Copper(i)-catalysed stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes with bis(pinacolato)diboron

Article abstract of DOI:10.1039/c8ob01778f

A stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes to prepare (Z)-1-bromo-1-alkenylboronate esters using copper(i) catalysts was developed. The debromoborylation of various aliphatic 1,1-dibromo-1-alkenes in the presence of a copper(i) catalyst and bis(pinacolato)diboron proceeded smoothly to produce (Z)-1-bromo-1-alkenylboronate esters in good yields with only Z geometry.

Full text of DOI:10.1039/c8ob01778f

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Copper(I)-Catalysed Stereoselective Debromoborylation of
Aliphatic 1,1-Dibromo-1-Alkenes with Bis(pinacolato)diboron
Received 00th January 20xx,
Accepted 00th January 20xx
*
Yadong Pang, Ryoto Kojima and Hajime Ito
DOI: 10.1039/x0xx00000x
www.rsc.org/
A stereoselective debromoborylation of aliphatic 1,1-dibromo-1-
alkenes to prepare (Z)-1-bromo-1-alkenylboronate esters using
copper(I) catalysts was developed. The debromoborylation of
various aliphatic 1,1-dibromo-1-alkenes in the presence of a
copper(I) catalyst and bis(pinacolato)diboron proceded smoothly
to produce (Z)-1-bromo-1-alkenylboronate esters in good yields
with only Z geometry.
a. Coventional synthesis (hydroboration of alkynyl bromides)
H
H
OR2
B
2
HBBr
2
•SMe
2
BBr2
R OH
R1
C
C Br
R1
R1
OR2
Br
Br
b. Attempted synthesis with Pd-catalysed reactiona
PdCl
2
(PPh
3 2
) (3 mol %)
Br
B(pin)
PPh
3
(6 mol %)
1
a
+
Br
Br
+
(pin)B−B(pin), (1.1 equiv.)
56%
1
a
KOPh, toluene, 50 °C, 24 h
3a, < 5%
Organoboronic acids and their derivatives, especially
alkenylboronate esters, are powerful and versatile reagents in
organic synthesis because of their high stability, low toxicity,
and synthetic utility in many reactions such as the Suzuki–
B(pin)
+
B(pin)
B(pin)
+
mixture
1
trace
≈15%
Miyaura cross-coupling reaction. In addition, (Z)-1-bromo-1-
aThe yields were determined by GC analysis
alkenylboronate esters are useful organoboron synthetic
intermediates in organic synthesis. They are known to undergo
2
cross-coupling reactions with organozinc reagents and
Scheme 1 Synthesis of (Z)-1-bromo-1-alkenylboronate esters.
intramolecular nucleophilic substitution reactions with
3
4
To develop a more convenient reaction pathway to
nucleophiles such as hydrides,
4
Grignard reagents,
5
organolithium reagents,
6
trimethylsilylmethyllithium
allylmagnesium
bromide, alkenylboronate esters, we first considered the Pd-catalysed
7
and trimethylgermyllithium. borylation with bis(pinacolato)diboron, which was developed
However, only one method to synthesise (Z)-1-bromo-1- by Miyaura and Ishiyama and is a standard procedure for
alkenylboronate esters has been developed: hydroboration of transformation of alkenyl bromide. However, similar to the
2
-7
10
alkynyl bromides (Scheme 1a). The synthesis of alkynyl results already reported by Cao’s group, the Pd-catalysed
halides requires harsh reaction conditions and has poor borylation of 1,1-dibromo-1-alkene 1a failed. Only a small
functional group compatibility. Therefore, the development of amount of the desired product was obtained along with a
a simple, mild and efficient method for the direct preparation monoborylated alkene and a diboryl alkene in a complex
9
of (Z)-1-bromo-1-alkenylboronate esters remains highly mixture. (Scheme 1b).
desirable. Our research focuses on the stereoselective
Very recently, several groups reported copper(I)-catalysed
debromoborylation of 1,1-dibromo-1-alkenes, which are reactions of 1,1-difluoro-1-alkenes. Three different groups (led
readily available from the corresponding carbonyl compounds by Cao, Ogoshi and Niwa, and Wang) independently reported
8
through the Wittig reaction.
monodefluoroborylation reactions of aryl 1,1-difluoro-1-
alkenes with bis(pinacolato)diboron in the presence of a
copper(I) catalyst to afford (Z)-1-fluoro-1-alkenylboronate
1
0-12
esters (Scheme 2a).
This reaction proceeds through the
addition of a borylcopper(I) intermediate to the 1,1-difluoro-1-
alkene and subsequent β-elimination to give the
corresponding defluoroborylation products. At the almost
same time, we and Shi’s group also reported selective
hydrodefluorinations of aryl 1,1-difluoro-1-alkenes with a
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copper(I) catalyst to produce monofluoroalkenes, in which the Substrates with aryl groups (1a
Journal Name
–
e
) or a heteroaryl moiety 1f
1
3,14
same key intermediate would be present (Scheme 2a).
Inspired by these results and the similar reactivity of F and the corresponding products [(Z)-3a
Br, we envisioned that the selective debromoborylation of 1,1- moderate isolated yields, [(Z)-3a, 85% (55%); (Z)-3b, 77% (52%);
dibromo-1-alkenes should be possible. Herein, we report a (Z)-3c, 83% (58%); (Z)-3d, 81% (62%); (Z)-3e, 71% (55%); (Z)-3f
novel and efficient method for the synthesis of (Z)-1-bromo-1- 87% (62%)]. The reactions of substrates with simple alkyl
alkenylboronate esters via copper(I)-catalysed stereoselective chains (1g ) gave the desired products in high NMR yields and
did not hamper this debromoborylation process and afforded
–
f
] in high NMR and
,
–
j
debromoborylation of aliphatic 1,1-dibromo-1-alkenes with moderate isolated yields [(Z)-3g, 92% (59%); (Z)-3h, 83% (62%);
bis(pinacolato)diboron in the presence of a copper(I) catalyst (Z)-3i, 90% (57%); (Z)-3j, 85% (58%)]. Substrates with chlorine
(Scheme 2b).
(
1k), alkene (1l), carbamate (1m) and imide (1n) functional
groups were also tolerated [(Z)-3k, 77% (57%); (Z)-3l, 90%
54%); (Z)-3m, 75% (51%); (Z)-3n, 66% (50%)]. Unfortunately,
(
when (2,2-dibromovinyl)cyclohexane 1o, which bears a tertiary
carbon at the α-position of the double bond of the 1,1-
dibromo-1-alkene, was used as a substrate under the optimal
reaction conditions, no reaction occurred and the desired
product (Z)-3o was not obtained, probably because of steric
hindrance. Furthermore, when (2,2-dibromovinyl)benzene 1p
was used as a substrate, the starting material was recovered
mostly and the desired product (Z)-3p was also not obtained
even under the optimised conditions.
Table 1 Screening of reaction conditions for the debromoborylation of aliphatic
[
a]
1
,1-dibromo-1-alkenes
Scheme 2 Copper(I)-catalysed reactions of 1,1-dihalo-1-alkenes.
Our research commenced with the screening of reaction
conditions for the borylation of (4,4-dibromobut-3-en-1-
yl)benzene 1a with bis(pinacolato)diboron as the model
reaction (Table 1). Initially, a trace amount of the desired
product was observed in the absence of a ligand (entry 1).
Then, we found that Xantphos was a preferred ligand among
[
b]
entry
ligand
-
base
yield (%)
1
2
3
4
5
6
7
8
9
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
4
7
[c]
PPh
3
3
common ligands such as PPh , dppp, dppbz, IPr·HCl, and 1,10-
phen (entries 2–7). Further screening of a series of different
bases revealed that only NaOMe (2.0 equiv.) could afford the
desired product (Z)-3a in good yield (entries 8–13). In
particular, the use of a relatively strong base, sodium tert-
butoxide, could afford the corresponding bromoalkyne as a
major by-product and no desired product was obtained (entry
dppp
61
dppbz
58
IPr·HCl
13
1,10-phen
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
18
85
10). To our delight, this debromoborylation reaction occurred
[
d]
NaOMe
58
with high (Z)-selectivity and no (E)-isomer was detected by GC
and NMR analyses. The structure of the favourable
stereoisomer was confirmed by single-crystal X-ray diffraction
analysis of (Z)-3n (see ESI).
KOMe
Na(O-t-Bu)
KOAc
51
[
e]
1
0
trace
With the optimal reaction conditions in hand (Table 1, entry
11
trace
trace
trace
[b]
7), a series of aliphatic 1,1-dibromo-1-alkene substrates that
1
1
2
3
K
2
CO
3
were prepared from aliphatic aldehydes was examined to
investigate the scope of the debromoborylation reaction
LiOMe
[
a]
(Table 2). The debromoborylation reaction proceeded
Reaction conditions: 1a (0.25 mmol), 2 (0.3 mmol), solvent (1 mL), 3 h; Yields were
1
[c]
[d]
[e]
efficiently to give the corresponding (Z)-brominated alkenyl determined by H NMR analysis; 10 mol % was used; 1.5 equiv. was used. 1-
1
Bromo-4-phenyl-but-4-yne was detected in approx. 40% yield by H NMR analysis.
boronate esters
isomer was observed in each case. However, we found that
purification of the boronate esters (Z)- without loss was
3 in moderate to good yields and no (E)-
3
difficult using typical chromatographic techniques because
they were easily hydrolysed in silica gel; thus, the isolated
yields were lower than the corresponding NMR yields.
2
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(
Z)-
3,
along with generation of LCuBr. The other
[
a]
Table 2 Scope of the debromoborylation of aliphatic 1,1-dibromo-1-alkenes
conformational isomer of the intermediate III, which can
afford (E)-3, should be less energetically favourable than II
because of the steric repulsion between the alkyl group and
bulky B(pin). This can explain the exclusive formation of the
(
Z)-isomer of
3.
Finally, LCuBr further reacts with
bis(pinacolato)diboron and NaOMe to regenerate the active
species LCu–B(pin) and complete the catalytic cycle.
Scheme 3 Plausible mechanism for the copper(I)-catalysed stereoselective
debromoborylation
bis(pinacolato)diboron.
of
aliphatic
1,1-dibromo-1-alkenes
with
In conclusion, we have developed a new and efficient
method to synthesise (Z)-1-bromo-1-alkenylboronate esters
via copper(I)-catalysed stereoselective debromoborylation of
aliphatic 1,1-dibromo-1-alkenes with bis(pinacolato)diboron in
the presence of NaOMe and Xantphos at 30 °C. The borylation
reaction exhibits a wide substrate scope, good functional
group compatibility and affords a variety of (Z)-brominated
borylation products in moderate to good yields. At the same
time, our study is the first example of the selective
debromoborylation of 1,1-dibromo-1-alkenes, which is
expected to become a powerful synthetic approach to
construct a broad range of intermediates and materials.
[
a]
Reaction conditions: 1 (0.25 mmol), 2 (0.3 mmol), solvent (1 mL). Yields were
1
[b]
determined by H NMR spectroscopy; isolated yields are shown in parentheses. CuCl
(
10 mol %), Xantphos (10 mol %), and solvent (1.5 mL) were used
1
0-15
Conflicts of interest
Based on the above observations and previous reports,
a
mechanism for the copper(I)-catalysed stereoselective There are no conflicts to declare.
debromoborylation of aliphatic 1,1-dibromo-1-alkenes with
bis(pinacolato)diboron is proposed (Scheme 2). Initially,
transmetallation of the phosphine-ligated copper(I) catalyst Acknowledgements
LCuOMe, which is generated in situ from LCuCl and NaOMe,
This work was supported by the Japan Society for the
with bis(pinacolato)diboron provides the nucleophilic
phosphine-coordinated borylcopper(I) complex LCu–B(pin).
Subsequent insertion of the carbon-carbon double bond of the
Promotion of Science (JSPS) KAKENHI (Grant Number
JP18H03907). We thank Natasha Lundin, PhD, from Edanz
Group (www.edanzediting.com/ac) for editing a draft of this
manuscript.
1
,1-dibromo-1-alkene
borylcopper(I) complex would lead to the generation of β-
borylalkylcopper(I) species with the perfect regioselectivity
1
into the Cu–B bond of the
I
since forming the C–B bond should be occurred at the more
electron-positive olefinic carbon. β-Elimination of the
borylalkylcopper(I) intermediate II affords the desired product
Notes and references
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