Intramolecular trapping of esters by 1-lithio-1-bromocyclopropanes

Article abstract of DOI:10.1016/S0040-4020(00)00385-9

Reaction of 2-acyloxymethyl-1,1-dibromocyclopropanes with methyllithium at -90°C leads to selective bromine-lithium exchange and intramolecular cyclisation to give a 1-bromo-3-oxabicyclo[3.1.0]hexan-2-ol. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00385-9

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4799±4810
Intramolecular Trapping of Esters by
1-Lithio-1-bromocyclopropanes
a
b
b
Mark S. Baird,a, Florian A. M. Huber, Viacheslav V. Tverezovsky and Ivan G. Bolesov
*
aChemistry Department, University of Wales, Bangor, Gwynedd LL57 2UW, UK
bChemistry Department, Lomonosov Moscow State University, Vorobiovy Gory, Moscow 119899, Russia
Received 16 March 2000; revised 19 April 2000; accepted 8 May 2000
AbstractÐReaction of 2-acyloxymethyl-1,1-dibromocyclopropanes with methyllithium at 2908C leads to selective bromine±lithium
exchange and intramolecular cyclisation to give a 1-bromo-3-oxabicyclo[3.1.0]hexan-2-ol. q 2000 Elsevier Science Ltd. All rights reserved.
The reaction of 1,1-dibromocyclopropanes with methyl-
lithium is known to lead to a very rapid lithium±halogen
exchange, followed in most cases by formal elimination of
lithium bromide to produce a cyclopropylidene (or a
related carbenoid).1 If the reaction is carried out at low
temperature or, in some cases, if there is a co-ordinating
group present in the molecule, the organolithium may be
trapped in intermolecular processes by reaction with
electrophiles.1 There are many examples of intramolecular
trapping of the cyclopropylidene; thus insertion into CH
bonds is a unique reaction of carbenes and is of considerable
synthetic potential,2,3 e.g. in the presence of monocyclic
ethers,4 sul®des5 and amines6 of the general structure (1)
insertion occurs exclusively at the CH bond adjacent to
the heteroatom and 5,6-related to the carbenic carbon
(1,5-insertion) to give (4) (Scheme 1). This type of insertion
was the key step in the total synthesis of the natural product
3,4-methanoproline.7
derived from the cyclopropylidene are isolated.8 In another
type of process, the reaction of the tetrabromide (5) with
methyllithium leads to the tetracyclic diketone (6)
apparently by a double intramolecular trapping of the
derived lithiobromides by the ester group in the adjacent
cyclopropane ring.9 In a rather simpler system, methyl
3-(2,2-dibromocycloprop-1-yl)propanoate is converted
into 1-bromobicyclo[3.1.0]hexan-2-one by reaction with
methyllithium.10
There are fewer cases of similar intramolecular reactions of
the lithiobromides acting as nucleophiles; one such is the
1,3-elimination of BrCl from 1,1-dibromo-2-chloromethyl-
cyclopropanes on reaction with methyllithium.8 It is to be
noted that with the related 2-(2-haloethyl)- or 2-(3-halo-
propyl)- systems no cyclisation is observed and only allenes
We now report that reaction of the esters (15), (16) derived
from cyclopropylmethanols with methyllithium leads to the
intramolecular trapping of a lithiobromocyclopropane
with the formation of a ®ve-membered ring (Scheme 3).11
The corresponding reaction of amides will be described
elsewhere.
Scheme 1.
Keywords: intramolecular trapping; esters; 1-lithio-1-bromocyclopropanes.
* Corresponding author. Tel.: 144-1248-382-374; fax: 144-1248-370-528; e-mail: chs028@bangor.ac.uk
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00385-9

4800
M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
Scheme 2.
Two cyclopropanecarboxylic acids were prepared accord-
ing to literature procedures,7,12 (8) by the reaction of methyl
methacrylate with bromoform and aqueous sodium
hydroxide in the presence of a phase transfer catalyst,13
and subsequent acid hydrolysis, and (7) by addition of
dibromocarbene to 1,3-butadiene to give 1,1-dibromo-2-
vinylcyclopropane, followed by oxidation to the acid with
potassium permanganate.14 Both acids (7) and (8) are now
available in enantiomerically pure form by resolution.14 For
this work, however, racemic material was used. The acids
were converted into the corresponding acid chlorides (9),
(10) by reaction with thionyl chloride, and these were
reduced to the alcohols (11), (12) (Scheme 2).7
and deprotection (50% overall yield, after distillation of
the crude product).
A range of esters of general structure (15) and (16)
(Scheme 3) was prepared by standard methods. Esters
with R1ˆmethyl, tri¯uoromethyl and n-propyl were made
from the alcohols (11), (12) by treatment with the corre-
sponding acid anhydride in the presence of trimethylsilyl
tri¯uoromethane sulfonate (TMSOTf) as catalyst.15 The
benzoates and acrylates were prepared upon treatment
with the appropriate acid chloride in the presence of triethyl-
amine, the isobutyrate and pivaloate by treatment with acid
chloride in pyridine in the presence of 4-dimethylamino-
pyridine (DMAP) as catalyst (Table 1).
Racemic alcohol (11) was also prepared by an alternative
route from allyl alcohol by protection with 2-methoxy-
propene as (13), dibromocyclopropanation to give (14)
Reaction of esters (15), (16) with a slight excess of methyl-
lithium at 2908C for 30 min, followed by quenching with
Scheme 3.
Table 1. Preparation of esters and their reactions with methyllithium in diethyl ether at 2908C
Method
R1
RˆH
RˆMe
Ester, %
Product, %
Ester, %
Product, %
Ac2O, TMSOTf
Me
(15a), 86
(15b), 92
(15c), 88
(15d), 62
(15e), 35
±
(17a), 551(11), 10
(17b), 46
(11), 90
(16a), 88
(16b), 93
±
(16d), 52
(16e), 44
(16f), 99
(16g), 89
(18a), 60
(18b), 74
(n-PrCO)2O, TMSOTf
(CF3CO)2O, TMSOTf
PhCOCl, Et3N
CH2ˆCHCOCl, Et3N
i-PrCOCl, Py, DMAP
t-BuCOCl, Py, DMAP
n-Pr
CF3
Ph
Vinyl
i-Pr
t-Bu
(17d), 64
(27), 39
(18d), 82
(18e), 68
(18f), 80
(18g), 81
±

M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
4801
signals in the crude mixture could not be assigned with
certainty to a second isomer. The stereochemistry at C-2
of the hemiacetal (18a) was assigned as that with the methyl
group endo to the cyclopropane on the basis of n.O.e studies
which established reciprocal enhancements (1%) of Hb and
Hf (but not Ha and Hg), locating these protons as endo, an
enhancement of Hb on irradiation CHd3, only possible if both
groups are endo, and an enhancement of the signals for
both Ha and Hg on irradiation of methyl CHc3, locating
both protons exo (Fig. 1).
Figure 1. Proton n.O.e enhancements for (18a).
Con®rmation of this stereochemistry came from a single
crystal X-ray structure determination of the hemiacetal
(18d) which again showed the phenyl group on the hemi-
acetal centre endo to the cyclopropane moiety.17 The stereo-
chemistry of other products was assigned by analogy.
ammonium chloride either at low temperature or after
warming to 08C led to the hemiacetals (17), (18) (Scheme
3). The products of the intramolecular trapping are
summarised in Table 1.
The formation of products (17) or (18) apparently involves a
lithium±bromine exchange in (15) or (16) and cyclisation of
the derived lithiocyclopropane by attack at the ester group.
It is not clear whether the exchange leads stereoselectively
to the syn-lithio-ester, or whether a more complex process
occurs in which the two isomeric lithiobromides are formed
and equilibrate, but only one isomer cyclises. Nonetheless,
no products of intermolecular trapping of the anti-lithio
ester were observed. It is interesting to note that reaction
of 2,2-dibromocyclopropane carboxylic acid with methyl-
lithium leads exclusively to trans-2-bromocyclopropane
carboxylic acid, a reaction once again apparently proceed-
ing through the cis-2-lithio-trans-2-bromo- compound.16
Neither was there any evidence for the formation of
products derived from cyclopropylidene intermediates
(e.g. allenes).
Although these reactions appear to represent the ®rst
example of such a cyclisation by reaction of 1,1-dibromides
with an alkyllithium, it is known that the sulphone (19)
reacts with n-butyllithium by proton removal from C-1
followed by cyclisation to give the hemiacetal (20,
Scheme 4).18
A similar cyclisation occurred when 2-(hydroxymethyl)-
cyclopropyl phenyl sul®de (21) was treated ®rst with an
excess of n-butyllithium and then with dimethylformamide
to give the bicycle (22) (Scheme 5), an intermediate lithio-
cyclopropane apparently being trapped ®rst as the aldehyde,
which then cyclised.19 In both cases the stereocentre of the
hemiacetal was not de®ned although a single diastereomer
was apparently obtained.
In the cases of the hemiacetals (18a), (18b), (18d) (see
Table 1) the NMR spectra in deuterochloroform showed
only the presence of the cyclic form. However, for the
In case of the tri¯uoroacetic acid ester (15c), no cyclisation
took place; instead the ester was hydrolysed to the alcohol
(11). Thus attack of methyllithium at the ester carbonyl was
faster than lithium±halogen exchange. When the reaction
was carried out with the acetic acid ester (15a) only 10%
hydrolysed product was observed and the main product was
the hemiacetal (17a). The other reactions did not afford any
hydrolysis products.
1
analogous hemiacetals (17a), (17b), (17d), the H NMR
spectra in deuterated solvents were more complicated and
could be interpreted in terms of an equilibrium between the
hemiacetal and the corresponding keto-alcohols (23a),
(23b), (23d) (Scheme 6). The signal for the endo proton at
C-4 in the hemiacetal (17d) appeared as a doublet and not a
double doublet because the vicinal coupling constant is zero
as the torsion angle between Hendo-4 and H-5 is close to 908.
The hemiacetal (17d) and keto-alcohol (23d) were readily
A single diastereomer was isolated from the intramolecular
cyclisation in each case after chromatography; minor
Scheme 4.
Scheme 5.

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M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
Scheme 6.
Table 2. Equilibrium hemiacetal/keto-alcohol in various deuterated solvents
R1
Compounds
Solvent
Ratio of hemiacetal:
keto-alcohola
Me
n-Pr
Ph
(17a)/(23a)
(17b)/(23b)
(17d)/(23d)
CDCl3
Benzene-d6
CDCl3
Toluene-d8
CDCl3
CD3OD
81: 19
84: 16
58: 42
67: 33
43: 57
58: 42
100: 0
toluene-d8
a Ratios measured after 1 h in deuterated solvent.
distinguished in the 13C NMR spectrum, only the CH2 group
of the cyclopropane moiety having a comparable chemical
shift, e.g. C-2 of hemiacetal (17d) appeared at 104.6 ppm
while in the ring-opened structure (23d) this carbon gave a
signal at 195.2 ppm.
When samples of (17a) and (17b) in deuterochloroform
were re-measured after one or more days, the NMR spec-
trum had become highly complex. It was not clear whether
the compounds simply decomposed or if other diastereo-
mers with the opposite con®guration at the hemiacetal
carbon were formed. A similar equilibrium has been
reported in closely related acetals (25).21 The bicyclic
system was obtained from reaction of the lactone (24)
with phenylmagnesium bromide (Scheme 7). The authors
quoted a ratio of hemiacetal to keto-alcohol of 25 to 75 in
deuterated methanol.
The observed ratios between those two species are
summarised in Table 2 below.
Generally the equilibrium was on the side of the hemiacetal;
one exception was compound (17d), which in deutero-
chloroform showed more keto-alcohol than hemiacetal
present. Surprisingly, in deuterated toluene the same
compound (17d) did not show any equilibrium at all. Thus
the equilibrium position depends on structural properties of
the hemiacetalÐsubstituents on the hemiacetal centre (R1
either Me, n-Pr or Ph) and group R on the cyclopropane ring
(whether there is a methyl group or only a proton) and on
properties of solvent (polarity and acidity). The reversibility
of this equilibrium was tested with compound (17d). The
compound was ®rst dissolved in deuterated methanol and
The reactions of esters (15) and (16) with methyllithium
generally followed a similar pattern. The most signi®cant
difference was in the reaction of acrylates (15e) and (16e)
with methyllithium. The ester (16e) gave the expected
product, the hemiacetal (18e); however, the reaction of
ester (15e) with methyllithium followed a rather different
course, leading to the bicyclic ketone (27) as the sole
product (Scheme 8).
1
showed a ratio of 58: 42 in the H NMR spectrum. The
This reaction may be explained in terms of initial formation
of a hemiacetal species (28) as above, followed by ring-
opening to a keto-alcohol (29) and recyclisation by
attack of the alcoholate at the b-position of the derived
a,b-unsaturated ketone. The bicyclic ketone (27) exhibited
an unusual double carbonyl peak with maxima at 1711 and
1692 cm21; similar peaks have been reported in related
solvent was evaporated and the same sample was dissolved
in deuterated toluene. Now only signals of the hemiacetal
were present in the H NMR spectrum. The solvent was
1
evaporated and the spectrum was recorded once again in
deuterated methanol. A ratio of hemiacetal to keto-alcohol
almost identical to above was observed.20
Scheme 7.

M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
4803
Scheme 8.
systems.22 In the 13C NMR spectrum, the carbonyl carbon
gave a signal at 199.3 ppm. Peaks at 67.2 and 69.7 ppm
were the signals for the CH2 groups next to the ring-oxygen.
In the 1H NMR, the two CH2 groups at C-4 and C-5 gave for
each proton a `ddd' multiplicity with signals at 2.04 and
2.28 ppm (2£H5) and at 2.69 and 3.20 ppm (2£H-4). In
contrast to the above hemiacetal system (17d), both H-2
protons appeared as double doublets due to an altered
torsion angle (.908 and thus non-zero vicinal coupling
constants between both and the proton on C-1.
(52%). The 13C NMR spectra of the products gave correct
signals for the ester carbonyl in the region of 170 ppm and
for the ketone at 200 ppm.
The corresponding oxidations of (17a) and (18a) afforded
two products in ratio ca. 60 to 40 in each case. The
major products were again the keto-esters (32) and (33);
the minor products were identi®ed as diesters (34)23
and (35) (Scheme 10). In neither case was the mixture
separated.
1-Bromo-2-propyl-3-oxabicyclo[3.1.0]hexan-2-ol (17b) and
its methyl analogue (18b) were oxidatively ring-opened
using periodic acid and catalytic amounts of ruthenium
trichloride, 7 to give the corresponding 2-bromo-2-butyroyl-
cyclopropanecarboxylic acids, which were isolated as their
methyl esters (30) and (31), Scheme 9. With hemiacetal
(18b), the oxidation gave a higher yield of (31) (72%)
with 2 mol equiv. than with 14 mol equiv. of periodic acid
If the 2,2-dibromocyclopropanecarboxylic acid is regarded
as the starting point of the synthesis, the overall transforma-
tion achieved is therefore a stereoselective acylation cis to
the acid group (Scheme 11).
The oxidative ring-opening could also be carried out with
PCC, leading in the case of (18g) to the keto-aldehyde (36),
and with manganese dioxide in re¯uxing toluene in the
Scheme 9.
Scheme 10.
Scheme 11.

4804
M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
Scheme 12.
Scheme 13.
presence of ethoxycarbonyltriphenylphosphorane, when an
in situ Wittig reaction was observed (Scheme 12).24
All new compounds were homogenous by TLC or by GLC.
GLC was conducted using a Carlo Erba HRGC 5300 (F.I.D.,
on a capillary column). TLC was performed using Aldrich
silica plates coated with silica gel 60 (F254). Compounds
were visualised by examination under an ultraviolet source,
by exposure to iodine vapour or by contact with phos-
phomolybdic acid hydrate (2% solution in ethanol) followed
by heating to 1808C. Column chromatography was
conducted with Fisher Scienti®c Silica Gel 60 under
medium pressure.
Reduction of the hemiacetal (17b), or the corresponding
ring-opened hydroxyketone, with lithium aluminium
hydride in ether was not stereoselective, leading to a
mixture of isomeric diols (38a), (38b) (Scheme 13) which
could be separated by column chromatography on silica.
The above results show that reaction of 2-acyloxymethyl-
1,1-dibromocyclopropanes with methyllithium at 2908C
leads to the stereoselective formation of bicyclic hemi-
acetals. The presence or absence of a methyl group at C-1
of the cyclopropane proved to play an important role in the
outcome of the reaction and the stability of the products.
Reductions and oxidations of the derived hemiacetals led to
ring-opened products. Other reactions such as addition of
Grignard and Wittig reagents or protection of the hydroxy-
group of the hemiacetal were not successful. The
applications of the bicyclic hemiacetals in the synthesis of
biologically active cyclopropanes is being examined; the
wide range of such compounds has recently been
reviewed.25
Melting points are uncorrected. Infrared spectra were
obtained as KBr discs or as liquid ®lms on a Perkin Elmer
1600 FTIR spectrometer. Low resolution mass spectra were
obtained on a Finnigan 8430 spectrometer. Accurate mass
measurements refer to 79Br for monobromides and for
79Br81Br for dibromides unless stated and were obtained
from the Swansea Mass Spectrometry Service. Micro-
analyses were performed on a Carlo Erba Model 1106
CHN analyser.
NMR spectra were recorded in CDCl3 unless otherwise
stated on a Bruker AC250 at 250 MHz for protons and
62.9 MHz for carbon and in the latter case were broad-
band decoupled; DEPT spectra were also run and the
signs of signals (1 for CH, CH3; 2 for CH2) are indicated
on the data for the broad-band decoupled spectrum. Those
signals with no sign in such a spectrum are quaternary.
When a n.O.e difference spectra was obtained from the
Edinburgh University Ultra High Field NMR Service,
conditions were as follows: recorded on a Bruker
360 MHz spectrometer, a total of 512 scans per FID, inter-
leaved in blocks of 32 each with 4 `dummy scans', using
Bruker program N.O.EMULT.AU; irradiation period: 7 s;
90 degree pulse, FID acquisition time: 2 s; sample station-
ary. Data were processed with 1 Hz line broadening.
General Experimental Details
Reagents were obtained from commercial suppliers
(Aldrich, Lancaster) and were used without further puri®ca-
tion unless otherwise stated. Solvents were puri®ed when
necessary using the methods suggested in `Puri®cation of
Laboratory Chemicals' by D. D Perrin, W. L. F. Armarego
and D. R. Perrin.26 Dichloromethane was distilled over
calcium hydride, diethyl ether over sodium wire. Petroleum
ether was of boiling point 40±608C unless otherwise stated.
Reactions were performed using oven dried glassware
(1608C) cooled under a stream of dry nitrogen or argon;
the experiments were conducted under a positive atmo-
sphere of one of these gases. Organic solutions were dried
over anhydrous magnesium sulfate, and, unless stated, were
evaporated at 14 mmHg. Yields quoted are for puri®ed
compounds unless otherwise stated. Any ratios given are
(2,2-Dibromocyclopropyl)methanol (11).7 3-(1-Methoxy-
1-methylethoxy)propene (11.5 g, 0.088 mol) [prepared
from allyl alcohol (10 g, 0.172 mol) as described]11 was
added to a mixture of bromoform (15.8 ml, 0.177 mol),
dichloromethane (50 ml), n-hexadecyltrimethylammonium
bromide (1.5 g) and triethylamine (4 drops). The mixture
was stirred vigorously and sodium hydroxide (35 g,
0.883 mol) in water (35 ml) was added slowly at below
1
calculated by comparing integrals of protons in the H
NMR spectra unless otherwise stated.

M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
4805
258C. After 27 h at 208C, brine (120 ml) was added and the
mixture was extracted with dichloromethane (4£120 ml).
The combined organic layers were dried and the solvent
was removed. Petrol (150 ml) was added and the mixture
was ®ltered through a layer of celite, which was washed
with ether (50 ml). Removal of the solvent and distillation
of unreacted bromoform at 30±408C at 0.5 mmHg gave
crude, already largely deprotected alcohol (11) as brown
oil. To complete the deprotection, the oil was dissolved in
dichloromethane (50 ml); water (25 ml) and p-toluenesul-
fonic acid (1 g) were added. After stirring for 30 min, the
aqueous layer was extracted with dichloromethane
(2£25 ml). The combined organic layers were washed
with water (100 ml), dried and evaporated. Distillation
gave (2,2-dibromocyclopropyl)methanol (11) (10.2 g,
50%); bp 828C at 0.3 mmHg. Compound (11) was also
prepared as previously described and shown to be identical
by n.m.r. and i.r. to the product above.7
and tri¯uoroacetic anhydride (0.67 ml, 4.78 mmol) gave 2,2-
dibromocyclopropylmethyl tri¯uoroacetate (15c) (1.5 g,
88%) as a colourless liquid (Found M1: 325.8588.
C6H5Br2F3O2 requires: 325.8588) which showed dH: 1.57
(1H, t, Jˆ7.4 Hz), 1.95 (1H, dd, Jˆ7.4, 10.4 Hz), 2.09 (1H,
dddd, Jˆ6.5, 7.4, 7.5, 10.4 Hz), 4.45 (1H, dd, Jˆ7.5,
11.7 Hz), 4.52 (1H, dd, Jˆ6.5, 11.7 Hz); dC: 23.1, 27.02,
28.01, 69.22, 114.3 (q, JCF 285 Hz), 157 (q, JCF 43 Hz);
vmax: 1789 s, 1368 s, 1333 m, 1226 s, 1168 s, 1108 s, 959
m, 775 m, 730 s, 689 s cm21; m/z, %: 328, 1; 326, 2; 324, 1
(M1); 214, 41; 212, 100; 210, 37; 201, 9; 199, 13; 197, 9; 188,
10; 186, 22; 184, 10; 133, 23; 131, 26; 69, 93; 51, 29.
2,2-Dibromo-1-methylcyclopropylmethyl acetate (16a).
(2,2-Dibromo-1-methylcyclopropyl)methanol (12) (1.7 g,
6.97 mmol) and acetic anhydride (0.72 ml, 7.67 mmol)
gave 2,2-dibromo-1-methylcyclopropylmethyl acetate
(16a) (1.75 g, 88%) as a colourless liquid (Found M1:
285.9027. C7H10Br2O2 requires: 285.9027) which showed
dH: 1.45 (3H, s), 1.49 (1H, d, Jˆ7.7 Hz), 1.65 (1H, d
Jˆ7.7 Hz), 2.12 (3H, s), 4.08 (1H, d, Jˆ11.6 Hz), 4.34
(1H, d, Jˆ11.6 Hz); dC: 20.91, 29.7, 32.82, 34.4, 70.22,
170.8; nmax: 2993 m, 2968 m, 2933 m, 1738 s, 1459 s, 1431
s,1387 s, 1378 s, 1364 s, 1246 s, 1162 m, 1036 s, 989 s, 851
m, 696 s cm21; m/z, %: 288, 0.1; 286, 0.2; 284, 0.1 (M1);
246, 2; 244, 4; 242, 2; 228, 8; 226, 15; 224, 7; 147, 8; 145, 7;
100, 100; 72, 13; 66, 20; 65, 25.
General procedure for syntheses of compounds (15a)±
(15c), (16a), (16b)
A solution of alcohol (1 mmol) in dichloromethane (5 ml)
was treated with the corresponding anhydride (1.1±2 mmol)
at 08C, followed by addition of trimethylsilyl tri¯uoro-
methanesulfonate (7 mg, 3 mol%). On completion, the reac-
tion (TLC) was treated with sat. aq. NaHCO3, and the
aqueous phase was extracted with dichloromethane. The
organic extracts were washed with aqueous NaHCO3 (£3)
and water, dried and the solvent evaporated. Generally, the
products did not require further puri®cation.
2,2-Dibromo-1-methylcyclopropylmethyl butyrate (16b).
(2,2-Dibromo-1-methylcyclopropyl)methanol (12) (12.2 g,
50 mmol) and butyric anhydride (15.8 g, 100 mmol) gave,
after removal of excess butyric anhydride in vacuo
(3 mmHg, 808C) and distillation of the residue at 1408C
and 0.3 mmHg, 2,2-dibromo-1-methyl-cyclopropylmethyl
butyrate (16b) (14.6 g, 46.5 mmol, 93%) as a colourless
liquid (Found M1: 313.9340. C9H14Br2O2 requires:
313.9340) which showed dH: 0.96 (3H, t, Jˆ7.4 Hz), 1.45
(3H, s), 1.49 (1H, t, Jˆ7.7 Hz), 1.65 (1H, d, Jˆ7.7 Hz), 1.68
(2H, qt, Jˆ7.4, 7.5 Hz), 2.35 (2H, t, Jˆ7.5 Hz), 4.08 (1H, d,
Jˆ11.6 Hz), 4.34 (1H, d, 11.6 Hz); dC: 13.61, 18.42,
2,2-Dibromocyclopropylmethyl acetate (15a). (2,2-Dibro-
mocyclopropyl)methanol (11) (0.6 g, 2.61 mmol) and acetic
anhydride (0.27 ml, 2.87 mmol) gave 2,2-dibromocyclopro-
pylmethyl acetate (15a) (0.61 g, 86%) as a colourless oil
(Found M1: 271.8871. C6H8Br2O2 requires: 271.8871)
which showed dH: 1.44 (1H, t, Jˆ7.4 Hz), 1.84 (1H, dd,
Jˆ7.4, 10.4 Hz), 1.97 (1H, dddd, Jˆ5.8, 7.4, 8.2,
10.4 Hz), 2.11 (3H, s), 4.05 (1H, dd, Jˆ8.2, 11.9 Hz),
4.28 (1H, dd, Jˆ5.9, 11.9 Hz); dC: 20.91, 24.8, 26.82,
28.91, 65.82, 170.8; nmax: 2953 w, 1742 s, 1438 w, 1369
s, 1235 s, 1109 m, 1036 s, 687 s cm21; m/z, %: 272, 0.5; 272,
1; 270, 0.5 (M1); 214, 6; 212, 8; 210, 5; 201, 9; 133, 5; 86,
14; 43, 100.
20.81, 28.4, 32.72, 34.4, 35.92, 69.92, 173.1; nmax
:
3077 w, 2966 s, 2934 s, 2875 m, 1738 s, 1461 s, 1431 m,
1380 m, 1356 m, 1303 m, 1282 m, 1254 s, 1173 br. s, 1090 s,
1044 s, 996 s, 695 s cm21; m/z, %: 316, 0.1; 314, 0.2; 312,
0.1 (M1); 228, 1; 226, 2; 224, 1; 128, 16; 71, 100; 65, 12.
2,2-Dibromocyclopropylmethyl benzoate (15d). Benzoyl
chloride (0.56 ml, 4.8 mmol) was added to a stirred solution
of (2,2-dibromocyclopropyl)methanol (11) (1.0 g, 4.3
mmol) and triethylamine (0.67 ml, 4.8 mmol) in ether
(10 ml). The mixture was stirred at room temperature for
12 h, ®ltered and evaporated. Chromatography on silica
(petrol±ether, 3:1) gave 2,2-dibromocyclopropylmethyl
benzoate (15d) (900 mg, 62%) as a colourless oil (Found
M1: 333.9027. C11H10Br2O2 requires: 333.9027) which
showed dH: 1.56 (1H, t, Jˆ7.5 Hz), 1.91 (1H, dd, Jˆ7.5,
10.4 Hz), 2.15 (1H, dddd, Jˆ6.0, 7.5, 8.2, 10.4 Hz), 4.32
(1H, dd, Jˆ8.2, 12.0 Hz), 4.58 (1H, dd, Jˆ6.0, 12.0 Hz),
7.44±7.64 (3H, m), 8.08±8.12 (2H, m); dC: 24.7, 27.02,
29.11, 66.22, 128. 41, 129.71, 133.2, 166.2; nmax: 3063
w, 2952 w, 1722 s, 1602 w, 1451 m, 1341 m, 1314 m, 1270
s, 1176 m, 1111 s, 1070 m, 1026 m, 711 s, 687 m cm21; m/z,
%: 336, 2; 334, 4; 332, 2 (M1); 148, 8; 105, 100; 77, 28.
2,2-Dibromocyclopropylmethyl butyrate (15b). (2,2-
Dibromocyclopropyl)methanol (11) (2.2 g, 9.6 mmol) and
butyric anhydride (1.72 ml, 10.5 mmol) gave 2,2-dibromo-
cyclopropylmethyl butyrate (15b) (2.63 g, 92%) as a colour-
less liquid (Found M1: 299.9184. C8H12Br2O2 requires:
299.9184) which showed dH: 0.97 (3H, t, Jˆ7.4 Hz), 1.45
(1H, t, Jˆ7.4 Hz), 1.69 (2H, sextet, Jˆ7.4 Hz), 1.84 (1H,
dd, Jˆ7.4, 10.4 Hz), 1.99 (1H, dddd, Jˆ5.9, 7.4, 8.2,
10.4 Hz), 2.34 (2H, t, Jˆ7.4 Hz), 4.05 (1H, dd, Jˆ8.2,
11.9 Hz), 4.29 (1H, dd, Jˆ5.9, 11.9 Hz); dC: 13.61,
18.42, 24.8, 26.82, 29.01, 36.02, 65.52, 173.4; nmax
:
;
2965 m, 2875 w, 1739 s, 1176 s, 1107 m, 686 m cm21
m/z, %: 302, 0.5; 300, 1; 298, 0.5 (M1); 214, 2; 212, 6;
210, 3; 133, 5; 131, 5; 114, 10; 71, 100.
2,2-Dibromocyclopropylmethyl tri¯uoroacetate (15c).
(2,2-Dibromocyclopropyl)methanol (11) (1.0 g, 4.35 mmol)

4806
M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
2,2-Dibromocyclopropylmethyl acrylate (15e). Acryloyl
chloride (0.78 ml, 9.6 mmol) was added to a stirred solution
of (11) (1.6 g, 7.7 mmol) and triethylamine (1.58 ml,
11.3 mmol) in dry ether (40 ml) at 08C; triethylammonium
chloride precipitated. After 2 h at room temperature the
mixture was treated with hydrochloric acid (2%, 35 ml) to
dissolve the precipitate. The aqueous layer was extracted
with ether (3£40 ml) and the combined organic layers
were dried and evaporated. Chromatography on silica
(petrol±ether, 5:1) gave 2,2-dibromocyclopropylmethyl
acrylate (15e) (700 mg, 35%) as a colourless oil (Found
M1: 283.8871, C7H8Br2O2 requires: 283.8871) which
showed dH: 1.48 (1H, t, Jˆ7.5 Hz), 1.86 (1H, dd, Jˆ7.5,
10.4 Hz), 2.04 (1H, dddd, Jˆ6.0, 7.5, 8.2, 10.4 Hz), 4.16
(1H, dd, Jˆ8.2, 12.0 Hz), 4.38 (1H, dd, Jˆ6.0, 12.0 Hz),
5.89 (1H, dd, Jˆ1.5, 10.4 Hz), 6.17 (1H, dd, Jˆ10.4,
17.3 Hz), 6.47 (1H, dd, Jˆ1.5, 17.3 Hz); dC: 24.7, 26.92,
28.91, 65.92, 128.01, 131.52, 165.9; nmax: 2953 m,1728
s, 1634 s, 1444 m, 1409 s,1394 s, 1341 m, 1294 s, 1269 s,
1185 s, 1109 s, 1058 s, 985 s, 809 s, 689 s cm21; m/z, %:
286, 0.5; 284, 2; 282, 0.5 (M1); 214, 20; 212, 47; 210, 25;
133, 20; 131, 29; 98, 100; 70, 44.
(2.4 ml, 22.5 mmol) at room temperature. The mixture
was stirred for 2 h at 608C then poured into cold water
(150 ml) and extracted with ether (2£50 ml). The combined
extracts were washed with 5% hydrochloric acid
(2£100 ml), water (50 ml), dried and the solvent was evapo-
rated to yield 2,2-dibromo-1-methylcyclopropylmethyl
isobutyrate (16f) (4.67 g, 14.8 mmol, 99%) as a colourless
liquid which was one spot by t.l.c. (Found M1NH14 :
329.9704. C9H18Br2NO2 requires: 329.9702) which showed
dH: 1.15 (6H, d, Jˆ7.0 Hz), 1.40 (3H, s), 1.44 (1H, d,
Jˆ7.7 Hz), 1.61 (1H, d, Jˆ7.7 Hz), 2.57 (1H, heptet,
Jˆ7.0 Hz), 4.02 (1H, d, Jˆ11.6 Hz), 4.29 (1H, d,
Jˆ11.6 Hz); dC: 19.01, 20.91, 28.6, 32.82, 33.91, 34.4,
70.02, 176.8; nmax: 2973 s, 2934 m, 2875 w, 1737 br. s,
1469 m, 1389 m, 1257 m, 1189 s, 1152 s, 1075 m, 1033 m,
990 m, 695 m cm21; m/z, % (CI, NH3): 334, 50; 332, 100;
330, 48 (M1NH14 ); 316, 14; 314, 26; 312, 14 (M1); 229, 7;
228, 12; 227, 12; 226, 18; 225, 8; 224, 13; 147, 12; 145, 11;
138, 25; 105, 36.
2,2-Dibromo-1-methylcyclopropylmethyl pivaloate (16g).
A solution of (12) (3.66 g, 15.0 mmol) and 4-dimethyl-
aminopyridine (183 mg, 1.5 mmol) in dry pyridine (35 ml)
was treated with pivaloyl chloride (3.7 ml, 30 mmol) at
room temperature. The mixture was stirred for 2 h at
558C; work up as above and distillation afforded 2,2-
2,2-Dibromo-1-methylcyclopropylmethyl benzoate (16d).
Benzoyl chloride (2.86 ml, 24.6 mmol) was added to a stir-
red solution of (12) (3.0 g, 12.3 mmol) and triethylamine
(3.42 ml, 24.6 mmol) in dry ether (40 ml); triethylammo-
nium chloride precipitated. The mixture was re¯uxed for
24 h and then ®ltered. The solvent was removed; chromato-
graphy on silica (petrol±ether, 5:1) gave 2,2-dibromo-1-
methylcyclopropylmethyl benzoate (16d) (2.22 g, 52%) as
a colourless oil (Found M1: 347.9184. C12H12Br2O2
requires: 347.9184) which showed dH: 1.57 (3H, s), 1.58
(1H, d, Jˆ7.7 Hz), 1.78 (1H, d, Jˆ7.7 Hz), 4.35 (1H, d,
Jˆ11.6 Hz), 4.65 (1H, d, 11.6 Hz), 7.45±7.64 (3H, m),
8.09±8.13 (2H, m); dC: 21.11, 28.8, 33.02, 34.3, 70.72,
128.51, 129.71, 129.81, 133.2, 166.3; nmax: 2992 w, 2964
w, 2931 w, 1721 s, 1602 w, 1451 m, 1386 w, 1314 m, 1270
s, 1175 m, 1115 s, 1070 m, 1026 m, 973 m, 710 s cm21; m/z,
%: 348, 1 (M1); 162, 11; 105, 100; 77, 35.
dibromo-1-methylcyclopropylmethyl
pivaloate
(16g)
(4.4 g, 13.3 mmol, 89%) as a colourless liquid (Found
M1NH14 : 343.9858. C10H20Br2NO2 requires: 343.9861),
bp 1408C (0.3 mmHg), dH: 1.19 (9 H, s), 1.41 (3H, s),
1.45 (1H, d, Jˆ7.7 Hz), 1.65 (1H, d, Jˆ7.7 Hz), 4.01 (1H,
d, Jˆ11.6 Hz), 4.28 (1H, d, Jˆ11.6 Hz); dC: 20.91, 27.21,
28.7, 32.82, 34.3, 38.8, 70.12, 178.1; nmax: 2971 s, 2933 m,
2872 m, 1732 br.s, 1480 m, 1459 m, 1284 s, 1154 br.s, 1035
m, 986 m, 695 m cm21; m/z, % (CI, NH3): 348, 6; 346, 9;
344, 5 (M1NH14 ); 330, 17; 328, 34; 326, 15 (M1); 249, 4;
247, 4; 246, 4; 244, 6; 229 46; 227, 40; 226, 52; 224, 46;
186, 12; 142, 88; 102, 100.
1-Bromo-2-methyl-3-oxabicyclo[3.1.0]hexan-2-ol (17a).
Methyllithium in ether (1.13 ml, 1.70 mmol, 1.5 M) was
added dropwise with stirring to 2,2-dibromocyclopropyl-
methyl acetate (15a) (420 mg, 1.54 mmol) in ether (10 ml)
at 2908C. After 45 min the solution was allowed to warm to
2758C. Sat. aq. NH4Cl (5 ml) was added and the aqueous
layer was extracted with ether (2£10 ml). The combined
organic layers were dried and evaporated. Chromatography
on silica (petrol±ether, 1:1) gave a mixture of 1-bromo-2-
methyl-3-oxabicyclo[3.1.0]hexan-2-ol (17a) (55%) and
(2,2-dibromocyclopropyl)methanol (11) (10%) (200 mg,
ratio 83:17). Compound (17a) showed nmax: 3389 br. s,
2991 m, 2939 m, 2884 m, 1698 m, 1430 m, 1382 m, 1361
m, 1328 m, 1252 m, 1214 m, 1160 s, 1093 s, 1044 s, 976 s,
949 s, 869 m, 791 m cm21; m/z, %: 177, 27; 175, 38
(M12OH); 131, 2; 53, 16; 43, 100. M1 was not observed.
In solution, an equilibrium between (17a) and 1-(1-bromo-
2-hydroxymethylcyclopropyl)ethanone (23a) was observed
by NMR; ratio (17a) to (23a) in CDCl3, 81:19; in benzene-
d6, 84:16. Hemiacetal (17a) showed dH: 0.97 (1H, dd,
Jˆ5.0, 5.7 Hz), 1.19 (1H, dd, Jˆ5.7, 8.4 Hz), 1.48 (3H,
s), 1.96 (1H, ddd, 2.8, 5.0, 8.4 Hz), 2.90 (1H, s), 3.67 (1H,
d, Jˆ8.6 Hz), 4.13 (1H, dd, Jˆ2.8, 8.6 Hz); dC (benzene-
d6): 18.52, 21.21, 25.31, 39.6, 65.92, 103.7. Keto-alcohol
2,2-Dibromo-1-methylcyclopropylmethyl acrylate (16e).
Acryloyl chloride (0.90 ml, 11.0 mmol) was treated with
(12) (2.5 g, 10.2 mmol) and triethylamine (2.86 ml,
20.5 mmol) in dry ether (40 ml) at 08C as for (15e).
Chromatography on silica (petrol±ether, 5:1) gave 2,2-
dibromo-1-methyl-cyclopropylmethyl acrylate (16e) (1.3 g,
44%) as a colourless oil (Found M1: 297.9027. C8H10Br2O2
requires: 297.9027) which showed dH: 1.44 (3H, s), 1.48
(1H, d, Jˆ7.7 Hz), 1.65 (1H, d, Jˆ7.7 Hz), 4.15 (1H, d,
Jˆ11.7 Hz), 4.41 (1H, d, 11.7 Hz), 5.85 (1H, dd, Jˆ1.5,
10.3 Hz), 6.15 (1H, dd, Jˆ10.3, 17.3 Hz), 6.44 (1H, dd,
Jˆ1.5, 17.3 Hz); dC: 20.91, 28.6, 32.92, 34.3, 70.22,
128.01, 131.42, 165.6; nmax: 2993 w, 2966 w, 2933 w,
1727 s, 1634 m, 1458 m, 1407 s, 1384 m, 1295 s, 1268 s,
1185 s, 1058 s, 1033 m, 985 s, 808 m, 695 s cm21; m/z, %:
300, 1; 298, 2; 296, 1 (M1); 228, 16; 226, 32; 224, 19; 188,
8; 186, 14; 184, 8; 147, 22; 145, 18; 112, 100; 107, 16.
2,2-Dibromo-1-methylcyclopropylmethyl
isobutyrate
(16f). A solution of (12) (3.66 g, 15.0 mmol) and
4-dimethylaminopyridine (183 mg, 1.5 mmol) in dry
pyridine (35 ml) was treated with isobutyryl chloride

M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
4807
(23a) showed dH: 2.13 (1H, m), 2.57 (3H, s), 3.34 (1H, dd,
Jˆ9.1, 12.0 Hz), all other peaks underneath alcohol (11)
peaks; dC (benzene-d6): 22.52, 30.01, 37.0, 37.41,
59.82, CO peak not detected.
932 m, 884 s, 785 m, 762 s, 705 s cm21; m/z, %: 256, 9; 254,
4 (M1); 239, 4; 237, 4; 175, 12; 134, 25; 132, 17; 105, 100;
77, 42; 53, 77. In solution, an equilibrium between (17d)
and (1-bromo-2-hydroxymethylcyclopropyl)phenyl metha-
none (23d) was observed; ratio (17d) to (23d) in CDCl3,
43:57; in CD3OD, 58:42; in toluene-d8, 100:0; (17d) showed
dH (CD3OD): 1.03 (1H, dd, Jˆ5.1, 6.0 Hz), 1.10 (1H, dd,
Jˆ6.0, 8.4 Hz), 2.07 (1H, ddd, 2.9, 5.1, 8.4 Hz), 3.86 (1H, d,
Jˆ8.5 Hz), 4.30 (1H, dd, Jˆ2.9, 8.5 Hz), 7.30±7.40 (3H,
m), 7.59±7.65 (2H, m); dC (CD3OD): 19.72, 27.81, 42.1,
67.82, 104.6, 127.91, 129.01, 129.61, 141.0. Compound
(23d) showed dH (CD3OD): 1.46 (1H, dd, Jˆ6.6, 9.9 Hz),
1.70 (1H, dd, Jˆ6.6, 7.4 Hz), 2.24 (1H, ddd, 6.6, 7.4,
9.9 Hz), 3.43 (2H, d, Jˆ6.6 Hz) 7.38±7.56 (3H, m), 8.07±
8.11 (2H, m); dC (CD3OD): 18.92, 34.31, 35.0, 61.62,
129.61, 131.31, 134.81, 136.8, 195.2.
1-Bromo-2-propyl-3-oxabicyclo[3.1.0]hexan-2-ol (17b).
1.5 M Methyllithium in ether (1.22 ml, 1.83 mmol) was
added dropwise to 2,2-dibromocyclopropylmethyl butyrate
(15b) (500 mg, 1.67 mmol) in ether (10 ml) at 2908C. The
solution was stirred for 1 h at 2908C and quenched with
water (5 ml). The aqueous layer was extracted with ether
(2£10 ml). The combined organic layers were dried and
evaporated. Chromatography on silica (petrol±ether, 1:1)
gave 1-bromo-2-propyl-3-oxabicyclo[3.1.0]hexan-2-ol (17b)
(170 mg, 46%) as a white solid, mp 51±538C (Found: M1,
220.0099. C8H13BrO2 requires: 220.0099. Found: C 43.9, H
6.0. C8H13BrO2 requires: C 43.46, H 5.93) showed nmax
:
3362 br.s, 2959 s, 2932 s, 2874 m, 1696 w, 1458 m, 1408
m, 1338 m, 1240 m, 1151 s, 1110 s, 1070 m, 1046 s, 1002 s,
973 s, 945 s, 882 s, 710 m cm21; m/z, %: 222, 5; 221, 3, 220,
3 (M1); 205, 60; 203, 66; 179, 41; 177, 30; 134, 24; 99, 20;
97, 16; 71, 42; 69, 20; 53, 100. In solution, an equilibrium
between (17b) and 1-(1-bromo-2-hydroxymethylcyclo-
propyl)-butan-1-one (23b) was observed by NMR; ratio
(17b) to (23b) in CDCl3, 58:42; in toluene-d8, 67:33. The
hemiacetal (17b) showed dH: 0.94 (3H, t, Jˆ7.2 Hz), 1.03
(1H, dd, Jˆ4.8, 6.0 Hz), 1.22 (1H, dd, Jˆ6.0, 8.5 Hz),
1.45±1.85 (4H, m), 1.92 (1H, ddd, 2.8, 4.8, 8.5 Hz), 2.67
(1H, s), 3.66 (1H, d, Jˆ8.6 Hz), 4.13 (1H, dd, Jˆ2.8,
8.6 Hz); dC (toluene-d8): 15.41, 17.92, 19.42, 25.91,
38.62, 40.6, 66.62, 105.2. The keto-alcohol (23b) showed
dC (toluene-d8): 14.41, 18.72, 22.62, 37.71, 38.9, 44.42,
60.62, 204.6.
7-Bromo-3-oxabicyclo[5.1.0]octan-6-one (27). Methyl-
lithium in ether (0.96 ml, 1.39 mmol, 1.5 M) was added
dropwise to a 2,2-dibromocyclopropylmethyl acrylate (15e)
(330 mg, 1.16 mmol) in ether (10 ml) at 2908C. After stir-
ring for 50 min at below 2808C, work up as above and
chromatography on silica (petrol±ether, 2:1) gave 7-bromo-
3-oxabicyclo[5.1.0]octan-6-one (27) (92 mg, 39%) as a
white solid, mp 318C (Found M1: 203.9786. C7H9BrO2
requires: 203.9786) which showed dH (benzene-d8): 1.21
(1H, dd, Jˆ5.8, 9.1 Hz), 1.40 (1H, dddd, Jˆ2.5, 4.3, 7.7,
91 Hz), 1.49 (1H, dd, Jˆ5.8, 7.7 Hz), 2.04 (1H, ddd,
Jˆ4.3, 10.6, 13.5 Hz), 2.28 (1H, ddd, Jˆ2.3, 5.0, 13.5 Hz),
2.69 (1H, ddd, Jˆ2.3, 10.6, 12.4 Hz), 3.20 (1H, ddd, Jˆ4.3,
5.0, 12.4 Hz), 3.21 (1H, dd, Jˆ2.5, 13.6 Hz), 3.28 (1H, dd,
Jˆ4.3, 13.6 Hz); dC (benzene-d8): 23.22, 29.81, 42.3,
43.22, 67.22, 69.72, 199.3; nmax: 2937 w, 2862 m, 1711
m, 1692 s, 1294 m, 1261 m, 1166 m, 1141 s, 1034 m,
904 cm21; m/z, %: 206, 5; 204, 4 (M1); 178, 5; 176, 12;
148, 9; 146, 10; 133, 10; 125, 70; 97, 18; 69, 75, 53, 100.
Reaction of 2,2-dibromocyclopropylmethyl tri¯uoro-
acetate (15c) with methyllithium
1-Bromo-2,5-dimethyl-3-oxabicyclo[3.1.0]hexan-2-ol (18a).
Methyllithium in ether (1.37 ml, 2.06 mmol, 1.5 M) was
added dropwise to 2,2-dibromo-1-methylcyclopropyl-
methyl acetate (16a) (490 mg, 1.70 mmol) in ether (10 ml)
at 2908C. Work up as above and chromatography on silica
(petrol±ether, 2:1) gave (16a) (60 mg) and a colourless oil,
1-bromo-2,5-dimethyl-3-oxabicyclo[3.1.0]hexan-2-ol (18a)
(186 mg, 52% [60% based on recovered starting material])
(Found M1: 205.9942. C7H11BrO2 requires: 205.9942)
which showed dH: 0.89 (1H, d, Jˆ5.9 Hz), 1.10 (1H, d,
Jˆ5.9 Hz), 1.35 (3H, s), 1.50 (3H, s), 3.14 (1H, br. s),
3.72 (1H, d, Jˆ8.4 Hz), 3.88 (1H, d, Jˆ8.4 Hz); dC:
Methyllithium in ether (0.61 ml, 0.97 mmol, 1.5 M) was
added dropwise to 2,2-dibromocyclopropylmethyl tri¯uoro-
acetate (15c) (300 mg, 0.92 mmol) in ether (15 ml) at
2908C as above. The solution was stirred for 30 min at
2908C then warmed to 08C over 30 min and quenched
with sat. aq. NH4Cl (5 ml). The aqueous layer was extracted
with ether (2£10 ml). The combined organic layers were
dried and evaporated to give (2,2-dibromocyclopropyl)-
methanol (11) (190 mg, 90%) as a colourless oil, identical
by NMR and IR to the material prepared above and to that
reported.7
15.21, 21.91, 23.82, 28.1, 47.4, 70.82, 104.5; nmax
:
1-Bromo-2-phenyl-3-oxabicyclo[3.1.0]hexan-2-ol (17d).
1.5 M Methyllithium in ether (0.72 ml, 1.09 mmol) was
added dropwise to 2,2-dibromocyclopropylmethyl benzoate
(15d) (300 mg, 0.90 mmol) in ether (10 ml) at 2908C. The
solution was stirred for 40 min at below 2808C. Water
(5 ml) was added and the aqueous layer was extracted
with ether (2£10 ml). The combined organic layers were
dried and evaporated. Chromatography on silica (petrol±
ether, 1:1) gave 1-bromo-2-phenyl-3-oxabicyclo[3.1.0]-
hexan-2-ol (17d) (146 mg, 64%) as a white solid, mp
1418C (Found: C 51.9, H 4.3. C11H11BrO2 requires: C
51.79, H 4.35) which showed nmax: 3360 br. s, 3091 m,
2948 m, 2887 s, 1451 m, 1411 s, 1333 m, 1240 s, 1222 s,
1145 s, 1092 s, 1077 s, 1056 s, 1045 s, 1017 s, 1000 s, 954 s,
3397 br. s, 2954 m, 2933 m, 2878 m, 1446 m, 1389 m,
1315 m, 1212 m, 1171 s, 1077 s, 997 s, 952 s, 883 s, 807
m, 754 m cm21; m/z, %: 208, 2; 206, 2 (M1); 193, 21; 191,
20; 175, 6; 173, 4; 151, 12; 149, 11; 148, 13; 146, 10; 127,
16; 67, 100.
1-Bromo-5-methyl-2-propyl-3-oxabicyclo[3.1.0]hexan-
2-ol (18b). Methyllithium in ether (22.3 ml, 33.4 mmol,
1.5 M) was added to 2,2-dibromo-methylcyclopropylmethyl
butyrate (16b) (10.00 g, 31.8 mmol) in ether (150 ml) at
2908C over 5 min. The solution was stirred for 30 min at
2908C then warmed to 08C for 30 min. Work up as above
gave crude 1-bromo-5-methyl-2-propyl-3-oxabicyclo[3.1.0]-

4808
M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
hexan-2-ol (18b) (7.75 g, 99%). For analytical purposes,
chromatography of 1.14 g of crude product on silica
(petrol±ether, 1:1) gave pure (18b) (840 mg, 74%) as a
white solid, mp 49±518C (Found M1: 234.0255.
C9H15BrO2 requires: 234.0255. Found: C 46.5, H 6.5.
C9H15BrO2 requires: C 45.98, H 6.43) which showed dH:
0.91 (1H, d, Jˆ6.0 Hz), 0.96 (3H, t, Jˆ7.2 Hz), 1.18 (1H,
d, Jˆ6.0 Hz), 1.35 (3H, s), 1.40±1.95 (4H, m), 2.65 (1H, s),
3.73 (1H, d, Jˆ8.4 Hz), 3.88 (1H, d, Jˆ8.4 Hz); dC: 14.41,
to reach 08C over 30 min then worked up as above.
Chromatography on silica (80 g, petrol±ether, 75:25) gave
1-bromo-2-isopropyl-3-oxabicyclo[3.1.0]hexan-2-ol (18f)
(2.73 g, 11.6 mmol, 80%) as a colourless oil (Found
MH1: 235.0331. C9H16BrO2 requires: 235.0334) which
showed dH: 0.91 (1H, d, Jˆ6.0 Hz), 0.98 (3H, d,
Jˆ6.9 Hz), 1.09 (3H, d, Jˆ6.9 Hz), 1.22 (1H, d,
Jˆ6.0 Hz), 1.28 (3H, s), 2.03 (1H, qq, Jˆ6.9, 6.9 Hz),
2.61 (1H, s), 3.67 (1H, d, Jˆ8.4 Hz), 3.81 (1H, d,
Jˆ8.4 Hz); dC: 15.61, 17.41, 17.71, 23.32, 27.0,
34.81, 46.1, 70.62, 106.5; nmax: 3462 br. s, 2968 s, 2931
s, 2876 s, 1472 m, 1388 m, 1316 w, 1162 m, 1066 s, 1017 s,
944 s cm21; m/z, % (CI, NH3): 252, 4; 250, 3; 237, 2; 235, 3
(MH1); 219, 94; 217, 100; 155, 2; 111, 2.
15.21, 16.72, 23.92, 27.3, 38.12, 47.2, 70.72, 105.4; nmax
:
3425 br. s, 2961 s, 2931 s, 2873 s, 1456 s, 1390 s, 1315 m,
1294 m, 1267 m, 1245 m, 1162 s, 1127 m, 1103 m, 1086 m,
1039 s, 1011 s, 954 s, 909 m, 880 m, 859 m, 804 m, 755
m cm21; m/z, %: 236, 6; 234, 8 (M1), 193, 29; 191, 41; 179,
6; 177, 6; 148, 12; 146, 12; 111, 41; 86, 26; 84, 43; 71, 42; 67,
100; 43, 58; 41, 90.
1-Bromo-2-t-butyl-3-oxabicyclo[3.1.0]hexan-2-ol (18g).
Methyllithium in ether (9.6 ml, 1.2 mol equiv., 1.5 M) was
added dropwise to 2,2-dibromo-1-methylcyclopropyl-
methyl pivaloate (16g) (3.94 g, 12.0 mmol) in ether
(60 ml) at 2908C over 10 min. The solution was allowed
to reach 08C over 30 min; quenching and work-up as above
1-Bromo-5-methyl-2-phenyl-3-oxabicyclo[3.1.0]hexan-
2-ol (18d). Methyllithium in ether (2.77 ml, 3.60 mmol,
1.5 M) was added dropwise to 2,2-dibromo-1-methylcyclo-
propylmethyl benzoate (16d) (1.0 g, 2.87 mmol) in ether
(25 ml) at 2908C. The solution was stirred for 20 min at
2908C and quenched with sat. aq. NH4Cl (10 ml). Work up
as above and recrystallisation from ethyl acetate gave
1-bromo-5-methyl-2-phenyl-3-oxabicyclo-[3.1.0]hexan-2-
ol (18d) (631 mg, 82%) as a white solid, mp 1428C (Found:
C 53.63, H 4.90. C12H13BrO2 requires: C 53.55, H 4.87)
which showed dH: 0.81 (1H, d, Jˆ6.2 Hz), 1.17 (1H, d,
Jˆ6.2 Hz), 1.39 (3H, s), 3.92 (1H, d, Jˆ8.4 Hz), 4.05
(1H, d, Jˆ8.4 Hz), 7.33±7.36 (3H, m), 7.62±7.65 (2H,
m); dC: 15.61, 23.82, 28.6, 48.1, 71.22, 104.2, 126.21,
128.51, 128.81, 139.4; nmax: 3354 s, 2966 m, 2931 m, 2876
s, 1448 s, 1411 s, 1323 m, 1275 s, 1165 s, 1071 s, 1015 s,
gave
1-bromo-2-t-butyl-3-oxabicyclo[3.1.0]hexan-2-ol
(18g) (2.4 g, 9.7 mmol, 81%) as a colourless oil (Found
MH1: 249.0488. C10H18BrO2 requires: 249.0490) which
showed dH: 0.98 (1H, d, Jˆ6.2 Hz), 1.10 (9H, s), 1.28
(3H, s), 1.42 (1H, d, Jˆ6.2 Hz), 2.56 (1H, s), 3.68 (1H, d,
Jˆ8.4 Hz), 3.80 (1H, d, Jˆ8.4 Hz); dC: 13.11, 25.82, 26.1,
39.8, 44.8, 70.32, 107.4; nmax: 3498 br. s, 3081 w, 2961 s,
2875 s, 1486 s, 1463 s, 1396 s, 1365 s, 1249 m, 1214 m,
1167 m, 1079 s, 1050 s, 1006 s, 954 s, 868 m, 754 m cm21
;
m/z, % (CI, NH3): 250, 4; 248, 7 (M1); 234, 9; 233, 87; 231,
100; 210, 6; 208, 6; 193, 40; 191, 42; 175, 9; 173, 7; 146, 18;
111, 52.
954 s, 920 s, 878 s, 768 s, 752 s, 702 s, 655 s, 596 m cm21
;
m/z, %: 270, 5; 268, 3 (M1), 253, 4; 251, 5; 162, 12; 148, 18;
115, 15; 105, 30; 77, 100; 65, 32; 51, 32.
2-Bromo-2-butyrylcyclopropanecarboxylic acid methyl
ester (30). Water (3 ml), periodic acid (1.5 g, 6.56 mmol)
and ruthenium trichloride hydrate (5 mg, 0.05 mol equiv.)
were added to 1-bromo-2-propyl-3-oxabicyclo[3.1.0]hexan-
2-ol (17b) (100 mg, 0.45 mmol) in carbon tetrachloride
(2 ml) and acetonitrile (2 ml). The mixture was re¯uxed
for 12 h. Water (5 ml) was added, the mixture was extracted
with ether (3£10 ml), the combined organic layers were
washed with water (2£20 ml), dried and concentrated to
ca. 6 ml and a solution of diazomethane in ether was
added. The solvent and excess diazomethane were removed.
Chromatography on silica (petrol±ether, 5:1) gave methyl 2-
bromo-2-butyrylcyclopropane carboxylate (30) (74 mg,
66%) as a colourless oil which showed dH: 0.90 (3H, t,
Jˆ7.3 Hz), 1.61 (2H, sextet, Jˆ7.3 Hz), 1.62 (1H, dd,
Jˆ7.0, 9.4 Hz), 2.12 (1H, t, Jˆ7.0 Hz), 2.45 (1H, dd,
Jˆ7.0, 9.4 Hz), 2.55 (1H, td, Jˆ7.3, 17.8 Hz), 2.89 (1H,
td, Jˆ7.3, 17.8 Hz), 3.68 (3H, s); dC: 13.51, 17.22,
1-Bromo-5-methyl-2-vinyl-3-oxabicyclo[3.1.0]hexan-2-ol
(18e). Methyllithium in ether (0.65 ml, 0.84 mmol, 1.3 M)
was added dropwise to 2,2-dibromo-1-methylcyclopropyl-
methyl acrylate (16e) (200 mg, 0.67 mmol) in ether (10 ml)
at 2908C. The solution was stirred for 40 min at below
2808C. Work up as above and chromatography on silica
(petrol±ether, 1:5) gave 1-bromo-5-methyl-2-vinyl-3-oxa-
bicyclo[3.1.0]hexan-2-ol (18e) (100 mg, 68%) as a white
solid, mp 638C which showed dH: 1.44 (3H, s), 1.48 (1H,
d, Jˆ7.7 Hz), 1.65 (1H, d, Jˆ7.7 Hz), 4.15 (1H, d,
Jˆ11.7 Hz), 4.41 (1H, d, 11.7 Hz), 5.85 (1H, dd, Jˆ1.5,
10.3 Hz), 6.15 (1H, dd, Jˆ10.3, 17.3 Hz), 6.44 (1H, dd,
Jˆ1.5, 17.3 Hz); dC: 20.91, 28.6, 32.92, 34.3, 70.22,
128.01, 131.42, 165.6; nmax: 3340 br. s, 2962 m, 2885
m, 1419 m, 1389 w, 1214 m, 1176 s, 1088 m, 1044 s,
1021 m, 983 s, 954 m, 039 s, 880 m, 803 m, 760 m, 681
m, 502 m cm21; m/z, %: 221, 4; 220, 5; 219, 5 (M1); 218, 7;
217, 40; 215, 60; 203, 25; 201, 37; 137, 98; 108, 84; 67, 52;
55, 100; 53, 53. It was not possible to obtain good CHN
values for (18e).
21.92, 31.81, 37.4, 41.72, 52.51, 168.9, 200.1; nmax
:
2963 s, 2877 m, 1732 s, 1439 s, 1373 s, 1273 m, 1207 s,
1181 s, 1141 s, 1066 m, 1009 m, 936 m, 915 m, 733 s cm21
;
m/z, %: 222, 56; 220, 6 (M12CO); 205, 2; 203, 2; 169, 9;
149, 7; 98, 7; 81, 9; 71, 57; 59, 23; 55, 19; 43, 100 (M1 was
not observed).
1-Bromo-2-isopropyl-3-oxabicyclo[3.1.0]hexan-2-ol (18f).
1.5 M Methyllithium in ether (11.7 ml, 1.2 mol equiv.)
was added dropwise to 2,2-dibromo-1-methylcyclopropyl-
methyl isobutyrate (16f) (4.59 g, 14.6 mmol) in ether
(100 ml) at 2908C over 10 min. The solution was allowed
2-Bromo-2-butyryl-1-methylcyclopropanecarboxylic acid
methyl ester (31). (a) Water (0.6 ml), periodic acid
(202 mg, 0.88 mmol) and ruthenium trichloride hydrate
(2 mg, 0.02 mol equiv.) were added to 1-bromo-5-methyl-

M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
4809
2-propyl-3-oxabicyclo[3.1.0]hexan-2-ol (18b) (99 mg,
0.42 mmol) in carbon tetrachloride (0.6 ml) and acetonitrile
(0.6 ml). The mixture was re¯uxed for 30 min, when it was
black, then extracted with ether (3£3 ml). The combined
organic layers were dried and evaporated to give 2-bromo-
(M12CH3); 191, 7; 189, 13; 163, 24; 141, 100; 99, 67; 82,
18; 59, 20; 53, 19.
2-Acetyl-2-bromo-1-methylcyclopropanecarboxylic acid
methyl ester (33) and 1-bromo-2-methylcyclopropane-
1,2-dicarboxylic acid dimethyl ester (35). Water (3 ml),
periodic acid (2.77 g, 12.17 mmol) and ruthenium trichlor-
ide hydrate (9 mg, 0.05 mol equiv.) was added to 1-bromo-
2,5-dimethyl-3-oxabicyclo[3.1.0]-hexan-2-ol (18a) (180 mg,
0.87 mmol) in carbon tetrachloride (2 ml) and acetonitrile
(2 ml). The mixture was re¯uxed for 12 h. Work up as
above gave a mixture of methyl 2-acetyl-2-bromo-1-methyl-
cyclopropane carboxylate (33) and dimethyl 1-bromo-2-
methylcyclopropane-1,2-dicarboxylate (35) (194 mg in
total, compounds not separated, ratio by GLC, 58:42)
(nmax: 1789 m, 1735 s cm21). Compound (33) showed dH:
1.21 (1H, d, Jˆ6.6 Hz), 1.63 (3H, s), 2.34 (1H, d, Jˆ6.6 Hz),
2.39 (3H, s), 3.64 (1H, s); m/z, %: 235, 0.1; (M1); 221, 0.1;
205, 5; 177, 8; 176, 13; 175, 13; 174, 8; 155, 100; 96, 37; 53,
33. Compound (35) showed dH: 1.26 (1H, d, Jˆ6.6 Hz), 1.58
(3H, s), 2.33 (1H, d, Jˆ6.6 Hz), 3.63 (3H, s), 3.71 (1H, s);
m/z, %: 252, 6; 250, 3 (M1); 221, 23; 220, 18; 219, 24; 218,
31; 192, 40; 190, 23; 175, 20; 171, 100, 139, 25; 112, 30;
111, 30; 83, 33; 69, 25; 59, 44; 53, 84. The mixture showed
dC: 19.41, 19.81, 27.41, 27.92, 28.42, 31.9, 33.2, 38.8,
46.7, 52.61, 52.61, 53.41, 168.1, 170.9, 171.0, 199.4.
2-butyryl-1-methylcyclopropanecarboxylic acid, as
a
colourless oil (100 mg, 0.40 mmol, 80% pure by 1H
NMR), which showed: dH: 0.89 (3H, t, Jˆ7.4 Hz), 1.26
(1H, d, Jˆ6.6 Hz), 1.20±1.80 (2H, m), 1.62 (3H, s), 2.35
(1H, d, Jˆ6.6 Hz), 2.54 (1H, dt, Jˆ17.8, 7.3 Hz), 2.86 (1H,
dt, Jˆ17.8, 7.3 Hz), 10.42 (1H, s); dC: 13.51, 17.32,
19.41, 28.12, 32.0, 41.62, 47.6, 176.4, 201.0; nmax
:
3376 br. m, 3093 w, 2966 m, 2935 m, 2876 w, 1723 s,
1704 s, 1456 m, 1417 w, 1296 m, 1200 m, 930 m cm21
.
Attempts to purify the crude acid failed; it was dissolved in
ether (1 ml) and a solution of diazomethane in ether was
added. The solvent and excess diazomethane were removed.
Chromatography on silica (3 g, petrol±ether, 3:1) gave
methyl 2-bromo-2-butyryl-1-methylcyclopropane carboxy-
late (31) (79 mg, 72% based on (18b)) as a colourless oil
(Found M1: 262.0205. C10H15BrO3 requires: 262.0205)
which showed dH: 0.98 (3H, t, Jˆ7.4 Hz), 1.26 (1H, d,
Jˆ6.5 Hz), 1.63 (2H, sextet, Jˆ7.4 Hz), 1.68 (3H, s), 2.41
(1H, d, Jˆ6.5 Hz), 2.60 (1H, td, Jˆ7.4, 17.8 Hz), 2.92 (1H,
td, Jˆ7.4, 17.8 Hz), 3.68 (3H, s); dC: 13.61, 17.32, 19.91,
27.92, 33.0, 41.92, 47.1, 52.51, 176.4, 201.6; nmax: 2963
m, 1732 s, 1456 m, 1436 m, 1303 s, 1199 s, 1166 s cm21
;
m/z, %: 264, 16; 262, 17 (M1), 233, 6; 203, 9; 183, 100; 175,
10; 173, 10; 124, 11; 71, 33; 53, 17.
1-Bromo-1-(1-keto-2,2-dimethylpropanyl)-2-methyl-2-
formylcyclopropane (36). A solution of 1-bromo-2-t-butyl-
3-oxabicyclo[3.1.0]hexan-2-ol (18g) (125 mg, 0.50 mmol)
in dry dichloromethane (1 ml) was added to a solution of
PCC (162 mg, 0.75 mmol) in dichloromethane (10 ml). The
mixture was re¯uxed for 15 h. Ether (10 ml) was added and
the solution was columned through silica (10 g, 4:6 ether:-
petrol) to yield a mixture of 1-bromo-1-(1-keto-2,2-
(b) Water (3 ml), periodic acid (2.8 g, 12.3 mmol) and
ruthenium trichloride hydrate (9 mg, 0.05 mol equiv.)
were added to (18b) (200 mg, 0.85 mmol) in carbon tetra-
chloride (2 ml) and acetonitrile (2 ml). The mixture was
re¯uxed for 12 h. Water (5 ml) was added, the mixture
was extracted with ether (3£10 ml), the combined organic
layers were washed with water (2£20 ml) and dried. The
solvent was removed to give 2-bromo-2-butyryl-1-methyl-
cyclopropanecarboxylic acid. Crude acid was dissolved in
ether (10 ml) and treated with diazomethane in ether as in
(a) to give (31) (116 mg, 52%), identical to that above.
dimethylpropanyl)-2-methyl-2-formylcyclopropane
(36)
and starting material (it was not possible to separate the
two compounds) (107 mg, 0.43 mmol, 86% total) as a
colourless oil (ratio (36) to (18g) 90:10 by 1H NMR)
which showed dH: 1.27 (9H, s), 1.42 (1H, d, Jˆ7.1 Hz),
1.60 (3H, s), 2.41 (1H, d, Jˆ7.1 Hz), 8.91 (1H, s); dC:
18.41, 26.5, 28.71, 29.72, 44.2, 46.1, 177.51, 205.2;
2-Acetyl-2-bromocyclopropanecarboxylic acid methyl
ester (32) and 1-bromocyclopropane-1,2-dicarboxylic
acid dimethyl ester (34). Water (3 ml), periodic acid
(1.6 g, 7.25 mmol) and ruthenium trichloride hydrate
(5 mg, 0.05 mol equiv.) were added to 1-bromo-2-methyl-
3-oxabicyclo[3.1.0]hexan-2-ol (17a) (100 mg, 0.52 mmol)
in carbon tetrachloride (2 ml) and acetonitrile (2 ml). The
mixture was re¯uxed for 12 h. Water (5 ml) was added, the
mixture was extracted with ether (3£10 ml), the combined
organic layers were washed with water (2£20 ml) and dried.
The volume was reduced to ca. 10 ml and a solution of
diazomethane in ether was added. The solvent and excess
diazomethane were removed to give methyl 2-acetyl-2-
bromocyclopropane carboxylate (32) and dimethyl
1-bromocyclopropane-cis-1,2-dicarboxylate (34) (98 mg in
total, compounds not separated, ratio by GLC, 57:43). The
data of (34) were identical to those reported.23 Compound
(32) showed dH: 1.64 (1H, dd, Jˆ6.7, 9.6 Hz), 2.12 (1H,
dd, Jˆ6.7, 7.3 Hz), 2.39 (3H, s), 2.47 (1H, dd, Jˆ7.3,
9.6 Hz), 3.68 (1H, s); dC: 27.41, 21.92, 31.81, 37.6,
52.51, 169.1, 197.7; m/z, % (GC/MS): 207, 0.5; 205, 0.5
nmax: 3084 w, 2968 s, 2933 m, 2872 m, 1717 s, 1696 s,
1479 m, 1459 m, 1366 m, 1155 m, 1087 m, 1002 m, 992
m, 945 m, 895 m cm21; m/z, % (CI, NH3): 266, 7; 264, 10;
250, 12; 249, 84; 248, 13; 247, 100 (MH1); 219, 8; 217, 10;
167, 14; 139, 4; 111, 4.
1-Bromo-1-(1-keto-2,2-dimethylpropanyl)-2-methyl-2-
(trans-2-ethoxycarbonylvinyl)cyclopropane (37). Acti-
vated manganese dioxide (0.3 g, 3.4 mmol) was added to
a stirred solution of (18g) (249 mg, 1.00 mmol) and ethoxy-
carbonylmethylenetriphenylphosphorane (418 mg, 1.2 mmol)
in dry toluene (25 ml) and the mixture was heated to re¯ux.
Two further portions of manganese dioxide (0.3 g each)
were added after 45 and 90 min. In 4 h, glc showed that
40% of starting material was consumed. After 30 h, a further
portion of manganese dioxide (0.5 g) and ethoxycarbonyl-
methylenetriphenylphosphorane (418 mg, 1.2 mmol) were
added. After 18 h more at re¯ux, the cooled mixture was
passed through celite (5 g, washing with ether-petrol, 1:1).
The crude product was columned on silica to yield starting
material (47 mg, 0.19 mmol) and 1-bromo-1-(1-keto-2,2-

4810
M. S. Baird et al. / Tetrahedron 56 (2000) 4799±4810
Cyclopropylidene in Methoden der Organischen Chemie;
Houbel-Weyl: Verlag Stuttgart, 1989; E19b, p 391.
2. (a) Arct, J.; Skattebùl, L. Acta Chem. Scand., Ser. B 1982, 36,
593. (b) Skattebùl, L.; Nilsen, N. O.; Myhren, F. Acta Chem.
Scand., Ser. B 1986, 40, 782. (c) Skattebùl, L.; Stenstrùm, Y.;
Stjerna, M.-B. Acta Chem. Scand., Ser. B 1988, 42, 475.
3. Bolesov, I. G.; Tverezovsky, V. V.; Grishin, Y. K. Zh. Org.
Khim. 1997, 33 (1), 135.
dimethylpropanyl)-2-methyl-2-(trans-2-ethoxycarbonylvinyl)-
cyclopropane (37) (193 mg, 0.61 mmol, 61%) as a colour-
less liquid (Found MH1: 317.0754. C14H22BrO3 requires:
317.0752) which showed dH: 1.24 (3H, t, Jˆ7.1 Hz), 1.25
(9H, s), 1.27 (1H, d, Jˆ6.8 Hz), 1.58 (3H, s), 2.11 (1H, d,
Jˆ6.8 Hz), 4.12 (1H, dq, Jˆ10.9, 7.1 Hz), 4.18 (1H, dq,
Jˆ10.9, 7.1 Hz), 5.88 (1H, d, Jˆ15.6 Hz), 6.24 (1H, d,
Jˆ15.6 Hz); dC: 14.21, 19.11, 26.5, 28.11, 29.92, 44.0,
46.4, 60.52, 121.61, 148.61, 165.7, 207.5; nmax: 2983 s,
2934 m, 2908 m, 2873 m, 1720 s, 1693 s, 1644 s, 1479 m,
1462 m, 1394 m, 1366 s, 1315 s, 1266 s, 1242 m, 1180 s,
1063 m, 1037 s, 997 s, 955 m, 868 m cm21; m/z, % (CI,
NH3): 318 (44), 316 (54), 272 (14), 270 (32), 237 (28), 191
(68), 186 (100), 135 (60), 120 (80), 108 (64), 107 (81).
4. Baird, M. S. J. Chem. Soc., Chem. Commun. 1971, 1145.
5. Baird, M. S.; Kaura, A. C. J. Chem. Soc., Chem. Commun. 1976,
356.
6. Baird, M. S. J. Chem. Res. 1981, S352.
7. Tverezovsky, V. V.; Baird, M. S.; Bolesov, I. G. Tetrahedron
1997, 53, 14773.
8. Nilsen, N. O.; Skattebol, L.; Baird, M. S.; Buxton, S. R.;
Slowey, P. D. Tetrahedron Lett. 1984, 2887.
1-(1-Bromo-2-hydroxymethylcyclopropyl)butan-1-ol (38).
1-Bromo-2-propyl-3-oxabicyclo[3.1.0]hexan-2-ol
(17b)
9. Kratzat, K.; Nader, F. W.; Schwarz, T. Angew. Chem. Int. Ed.
Engl. 1981, 20, 589.
10. Baird, M. S. Unpublished results.
(60 mg, 0.27 mmol) in ether (8 ml) was added dropwise to
a suspension of LiAlH4 (23 mg, 6.0 mmol) in ether (8 ml) at
2808C. The mixture was stirred for 1 h at 2708C and then
allowed to warm to room temperature. Work-up as above
and chromatography on silica (petrol±ether, 1:5) gave two
diastereomers of 1-(1-bromo-2-hydroxymethylcyclopropyl)-
butan-1-ol (38) (total 45 mg, 74%). Diastereomer (38a)
(fraction 1; 20 mg), a white solid, mp 728C (Found: C
43.5, H 6.8. C8H15BrO2 requires: C 43.07, H 6.78) showed
dH: 0.81 (1H, t, Jˆ6.7 Hz), 0.93 (3H, t, Jˆ7.4 Hz), 1.42
(2H, sextet, Jˆ7.4 Hz), 1.44 (1H, dd, Jˆ6.7, 9.6 Hz),
1.61±1.80 (2H, m), 1.91 (1H, dddd, Jˆ5.8, 6.7, 9.6,
10.9 Hz), 3.10 (1H, t, 6.6 Hz), 3.27 (1H, dd, 10.9,
12.1 Hz), 4.04 (1H, dd, 5.8, 12.1 Hz); dC: 14.11, 18.62,
20.12, 29.41, 38.42, 43.9, 63.02, 74.71; nmax: 3320 br. s,
2953 s, 2913 m, 2868 m, 1464 m, 1376 m, 1332 s, 1268 w,
1166 m, 1145 m, 1111 s, 1080 s, 1028 s, 969 m, 840 m, 628
m cm21; m/z, %: 207, 100; (M12OH); 128, 46; 127, 53; 85,
48; 55, 25. Diastereomer (38b) (colourless oil; 25 mg; frac-
tion 2) showed dH: 0.92 (3H, t, Jˆ7.2 Hz), 1.0 (1H, t,
Jˆ7.0 Hz), 1.39 (1H, dd, Jˆ7.0, 9.9 Hz), 1.43±1.58 (2H,
m), 1.60±1.78 (2H, m), 1.89 (1H, ddd, Jˆ7.0, 7.3, 9.9 Hz),
3.18 (1H, dd, 3.5, 9.0 Hz), 3.65 (1H, dd, 7.3, 11.6 Hz), 3.71
(1H, dd, 7.0, 11.6 Hz); dC: 14.01, 18.92, 20.02, 30.31,
39.02, 45.2, 61.52, 74.71; nmax: 3354 br. s, 2959 s, 2872 s,
1640 w, 1445 m, 1380 m, 1313 m, 1256 m, 1158 m, 1108 m,
1074 m, 1036 s cm21; m/z, %: 207, 0.4; 205, 0.8 (M12OH);
181, 3; 179, 5; 163, 17; 137, 16; 107, 15; 81, 23; 73, 16; 69,
16; 53, 46; 43, 100 (M1 was not observed).
11. A preliminary account has already appeared: Baird, M. S.;
Huber, F. A. M.; Tverezovsky, V. V.; Bolesov, I. G. Tetrahedron
Lett. 1998, 39 9081.
12. Seyferth, D. J. Org. Chem. 1966, 31, 4079.
13. (a) Baird, M. S.; Baxter, A. G. W. J. Chem. Soc., Perkin Trans.
1 1979, 2317. (b) Sydnes, L. K. Acta Chem. Scand., Ser. B 1977,
31, 823.
14. Baird, M. S.; Licence, P.; Tverezovsky, V. V.; Bolesov, I. G.;
Clegg, W. Tetrahedron 1999, 55, 2773.
15. Procopiou, P. A.; Baugh, S. P. D.; Flack, S. S.; Inglis, G. G. A.
J. Chem. Soc., Chem. Commun. 1996, 2625.
16. Sydnes, L. K.; Skare, S. Can. J. Chem. 1984, 62, 2073.
17. This structure was determined by the EPSRC Crystallography
Service, Southampton University. We thank Dr S. Coles for carry-
ing out the determination, the full results of which will be
described elsewhere.
18. Gaoni, Y. J. Org. Chem. 1982, 47, 2564.
19. Trost, B. M.; Ornstein, P. L. J. Org. Chem. 1982, 47, 748;
Trost, B. M.; Ornstein, P. L. Tetrahedron Lett. 1983, 2833.
20. Because the hemiacetal and keto-alcohol forms may equi-
librate, the observation of a single diastereoisomer may re¯ect
thermodynamic rather than kinetic control. Indeed simple MM2
calculations (with molecular dynamics) using ChemOf®ce Ultra
indicated that the endo-alcohol should be of lower energy than
the exo-alkyl isomer.
21. Berrier, C.; Bonnaud, B.; Patoiseau, J. F.; Bigg, D. Tetrahedron
1991, 47, 9629.
22. Paquette, L. A.; Begland, R. W.; Storm, P. C. J. Am. Chem.
Soc. 1970, 92, 1971.
Acknowledgements
23. (a) McDonald, R. N.; Reitz, R. R. J. Org. Chem. 1972, 37,
2418. (b) Saegusa, T. J. Org. Chem. 1973, 38, 2319.
24. Blackburn, L.; Wei, X.; Taylor, R. J. K. J. Chem. Soc., Chem.
Commun. 1999, 1337.
This work was carried out with the support of the INTAS
program (96-1325) and INTAS Fellowship grant for Young
Scientists (YSF98-137).
25. Salaun, J.; Baird, M. S. Curr. Med. Chem. 1995, 2, 511.
26. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Puri®cation of
Laboratory Chemicals, 3rd ed.; Pergamon Press: Oxford, 1988.
References
1. For collected references see Bakkes, J.; Brinker, U. H.