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found that by changing the ligand to bathophenanthroline (129), the Ni-
catalyzed cross-coupling of a variety of secondary alkyl bromides to
phenylboronic acid could be achieved in good yield [eqn (11.34)].
95
Notable
drawbacks to the initially disclosed catalytic system were the inability to
couple alkyl chlorides (primary or secondary), primary alkyl bromides or
sterically hindered aryl boronic acids.
(11
:
34)
These limitations were addressed in subsequent work by Fu's group by the
introduction of amino alcohols as ligands for the Ni-catalyzed system.
96
Remarkably, in the presence of an air-stable NiCl
2
glyme precatalyst and the
amino alcohol prolinol, secondary alkyl chlorides were successfully cross-
coupled with phenylboronic acid. Interestingly, the application of a similar
amino alcohol-ligated Ni-catalyzed system for the coupling of endo-2-bro-
monorbornane (131) to phenylboronic acid led exclusively to the
thermodynamically favored exo-cross-coupled product 132 (Scheme 11.14),
97
corroborating evidence
98
that oxidative addition to Ni proceeds via a radical
pathway under these conditions.
99
Ph
Br
Conditions
Conditions
Br
84% Yield
131
91% Yield
132
133
+
+
> 20:1
exo:endo
Ph
-B(OH)
2
Ph
-B(OH)
2
Conditions =
NiI
2
,
trans-
2-amino-cyclohexanol,
2 eq. NaHMDS,
i
PrOH, 60 °C
Scheme 11.14 Ni-catalyzed Suzuki-Miyaura coupling demonstrating configurational
instability of the alkyl halide during the overall reaction sequence.
Alkyl-alkyl Suzuki-Miyaura couplings were made possible with only minor
modifications to the reaction conditions. Thus alkyl-9-BBN boranes such as
134 were successfully coupled with secondary alkyl iodides, bromides and
even chlorides at room temperature [eqn (11.35)].
100,101
Key to the successful
coupling of the alkyl-9-BBN reagents was the use of KO
t
Bu as a base and
i
BuOH as an additive, which the authors speculated may be involved in the
formation of reactive four-coordinate borate species that were detectable by
11
B NMR spectroscopy. Interestingly, under previously optimized con-
ditions,
95,102
less than 5% yield was observed.
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