Dendrimeric organochalcogen catalysts for the activation of hydrogen peroxide: Origins of the "dendrimer effect" with catalysts terminating in phenylseleno groups

Article abstract of DOI:10.1021/ja0367593

Several scenarios were evaluated to explain the large "dendrimer effect" observed in the bromination of cyclohexene with H₂O ₂ and NaBr catalyzed by the addition of Frechet-type dendrimers terminating in -O(CH₂)₃SePh groups. Although phenylseleninic acid was an efficient catalyst for the oxidation of NaBr with H₂O₂, first-order rate constants for the selenoxide elimination were too small to produce PhSeO₂H at a rate sufficient to explain the rates of catalysis and no dendrimer effect was observed in the rates of selenoxide elimination. An induction period was observed using 1-SePh as a catalyst for the oxidation of Br- with H₂O₂. The addition of preformed selenoxide 1-Se(=O)Ph gave immediate catalysis with no induction period. However, rates of oxidation of the selenides with H ₂O₂ under homogeneous or biphasic conditions or with t-BuOOH under homogeneous conditions were too slow to account for the rates of catalysis, and no dendrimer effect was observed in the rates of oxidation. The primary oxidant for converting selenides to selenoxides was "Br+" produced initially by the uncatalyzed background reaction of H₂O ₂ with NaBr and then produced catalytically following formation of selenoxide groups. Autocatalysis is observed, and the rate of oxidation increases with the number of SePh groups. Autocatalysis is the source of the large dendrimer effect observed with the SePh series of catalysts.

Full text of DOI:10.1021/ja0367593

Published on Web 09/20/2003
Dendrimeric Organochalcogen Catalysts for the Activation of
Hydrogen Peroxide: Origins of the “Dendrimer Effect” with
Catalysts Terminating in Phenylseleno Groups
Michael D. Drake, Frank V. Bright, and Michael R. Detty*
Contribution from the Department of Chemistry, The State UniVersity of New York at Buffalo,
Buffalo, New York 14260
Received June 18, 2003; E-mail: mdetty@acsu.buffalo.edu
Abstract: Several scenarios were evaluated to explain the large “dendrimer effect” observed in the
bromination of cyclohexene with H
terminating in -O(CH SePh groups. Although phenylseleninic acid was an efficient catalyst for the oxidation
of NaBr with H , first-order rate constants for the selenoxide elimination were too small to produce
PhSeO H at a rate sufficient to explain the rates of catalysis and no dendrimer effect was observed in the
2 2
O and NaBr catalyzed by the addition of Frech e´ t-type dendrimers
2 3
)
2
O
2
2
rates of selenoxide elimination. An induction period was observed using 1-SePh as a catalyst for the oxidation
-
of Br with H
2
O
2
. The addition of preformed selenoxide 1-Se(dO)Ph gave immediate catalysis with no
under homogeneous or biphasic
2 2
induction period. However, rates of oxidation of the selenides with H O
conditions or with t-BuOOH under homogeneous conditions were too slow to account for the rates of
catalysis, and no dendrimer effect was observed in the rates of oxidation. The primary oxidant for converting
+
selenides to selenoxides was “Br ” produced initially by the uncatalyzed background reaction of H
2
O
2
with
NaBr and then produced catalytically following formation of selenoxide groups. Autocatalysis is observed,
and the rate of oxidation increases with the number of SePh groups. Autocatalysis is the source of the
large dendrimer effect observed with the SePh series of catalysts.
Introduction
Chart 1. Organochalcogenide Catalysts
Dendrimer molecules are constructed with a controlled
architecture that allows molecular properties to be designed and
1
tailored. This feature is advantageous in the design of den-
drimeric catalysts where catalytic functionality can be placed
2
at the termini of the individual arms of the dendrimer or within
the dendrimer architecture.3 In some catalytic systems, a
“
dendrimer effect” has been observed in which nonstatistical
changes in catalytic activity are observed with increasing
4
numbers of catalytic groups. We have described one of the
more striking examples of a dendrimer effect in the catalytic
activity of a series of Frech e´ t-type1 dendrimers terminating
in phenylchalcogeno groups (Chart 1).2 In the phenyltelluro
a,f
e
(
(
(
1) For recent reviews see: (a) Grayson, S. M.; Fr e´ chet, J. M. M. Chem. ReV.
2
1
001, 101, 3819-3867. (b) Fisher, M.; V o¨ gtle, F. Angew. Chem., Int. Ed.
999, 38, 884-905. (c) Dendrimers; Top. Curr. Chem. 1998, 197. (d)
Gorman, C. AdV. Mater. 1998, 295-309. (e) Newkome, G. R.; Moorefield,
C.; V o¨ gtle, F. Dendritic Macromolecules: Concepts, Synthesis, Perspec-
tiVes; VCH: Weinheim, Germany, 1996. (f) Fr e´ chet, J. M. J. Science 1994,
2
63, 1710-1715. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III.
(TePh) series, the catalytic activity increased statistically with
the number of TePh groups and each TePh group had roughly
the same reactivity (Figure 1). In contrast, the catalytic activity
per SePh group in the phenylseleno (SePh) series increased
dramatically as the number of SePh groups per molecule
Angew. Chem., Int. Ed. Engl. 1990, 29, 138-175.
2) For a few illustrative examples see: (a) Cuadrado, I.; Mor a´ n, M.; Casado,
C.; Alonso, B.; Lobete, F.; Garc ´ı a, B.; Ibistate, M.; Losanda, J. Organo-
metallics 1996, 15, 5278-5280. (b) Chow, H.-F.; Mak, C. C. J. Org. Chem.
1
997, 62, 5116-5127. (c) Bourque, S. C.; Maltais, F.; Xiao, W.-J.; Tardif,
O.; Alper, H.; Arya, P. J. Am. Chem. Soc. 1999, 121, 3035-3038. (d) Liao,
Y.-H.; Moss, J. R. Organometallics 1996, 15, 4307-4316. (e) Francavilla,
C.; Drake, M. D.; Bright, F. V.; Detty, M. R. J. Am. Chem. Soc. 2001,
1
23, 57-67.
(4) For a few examples of cooperativity or a dendrimer effect see: (a) Lee,
J.-J.; Ford, W. T.; Moore, J. A.; Li, Y. Macromolecules 1994, 27, 4632-
4634. (b) Enomoto, M.; Aida, T. J. Am. Chem. Soc. 1999, 121, 874-875.
(c) Kleij, A. W.; Gossage,. A.; Jastrzebski, J. T. B. H.; Boersma, J.; van
Koten, G. Angew. Chem., Int. Ed. 2000, 39, 176-178. (d) Breinbauer, R.;
Jacobseen, E. N. Angew. Chem., Int. Ed. 2000, 39, 3604-3607.
3) For a few illustrative examples see: (a) Zhao, M.; Sun, L.; Crooks, R. M.
J. Am. Chem. Soc. 1998, 120, 4877-4878. (b) Balogh, L.; Tomalia, D. A.
J. Am. Chem. Soc. 1998, 120, 7355-7356. (c) Piotti, M. E.; Rivera, Jr.,
F.; Bond, R.; Hawker, C. J.; Fr e´ chet, J. M. M. J. Am. Chem. Soc. 1999,
1
21, 9471-9472.
1
2558 J. AM. CHEM. SOC. 2003, 125, 12558-12566
9
10.1021/ja0367593 CCC: $25.00 © 2003 American Chemical Society

Dendrimeric Organochalcogen Catalysts
A R T I C L E S
Scheme 2
the SePh group. For many organochalcogenide catalysts con-
taining a single organochalcogenide group, the rate of oxidation
6
with H2O2 is the rate-determining step. Should the dendrimer
architecture accelerate the oxidation of selenides to selenoxides
to a greater extent than the oxidation of the corresponding
tellurides, then the rate of oxidation might be responsible for
the dendrimer effect.
Figure 1. Relative rate constants for catalysis per phenylchalcogeno group,
krel/EPh), in molecules with n arms terminating in phenylchalcogeno groups.
Scheme 1
The catalytic activity of either organoselenides or organo-
tellurides with H2O2 is presumed to involve the corresponding
selenoxides or telluroxides, respectively. The syn-elimination
of an organoselenenic acid (RSeOH) from a selenoxide with
7
â-hydrogens to produce an olefin has no parallel reaction for
telluroxides. While no appreciable selenoxide elimination has
been observed previously in reactions of 1-SePh, 3-SePh,
2e
6
-SePh, or 12-SePh with H2O2, some selenoxide elimination,
as illustrated in Scheme 2 for 1-SePh, cannot be rigorously
excluded. Under the conditions of reaction, any PhSeOH
produced from selenoxide elimination would be rapidly oxidized
8
by H2O2 to phenylseleninic acid (PhSeO2H), which then might
9
-11
function as a catalyst for H2O2.
If the dendrimers with a
greater number of SePh groups were to produce more PhSeO2H
as a catalyst for H2O2 than molecules with fewer SePh groups,
then the dendrimer effect might result from these differences.
The effects of the dendrimer architecture on the rates of
oxidation and the rates of production of PhSeO2H were our
starting points for the evaluation of the dendrimer effect. We
increased. The apparent increase in relative reactivity per SePh
group is a factor of 75 from 3-phenoxy-1-phenylselenopropane
(
1-SePh) with one SePh group to 12-SePh with twelve SePh
groups.
The reaction of interest in the current work is the bromination
-
examined PhSeO2H as a catalyst for the oxidation of Br with
H2O2, and we examined the rate of oxidation of selenides to
selenoxides 1-Se(dO)Ph, 3-Se(dO)Ph, 6-Se(dO)Ph, and 12-
Se(dO)Ph as well as the rate of selenoxide elimination in these
same systems.
of cyclohexene with NaBr and H2O2 in the presence of a catalyst
from Chart 1 in a two-phase system of CH2Cl2 and pH 6
phosphate buffer. The reaction is thought to follow the sequence
shown in Scheme 1. In the absence of catalyst, the oxidation of
-
Results and Discussion
Br with H2O2, while thermodynamically favored, is a relatively
-
5
-1 -1 5
slow process (kOX ≈ 1.7 × 10
M
s ), and brominated
Phenylseleninic Acid as a Catalyst for the Oxidation of
products 1 and 2 are formed slowly. The addition of an
organochalcogenide catalyst gives oxidation of the chalcogen
atom to the corresponding chalcogen oxide, hydration to the
dihydroxychalcogenane, introduction of Br as a ligand, and,
finally, reductive elimination of “Br ” (as Br2 or BrOH) and
2e
Bromide with H2O2. In our earlier studies, we did not see
1
formation of allyl ethers by H NMR spectroscopy in the time
course of our reactions as evidence for selenoxide elimination.
However, if the catalytic activity of PhSeO2H were sufficiently
great, even a small amount of PhSeO2H produced by selenoxide
elimination might be responsible for the dendrimer effect
observed in the SePh series of Chart 1. If PhSeO2H were the
-
+
chalcogen(II) compound to start the cycle over. Typically,
organotellurides are much more active catalysts than the
corresponding selenide. The TePh series in Figure 1 illustrates
the “expected” behavior of dendrimeric catalysts with statistical
increases in catalytic activity as the catalytic group number per
dendrimer increases.
Significantly greater than statistical increases in reaction rates
were observed as the number of catalytic groups in the SePh
series increased. This trend requires cooperativity either (1) to
accelerate the rate-determining step of the catalytic cycle for
each SePh group or (2) to accelerate the formation of a new
catalytic group that is a more efficient catalyst for H2O2 than
(6) (a) You, Y., Ahsan, K., Detty, M. R. J. Am. Chem. Soc. 2003, 125, 4918-
4
927. (b) Detty, M. R.; Zhou, F.; Friedman, A. E. J. Am. Chem. Soc. 1996,
118, 313-318.
(
7) (a) Walter, R.; Roy, J. J. Org. Chem. 1970, 36, 2561-2563. (b) Jones, D.
N.; Mundy, D.; Whitehouse, R. D. J. Chem. Soc., Chem. Commun. 1970,
8
6-88. (c) Sharpless, K. B.; Young, M. W.; Lauer, R. F. Tetrahedron
Lett. 1973, 1979-1982. (d) Reich, H. J.; Reich, I. L.; Renga, J. M. J. Am.
Chem. Soc. 1973, 95, 5813-5815.
(8) Hori, T.; Sharpless, K. B. J. Org. Chem. 1978, 43, 1689-1697.
(
9) (a) Reich, H. J.; Chow, F.; Peake, S. L. Synthesis 1978, 299-301. (b) ten
Brink, G. J.; Fernandes, B. C. M.; Van Vliet, M. C. A.; Arends, I. W. C.
E.; Sheldon, R. A. J. Chem. Soc., Perkin Trans. 1 2001, 224.
(
10) (a) Syper, L.; Mlochowski, J. Tetrahedron 1987, 43, 207-213. (b) ten Brink,
G. J.; Vis, J.-M.; Arends, I. W. C. E.; Sheldon, R. A. J. Org. Chem. 2001,
6
6, 2429-2433. (c) ten Brink, G.-J.; Vis, M. J.; Arends, I. W. C. E.;
Sheldon, R. A. Tetrahedron 2002, 3977-3983.
(11) Back, T. G.; Dyck, B. P. J. Am. Chem. Soc. 1997, 119, 2079.
(
5) Mohammed, A.; Liebhafsky, H. A. J. Am. Chem. Soc. 1934, 56, 1680-
1
685.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003 12559

A R T I C L E S
Drake et al.
active catalyst, then changes in dendrimer architecture across
the SePh series should impact the rate of formation of PhSeO2H
either through the rate of elimination of the selenoxide, kELIM,
or through the rate of oxidation of the selenide to the selenoxide,
kOX. While seleninic acids have not been previously described
as catalysts for halide salt oxidation with H2O2, they have been
efficient catalysts for H2O2 activation in other reactions including
8
8
epoxidations, oxidation of sulfides to sulfoxides and sulfones,
9
Baeyer-Villiger oxidations, oxidation of aldehydes to car-
boxylic acids,9 and oxidation of thiols to disulfides.
c
10
Phenylseleninic acid was evaluated as a catalyst for the
oxidation of Br- with H2O2 in the two-phase system under
2e
-
conditions described in our earlier work. The oxidation of Br
with H2O2 in control experiments (no catalyst) was followed
by the rate of bromination of cyclohexene as shown in Scheme
1
to give trans-1,2-dibromocyclohexane (1) and trans-2-
bromocyclohexanol (2) in a two-phase system of 0.5 M
cyclohexene in CH2Cl2 for the organic phase and an aqueous
phase of H2O2 (3.0 M) and NaBr (2.0 M) in pH 6 phosphate
buffer (0.1 M) at 298.0 ( 0.1 K. The concentrations of
cyclohexene and Br remain essentially unchanged over the
course of reaction as H2O2 is consumed. The pseudo-first-order
Figure 2. Rate of the appearance of products in the PhSeO2H-catalyzed
-3
(
2.3 × 10 M) bromination of cyclohexene (0.5 M in CH2Cl2) with 3 M
H O and 2.0 M NaBr in pH 6 phosphate buffer (filled circles) relative to
2 2
the uncatalyzed reaction (open circles). The inset shows the first-order plot
of the data where ln A ) ln(A∞ - At), where A∞ is the concentration at
infinity and At is the concentration at time t.
-
than nkCAT(PhSeO H) (7.3 × 10 M-2 s-1), which suggests
-1
rate constant, kOBS, for the appearance of products in the
2
-
5
uncatalyzed or control reaction (kCONTR) was (5.8 ( 0.1) × 10
that the reaction is not being catalyzed by PhSeO H alone even
2
-1
s
for the average of triplicate runs (( standard deviation). In
with complete selenoxide elimination.
the catalyzed reaction, kOBS has contributions from the control
and the catalyzed processes. A rate constant for catalysis, kCAT,
can be calculated from kOBS for the catalyzed reaction according
to
Rate of Selenoxide Elimination in Oxidized Catalysts. For
the selenide catalysts of Chart 1, PhSeO H can only be produced
2
following selenoxide elimination of PhSeOH and subsequent
oxidation. The rates of selenoxide elimination, kELIM (Scheme
2
), in oxidized 1-SePh, 3-SePh, 6-SePh, and 12-SePh were
-
kOBS ) kCAT[Br ][catalyst] + k
(1)
1
CONTR
measured by H NMR spectroscopy. The selenides were
oxidized to the corresponding selenoxides 1-Se(dO)Ph, 3-Se-
which rearranges to
kCAT
(
dO)Ph, 6-Se(dO)Ph, and 12-Se(dO)Ph either with N-
12
chlorosuccinimide followed by hydrolysis of the intermediate
chloroselenonium salt or with H2O2. Both procedures gave the
kOBS - kCONTR
)
(2)
-
1
[
Br ][catalyst]
same oxidized product. H NMR and mass spectra for 1-Se-
(
dO)Ph, 3-Se(dO)Ph, and 6-Se(dO)Ph (Figures S1-S3) and
-
3
The addition of 2.3 × 10 M PhSeO2H in the organic phase
1
the H NMR spectrum for 12-Se(dO)Ph (Figure S4) are
compiled in the Supporting Information.
Selenoxide elimination in oxidized 1-Se(dO)Ph produces
allyl phenyl ether and PhSeOH as shown in Scheme 2. For 3-Se-
accelerated the appearance of brominated products with kOBS
-
4
-1
of (3.4 ( 0.3) × 10
s
for the average of triplicate runs.
The reaction followed pseudo-first-order kinetics as shown in
Figure 2. According to eq 2, the rate constant for catalysis, kCAT
(dO)Ph, 6-Se(dO)Ph, and 12-Se(dO)Ph, selenoxide elimina-
-
2
-2 -1
for PhSeO2H, is (6.1 ( 0.5) × 10
M
s . From 100 mmol
tion leads to multiple allyl aryl ether groups and PhSeOH. The
rates of selenoxide elimination in 1-Se(dO)Ph, 3-Se(dO)Ph,
6
of olefinic proton appearance for the allyloxy groups by H
NMR spectroscopy. For 3-Se(dO)Ph, 6-Se(dO)Ph, and 12-
Se(dO)Ph, the 12 aromatic protons of the 1,1,1-tris(4-hydroxy-
phenyl)ethyl core served as a 12-proton internal standard (Figure
S5, Supporting Information). The chemical shifts of the AA′BB′
pattern were separated from all other aromatic and olefinic
signals in reduced, oxidized, and eliminated forms. For 1-Se-
of H2O2, 3.4 mmol of brominated products was produced from
excess cyclohexene in both the catalyzed and uncatalyzed
reactions, which is consistent with our earlier work with the
catalysts of Chart 1.2
-Se(dO)Ph, and 12-Se(dO)Ph were determined by the rate
1
e
If PhSeO2H were the actual catalyst in the dendrimer-
catalyzed reaction of Scheme 1, then values of kCAT for the
dendrimer would be less than or equal to (in the case of complete
selenoxide elimination) a multiple of the number of dendrimer
arms (n) and kCAT for PhSeO2H. This is true for 1-SePh-,
-
3
3
2
-SePh-, and 6-SePh-catalyzed reactions (kCAT of 1.2 × 10 ,
(
dO)Ph, the entire aromatic region was integrated as a 10-
-
2
-1
-2 -1
.8 × 10 , and 2.1 × 10
M
s , respectively, although
proton internal standard. Rate constants for selenoxide elimi-
nation, kELIM, at 323.0 ( 0.3 K in CDCl3 are compiled in Table
1
the reported value for 1-SePh is inaccurate on the basis of the
work described herein),2 where the observed catalysis is
a fraction of the value predicted by the quantity nkCAT-
e
and represent the average of duplicate runs.
Oxidation of 3-SePh, 6-SePh, and 12-SePh to 3-Se(dO)-
-
2
-1
-1
-2 -1
(
PhSeO2H): 6.2 × 10 , 1.2 × 10 , and 3.7 × 10
M
s ,
Ph, 6-Se(dO)Ph, and 12-Se(dO)Ph, respectively, gives poly-
selenoxides, and each sequential elimination of PhSeOH
respectively. Partial selenoxide elimination to generate PhSeO2H
could be responsible for the observed catalysis; however, kCAT
1.08 M s ) for the 12-SePh-catalyzed reaction is higher
-
2
-1 2e
(
(12) Detty, M. R. J. Org. Chem. 1980, 45, 274-277.
12560 J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003

Dendrimeric Organochalcogen Catalysts
A R T I C L E S
Table 1. Rate Constants for Selenoxide Elimination (kELIM), Oxidation with t-BuOOH [kOX(t-BuOOH)], and Oxidation with H2O2 [kOX(H2O2)]
and the Rate Constant for Catalysis (kCAT) for Selenides/Selenoxides Derived from 1-SePh, 3-SePh, 6-SePh, and 12-SePh
k
ELIM,a,b
k
OX(t-BuOOH),a-c
k
OX(H
2
O
2
),c,d
k
CAT,e
M-2 s-1
compd
s-
1
M-1 s-1
M-1 s-1
-
4
-3
-3
-3
-3
-6
-5
-5
-5
-2 f
1
3
6
1
-SePh/1-Se(dO)Ph
-SePh/3-Se(dO)Ph
-SePh/6-Se(dO)Ph
2-SePh/12-Se(dO)Ph
(5.6 ( 0.9) × 10
(5.60 ( 0.01) × 10
(1.85 ( 0.01) × 10
(1.96 ( 0.04) × 10
(2.40 ( 0.04) × 10
(2.38 ( 0.08) × 10
(8.1 ( 0.5) × 10
(1.3 ( 0.1) × 10
(1.0 ( 0.1) × 10
(1.8 ( 0.5) × 10
(2.2 ( 0.1) × 10
-
-
4
4
-2 g
2.8 × 10
-
4
-1 g
(5.7 ( 0.2) × 10
2.1 × 10
(6.20 ( 0.08) × 10
1.08g
a
In CDCl3 at 323.0 ( 0.3 K. Average of duplicate runs. c 0.5 M t-BuOOH. d In a two-phase mixture of CDCl3/pH 6 phosphate buffer containing 3.4
b
e
f
M H2O2. 0.5 M cyclohexene in CH2Cl2/pH 6 phosphate buffer containing 3.0 M H2O2 and 2.0 M NaBr. Calculated according to eq 2. Average of triplicate
runs (( standard deviation). Reference 2e.
g
Figure 3. Rate of the appearance of products in the bromination of
cyclohexene (0.5 M in CH2Cl2) with 3 M H2O2 and 2.0 M NaBr in pH 6
phosphate buffer catalyzed with 3-SePh, 6-SePh, or 12-SePh.
Figure 4. Rate of the appearance of products in the bromination of
cyclohexene (0.5 M in CH Cl ) with 3 M H O and 2.0 M NaBr in pH 6
2
2
2
2
-
2
phosphate buffer catalyzed by 2.8 × 10 M 1-SePh (open circles) or 2.8
-
2
×
10 M 1-Se(dO)Ph (filled circles).
produces a “new” compound that might impact the rate of
elimination of the next selenoxide group. The structural differ-
ences generated by sequential elimination of each selenoxide
had essentially no impact on the rates of elimination. A single
rate was observed, within our measurement precision, throughout
the selenoxide elimination in 3-Se(dO)Ph, 6-Se(dO)Ph, or 12-
Se(dO)Ph. Furthermore, the different monomer and dendrimer
architectures among 1-Se(dO)Ph, 3-Se(dO)Ph, 6-Se(dO)Ph,
and 12-Se(dO)Ph had little impact on kELIM. At 323 K in
CDCl3, the rates of selenoxide elimination for all four com-
3
.0 M H2O2 in pH 6 phosphate buffer at 296.0 ( 0.1 K gave
immediate formation of brominated products 1 and 2 at a rate
faster than the uncatalyzed rate with no apparent induction
period during the time intervals we were able to sample.
Our first insight into the actual catalytic functional group
using 1-SePh, 3-SePh, 6-SePh, and 12-SePh as catalysts came
from the product vs time profile using 1-SePh as a catalyst. In
-
3
our original work, the concentration of 1-SePh was 2.5 × 10
M and the contribution from the uncatalyzed reaction to the
overall velocity was greater than that of the catalyzed reaction
-
4
-4 -1
pounds were nearly identical (5.6 × 10 to 6.2 × 10 s )
with a half-life of approximately 1200 s. At 298 K in the CH2-
Cl2/pH 6 buffer mixture, the rate of elimination was much slower
2
e
under these conditions. We were not surprised by this since
selenides typically are much poorer catalysts than the corre-
sponding tellurides. We reexamined the reaction of Scheme
4
13
with half-lives in excess of 10 s.
Oxidation of 1-TePh either with N-chlorosuccinimide12
followed by hydrolysis of the intermediate chlorotelluronium
salt or with H2O2 gave 1-Te(dO)Ph. In contrast to the thermal
lability of 1-Se(dO)Ph, 3-Se(dO)Ph, 6-Se(dO)Ph, and 12-
Se(dO)Ph, the telluroxide was quite stable and no elimination
products were observed with 1-Te(dO)Ph even after 6 h at
-2
1 using a higher concentration of 1-SePh (2.8 × 10 M) and
found some surprising results. Specifically, during the initial 1
h of reaction, the rate of appearance of products was slow [kOBS
-
5
-1
of (6.3 ( 0.1) × 10
s
at 298 K based on the average of
-
2
duplicate runs with 2.8 × 10 M 1-SePh], nearly identical to
-
3
that observed with 2.5 × 10 M 1-SePh, and only slightly
-
5
-1
3
23 K.
greater than the uncatalyzed background rate (5.8 × 10 s )
as shown in Figure 4. After 1 h, the rate of appearance of
brominated products accelerated. The lack of an increase in the
initial rate at a much higher concentration of 1-SePh and the
apparent induction period suggested that 1-SePh was not the
active catalyst in the system.
Selenoxide Elimination and Catalysis. On the basis of
values of kELIM, if the active catalyst for the reaction of Scheme
from 3-SePh, 6-SePh, or 12-SePh were derived from
1
selenoxide elimination, then an induction period (>1200 s)
should be observed prior to the maximum reaction velocity to
accommodate oxidation of the selenide, selenoxide elimination,
and oxidation of PhSeOH to PhSeO2H. As shown in Figure 3,
the addition of 3-SePh, 6-SePh, or 12-SePh to a two-phase
mixture of 0.5 M cyclohexene in CH2Cl2 and 2.0 M NaBr and
The induction period observed with 1-SePh was not related
to selenoxide elimination. When 1-SePh in CH Cl was stirred
2
2
(13) Detty, M. R.; Gibson, S. L. Organometallics 1992, 11, 2147-2156.
J. AM. CHEM. SOC. VOL. 125, NO. 41, 2003 12561
9

A R T I C L E S
Drake et al.
with 3.0 M H2O2 and 2.0 M NaBr in pH 6 phosphate buffer,
the oxidation to the selenoxide was complete after 1 h. However,
no allyl phenyl ether was detected in the organic phase by H
Oxidation of the SePh Series with t-BuOOH as Oxidant.
The progress of oxidation of 1-SePh, 3-SePh, 6-SePh, and 12-
SePh with excess t-BuOOH in CDCl3 was easily monitored by
1
1
NMR spectroscopy. Shaking a CH2Cl2 solution of the selenoxide
H NMR spectroscopy. The SePh group ortho protons were
1
1
-Se(dO)Ph with 5% aqueous sodium bisulfite gave reduced
-SePh in nearly quantitative recovered yield. These results
diagnostic for SePh group oxidation to the corresponding
Se(dO)Ph group. As the SePh group, the ortho protons appeared
in the chemical shift range δ 7.4-7.5. As the Se(dO)Ph group,
the phenyl ring ortho protons appeared at δ 7.7. As before, the
12 aromatic protons of the 1,1,1-tris(4-hydroxyphenyl)ethyl core
served as a 12-proton internal standard to determine 3-Se(dO)-
Ph/3-SePh, 6-Se(dO)Ph/6-SePh, and 12-Se(dO)Ph/12-SePh
ratios while the two Se(dO)Ph group ortho protons were
integrated against the remaining eight aromatic protons to
determine 1-Se(dO)Ph/1-SePh ratios.
suggest that selenoxide elimination is not important in the
formation of the active catalyst with 1-SePh.
The Selenoxide as Catalyst. One alternative to the selenoxide
elimination generating the active catalyst with 1-SePh is that
oxidation of 1-SePh to 1-Se(dO)Ph is responsible for the
induction period observed in Figure 4 and that 1-Se(dO)Ph is
the actual catalyst in the system. It is known that selenoxides
1
4
catalyze the decomposition of H2O2 to give O2 and H2O,
indicating that selenoxides interact with H2O2 in solution.
The concentrations of 1-SePh, 3-SePh, 6-SePh, and 12-SePh
When 1-Se(dO)Ph was prepared by oxidation of 1-SePh
with either N-chlorosuccinimide12 or H2O2 and added to the two-
phase mixture of cyclohexene, NaBr, and H2O2, no induction
period was observed as shown in Figure 4 and pseudo-first-
order kinetics were followed. Furthermore, in the absence of
H2O2, 0.1 M solutions of selenoxide gave no bromination of
were adjusted to keep the concentration of SePh groups constant
-3
at 2.5 × 10 M, and the concentration of t-BuOOH was kept
-2
constant at 5 × 10 M. While the large excess of t-BuOOH
allowed pseudo-first-order kinetics to be followed, the excess
oxidant was also necessary to have oxidation occur within a
practical time frame.
0
.5 M cyclohexene in CH2Cl2 after 24 h of stirring with 2 M
At ambient temperature, the half-lives for oxidation under
these conditions were all >5 h for 1-SePh, 3-SePh, 6-SePh,
and 12-SePh and some selenoxide elimination was observed.
At 323.0 ( 0.3 K, selenoxide elimination was fast relative to
the rate of oxidation, kOX(t-BuOOH), no buildup of selenoxide
was observed, and kOX(t-BuOOH) was determined from the rate
of appearance of the olefinic protons from the allyloxy groups
as described above. Values of kOX(t-BuOOH) at 323 K in CDCl3
are compiled in Table 1 and represent the average of duplicate
runs. The observed pseudo-first-order rate constants for oxida-
NaBr in pH 6 phosphate buffer. These results suggest that the
actual catalyst in bromide oxidation is the selenoxide and not
-
2
the selenide. For 2.8 × 10 M 1-Se(dO)Ph, kOBS was (1.28
0.05) × 10 based on the average of triplicate runs,
which corresponds to kCAT of (2.2 ( 0.1) × 10
-Se(dO)Ph according to eq 2.
Oxidation of Organochalcogenide Compounds. Typically,
organotellurides are oxidized much more rapidly than the
-
3
-1
(
s
-
3
-2 -1
M
s
for
1
15
corresponding organoselenides with a variety of oxidants. The
rates of oxidation of monotellurides 1-TePh and 1-SePh with
H2O2 were followed in a stopped-flow spectrometer under
pseudo-first-order conditions. Final concentrations of 1.03 ×
-5
tion were similar and fell in the range 9.25 × 10 to 1.20 ×
-4 -1
1
1
0
s , which correspond to second-order rate constants of
-3
-3
-1 -1
.85 × 10 to 2.40 × 10
M
s
at 323 K (Table 1).
-
3
-2
1
0
M chalcogenide and 1.03 × 10 M H2O2 at 276.8 ( 0.4
Nominal increases in the rate of oxidation were observed in
K gave observed rate constants for oxidation of (1.10 ( 0.01)
10
based on the average of 7-10 independent runs, which
the order 1-SePh < 3-SePh < 6-SePh ≈ 12-SePh.
-1
-1
-6 -1
×
s
for 1-TePh and (1.20 ( 0.01) × 10
s
for 1-SePh
Oxidation of the SePh Series with H2O2 in the Two-phase
Mixture CDCl3/pH 6 Buffer. The increases in rate observed
under homogeneous conditions did not account for the den-
drimer effect observed in catalysis for the SePh series. The rates
of oxidation with H2O2 were also measured under pseudo-first-
order conditions in a two-phase system of CDCl3 and 3.4 M
-
1
correspond to second-order rate constants of 10.7 ( 0.1 M
-
1
-4
-1 -1
s
for 1-TePh and (1.2 ( 0.1) × 10
M
s
for 1-SePh in
MeOH. On the basis of these rate constants, oxidation of the
Te atoms of the TePh series under the conditions of Scheme 1
would be g95% complete within 1 s while the half-life for the
oxidation of the Se atoms of the SePh series would be on the
1
H2O2 in pH 6 phosphate buffer using H NMR spectroscopy
3
on aliquots of the reaction mixture over the first 6 × 10 s of
3
order of 5 × 10 s.
reaction. At 296 ( 1 K, pseudo-first-order kinetics were
The data shown in Figure 3 clearly indicate that no induction
period is observed with 3-SePh, 6-SePh, or 12-SePh as catalyst.
Hence, if a selenoxide functionality were the actual catalytic
group in these systems, the lack of an induction period would
suggest that oxidation is much more rapid in the dendrimeric
selenides relative to 1-SePh. Although the lack of dendrimer
solubility in MeOH precluded measurement of the rates of
oxidation under the conditions described above, the oxidations
of 1-SePh, 3-SePh, 6-SePh, and 12-SePh were followed under
homogeneous conditions using tert-butyl hydroperoxide (t-
BuOOH) as oxidant in CDCl3.
-
5
followed and values of kOBS for the oxidation were 2.9 × 10
to 5.3 × 10 s , which correspond to second-order rate
constants of 8.1 × 10 to 1.8 × 10 (Table 1). Again,
the rates of oxidation in the two-phase system of CDCl3 and
.4 M H2O2 in pH 6 phosphate buffer at 298 K in the absence
-
5
-1
-6
-5
-1 -1
M
s
3
of bromide were too slow to accommodate the observed kinetic
4
profile of catalysis with half-lives for oxidation of >10 s for
all four compounds 1-SePh, 3-SePh, 6-SePh, and 12-SePh.
+
Oxidation with H2O2 and Bromide. Br as Oxidant. While
the oxidation of the organotelluride catalysts with H2O2 is rapid
and essentially complete within 1 s for the conditions of reaction
studied here, the oxidation of selenides to selenoxides with H2O2
is too slow to accommodate the observed kinetics for cyclo-
hexene bromination. Furthermore, the dendrimer architecture
did not accelerate the SePh series rate of oxidation with H2O2
(
14) (a) Reich, H. J.; Wollowitz, S.; Trend, J. E.; Chow, F.; Wendelborn, D. F
J. Org. Chem. 1978, 43, 1697. (b) Henriksen, L.; Jakobsen, S. J. Chem.
Soc., Chem. Commun. 2001, 2448-2449.
(15) (a) Detty, M. R.; Friedman, A. E. Organometallics 1994, 13, 533-539.
(
b) Detty, M. R.; Friedman, A. E.; McMillan, M. Organometallics 1994,
1
3, 3338-3345.
12562 J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003

Dendrimeric Organochalcogen Catalysts
or t-BuOOH) to the extent necessary to explain the dendrimer
A R T I C L E S
(
effect observed in catalysis. One is left with the conclusion that
+
the Br species formed in the background reaction must be
responsible for the initial oxidation of the selenide groups to
+
the corresponding selenoxides. Sources of Br (Br2, BrOH)
oxidize Se(II) to Se(IV) with significantly larger second-order
rate constants for oxidation than H2O2.15 The production of Br
in the background reaction is sufficient to oxidize the orga-
noselenides to the corresponding selenoxides.
+
In the uncatalyzed reaction shown in Scheme 1, a combined
3
1
1
.4 mmol of brominated products 1 and 2 was produced from
00 mmol of H2O2 with an observed rate constant of 5.8 ×
-
5
-1
0
s
for production of 1 and 2. All 100 mmol of H2O2 is
2e
-
consumed in this process. In the oxidation of Br with H2O2,
the bulk of the H2O2 is decomposed by the Br that is produced
according to eq 3. The initial concentration of H2O2 is 3 M,
+
1
6
Figure 5. Autocatalytic behavior of the oxidation of 1-SePh, 3-SePh,
6-SePh, and 12-SePh with 3.0 M H2O2 and 2.0 M NaBr in a two-phase
mixture of CDCl3 and pH 6 phosphate buffer at 296 ( 1 K, where ln A )
ln(A∞ - At), where A∞ is the concentration at infinity and At is the
concentration at time t.
+
1
+
Br + H O f HBr + / O + H
(3)
2
2
2
2
-
4
and the initial velocity for consumption of H2O2 is 1.7 × 10
M s based on kCONTR for the background reaction of 5.8 ×
. As discussed above, kCONTR includes the Br
-
1
-
5
-1
-
1
0
s
Reaction of Cyclohexene with NaBr and 3-Se(dO)Ph. In
earlier work, we demonstrated that diorganodihydroxyselenium-
concentration of 2 M, which is assumed to remain essentially
constant during the reaction. However, if only 3.4% of this Br+
is captured by substrate, the “effective” initial velocity for
(IV) and -tellurium(IV) compounds were mechanistically similar
as oxidants, but that the rate constants associated with Se(IV)
species were several orders of magnitude slower than those
+
-6
-1
production of Br is approximately 5.8 × 10 M s .
-
2
For the 2.8 × 10 M 1-SePh used to generate the data of
1
5b,17
associated with Te(IV) species.
We examined the bromi-
Figure 4, the background reaction alone from 3 M H2O2 and 2
nation of cyclohexene with preformed 3-Se(dO)Ph (0.1 M) in
CH2Cl2/pH 6 phosphate buffer containing 2 M NaBr. After 24
h, no bromination products were detected by gas chromatog-
raphy, which indicates that the Se(II)/Se(IV) redox cycle does
not contribute in any significant way to the bromination of
cyclohexene with H2O2 and NaBr. The formation of brominated
products is due to the selenoxide-catalyzed reaction and the
uncatalyzed background reaction.
+
M NaBr would produce enough Br to oxidize all of the selenide
3
in approximately 5 × 10 s. As shown in Figure 4, the rate of
bromination of cyclohexene reaches a maximum at approxi-
3
mately 5 × 10 s, which is consistent with this analysis. The
data of Figure 3 show no induction period for catalysis of the
bromination of cyclohexene with 3-SePh, 6-SePh, or 12-SePh.
-
3
-3
Oxidation of the 2.5 × 10 M 3-SePh (7.5 × 10 M in SePh
-3
-2
groups), 2.5 × 10 M 6-SePh (1.5 × 10 M in SePh groups),
-
4
-3
and 4 × 10 M 12-SePh (4.8 × 10 M in SePh groups) used
Summary and Conclusions
in these reactions with 3.0 M H2O2 and 2.0 M NaBr would
3
3
require between 1 × 10 and 2 × 10 s to generate sufficient
The dendrimeric organoselenides and -tellurides of Chart 1
+
-
Br via the background reaction alone. However, each SePh
catalyze the oxidation of Br with H O by two completely
2
2
group that is oxidized to a Se(dO)Ph group produces a new
catalytic site capable of generating Br from H2O2 and NaBr,
and one might expect the oxidation to be autocatalytic.
The rates of oxidation of 1-SePh, 3-SePh, 6-SePh, and 12-
different mechanisms. The dendrimeric organotellurides are
rapidly oxidized to the corresponding dendrimeric organotel-
luroxides with H O under the conditions of reaction. On the
+
2
2
-
1 -1
basis of the second-order rate constant of 10.7 M
s
for the
SePh in a two-phase mixture of CDCl3 and 3.0 M H2O2 and
oxidation of 1-TePh with H O , the oxidations of 1-TePh,
2
2
1
2
.0 M NaBr in pH 6 phosphate buffer were determined by H
6-TePh, and 12-TePh would all be g95% complete in e1 s!
-
+
NMR spectroscopy at 296 ( 1 K. As shown in Figure 5, the
rate constant for catalysis increases with time for all four systems
and initial rate constants for oxidation increase with the number
of SePh groups. Oxidation was ∼95% complete for 1-SePh,
Subsequent reaction of the telluroxide with Br produces Br
and reduced telluride, which is rapidly reoxidized to continue
the catalytic cycle as shown in Scheme 1 for E ) Te.
In contrast, the dendrimeric organoselenide-catalyzed reac-
tions with H2O2 differ in three significant ways from the
corresponding organotelluride systems: (1) Oxidations with
H2O2 are much slower with half-lives on the order of several
hours. (2) The catalyst in these systems is the selenoxide
oxidation state [Se(IV)] and not the selenide oxidation state [Se-
(II)]. (3) The actual oxidant in the selenide-catalyzed reaction
3
3
3
×
-SePh, 6-SePh, and 12-SePh after 3.6 × 10 , 2.4 × 10 , <6
2
2
10 , and <1.2 × 10 s, respectively. For each of these
reactions, the concentration of SePh groups was held constant
-
2
at approximately 1 × 10 M.
(
16) (a) Bray, W. C.; Livingston, R. S. J. Am. Chem. Soc. 1923, 45, 5, 1251-
1
273. (b) Everett, R. R.; Butler, A. Inorg. Chem. 1989, 28, 393-395. (c)
Everett, R. R.; Soedjak, H. S.; Butler, A. J. Biol. Chem. 1990, 265, 15671-
+
is the Br that is initially generated via the uncatalyzed
1
5679. (d) de la Rosa, R. I.; Clague, M. J.; Butler, A. J. Am. Chem. Soc.
992, 114, 760-761. (e) Espenson, J.; Pestovsky, O.; Huston, P.; Staudt,
1
background reaction and then by selenoxide-catalyzed processes
S. J. Am. Chem. Soc. 1994, 116, 2869-2877. (f) Colpas, G. J.; Hamstra,
B. J.; Kampf, J. W.; Pecoraro, V. L. J. Am. Chem. Soc. 1994, 116, 3627-
3
628. (g) Colpas, G. J.; Hamstra, B. J.; Kampf, J. W.; Pecoraro, V. L. J.
(17) Detty, M. R.; Friedman, A. E.; Oseroff, A. J. Org. Chem. 1994, 59, 8245-
Am. Chem. Soc. 1996, 118, 3469-3478.
8249.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003 12563

A R T I C L E S
Drake et al.
+
increased production of Br . Each sequential oxidation is
+
accelerated due to further increases in the local Br concentra-
tion. The large dendrimer effect observed in the SePh series of
dendrimers in Chart 1 is associated with the rate of in situ
production of the actual catalystsnamely, the oxidation of the
selenide to the corresponding selenoxide.
Since 3-SePh, 6-SePh, and 12-SePh are rapidly oxidized
under the conditions of reaction, values of kCAT starting with
unoxidized selenide or oxidized selenoxide are identical for
3
-Se(dO)Ph/3-SePh, 6-Se(dO)Ph/6-SePh, and 12-Se(dO)-
Ph/12-SePh. In contrast, the oxidation of 1-SePh to 1-Se(dO)-
Ph is relatively slow. We compared values of kCAT for 3-SePh,
6
-SePh, and 12-SePh for the bromination of cyclohexene with
kCAT for 1-Se(dO)Ph to determine whether there was a
dendrimer effect associated with the corresponding selenoxides.
-
2
-2 -1
For 1-Se(dO)Ph, kCAT was 2.1 × 10
M
s . From our
2
e
-2
-2 -1
earlier work, kCAT was 2.8 × 10
M
s
for 3-Se(dO)Ph,
-
1
-2 -1
-2 -1
2
.1 × 10
M
s
for 6-Se(dO)Ph, and 1.08 M
s
for
Figure 6. A cartoon representation for the autocatalytic oxidation of
dendrimeric polyorganoselenides. The large circles enclosing the dendrimers
represent the local environment around the dendrimer (the “dendrimer
sphere”) as opposed to the bulk solution. (A) Br+ diffuses into the dendrimer
12-Se(dO)Ph. In this comparison, the reactivity per catalytic
group increases by a factor of 4 from the monomer 1-Se(dO)-
Ph to 12-Se(dO)Ph, which is more typical of other dendrimer
4
-
effects that have been reported. The apparent increase in
sphere or is generated via reaction of H2O2 and Br that have diffused into
the dendrimer sphere. (B) Oxidation of the first selenide generates a
selenoxide group that begins the catalyzed reaction of H2O2 and Br within
catalytic activity per functional group with increasing numbers
of SePh groups in the 1-Se(dO)Ph, 3-Se(dO)Ph, 6-Se(dO)-
Ph, and 12-Se(dO)Ph series is actually the product of the
differences in the rate of oxidation of selenides to selenoxides
(a factor of roughly 30 due to autocatalysis) as well as a modest
dendrimer effect (a factor of 4) for the bromination of cyclo-
hexene.
-
the dendrimer sphere. The oxidation of the second selenide is accelerated
+
by the higher local concentration of Br , even though it is diffusing into
the bulk solution. (C) The process is repeated with an accelerated rate for
the next oxidation. (D) Oxidation of the final selenide group will have the
+
fastest rate due to the much higher local concentration of Br , even though
it is diffusing into the bulk solution.
Scheme 3
The selenoxide group appears to be a highly reactive catalytic
group for the activation of H2O2 in addition to its known
1
4
catalase-like ability to decompose H2O2. We are currently
examining stereoelectronic effects on the efficiency and reactiv-
ity of selenoxide catalysts, and we are designing polyfunctional,
dendrimeric selenoxides that cannot undergo selenoxide elimi-
nation reactions.
Experimental Section
General Methods. Solvents and reagents were used as received from
Sigma-Aldrich Chemical Co. (St. Louis, MO). NMR spectra were
recorded at 23 °C (unless otherwise noted) on a Varian Gemini-300,
Inova 400, or Inova 500 instrument with residual solvent signal as the
as well. The catalytic cycle for the selenoxide is summarized
in Scheme 3.
As shown in Figure 5, the oxidation of the selenides with
Br+ becomes autocatalytic as the reaction progresses and the
rate of oxidation increases with the number of catalytic groups.
The cartoon of Figure 6 summarizes the process for a poly-
functional dendrimer. Oxidation of the first selenide residue
occurs via diffusion of Br+ into the dendrimer sphere or via
internal standard: CDCl (δ 7.26 for proton, δ 77.16 for carbon).
3
Compounds 1-TePh, 1-SePh, 3-SePh, 6-SePh, and 12-SePh were
prepared according to ref 2e.
General Procedures for the Oxidation of Selenides. A. Prepara-
tion of Selenoxide Catalysts Using NCS. The selenide and N-
chlorosuccinimide (15.0 equiv/SePh group on the catalyst) were stirred
-
the uncatalyzed oxidation of Br with H2O2 within the den-
drimer sphere. The new selenoxide functionality catalyzes the
in 1/1 methanol/CH
h. An equal volume of CH Cl and 1.5 times that volume of 10%
aqueous NaOH were added to the reaction mixture, and the resulting
mixture was stirred for an additional 5 min at ambient temperature.
2 2
Cl (10 mL/mmol of PhSe groups) at 0 °C for 0.5
-
oxidation of more Br with H2O2, which can increase the local
2
2
+
concentration of Br in two different ways. In one, the “point”
+
production of Br at the catalytic site creates a concentration
The organic layer was removed, dried with Na
to yield the selenoxide, which was used without further purification.
B. Preparation of Selenoxide Catalysts Using H and NaBr.
Sodium bromide (0.412 g, 4.0 mmol, 2.0 M), 30% H (1.0 mL), pH
.0 phosphate buffer (0.23 M, 1.0 mL), and 0.8 mL of a CDCl stock
2 4
SO , and concentrated
+
gradient of Br as it diffuses into the bulk solution. While the
initial oxidation of a variety of organoselenides is rapid (kOX of
2
O
2
5
6
-1 -1 15
1
0 -10 M s ), it is still slow relative to diffusion. In the
2 2
O
second, the microenvironment of the dendrimer may “hold” the
6
3
+
Br within the dendrimer sphere by providing a more favorable
solution (∼10 mg/mL) of selenide were combined and stirred at room
+
medium for Br through a combination of polar interactions
and/or π-interactions.3
c,18
(18) (a) Hawker, C. J.; Wooley, K. L.; Fr e´ chet, J. M. J. J. Am. Chem. Soc.
1
993, 115, 4375-4376. (b) B a¨ hr, A.; Felber, B.; Schneider, K.; Diederich,
After formation of the first selenoxide group in the dendrimer,
oxidation of the next SePh group is accelerated due to the
F. HelV. Chim. Acta 2000, 83, 1346-1377. (c) Davis, A. V.; Driffield,
M.; Smith, D. K. Org. Lett. 2001, 3, 3075-3078.
12564 J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003

Dendrimeric Organochalcogen Catalysts
A R T I C L E S
temperature for 10 min (6-SePh and 12-SePh) or 100 min (1-SePh
and 3-SePh). The CDCl layer was removed and placed into an NMR
3
oxidation of 1-SePh (0.209 g, 0.72 mmol) with NCS was followed to
give 1-Se(dO)Ph (0.220 g, 0.72 mmol). The general procedure for
tube with no further purification.
2 2
the kinetic analysis of catalyzed reactions of H O and bromide in pH
Data for 1-Se(dO)Ph: 1H NMR (500 MHz, CDCl
) δ 7.72 (d·d, 2
6.0 phosphate buffer was followed using 1-Se(dO)Ph (0.220 g, 0.72
mmol) as the catalyst. The infinity point was obtained by allowing the
reaction to stir at room temperature for 24 h, followed by GC analysis
of the organic layer for the amounts of brominated products 1 and 2
present.
3
H, J ) 1.5, 8.0 Hz), 7.48-7.53 (m, 3 H), 7.26 (t, 2 H, J ) 8.0 Hz),
.94 (t, 1 H, J ) 7.5 Hz), 6.84 (d, 2 H, J ) 8.5 Hz), 3.98-4.05 (m, 2
H), 3.03-3.08 (m, 1 H), 2.93-2.98 (m, 1 H), 2.24-2.32 (m, 1 H),
6
80
+
2
.00-2.08 (m, 1 H); ESMS m/z 309 (C15
for C15 Se: C, 58.64; H, 5.25. Found: C, 59.04; H, 5.52.
Data for 3-Se(dO)Ph: 1H NMR (500 MHz, CDCl
) δ 7.71 (d·d, 6
H, J ) 1.5, 8.0 Hz), 7.48-7.53 (m, 9 H), 6.94 (d, 6 H, J ) 8.5 Hz),
16 2
H O Se + H ). Anal. Calcd
H O
16 2
A plot of ln(A
products 1 and 2 at infinity and A
∞
- A
t
), where A
∞
is the concentration of brominated
t
is the concentration of brominated
3
products 1 and 2 at time t, as a function of time is linear with the slope
defined as -kOBS. The values in Table 1 are the average of triplicate
runs (( standard deviation).
Procedure for the Kinetic Analysis of the One-Phase Oxidation
of Selenium Catalysts with tert-Butyl Hydroperoxide. Deuteriochlo-
roform (0.8 mL), tert-butyl hydroperoxide (0.100 mL, 5.0 M in decane,
0.5 mmol, 0.55 M), and a selenide [1-SePh (0.0082 g, 0.028 mmol,
6
2
.72 (d, 6 H, J ) 9.0 Hz), 3.95-4.02 (m, 6 H), 3.01-3.06 (m, 3 H),
.92-2.97 (m, 3 H), 2.22-2.30 (m, 3 H), 2.06 (s, 3 H), 1.99-2.04
8
0
+
(
m, 3 H); ESMS m/z 949 (C47
Data for 6-Se(dO)Ph: 1H NMR (500 MHz, CDCl
2 H, J ) 1.5, 8.0 Hz), 7.46-7.52 (m, 18 H), 6.97 (d, 6 H, J ) 9.0
H
48
O
6
Se
3
+ H ).
3
) δ 7.70 (d·d,
1
Hz), 6.81 (d, 6 H, J ) 9.0 Hz), 6.52 (d, 6 H, J ) 2.0 Hz), 6.30 (s, 3
H), 4.90 (s, 6 H), 3.95-4.02 (m, 12 H), 3.01-3.06 (m, 6 H), 2.89-
-
2
-2
3.5 × 10 M), 3-SePh (0.0084 g, 0.0093 mmol, 1.2 × 10 M), 6-SePh
-3
2
.95 (m, 6 H), 2.23-2.31 (m, 6 H), 2.07 (s, 3 H), 1.98-2.05 (m, 6 H);
(0.0087 g, 0.0047 mmol, 5.8 × 10 M), or 12-SePh (0.0088 g, 0.0023
8
0
+
-3
ESMS m/z 1957 (C95
H
96
O
15 Se
6
+ H ).
mmol, 2.9 × 10 M)] were placed in an NMR tube. The temperature
1
1
Data for 12-Se(dO)Ph: H NMR (500 MHz, CDCl
3
) δ 7.69 (d,
of the NMR probe was set to 323.0 K, and H NMR spectra were taken
2
6
4
4 H, J ) 6.5 Hz), 7.45-7.50 (m, 36 H), 6.97 (d, 6 H, J ) 8.5 Hz),
.83 (d, 6 H, J ) 8.5 Hz), 6.65 (s, 6 H), 6.51 (s, 15 H), 6.30 (s, 6 H),
.92 (s, 6 H), 4.91 (s, 12 H), 3.94-4.01 (m, 24 H), 2.99-3.05 (m, 12
every 5 min for 110 min. Oxidation of the selenium catalysts was the
rate-determining step in the process and was slow relative to selenoxide
elimination. Therefore, the rate of the appearance of the olefinic allyloxy
protons was identical to the rate of oxidation. The appearance of signals
(500 MHz) at δ 6.02 (ddt, 1 H, J ) 5.0, 10.5, 16, 1H), 5.38 (dq, 1 H,
J ) 1.5, 17.5 Hz), and 5.25 (dq, 1 H, J ) 1.5, 10.5 Hz) was monitored
as a function of time. The allylic protons appeared at δ 4.50 (dt, J )
1.5, 5.5 Hz). For 3-Se(dO)Ph, 6-Se(dO)Ph, and 12-Se(dO)Ph, the
aromatic protons of the 1,1,1-tris(4-hydroxyphenyl)ethyl core (500
MHz, δ 6.97 (d, 6 H, J ) 8.5 Hz), 6.83 (d, 6 H, J ) 8.5 Hz) were used
as an internal standard for integration. For 1-Se(dO)Ph, the three para
and meta protons of the Se(dO)Ph ring and the five protons of the
phenoxy ring [7.48-7.53 (m, 3 H), 7.26 (t, 2 H, J ) 8.0 Hz), 6.94 (t,
1 H, J ) 7.5 Hz), 6.84 (d, 2 H, J ) 8.5 Hz)] were used as an eight-
H), 2.88-2.93 (m, 12 H), 2.23-2.29 (m, 12 H), 2.08 (s, 3 H), 1.98-
2
.03 (m, 12 H); no parent ion observed by mass spectrometry.
The oxidized selenides were difficult to characterize due to mixtures
of diastereomers (for 3-Se(dO)Ph, 6-Se(dO)Ph, and 12-Se(dO)Ph)
and elimination reactions. A sample of the oxidized material in CH
Cl (100 mg in 10 mL) was shaken with two 10 mL aliquots of 5%
aqueous sodium bisulfite to reduce the selenoxide groups to selenide
groups. The organic phase was dried over Na SO and concentrated to
give 1-SePh, 3-SePh, 6-SePh, and 12-SePh, respectively, which were
identical to authentic materials.
General Procedure for the Kinetic Analysis of the Bromination
of Cyclohexene with 3.0 M H and 2.0 M NaBr in pH 6.0
2
-
2
2
4
2
e
2
O
2
proton internal integration standard. A plot of ln(INT
∞
- INT
t
), where
Phosphate Buffer. Sodium bromide (6.63 g, 0.064 mmol) was added
to a stirred (constant-rate, overhead stirrer at 50 rpm with a 2.0 in. stir
blade), two-phase mixture of seleninic acid (9.1 mg, 0.048 mmol, 2.3
INT is the integral of the olefinc protons at infinity and INT
∞
t
is the
integral of the olefinic protons at time t, as a function of time is linear
with the slope defined as -kOX(t-BuOOH). The values in Table 1 are
the average of duplicate runs.
-
3
×
10 M), selenide or selenoxide catalyst (except in control reactions
where no selenide was added), cyclohexene (4.10 g, 0.050 mmol), and
diphenyl ether (20 mg, 1 mg/mL, inert to reaction conditions) in 20
Procedure for the Kinetic Analysis of the Two-Phase Oxidation
of Selenium Catalysts with H
30% H (6.25 mL, 55 mmol, 3.4 M), pH 6.0 phosphate buffer (10
mL), NaBr, if used (3.32 g, 32 mmol, 2.0 M), and 1-SePh (0.015 g,
2 2
O . Deuterated chloroform (10 mL),
mL of CH
buffer (0.23 M) and 12.5 mL of 30% H
2
Cl
2
and an aqueous phase of 20 mL of pH 6.0 phosphate
(110 mmol) in a constant-
2 2
O
2
O
2
-
3
temperature bath at 298.0 ( 0.1 K. Aliquots (<1 mL) were withdrawn
at the appropriate time, placed in a glass culture tube (13 × 100 mm),
0.052 mmol, 5.2 × 10 M), 3-SePh (0.037 g, 0.041 mmol, 4.1 ×
-
3
-
3
10 M), 6-SePh (0.035 g, 0.019 mmol, 1.9 × 10 M), or 12-SePh
-
4
and frozen in a CO
2
/acetone bath. The samples were thawed, and the
(0.037 g, 0.0097 mmol, 9.7 × 10 M) were combined and stirred at
organic layer was analyzed by gas chromatography. The rate of
appearance of brominated products 1 and 2 was compared to that of
the internal standard, diphenyl ether. Infinity points for the pseudo-
first-order kinetics (constant bromide concentration of 2.0 M) were
determined at 48 h for each kinetic run.
296 K for 100 min, or until oxidation was complete. Aliquots of the
CDCl
3
3
phase (<0.5 mL) were placed in an NMR tube, and CDCl was
added to give a volume of 1.0 mL. Samples were then placed in a
1
2
CO /acetone bath until H NMR spectra were acquired. The percentage
of oxidation was determined by integration of the ortho protons of Se-
(dO)Ph [500 MHz δ 7.70 (dd, J ) 1.5, 8.0 Hz)] vs the 12 aromatic
protons of the 1,1,1-tris(4-hydroxyphenyl)ethyl core (500 MHz, δ 6.97
(d, 6 H, J ) 8.5 Hz), 6.83 (d, 6 H, J ) 8.5 Hz) for 3-SePh, 6-SePh,
and 12-SePh, or, for 1-SePh, the 3 para and meta protons of the Se-
(dO)Ph ring and the 5 protons of the phenoxy ring [7.48-7.53 (m, 3
H), 7.26 (t, 2 H, J ) 8.0 Hz), 6.94 (t, 1 H, J ) 7.5 Hz), 6.84 (d, 2 H,
J ) 8.5 Hz)].
A plot of ln(A
products 1 and 2 at infinity and A
∞
- A
t
), where A
∞
is the concentration of brominated
is the concentration of brominated
t
products 1 and 2 at time t, as a function of time is linear with the slope
defined as -kOBS. The values in Table 1 are the average of triplicate
runs (( standard deviation).
Kinetic Analysis of the 1-SePh-Catalyzed Reaction of H
2 2
O and
Bromide in pH 6.0 Phosphate Buffer. The general procedure was
-
2
followed using 1-SePh (0.201 g, 0.69 mmol, 2.8 × 10 M) as the
catalyst. Aliquots were withdrawn over 4 h. The infinity point was
obtained by allowing the reaction to stir at room temperature for 24 h,
followed by GC analysis of the organic layer for the amounts of 1 and
An infinity point was taken after 24 h at 323 K. A plot of ln(INT
- INT ), where INT is the integral of the olefinic protons at infinity
and INT is the integral of the olefinic protons at time t, as a function
∞
t
∞
t
2 2
of time is linear with the slope defined as -kOX(H O ). The values in
2
present relative to diphenyl ether.
Table 1 are the average of duplicate runs.
Kinetic Analysis of the 1-Se(dO)Ph-Catalyzed Reaction of H
O
2 2
Procedure for Determining the Rate of Elimination of Phenyl-
and Bromide in pH 6.0 Phosphate Buffer. The general method for
selenenic Acid from Selenoxide Catalysts. The selenoxide catalyst
J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003 12565

A R T I C L E S
Drake et al.
was prepared by either of the oxidation procedures described above,
compartment, which allowed for variable-temperature experimentation.
The optical detection cell was set up in the 2 mm path length. First-
and second-order curve fitting and rate constants used a Marquardt
algorithm19 based on the routine Curfit.
3
taken up in CDCl , and placed in a capped NMR tube. The temperature
1
of the NMR probe was set to 323 K, and a H NMR spectrum was
taken every 5 min for 110 min. The appearance of the olefinic allyloxy
protons (500 MHz) at δ 6.02 (ddt, 1 H, J ) 5.0, 10.5, 16 Hz, 1H),
20
-
3
Oxidation of 1-TePh and 1-SePh. Stock solutions of 2.06 × 10
M 1-TePh or 1-SePh and 2.06 × 10 M H in MeOH were
prepared. These two solutions were mixed in the stopped-flow
-
2
5
.38 (dq, 1 H, J ) 1.5, 17.5 Hz), and 5.25 (dq, 1 H, J ) 1.5, 10.5 Hz)
2 2
O
was monitored as a function of time. The allylic protons appeared as
a new signal at δ 4.50 (dt, J ) 1.5, 5.5 Hz). For 3-Se(dO)Ph, 6-Se-
-
3
spectrometer to give concentrations of 1.03 × 10 M telluride and
1.03 × 10 M H , and the increase in absorbance at 352 nm for
1-TePh or 1-SePh was measured as a function of time for 7-10
independent runs (( standard deviation). A plot of ln(A - A ), where
is the concentration of 1-Te(dO)Ph or 1-Se(dO)Ph at infinity and
is the concentration of 1-Te(dO)Ph or 1-Se(dO)Ph at time t, as a
-
2
(
dO)Ph, and 12-Se(dO)Ph, the aromatic protons of the 1,1,1-tris(4-
hydroxyphenyl)ethyl core (500 MHz, δ 6.97 (d, 6 H, J ) 8.5 Hz),
.83 (d, 6 H, J ) 8.5 Hz) were used as an internal standard for
integration. For 1-Se(dO)Ph, the entire aromatic region (500 MHz, δ
2 2
O
6
∞
t
A
A
∞
7
.72-6.83) was used as a 10-proton internal integration standard.
t
An infinity point was taken after 24 h at 323 K. A plot of ln(INT
∞
function of time is linear with the slope defined as -kOBS. The second-
order rate constant, kOX(H ) was calculated by dividing kOBS by the
concentration (1.03 × 10 M).
-
INT
and INT
of time is linear with the slope defined as -kELIM. The values in Table
t
), where INT
∞
is the integral of the olefinic protons at infinity
2 2
O
-
2
t
is the integral of the olefinic protons at time t, as a function
2 2
H O
Acknowledgment. We thank the Office of Naval Research
N00014021-0836), the National Science Foundation (CHE-
1
are the average of duplicate runs.
Procedure for the Attempted Bromination of Cyclohexene with
-Se(dO)Ph and NaBr. Oxidation of 3-SePh (0.45 g, 0.50 mmol)
(
3
0108521), and the Petroleum Research Fund, administered by
the American Chemical Society, for grants in support of this
work.
with N-chlorosuccinimide (2.315 g, 17.3 mmol, 45.0 equiv) in 30 mL
of 1/1 CH OH/CH Cl according to the procedure described above gave
-Se(dO)Ph (0.45 g, 0.48 mmol, 96%). Cyclohexene (0.21 mL, 2.0
3
2
2
3
1
Supporting Information Available: H NMR and mass
mmol), 3-Se(dO)Ph (0.45 g, 0.48 mmol), and NaBr (1.05 g, 10.2
mmol, 2 M) in a two-phase mixture of pH 6.0 phosphate buffer (5
1
spectra for 1-Se(dO)Ph, 3-Se(dO)Ph, and 6-Se(dO)Ph, H
1
mL) and CH
2
Cl
2
(5 mL) were stirred at room temperature for 24 h.
NMR spectrum for 12-Se(dO)Ph, and typical H NMR traces
The organic phase was analyzed for trans-1,2-dibromocyclohexane (1)
and trans-2-bromocyclohexanol (2) both by H NMR and by gas
for selenoxide elimination. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
chromatography. Neither 1 nor 2 was detected by either method.
Stopped-Flow Experiments. All stopped-flow experiments were
performed on an SX18 stopped-flow spectrometer (Applied Photo-
physics, Leatherhead, U.K.). The sample-handling unit was fitted with
two drive syringes that are mounted inside a thermostated bath
JA0367593
(
19) Marquardt, D. W. J. Soc. Ind. Appl. Math. 1963, 11, 431.
20) Curfit is found in Bevington, P. R. Data Reduction and Error Analysis for
the Physical Sciences; McGraw-Hill: New York, 1969.
(
12566 J. AM. CHEM. SOC.
9
VOL. 125, NO. 41, 2003