Angewandte Chemie International Edition
10.1002/anie.201807775
COMMUNICATION
Support for the cycle described in Figure 3a was obtained by
P
3
1
P
P
P NMR analysis of a Pd/MandyPhos complex. The kinetic
P
Pd
profile of the reaction suggests that complex E (Figure 3a) is the
Pd
Ph
R
Ph
Me
catalyst resting state and we found that a species consistent with
B(neo)
B(neo)
this structure is generated upon treatment of Pd(OAc)
2
with
TS
Ar
MandyPhos ligand L1 and an excess of "ate" complex 42: at
Ph
3
1
SM
isopropenyl
3.82
2
3 °C and 50 °C, the P NMR indicates the formation of two
isomeric bisphosphine Pd complexes in which the phosphorous
SMvinyl
3
.23
5.03
TS
22
atoms within each isomer are non-equivalent.
This complex
P
P
could also be prepared from Pd (dba) , L1 and excess 42.
2
3
Consistent with the claim of E being a resting state, addition of
Pd
H
-30.62
Ph
P
P
Pd
PhOTf leads to the catalytic generation of conjunctive coupling
1
31
B(neo)
p-Tol
-33.28
product ( H NMR analysis) but no change to the P NMR
spectrum.
R
Ph
B(neo)
PDT Ar
Of relevance to the unanticipated high reactivity of hindered
a-substituted alkenylboron-derived "ate" complexes in Table 2,
when the kinetic profile of substrate 1 (Table 1, B(pin) derivative)
was examined, it also exhibited zero-order kinetics with a rate
Figure 4. Energetics of Metallate Rearrangement. The ligand on Pd is dppf.
Optimized geometries calculated using DFT (BP86/Def2-SVP; PCM solvent
model with THF). ΔG Values are in kcal/mol; final energies calculated using DFT
(
M06/def2-TZVPP//def2-SVP; PCM solvent model with THF). Hydrogen atoms
(
rate=2.01 mM/min, see Supplementary Material) near that of the
were removed from displayed structure for clarity.
unsubstituted case, indicating that the metallate shift remains a
low-activation-barrier step in the catalytic cycle. To gain insight
about the effects of substrate substitution on this elementary
transformation, it was analyzed by DFT using dppf as a model for
In conclusion, we have established conditions under which
the Pd-catalyzed conjunctive cross-coupling can operate on a-
substituted boron "ate" complexes in an efficient and selective
fashion and deliver versatile tertiary boronic ester products.
Mechanistic experiments support a catalytic cycle where oxidative
addition is turnover limiting, and the catalyst resting state appears
to be an off-cycle Pd(0) coordinated to the "ate" complex, with the
C-C bond-forming metallate shift occurring by a low barrier 1,2-
migration.
the more conformationally flexible MandyPhos ligand.
As
depicted in Figure 4, the barrier for the metallate shift from the
unsubstituted vinyl complex is low, requiring only 5.03 kcal/mol for
the ground state olefin complex to reach the transition state. Of
2
3
note, when the vinyl group is replaced with an isopropenyl group
the olefin complex is destabilized by 3.23 kcal/mol; however, the
barrier for the metallate shift is smaller (3.82 kcal/mol), such that
the overall barrier for the metallate shift of the vinyl substrate is
2
4
only 1 kcal/mol lower than that for isopropenyl "ate" complexes.
For both substrate classes, the metallate shift is highly exergonic
suggesting that the unexpected tolerance of conjunctive coupling
to highly hindered substrates can be traced to an early transition
state for metallate shift where only nascent C-C torsional
interactions are present.
Acknowledgements
This work was supported by the NIH (R35-GM1217140). We
thank Solvias for providing MandyPhos ligand, and we thank Dr.
Thusitha Jayasundera for assistance with NMR spectroscopy.
Keywords: Cross Coupling • Boron • Asymmetric Catalysis •
Quaternary Center
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1
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