Angewandte
Chemie
[
a,b]
idine), [dtbpyPdCl ], and bipyrimidine catalyst 1 provided
Table 1: Comparison of site-selectivity for arene H/D exchange at 25%
conversion with site-selectivity obtained in electrophilic aromatic
bromination.
2
À1
TOFs of 0.0002, 0.002, and 0.003 s , respectively, under
[
10d]
identical conditions.
The catalysts were also compared on
the basis of turnover numbers (TONs). Complexes 3a–c
achieved the statistical maximum TON of 242 after
[11,12]
2
4 hours,
which is also superior to the results with
[
dtbpyPtCl ], [dtbpyPdCl ], and 1 (TON = 144 Æ 12, 90 Æ 18,
2
2
[10d]
and 94 Æ 13 under analogous conditions).
Lowering the
À
Entry
R
H/D exchange
ortho/meta/para
(catalyst)
Ar S
ortho/meta/para
E
catalyst loading of 3a to 0.1 mol% resulted in turnovers of
3
273 Æ 110 after 48 hours at 1508C, which demonstrates the
high activity and stability of this species, even upon prolonged
heating at elevated temperatures. Finally, we decreased the
reaction temperature to 1008C. As shown in Figure 1,
[a]
[c]
1
2
3
4
Et
CO Et
Br
Br
1.70:1.33:1 (3a)
1.26:2:1.33 (3a)
2.92:1.19:1 (3a)
1.72:0.06:1
[
[
a]
a]
[d]
0:2:0
2
[c]
0.48:0.01:1
[
b]
[c]
1.15:0.28:1 (DCl/THF)
0.48:0.01:1
[
dtbpyPtCl ], [dtbpyPdCl ], and 1 promoted very little H/D
2
2
exchange under these conditions, whilst 3a–c maintained high
activity.
[a] Conditions: 3a (3.0 mg, 2.5 mmol, 0.5 mol%), AgBF4 (1.9 mg,
5.0 mmol, 1.0 mol%), RPh (0.50 mmol, 1.0 equiv), [D ]AcOH (0.71 mL,
5 equiv), 1508C. [b] Conditions: BrPh (26.3 mL, 39.3 mg, 0.250 mmol,
.00 equiv), [D ]TFA (0.51 mL, 0.719 g, 6.25 mmol, 25.0 equiv), DCl in
4
2
1
1
D O (35%, 0.05 mL), 38 h, 1508C. [c] See Ref. [13]. [d] See Ref. [14].
2
TFA=trifluoroacetic acid, THF=tetrahydrofuran.
The substrate scope of H/D exchange reactions catalyzed
by 3a was also investigated. As summarized in Figure 2,
naphthalene, veratrole, 1,2-dichlorobenzene, bromobenzene,
ethylbenzoate, (H C) CCH Ph, sec-butylbenzene, cumene,
3
3
2
Figure 1. Turnover numbers for H/D exchange between benzene and
[D ]AcOH at 1008C, catalyzed by 1, 3a–c, [dtbpyPtCl ], and
4 2
[
dtbpyPdCl ] after 2 h (white), 24 h (light gray), and 48 h (dark gray).
2
Conditions: catalyst (2 mol%, 5 mmol), benzene (22.3 mL,
0
.250 mmol), AgBF (1.9 mg, 10 mmol), [D ]AcOH (0.37 mL, 6.5 mmol,
4
4
2
5 equiv relative to benzene).
Figure 2. Substrate scope of H/D exchange catalyzed by 3a; numbers
in small font are %D incorporation. Conditions: 3a (3.0 mg, 2.5 mmol,
2.0 mol%), substrate (0.125 mmol, 1.00 equiv), AgOTf (5.0 mmol,
4
.0 mol%), [D ]AcOH (0.36 mL, 0.40 g, 6.25 mmol, 50 equiv), 48 h
4
There are two possible explanations for the high H/D
(naphthalene, veratrol, PhBr) or 168 h (other substrates). Tf=trifluor-
exchange activity of 3a–c. The first is that the cationic ligands
enhance the reactivity of the coordinated metal center
towards arene CÀH cleavage to generate metal s-aryl
omethanesulfonyl.
intermediates (through an organometallic mechanism). An
alternative possibility is that the Lewis acidic metal centers
promote proton catalysis through an electrophilic aromatic
and trifluorotoluene all underwent extensive (48–98%)
aromatic H/D exchange with CD CO D. Significant (2–8%)
3
2
3
deuteration was also observed at unactivated sp CÀH sites
along the alkyl chains. In an interesting contrast, substrates
that do not bear a tethered aromatic group (e.g. cyclooctane,
2,2,3,3-tetramethylbutane, and methane) did not show H/D
exchange reactivity with catalyst 3a under analogous con-
ditions. This observation suggests that the arene moiety plays
substitution (ArÀS ) pathway. To gain insight into the
E
mechanism for H/D exchange, we examined the site-selec-
tivity of D incorporation with catalyst 3a for a variety of
substituted arenes at partial (ca. 25%) conversion. Table 1
1
compares the observed selectivity (as determined by H NMR
3
spectroscopy) to the product ratio for electrophilic bromina-
a role in directing the catalyst to the unactivated sp sites,
[13,14]
[15]
[16]
tion
(Table 1, entries 1–3); furthermore, the selectivity of
likely via cyclometalation or p-coordination. The obser-
vation of aliphatic H/D exchange provides further evidence to
support an organometallic mechanism, as this side reaction is
expected to be negligible under proton catalysis.
The H/D-exchange experiments probed the reactivity of
3a–c in CÀH bond cleavage, which is only the first step of a
DCl/CF CO D-catalyzed H/D exchange with bromobenzene
3
2
is shown in entry 4. In all cases, the site selectivity with 3a
differed dramatically from that observed in ArÀS . This is
E
strongly suggestive of an organometallic pathway for the
platinum/palladium-catalyzed H/D exchange reactions.
Angew. Chem. Int. Ed. 2010, 49, 5884 –5886
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5885