DOI: 10.1002/chem.201601320
Communication
&
Synthetic Methods
Cross-Electrophile Coupling of Vinyl Halides with Alkyl Halides
In contrast to these previous efforts, our recent mechanistic
studies demonstrated that less vinyl dimer would be formed at
lower catalyst concentration.[5] However, there were no reports
of these couplings below 12.5 mm (5 mol%) nickel concentra-
tion, because at lower concentrations the reactions became
slow and did not reach completion. Previously reported condi-
tions have required stoichiometric additives (MgCl2, pyridine),
long reaction times (24 h), or higher temperatures (40–808C),
even with relatively high catalyst loadings (7–10 mol% nick-
el).[4b,6] During our mechanistic studies,[5] we had found that
the addition of TMS-Cl to the metallic reductant (Mn powder)
accelerated the rate of cross-electrophile coupling reactions
while maintaining selectivity at a given catalyst concentra-
tion.[7] Herein, we report modified conditions that allow the se-
lective coupling of a variety of vinyl bromides with primary
and secondary alkyl halides.
Abstract: An improved method for the reductive coupling
of aryl and vinyl bromides with alkyl halides that gave
high yields for a variety of substrates at room temperature
with a low (2.5 to 0.5 mol%) catalyst loading is presented.
Under the optimized conditions, difficult substrates, such
as unhindered alkenyl bromides, can be coupled to give
the desired olefins with minimal diene formation and
good stereoretention. These improved conditions also
worked well for aryl bromides. For example, a gram-scale
reaction was demonstrated with 0.5 mol% catalyst load-
ing, whereas reactions at 10 mol% catalyst loading com-
pleted in as little as 20 minutes. Finally, a low-cost single-
component pre-catalyst, (bpy)NiI2 (bpy=2,2’-bipyridine)
that is both air- and moisture-stable over a period of
months was introduced.
Starting from our reported conditions in DMF,[4b,5] we found
that trace benzonitrile[8] in N,N-dimethylacetamide (DMA) pro-
vided more consistent results. Although initial reactions gave
primarily the dimeric diene product 4a (Table 1, entries 1–3),
additional sodium iodide improved the yield (entry 4), presum-
ably by forming a more reactive alkyl iodide in situ.[4b] Lower-
ing the catalyst loading to 1 mol% (Table 1, entry 5) and
changing the solvent from DMA to N,N’-dimethylpropyleneur-
ea (DMPU) further improved the yield (Table 1, entries 5–8).
The cross-electrophile coupling of aryl halides with alkyl hal-
ides has seen rapid development in the previous six years.[1]
This work has been motivated both by the large number of
available organic halides and the realization that in some
cases, cross-electrophile coupling can succeed where cross-
coupling with organometallic reagents had failed.[2] Although
a wide variety of functionalized aryl bromides have been cou-
pled in high yield,[3] fewer examples of vinyl bromides have ap-
peared.[4] We reported reasonable yields with 1,2-disubstituted
vinyl bromides,[4b] but less hindered vinyl bromides coupled in
lower yield because of competing diene formation (Scheme 1).
Indeed, formation of dimers is the major challenge in cross-
electrophile coupling.[1b,c] To date, this challenge had been ad-
dressed through ligand design.
Table 1. Reaction optimization.[a]
Entry
x
NaI [mol%]
Solvent
Yield 3a [%][b]
Yield 4a [%][b]
1[c]
2
3
4
5.0
5.0
5.0
5.0
1.0
1.0
1.0
1.0
5.0
–
–
DMA
DMA
DMA
DMA
DMA
DMA
DMF
12
15
36
57
62
71
61
27
19
14
15
10
7
11
4
n.d.
25
50
50
50
50
50
25
5
6[d]
7[d]
8[d]
9[f]
DMPU
DMPU
88 (80)[e]
44
Scheme 1. Challenges in the cross-electrophile coupling of vinyl bromides
with alkyl bromides.
[a] Reactions were performed on 0.5 mmol scale (0.25m) with a 1:1 ratio
of starting materials, benzonitrile (5 mol%), chlorotrimethylsilane
(20 mol%), manganese metal (2 equiv). [b] Determined by GC by using
dodecane as an internal standard; yields of 4a are uncorrected. [c] 608C,
2 h. [d] (bpy)NiI2 was used as a precatalyst. [e] Isolated yield. [f] As in
Ref. [4b]. n.d.=not determined, dmbpy=4,4’-dimethoxy-2,2’-bipyridine,
DMA=N,N-dimethylacetamide, DMF=N,N-dimethylformamide, DMPU=
N,N’-dimethylpropyleneurea.
[a] K. A. Johnson, Dr. S. Biswas, Prof. D. J. Weix
Department of Chemistry, University of Rochester
Rochester, NY 14627-0216 (USA)
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2016, 22, 7399 – 7402
7399
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim