Carbanionic rearrangements of halomethylenecyclobutanes. The role of the halogen

Article abstract of DOI:10.1021/jo9810866

The carbanionic ring enlargement of (halomethylene)cyclobutanes to 1- halocyclopentenes has been extended to the fluoro analogues. At 180 °C, 3- hexyl-1-(fluoromethylene)cyclobutane provides better yields of rearranged product than the corresponding chloride, bromide, or iodide. At temperatures < 100 °C, the yield of ring-enlarged product follows the order I > Br > Cl, and the fluoride does not react. Experiments with labeled substrates show that, in general, the larger the halide and the higher the reaction temperature, the greater the preference for double migration over Single migration as a mechanistic pathway. The trifluormethyl group is ineffective in promoting anionic rearrangement.

Full text of DOI:10.1021/jo9810866

8880
J . Org. Chem. 1998, 63, 8880-8887
Ca r ba n ion ic Rea r r a n gem en ts of Ha lom eth ylen ecyclobu ta n es. Th e
Role of th e Ha logen
Zhengming Du, Melissa J . Haglund, Lauri A. Pratt, and Karen L. Erickson*
Carlson School of Chemistry, Clark University, Worcester, Massachusetts 01610
Received J une 8, 1998
The carbanionic ring enlargement of (halomethylene)cyclobutanes to 1-halocyclopentenes has been
extended to the fluoro analogues. At 180 °C, 3-hexyl-1-(fluoromethylene)cyclobutane provides better
yields of rearranged product than the corresponding chloride, bromide, or iodide. At temperatures
< 100 °C, the yield of ring-enlarged product follows the order I > Br > Cl, and the fluoride does
not react. Experiments with labeled substrates show that, in general, the larger the halide and
the higher the reaction temperature, the greater the preference for double migration over single
migration as a mechanistic pathway. The trifluormethyl group is ineffective in promoting anionic
rearrangement.
Sch em e 1
In tr od u ction
The base-induced regio- and stereospecific rearrange-
ment of halomethylenecyclobutanes to 1-halocyclopen-
tenes1 is a unique and intriguing reaction as it appears
to be an example of a “forbidden” 1,2-alkyl-to-carbanion
shift.2 To explain the accumulated experimental data on
this reaction, two competing mechanistic pathways were
postulated, both proceeding from an initially formed vinyl
anion.1 In Scheme 1 rehybridization of the vinyl anion
to a 1,2-carbene anion occurs. After suitable bond rota-
tion to align orbitals, ring enlargement ensues by single
migration of a ring carbon. Alternately, Scheme 2 depicts
a double migration process where both the halide and a
ring carbon migrate analogous to the Beckmann rear-
rangement of oximes. Experimental evidence supports
the simultaneous operation of both of these processes.1
(Bromo-, (chloro-, and (iodomethylene)cyclobutane all
undergo base-induced rearrangement to the correspond-
ing 1-halocyclopentenes,3 but the extent of double and
single migration as a function of the halogen is not
known, and the fluoro analogue has never been investi-
gated. The present study was undertaken to determine
what influence the nature of the halogen has on the
mechanistic course of the reaction, and whether fluorines
placed â to the negative charge facilitate the rearrange-
ment process.
Sch em e 2
We are aware of only one instance where a vinyl
carbanion has been pictured as a resonance hybrid with
a 1,2-carbene anion as a contributing form. In 1985
Shainyan and co-workers4 postulated the intermediacy
of a 1,2-carbene anion to explain the rearrangement of
â,â-dihalovinyl sulfones to R,â-dihalovinyl sulfones, a
process akin to that outlined in Scheme 1 with halide
(1) Samuel, S. P.; Niu. T-Q.; Erickson, K. L. J . Am. Chem. Soc.
1989, 111, 1429 and references therein.
(2) For a theoretical study of such reactions and leading references,
see: Borosky, G. J . Org. Chem. 1998, 63, 3337.
(3) Erickson, K. L.; Markstein, J .; Kim, K. J . Org. Chem. 1971, 36,
1024.
(4) Shainyan, B. A.; Mirskova, A. N.; Vitkovskii, V. Yu. J . Org.
Chem., USSR (Engl. Transl.) 1985, 21, 877.
rather than carbon migrating. Also possible, but not
considered by these authors, is a Beckmann type of
double migration analogous to that shown in Scheme 2.
Shainyan attributes stabilization of the 1,2-carbene anion
10.1021/jo9810866 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/05/1998

Carbanionic Rearrangements of (Halomethylene)cyclobutanes
J . Org. Chem., Vol. 63, No. 24, 1998 8881
form to the two halo substituents R to the negative
charge. In the (halomethylene)cyclobutane case (Scheme
1) the carbene anion form should be favored if the
halogen is effective at stabilizing an R-carbene and a
â-carbanion and rearrangement then becomes possible.
If the halide is a poor migrating/leaving group, single
migration should be favored and double migration should
be minimized as well as irreversible halide loss. When
the halide dissociates from the organic moiety, a vi-
nylidene carbene is formed which undergoes polymeri-
zation and/or trapping by base to give halide-free prod-
ucts.1 The extent of single migration is expected to
increase in the order F > Cl > Br > I with the Beckmann-
like process increasing in the opposite direction. To
determine the ratio of single to double migration as a
function of the halide substituent, a series of 3-hexyl-1-
(halomethylene)-13C-cyclobutanes was examined. These
compounds do not have any R-substituents to influence
the reaction, and, with the fluoro compound in particular,
the reduced volatility allows for easier handling. The
effect of allylic fluoro substituents was also investigated.
Syn t h esis of Met h ylen ecyclob u t a n es. F lu or o-
m eth ylen ecyclobu ta n es (3 a n d 8). The cycloaddition
reaction between dichloroketene and 1-octene mediated
by ultrasound5 formed 2,2-dichloro-3-hexylcyclobutanone
(1) quantitatively, and dechlorination6 occurred in >90%
yield to give 3-hexylcyclobutanone (2). The Wittig reac-
tion of 2 with (fluoromethylene)triphenylphosporane7,8
afforded 1-(fluoromethylene)-3-hexylcyclobutane (3) in
91% yield. The Wittig reaction of 2 with (methylene-13C)-
triphenylphosphosporane gave 3-hexyl-1-(methylene-13C)-
cyclobutane also in >90% yield. This was converted to
epoxide 5 which was then cleaved with N-ethyldiisopro-
pylamine tris(hydrofluoride) (“Hunig’s base”)9 in the pres-
ence of a 5-fold excess of N-ethyldiisopropylamine. Under
these conditions, fluorohydrin 6 was formed quantita-
tively. When lesser amounts of N-ethyldiisopropylamine
carboxaldehyde was produced, presumably from forma-
tion of the isomeric fluorohydrin and its subsequent
dehydrofluorination. Dehydration of 6 gave an 87% yield
of 1-(fluoromethylene-13C)-3-hexylcyclobutane.
3,3-Bis(ethylthio)-2,2,4,4-tetramethyl-1-(fluoromethyl-
ene)cyclobutane (8) was easily prepared by a Wittig
reaction on monoprotected 2,2,4,4-tetramethylcyclobu-
tane-1,3-dione 7.10
(Ch lor o-, (Br om o-, a n d (Iod om eth ylen e)cylcobu -
ta n es (12, 13, a n d 18). The application of the above
epoxide sequence for the preparation of the other labeled
(halomethylene)cyclobutanes was not entirely satisfac-
tory. Although (unlabeled) epoxide 5 underwent quan-
titative ring opening with lithium chloride, bromide, or
iodide11 to give the corresponding halohydrins 9-11,
dehydration of the chloro- and bromohydrins afforded the
halomethylene compounds 12 and 13 in only modest
yields, and iodohydrin 11 did not dehydrate but reformed
the epoxide.
The labeled (chloro-, (bromo-, and (iodomethylene)-
cyclobutanes were prepared more efficiently by dehydro-
halogenation of the 1,2-dihalides. 1-Chloro-1-(chloro-
methyl-13C)-3-hexylcyclobutane (14) was made from the
reaction of labeled epoxide 5 with Ph3P/CCl4.12
1-Bromo-1-(bromomethyl-13C)-3-hexylcyclobutane (15)
and 1-iodo-1-(iodomethyl-13C)-3-hexylcyclobutane (16) were
prepared by halogenation of 3-hexyl-1-(methylene-13C)-
cyclobutane (4). Dehydrohalogenation with alcoholic
hydroxide afforded the chloro- (12) and bromomethylene
(13) compounds, but the diiodide reverted to alkene 4
under these conditons. Addition of iodine monochloride
to 4 gave 1-chloro-3-hexyl-1-(iodomethyl-13C)cyclobutane
(17), which underwent dehydrochlorination to give 3-hexyl-
1-(iodomethylene-13C)cyclobutane (18).
were used, the yield of 6 dropped and 3-hexylcyclobutane-
(5) (a) Bak, D. A.; Brady, W. T. J . Org. Chem. 1979, 44, 107. (b)
Mehta, G.; Rao, H. S. P. Synth. Commun. 1985, 15, 991.
(6) J effs, P. W.; Molina, G.; Cass, M. W.; Cortese, N. A. J . Org. Chem.
1982, 47, 3871.
(7) Burton, D. J .; Wiemers, D. M. J . Fluorine Chem. 1985, 27, 85.
(8) Burton, D. J .; Greenlimb, P. E. J . Org. Chem. 1975, 40, 2796.
(9) Suga, H.; Hamatani, T.; Schlosser, M. Tetrahedron 1990, 46,
4247.
(10) Paquer, D.; Reffet, D.; Vazeux, M. Recl. Trav. Chim. Pays-Bas
1978, 97, 284.
(11) Bajwa, J . S.; Anderson, R. C. Tetrahedron Lett. 1991, 32, 3021.
(12) Isaacs, N. S.; Kirkpatrick, D. Tetrahedron Lett. 1972, 3869.

8882 J . Org. Chem., Vol. 63, No. 24, 1998
Du et al.
Control studies established that 22-24 do not come
from 4-hexyl-1-fluorocyclopentene (21). 3-Hexylcyclo-
pentanone (22) is the hydrolysis product of the corre-
sponding tert-butoxy enol ether 25, which arises when
tert-butoxide traps the cyclopentyne.3,15 4-Hexylcyclo-
pentene (24) likely arises from hydride transfer from the
LDA16 to 4-hexylcyclopentyne. With LDA as the base,
carbene formation from the halovinyl anion becomes
more competitive, a consequence of the strong Li-F in-
teraction favoring metal-assisted ionization.17 The cy-
clopentene dimer (23) is not produced with other (ha-
lomethylene)cyclobutanes and the high reaction temper-
ature necessary for the vinyl fluoride rearrangement may
account for the dimer’s formation.18
1-(Tr iflu or oeth ylid en e)-3-h exylcyclobu ta n e (20).
This compound was prepared from 3-hexyl-1-(methylene)-
cyclobutane (4). Triethylborane-catalyzed addition of
trifluoroiodomethane13 gave 19 as a mixture of diaster-
eomers which were directly dehydroiodinated to give 20.
Tetramethyl(fluoromethylene)cyclobutane 8 failed to
produce the ring-enlarged fluoride. This was surprising,
as the analogous bromo compounds (with an ethoxy group
at the 3-position) gave excellent yields of the ring-
enlarged bromides.1,19 Vinyl fluoride 8 with tert-butoxide
gave only the tert-butyl enol ether substitution product,
leading to 3,3-bis(ethylthio)-2,2,4,4-tetramethylcyclobu-
tane carboxaldehyde (26) after hydrolysis. With LDA the
carbene-cyclpentyne pathway afforded 4,4-bis(ethylthio)-
3,3,5,5-tetramethylcyclopentene (27), but no ring-en-
larged fluoride.
Resu lts a n d Discu ssion
Compared to the other halogens, fluorine is a much
weaker stabilizer of an adjacent negative charge,14 and
harsher reaction conditions were necessary to generate
the initial fluorovinyl carbanion. Complete reaction of
1-(fluoromethylene)-3-hexylcyclobutane (3) with potas-
sium tert-butoxide was effected in a sealed tube at 180-
185 °C in 10-15 min. Two major volatile products were
isolated after hydrolysis, 1-fluoro-4-hexylcyclopentene
(21) and 3-hexylcyclopentanone (22), in ∼2:1 ratio. A
trace of a hydrocarbon tentitatively identified as dimer
23 was also produced. When 3 was treated with lithium
diisopropylamide (LDA)-THF complex in cyclohexane at
-20 °C, rearranged fluoride 21 and 4-hexylcyclopentene
(24) were produced in a relative ratio of 1:2.
Rearrangement of 3-hexyl-1-(fluoromethylene)cyclobu-
tane (3) did not occur after 1 h in refluxing heptane (98
°C), conditions under which all of the other (halometh-
ylene)cyclobutanes reacted to give the rearrangement
products shown below. A comparison of the product
mixtures as a function of halide and reaction conditions
(14) Chambers, R. D.; Bryce, R. In Comprehensive Carbanion
Chemistry, Part C. Ground and Excited-State Reactivity; Buncel, E.,
Durst, T., Eds.; Elsevier: New York, 1987; Chpt. 5.
(15) Erickson, K. L.; Wolinsky, J . J . Am. Chem. Soc. 1965, 87,
1142.
(16) Newcomb, M.; Burchill, M. T.; Deeb, T. M. J . Am. Chem. Soc.
1988, 110, 6528.
(17) Topolski, M.; Duraisamy, M.; Rachon, J .; Gawronski, J .;
Gawronska, K.; Goedken, V.; Walborsky, H. M. J . Org. Chem. 1993,
58, 546 and references therein.
(18) 1-Cyclopentenylcyclopentene has been reported when cyclo-
pentyne is generated from 1,2-dibromocyclopentene and n-BuLi: Wit-
tig, G.; Heyn, J . Liebigs Ann. Chem. 1969, 726, 57.
(19) Erickson, K. L. J . Org. Chem. 1971, 36, 1031.
(13) Takeyama, Y.; Ichinose, Y.; Oshima, K.; Utimoto, K. Tetrahe-
dron Lett. 1989, 30, 3159.

Carbanionic Rearrangements of (Halomethylene)cyclobutanes
J . Org. Chem., Vol. 63, No. 24, 1998 8883
Ta ble 1. Rea r r a n gem en t P r od u cts of
3-Hexyl-1-(h a lom eth ylen e)cyclobu ta n es
% yield of
% yield of
temp (°C)
(Solvent)
halocyclopentene cyclopentanone
compd
(b/a ratio)
(b/a ratio)
3
180 (none)
98 (heptane)
180 (none)
98 (heptane)
180 (none)
160 (pentadecane)
98 (heptane)
180 (none)
40 (1.52)
0
18 (2.08)
trace
10 (1.05)
8 (1.37)
0
0
12
13
32 (2.80)
58 (1.45)
20 (2.84)
18 (2.54)
63 (1.35)
21 (3.88)
83 (2.10)
86 (1.85)
5 (1.40)
18
0
0
0
is shown in Table 1. The ratio of single migration
(Scheme 1) to double migration (Scheme 2) was detected
by 13C NMR. In all cases studied, the label was found in
the rearranged products at both vinyl carbons. The
relative amount of label at each, however, was a function
of the reaction temperature and the nature of the halide.
There are several factors operating in the stabilization/
destabilization of the halovinyl anion: inductive with-
drawal effects (Iσ), resonance effects, and electron-pair
repulsion effects (Iπ).14 The first two effects stabilize the
vinyl carbanion and the last, aggravated by the planar
nature of the vinyl carbanion, destabilize it. In the case
of the vinyl fluoride, with a short C-X bond, the
98 (heptane)
69 (hexane)
Sch em e 3
destabilizing Iπ effect cancels the stabilizing Iσ effect.
Moreover, resonance stabilization is prohibited here by
the inability of fluorine to expand its octet. This is
reflected in the higher temperature needed to generate
the fluorovinyl anion. The temperature is important in
controlling the ratio of single to double migration. Double
migration, where two bonds must be broken, is preferred
at higher temperatures.
Both single and double migration mechanisms involve
rehybridization of the initial vinyl anion in order to
permit free rotation and attainment of the proper geom-
etry required for rearrangement.1,20 Scheme 3 illustrates
the Newman projection of the rehybridized halovinyl
anion and the two pathways for it to rearrange to the
halocyclopentene system. Counterclockwise rotation by
45° gives conformer 31 in which both the empty p-orbital
and the carbon-halide bond are coplanar with the two
ring carbon bonds. Migration of the halide and the ring
carbon may be synchronous or involve an intermediate
carbene-halide complex (33), as depicted in Schemes 2
and 4.1,21 Alternately, a 45° clockwise rotation gives
conformer 32 where the empty p-orbital is aligned with
a ring carbon bond, but the carbon-halide bond is not.
Here, the ring carbon migrates, but the halide does not.
Because of electron pair repulsion, conformer 31 is
expected to require higher temperatures for its formation
than conformer 32. However, 31 can undergo halide-
assisted carbon migration while 31 must undergo unas-
sisted carbon migration. If conformer 31 rearranges
faster than 32, then the increase in the ratio of double
to single migration at higher temperatures shown in
Table 1 becomes understandable. Table 1 also shows
that the ratio of double to single migration decreases in
the order I > Br, Cl > F which reflects the decreasing
Sch em e 4
effectiveness of the halogen as a neighboring group and
increasing C-X bond strength. Complete dissociation of
the halide from the organic moiety (R-elimination) leads
(20) Du, Z.; Erickson, K. L. Manuscript in preparation.
(21) Erickson, K. L. J . Org. Chem. 1973, 38, 1463.

8884 J . Org. Chem., Vol. 63, No. 24, 1998
Du et al.
Ta ble 2. NMR Ch em ica l Sh ift Va lu es of th e Vin yl
to nonhalogenated products, and this becomes the major
reaction pathway at 180 °C.
Ca r bon s a n d Vin yl Hyd r ogen s of
1-(Ha lom eth ylen e)-3-h exylcyclobu ta n es a n d
1-Ha lo-4-h exylcyclop en ten es
The label distribution in the cyclopentanone 22 is also
a function of the halide and the reaction temperature.
3-Hexylcyclopentanone comes from hydrolysis of tert-
butyl enol ether 25; 25 may be generated by attack of
the tert-butoxy anion on the intermediate vinyl carbene-
halide complex 33 as well as on the cyclopentyne. At 180
°C, the vinyl carbene-fluoride complex (33, X ) F)
persists longer than the vinyl carbene-chloride complex
(33, X ) Cl), leading to larger amounts of 22b. At 98
°C, the vinyl carbene-chloride and bromide complexes
are of comparable stability. No cyclopentanone was
detected in reactions of the vinyl iodide; in this case
double migration apparently occurs rapidly enough to
preclude butoxide trapping.
Because fluorine is very effective at stabilizing a â-
negative charge, methylenecylcobutanes with allylic
fluoro groups were synthesized and examined for their
ability to undergo carbanionic rearrangement. Exocyclic
allylic fluorides 20 stabilize the initially formed vinyl
anion. However, 3-hexyl-1-(trifluoromethylmethylene)-
cyclobutane (20) did not undergo base-induced rear-
rangement. When treated with potassium tert-butoxide
at 100 °C, 20 gave only recovered starting material
together with hydrolysis product 3-hexylcyclobutylidene
acetic acid (34). With phenyllithium at 25 °C only 20
was recovered, and with n-butyllithium in refluxing hex-
ane (14 h) 20 was recovered as part of a complex product
mixture but no rearranged material was detected.
13C (ppm)
13C (ppm)
1H (ppm)
Ha
1H (ppm)
Hb
X
Ca
Cb
Ca
Cb
H
F
Cl
Br
I
4.71
6.35
5.71
5.77
5.70
105.2
141.4
108.2
96.4
148.0
118.6
140.6
143.8
151.1
5.37
4.89
5.58
5.76
6.04
130.0
161.1
131.3
119.6
91.8
130.0
101.2
125.7
130.2
139.4
68.7
I except for H-1 in the methylenecyclobutane series
where there is negligible difference in deshielding by Cl,
Br, and I. In acyclic vinyl halides this same order is
followed.22
Con clu sion s
The base-induced rearrangement of (halomethylene)-
cyclobutanes to 1-halocyclopentenes has been extended
to vinyl fluorides, but high temperatures are required in
order to form the fluorovinyl anion. Of the two pathways
leading to ring enlargement, double migration is favored
over single migration at higher temperatures and with
increasing halide size. Fluorines â to the negative charge
are not sufficient to induce the rearrangement.
Exp er im en ta l Section
Gen er a l P r oced u r es. Chemical reagents were purchased
from commercial sources and were used without purification
unless noted otherwise. Reaction solvents were reagent grade.
Ether and tetrahydrofuran were dried by distillation from
sodium benzophenone ketyl in an inert atmosphere. Pyridine
was dried by distillation from CaH2. All reactions were carried
out with oven-dried glassware. MgSO4 was the drying agent
used in all standard reaction workups. Solvent removal was
effected by rotary evaporation unless specified otherwise. All
melting and boiling points are uncorrected.
Analytical thin-layer chromatography (TLC) was performed
on commercial BakerFlex (silica gel IB2F) plates, and prepara-
tive TLC was done on Brinkmann HF 254+366 type 60 silica
gel. Visualization was by UV light, exposure to I2 vapors, and/
or H2SO4 spray. Vacuum liquid chromatography (VLC) was
performed with silica gel (EM no. 7736, type 60). Flash column
chromatography (FCC) was performed on J . T. Baker 40 µm
silica gel under a positive pressure of nitrogen. Analytical and
preparative vapor phase chromatography (VPC) was carried
out with 10% Carbowax 20M on Anakrom Q, 80/100 columns
(10 ft × 1/8 in. or 10 ft × 1/4 in.).
NMR Sp ectr a l P a r a m eter s of (Ha lom eth ylen e)-
cyclobu ta n es. A comparison of the 1H and 13C chemical
shift values of the 1-(halomethylene)-3-hexylcyclobutanes
and the 1-halo-4-hexylcyclopentenes provides a good
illustration of the effect of the halogen on the electronic
distribution at the vinylic carbons. C-1 is deshielded by
the Iσ effect, and C-2 is shielded by the Iπ effect. Table 2
gives the chemical shift values for the vinyl carbons and
the vinyl hydrogens of 3-hexyl-1-(methylene)cyclobutane
(4) and the fluoro- (3), chloro- (12), bromo- (13), and iodo-
(18) derivatives. Also listed are the corresponding values
for halocyclopentenes 21, 28, 29, and 30. Both deshield-
IR spectra of liquid samples were run neat, and solids were
run as KBr pellets. 1H NMR spectra were determined at 200
MHz in CDCl3 with TMS (0.00 ppm) as the internal reference.
13C NMR spectra were recorded at 50.3 MHz with CDCl3 as
the solvent and reference (77.0 ppm). 13C NMR assignments
were made on the basis of chemical shifts and proton multi-
plicities (from APT spectra). Chemical shifts of 19F NMR
spectra were recorded at 188.1 MHz in CDCl3 with CFCl3 as
the internal reference (0.0 ppm). Quantitative 13C NMR
analyses of 13C-enriched compounds were carried out as
described previously.1 Elemental analyses were performed by
Desert Analytics, Tucson, AZ.
(22) Pretsch, E.; Clerc, T.; Seibel, J .; Simon, W. In Tables of Spectral
Data for Structure Determination of Organic Compounds, 2nd ed.;
Fresenius, W., Huber, J . F. K., Pungor, E., Rechnitz, G. A., Simon,
W., West, T. S., Eds.; Springer-Verlag: New York, 1989.
ing and shielding trends follow the order F . Cl > Br >

Carbanionic Rearrangements of (Halomethylene)cyclobutanes
J . Org. Chem., Vol. 63, No. 24, 1998 8885
3-Hexylcyclobu ta n on e (2). A mixture of 6.5 g (0.10 mol)
of Zn powder, 5.6 g (0.05 mol) of 1-octene, and 250 mL of dry
ether under N2 was placed in an ultrasonic water bath
maintained at 15-20 °C.4 With sonication, a solution of
trichloroacetyl chloride (12.7 g, 0.075 mol) in 135 mL of dry
ether was added dropwise over 1 h; sonication was continued
for an additional 30 min. The reaction mixture was treated
with 10 mL of H2O and filtered through Celite. The filtrate
was extracted with ether and washed with H2O, saturated
NaHCO3, and saturated NaCl. After the solvent was dried
and removed, 2,2-dichloro-3-hexylcyclobutanone (1) was ob-
tained as a yellow brown oil (10.4 g, ∼100%), IR (neat) 2925,
1808 cm-1. Crude 1 was diluted with HOAc (10 mL) and added
dropwise to a rapidly stirred mixture of Zn dust (21 g, 0.32
mol) in HOAc (30 mL). After complete addition, the mixture
was stirred at 80 °C for 2 h and then cooled and 5 mL of H2O
was added. The mixture was filtered through Celite, the
filtrate was then washed with water, saturated NaHCO3, and
saturated NaCl and dried, and the solvent was removed.
Vacuum distillation gave 3-hexylcyclobutanone (2), bp1.8 ) 87-
88 °C (7.01 g, 91%). The spectral properties of 2 were identical
to those previously reported.23
1-(methylene-13C)cyclobutane (4) (10% enriched, 2.70 g, 17.7
mmol) was added dropwise. After 3 h of stirring at 25 °C, the
mixture was filtered, and the solid was washed with 20 mL of
CH2Cl2. The combined washings and filtrate were washed
with saturated NaHCO3, H2O, and saturated NaCl. After
drying, the solvent was evaporated, and the pale yellow residue
was chromatographed on silica gel with pentane:diethyl ether
(5:1) to give 2.97 g (∼100%) of 5-hexyl-1-oxaspiro[2.3]hexane-
2-13C (5) (10% enriched), colorless oil, as a mixture of diaster-
1
eomers: IR 3038, 2924, 1467, 1398 1131, 930 cm-1; H NMR
δ 0.87 (t, J ) 5.9 Hz), 1.28 (br s), 1.50 (m), 1.91-2.05 (m),
2.05-2.40 (m), 2.54 (m), 2.67 (s), 2.71 (s).
HF (48%, 12.5 g, 0.300 mmol) was added dropwise to a
solution of N-ethyldiisopropylamine (12.0 g, 0.100 mol) in
diethyl ether (30 mL) at 0 °C in a polyethylene flask. The
mixture was stirred at 25 °C for 1 h. The solvent was removed
by distillation, and the residue was transferred to a flask
epuipped with a Dean-Stark trap. Benzene (40 mL) was
added, and the solution was refluxed for 5 h. After 4.5 mL of
H2O had separated, the benzene was fractionally distilled, and
the residue was distilled under reduced pressure to give
N-ethyldiisopropylamine-tris(hydrofluoride) “Hunig’s hydro-
fluoride”, 14.3 g (76%): bp4 ) 93-95 °C; lit.8 bp4.0 ) 93-95
3-Hexyl-1-(m eth ylen e-13C)cyclobu ta n e (4). Potassium
tert-butoxide (2.24 g, 20.0 mmol) and (methyl-13C)triphen-
ylphosphonium iodide (10% enriched, 7.90 g, 19.5 mmol) in
20 mL of dry THF was stirred at 25 °C under N2 for 1 h, during
which time the color of the solution became yellow. 3-Hex-
ylcyclobutanone (2) (3.00 g, 19.5 mmol) was added dropwise,
and the reaction mixture was stirred for an additional 24 h at
25 °C. Vacuum filtration removed the solids, and distillation
removed the THF. The residue was extracted with pentane,
and the pentane layer was washed with 50% aqueous metha-
nol and then dried. The solvents were removed by distillation,
and the residue was chromatographed on silica gel with
pentane:diethyl ether (15:1) to give 2.70 g (91%) of 4 as a
°C; IR 2991, 2683 (br), 1807 (br), 1469 (br), 1134 cm-1
.
A mixture of epoxide 5 (2.97 g, 17.7 mmol), N-ethyldiiso-
propylamine (15.0 g, 116 mmol), and Hunig’s hydrofluoride
(3.40 g, 18.0 mmol) was heated for 3 h at 150 °C. After dilution
with diethyl ether (50 mL), the organic layer was washed with
10% HCl, H2O, and saturated NaCl and dried and the solvent
removed. The residue was flash chromatographed on silica
gel with hexane:ethyl acetate (3:1) to give 3.27 g (98%) of
1-(fluoromethyl-13C)-3-hexylcyclobutanol (6) (10% enriched),
colorless oil, as a mixture of diastereomers: IR 3382, 2925,
1
1462, 1287, 1020 cm-1; H NMR δ 0.86 (t, J ) 6.5 Hz), 1.24
(br s), 1.38 (m), 1.6-1.8 (m), 2.1-2.5 (m), 4.19 (d J ) 51.5 Hz),
4.43 (d J ) 51.5 Hz); 19F NMR δ -228.4 (t, J ) 51.4 Hz),
-228.6 (t, J ) 51.6 Hz).
colorless oil: IR 3073, 2921, 2853, 1676, 1466 873 cm-1 1H
;
NMR δ 0.88 (3H, t, J ) 6.3 Hz), 1.26 (8H, m), 1.45 (2H, m),
2.28 (3H, m), 2.73 (2H, m), 4.71 (2H, m); 13C NMR δ 14.1 (CH3),
22.7 (CH2), 27.5 (CH2), 29.3 (CH2), 30.3 (CH), 31.9 (CH2), 36.6
(CH2), 37.7 (CH2, 2 carbons), 105.2 (dCH2), 148.0 (dC).
To 6 (1.62 g, 8.60 mmol) in 20 mL of dry pyridine at 0-5 °C
was added 4 mL of POCl3. The mixture was stirred for 20 h
at 25-30 °C, diluted with petroleum ether (40 mL), and slowly
quenched with H2O (20 mL). The mixture was extracted with
petroleum ether and washed with dilute HCl followed by brine.
After the solvent was dried and removed, the residue was
chromatographed on silica gel with pentane:diethyl ether (5:
1) to give 1.28 g (87%) of 1-(fluoromethylene-13C)-3-hexylcy-
clobutane (3) (10% enriched).
3,3-Bis-(eth ylth io)-2,2,4,4-tetr am eth ylcylobu tan on e (7).
The method of Paquer and co-workers10 was followed, but the
reaction time was extended to two weeks to provide an 88%
yield of 7: bp0.07 ) 62-64 °C; lit.9 bp2.5 ) 100 °C; IR and 1H
NMR agreed with those in ref 9 (note that the number of
hydrogens at δ 1.35 is quoted as 9 rather than 12 in ref 10);
13C NMR δ 13.7 (CH3), 22.2 (CH3), 25.6 (CH2), 67.0 (C-2, C-4),
70.2 (C-3), 219.2 (C-1).
1-(F lu or om eth ylen e)-3-h exylcyclobu ta n e (3). Method
A. (Fluoromethyl)triphenylphosphonium tetrafluoroborate was
prepared from triphenylphosphine, tribromofluoromethane,
and sodium bromide as described by Burton and Wiemers.7
The product was purified by VLC (EtOAc:MeOH, 95:5) followed
by recrystallization from CH2Cl2. A solution of 0.46 g (1.2
mmol) of (fluoromethyl)triphenylphosphonium tetrafluorobo-
rate in 8 mL of dry THF under Ar was cooled to -78 °C. To
this stirred solution was added dropwise 0.75 mL of 1.6 M (1.2
mmol) n-BuLi in hexane. After complete addition, the mixture
was stirred for 30 min at -78 °C, and then 0.185 g of
3-hexylcyclobutanone (2) was added dropwise. Stirring was
continued at -78 °C for 2 h, the mixture was warmed to 0 °C,
and 0.125 g of solid KO-t-Bu was added. The mixture was
warmed to 25 °C and stirred for 2 h. Ether was added, and
the mixture was filtered through Celite. The filtrate was
washed with saturated NaCl until the washings were neutral.
The organic layer was dried and the solvent removed. The
dark brown residue was flash distilled and further purified
by VPC to give 0.008 g of recovered 2 and 0.186 g (91%)
l-(fluoromethylene)-3-hexylcyclobutane (3): IR 3089, 2955,
3,3-Bis-(et h ylt h io)-1-(flu or om et h ylen e)-2,2,4,4-t et r a -
m eth ylcyclobu ta n e (8). Ketone 7 was converted to 8 with
(fluoromethylene)triphenyphosphorane as described for 3 above
(method A). The product was purifed by VLC on silica gel
(pentane) followed by VPC to give a 33% yield of 8: IR 2964,
1
2929, 1698, 1086, 1035 cm-1; H NMR δ 1.22 (6H, t, J ) 7.5
Hz), 1.38 (6H, s), 1.49 (6H, s), 2.57 (4H, q, J ) 7.5 Hz), 6.36
(1H, d, J ) 83.2 Hz); 13C NMR δ 13.8 (CH3), 25.6 (CH3), 25.7
(CH2), 27.4 (CH3), 47.8 (d, J ) 10.2 Hz, C-2 or C-4), 50.1 (d, J
) 2.6 Hz, C-2 or C-4), 75.1 (C-3), 136.6 (d, J ) 4.8 Hz, C-1),
142.2 (d, J ) 251.8 Hz, CHF); 19F NMR δ -147.2 (d, J ) 83.9
Hz); HRMS calcd for C11H18FS2 [(M - C2H5)+] 233.0830.
Found 233.0847.
1
2923, 1711, 1093, 1067 cm-1; H NMR δ 0.88 (3H, t, J ) 6.8
Hz, 1.26 (8H, m), 1.43 (2H, m), 2.25 (3H, m), 2.73 (2H, m),
6.35 (1H, d of quintets J ) 85.6, 2.4 Hz); 13C NMR δ 14.1 (CH3),
22.6 (CH2), 27.1 (CH2), 29.2 (CH2), 31.1 (d, J ) 10.0 Hz, CH2),
31.8 (CH), 31.8 (d, J ) 5.1 Hz, CH2), 31.9 (CH2), 36.5 (CH2),
118.6 (d, J ) 11.4 Hz, C-1), 141.4 (d, J ) 244.9 Hz, CHF); 19
F
1-(Ha lom eth ylen e)-3-h exylcyclobu ta n es (9, 10, 11). To
a solution of unlabeled epoxide 5 (168 mg, 1.00 mmol) and
acetic acid (180 mg, 3.00 mmol) in dry THF (10 mL) was added
anhydrous LiX (X ) Cl, Br, I, 1.60 mmol), and the reaction
mixture was stirred at 25 °C. After completion of the reaction
(TLC monitoring: I, 30 min; Br, 6 h; Cl, 24 h), the reaction
mixture was diluted with H2O and extracted with ether. The
organic layer was washed with H2O and dried and the solvent
NMR δ -143.3 (d, J ) 85.6 Hz). Anal. Calcd for C11H19F: C,
77.60; H, 11.25. Found: C, 77.38; H, 11.17.
Method B. A solution of m-chloroperoxybenzoic acid (4.58
g, 21.2 mmol) in CH2Cl2 (20 mL) was cooled to 0 °C. 3-Hexyl-
(23) Schmit, C.; Falmagne, J . B.; Escudero, J .; Vanlierde, H.; Ghosez,
L. Org. Synth. 1990, 69, 199.

8886 J . Org. Chem., Vol. 63, No. 24, 1998
Du et al.
evaporated. The residue was dissolved in ether and passed
through a short columm of silica gel to remove traces of
inorganic salts giving the halohydrins (9, 10, and 11) quan-
titatively.
1-(2,2,2-Tr iflu or o-1-iodoeth yl)-3-h exylcyclobu ta n e (19).
The method of Takeyama (et al.13 was followed. Gaseous CF3I
(37 mL) was condensed into a vessel under Ar cooled to -35
°C. To this were added 135 mL of hexane and 2.70 g (0.0175
mol) of 3-hexyl-1-(methylene)cyclobutane (4). Triethylborane
(19.55 mL) was added, and the mixture was stirred at -35 °C
for 5 h. The solvent was removed to give a 79% yield of crude
1-(2,2,2-Trifluoro-1-iodoethyl)-3-hexylcyclobutane (19).13
To a solution of 9.0 g KOH in 120 mL of 95% EtOH was
added 9.35 g of 19, and the mixture was refluxed for 4 h.
Water was added followed by ether extraction. After the
solvent was dried and removed, the residue was subjected to
vacuum flash distillation to give 4 mL of a yellow liquid
containing three components. VPC separation afforded 20 as
the major component: IR 2925, 1715, 1350, 1280, 1185, 1120,
To a stirred solution of crude halohydrin (1 mmol) in dry
pyridine (5 mL) at 0-5 °C was added 1 mL of POCl3, and the
mixture was stirred 20 h at 25 °C. The reaction mixture was
diluted with petroleum ether (10 mL) and slowly quenched
with water (10 mL). The mixture was extracted with petro-
leum ether and washed with dilute HCl followed by brine.
After drying and removal of the solvent, the residue was
chromatographed on silica gel with pentane:diethyl ether (5:
1) to give 12 (70 mg, 42%), 13 (90 mg, 40%), and starting
epoxide 5 (80 mg) from 11.
1-(Ch lor om et h ylen e-13C)-3-h exylcyclob u t a n e (12).
A
1
1065 cm-1; H NMR δ 0.87 (3H, t), 1.25 (8H, br s), 1.48 (2H,
mixture of epoxide 5 (1.0 g, 6.0 mmol), triphenylphosphine (2.3
g, 9.0 mmol), and CCl4 (10 mL) was refluxed under N2 for 2 h.
The solution was diluted with ether and then washed with
water and brine. The organic layer was dried and the solvent
removed. The residue (crude 14) was refluxed with a solution
of 0.8 g of NaOH (20 mmol) in 10 mL of 95% EtOH for 30
min, and then H2O was added. The mixture was extracted
with pentane, and the pentane extracts were washed with H2O
and dried. The pentane was removed by fractional distillation,
and the residue was flash distilled to give 0.7 g, 63% of 12:
m), 2.3-2.5 (2H, m), 2.52 (1H, heptet), 2.7-3.3 (2H, m), 5.34
(1H, m); 13C NMR δ 14.0 (CH3), 22.7 (CH2), 27.3 (CH2), 29.3
(CH2), 31.0 (CH), 31.9 (CH2), 36.5 (CH2), 36.9 (CH2), 37.1 (CH2),
110.1 (CH, q, J ) 33.6 Hz), 123.9 (CF3, q, J ) 270.0 Hz), 154.0
(C-1, q, J ) 6.8 Hz); 19F δ -60.4. Anal. Calcd for C12H19F3:
C, 65.41; H, 8.71. Found: C, 65.21; H, 8.69.
Gen er a l P r oced u r e for P ot a ssiu m ter t-Bu t oxid e-
In d u ced Rea r r a n gem en t of (Ha lom eth ylen e)cyclobu -
ta n es 3, 9, 10, a n d 11. The vinyl halides were treated with
KOt-Bu under four different sets of reaction conditions: at 180
°C in absence of solvent, at 160 °C in pentadecane, at 98 °C in
refluxing heptane, and at 69 °C in refluxing hexane. In all
cases chromatographically pure samples were used.
Freshly sublimed KOt-Bu (0.28 g, 2.5 mmol) was suspended
in solvent (5 mL) in a flask equipped with a reflux condenser,
a drying tube, a magnetic stirrer, an N2 inlet, and a septum
cap. The system was heated in an oil bath to the desired
temperature, and the vinyl halide (1.0 mmol) was injected by
syringe. In the case of the vinyl fluoride with no solvent, the
reactants were mixed at 25 °C, sealed in a reaction tube, and
heated to the desired temperature. The temperature was
maintained for 30 min, the mixture was cooled, and H2O was
added. The reaction mixture was extracted with pentane, the
combined pentane layers were washed with H2O, and the
pentane was removed by fractional distillation. The residue
was subjected to flash distillation under reduced pressure
followed by preparative VPC purification of products. All
yields reported are isolated yields of purified products. See
Table 1.
1
IR 3073, 2924, 1674, 1467 cm-1; H NMR δ 0.89 (3H, t, J )
7.2 Hz), 1.27 (8H, br s), 1.50 (2H, m), 2.26 (3H, m), 2.81 (2H,
m), 5.71 (1H, quintet, J ) 2.4 Hz); 13C NMR δ 14.1 (CH3), 22.6
(CH2), 27.2 (CH2), 29.2 (CH2), 30.3 (CH), 31.9 (CH2), 35.1 (CH2),
35.3 (CH2), 36.5 (CH2), 108.2 (dCHCl), 140.6 (dC). Anal. Calcd
for C11H19Cl (unlabeled sample): C, 70.66; H, 10.26. Found:
C, 70.81; H, 10.36.
1-(Br om om eth ylen e-13C)-3-h exylcyclobu ta n e (13).
A
solution of labeled alkene 4 (1.00 g, 6.60 mmol) in CH2Cl2 (30
mL) was cooled to 0 °C, and bromine (0.64 g, 8.0 mmol) was
added dropwise. Stirring was continued at 0 °C for 15 min
after the addition was complete. The solution was washed
with aqueous NaHSO3, 6 M HCl (until the washings were
acidic), H2O, and brine. The organic layer was dried, and the
solvent was removed. The residue (crude 15) was dehydro-
halogenated as described above for 12 to give 0.88 g, 58% of
13: IR 3074, 2922, 1664, 1466 cm-1; 1H NMR δ 0.88 (3H, t, J
) 6.8 Hz), 1.26 (8H, br s), 1.46 (2H, m), 2.25 (3H, m), 2.72
(2H, m), 5.77 (1H, quintet, J ) 2.4 Hz); 13C NMR δ 14.1 (CH3),
22.6 (CH2), 27.2 (CH2), 29.2 (CH2), 29.5 (CH), 31.8 (CH2), 36.4
(CH2), 36.5 (CH2), 37.1 (CH2), 96.4 (dCHBr), 143.8 (dC). Anal.
Calcd for C11H19Br (unlabeled sample): C, 57.15; H, 8.28.
Found: C, 57.14; H, 8.21.
3-Hexyl-1-(iod om eth ylen e-13C)cyclobu ta n e (18). Iodine
(0.64 g, 8.0 mmol), NaI (0.60 g, 4.00 mmol), CuO (0.30 g, 3.90
mmol), and 48% HBF4 (0.73 g, 4.00 mmol) were added to a
solution of alkene 5 (1.00 g, 6.60 mmol) in CH2Cl2 at 0 °C.
Stirring was continued at 0 °C for 50 min after the addi-
tion was complete. The mixture was filtered and washed with
CH2Cl2. The organic layer was washed with H2O and brine
and then dried and the solvent removed to give crude 16.
Attempted dehydrohalogenation of 16 as described for 12 gave
only recovered alkene 4 in 58% yield.
A solution of labeled alkene 4 (1.00 g, 6.60 mmol) in
CH2Cl2 (30 mL) was cooled to 0 °C. Iodine monochloride (1.22
g, 7.50 mmol) in CH2Cl2 (2 mL) was added dropwise, and
stirring was continued at 20 °C for 30 min after the addition
was complete. The solution was then washed with aqueous
NaHSO3, 6 M HCl (until the washings were acidic), H2O, and
brine. The organic layer was dried, and the solvent was
removed. The residue (crude 17) was dehydrohalogenated in
the same manner as described above for 12 to give 0.90 g, 49%
of 18: IR 3076, 2925, 1651, 1458 cm-1; 1H NMR δ 0.88 (3H, t,
J ) 6.8 Hz), 1.26 (8H, br s), 1.44 (2H, m), 2.10 (1H, m), 2.17
(2H, m), 2.65 (2H, m), 5.70 (1H, quintet, J ) 2.4 Hz); 13C NMR
δ 14.1 (CH3), 22.6 (CH2), 27.3 (CH2), 28.3 (CH), 29.2 (CH2),
31.9 (CH2), 36.3 (CH2), 37.7 (CH2), 40.9 (CH2), 68.7 (dCHI),
151.1 (dC). Anal. Calcd for C11H19I (unlabeled sample): C,
47.49; H, 6.88. Found: C, 47.89; H, 6.70.
1-Flu or o-1-13C-4-h exylcyclopen ten e (21a) an d 1-Flu or o-
2-13C-4-h exylcyclop en ten e (21b): IR 3084, 2924, 1682, 1179
cm-1; 1H NMR δ 0.88 (3H, t, J ) 6.5 Hz), 1.27 (8H, br s), 1.42
(2H, m), 1.89 (m), 2.16 (m), 2.25-2.55 (m) 4.89 (1H, m); 13C
NMR δ 14.1 (CH3), 22.6 (CH2), 27.6 (CH2), 29.3 (CH2), 31.8
(CH2), 33.3 (d, J ) 8.4 Hz, CH2), 35.2 (d, J ) 19.1 Hz, CH2),
35.3 (CH), 36.8 (CH2), 101.2 (d, J ) 10.7 Hz, CH), 161.1 (d, J
) 276.4 Hz, CF); 19F NMR δ -121.4. HRMS: Calcd for
C
11H19F (M+): 170.1471. Found: 170.1469.
3-Hexyl-1-13C-cyclop en ta n on e (22a ) a n d 3-Hexyl-5-13C-
cyclop en ta n on e (22b): IR 2925, 1744 cm-1; 1H NMR δ 0.88
(3H, t, J ) 6.7 Hz), 1.28 (8H, m), 1.38 (2H, m), 1.78 (1H, dd,
J ) 8.9 Hz, further split), 2.0-2.5 (6H, m); 13C NMR δ 14.1
(CH3), 22.6 (CH2), 27.8 (CH2), 29.3 (CH2), 29.5 (CH2), 31.8
(CH2), 35.7 (CH2), 37.2 (CH), 38.6 (CH2), 45.3 (CH2), 220.2
(C-1). Anal. Calcd for C11H20O (unlabeled sample): C, 78.51;
H, 11.98. Found: C, 78.22; H, 11.90. 2,4-Dinitrophenylhy-
drazone derivative, mp 103.5-104.5 (EtOH).
1-(4-Hexylcyclop en ten yl)-4-h exylcyclop en ten e (23): 1H
NMR (500 MHz) δ 0.88 (6H, t, J ) 6.8 Hz), 1.24 (16H, br s),
1.39 (4H, m), 1.97 (2H, m), 2.17 (2H, m), 2.34 (2H, m), 2.47
(2H, m), 2.58 (2H, m), 5.58 (2H, m); 13C NMR δ 14.1 (CH3),
22.6 (CH2), 27.8 (CH2), 29.3 (CH2), 31.8 (CH2), 36.5 (CH2), 37.4
(CH), 37.8 (CH2), 43.6 (CH2 ), 125.7 (CH), 131.3 (C-1).
1-Ch lor o-1-13C-4-h exylcyclopen ten e (28a) an d 1-Ch lor o-
2-13C-4-h exyl-cyclop en ten e (28b): IR 3070, 2926, 1628, 1466
cm-1; 1H NMR δ 0.88 (3H, t, J ) 6.7 Hz), 1.27 (8H, br s), 1.39
(2H, m), 2.00 (1H, m), 2.21-2.70 (4H, m), 5.58 (1H, m); 13C
NMR δ 14.1 (CH3), 22.6 (CH2), 27.8 (CH2), 29.3 (CH2), 31.8
(CH2), 36.5 (CH2), 37.4 (CH), 37.7 (CH2), 43.6 (CH2), 125.7

Carbanionic Rearrangements of (Halomethylene)cyclobutanes
J . Org. Chem., Vol. 63, No. 24, 1998 8887
(CH), 131.3 (CCl). Anal. Calcd for C11H19Cl (unlabeled
sample): C, 70.66; H, 10.26. Found: C, 70.33; H, 10.35.
1-Br om o-1-13C-4-h exylcyclopen ten e (29a) an d 1-Br om o-
2-13C-4-h exylcyclop en ten e (29b): IR 3066, 2924, 1622, 1463
cm-1; 1H NMR δ 0.87 (3H, t, J ) 7.2 Hz), 1.25 (8H, br s), 1.38
(2H, m),1.94 (1H, m), 2.34 (3H, m), 2.66 (1H, m), 5.57 (1H,
m); 13C NMR δ 13.9 (CH3), 22.5 (CH2), 27.6 (CH2), 29.2 (CH2),
31.6 (CH2), 36.2 (CH2), 37.8 (CH), 38.6 (CH2), 45.6 (CH2), 119.6
(CBr), 130.2 (CH). Anal. Calcd for C11H19Br (unlabeled
sample): C, 57.15; H, 8.28. Found: C, 57.07; H, 8.40.
1-Iod o-1-13C-4-h exylcyclop en ten e (30a ) a n d 1-Iod o-2-
13C-4-h exylcyclop en ten e (30b): IR 3070, 2923, 1609, 1465
150 °C in a sealed tube with excess KOt-Bu for 1 h. Water
was added and the aqueous was extracted with pentane. After
the pentane was dried and removed, 8 was recovered in 70%
yield. The reaction was repeated with 26 mg (0.10 mmol) of 8
at 180-185 °C. Workup afforded 16 mg of product mixture
which was subjected to preparative TLC to give 3,3-bis-
(ethylthio)-2,2,4,4-tetramethylcyclobutanecarbaldehyde (26):
1
IR 2964, 2745, 2705, 1711 cm-1; H NMR δ 1.23 (6H, t, J )
7.5 Hz), 1.36 (6H, s), 1.47 (6H, s), 2.56 (2H, q, J ) 7.5 Hz),
2.56 (1H, d, J ) 3.7 Hz), 2.58 (2H, q, J ) 7.5 Hz), 9.92 (1H, d,
J ) 3.7 Hz); HRMS calcd for C13H25OS2 [(M + 1)+] 261.1349.
Found 261.1347.
cm-1 1H NMR δ 0.88 (3H, t, J ) 6.7 Hz), 1.26 (8H, br s),
;
Rea ction of 3,3-Bis-(eth ylth io)-2,2,4,4-tetr a m eth yl-1-
(flu or om eth ylen e)cyclobu ta n e (8) w ith LDA. The reac-
tion was carried out as described for 21 with 26 mg (0.10 mmol)
of 8 and 0.11 mmol of LDA and a reaction time of 1 h. Workup
afforded a 28% yield of 4,4-bis-(ethylthio)-3,3,5,5-tetrameth-
ylcyclopentene (27) isolated by preparative TLC: IR 3062,
2959, 2927, 1601, 1452, 878, 698 cm-1; 1H NMR δ 1.22 (6H, t,
J ) 7.5 Hz), 1.37 (12H, s), 2.58 (4H, q, J ) 7.5 Hz), 4.74 (2H,
s); 13C NMR δ 13.9 (CH3), 25.6 (CH2), 26.7 (CH3), 43.0 (C-3,C-
5), 52.7 (C-4), 100.5 (CH); HRMS calcd for C13H25S2 [(M + 1)+]
245.1399. Found 245.1387.
1.39 (2H, m), 1.98 (1H, m), 2.38 (3H, m), 2.70 (1H, m), 6.04
(1H, m); 13C NMR δ 14.1 (CH3), 22.6 (CH2), 27.9 (CH2), 29.4
(CH2), 31.8 (CH2), 36.2 (CH2), 38.7 (CH), 40.4 (CH2), 50.0 (CH2),
91.8 (CI), 139.4 (CH). Anal. Calcd for C11H19I (unlabeled
sample): C, 47.49; H, 6.88. Found: C, 47.75; H, 6.60.
Rea ction of 1-F lu or o-4-h exylcyclop en ten e (21) w ith
P ota ssiu m ter t-Bu toxid e. A 40 mg sample of a 1.52/1.00
mixture of 21b/21a was allowed to react with excess KOt-Bu
at 180 °C in a sealed tube for 30 min. Workup afforded an
80% recovery of 21 with the same b/a ratio.
Rea ction of 1-F lu or o-4-h exylcyclop en ten e (21) w ith
LDA. Lithium diisopropylamide mono(tetrahydrofuran), 1.5
M in cyclohexane (0.44 mL, 0.66 mmol), was cooled to -20
°C, and 110 mg (0.65 mmol) of 21 was injected. The mixture
was stirred at -20 °C for 30 min. Aqueous HCl was added,
the mixture was extracted with pentane and dried, and the
solvents were removed. Following flash distillation, VPC
purification afforded 4-hexylcyclopentene (24) (29% yield) and
1-fluoro-4-hexylcyclopentene (21) (15% yield). 4-Hexylcyclo-
R ea ct ion of 3-Hexyl-1-(2,2,2-t r iflu or oet h ylid en e)cy-
clobu ta n e (20) w ith P ota ssiu m ter t-Bu toxid e. Freshly
sublimed KOt-Bu (0.10 g, 0.91 mmol) was heated to 100 °C,
and then 200 mg (0.91 mmol) of 20 was injected into the base.
The temperature was maintained for 10 min. Water was
added, and the mixture was extracted with pentane. The
aqueous layer was acidified and extracted with ether. The
pentane extract gave recovered 20, and the ether extract gave
a 40% yield of (3-hexylcyclobutylidene)acetic acid (34) after
purification by VLC (CH2Cl2:EtOAc, 75:25): IR 1690, 1660,
1250 cm-1; 1H NMR δ 0.88 (3H, t, J ) 6.8 Hz), 1.27 (8H, br s),
1.48 (2H, m), 2.3-2.5 (3H, m), 2.64 (1H, m), 2.81 (1H, m), 3.25
(1H, m), 5.62 (1H, quintet, J ) 2.2 Hz); 13C NMR δ 14.1 (CH3),
22.6 (CH2), 27.3 (CH2), 29.2 (CH2), 31.2 (CH), 31.8 (CH2), 36.5
(CH2), 38.4 (CH2), 39.8 (CH2), 112.4 (dCH), 168.9 (dC), 172.2
(OdC).
1
pentene (24): IR 3054, 2957, 1616 cm-1, H NMR δ 0.88 (3H,
t, J ) 6.8 Hz); 1.27 (10H, br s), 1.95 (2H, dd, further split),
2.24 (1H, heptet), 2.48 (2H, dd, further split), 5.65 (2H, br s);
13C NMR δ 14.1 (CH3), 22.7 (CH2), 28.4 (CH2), 29.5 (CH2), 31.9
(CH2), 36.6 (CH2), 37.7 (CH), 39.0 (CH2, 2C), 130.0 (CH, 2C);
HRMS calcd for C11H20 152.1560. Found 152.1533.
Rea ction of 1-F lu or o-4-h exylcyclop en ten e (21) w ith
P ota ssiu m ter t-Bu toxid e. A 15 mg sample of 21 was
subjected to the same reaction conditions as reported for 3.
Only recovered 21 was obtained.
Ack n ow led gm en t. We thank Dr. M. R. Brennan for
assistance with some of the NMR experiments.
Rea ction of 3,3-Bis-(Eth ylth io)-2,2,4,4-tetr a m eth yl-1-
(flu or om eth ylen e)cyclobu ta n e (8) w ith P ota ssiu m ter t-
Bu toxid e. A 13 mg (0.05 mmol) sample of 8 was heated at
J O9810866