0
through a syn SE process with complete stereochemical
bulkier silanolate at the palladium center to form the
requisite SiꢀOꢀPd linkage; however the excellent γ-selec-
tivity of (Z)-1b warranted further study.
fidelity.6 Taken together, these studies provide a structural
model of transmetalation that invokes a tetracoordinate
Pd(II) intermediate bearing a single ancillary ligand, and
also highlights the importance of the E vinylic substituent
R1 in its placement relative to the palladium ligand pe-
riphery (Scheme 1). In addition, recent mechanistic studies
with isolated palladium(II) silanolate complexes indicate
that nucleophilic attack at silicon to form hypervalent
10-Si-5 species can have a dramatic effect on the rate of
transmetalation.7 This model prompted our investigation
of the effect of the silanolate olefin geometry and non-
transferable group on reaction generality, rate, and selec-
tivity when combined with bulky, monodentate phophine
ligands. Our ultimate goal was to identify catalysts that are
both more active and less sensitive to the electronic proper-
ties of the substrate.
Table 1. Effect of Silanolate Nontransferable Group and Olefin
Geometrya
conv,
%
yield
γ,b %
entry
1, R
R1
R2
γ/Rc
1
2
3
4
1a, Me
1a, Me
1b, Et
1b, Et
Me
H
H
96
100
15
57
92
4
42:1
18:1
ꢀ
Me
H
Me
H
Me
69
67
>99:1
Scheme 1. Summary of the Proposed Mechanism Illustrating
the Key Transmetalation Transition-State Structure i
a Reactions performed on 0.1 mmol scale, 2a = 3,5-dimethylbro-
mobenzene, and aryl = 3,5-dimethylbenzene. b Determined by GC
analysis. c GC peak area ratio of crude reaction mixtures.
Determining the effect of other bulky, monodentate
phosphonium tetrafluoroborate salts required ready ac-
cess to a variety of ligands. The tetrafluoroborate salts
provide a number of technical advantages and similar
reactivity (after in situ deprotonation) to the correspond-
ing trialkylphosphines.4 These technical advantages
are offset when an air-sensitive phosphine is needed that
requires purification or further synthetic elaboration. A
significant drawback of these salts is the inability to purify
them by silica gel chromatography or recover them from
alkaline or ionic reaction conditions. Conversely, bench-
stable phosphine•borane adducts can be carried through
multistep synthesis, employing reductive, oxidative, aque-
ous acidic, or strongly basic conditions, and be easily
purified by recrystallization, sublimation, or silica-gel
chromatography.8 Moreover, trialkylphosphine•borane
adducts can be handled without the use of rigorous
Schlenk technique or a drybox.
To achieve the synthesis of trialkylphosphonium tetra-
fluoroborate salts that bypasses the handling of pyro-
phoric trialkylphosphines, experimental conditions were
developed to transform air-stable phosphine•borane ad-
ducts directly into phosphonium tetrafluoroborate salts
(Scheme 2). Preparation of 3began by treatment of Cy2PCl9
with t-BuLi at ꢀ78 °C,10 followed by addition of BH3•THF
In a preliminary evaluation of bulky monodentate
phosphine ligands, the combination of Pd(dba)2 and
t-BuCy2PHþBF4 (3) provided a highly reactive catalyst
ꢀ
for the cross-coupling of allylic silanolate salts with aro-
matic bromides. Therefore, this ligand was used to study
the effect of the nontransferable group and olefin geometry
of the allylic silanolate on the efficiency and selectivity of
the cross-coupling reaction (Table 1). The use of an allylic
silanolate with nontransferable methyl groups and (E)-
olefin geometry (E)-1a provided a 57% yield of 5a and 42:1
site selectivity favoring the γ-coupled product (entry 1).
Changing the olefin geometry to Z raised the yield of 5a to
92% with slightly lower γ-selectivity (entry 2). Low reac-
tivity was exhibited by the more bulky, diethyl substituted
silanolate(E)-1bwithonly 15% conversion ofthe aromatic
bromide observed (entry 3). Strikingly, the combination of
(Z)-olefin geometry and nontransferable ethyl groups (Z)-
1b led to higher reaction efficiency (conversion) and ex-
quisite γ-selectivity at a slightly reduced reaction conver-
sion (entry 4). The superior reactivity of (Z)-silanolates
relative to (E)-silanolates under these conditions sup-
ported our hypothesis that the disposition of the vinylic
methyl group in the transmetalation transition-state struc-
ture i is important. The lower conversion observed for
diethylsilanolates suggests a slower displacement by the
(8) Staubitz, A.; Robertson, A. P. M.; Sloan, M. E.; Manners, I.
Chem. Rev. 2010, 110, 4023–4078.
(9) Issleib, K.; Seidel, W. Chem. Ber 1959, 92, 2681–2694.
(10) Jan, D.; Delaude, L.; Simal, F.; Demonceau, A.; Noels, A. F. J.
Organomet. Chem. 2000, 606, 55–64.
(11) (a) McKinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994, 35,
9319–9322. (b) McKinstry, L.; Livinghouse, T. Tetrahedron 1995, 51,
7655–7666. (c) McKinstry, L.; Overberg, J. J.; Soubra-Ghaoui, C.;
Walsh, D. S.; Robins, K. A.; Toto, T. T.; Toto, J. L. J. Org. Chem.
2000, 65, 2261–2263.
(6) Denmark, S. E.; Werner, N. S. J. Am. Chem. Soc. 2010, 132, 3612–
3620.
(7) Denmark, S. E.; Smith, R. C. J. Am. Chem. Soc. 2010, 132, 1243–
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