Angewandte Chemie International Edition
10.1002/anie.201903890
COMMUNICATION
to our prior arylboration reaction.[14] The ligand effects are
illustrated in Table 1. It was surprising that many ligands
commonly employed in nickel catalysis, including bipyridine (L1
and L3), 1,10-phenanthroline (L2 and L4), PyrBox (L5),
tripyridine (L6) and pyrimine (L7) failed to gave rise to the desired
product 4a in more than a trace amount. However, when an
unusual pyridyl carboxamide[18] L8 was employed, the 1,1-
alkylboration product 4a was obtained in 69% yield. Further
optimization of this type of ligand improved the yield to 91% (L9).
Comparing with L9 and L10, indicates that the methyl substituent
adjacent to the nitrogen atom of the pyridine ring is very important.
A user-friendly and air-stable nickel complex was prepared with
L9, leading to a similar isolated yield. Notably, the excellent 1,1-
selectivity reveals that the reaction is initiated by the alkene
insertion into a Ni-B bond, rather than the oxidative addition of the
alkyl electrophile, despite utilizing a highly reactive one.
bonds. To further demonstrate the good compatibility of this
method, biologically interesting, complex molecules (4w and 4x)
were also synthesized. Interestingly, the α,β-unsaturated ketone
was also well-tolerated in this nickel-catalyzed system (4w).
To further assess the generality of these catalytic conditions,
we next investigated the reaction of terminal olefin 1a with a
number of different alkyl electrophiles. A series of substituted
benzyl bromides were examined. Both electron-rich and -deficient
substituents did not greatly affect the reactivity. Remarkably, the
aryl chloride, bromide and even iodide were all well-tolerated in
this mild nickel-catalyzed condition, which open avenues for
further downstream cross-couplings. Furthermore, heterocyclic
benzyl bromides and benzyl chlorides were also suitable
substrates (2m-2o). It should be noted that allyl bromides, while
somewhat less reactive than the benzyl halides, were also able to
generate the corresponding homoallyl boronic esters under the
same reaction conditions, with extraordinary 1,1-regioselecitivity
(2p-2r). Unfortunately, secondary benzyl bromides (2s) and
unactivated alkyl bromides (2t) failed to yield the product under
these reaction conditions.
Table 1. Reaction Development [a]
In addition to aliphatic olefins, a diversity of vinylarenes, could
also undergo alkylboration under the standard conditions (Table
3
), but only 1,2-products were isolated in these reactions,
consistent with Yoshida’s copper-catalyzed system. [ This is
likely due to the stability of benzyl nickel intermediates. However,
it is still difficult to get details on the selectivity between the
benzylic position versus α-position of the boron group from the
above results.
9]
To get insight into the regioselectivity of this system, as
illustrated in Scheme 1, allylbenzene and a couple of other allyl
substituted functional groups were examined in the following
studies. The 1,1-product 7 was still dominated in the reaction of
allylbenzene with a regioisomeric ratio of 6:1, which exhibits a
reversed selectivity with our previous arylboration reaction.
Further competence of bond formation between α-position of an
ester, amide and cyano group versus α-position of the boron
group was explored. We were pleased to find that all three
reactions afforded the 1,1-difunctionalized products in good yields
with good selectivity. These results support the notion that the
good regioselectivity is dictated by the new catalyst.
To further explore the potential scope of this 1,1-alkylboration,
gaseous ethylene was utilized in this reaction. As shown in
Scheme 2a, only with a balloon pressure, the desired product 11
could be obtained in 61% yield at a 10 mmol scale with 1 mol %
catalyst loading.
[
1
a] General conditions: NiBr
2
·DME (5 mol %), Ligand (5 mol %), 1a (0.4 mmol,
.0 equiv), 2a (0.6 mmol, 1.5 equiv), 3 (0.6 mmol, 1.5 equiv), LiOMe (0.8 mmol,
.0 equiv), in Dioxane (2.5 mL), stirred at 30 °C for 12 h. GC yields against
2
naphthalene. [b] Isolated yield at 0.4 mmol scale. DME = Dimethoxyl ethane.
Having identified the optimal reaction conditions, we next
turned our attention to investigate the generality of this Ni-
catalyzed reaction. As illustrated in Table 2, the olefin partner was
first studied. Unactivated terminal alkenes bearing a wide range
of flexible functional groups including esters, ethers, ketones,
amides, cyano, alcohols, tosylates, and epoxides, as well as
functionalized thiophene, pyrrole and indoles were examined. All
could successfully transform to the corresponding arylboration
products in good to excellent yields with an extraordinary
regioisomeric ratio (rr > 20:1). The 1,1-alkylboration product was
obtained in a good yield from 1-heptene (4b), which indicates that
the regioselectivity is governed by the catalyst not coordinating
groups. It is noteworthy that homoallyl bromide was able to furnish
the alkylboration product in a very good yield with the bromide
intact (4e), and no cyclization products (5 or 6 member-ring) were
detected in the reaction of 6-bromohexene (4n). Moreover, the
substrates containing multiple double bonds, selectively reacted
with the monosubstituted olefins (4s-4v), indicating this reaction
exhibits good chemoselectivity among different types of double
Finally, a series of experiments were performed to shed light
on the mechanism of this transformation (please see SI for more
details and discussions). First of all, no signal was detected when
the reaction was monitored by electron paramagnetic resonance
(EPR) spectroscopy, which suggests that the catalyst resting
states are Ni(0) or Ni(II) species.[19] Therefore, the reaction is less
likely involving a single Ni(I/III) catalytic cylce.[20, 21] No Suzuki-
Miyaura cross-coupling product was observed in the reaction of
1,1-diboron compound with 2a under the optimal conditions
(Scheme 2b), which rules out the possibility that the 1,1-diboron
compound 12 serves as the intermediate in this alkylboration
reaction.[ Furthermore, a terminal deuterium-labeled olefin, [d]-
1a, was prepared and examined in the reaction (Scheme 2c). The
product ([d]-4a) was isolated in 90% yield, with 53% D-atom
migration to the β-position. Moreover, the addition of vinyl boronic
17]
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