C O M M U N I C A T I O N S
Scheme 1. Synthesis and NOESY NMR Cross-Peaks of 12, 13,
and 14; Crystal Structure of 12a
monoarylation. Primary aliphatic amines and anilines were coupled
with aryl chlorides at low catalyst loadings and with fast reaction
times, demonstrating the exceptional reactivity and stability of the
catalyst derived from 1. Finally, isolation of oxidative addition
complexes of 1 has led to insight into the importance of the methoxy
substitutent proximal to the phosphine for the reactivity of this
catalyst system. Further studies into the origin of the reactivity of
1 are currently underway in our laboratories.
Acknowledgment. We thank the National Institutes of Health
(NIH) for financial support of this project (Grant GM-58160). We
thank Merck and BASF (Pd compounds) for additional support.
M.R.B. thanks the NIH for a postdoctoral fellowship (GM-F32-
75685). We thank Dr. David S. Surry for helpful discussions and
Dr. Kelvin Billingsley for the preparation of 4. The Varian NMR
instrument used was supported by the NSF (Grants CHE 9808061
and DBI 9729592).
precipitation of the Pd(II) complex, which crystallizes as a single
conformer. Freshly prepared solutions of the isolated complexes
display only signals from the major conformer (1H and 31P NMR).
However, rapid isomerization is observed, with the minor isomer
becoming detectable within 5 min at room temperature.19
Subjecting either 2 or 4 to the conditions shown in Scheme 1
provided dramatically different results from those obtained using
1. The in situ 31P NMR spectrum from the reaction of 2 is complex
and shows broad resonances that we have yet to deconvolute. The
reaction with 4 results in the formation of Pd black. These
differences, to the extent that they reflect the behavior of the
resulting Pd(II) complexes, may be related to the observed
differences in reactivity observed with these ligands.
X-ray crystal analysis of 12 revealed that the complex exists as
a monomer in solid state, and, although some disorder about the
Br atom was observed, the resulting structure clearly demonstrates
that the Pd center is bound over the triisopropylphenyl ring (Scheme
1). In solution, the conformations of the major and minor rotamers
are analogous in 12, 13, and 14 (1H NMR).20 For all three
complexes, both conformers display 1H NMR resonances consistent
with D2 symmetry. NOESY NMR analysis of an equilibrated
sample of 14 (2:1 mixture) allowed the assignment of the solution
state conformation of both rotomers. The conformation of the major
rotamer 14a is the same as that observed in the solid state. In the
minor isomer 14b, the P-CAr bond is rotated by 180°, and the
palladium atom is chelated by the phosphine atom and the proximal
methoxy group. Important cross-peaks used in these assignments
are summarized in Scheme 1. Compounds 12, 13, and 14 are active
precatalysts in C-N bond-forming reactions.
Two notable points arise from the structural data. First, the NMR
data demonstrate that the Pd(II) aryl halide complexes of 1 likely
remain monomeric in solution and are not in equilibrium with the
non-D2 symmetric dimeric form.15 Second, the observed monomeric
equilibrium demonstrates that the proximal methoxy does not
prevent rotation about the P-CAr bond. Theoretical studies have
shown that this rotation may play an important role in catalytic
systems with other biarylphosphines.9 The implications of these
findings are not yet fully understood, and further studies to clarify
the role of the methoxy groups in 1 are ongoing.
Supporting Information Available: Procedural, spectral, and
crystallographic data. This material is available free of charge via the
References
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(7) Details of the synthesis of 1 are in the Supporting Information.
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(11) (a) An extra equivalent of ligand was added to reactions at temperatures
above 80 °C to help stability. No attempt has been made to minimize the
quantity of additional ligand. (b) Attempts to use primary aliphatic amines
or amides in cross-coupling reactions with mesylates have been unsuccessful
because of sulfonyl transfer side reactions.
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(15) For these reactions conducted at room temperature, an extra equivalent of
1 was not required in order to create the most stable catalytic system.
(16) Biscoe, M. R.; Barder, T. E.; Buchwald, S. L. Angew. Chem., Int. Ed. 2007,
46, 7232.
(17) Cabello-Sanchez, N.; Jean, L.; Maddaluno, J.; Lasne, M.; Rouden, J. J.
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(19) Concentrations measured versus an internal standard.
(20) In particular, the methoxy and isopropyl resonances are diagnostic in this
assessment, see Supporting Information
In summary, a new ligand with unprecedented reactivity for C-N
cross-coupling reactions has been developed. Use of this ligand
has allowed Pd-catalyzed amination reactions of aryl mesylates to
take place in high yield. Arylations of methylamine were also
performed for the first time with exceptional selectivities for
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