TABLE 2. Half-Lives in Decarboxylation Rates of Sulfonium Salts
4-7
center did not offer an improvement in the levels of epoxide
conversion despite a significant acceleration in the rates of
decarboxylation.
Experimental Section
Representative Procedure for the Preparation of Sulfonium
Salts. A 250 mL round-bottomed flask (RBF) equipped with a stir
bar, septum, and drying tube was charged with 5.6 g of iodoacetic
acid (30.0 mmol, 1.5 equiv). The solid was dissolved using
acetonitrile (30 mL). Once in solution, 22.1 mmol of sulfide (1.0
equiv) was added in one portion at room temperature. In a separate
flask, 7.7 g of silver triflate (30 mmol, 1.5 equiv) was dissolved in
10.0 mL of acetonitrile. The silver triflate solution was added
dropwise at room temperature via syringe to the solution of sulfide
and iodoacetic acid. Precipitation was observed immediately. The
suspension was monitored by TLC until completion of reaction,
approximately 48 h. The silver salts were removed via filtration
using a medium-sized glass funnel and filter paper (#2 Whatman).
The solution was concentrated in vacuo without external heat. The
resulting solid was triturated with MTBE (100 mL), filtered, and
dried under vacuum. Precipitation of the sulfonium salts could as
well be affected by addition of an ethereal solvent to the crude
reaction mixture.12
entry
sulfonium salt
t1/2 (min)
1
2
3
4
4 (R ) H)
13.3
1.3
1.2
5 (R ) CN)
6 (R ) NO2)
7 (R ) OCH3)
85.6
SCHEME 4
improvement in epoxidation efficiency. In fact, we were unable
to detect more than traces of epoxide from reaction of either 5
or 6 with even the electron-deficient aldehydes. It is interesting
that reaction of sulfonium salt 4 with 2,6-dichlorobenzalde-
hyde yielded the desired oxirane in only 12% when operating
at room temperature. Warming to 65 °C, the level of conversion
increased to 94%. To explain the above results, we propose that,
at high temperatures, the decarboxylation rate is high providing
relatively high levels of ylide that can be trapped by carbonyl
compounds, particularly, the more electrophilic (electron-
deficient) ones. As the electrophilicity of the carbonyl compound
decreases, the forward rate of epoxidation slows down and fails
to compete effectively with ylide fragmentation and other side
reactions. Conversely, when the rate of decarboxylation is
increased through electronic manipulation (aryl group substit-
uents), the rate of epoxidation also slows down as the ylide
(now more stable) is less reactive.
(Carboxymethyl)methylphenylsulfonium Trifluoromethane-
sulfonate (4). From the combination of thioanisole (5.23 mL, 44.5
mmol), iodoacetic acid (5.5 g, 29.6 mmol) in 4.0 mL of acetonitrile,
and silver triflate (8.0 g, 31.1 mmol) in 5.0 mL of acetonitrile, 7.2
g of (carboxymethyl)methylphenylsulfonium trifluoromethane-
sulfonate (22.2 mmol, 96% yield) was obtained after precipitation
and isolation of solid by filtration. Formula weight: 332.32 g/mol.
1
Mp: 124-125 °C. H NMR (300 MHz, D2O): δ 7.92-7.65 (m,
5H), 4.79 (br s), 4.64 (d, J ) 16.0 Hz, 2H), 4.55 (d, J ) 10.7
Hz, 2H), 3.23 (s, 3H). 13C NMR (75.5 MHz, D2O): δ 169.8,
137.3, 133.6, 132.6, 125.9, 122.2 (q, J ) 317.0 Hz (CF3)), 51.8
(CD2COOD), 28.8. IR (neat (ATR corrected)): 3039 (m), 2991
(m), 2941 (m), 1732 (s) cm-1. GC/MS (70 eV, LREI, HP-5): M+
(-OTf, -carboxymethyl) 124, (tR 5.49 min). GC (AT-5): tR 5.27
min (thioanisole). HRMS (M+ - OTf) calcd 183.04810; found
183.0474.
Carboxymethyl-4-cyanophenylmethylsulfonium Trifluoro-
methanesulfonate (5). From the combination of 4-cyanothioanisole
(6.02 g, 40.3 mmol), iodoacetic acid (5.0 g, 26.9 mmol) in 2.5 mL
of acetonitrile, and silver triflate (7.25 g, 28.2 mmol) in 5.0 mL of
acetonitrile, 7.4 g of carboxymethyl-4-cyanophenylmethylsulfonium
trifluoromethanesulfonate (20.7 mmol, 77% yield) was obtained
after precipitation and isolation of solid by filtration. Mw: 357.33
In terms of possible side reactions, unstabilized sulfur ylides
are known to react with sulfonium ions (powerful methylating
agents) to form new sulfonium salts.10 One likely side reaction
in our system would be initial protonation of sulfur ylide i to
form a dimethylsulfonium species which, in turn, alkylates
another ylide molecule to form mixtures of dimethyl or ethyl
methyl sulfonium derivatives (Scheme 4).11
1
g/mol. Mp: 136-138 °C. H NMR (300 MHz, D2O): δ 8.09-
8.04 (m, 4H), 4.79 (br s), 4.68-4.46 (m, 2H), 3.25 (s, 3H). 13C
NMR (75.5 MHz, D2O): δ 167.1, 134.7, 131.0, 130.2, 129.6, 126.1,
119.8 (q, J ) 317.0 Hz (CF3)), 117.7, 117.3, 49.6 (CD2COOD),
28.3, 26.0. IR (neat (ATR corrected)): 2240 (m), 2953 (m), 3043
(m), 3093 (m) cm-1. GC/MS (70 eV, LREI, HP-5): M+ (-OTf,
-carboxymethyl) 149, (tR 10.51 min). GC (AT-5): tR 9.69 min
((4-cyanophenyl)methyl sulfide). HRMS (M+ - OTf) calcd 208.0432;
found 208.0441.
Carboxymethyl-4-nitrophenylmethylsulfonium Trifluoro-
methanesulfonate (6). From the combination of methyl-4-nitro-
phenyl sulfide (6.82 g, 40.3 mmol), iodoacetic acid (5.0 g, 26.9
mmol) in 2.5 mL of acetonitrile, and silver triflate (7.25 g, 28.2
mmol) in 5.0 mL of acetonitrile, 4.2 g of carboxymethyl-4-nitro-
phenylmethylsulfonium trifluoromethanesulfonate (11.1 mmol, 28%
yield) was obtained after precipitation and isolation of solid by
Research in our group continues in the areas of (1) under-
standing the kinetics of the reaction, (2) increasing the scope
of substrate using modified sulfonium salts, and (3) the
preparation and use of a chiral, nonracemic sulfide promoter.
The results from these studies will be reported in due course.
In conclusion, methylidene transfer to aldehyde functionality
using decarboxylation of arylcarboxymethylsulfonium betaines
has been achieved. An improvement in the levels of epoxide
conversion and isolated yield was observed upon replacement
of the octyl substituent on the sulfur atom with phenyl. The
levels were significant especially when working with electron-
rich or neutral aryl aldehydes. Electronic tuning of the sulfonium
(10) Corey, E. J.; Jautelat, M.; Oppolzer, W. Tetrahedron Lett. 1967,
2325.
(11) (a) For formation of alkyldimethylsulfonium salts via the decar-
boxylation of carboxymethylbetaine functionality, see: Burness, D. J. Org.
Chem. 1959, 24, 849. (b) For a discussion on ylide methylation, see:
Gololobov, Y. G.; Nesmeyanov, A. N.; Lysenko, V. P.; Boldeskul, I. E.
Tetrahedron 1987, 43, 2609
(12) Attempts to force precipitation of additional sulfonium salt from
the filtrate a second time resulted in impure mixtures of the desired
sulfonium salt. Multigram quantities of each system were obtained with
the first filtration. Recrystallization of the impure salts requiring elevated
temperatures was not considered.
J. Org. Chem, Vol. 71, No. 21, 2006 8289