Debrominations of vic-Dibromides with Diorganotellurides. 2. Catalytic Processes in Diorganotelluride

Full text of DOI:10.1021/jo971504r

J . Org. Chem. 1998, 63, 177-180
177
Notes
Sch em e 1
Debr om in a tion s of vic-Dibr om id es w ith
Dior ga n otellu r id es. 2. Ca ta lytic P r ocesses
in Dior ga n otellu r id e
Timothy S. Butcher and Michael R. Detty*
Department of Medicinal Chemistry, School of Pharmacy,
SUNY at Buffalo, Amherst, New York 14260, and
Department of Chemistry, SUNY at Buffalo,
Amherst, New York 14260
Sch em e 2
Received August 13, 1997
The protection/deprotection of olefins via bromination/
debromination has been explored with a variety of
different debrominating agents.1-6 The utility of such
methods is dependent upon the selectivity of the process
toward vic-dibromides with different substituent patterns
and upon other functionality in the substrates being inert
to the conditions of debromination.
Several classes of organotellurium reagents have been
utilized for debromination reactions4-6 and catalytic
variations have been developed for several.5,6 The method
of Engman5 utilizing sodium 2-thienyl telluride is per-
haps the most practical. As shown in Scheme 1, the
Engman process uses sodium borohydride to reduce di-
2-thienyl ditelluride to sodium 2-thienyl telluride. While
most vic-dibromides are converted to olefins with this
process, the method is limited to vic-dibromides with
functional groups that do not react with sodium borohy-
dride.
Diorganotellurides have also been useful as reagents
for the debromination of vic-dibromides giving olefin and
Te(IV) dibromide as shown in Scheme 2.4a,b,f,6 Diorga-
notellurides, while nucleophilic, are unreactive toward
most organic functionality. In the preceding paper, we
have shown that stoichiometric variants of Scheme 2
have dibromide reactivities that parallel bromonium ion
stabilities.4f The stoichiometric reactions are also limited
by the reversibility of the process, which gives mixtures
of both vic-dibromide and olefin.4f A catalytic version of
Scheme 2 has been described by Suzuki, Kondo, and
Osuka in which 5 mol % of (p-CH3OC6H4)2Te can be
recycled in the reaction using bisulfite as the reducing
agent.6 This variation of the reaction was reported to
work only with substrates with at least one benzylic
bromide (or heterocyclic equivalent). In this paper, we
describe modifications to the procedure of Suzuki, Kondo,
and Osuka,6 which are more general for vic-dibromides.
Resu lts a n d Discu ssion
A. Ca ta lysis w ith Dior ga n otellu r id es. Catalytic
reactions related to Scheme 2 are bound by certain
constraints. The diorganotelluride catalyst, the vic-
dihalide, and the olefinic substrate must be unreactive
toward the reducing agent. The kinetics of the dehalo-
genation with a catalytic amount of diorganotelluride
should be sufficiently rapid to give product in a syntheti-
cally useful time frame. The substrate, catalyst, and
product should be stable to the thermal conditions of the
reaction as well as to the solvents used. Finally, reduc-
tion of the Te(IV) compound should be rapid and should
regenerate the diorganotelluride as the only product of
reduction.
(1) With iodide: (a) Plattner, P. A.; Heusser, H.; Segre, Helv. Chim.
Acta 1948, 31, 249-255. (b) Solo, A. J .; Singh, B. J . Org. Chem. 1965,
30, 1658-1659. (c) Landini, D. Synthesis 1975, 397-399.
(2) With Na2S: (a) Landini, D. J . Org. Chem. 1984, 49, 152-153.
(b) Nakayama, J .; Machida, H.; Hoshino, M. Tetrahedron Lett. 1983,
3001-3004.
(3) With zinc and magnesium: Baciocchi, E. In Chemistry of
Functional Groups, Supplement D, Part 1; Patai, S., Rappoport, H.,
Eds.; Wiley: New York, 1983.
(4) With tellurium reagents: (a) Campos, M. d. M.; Petragnani, N.;
Thome´, C. Tetrahedron Lett. 1960, (15) 5-8. (b) Campos, M. M.;
Petragnani, N. Chem. Ber. 1961, 94, 1759-1762. (c) Ramasamy, K.;
Kalyanasundarani, S. K.; Shammugan, P. Synthesis 1978, 311-312.
(d) Suzuki, H.; Inouye, M. Chem. Lett. 1985, 225-228. (e) Huang, X.;
Hou, Yu Q. Synth. Commun. 1988, 18, 2201-2205. (f) Butcher, T. S.;
Zhou, F.; Detty, M. R. J . Org. Chem. 1997, 63, 167-174. D. N.
Tetrahedron Lett. 1990, 31, 6291-6294. (h) Barton, D. H. R.; McCom-
bie, S. W. J . Chem. Soc., Perkin Trans. 1 1975, 1574-1578. (i) Barton,
D. H. R.; Bohe, L.; Lusinchi, X. Tetrahedron Lett. 1987, 28, 6609-
6612. (j) Desilva, K. G. K.; Monsef-Mirzai, Z.; McWhinnie, W. R. J .
Chem. Soc., Dalton Trans. 1983, 2143-2146.
Selection of Ca ta lysts. The procedure developed by
Suzuki, Kondo, and Osuka utilized (p-CH3OC6H4)2Te as
the catalyst for debromination reactions.6 This catalyst
only worked with vic-dibromides with at least one ben-
zylic bromide (or heterocyclic equivalent). We have found
that the more electron-rich diorganotellurides 1-3 are
better debrominating agents than (p-CH3OC6H4)2Te in
stoichiometric reactions.4f Tellurides 1-3 debrominate
vic-dibromides to give olefins and the Te(IV) dibromides
4-6, respectively.4f
(5) Engman, L. Tetrahedron Lett. 1982, 23, 3601-3602.
(6) Suzuki, H.; Kondo, A.; Osuka, A. Bull. Chem. Soc. J pn. 1985,
58, 1335-1336.
S0022-3263(97)01504-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/09/1998

178 J . Org. Chem., Vol. 63, No. 1, 1998
Notes
Ta ble 1. Ca ta lytic Debr om in a tion s w ith
Dior ga n otellu r id es
Selection of Red u cin g Agen ts. Several mild pro-
cedures have been reported for the reduction of Te(IV)
compounds to Te(II) derivatives.6-10 In the one reported
catalytic variation of Scheme 2, sodium bisulfite was used
to reduce (p-CH3OC6H4)2TeBr2 to (p-CH3OC6H4)2Te.6
Telluroxides and Te(IV) dihalides have been reduced to
tellurides by aromatic and aliphatic thiols, which in turn
were oxidized to disulfides.9,10 Sodium ascorbate has
been utilized for the reduction of diorganotellurium(IV)
dihalides to diorganotellurides under very mild condi-
tions.11 Most organic functional groups are unreactive
toward bisulfite, thiols, and ascorbate.
The reactivity of organic functional groups toward the
reducing agents can be further diminished by separating
the organic substrates from the reducing agent in two-
phase systems. Sodium bisulfite in aqueous benzene
gave at least 20 turnovers of (p-CH3OC6H4)2Te in reactive
substrates.6 A catalytic, two-phase system using 1,2-
dibromotetrachloroethane as a brominating agent of
Te(II) has been described in which telluroxides produced
in situ are the working oxidant for the oxidation of
various organic substrates.9b At alkaline pH, the Te(IV)
dibromides were hydrolyzed to the corresponding tel-
luroxide. Telluroxides are more water-soluble than the
corresponding Te(IV) dibromides and Te(II) diorgano-
tellurides.10d,12 Hydrolysis of the Te(IV) dibromides of
Scheme 2 to the corresponding telluroxides should allow
reduction of the Te(IV) dibromides to occur in the aqueous
phase. The Te(IV) reducing agents sodium bisulfite,
sodium ascorbate, and the thiol glutathione (GSH) are
water soluble and should be useful in two-phase systems.
We examined sodium bisulfite as a reducing agent for
4-6 (prepared by oxidative addition of bromine to the
tellurides) but found its selectivity to be somewhat
unfavorable. Although Te(IV) derivatives 4-6 are readily
reduced to tellurides 1-3 with sodium bisulfite, heating
1-3 with 1.0 M aqueous sodium bisulfite (required for
the slower reacting substrates) as a refluxing, two-phase
mixture with CHCl3 gave detelluration. A suspension
of tellurium metal was produced from all three tellurides
upon heating with 1.0 M aqueous sodium bisulfite (≈ 3
ous phase at pH 8.9, reduction of 4-6 with either GSH
or sodium ascorbate was faster than reduction at pH 6.0
or at pH 7.0.
Tellurides 1-3 were stable to either GSH or sodium
ascorbate (initial 3-fold molar excess at 0.45 M in buffer)
in a refluxing, two-phase system of CHCl3 and 0.25 M
phosphate buffer at pH 8.9. The corresponding Te(IV)
bromides 4-6 were reduced under these same conditions
to give the tellurides 1-3, quantitatively.
1
Ca ta lytic Debr om in a tion s. Two-phase mixtures of
telluride and erythro-1,2-dibromo-1,2-diphenylethane in
CHCl3 with 3 equiv of either GSH or sodium ascorbate
in 0.25 M phosphate buffer at pH 8.9 gave nearly
quantitative conversion to trans-stilbene (g98% stereo-
h), and the H NMR signals associated with 1-3 disap-
peared with time. Similar reactions with (p-CH3OC6H4)2-
Te gave tellurium metal in a much slower reaction (no
tellurium observed after 24 h in refluxing 1.0 M aqueous
sodium bisulfite/CHCl3).
The use of 1.0 M GSH or sodium ascorbate did not give
observable levels of detelluration of 1-3 in two-phase
mixtures with CHCl3. The Te(IV) dibromides 4-6 were
reduced quantitatively under these conditions. However,
the rate of reduction of 4-6 was influenced by the pH of
the aqueous layer. In two-phase systems with an aque-
1
selectivity by H NMR) after 250 h at ambient temper-
ature (entry 1, Table 1). The diorganotelluride was used
in catalytic amounts (0.1 equiv for 1 and 3, 0.25 equiv
for 2) and was readily separated from the olefin via
chromatography on silica gel. Importantly, control reac-
tions showed no olefin products in the absence of tel-
luride.
This procedure was applied to the other vic-dihalides
of Table 1. The debromination reactions generated the
corresponding mono-, di-, and trisubstituted olefins,
which were stable to the catalysts 1-3 as well as to the
reducing agents (either GSH or sodium ascorbate) in
refluxing buffer/CHCl3 mixtures. For precursors to 1,2-
disubstituted olefins, the erythro-dibromides gave the
corresponding trans-olefins in g98% stereoselectivity
while threo-dibromides gave cis-olefins in g98% stereo-
selectivity. The vic-dibromides were stable to the condi-
tions of reaction in the absence of telluride catalyst.
Unlike reactions with (p-CH3OC6H4)2Te, catalysts 1-3
slowly gave monosubstituted olefins from 1,2-dibromoal-
(7) Engman, L.; Persson, J .; Andersson, C. M.; Berglund, M. J .
Chem. Soc., Perkin Trans. 2 1992, 1309-1314.
(8) (a) Petragnani, N.; Comasseto, J . V. Synthesis 1991, 793-817
and 897-919. (b) Irgolic, K. J . In Houben-Weyl Methoden der Orga-
nischen Chemie: Organotellurium Chemistry; Klamann, D., Ed.; Georg
Thieme: New York, 1990; Vol. E12b.
(9) (a) Barton, D. H. R.; Finet, J .-P.; Giannotti, C.; Thomas, M.
Tetrahedron Lett. 1988, 29, 2671-2674. (b) Ley, S. V.; Meerholz, C.
A.; Barton, D. H. R. Tetrahedron 1981, 37, Suppl. No. 1, 213-223.
(10) (a) Detty, M. R. Phosphorus Sulfur Silicon 1992, 4, 367-375.
(b) Detty, M. R.; Gibson, S. L. Organometallics 1992, 11, 2147-2155.
(c) Engman, L.; Stern, D.; Pelcman, M. J . Org. Chem. 1994, 59, 1973-
1979. (d) Detty, M. R.; Friedman, A. E.; Oseroff, A. R. J . Org. Chem.
1994, 59, 8245-8250.
(11) Engman, L.; Persson, J . Synth. Commun. 1993, 23, 445-448.
(12) Detty, M. R.; Zhou, F.; Friedman, A. E. J . Am. Chem. Soc. 1996,
118, 313-318.

Notes
J . Org. Chem., Vol. 63, No. 1, 1998 179
stereoselectivity by 1H NMR. Although iodide alone
initiates debromination reactions,1 synergy was apparent
with combinations of telluride and iodide (entries 5 and
6, method C, Table 1).
Sch em e 3
The synergy between iodide and telluride for debro-
minations of threo-dibromides was not observed with
other substrates. Debrominations of 1,2-dibromodecane
and threo-5,6-dibromodecane with 1 equiv of Bu4NI1c
were not accelerated by the addition of 0.25 equiv of 1.
Cyclic tr a n s-Dibr om id es. The cyclic dibromides
trans-1,2-dibromocyclohexane and trans-1,2-dibromocy-
cloheptane gave no debromination with 0.25 equiv of 1-3
and 3 equiv of GSH or sodium ascorbate after 300 h in
refluxing buffer/CHCl3. These results parallel those
observed in stoichiometric reactions with 1 and 2.4a,f
kanes and internal disubstituted olefins from erythro-
and threo-dibromides.
Com p etition Exp er im en ts. To establish relative
rates of reaction for various dibromide substrates, we set
up competition experiments between pairs of dibromides
(0.10 M) and catalytic quantities of telluride 2 (0.025 M)
in CDCl3 and GSH (0.30 M) in phosphate buffer at pH
8.9 The ratio of olefinic products was measured after 1
half-life for the more reactive component. Competition
between 1,2-dibromo-2-methyl-1-phenylpropane and 2,3-
dibromo-2-methylpentane gave 2-methyl-1-phenylpro-
pene and 2-methyl-2-pentene, respectively, in an 82:18
ratio after 5 h. Competition between 1,2-dibromo-2-
methyl-1-phenylpropane and erythro-1,2-dibromo-1-phen-
ylpropane gave 2-methyl-1-phenylpropene and trans-1-
phenylpropene, respectively, in a 52:48 ratio after 5 h.
Competition between 2,3-dibromo-2-methylpentane and
erythro-5,6-dibromodecane gave 2-methyl-2-pentene and
trans-5-decene in an 83:17 ratio after 21 h. Competition
between erythro-5,6-dibromodecane and 1,2-dibromode-
cane gave trans-5-decene and 1-decene, respectively, in
a 87:13 ratio after 88.5 h while competition between 1,2-
dibromodecane and threo-2,3-dibromopentane gave
1-decene and cis-2-pentene, respectively, in a 67:33 ratio.
Nearly identical results were obtained using sodium
ascorbate as reducing agent. On the basis of these
results, the relative rates of reaction, which were similar
to relative rates observed in stoichiometric reactions,4f
were
Su m m a r y a n d Con clu sion s
We have described more efficient diorganotelluride
catalysts for the conversion of vic-dibromides to the
corresponding olefins. These catalysts, which are more
electron rich than (p-CH3OC6H4)2Te, provide terminal
olefins and cis- and trans-1,2-disubstituted olefins from
appropriate precursors (although these reactions are
slow). Sodium ascorbate and GSH are efficient reducing
agents for the Te(IV) derivatives produced in the catalytic
reaction. The catalytic reaction is similar to the stoichio-
metric reaction with respect to substrate reactivities,
which follow bromonium ion stabilities. Of the acyclic
derivatives, threo-2,3-dibromopentane and threo-2,3-di-
bromo-4-methylpentane were the slowest reacting sub-
strates (perhaps due to eclipsing interactions in a bro-
monium ion4f intermediate). A combination of iodide
catalysis and diorganotelluride scavenging of free halogen
intermediates accelerated the debromination of these
substrates to give the corresponding cis-olefins with high
stereoselectivity.
Exp er im en ta l Section
Gen er a l Meth od s. Solvents (ethyl acetate, hexanes, chlo-
roform, dichloromethane), deuteriochloroform, magnesium sul-
fate, trans-stilbene, trans-1-phenylpropene, 1-decene, trans-5-
decene, cis-2-pentene, cis-4-methyl-2-pentene, 2-methyl-1-phenyl-
propene, 2-methyl-2-pentene, and mono- and dibasic salts of
potassium phosphate were used as received from Aldrich
Chemical Co. Catalyst 1 and dibromide 4 were prepared
according to ref 7. Catalyst 3 and Te(IV) derivative 6 were
prepared according to ref 13. Catalyst 2 and Te(IV) dibromide
5 were prepared according to ref 4f. The dibromide substrates
were prepared from the corresponding olefins according to ref
4f. Preparative reactions were stirred magnetically. Concentra-
tion in vacuo was performed on a Bu¨chi rotary evaporator.
Nuclear magnetic resonance (NMR) spectra were recorded at
30.0 °C on a Varian Gemini-300 instrument with residual
solvent signal as internal standard: CDCl3 (δ 7.26 for proton, δ
77.0 for carbon).
Gen er a l P r oced u r e for Ca ta lytic Debr om in a tion s of vic-
Dibr om id es. Initial reactions on a smaller scale were moni-
tored by 1H NMR prior to larger scale preparative runs. The
substrate (0.2 mmol) and the catalyst [for 1, 18 mg (0.050 mmol)
or 7.4 mg (0.020 mmol); for 2, 15 mg (0.050 mmol); for 3, 16 mg
(0.050 mmol) or 6.5 mg (0.020 mmol)] in 2 mL of CDCl3 (0.1 M
in substrate) were combined with the reducing agent [GSH
(0.184 g, 0.60 mmol) or sodium ascorbate (0.12 g, 0.60 mmol)]
in 2 mL of 0.25 M potassium phosphate buffer (pH 8.9). The
reaction mixtures were sealed in vials and were stirred at
ambient temperature or in an oil bath at 80 °C (See Table 1 for
Debr om in a tion of th r eo-Dibr om id es. Debromina-
tions of threo-2,3-dibromopentane and threo-2,3-dibromo-
4-methylpentane (entries 5 and 6, respectively, Table 1)
with catalytic or stoichiometric4f quantities of either 1
or 2 were slow in refluxing CHCl3/buffer mixtures.
Similar substrates are slow using iodide as a catalyst for
debrominations.1c Presumably, iodide reacts with the
dibromide to give IBr2 and species in equilibrium with
IBr2.
If debrominations with iodide were reversible, then
reactions might be accelerated by using the diorganotel-
luride as a scavenger of the IBr or Br2 produced in the
reaction as shown in Scheme 3. Reactions of threo-2,3-
dibromopentane and threo-2,3-dibromo-4-methylpentane
with telluride 1 were accelerated by the addition of 1
equiv of Bu4NI to the reaction mixtures. Debrominations
were complete under these conditions giving cis-2-pen-
tene and cis-4-methyl-2-pentene, respectively, with g98%
(13) Detty, M. R.; Williams, A. J .; Hewitt, J . M.; McMillan, M.
Organometallics 1995, 14, 5258-5265.

180 J . Org. Chem., Vol. 63, No. 1, 1998
Notes
details). The structures of the olefinic products were confirmed
by comparison of 1H and 13C NMR spectra with those of
authentic samples. The progress of reaction was monitored
periodically by 1H NMR using residual CHCl3 as an internal
standard. Conversions reported in Table 1 are the average of
at least two runs. Blank runs were setup in an identical manner
except that the telluride catalyst was omitted. The progress of
reaction was monitored by 1H NMR using residual CHCl3 as an
internal standard.
P r ep a r a tive Ca ta lytic Rea ction s. The substrate (3.00
mmol) and diorganotelluride 1 [(108 mg, 0.30 mmol) or (276 mg,
0.75 mmol)], 2 (232 mg, 0.75 mmol), or 3 (107 mg, 0.30 mmol)
were dissolved in 20 mL of CHCl3. This solution was combined
with the reducing agent [glutathione (2.76 g, 9.0 mmol) or
sodium ascorbate (1.80 g, 9.0 mmol)] in 20 mL of 0.25 M
potassium phosphate buffer (pH 8.9). The resulting mixtures
were heated at reflux for the time periods indicated in Table 1.
Aliquots of the reaction mixture were sampled periodically by
1H NMR. The organic layer was separated, and the aqueous
phase was extracted with CH2Cl2. The combined organics were
dried over MgSO4 and carefully concentrated. trans-Stilbene
was isolated by chromatography on a small plug of SiO2 (5%
EtOAc-hexanes) followed by recrystallization from hexanes.
trans-1-Phenyl-1-propene and 2-methyl-1-phenylpropene were
isolated by chromatography on SiO2 (hexanes). 1-Decene (0.1
Torr, 140 °C) and trans-5-decene (0.1 Torr, 150 °C) were distilled
from the organic residue using a molecular still. cis-2-Pentene,
cis-4-methyl-2-pentene, and 2-methyl-2-pentene were not readily
separated from CHCl3.
Gen er a l P r oced u r e for Com p etition Exp er im en ts. The
dibromides (0.20 mmol) and telluride 2 (15.0 mg, 0.05 mmol)
were dissolved in 2.0 mL of CDCl3. The resulting solution was
added to 6.0 mmol of either GSH or sodium ascorbate in 2.0 mL
of 0.25 M phosphate buffer at pH 8.9. The resulting mixtures
were heated at reflux. After the indicated times (see text),
product ratios were measured by 1H NMR spectroscopy and
averaged for duplicate runs.
Ack n ow led gm en t. The authors acknowledge the
donors of the Petroleum Research Fund, administered
by the American Chemical Society, for partial support
of this research.
J O971504R