Oxidative addition of aryl tosylates to palladium(0) and coupling of unactivated aryl tosylates at room temperature

Article abstract of DOI:10.1021/ja035835z

Aryl tosylates are attractive substrates for Pd-catalyzed cross-coupling reactions, but they are much less reactive than the more commonly used aryl triflates. We report the oxidative addition of aryl tosylates to Pd(PPF-t-Bu)[P(o-tolyl)₃] and

Full text of DOI:10.1021/ja035835z

Published on Web 06/28/2003
Oxidative Addition of Aryl Tosylates to Palladium(0) and Coupling of
Unactivated Aryl Tosylates at Room Temperature
Amy H. Roy and John F. Hartwig*
Department of Chemistry, Yale UniVersity, P.O. Box 208107, New HaVen, Connecticut 06520-8107
Received April 28, 2003; E-mail: John.Hartwig@yale.edu
The oxidative addition of aryl halides and sulfonates to pal-
ladium(0) is a fundamental organometallic transformation.1 Many
studies have been conducted on the oxidative addition of aryl halides
to palladium(0),2-11 but fewer studies have been conducted on the
oxidative addition of aryl sulfonates.9,11,12 The oxidative addition
of aryl tosylates is particularly rare because of the low reactivity
of this substrate. Yet, palladium-catalyzed couplings of aryl tosylates
would be more attractive than the more common reactions of
triflates because they are more crystalline than aryl triflates and
are generated from less expensive reagents.
Cross couplings of aryl tosylates with nickel,13-15 iron,16,17 cop-
per,18 or palladium catalysts have required high temperatures, ac-
tivated aryl tosylates, or high catalyst loadings.14,19-22 Although
complexes of hindered alkylphosphines have recently reacted with
aryl chlorides,23 most of them do not add aryl tosylates that lack
activating groups. We report a Pd(0) complex that oxidatively adds
aryl tosylates at room temperature to form isolable arylpalladium-
(II) tosylate complexes. This mild activation created palladium-
catalyzed couplings of aryl tosylates with aryl Grignard reagents
and amines at room temperature or at elevated temperatures with
low loadings.
has been typically attributed to coordination of the anion to Pd(0)
prior to oxidative addition.3,5,12,26 Thus, we measured the order of
reaction in different reagents by 31P NMR spectroscopy at 55 °C
in THF solvent in the presence and absence of added bromide. The
concentration of PhOTs was varied from 0.062 to 0.45 M;
[N(octyl)4Br] was varied from 0 to 0.34 M, and [P(o-tolyl)3] was
varied from 0.088 to 0.26 M. Compound 1 was formed in situ from
Pd[P(o-tolyl)3]2 and PPF-t-Bu. Excellent fits to a first-order decay
of 1 were obtained.27 A first-order dependence of kobs on [PhOTs]
in both the presence and absence of added bromide was observed.
Plots of 1/kobs vs [P(o-tolyl)3] from reactions in the presence and
absence of added N(octyl)4Br were linear, indicating that the
reaction is inverse first order in P(o-tolyl)3.
Plots of kobs vs [NR4X] from reactions conducted with added
bromide and PF6 were linear with a positive slope and a clear,
nonzero y-intercept. The value of kobs for reaction in the absence
of bromide [(4.1 ( 0.6) × 10-4 s-1)] matched the y-intercept of
the plot of kobs vs [N(octyl)4Br] [(3.9 ( 0.6) × 10-4 s-1)] and the
plot of kobs vs [NBu4PF6] [(3.3(0.7) × 10-4)]. The slope of the
plot of kobs vs [NBu4PF6] was roughly 4 times greater than that of
the plot of kobs vs [N(octyl)4Br]. Thus, reactions in the presence of
[NBu4PF6] were faster than those conducted with added bromide.
Low solubility of 1 limited quantitative data, but reactions in DMF
and NMP were faster than reactions in less polar solvents. With 5
equiv of P(o-tol)3 at 55 °C, reactions in DMF and NMP appeared
complete in 0.5 h instead of 3.5 h in C6H6 or THF. Oxidative
addition of PhOTs to 2 was complete within 5 min at 25 °C in
THF, C6H6, or DMF.
Potential mechanisms for the reaction in eq 1 are shown in
Scheme 1. Path A begins with direct oxidative addition of aryl
tosylate to the 16-electron complex 1, followed by dissociation of
P(o-tolyl)3. In the presence of bromide, the halogen would replace
the coordinated tosylate after addition. This pathway predicts first-
order behavior in aryl tosylate and zero-order behavior in both
bromide and P(o-tolyl)3. This pathway is inconsistent with the
observed inverse-order behavior in P(o-tolyl)3 and the positive-
order behavior in bromide.
Path B is initiated by dissociation of P(o-tolyl)3 from 1, irrever-
sible oxidative addition of aryl tosylate and subsequent more rapid
exchange of bromide for tosylate to form 5 if bromide is present.
This pathway predicts first-order behavior in aryl tosylate, inverse-
order behavior in P(o-tolyl)3, and zero-order behavior in added
bromide. The kinetic orders in PhOTs and added P(o-tol)3 are
consistent with reaction by path B in the absence of added bromide.
Taken alone, the acceleration of rate by added bromide suggests
that path C, which involves initial associative or dissociative
exchange of bromide for P(o-tolyl)3 and subsequent irreversible
oxidative addition of aryl tosylate to the anionic Pd(0), occurs
concurrently with path B in the presence of added bromide. This
pathway predicts a reaction that is first order in aryl tosylate, inverse
order in P(o-tolyl)3, and first order in bromide. However, faster
Pd(0) complexes generated from sterically hindered versions of
the commercially available Josiphos ligands24,25 underwent addition
of aryl tosylate under mild conditions. Reaction between Pd[P(o-
tolyl)3]2 and PPF-t-Bu or CyPF-t-Bu at room temperature formed
Pd(PPF-t-Bu)[P(o-tolyl)3] (1) or Pd(CyPF-t-Bu)[P(o-tolyl)3] (2, eq
1). Subsequent treatment of 1 with PhOTs produced the phenylpal-
ladium tosylate complex 3 in 85% yield (eq 1) after 16 h at room
temperature by the first oxidative addition of an aryl tosylate to
generate an isolable addition product. Reaction in the presence of
N(octyl)4Br formed the phenylpalladium bromide complex 5 in 95%
yield after only 9 h. Reactions of phenyl tosylate with CyPF-t-Bu
complex 2 were even faster. Phenylpalladium tosylate 4 formed
from 2 in 92% yield in less than 5 min. The same reaction in the
presence of bromide formed the bromide complex 6 in 94% yield
in less than 5 min. Two isomeric versions of 3-6 could form, but
only one product that contained the palladium-bound phenyl cis to
the smaller phosphine was observed by NMR and X-ray diffraction
(see Supporting Information). Reactions of the analogues of 1
containing Josiphos ligands that lack a tert-butyl group formed the
addition product in lower yields and with slower rates.
Added anions have been shown to influence the mechanisms of
oxidative addition of aryl halides and sulfonates to Pd(0). This effect
9
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J. AM. CHEM. SOC. 2003, 125, 8704-8705
10.1021/ja035835z CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
The palladium-catalyzed amination of aryl tosylates at 110 °C
was reported previously,19,22 but the mild additions of aryl tosylates
now allow for the amination of aryl tosylates under milder condi-
tions. Octylamine and phenyl tosylate underwent coupling at room
temperature in 76% yield after only 6 h in toluene in the presence
of 1 mol % PdCl2(PPF-t-Bu) and 2.5 equiv of NaO-t-Bu (eq 2). In
addition, reaction in the presence of 1 mol % of PPF-t-Bu and
commercially available PdCl2(PhCN)2 formed the arylamine in 72%
yield after 6 h. The increased rate of addition by the Pd(0) complex
of CyPF-t-Bu further increased the rate of amination. Octylamine
coupled with phenyl tosylate in 74% yield after 2 h at 25 °C.
The mild activation of aryl tosylates reported here has several
important consequences. First, the mild addition allows for pal-
ladium-catalyzed Kumada and amination reactions with unactivated
aryl tosylates at room temperature. Second, the rapid oxidative addi-
tion step shows that the scope of couplings of aryl tosylates can be
limited by transmetalation and reductive elimination15 instead of
oxidative addition. As a result, aryl tosylates may ultimately replace
the more expensive and less convenient aryl triflates in many
coupling applications.
Table 1. Pd-Catalyzed Couplings of ArOTs and ArMgBra
Acknowledgment. We thank the NIH (GM58108) for support,
Johnson-Matthey for a gift of PdCl2, Solvias AG for a gift of CyPF-
t-Bu, and Merck Research Laboratories for unrestricted support.
Supporting Information Available: Experimental methods, kinetic
data, procedures, and spectral data; X-ray crystallographic data for 5
and 6 (PDF); X-ray crystallographic files for 5 and 6 (CIF). This
material is available free of charge via the Internet at http://pubs.acs.org.
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