1-bromobicyclo[1.1.0]butane as an easily obtainable C4-building block: A novel route to cyclobutanone

Full text of DOI:10.1021/jo980190k

J . Org. Chem. 1999, 64, 6085-6086
6085
1-Br om obicyclo[1.1.0]bu ta n e a s a n Ea sily
Obta in a ble C4-Bu ild in g Block : A Novel
Rou te to Cyclobu ta n on e†
J u¨rgen Weber,‡ Ulrike Haslinger,§ and
Udo H. Brinker*,§
F igu r e 1. Preparation of 1-carboethoxybicyclo[1.1.0]butane
(4).
phase transfer conditions applying ultrasound.7 The
addition product, 1,1-dibromo-2-chloromethylcyclopro-
pane (1), was isolated in 86% yield. 1,3-Ring-closure of 1
to bicyclobutane 28 was accomplished through reaction
with methyllithium at -78 °C. A subsequent metal-
halogen exchange reaction with tert-butyllithium results
in the corresponding lithiobicyclobutane 3, which was
previously prepared by deprotonation of the highly
volatile parent bicyclobutane with alkyllithiums.8 Lithium
compound 3 (Figure 1) is valuable for introducing a
variety of substituents in the bridgehead position of
bicyclobutane.9 For example, trapping of 3 with ethyl
chloroformate gives 1-carboethoxybicyclobutane 45a in an
overall yield of 23% in a simple three-step, one-pot
reaction starting from cyclopropane 1.
Preliminary study and a similar example in the
literature5c show that when a leaving group such as
bromine is located at the bridgehead position of bicy-
clobutane 2, a halohydrin intermediate 6 (Figure 2) is
formed during the addition of water. The loss of the
bromide ion generates carbocation 7 and consequently
cyclobutanone (9).
Department of Chemistry, State University of New York,
Binghamton, New York 13902-6016, and
Institut fu¨r Organische Chemie, Universita¨t Wien,
Wa¨hringer Strasse 38, 1090 Wien, Austria
Received February 3, 1998
In tr od u ction
Carbocyclic four-membered ring compounds have
emerged from the provenance of pure academic fascina-
tion to important building blocks in organic synthesis.
Although a number of cyclobutane derivatives are readily
available through a variety of ring formation reactions,
many synthetic routes still rely on the transformation of
existing cyclobutane rings.1 The formation of cyclobutane
derivatives from substituted bicyclo[1.1.0]butanes have
been previously observed and the corresponding reaction
mechanisms were investigated.2 However, this route was
seldom considered as a major strategy in synthesis.
The high strain energies of bicyclobutanes3 are respon-
sible for the enormous reactivity of this class of com-
pounds. The central bond, which is akin to an olefinic
double bond, undergoes addition reactions with a large
variety of electrophilic reagents.4 Acid-catalyzed electro-
philic additions of methanol or water usually occur
without major skeletal rearrangements during the for-
mation of cyclobutane derivatives.5
Resu lts a n d Discu ssion
The preparation of 1-bromobicyclo[1.1.0]butane (2)
(Figure 1) was performed according to Skattebøl and
Baird et al.6 The first step of the synthesis, dibromocar-
bene addition to allyl chloride, was carried out under
F igu r e 2. Acid-catalyzed rearrangements of 1-bromobicyclo-
[1.1.0]butane (2).
‡ State University of New York.
§ Universita¨t Wien.
†Carbene Rearrangements, part 50. For part 49, see: Xu, L.;
Brinker, U. H. In Sonochemical Organic Synthesis; Luche, J . L., Ed.;
Plenum: New York, 1998; p 354.
(1) (a) Bellus, D.; Ernst, B. Angew. Chem., Int. Ed. Engl. 1988, 27,
797 and references therein. (b) Seebach, D. In Houben-Weyl: Methoden
der Organischen Chemie; Thieme: Stuttgart, 1971; Vol. IV/4, pp 408-
412.
It is known that vinyl halides can be transformed into
ketones with acids such as sulfuric acid.10 Therefore,
when cation-exchange resin DOWEX 50 WX4 and water
were added to 1-bromobicyclo[1.1.0]butane (2) at -78 °C,
it was no surprise that small amounts of cyclobutanone
(9) were formed in addition to 1-bromocyclobutene (8),
the major product. Moreover, some 1,1-dibromocyclobu-
tane was also detected and probably results from addition
of HBr to 8. Monitoring of the reaction by GC-MS showed
that after the reaction warmed up to room temperature
within 2 h, around two-thirds of 8 was hydrolyzed to 9.
(2) (a) Hoz, S. In The Chemistry of the Cyclopropyl Group; Rappoport,
Z., Ed.; Wiley: New York 1987; Part 2, p 1121. (b) Wong, H. N. C. In
Houben-Weyl: Methoden der Organischen Chemie; de Meijere, A., Ed.;
Thieme: Stuttgart, 1997; Vol. E 17 e, pp 41-58.
(3) (a) Wiberg, K. B. In The Chemistry of the Cyclopropyl Group;
Rappoport, Z., Ed.; Wiley: New York, 1987; Part 1, p 1. (b) Estrain
(bicyclo[1.1.0]butane) ) 66 kcal mol-1
.
(4) (a) Christl, M. In Advances in Strain in Organic Chemistry;
Halton, B., Ed.; J AI: Greenwich, CT, 1995; Vol. 4. (b) For reactions of
bicyclo[1.1.0]butanes with nucleophiles, see: Azran, C.; Hoz, S.
Tetrahedron 1995, 51, 11421. (c) For reactions with carbenes, see: Xu,
L.; Miebach, T.; Brinker, U. H. Tetrahedron Lett. 1991, 32, 4461 and
references therein.
(7) (a) Xu, L.; Tao, F. Synth. Commun. 1988, 2117. (b) Xu, L.;
Brinker, U. H. In Sonochemical Organic Synthesis; Luche, J . L., Ed.;
Plenum: New York, 1998; p 354.
(5) (a) Wiberg, K. B.; Lampman, G. M.; Ciula, R. P.; Connor, D. S.;
Schertler, P.; Lavanish, J . Tetrahedron 1965, 21, 2749. (b) Blanchard,
E. P., J r.; Cairncross, A. J . Am. Chem. Soc. 1966, 88, 487. (c) Hoz, S.;
Livneh, M.; Cohen, D. J . Org. Chem. 1986, 51, 4537.
(6) Nilsen, N. O.; Skattebøl, L.; Baird, M. S.; Buxton, S. R.; Slowey,
P. D. Tetrahedron Lett. 1984, 25, 2887.
(8) Du¨ker, A.; Szeimies, G. Tetrahedron Lett. 1985, 26, 3555.
(9) (a) Gassman, P. G.; Mullins, M. J . Tetrahedron Lett. 1979, 4457.
(b) Szeimies, G.; Philipp, F.; Baumga¨rtel, O.; Harnisch, J . Tetrahedron
Lett. 1977, 2135. (c) Kenndoff, M.; Singer, A.; Szeimies, G. J . Prakt.
Chem. 1997, 339, 217.
(10) Wichterle, O. Collect. Czech. Chem. Commun. 1947, 12, 93.
10.1021/jo980190k CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999

6086 J . Org. Chem., Vol. 64, No. 16, 1999
Notes
P r ep a r a tion of 1-Br om obicyclo[1.1.0]bu ta n e (2).6,8 At
-78 °C and under an inert gas atmosphere, 11.2 g (45 mmol) of
dibromocyclopropane 1 in 20 mL of dry diethyl ether were
treated with 33 mL of a 1.4 M solution of methyllithium in
diethyl ether. The mixture was allowed to warm to -60 °C over
a period of 4 h. The cold bath was then removed, and all volatile
compounds were condensed into a trap. The condensation was
completed under slight heating with a water bath (35 °C). Under
basic conditions (NaOH, diethyl ether), 2 can be stored in a
freezer for several days without significant decomposition.
Cyclobutanone (9) was separated from the remaining
1-bromocyclobutene (8) and 1,1-dibromocyclobutane by
exhaustive extraction with ice water. The aqueous phase
was then extracted with dichloromethane. Isolation of 9
was accomplished by exhaustive distillation through a
Spaltrohr column. The isolated yield of cyclobutanone (9)
over two steps after distillation was 28%. Cyclobutanone-
p-tosylhydrazone could be formed in 31% overall yield
starting from cyclopropane 1 by the reaction of crude
cyclobutanone (9) with p-toluenesulfonylhydrazide.
Despite the large number of published syntheses,
cyclobutanone (9) had still not been simply and cheaply
made.1a The novel route to cyclobutanone (9), described
here, represents an inexpensive and short three-step
synthesis starting from allyl chloride.
P r ep a r a tion of Cyclobu ta n on e (9) fr om 1-Br om o[1.1.0]-
bicyclobu ta n e (2). The etheral solution of bromobicyclobutane
2, was cooled to -78 °C, and 5 g of DOWEX 50 WX4 and 5 mL
of water were added. The mixture was allowed to warm to room
temperature overnight and was analyzed on the analytical gas
chromatograph HP6890 with MSD HP5973: column HP-5 M,
phenyl methyl siloxane, 30 m × 250 µm capillary; flow 0.8 mL/
min; temperature program injection temperature 150 °C, oven
temperature initial 40 °C for 5 min and then ramp 30 °C/min
up to 200 °C, 2 min at 200 °C; ratio of 8: 9 ) ca. 1:2. The reaction
mixture was filtered and extracted 10 times with 45-mL portions
of ice water until no cyclobutanone (9) could be detected in the
ether phase by GC. The aqueous phase was saturated with
sodium chloride and extracted 15 times with 15-mL portions of
dichloromethane until no cyclobutanone (9) could be detected
in the aqueous phase. The organic phase was dried over
magnesium sulfate. The dichloromethane was carefully distilled
off through a 20-cm Spaltrohr column: yield 0.89 g (28%,
purity: 99%) of cyclobutanone (9) over two steps starting from
cyclopropane 1.
Exp er im en ta l Section
P r ep a r a tion of 1,1-Dibr om o-2-ch lor om eth ylcyclop r o-
p a n e (1) Usin g th e Ultr a son ic Meth od .7 The following
reagents were added to a 250-mL flask in the given order: (1)
32 g (0.8 mol), a 10-fold excess, of powdered sodium hydroxide,
(2) 50 mL of methylene chloride, (3) 9.2 g (120 mmol) of allyl
chloride, (4) 20.2 g (80 mmol) of bromoform, and (5) about 30
mg of triethylbenzylammonium chloride (TEBA). The flask was
fitted with a reflux condenser and a bubbler. The setup was
immersed in the bath of an ultrasonic cleaner (35 kHz), and the
mixture was sonicated for 40 min. The initiation of the reaction,
as indicated by the evolution of gas or discoloration of the
mixture, could be observed immediately. The crude yield was
25 g, and a GC analysis showed a small amount of leftover
bromoform. The inorganic solids were removed by suction
filtration through a filter agent (Celite 545). The solvents were
removed with a rotary evaporator. An optional purification
procedure entails the addition of pentane and silica gel to the
residue, followed by filtration and evaporation of the solvent.
Distillation of the mixture was performed in vacuo: bp 68-72
°C (10 mmHg). Further purification was accomplished through
column chromatography (pentane/ether 98:2): yield 17.0 g (86%).
Ack n ow led gm en t. We are indebted to the Petro-
leum Research Fund, administered by the American
Chemical Society, for financial support. We thank
Chemetall, Frankfurt, Germany, for a generous gift of
methyllithium.
J O980190K