Stereospecific and Stereoselective Suzuki–Miyaura Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 543

L n Ni II X 2
Preactivation

R-R'

L n Ni I

X

M-R

RE

TM

M- X

R'

L n Ni III R

L n Ni I

R

X

OA (1)

OA (2)

R

L n Ni II

R' X

X

+ R'￿

Scheme 11.15 Proposed mechanism for the Ni-catalyzed Suzuki-Miyaura coupling
of alkyl halides.

enantiopure catalyst may be capable of differentiating between the two en-
antiomers of the starting material. 104 Reactions with enantiopure a-chlor-
oamides display little or no erosion of enantiopurity of the starting alkyl
halide (see below), implying that there is no apparent reversibility in the
oxidative addition with these substrates. 104,109 However, in the case of a-
bromoamides, the unreacted starting material remains racemic throughout
the reaction.
Elegant studies by Taylor and Jarvo demonstrated that at room tempera-
ture, non-benzylic Ni-C bonds are configurationally stable under typical
Suzuki-Miyaura reaction conditions [eqn (11.38)], 110 providing further evi-
dence for the proposal that the scrambling of stereochemistry observed in
Fu-type couplings of secondary alkyl halides is a feature of the oxidative
addition step, not instability of the resulting alkyl-metal intermediate.

(11 : 38)

Although activated alkyl bromides are not needed in the chemistry reported
thus far, the observation of some levels of substrate specificity led the authors
to propose that some interaction between functionality on the alkyl halide and
the catalyst was important. 103 Namely, it was observed that homobenzylic
halides undergo Suzuki-Miyaura cross-coupling with high enantioselectivity,
but dramatically reduced enantiomeric excess is observed in the one-carbon
homologs (Scheme 11.16). 103 These results suggest the presence of an inter-
action between the aryl group and the chiral catalyst, enabling the Ni complex