Facile Solvolyses of Triflates
CHART 2. Tr ifla te/Mesyla te Ra te Ra tios (kOTf
/
does the triflate leaving group. Therefore, DMSO-d6 is a
very reasonable solvent for cationic processes involving
triflates even though this solvent cannot be a hydrogen
bond donor.
k
OMs) in DMSO-d 6
Exp er im en ta l Section
P r ep a r a tion of Tr ifla tes. The preparations of triflates 5,19
9,4 21,6 23,6 24,7 25,8 29,10 33,11a and 3915 have previously been
described, as has the preparation of t-BuCH(OMs)CO-t-Bu
(44).20
P r ep a r a tion of t-Bu CH(OTf)CO2CH3 (14). A solution of
327 mg of methyl 2-hydroxy-3,3-dimethylbutanoate21 and 379
mg of 2,6-lutidine in 4 mL of methylene chloride was cooled
to -20 °C, and 1.23 g of triflic anhydride was added dropwise.
The mixture was stirred at -20 °C for 25 min and was then
warmed to room temperature. The mixture was then trans-
ferred to a separatory funnel with ether and rapidly washed
with cold water, dilute HCl, and saturated NaCl solution. After
drying over a mixture of Na2SO4 and MgSO4, the solids were
removed by filtration and the solvent was removed using a
rotary evaporator. Distillation of the residue gave 351 mg
(56%) of triflate 14: bp 29-30 °C (0.08 mm);
44-47) in this solvent (Chart 2). While triflate 5 solvo-
lyzes in DMSO-d6 with a half-life of 11 min at 25 °C, the
corresponding mesylate t-BuCH(OMs)CO-t-Bu (44) has
a half-life of 10 h at 155 °C. This remarkable reactivity
difference corresponds to an extrapolated triflate/mesy-
late rate ratio of 1 × 109 at 25 °C. Comparable values
can be extrapolated for the triflates 21 and 33 the
corresponding mesylates.
1H NMR of 14
(CDCl3) δ 4.78 (s, 1 H), 3.84 (s, 3 H), 1.09 (s, 9 H); 13C NMR of
14 (CDCl3) δ 166.7, 118.5 (q, J ) 319 Hz), 90.8, 52.7, 35.0,
25.7; exact mass (EI) calcd for C8H14F3O5S 279.0514, found
279.0539.
A fourth example of this remarkable triflate/mesylate
rate ratio in DMSO-d6 comes from examination of triflate
29 and its mesylate analogue (CH3)2CCN(OMs) (46). The
mesylate 46 is quite unreactive in DMSO-d6, but it does
react at 100 °C with a half-life of 7.9 h (Table 1). Data in
Table 1 allow the determination of an extrapolated rate
constant of 2.99 × 10-9 s-1 at 25 °C. By way of contrast,
the triflate 29 reacts completely in DMSO-d6 before
spectra can be recorded. However, diluting the DMSO-
d6 with CDCl3 reduces the reactivity of triflates and 29
reacts with a half-life of 12.7 min at 25 °C in 15% DMSO-
d6/85% CDCl3. If one assumes that the reactivity of
triflate 29 in mixed DMSO-d6/CDCl3 systems parallels
that of triflate 5 (which is 557 times faster in pure
DMSO-d6 than in 15% DMSO-d6), then the estimated
half-life of triflate 29 in pure DMSO-d6 is 1 s. This
corresponds to a triflate/mesylate rate ratio of about 2 ×
108. These unusually high triflate/mesylate solvolysis rate
ratios (108 to 109) in DMSO-d6 suggest that solvolysis
reactions involving carbocations require electrophilic as
well as nucleophilic solvation and DMSO-d6 is a very good
nucleophilic solvator of developing carbocations. How-
ever, with the triflate leaving group, electrophilic solva-
tion of the developing triflate anion is not as important
as solvation of anions such as mesylate. Hence, triflates
have enhanced reactivity.
Con clu sion s. Certain triflates undergo very facile
solvolysis reactions when dissolved in DMSO-d6 giving
both rearranged and unrearranged products. Mecha-
nisms involve k∆ processes (which give carbocation rear-
rangements), kC processes, ks processes, as well as
“borderline” processes. The entire spectrum of carbocation
reactivity is therefore available to triflates in DMSO-d6.
The most remarkable feature of these reactions is the
high reactivity that triflates show in DMSO-d6. Certain
triflates give carbocation chemistry in DMSO-d6 at rates
that exceed those in the “traditional” highly ionizing
protic solvents trifluoroethanol and formic acid. Rates of
triflates can exceed that of analogous mesylates by factors
of 108-109. It is suggested that the mesylate leaving
group requires much more electrophilic solvation than
P r ep a r a tion of 1-Meth ylcyclop r op yl Mesyla te (45). A
solution of 275 mg of 1-methylcyclopropanol22 and 775 mg of
mesyl chloride in 4 mL of methylene chloride was cooled to
-10 °C, and 816 mg of Et3N in 1 mL of methylene chloride
was added dropwise. The mixture was warmed to room
temperature and then transferred to a separatory funnel using
ether and water. The ether extract was washed with water,
dilute hydrochloric acid, dilute NaOH solution, and saturated
NaCl solution and dried over MgSO4. After filtration, the
solvents were removed using a rotary evaporator, and the
residue was distilled to give 442 mg (77% yield) of mesylate
45: bp 42 °C (0.05 mm); 1H NMR (CDCl3) δ 3.00 (s, 3 H), 1.70
(s, 3 H), 1.26 (m, 2 H), 0.70 (m, 2 H); 13C NMR (CDCl3) δ 60.2,
39.9, 22.6, 12.8; exact mass (EI) calcd for C5H10O3S 150.0351,
found 150.0357.
P r ep a r a tion of (CH3)2CCN(OMs) (46). A solution of 410
mg of acetone cyanohydrin and 805 mg of mesyl chloride in 4
mL of methylene chloride was cooled to -10 °C, and 808 mg
of Et3N in 1.0 mL of methylene chloride was added dropwise.
The mixture was warmed to room temperature and then
transferred to a separatory funnel using ether and water. The
ether extract was washed water, dilute hydrochloric acid,
dilute NaOH solution, and saturated NaCl solution and dried
over MgSO4. After filtration, the solvents were removed using
a rotary evaporator to give 584 mg (74% yield) of mesylate
46, which was used for kinetic studies without further
purification: 1H NMR (CDCl3) δ 3.19 (s, 3 H), 1.91 (s, 6 H).
13C NMR (CDCl3) δ 118.2, 75.1, 40.2, 28.4; exact mass (EI)
calcd for C4H6NO3S 148.0069, found 148.0068. (M - CH3 peak.
There is no observable molecular ion.)
P r ep a r a tion of P h CH(OMs)CF 3 (47). A solution of 130
mg of R-(trifluoromethyl)benzyl alcohol and 122 mg of mesyl
chloride in 2 mL of methylene chloride was cooled to -10 °C,
and 122 mg of Et3N in 0.5 mL of methylene chloride was added
dropwise. The mixture was warmed to 0 °C and then trans-
ferred to a separatory funnel using ether and water. The ether
extract was washed with dilute hydrochloric acid and satu-
rated NaCl solution and dried over MgSO4. After filtration,
(19) Creary, X. J . Org. Chem. 1979, 44, 3938.
(20) Creary, X. J . Org. Chem. 1980, 45, 2419.
(21) Bessard, Y.; Crettaz, R. Tetrahedron 2000, 56, 4739.
(22) (a) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.
Synthesis 1991, 234. (b) DePuy, C. H.; Dappen, G. M.; Eilers, K. L.;
Klein, R. A. J . Org. Chem. 1964, 29, 2813.
J . Org. Chem, Vol. 69, No. 4, 2004 1233