectivity (rr) determined by GC and GCMS analysis. dmbpy=6,6’-
dimethyl-2,2’-bipyridine.
iodides underwent migratory hydroarylation smoothly. A variety
of functional groups were well-tolerated, including esters (3b),
a nitrile (3c), ethers (3f–3k), and a Boc-protected amino (3l).
Notably, both an easily reduced ketone (3d) and a boronic acid
pinacol ester potentially used for further coupling (3e) were all
left intact. In general, the substituents could be placed at para,
meta, or ortho position (3b–3p). However, a moderate yield
was obtained from an aryl iodide with an ortho-substituent
(3h), presumably due for steric reasons. Heterocycles such as
benzofuran (3m) and thiophene (3n, 3o) were also shown to
be competent coupling partners.
[a] The percentage isolated yield (0.15 mmol scale, average of two runs) is
given. The regioisomeric ratio (rr) represents the ratio of the major product
to the sum of all other isomers as determined by GC analysis. [b] 4-(4-
Methoxyphenyl)-1-butene was used. [c] 4-Methoxystyrene was used.
The coupling partners could include a variety of alkenyl
bromides which produce the corresponding migratory hydro-
alkenylation products (4a–4i) smoothly.[6aa,8] β-Aryl-conjugated
(E)-alkenyl bromides with various substituents are suitable
substrates (4a–4d). Good migratory coupling results were also
observed for heterocycles such as furyl- and thienyl-conjugated
alkenyl bromides (4f, 4g). Both β-alkyl-decorated alkenyl
Jiandong Liu received his B.S. from Qufu
Normal University in 2014, his M.S. from
Shanghai Institute of Technology in 2017, and
his Ph.D. degree from Shanghai University in
2020 (with Prof. Hegui Gong). He is currently
working as a postdoctoral associate at the
Shanghai Institute of Organic Chemistry (with
Prof. Shuli You). His main research interest is
asymmetric catalysis.
Shaolin Zhu received his B. S. from Nanjing
University in 2005 and a Ph.D. degree from
SIOC in 2010 (with Prof. Dawei Ma). Then he
worked as a postdoctoral associate at Prince-
ton (with Prof. David W. C. MacMillan, 2010–
2013) and postdoctoral fellow at MIT (with
Prof. Stephen L. Buchwald, 2013–2015). In
September 2015, he joined Nanjing University
as a professor, where his group‘s work has
focused primarily on asymmetric catalysis and
organic synthesis.
Hegui Gong received his Ph.D. degree from
the University of Texas at Austin (with Prof.
Michael J. Krische). After postdoctoral research
at the University of North Carolina at Chapel
Hill (with Prof. Michel R. Gagné), he was
appointed as a Full Professor at Shanghai
University in 2008, where his group‘s work has
focused primarily on reductive cross-cou-
plings.
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Table 3. Scope of alkene coupling partners.[a]
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Scheme 1. Gram-scale experiment with 0.5 equivalent borane dimeth-
ylsulfide (BMS).
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ylsulfide (BMS) in other NiH-catalyzed reactions is currently in
progress in our laboratory.
Acknowledgements
Support was provided by NSFC (21871173, 21572140).
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Alkenylation · Boranes · Homogeneous catalysis ·
Isomerization · Nickel
[a] The percentage isolated yield (0.15 mmol scale, average of two runs) is
given. The regioisomeric ratio (rr) represents the ratio of the major product
to the sum of all other isomers as determined by GC analysis.
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were suitable substrates.
We next explored the scope of the alkenes (Table 3). Both
terminal alkenes (5b–5f) and internal alkene (5g) underwent
this migratory hydroarylation smoothly. The reaction is insensi-
tive to the chain length between the C=C double bond and the
aryl group (5b vs 5c). Both electron-donating (5d) and
electron-withdrawing (5e, 5f) substituents on the remote
aromatic ring were likewise suitable for this reaction, even
when there was a substituent at the ortho-position (5f). A
variety of styrenes were also shown to be competent substrates
(5h–5p), regardless of the E/Z configuration. Notably,
a
structurally complex glucoside derivative (5n), as well as
heterocyclic thiophene (5p), were all competent coupling
partners.
The robustness of this reaction was further demonstrated
by a gram-scale experiment that used a reduced amount of
hydride source. As shown in Scheme 1, only 0.5 equivalent of
borane dimethylsulfide (BMS) as hydride source proved to be
sufficient for reaction performed on a 5 mmol scale.
In summary, we report that the low-cost borane dimeth-
ylsulfide (BMS) is an efficient hydride source for nickel-hydride
catalyzed migratory hydrofunctionalization reactions. With this
newly identified hydride source, migratory hydroarylation and
migratory hydroalkenylation proceed with broad substrate
scope under mild conditions. The application of borane dimeth-
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[8] Due to the formation of styrene product with a more steric hindered
secondary alkyl group at β-position, no further isomerization product or
subsequent alkenylation product was obtained.
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Manuscript received: January 4, 2021
Revised manuscript received: February 4, 2021
Accepted manuscript online: February 8, 2021
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