A Novel Route to Geminal Dibromocyclobutanes: Syntheses of 2-Substituted Cyclobutanone Acetals and Their Reaction with Boron Tribromide

Article abstract of DOI:10.1021/jo035295o

Nine 2-substituted cyclobutanone acetals, in addition to the parent cyclobutanone acetal, were synthesized from their corresponding cyclobutanones and subsequently treated with boron tribromide. The substituents were either alkyl chains or a phenyl and a

Full text of DOI:10.1021/jo035295o

A Novel Rou te to Gem in a l Dibr om ocyclobu ta n es: Syn th eses of
2-Su bstitu ted Cyclobu ta n on e Aceta ls a n d Th eir Rea ction w ith
Bor on Tr ibr om id e
Tore Nordvik and Udo H. Brinker*
Institut fu¨r Organische Chemie, Universita¨t Wien, Wa¨hringer Strasse 38, A-1090 Wien, Austria
Udo.Brinker@univie.ac.at
Received September 3, 2003
Nine 2-substituted cyclobutanone acetals, in addition to the parent cyclobutanone acetal, were
synthesized from their corresponding cyclobutanones and subsequently treated with boron
tribromide. The substituents were either alkyl chains or a phenyl and a benzyl group, respectively.
The major compounds obtained in these reactions were, in most cases, the geminal dibromocy-
clobutanes which were obtained in yields between 50 and 73%. A 2-fold excess of BBr3 and a reaction
time of 3 h at -78 °C afforded the best yields. In four cases no dibromide formation was observed
at all, and the cyclobutanone acetals were hydrolyzed to the corresponding cyclobutanone. This is
probably due to increased steric hindrance of the acetal and BBr3 in the transition state.
SCHEME 1. P r eviou s Syn th eses of
1,1-Dibr om ocyclobu ta n ea
In tr od u ction
Intra- and intermolecular reactions of small-ring car-
benes, e.g., cyclopropylidenes and cyclobutylidenes, re-
spectively, continue to be a field of growing interest.
These reactive species have been used for the construc-
tion of polycyclic compounds such as spiropentanes,1
spirohexanes,2 spirohexenes,3 and tricyclic compounds
comprising a three-, four-, and five-membered ring,
respectively.4 For the generation of cyclopropylidenes, the
nearly exclusive method in use is the reaction between
a readily available gem-dihalocyclopropane and alkyl-
lithium at low temperatures (<-50 °C).1a To this end,
gem-dibromocyclopropanes are reacted with methyl-
lithium in diethyl ether at -78 °C. In contrast, for
cyclobutylidenes, the method mostly applied is the Bam-
ford-Stevens reaction, where a sodium or lithium salt
of a cyclobutanone tosylhydrazone is thermally or pho-
tochemically decomposed,5 or flash-pyrolyzed,6 to gener-
ate the carbene. The drawback of this reaction, however,
is the relatively high temperature required (>150 °C).
In cases where thermally labile compounds are expected,
this method may not be the right choice, and an orga-
a
Key: (a) Br2 in CHCl3; (b) KOH, 110 °C; (c) HBr; (d) 50%
NaOH in water, TEBA; (e) Br2, HgO in CH2Cl2.
nometallic route to cyclobutylidenes or the corresponding
cyclobutylidenoids is preferred. To date, only two syn-
thetic preparations of geminal dibromocyclobutanes are
known. However, the syntheses of gem-dibromocyclobu-
tanes published in the literature so far are laborious and/
or give low yields (vide infra). This led us to develop a
more convenient and general synthesis of such com-
pounds.
In the first published preparation of 1,1-dibromocy-
clobutane (4), the double bond in cyclobutene (1) was
brominated to give trans-1,2-dibromocyclobutane (2),
which underwent elimination reaction upon treatment
with potassium hydroxide to give 1-bromo-1-cyclobutene
(3). Addition of hydrogen bromide afforded 1,1-dibro-
mocyclobutane (4) in an overall yield of 28% (Scheme 1).7
Later, 4 was synthesized in a two-step synthesis.8 Diethyl
malonate and 1,3-dibromopropane were reacted in aque-
ous sodium hydroxide solution with a phase-transfer
catalyst (triethylbenzylammonium chloride) yielding 1,1-
cyclobutanedicarboxylic acid (5), which also is com-
* To whom correspondence should be addressed. Phone: +43-1-
4277-52121. Fax: +43-1-4277-52140.
(1) (a) Backes, J .; Brinker, U. H. Cyclopropylidene. In Houben-Weyl
(Methoden der Organischen Chemie); Regitz, M., Ed.; Thieme: Stut-
tgart, 1989; Vol. E 19b, pp 391-510. (b) Cyclobutylidene. In ref 1a, pp
511-541.
(2) Brinker, U. H.; Boxberger, M. Angew. Chem., Int. Ed. Engl.
1984, 23, 974.
(3) Brinker, U. H.; Weber, J . Tetrahedron Lett. 1986, 27, 5371.
(4) Brinker, U. H.; Schrievers, T.; Xu, L. J . Am. Chem. Soc. 1990,
112, 8609.
(5) (a) Kirmse W. In Carbene Chemistry, 2nd ed.; Academic: New
York, 1971; pp 473-475. (b) Baron, W. J .; DeCamp, M. R.; Hendrick,
M. E.; J ones, M., J r.; Levin, R. H.; Sohn, M. B. In Carbenes; J ones,
M., J r., Moss, R. A., Eds.; Wiley: New York, 1973; Vol. 1, pp 42-44.
(6) (a) Brown, R. F. C. Pyrolytic Methods in Organic Chemistry;
Academic: New York, 1980. (b) Brinker, U. H.; Ko¨nig, L. Chem. Ber.
1983, 116, 882.
(7) (a) Willsta¨tter, R.; Bruce, J . Ber. Dtsch. Chem. Ges. 1907, 40,
3979. (b) Brinker, U. H.; Schenker, G. J . Chem. Soc., Chem. Commun.
1982, 679.
(8) Blankenship, C.; Paquette, L. A. Synth. Commun. 1984, 14, 983.
10.1021/jo035295o CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/06/2003
9394
J . Org. Chem. 2003, 68, 9394-9399

Novel Route to Geminal Dibromocyclobutanes
mercially available.9 The latter compound was converted
to 1,1-dibromocyclobutane by a double Hunsdiecker-
Borodin degradation in an overall yield of 11%.
SCHEME 2. Syn th eses of 2-Su bstitu ted Gem in a l
Dibr om ocyclobu ta n esa
No general synthesis of 2-substituted geminal dibro-
mocyclobutanes has been reported so far. A reinvestiga-
tion of the proposed ring enlargement of 1-(1-bromo-1-
p-tolylmethyl)cyclopropyl bromide to 1,1-dibromo-2-p-
tolylcyclobutane10 led only to ring opening to give the (Z)-
and (E)-isomers of 2,4-dibromo-1-p-tolyl-1-butene.11 This
was also the case when at C-1 a phenyl group was present
instead of a p-tolyl group.11
As described earlier, the synthesis of geminal dibro-
mocyclopropanes is much simpler than the preparation
of geminal dibromocyclobutanes. While dibromocarbenes
add to double bonds to give the corresponding geminal
dibromocyclopropanes in one step, the dibromo moiety
in four-membered rings has to be introduced in a totally
different fashion. The reaction of cyclobutanones with
phosphorus pentahalide to give geminal dihalocyclobu-
tanes is applicable for geminal dichlorocyclobutanes
only.12 While adamantanone and 7-norbornanone easily
are converted to 2,2-dibromoadamantane13 and 7,7-
dibromonorbornane,14 respectively, the reaction between
phosphorus pentabromide and cyclobutanone, however,
gave only a 77:23 mixture of 2-bromocyclobutanone and
2,2-dibromocyclobutanone.15 Moreover, the aforemen-
tioned method using substituted cyclobutenes as starting
materials cannot be applied when an unsaturated side
chain is present. Bromination and subsequent elimina-
tion or addition of hydrogen bromide is expected to also
brominate the pendant double bond. Therefore, a novel
method was sought which allows the introduction of a
gem-dibromo moiety in a four-membered ring through a
replacement of another geminal group.
a
Key: (a) n-BuLi, then RBr in dry THF; (b) trimethyl ortho-
formate on Montmorillonite K-10 in pentane; (c) BBr3 in dry
CH2Cl2, 3 h; (d) n-BuLi, then RCHO in dry THF, then H3O+; (e)
TsOH in water-saturated benzene.
TABLE 1. Isola ted Yield s (%) of Com p ou n d s 7, 8 a n d 9
entry
R
7
8
9
a
b
c
d
e
f
g
h
i
H
hexyl
isopropyl
tert-butyl
95
90
98
96
90
93
91
94
94
92
73
70
c
67a
44b
60b
45b
66b
72a
78a
45b
65a
c
isobutyl
50d
c
cyclohexyl
cyclobutylmethyl
cyclohexylmethyl
phenyl
57
62
c
j
benzyl
63
a
b
General procedure 1. General procedure 2. c Only the corre-
d
sponding cyclobutanone was formed. Cyclobutanone 7e could be
isolated in 19% yield.
Cyclobutanones in entries b, g, h, and j in Table 1 were
successfully synthesized via a complementary method.
Here, the anion of cyclobutanone N,N-dimethylhydrazone
(6) generated by a strong base reacted with an alkyl or
aryl bromide to give the desired cyclobutanone directly
upon treatment with a weak acid.19
Syn th esis of Cyclobu ta n on e Aceta ls. A plethora of
methods has been published for the synthesis of acetals
from the corresponding ketones.20 We chose to use the
version developed by Taylor and Chiang, since the
experiments can been done at room temperature and also
require a short reaction time.21 Trimethyl orthoformate
was applied on a clay, Montmorillonite K-10, and addition
of the cyclobutanone afforded the corresponding cyclobu-
tanone acetals (8) in uniformly high yields of 90-98%
(Table 1).
Resu lts a n d Discu ssion
Syn th eses of 2-Su bstitu ted Cyclobu tan on es. 2-Sub-
stituted cyclobutanones (7) are easily available through
a number of syntheses.16 In the study outlined here, two
methods were employed. The first procedure consists of
a Lewis acid-catalyzed rearrangement of 1-substituted
cyclopropyl phenyl sulfides (11) (Scheme 2). These
compounds were synthesized from cyclopropylphenyl
sulfide (10), which was reacted with butyllithium to
generate the cyclopropyl anion. Addition of the appropri-
ate aldehyde gave sulfides 11,17 which upon treatment
with acids, preferentially p-TsOH in water-saturated
benzene, rearranged smoothly to the corresponding cy-
clobutanones.18 The rearrangements were successful, but
reaction time and choice of the acid proved to be
important for optimum yields.
Bor on Tr ibr om id e-In d u ced Clea va ge of Cyclobu -
ta n on e Aceta ls. It is known that boron tribromide has
been used for cleavage of alkyl ethers to alkyl bromides
and alcohols.22 Methyl ethers of secondary or tertiary
alchohols give methanol and secondary or tertiary alkyl
(9) CAS registry number provided by the author: 5445-51-2.
(10) Salaun, J .; Hanack M. J . Org. Chem. 1975, 40, 1994.
(11) Nordvik, T., Brinker, U. H. J . Org. Chem. 2003, 68, 7092.
(12) Wittig, G.; Wilson, E. R. Chem. Ber. 1965, 98, 451.
(13) Geluk, H. W. Synthesis 1970, 652.
(19) Mino, T.; Masuda, S.; Nishio, M.; Yamashita, M. J . Org. Chem.
1997, 62, 2633.
(14) Bartlett, P. D.; Ho, M. S. J . Am. Chem. Soc. 1974, 96, 627.
(15) Schenker, G. MS Thesis, Ruhr Universita¨t Bochum, Germany,
1982, p 13.
(16) For a review, see: Fitjer, L. Cyclobutanes. Synthesis: By Ring
Enlargement. In Houben-Weyl (Methods of Organic Chemistry); de
Meijere, A., Ed.; Thieme: Stuttgart, 1997; Vol. E 17e, pp 251-316.
(17) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J . H.;
Bogdanowicz, M. J . J . Am. Chem. Soc. 1977, 99, 3080.
(18) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J . J .
Am. Chem. Soc. 1977, 99, 3088.
(20) For some examples comprising four-membered rings, see: (a)
Clerici, A.; Pastori, N.; Porta, O. Tetrahedron 2001, 57, 217. (b)
Malatesta, V.; J ennings, M.; Hackett, P. Can. J . Chem. 1983, 61, 366.
(c) Tolstikov, G. A.; Miftakhov, M. F.; Akhmetvaleev, R. R.; Balezina,
G. G.; Valeev, F. A. Zh. Org. Khim. 1990, 26, 2156. (d) Guziec, F. S.
J r.; SanFilippo, L. J . J . Org. Chem. 1991, 56, 3178. (e) Kirmse, W.;
Olbricht, T. Synthesis 1975, 174.
(21) Taylor, E. C.; Chiang, C.-S. Synthesis 1977, 467.
(22) McOmie, J . F. W.; Watts, M. L.; West, D. E. Tetrahedron 1968,
24, 2289.
J . Org. Chem, Vol. 68, No. 24, 2003 9395

Nordvik and Brinker
SCHEME 3. Bor on Tr ibr om id e-In d u ced Clea va ge of Cyclobu ta n on e Aceta ls
bromides, respectively, in the reaction with BBr3.23
However, only few examples for the cleavage of alkanone
acetals to gem-dibromoalkanes have been reported in the
literature.24 The boron tribromide-induced cleavage of
cyclobutanone acetals was performed in dichloromethane
at -78 °C for 3 h (Scheme 2), and the geminal dibro-
mocyclobutanes (9) were isolated in 50-73% yields (Table
1). Characteristic in the 1H NMR spectra of 9 is the
absorption of the tertiary proton at C-2 in the range of δ
3.25-3.52 ppm, while in the 13C NMR spectra the
corresponding carbon atoms all resonate between 62.6
and 65.0 ppm. Furthermore, the quaternary carbons with
the geminal dibromo substituents, with the exception of
the parent system (δ 57.3 ppm), absorb in the area of δ
38.9 and 40.0 ppm. The first step of the reaction mech-
anism probably consists of an attack of the reagent’s
boron atom at the ether oxygen in the cyclobutanone
acetal to form an ylide (Scheme 3). Loss of bromide leads
to an oxonium ion that either loses dibromomethoxybo-
rane and the resulting carbocation recombines with the
bromide ion or the bromide ion attacks the oxonium ion
in a SN2 reaction to give 1-bromo-1-methoxycyclobutane.
Repetition of these steps will lead to the geminal dibro-
mocyclobutanes directly. Dibromomethoxyborane is hy-
drolyzed ultimately to methanol and boric acid upon
treatment with water.
Nevertheless, in entries c, d, f, and i the geminal
dibromocyclobutanes 9 could not be observed at all. This
is probably due to the steric hindrance the substituents
at C-2 introduce to the molecule, thereby precluding
attack of the boron atom in boron tribromide at the
oxygen atom of one of the methoxy groups. Moreover, the
best molar ratio was found to be a 2-fold excess of boron
tribromide, while an equimolar addition of BBr3 or less
afforded only the ketone. It was also necessary to keep
the temperature at -78 °C for at least 3 h. A shorter
reaction time favored the cyclobutanone formation.25 The
cyclobutanones (7) obtained in the reaction probably stem
from acid-induced acetal cleavage of 8, but only in entry
e some cyclobutanone could be detected besides the
geminal dibromocyclobutane. To prevent hydrolysis of the
dibromocyclobutane, before workup with water and
sodium bicarbonate, pentane was added to the reaction
mixture. The geminal dibromocyclobutanes were isolated
using flash chromatography or bulb-to-bulb distillation,
and turned out to be stable at room temperature. Their
reaction with methyllithium will be part of a forthcoming
publication.
Exp er im en ta l Section
Gen er a l In for m a tion . Trimethyl orthoformate, Montmo-
rillonite K-10, and boron tribromide were used as purchased.
Dichloromethane was distilled from CaH2 prior to use. FT
NMR spectra were recorded on a DRX-400 or a DPX-250
spectrometer at the following Larmor frequencies: νo(1H) )
400 and 250 MHz, respectively, and νo (13C) ) 100 and 62.9
MHz, respectively. IR absorption spectra were recorded on an
IR spectrometer by pressing a drop of neat liquid between two
NaCl plates. MS assays were performed on a MAT 900
spectrometer. Analytical GC analyses were conducted using
a GC instrument outfitted with a 30 m poly(dimethylsiloxane)
capillary column (PE-1, 0.32 mm i.d., and 0.25 µm film
thickness) and a flame-ionization detector. The following
condition and temperature program was used: Toven,i ) 50 °C
(10 min), ramp + 5 °C/min, Toven,f ) 100 °C, ramp +15 °C/
min, Toven,f ) 250 °C (10 min), Tinjector ) 220 °C, TFID ) 250 °C,
and flow ) 2.1 mL of He/min. GC-MS analyses were con-
ducted using a GC instrument outfitted with a 30 m poly-
(methylphenylsiloxane) capillary column (HP-5MS (95% dim-
ethyl and 5% diphenyl), 0.25 mm i.d., and a 0.25 µm film
thickness). Flash chromatography was performed with use of
silica gel 60 (230-400 mesh) and hexanes as eluent. Mi-
croanalyses were performed by the Mikroanalytisches Labo-
ratorium am Institut fu¨r Physikalische Chemie der Universita¨t
Wien, Austria. Bulb-to-bulb distillation was performed using
a Kugelrohr apparatus.
Syn th esis of Su lfid es (11): Gen er a l P r oced u r e. To a
solution of cyclopropyl phenyl sulfide (20 mmol) in dry THF
(30 mL) at 0 °C was added n-BuLi (25 mmol). After 2 h, the
aldehyde was added. The mixture was allowed to reach room
temperature, and after 2 h, water (5 mL) and diethyl ether
(100 mL) were added. The organic layer was separated, washed
with brine, and dried (MgSO4), and the solvents were removed
in vacuo. Bulb-to-bulb distillation afforded the desired com-
pound.
1-(1-P h en ylth iocyclopr opyl)-2-m eth yl-1-pr opan ol (11c).
Yield: 87%. tR ) 26.60 min. Bp: 85 °C/0.01 Torr. 1H NMR
(400 MHz, CDCl3): δ 0.90 (d, 3H, J ) 6.6 Hz), 0.98 (d, 3H, J
) 6.6 Hz), 0.98-1.02 (m, 3H), 1.09-1.13 (m, 1H), 1.54 (d, 1H,
J ) 7.1 Hz), 2.10-2.21 (m, 1H), 2.77 (t, 1H, J ) 7.3 Hz), 7.15-
7.19 (m, 1H), 7.24-2.27 (m, 2H), 7.50-7.52 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 13.6, 16.3, 18.6, 19.9, 30.2, 33.4, 83.2,
126.3, 128.7, 130.2, 136.4. IR (neat): ν 3443, 3060, 3005, 2959,
2930, 2872, 1584, 1479, 1439, 1387, 1366, 1245, 1089, 1026,
982, 739, 692 cm-1. MS (m/z): 222 (67, M+), 179 (55), 161 (52),
151 (33), 150 (46), 149 (54), 135 (33), 118 (20), 117 (100), 116
(20), 110 (42), 109 (35), 91 (61), 77 (28), 73 (28), 71 (20), 69
(22), 65 (21), 55 (23), 51 (22).
(23) Youssefyeh, R. D.; Mazur, Y. Chem. Ind. (London) 1963, 609.
(24) For an example, see: Brinker, U. H.; Ritzer, J . J . Am. Chem.
Soc. 1981, 103, 2116.
(25) Attempts to treat the cyclobutanone acetals with B-bromo-9-
borabicyclo[3.3.1]nonane instead of boron tribromide led only to the
corresponding cyclobutanones. For an example of ether cleavage with
this reagent, see: Bhatt, M. V. J . Organomet. Chem. 1978, 156, 221.
1-(1-P h e n y lt h io c y c lo p r o p y l)-2,2-d im e t h y l-1-p r o -
p a n ol (11d ). Yield: 66%. tR ) 27.15 min. Bp: 100 °C/0.01
1
Torr. H NMR (400 MHz, CDCl3): δ 0.89-1.21 (m, 4H), 1.10
(s, 9H), 1.76 (d, 1H, J ) 8.1 Hz), 2.76 (d, 1H, J ) 7.8 Hz),
9396 J . Org. Chem., Vol. 68, No. 24, 2003

Novel Route to Geminal Dibromocyclobutanes
7.15-7.20 (m, 1H), 7.24-7.30 (m, 2H), 7.52-7.57 (m, 2H). 13
C
1.35 (m, 8H), 1.43-1.58 (m, 1H), 1.60-1.75 (m, 2H), 2.10-
2.25 (m, 1H), 2.82-3.12 (m, 2H), 3.20-3.35 (m, 1H). 13C NMR
(62.9 MHz, CDCl3): δ 14.0, 16.9, 22.5, 27.0, 29.1, 29.5, 31.6,
44.3, 60.6, 212.5. IR (neat): ν 2957, 2927, 2856, 1782, 1466,
1395, 1379, 1093, 1069, 757, 723 cm-1. MS (m/z): 154 (4, M+),
126 (5), 111 (8), 98 (100), 97 (18), 84 (38), 83 (27), 82 (27), 70
(43), 69 (35), 68 (10), 67 (12), 58 (16), 57 (18), 56 (58), 55 (97),
54 (12), 53 (11).
2-Isop r op ylcyclobu ta n on e (7c). tR ) 5.60 min. Bp: 150
°C. 1H NMR (400 MHz, CDCl3): δ 0.89 (d, 3H, J ) 6.8 Hz),
0.99 (d, 3H, J ) 6.6 Hz), 1.66-1.75 (m, 1H), 1.82-1.90 (m,
1H), 2.01-2.11 (m, 1H), 2.77-2.86 (m, 1H), 2.88-2.98 (m, 1H),
3.01-3.09 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 14.5, 19.8,
20.2, 28.9, 44.1, 67.4, 211.8. IR (neat): ν 2960, 2874, 1779,
1468, 1386, 1367, 1087 cm-1. MS (m/z): 112 (18, M+), 94 (18),
84 (30), 70 (21), 69 (100), 56 (44), 55 (74).
NMR (100 MHz, CDCl3): δ 15.9, 18.1, 27.4, 29.3, 37.5, 86.1,
126.1, 128.7, 129.7, 126.9. IR (neat): ν 3473, 3060, 2954, 2905,
2869, 1584, 1480, 1439, 1396, 1364, 1240, 1050, 1026, 1012,
976, 739, 692 cm-1. MS (m/z): 236 (36, M+), 180 (30), 179 (199),
161 (32), 151 (20), 149 (21), 135 (24), 117 (57), 110 (29), 109
(21), 91 (49), 73 (29), 57 (73). HRMS: calcd for C14H20OS
236.1235, found 236.1228. Anal. Calcd for C14H20OS: C, 71.14;
H, 8.52. Found: C, 70.92; H, 8.30.
1-(1-P h en ylth iocyclop r op yl)-3-m eth yl-1-bu ta n ol (11e).
Yield: 84%. tR ) 27.15 min. Bp: 100 °C/0.01 Torr. 1H NMR
(400 MHz, CDCl3): δ 0.84 (d, 3H, J ) 6.6 Hz), 0.90 (d, 3H, J
) 6.6 Hz), 0.96-1.02 (m, 2H), 1.02-1.09 (m, 2H), 1.36-1.43
(m, 1H), 1.46-1.54 (m, 1H), 1.74 (d, 1H, J ) 6.8 Hz), 3.36 (s,
1H), 7.13-7.19 (m, 1H), 7.23-7.30 (m, 2H), 7.44-7.49 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 13.9, 14.5, 21.7, 23.6, 24.6, 31.9,
44.2, 74.6, 126.0, 128.7, 129.2, 136.5. IR (neat): ν 3422, 3060,
2956, 2929, 2869, 1584, 1480, 1439, 1385, 1367, 1070, 1026,
991, 738, 692 cm-1. MS (m/z): 236 (32, M+), 180 (23), 151 (24),
150 (80), 149 (54), 135 (55), 117 (100), 110 (30), 109 (28), 105
(22), 91 (35). HRMS: calcd for C14H20OS 236.1235, found
2-ter t-Bu tylcyclobu ta n on e (7d ). tR ) 7.55 min. Bp: 70
1
°C/12 Torr. H NMR (400 MHz, CDCl3): δ 0.96 (s, 9H), 1.77-
1.87 (m, 1H), 1.96-2.06 (m, 1H), 2.71-2.81 (m, 1H), 2.87-
2.97 (m, 1H), 3.11-3.18 (m, 1H). 13C NMR (100 MHz, CDCl3):
δ 12.9, 27.1, 31.9, 44.3, 71.3, 212.0. MS (m/z): 126 (20, M+),
98 (21), 84 (13), 83 (100), 70 (33), 69 (84), 57 (16), 55 (34).
2-Isobu tylcyclobu ta n on e (7e). tR ) 11.25 min. Bp: 100
°C/12 Torr. 1H NMR (400 MHz, CDCl3): δ 0.88 (d, 3H, J ) 6.3
Hz), 0.91 (d, 3H, J ) 6.6 Hz), 1.32-1.40 (m, 1H), 1.59-1.75
(m, 3H), 2.17-2.26 (m, 1H), 2.87-2.97 (m, 1H), 2.98-3.09 (m,
1H), 3.28-3.38 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 17.8,
22.3, 22.7, 26.5, 38.6, 44.5, 59.2, 212.5. IR (neat): ν 2957, 2928,
2871, 1780, 1468, 1386, 1368, 1095, 1067 cm-1. MS (m/z): 126
(13, M+), 98 (42), 83 (11), 82 (33), 70 (25), 69 (61), 56 (72), 55
(100). HRMS: calcd for C8H14O 126.1045, found 126.1041.
Anal. Calcd for C8H14O: C, 76.14; H, 11.18. Found: C, 76.35;
H, 10.90.
236.1237. Anal. Calcd for
Found: C, 70.85; H, 8.73.
C14H20OS: C, 71.14; H, 8.52.
1-(1-P h en ylth iocyclop r op yl)cycloh exylm eth a n ol (11g).
Yield: 78%. tR ) 29.55 min. 1H NMR (400 MHz, CDCl3): δ
0.92-1.06 (m, 5H), 1.10-1.27 (m, 4H), 1.60-1.78 (m, 5H),
1.81-1.89 (m, 1H), 2.06 (d, 1H, J ) 12.9 Hz), 2.78 (s, 1H),
7.18-7.23 (m, 1H), 7.26-7.31 (m, 2H), 7.55-7.58 (m, 2H). 13
C
NMR (100 MHz, CDCl3): δ 13.6, 16.5, 25.9, 26.0, 26.4, 29.2,
30.0, 30.1, 43.1, 82.8, 126.4, 128.7, 130.4, 136.4. IR (neat): ν
3463, 2925, 2853, 1479, 1467, 1450, 1395, 1364, 1099, 1085,
985, 759 cm-1. MS (m/z): 262 (77, M+), 180 (35), 179 (59), 161
(41), 151 (53), 150 (88), 149 (53), 135 (34), 117 (100), 111 (21),
110 (50), 109 (38), 95 (36), 91 (64), 83 (66), 79 (21), 77 (30), 73
(23), 69 (21), 67 (24), 65 (24), 55 (78), 51 (21).
2-Cycloh exylcyclobu ta n on e (7f). tR ) 21.90 min. Bp: 65
°C/0.5 Torr. 1H NMR (250 MHz, CDCl3): δ 0.91-1.08 (m, 2H),
1.10-1.31 (m, 3H), 1.50-1.80 (m, 6H), 1.85-1.96 (m, 1H),
1-(1-P h en ylth iocyclop r op yl)p h en ylm eth a n ol
(11i).
Yield: 74%. tR ) 29.35 min. 1H NMR (400 MHz, CDCl3): δ
0.94-1.02 (m, 2H), 1.06-1.15 (m, 2H), 2.67 (s, 1H), 4.83 (s,
1H), 7.20-7.45 (m, 10H). 13C NMR (100 MHz, CDCl3): δ 11.5,
14.7, 32.1, 75.9, 126.2, 127.0, 127.8, 128.0, 128.8, 129.2, 135.7,
149.4. IR (neat): ν 3416, 3061, 3029, 2956, 2931, 2871, 1584,
1479, 1453, 1439, 1041, 1027, 739, 701 cm-1. MS (m/z): 256
(94, M+), 151 (20), 150 (87), 149 (100), 135 (29), 134 (41), 117
(85), 116 (42), 115 (36), 110 (25), 109 (23), 107 (58), 105 (58),
91 (37), 79 (43), 77 (52), 51 (25).
1.96-2.11 (m, 1H), 2.74-2.97 (m, 2H), 3.01-3.14 (m, 1H). 13
C
NMR (62.9 MHz, CDCl3): δ 14.4, 25.8, 25.9, 26.3, 30.3, 30.9,
38.5, 44.2, 66.4, 211.8. IR (neat): ν 2925, 2853, 1777, 1480,
1449, 1178, 1084, 1025, 739, 691 cm-1. MS (m/z): 152 (6, M+),
150 (17), 135 (15), 134 (33), 124 (32), 117 (22), 95 (18), 85 (10),
83 (12), 82 (34), 80 (100), 68 (23), 67 (45), 55 (27), 54 (22), 53
(11).
2-Cyclobu tylm eth ylcyclobu ta n on e (7g). tR ) 18.60 min.
1
Bp: 50 °C/0.2 Torr. H NMR (400 MHz, CDCl3): δ 1.54-1.68
Syn th esis of Cyclobu ta n on es: Gen er a l P r oced u r e 1.
Under an argon atmosphere at -10 °C, cyclobutanone N,N-
dimethylhydrazone 6 (10.0 mmol) was dissolved in dry THF
(50 mL) and n-BuLi in hexane (11.0 mmol) was added. After
the mixture was stirred at this temperature for 1 h, a solution
of alkyl bromide (10.0 mmol) in dry THF (8.0 mL) was slowly
added, and the mixture was stirred at room temperature. After
20 h, 2 M HCl (20 mL) was added, and the stirring was
continued for 1 h. The reaction mixture was extracted with
EtOAc (3 × 30 mL), the organic layers were collected, washed
with brine (10 mL), and dried (MgSO4), and the solvents were
removed in vacuo. Bulb-to-bulb distillation afforded the desired
compound. The cyclobutanones 7 in entries b, g, h, and j were
synthesized according to this procedure.
Syn th esis of Cyclobu ta n on es: Gen er a l P r oced u r e 2.
The sulfide 11 (50 mmol) and p-TsOH (25 mmol) were
dissolved in water-saturated benzene (100 mL), refluxed for 2
h, and then cooled to room temperature. Water (10 mL) and
dichloromethane (100 mL) were added. The layers were
separated, and the organic layers washed once with aqueous
bicarbonate solution (20 mL) and brine (20 mL) and dried
(MgSO4). Removal of the solvents in vacuo followed by bulb-
to-bulb distillation provided the desired compound. The cy-
clobutanones 7 in entries c, d, e, f, and i were synthesized
according to this procedure.
(m, 4H), 1.76-1.89 (m, 3H), 1.99-2.07 (m, 2H), 2.10-2.20 (m,
1H), 2.32-2.44 (m, 1H), 2.86-2.95 (m, 1H), 2.96-3.06 (m, 1H),
3.17-3.26 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 17.0, 18.4,
28.2, 28.3, 34.0, 36.5, 44.6, 58.9, 212.4. IR (neat): ν 2957, 2929,
2864, 1780, 1444, 1395, 1325, 1243, 1087, 756 cm-1. MS (m/
z): 138 (7, M+), 110 (58), 95 (11), 82 (41), 81 (23), 71 (24), 69
(15), 68 (72), 67 (100), 66 (11), 55 (61), 54 (46), 53 (18).
HRMS: calcd for C9H14O 138.1045, found 138.1047. Anal.
Calcd for C9H14O: C, 78.21; H, 10.21. Found: C, 78.13; H,
10.47.
2-Cycloh exylm eth ylcyclobu ta n on e (7h ). tR ) 23.55 min.
Bp: 50-52 °C/0.03 Torr. 1H NMR (400 MHz, CDCl3): δ 0.79-
0.97 (m, 3H), 1.10-1.29 (m, 3H), 1.30-1.41 (m, 2H), 1.58-
1.74 (m, 6H), 2.15-2.24 (m, 1H), 2.86-2.95 (m, 1H), 2.96-
3.07 (m, 1H), 3.29-3.39 (m, 1H). 13C NMR (100 MHz, CDCl3):
δ 17.9, 26.1, 26.2, 26.4, 33.0, 33.5, 35.9, 37.4, 44.5, 58.7, 212.6.
IR (neat): ν 2923, 2852, 1778, 1449, 1082, 757 cm-1. MS (m/
z): 166 (11, M+), 148 (12), 138 (37), 122 (16), 109 (14), 96 (26),
95 (19), 94 (96), 93 (17), 84 (15), 83 (87), 82 (45), 81 (34), 71
(19), 67 (37), 55 (100), 54 (11). HRMS: calcd for C11H18
O
166.1358, found 166.1354. Anal. Calcd for C11H18O: C, 79.46;
H, 10.91. Found: C, 79.23; H, 10.97.
2-P h en ylcyclobu ta n on e (7i). tR ) 22.50 min. Bp: 75-80
°C/0.5 Torr. 1H NMR (250 MHz, CDCl3): δ 2.17-2.32 (m, 1H),
2.47-2.61 (m, 1H), 2.97-3.11 (m, 1H), 3.16-3.31 (m, 1H),
4.51-4.59 (m, 1H), 7.25-7.37 (m, 5H). 13C NMR (62.9 MHz,
CDCl3): δ 17.6, 44.8, 64.5, 126.9, 128.5, 128.6, 136.5. 208.1.
2-Hexylcyclobu ta n on e (7b). tR ) 21.16 min. Bp: 50 °C/
0.2 Torr. 1H NMR (250 MHz, CDCl3): δ 0.88 (t, 3H), 1.20-
J . Org. Chem, Vol. 68, No. 24, 2003 9397

Nordvik and Brinker
IR (neat): ν 3060, 3028, 2963, 2926, 1782, 1686, 1602, 1496,
1449, 1393, 1201, 1072, 736, 698 cm-1. MS (m/z): 146 (9, M+),
120 (10), 118 (7), 105 (30), 104 (100), 78 (10), 77 (18).
2-Ben zylcyclobu ta n on e (7j). tR ) 23.30 min. Bp: 50 °C/
2830, 1467, 1384, 1367, 1259, 1226, 1156, 1123, 1042, 853, 758
cm-1. MS (m/z): 140 (7, M+ - CH4O), 126 (18), 98 (48), 97
(32), 91 (12), 84 (10), 83 (17), 82 (37), 70 (29), 69 (66), 67 (12),
57 (10), 56 (73), 55 (100). HMRS: Calcd for M+ - CH4O
140.1201, found 140.1197. Anal. Calcd for C10H20O2: C, 69.72;
H, 11.70. Found: C, 70.01; H, 11.32.
1
0.05 Torr. H NMR (400 MHz, CDCl3): δ 1.69-1.78 (m, 1 H),
2.11-2.20 (m, 1 H), 2.77-2.84 (m, 1 H), 2.87-2.90 (m, 1 H),
2.98-3.07 (m, 2 H), 3.54-3.64 (m, 1 H), 7.16-7.40 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ 16.6, 35.2, 44.5, 61.2, 126.3,
128.5, 128.7, 138.8, 210.9. IR (neat): ν 3062, 3028, 2990, 2950,
2925, 1778, 1603, 1496, 1454, 1394, 1228, 1205, 1082, 1030,
743, 700 cm-1. MS (m/z): 160 (38, M+), 131 (17), 118 (48), 117
(50), 104 (18), 91 (100), 65 (15).
Syn th esis of Cyclobu ta n on e Aceta ls 8: Gen er a l P r o-
ced u r e. Trimethyl orthoformate (3.0 mL) and Montmorillonite
K-10 (2.0 g) were stirred for 15 min, and then filtered. The
wet filter cake, hexane (20 mL) and the cyclobutanone (10
mmol) were stirred at room temperature until GC analysis
showed completition of the reaction. The mixture was filtered,
water (5 mL) was added, and the organic layer separated,
washed with NaHCO3 (10%, 5 mL), and dried (MgSO4).
Removal of the solvent in vacuo followed by flash chromatog-
raphy (hexane) on silica gel, or bulb-to-bulb distillation,
provided the desired compounds as colorless oils.
1,1-Dim eth oxycyclobu ta n e (8a ). tR ) 3.85 min. Bp: 112
°C. 1H NMR (250 MHz, CDCl3): δ 1.60-1.77 (m, 2 H), 2.13 (t,
4 H, J ) 8.0 Hz), 3.15 (s, 6 H). 13C NMR (62.9 MHz, CDCl3):
δ 11.3, 31.5, 48.3, 102.9. IR (neat): ν 2996, 2948, 2830, 1459,
1274, 1235, 1153, 1144, 1111, 1043, 846 cm-1. MS (m/z): 116
(0.1, M+), 88 (100), 85 (54), 58 (39), 57 (35), 55 (10), 53 (12).
2-Hexyl-1,1-d im eth oxycyclobu ta n e (8b). tR ) 23.20 min.
Bp: 65 °C/0.1 Torr. 1H NMR (400 MHz, CDCl3): δ 0.87 (t, 3H,
J ) 7.1 Hz), 1.15-1.35 (m, 8H), 1.35-1.45 (m, 2H), 1.50-1.62
(m, 1H), 1.77-1.94 (m, 2H), 2.09-2.16 (m, 1H), 2.30-2.40 (m,
1H), 3.14 (s, 3H), 3.16 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
14.0, 18.4, 22.6, 27.2, 28.8, 29.4, 30.1, 31.8, 44.7, 48.4, 48.5,
103.6. IR (neat): ν 2989, 2930, 2857, 2830, 1744, 1458, 1262,
1229, 1158, 1125, 1043, 857 cm-1. MS (m/z): 200 (0.4, M+),
172 (20), 169 (15), 137 (12), 135 (13), 101 (71), 98 (32), 97 (27),
89 (13), 88 (100), 85 (21), 84 (15), 70 (10), 69 (14), 58 (44), 57
(14), 56 (18), 55 (37). HRMS: calcd for C12H24O2 200.1776,
found 200.1773. Anal. Calcd for C12H24O2: C, 71.95; H, 12.07.
Found: C, 72.14; H, 11.71.
2-Cycloh exyl-1,1-d im eth oxycyclobu ta n e (8f). tR ) 23.85
1
min. Bp: 50 °C/0.05 Torr. H NMR (400 MHz, CDCl3): δ 0.74
(dq, 1H, J ) 12 Hz, J ) 3.6 Hz), 0.88 (dq, 1H, J ) 12.4 Hz, J
) 3.8 Hz), 1.08-1.31 (m, 3H), 1.34-1.48 (m, 2H), 1.60-1.72
(m, 4H), 1.75-1.81 (m, 1H), 1.84-1.92 (m, 1H), 1.93-2.00 (m,
1H), 2.04-2.16 (m, 2H), 3.13 (s, 3H), 3.14 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 16.5, 26.2, 26.4, 26.7, 28.7, 29.9, 33.5,
37.9, 48.1, 48.8, 50.4, 104.3. IR (neat): ν 2988, 2923, 2851,
2830, 1448, 1266, 1158, 1126, 1046, 854 cm-1. MS (m/z): 170
(22, M+), 127 (15), 89 (11), 88 (100), 58 (16), 57 (19), 56 (14).
HRMS: calcd for C12H22O2 170.1307, found 170.1310. Anal.
Calcd for C12H22O2: C, 72.68; H, 11.18. Found: C, 72.59; H,
11.02.
2-Cyclob u t ylm et h yl-1,1-d im et h oxycyclob u t a n e (8g).
tR ) 22.05 min. Bp: 50 °C/0.1 Torr. 1H NMR (400 MHz,
CDCl3): δ 1.22-1.32 (m, 1H), 1.48-1.71 (m, 4H), 1.74-1.85
(m, 3H), 1.86-1.94 (m, 1H), 1.97-2.06 (m, 2H), 2.10-2.18 (m,
1H), 2.22-2.37 (m, 2H), 3.15 (s, 3H), 3.17 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 18.5, 18.6, 28.4, 28.7, 29.0, 34.2, 37.5,
42.7, 48.4, 48.5, 103.7. IR (neat): ν 2948, 2857, 2830, 1444,
1260, 1241, 1158, 1125, 1042, 861, 758 cm-1. MS (m/z): 152
(30, M+ - CH4O), 123 (18), 110 (12), 109 (21), 98 (12), 97 (100),
92 (14), 91 (34), 85 (15), 84 (15), 82 (10), 81 (11), 79 (17), 71
(27), 68 (16), 67 (39), 65 (10), 60 (10), 57 (48), 57 (29), 55 (34),
54 (14), 53 (13), 50 (15). HMRS: calcd for M+ - CH4O
152.1201, found 152.1198. Anal. Calcd for C11H20O2: C, 71.70;
H, 10.94. Found: C, 71.99; H, 11.09.
2-Cycloh exylm et h yl-1,1-d im et h oxycyclob u t a n e (8h ).
tR ) 24.85 min. Bp: 50 °C/0.01 Torr. 1H NMR (400 MHz,
CDCl3): δ 0.78-0.99 (m, 2H), 1.13-1.33 (m, 5H), 1.35-1.48
(m, 2H), 1.60-1.75 (m, 5H), 1.78-1.95 (m, 2H), 2.11-2.18 (m,
1H), 2.44-2.53 (m, 1H), 3.14 (s, 3H), 3.18 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 19.0, 26.3, 26.4, 26.7, 28.9, 33.0, 34.3,
35.6, 37.7, 42.4, 48.5, 48.6, 103.8. IR (neat): ν 2989, 2923, 2852,
2830, 1448, 1266, 1230, 1159, 1123, 1043, 860, 758 cm-1. MS
(m/z): 184 (5, M+ - C2H4), 101 (47), 97 (17), 88 (100), 85 (18),
83 (28), 71 (62), 67 (12), 58 (19), 55 (17). HRMS: calcd for M+
- C2H4 184.1463, found 184.1458. Anal. Calcd for C13H24O2:
C, 73.54; H, 11.39. Found: C, 73.55; H, 11.25.
1,1-Dim eth oxy-2-p h en ylcyclobu ta n e (8i). tR ) 23.90
min. Bp: 70-75 °C/0.3 Torr. 1H NMR (400 MHz, CDCl3): δ
1.93-2.03 (m, 1H), 2.08-2.19 (m, 2H), 2.25-2.33 (m, 1H), 3.01
(s, 3H), 3.20 (s, 3H), 3.62 (t, 1H, J ) 8.6 Hz), 7.21-7.36 (m,
5H). 13C NMR (100 MHz, CDCl3): δ 19.2, 29.5, 48.7, 48.9, 51.0,
104.0, 126.4, 128.0, 128.9, 139.6. IR (neat): ν 3061, 3027, 2993,
2950, 2831, 1603, 1497, 1458, 1259, 1163, 1117, 1036, 861, 759,
698 cm-1. MS (m/z): 192 (6, M+), 164 (12), 129 (9), 104 (7), 91
(10), 89 (7), 88 (100), 58 (27). HRMS: calcd for C12H16O2
192.1150, found 192.1147. Anal. Calcd for C12H16O2: C, 74.96;
H, 8.39. Found: C, 74.90; H, 8.52.
2-Ben zyl-1,1-d im eth oxycyclobu ta n e (8j). tR ) 24.75 min.
Bp: 75 °C/0.01 Torr. 1H NMR (400 MHz, CDCl3): δ 1.27-1.37
(m, 1H), 1.64-1.74 (m, 1H), 1.80-1.89 (m, 1H), 2.08-2.16 (m,
1H), 2.56-2.66 (m, 2H), 2.85-2.94 (m, 1H), 3.01 (s, 3H), 3.14
(s, 3H), 7.06-7.13 (m, 3H), 7.16-7.21 (m, 2H). 13C NMR (100
MHz, CDCl3): δ 18.4, 28.6, 36.3, 45.8, 48.5, 48.7, 103.4, 125.7,
128.2, 128.8, 140.9. IR (neat): ν 3062, 3027, 2990, 2948, 2830,
1782, 1603, 1496, 1453, 1260, 1222, 1160, 1121, 959, 855, 747,
728, 700 cm-1. MS (m/z): 206 (1, M+), 178 (8), 175 (12), 174
(43), 173 (25), 143 (23), 142 (13), 141 (23), 131 (10), 129 (12),
128 (13), 118 (11), 117 (21), 115 (19), 103 (10), 91 (42), 89 (13),
88 (100), 77 (10), 65 (14), 58 (24), 55 (13), 51 (12). HRMS: calcd
1,1-Dim eth oxy-2-isop r op ylcyclobu ta n e (8c). tR ) 13.90
1
min. Bp: 40 °C/0.6 Torr. H NMR (400 MHz, CDCl3): δ 0.82
(d, 3H, J ) 6.8 Hz), 0.98 (d, 3H, J ) 6.6 Hz), 1.31-1.40 (m,
1H), 1.70-1.84 (m, 2H), 1.86-1.93 (m, 1H), 2.02-2.09 (m, 1H),
2.11-2.17 (m, 1H), 3.15 (s, 6H). 13C NMR (100 MHz, CDCl3) δ
16.8, 19.8, 22.8, 28.5, 28.8, 48.1, 48.6, 51.7, 104.1. IR (neat):
ν 2989, 2953, 2870, 2831, 1463, 1382, 1364, 1267, 1227, 1158,
1136, 1114, 1046, 856, 759 cm-1. MS (m/z): 158 (0.1, M+), 143
(1.6), 130 (15), 127 (11), 115 (62), 95 (13), 88 (100), 69 (12), 58
(26), 55 (11). HRMS: calcd for M+ - CH3 143.1072, found
143.1074. Anal. Calcd for C9H18O2: C, 68.31; H, 11.46.
Found: C, 68.58; H, 11.18.
1,1-Dim et h oxy-2-ter t-b u t ylcyclob u t a n e (8d ). tR
)
1
15.70 min. Bp: 50 °C/1 Torr. H NMR (400 MHz, CDCl3): δ
0.95 (s, 9H), 1.45-1.54 (m, 1H), 1.69-1.79 (m, 1H), 1.90-1.97
(m, 1H), 2.03-2.11 (m, 1H), 2.17-2.22 (m, 1H), 3.10 (s, 3H),
3.15 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 14.2, 27.7, 30.5,
44.3, 47.4, 48.0, 53.6, 104.4. IR (neat): ν 2990, 2954, 2870,
2831, 1467, 1362, 1274, 1216, 1155, 1115, 1037, 909, 856, 760,
736 cm-1. MS (m/z): 157 (5, M+ - CH3), 141 (11), 129 (55),
125 (14), 88 (100), 83 (11), 69 (14), 58 (26), 55 (10). HRMS:
molecular peak not found. Anal. Calcd for C10H20O2: C, 69.72;
H, 11.70. Found: C, 69.97; H, 11.39.
1,1-Dim eth oxy-2-isobu tylcyclobu ta n e (8e). tR ) 17.55
1
min. Bp: 60 °C/0.7 Torr. H NMR (400 MHz, CDCl3): δ 0.86
(d, 3H, J ) 6.6 Hz), 0.90 (d, 3H, J ) 6.6 Hz), 1.23-1.33 (m,
1H), 1.38-1.43 (m, 2H), 1.49-1.59 (m, 1H), 1.79-1.96 (m, 2H),
2.11-2.18 (m, 1H), 2.42-2.51 (m, 1H), 3.16 (s, 3H), 3.18 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 18.9, 22.2, 23.5, 26.0, 28.9,
39.1, 43.0, 48.5, 48.6, 103.8. IR (neat): ν 2990, 2953, 2870,
for
C13H18O2 206.1307, found 206.1311. Anal. Calcd for
C
13H18O2: C, 75.69; H, 8.79. Found: C, 75.85; H, 8.59.
Syn th esis of Gem in a l Dibr om ocyclobu ta n es: Gen er a l
P r oced u r e. Boron tribromide (1.94 mL, 5.05 g, 20.2 mmol)
9398 J . Org. Chem., Vol. 68, No. 24, 2003

Novel Route to Geminal Dibromocyclobutanes
was added dropwise to the cyclobutanone acetal 8 (10 mmol)
dissolved in dry CH2Cl2 (25 mL) at -78 °C. After 3 h, the dry
ice/acetone was replaced by an ice bath, and the reaction was
allowed to reach 0 °C. Pentane (100 mL) was added, and the
mixture was quenched with NaHCO3 (10%, 10 mL). The
organic layer was separated, washed with brine (5 mL), and
dried (MgSO4). Removal of the solvent in vacuo followed by
flash chromatography (hexane) on silica gel or bulb-to-bulb
distillation provided the desired compounds as colorless oils.
1.58-1.64 (m, 1H), 1.65-1.75 (m, 1H), 1.78-1.96 (m, 2H),
2.04-2.13 (m, 2H), 2.14-2.22 (m, 2H), 2.56 (sept, 1H, J ) 7.8
Hz), 3.27-3.33 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 18.4,
18.9, 20.9, 28.0 (two carbons), 33.9, 39.5, 45.8, 62.8. MS (m/z):
284 (0.5), 282 (1, M+), 280 (0.5), 256 (2), 254 (4), 252 (2), 203
(11), 201 (13), 175 (17), 173 (17), 121 (47), 94 (14), 93 (100), 91
(25), 85 (39), 83 (52), 81 (44), 79 (56), 77 (30), 69 (13), 68 (15),
67 (59), 65 (17), 55 (70), 53 (28), 51 (12). HRMS: calcd
for C9H1479Br2 279.9462, found 279.9465. Anal. Calcd for C9H14
Br2: C, 38.33; H, 5.00. Found: C, 38.59; H, 4.79.
-
1
1,1-Dibr om ocyclobu ta n e (9a ). tR ) 18.65 min; H NMR
(250 MHz, CDCl3): δ 2.20 (dt, 2H, J ) 7.5 Hz), 3.24 (t, 4H, J
) 7.4 Hz). 13C NMR (62.9 MHz, CDCl3): δ 18.2, 50.0, 57.3. IR
(neat): ν 2999, 2957, 2871, 1436, 1422, 1247, 1096, 1033, 840,
706 cm-1. MS (m/z): 216 (2), 214 (4, M+), 212 (2), 188 (22),
186 (48), 184 (25), 135 (82), 133 (80), 107 (13), 105 (14), 85
(50), 84 (13), 83 (83), 70 (10), 53 (100), 51 (20), 50 (16), 49 (25).
1,1-Dibr om o-2-h exylcyclobu ta n e (9b). tR ) 25.20 min.
1H NMR (400 MHz, CDCl3): δ 0.88-0.93 (m, 3H), 0.97-1.04
(m, 1H), 1.19-1.16 (m, 1H), 1.25-1.38 (m, 7H), 1.40-1.50 (m,
1H), 1.50-1.60 (m, 2H), 2.06 (“q”, 2H, J ) 8.1 Hz), 3.40 (t,
1H, J ) 6.8 Hz). 13C NMR (100 MHz, CDCl3): δ 14.0, 18.8,
21.0, 22.5, 27.7, 28.7, 31.6, 38.9, 39.5 (CBr2), 65.0. IR (neat):
1,1-Dib r om o-2-cycloh exylm et h ylcyclob u t a n e
(9h ).
1
tR ) 26.55 min. H NMR (400 MHz, CDCl3): δ 0.78-0.91 (m,
2H), 0.94-1.11 (m, 3H), 1.19-1.23 (m, 1H), 1.24-1.30 (m, 2H),
1.31-1.38 (m, 1H), 1.49-1.60 (m, 2H), 1.63-1.76 (m, 4H),
1.77-1.85 (m, 1H), 1.99-2.07 (m, 1H), 3.47-3.52 (m, 1H). 13
C
NMR (100 MHz, CDCl3): δ 19.1, 20.7, 26.0, 26.1, 26.4, 32.3,
33.5, 35.1, 40.0, 46.0, 62.6. IR (neat): ν 2923, 2851, 1448, 1423,
1217, 1163, 1028, 935, 890, 692, 620 cm-1. MS (m/z): 312 (1.5),
310 (3, M+), 308 (1.5), 233 (3), 231 (6), 229 (3), 149 (61), 109
(24), 96 (14), 95 (17), 87 (11), 85 (66), 84 (16), 83 (100), 82 (25),
81 (23), 69 (16), 67 (42), 56 (15), 55 (64), 53 (10). HRMS: calcd
for C11H1879Br2 307.9779, found 307.9778. Anal. Calcd for
C11H18Br2: C, 42.60; H, 5.85. Found: C, 42.85; H, 6.02.
1,1-Dibr om o-2-ben zylcyclobu ta n e (9j). tR ) 26.40 min.
ν 2955, 2927, 2857, 1466, 1207, 1156, 1029, 913, 693, 614 cm-1
.
MS (m/z): 300 (7), 298 (15, M+), 296 (8), 219 (5), 163 (12), 161
(13), 138 (11), 137 (100), 135 (13), 133 (12), 95 (78), 84 (14), 83
(31), 82 (10), 81 (87), 79 (12), 71 (10), 69 (59), 67 (52), 66 (11),
65 (18), 57 (15), 56 (28), 55 (61). HRMS: calcd for C10H1879Br2
295.9775, found 295.9782. Anal. Calcd for C10H18Br2: C, 40.29;
H, 6.08. Found: C, 40.23; H, 5.82.
1
Bp: 100 °C/0.001 Torr. H NMR (400 MHz, CDCl3): δ 0.62-
0.68 (m, 1 H), 0.80-0.86 (m, 1 H), 1.16-1.29 (m, 2 H), 3.21-
3.26 (m, 1 H), 3.38-3.44 (m, 1 H), 3.51 (t, 1 H, J ) 7.3 Hz),
7.16-7.27 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ 18.3, 21.2,
38.9, 44.8, 64.6, 127.2, 128.5, 129.4, 138.0. IR (neat): ν 3063,
3028, 2935, 1603, 1494, 1454, 1424, 1265, 1218, 1154, 1030,
941, 897, 748, 704, 688 cm-1. MS (m/z): 306 (0.1), 304 (0.2,
M+), 302 (0.1), 148 (11), 92 (32), 91 (100), 65 (10). HRMS: calcd
for C11H1279Br2 301.9306, found 301.9316. Anal. Calcd for
1,1-Dibr om o-2-isobu tylcyclobu ta n e (9e). tR ) 22.10 min.
Bp: 70-72 °C/0.5 Torr.1H NMR (400 MHz, CDCl3): δ 0.90 (d,
J ) 6.6 Hz, 3H), 0.97 (d, J ) 6.6 Hz, 3H), 1.01-1.13 (m, 2H),
1.32-1.38 (m, 1H), 1.50-1.55 (m, 1H), 1.73-1.80 (m, 1H),
1.85-1.95 (m, 1H), 2.02-2.10 (m, 1H), 3.43-3.48 (m, 1H). 13
C
C
11H12Br2: C, 43.46; H, 3.98. Found: C, 43.65; H, 3.98.
NMR (100 MHz, CDCl3): δ 19.1, 20.7, 21.5, 22.8, 25.9, 40.0,
47.4, 63.2. IR (neat): ν 2958, 2870, 1466, 1424, 1386, 1260,
1235, 1166, 1028, 917, 872, 692, 617 cm-1. MS (m/z): 272 (2),
270 (4, M+), 268 (2), 191 (10), 189 (10), 109 (100), 69 (35), 67
(44), 65 (11), 56 (45), 55 (18), 53 (14). HRMS: calcd for
C8H1479Br2 267.9462, found 267.9471. Anal. Calcd for
C8H14Br2: C, 35.59; H, 5.23. Found: C, 35.85; H, 5.05.
Ack n ow led gm en t. We thank Ms. S. Felsinger and
Ms. C. Tyl for the recording of 400 MHz 1H and 100
MHz 13C NMR spectra.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of 8c,g, 9b,e,g,h ,j. This material is available free of
charge via the Internet at http://pubs.acs.org.
1,1-Dib r om o-2-cyclob u t ylm et h ylcyclob u t a n e
tR ) 24.45 min; H NMR (400 MHz, CDCl3): δ 0.95-1.02 (m,
(9g).
1
1H), 1.05-1.12 (m, 1H), 1.30-1.36 (m, 1H), 1.49-1.57 (m, 1H),
J O035295O
J . Org. Chem, Vol. 68, No. 24, 2003 9399