Stereospecific and Stereoselective Suzuki–Miyaura Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 540

benzylic ammonium compounds, readily prepared by alkylation of the cor-
responding amine, provides another very valuable route for the synthesis of
chiral hydrocarbons. Simple monocyclic aromatic derivatives also work well
in this reaction, although lower yields are typically observed. Both of these
methods are important in that they permit the use of compounds that are
readily available in enantiomerically pure form as electrophiles for the
stereospecific Suzuki-Miyaura reaction.

(11 : 32)

125 126

11.3.2 Stereoconvergent Cross-Coupling of Secondary Alkyl
Electrophiles
An alternative to attempting to restrict the oxidative addition of secondary
alkyl electrophiles to stereoinvertive S N 2-like mechanisms would be to har-
ness the power of radical intermediates in the oxidative addition, permit
racemization and employ this in a dynamic kinetic resolution sense. This
concept would obviate the need for enantioselective synthesis of the elec-
trophile, which is certainly problematic in the case of halides and also might
widen the scope of the electrophiles that could be employed.
The greater activity of nickel catalysts towards oxidative addition of a wide
variety of halides and pseudohalides has long been exploited in the coupling
of sp 2 carbon centers. 90 In addition, nickel is more prone to radical mech-
anisms, which should not be as sensitive to steric bulk in the alkyl halide as
Pd and, most importantly, should permit the development of an enantio-
convergent mechanism. It is therefore no surprise that in the cross-coupling
of secondary alkyl halides, nickel catalysts have dominated the literature. 91
Building on the work of the groups of Rovis 78 and Knochel, 92,93 Zhou and
Fu were able to employ a catalytic amount of an Ni-PyBOX complex to effect
the Negishi cross-coupling of racemic secondary alkyl halides [eqn (11.33)]. 94

(11 : 33)

Applications of these findings to the Suzuki-Miyaura cross-coupling sys-
tem were not long in coming. However, the catalyst system described by
Zhou and Fu to couple secondary alkyl bromides to organozincs was not
effective for the analogous organoboron nucleophiles. They subsequently