114 J . Org. Chem., Vol. 62, No. 1, 1997
Ocampo et al.
solutions of 1a and 1,1-difluoro-2-methylpropene in toluene
demonstrated that, within experimental error, they have the
same detector response factor. The values of k of decarboxy-
lation were estimated by linear regression from the slope of
the plot of the natural logarithm of the fraction of area of 1a
versus time.
diradical and the zwitterion could essentially be “re-
garded as resonance forms, the relative importance of
which would be determined by the substituents at the
terminal centers”. We would add to this the proposition
that the relative importance of homolytic and dipolar
transition states, indeed whether a given reaction should
be concerted or proceed via a diradical or zwitterionic
intermediate, should also be strongly dependent upon the
polarity of the medium, which, along with the important
effect of substituents, would determine where a given
cycloreversion (-addition) mechanism should be located
within a continuous spectrum of possible concerted and
nonconcerted, polar and nonpolar mechanisms.
Ra tes of Ga s-P h a se Deca r boxyla tion of 1a : 2.8 ( 0.1 ×
o
o
10-5 s-1 at 202.4 C, 4.6 ( 0.2 × 10-5 s-1 at 207.7 C, 6.9 ( 0.2
× 10-5 s-1 at 211.2 C, 9.7 ( 0.1 × 10-5 s-1 at 215.5 C, 15.9 (
o
o
0.2 × 10-5 s-1 at 220.4 °C.
Kin etics of th e Deca r boxyla tion of 1 in Solu tion .
A
stock 0.04 M solution of 1 was prepared in the anhydrous
solvent containing R,R,R-trifluorotoluene of known concentra-
tion as internal standard. The decarboxylation was carried
out in sealed NMR tubes immersed in a thermostated silicon
oil bath set at the desired temperature, and the kinetics were
monitored by 19F-NMR analysis of samples quenched in an
2-propanol-dry ice bath at appropriate intervals of time. For
each experiment, the respective value of k of decarboxylation
was estimated by linear regression from the slope of the plot
of the natural logarithm of the fraction of area of 1 versus time.
Ra tes of Deca r boxyla tion of 1a in Aceton itr ile: 5.4 (
0.1 × 10-5 s-1 at 119.6 °C, 8.1 ( 0.1 × 10-5 s-1 at 125.8 °C, 1.3
( 0.1 × 10-4 s-1 at 130.2 °C, 2.0 ( 0.1 × 10-4 s-1 at 135.3 °C,
3.1 ( 0.1 × 10-4 s-1 at 140.2 °C.
Exp er im en ta l Section
Gen er a l. All NMR spectra were run in CDCl3 on a Varian
VXR-300 spectrometer, with 1H at 299.949 MHz using TMS
as reference; 19F at 282.202 MHz using CFCl3 as reference;
13C at 75.430 MHz using CDCl3 as reference at 77.0 ppm.
Syn th esis of Su bstr a tes 1. R,R-Difluoro â-lactones 1 were
prepared as previously reported.4 One equiv of the starting
R,R-difluoro-â-hydroxy acid was dissolved in the anhydrous
solvent, and 2.0 equivs of anhydrous pyridine were added
dropwise. Then, while cooling at 0-5 °C, 1.0 equiv of benze-
nesulfonyl chloride was added very slowly and the mixture
was vigorously shaken. After 18 h 1 was isolated as specifi-
cally indicated below.
Ra tes of Deca r boxyla tion of 1a in Mesitylen e: 4.1 (
0.2 × 10-5 s-1 at 168.1 °C, 6.3 ( 0.1 × 10-5 s-1 at 171.9 °C, 8.3
( 0.4 × 10-5 s-1 at 176.6 °C, 13.4 ( 0.3 × 10-5 s-1 at 181.5 °C,
19.8 ( 0.6 × 10-5 s-1 at 187.2 °C.
Ra te of Deca r boxyla tion of 1a in Tolu en e a t 171.8 °C:
6.7 ( 0.3 × 10-5 s-1
.
Syn th esis of 3,3-Diflu or o-4,4-dim eth yloxetan -2-on e (1a).
Starting from 2,2-difluoro-3-hydroxy-3-methylbutanoic acid
dissolved in tetraglyme and after 18 h of reaction, 1a was
vacuum transferred out of the reactant mixture at 0.05 mmHg,
in 60% yield, and the product exhibited the same spectroscopic
properties as those reported.4
Ra tes of Deca r boxyla tion of 1b in Solu tion a t 168.1
°C: In N,N-dimethylformamide (DMF) 1.07 ( 0.04 × 10-2 s-1
,
in acetonitrile 3.1 ( 0.2 × 10-3 s-1, in cyclohexanone 1.4 (
0.1 × 10-3 s-1, in benzene 1.5 ( 0.1 × 10-4 s-1, in mesitylene
1.1 ( 0.1 × 10-4 s-1, in cyclohexane 2.2 ( 0.1 × 10-5 s-1
.
1H NMR: δ 1.6 ppm (t, J H-F ) 1.5 Hz). 19F NMR: δ -121.2
ppm (p, J H-F ) 1.5 Hz). 13C NMR: δ 20.1 (t-like), 89.0 (t, J C-F
) 22.4 Hz), 119.4 (t, J C-F ) 291.1 Hz, CF2), 161.6 ppm (t, J C-F
) 32.2 Hz, CdO).
Ra tes of Deca r boxyla tion of 1c in Mesitylen e: 2.3 (
0.2 × 10-5 s-1 at 148.9 °C, 4.2 ( 0.1 × 10-5 s-1 at 156.5 °C, 1.2
( 0.1 × 10-4 s-1 at 169.2 °C, 1.5 ( 0.1 × 10-4 s-1 at 171.1 °C,
2.0 ( 0.1 × 10-4 s-1 at 175.0 °C.
Com p u ta tion a l Meth od ology. All ab initio calculations
were performed with the Gaussian92 program system.24
Semiempirical results were obtained using the AM1 parameter
set25 as implemented in MOPAC93. Transition structures
computed at the AM1 and RHF levels (and in the case of 7, at
the MP2 level) were characterized by harmonic frequency
analysis and verified by a single imaginary (negative) vibra-
tional frequency, analysis of which indicated motion along the
expected reaction coordinate. Hartree-Fock vibrational fre-
quencies and zero-point energy corrections were scaled by 0.89.
MP2 frequencies and zero-point energy corrections of 7 were
scaled by 0.94. AM1 geometries and energies of ground and
transition structures of 7 and 6 and the RHF/6-31G** ground-
state geometry of 7 were essentially identical to those of
previous studies by Moyano9 and Stephens,26 respectively. MP2
geometry optimizations and single-point energies utilized the
frozen-core approach.
Syn th esis of 4,4-Dieth yl-3,3-d iflu or ooxeta n -2-on e (1b).
Starting from 2,2-difluoro-3-hydroxy-3-ethylpentanoic acid
dissolved in tetraglyme, 1b was vacuum transferred out of the
reactant mixture at 0.05 mmHg, in 95% yield.
1H NMR: δ 1.0 (t, 6H, J H-H ) 7.6 Hz), 2.0 (q, 2H, J H-H
)
7.6 Hz), 2.0 ppm (q of t, 2H, J H-H ) 7.6 Hz, J H-F ) 1.5 Hz).
19F NMR: δ -122.1 ppm, (s). 13C NMR: 7.2 (s), 23.1 (t-like),
94.1 (t, J C-F ) 20.4 Hz), 119.9 (t, J C-F ) 291.3 Hz, CF2), 161.9
ppm (t, J C-F ) 32.2 Hz, CdO); IR (neat): 2987, 2943, 2886,
1858, 1460, 1370, 1312, 1206, 1172, 1142 cm-1
.
Syn th esis of 4,4-Diben zyl-3,3-diflu or ooxetan -2-on e (1c).
Starting from 3-benzyl-2,2-difluoro-3-hydroxy-4-phenylbutano-
ic acid (5c) dissolved in chloroform and after 18 h of reaction,
the solvent was evaporated, and the remaining white solid was
treated with dried hexanes. Evaporation of the hexane extract
gave rise to 1c, which was then recrystallized from hexanes
in 85% yield; mp 51-52 °C.
1H NMR (AB system): δ 3.15 (d, J H-F ) 15.3 Hz), 3.23 (d,
4H, J H-F ) 15.3 Hz), 7.06-7.10 (m, 4H), 7.30-7.33 ppm (m,
6H). 19F NMR: δ -118.4 ppm (s). 13C NMR: δ 36.9 (bs), 92.5
(t, J C-F ) 20.6 Hz), 120.2 (t, J C-F ) 293.0 Hz, CF2), 127.5,
128.6, 130.3 and 132.8 (aromatic carbons), 161.0 ppm (t, J C-F
Ack n ow led gm en t. Support of this research in part
by the National Science Foundation (U.S.A.) and Col-
ciencias (Colombia) is gratefully acknowledged. R.
Ocampo thanks the Universidad de Caldas (Colombia)
for a leave of absence. Academic Computing and
Network Services at Florida State University is grate-
fully acknowledged for an allocation of computing
resources.
) 32.4 Hz, CdO). IR (CHCl3): 1858 cm-1
. MS (EI) m/e:
288.0971 (36.7) [M•+ ) C17H14F2O2], 193.1079 (11.4) [C9H5F2O2],
166.0655 (12.1) [C10H8F2], 115.062 (13.2) [C6H8OF], 91.0563
(100) [C4H8FO], 65.0428 (23.2) [C2H6OF]. Anal. Calcd for
C17H14F2O2: C, 70.83; H, 4.89; F, 13.18. Found: C, 70.56; H,
5.06.
J O961648Q
Kin etic Mea su r em en ts. Kin etics of th e Ga s-P h a se
Deca r boxyla tion of 1a . The pyrolysis was carried out in a
Pyrex vessel immersed in a thermostated molten salt bath and
connected to a vacuum line. 1a was vacuum transferred into
the pyrolysis vessel which was maintained at the desired
temperature, and aliquots were removed by vacuum transfer
at appropriate intervals of time into 25 mL sample tubes and
analyzed by GC on a OV-17 column using a gas-sampling
valve. The analysis by both 19F NMR and GC of standard
(24) Frisch, M. J .; Trucks, G. W.; Head-Gordon, M.; Gill, P. M. W.;
Wong, M. W.; Foresman, J . B.; J ohnson, B. G.; Schlegel, H. B.; Robb,
M. A.; Replogle, E. S.; Gomperts, R.; Andres, J . L.; Raghavachari, K.;
Binkley, J . S.; Gonzalez, C.; Martin, R. L.; Fox, D. J .; Defrees, D. J .;
Baker, J .; Stewart, J . J . P.; Pople, J . A. Gaussian 92, Revision B;
Gaussian, Inc.: Pittsburgh, PA, 1992.
(25) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902.
(26) J alkanen, K. J .; Stephens, P. J . J . Phys. Chem. 1991, 95, 5446.