Synthesis of tertiary cyclobutanols through stereoselective ring expansion of oxaspiropentanes induced by Grignard reagents

Article abstract of DOI:10.1016/S0040-4020(00)00369-0

The stereoselectivity of the ring expansion of oxaspiropentanes to cyclobutanols induced by Grignard reagents has been studied. It has been found that the reaction occurs through the intermediacy of a cyclobutanone, formed stereospecifically, whereas the attack of the Grignard reagent on the carbonyl group of the cyclobutanone is stereospecific only in the case of the oxaspiropentanes derived from aldehydes. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00369-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4555±4563
Synthesis of Tertiary Cyclobutanols through Stereoselective Ring
Expansion of Oxaspiropentanes Induced by Grignard Reagents
*
Angela M. Bernard, Costantino Floris, Angelo Frongia and Pier P. Piras
Á
Dipartimento di Scienze Chimiche, Universita di Cagliari, Complesso Universitario di Monserrato, S.S. 554, Bivio per Sestu,
I-09042 Monserrato (Cagliari), Italy
Received 25 January 2000; revised 7 April 2000; accepted 27 April 2000
AbstractÐThe stereoselectivity of the ring expansion of oxaspiropentanes to cyclobutanols induced by Grignard reagents has been studied.
It has been found that the reaction occurs through the intermediacy of a cyclobutanone, formed stereospeci®cally, whereas the attack of the
Grignard reagent on the carbonyl group of the cyclobutanone is stereospeci®c only in the case of the oxaspiropentanes derived from
aldehydes. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
prepared by treating the corresponding oxaspiropentanes
with LiI or TsOH in re¯uxing dichloromethane for 24 h.
When we reacted 2a,b with a set of Grignard reagents
(Scheme 2) at 2708C, good yields of cyclobutanols 3a,
3b±7b were obtained as mixtures of diastereoisomers
separable by column chromatography.
Oxaspiropentanes are very important intermediates in
organic synthesis1,2 and are usually prepared by peracid
oxidation of methylenecyclopropanes,3±9 through nucleo-
philic addition of 1-lithio-1-bromocyclopropanes to ketones
at low temperatures10±12 or through reaction of sulphur
ylides with carbonyl compounds.13±17 They have also been
proposed as intermediates in the addition of diazomethane
to ketones9 and in the reaction of dimethylsulphonium
methylide with a-haloketones.13 Their versatility as
synthetic tools is clearly demonstrated by their capability
to react with nucleophiles18 and bases15±17,19,20 to give cyclo-
propanols, and to undergo ring expansion to cyclobutanones
by reaction with acidic reagents like protonic acids, lithium
or europium salts,1,2,5,6,15±18,20,21 or by thermal treatment.22,23
In the case of 2-methyl-1-(4-methylphenyl)-2-(phenoxy-
methyl) cyclobutanol 4b only the (E)-4b product was
isolated from the reaction mixture, while the diastereo-
isomer (Z)-4b was always obtained as an enriched mixture,
from which discernible 1H and 13C NMR data were reported.
The separation of (E)-7b from its diastereoisomer (Z)-7b
was more easily carried out from the mixture obtained
from the reaction of cyclobutanone 9b with benzylmagne-
sium chloride using the same experimental conditions. As
can be seen from Scheme 2 and from the data reported in
Table 1, aromatic, aliphatic and vinylic Grignard reagents
gave cyclobutanols, whereas the reaction with benzyl-
magnesium chloride led to a 60:40 mixture of cyclobutanols
(diastereoisomeric ratio 6:4) and the cyclopropanol 8,
probably coming from a nucleophilic attack on the epoxide
ring of the oxaspiropentane.
Results and Discussion
We report here on the reaction of oxaspiropentanes with
Grignard reagents as a useful method to prepare very ef®-
ciently tertiary cyclobutanols.24 Oxaspiropentanes 2a,b
were prepared by oxidation with m-CPBA of the previously
reported25 2-cyclopropylidene-aryloxy propanes 1a,b
(Scheme 1).
Occasionally variable amounts of cyclobutanones 9a,b were
obtained if an excess of m-CPBA was used, but in this case
the chromatographic puri®cation of the oxaspiropentane
posed no problem. The cyclobutanones 9a,b were also
Keywords: cyclopropanes; oxaspiropentanes; cyclobutanones; cyclo-
butanols; stereoselectivity; ring expansion; Grignard reagents.
* Corresponding author. Fax: 1390-70-675-4388;
e-mail: pppiras@vaxca1.unica.it
Scheme 1.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00369-0

4556
A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
Scheme 2.
Table 1. Reaction of oxaspiropentanes 2a,b with Grignard reagents
Entry
R
X
Reaction condition
Ar
Derivatives 3a, 3b±7b
Cyclobut./cycloprop.
(E)/(Z) ratio
Yields
1
2
3
4
5
6
C6H5
C6H5
p-Me-C6H4
CHvCH2
CH3
Br
Br
Br
Br
I
Et2O/THF
Et2O/THF
Et2O/THF
THF
Et2O/THF
Et2O/THF
p-MeO-C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
3a
3b
4b
5b
6b
7b
100:0
100:0
100:0
100:0
100:0
60:40
80:20
75:25
80:20
68:32
45:55
60:40
90
75
84
90
80
90
C6H5CH2
Cl
Scheme 3.
As a possible rationale of this reaction we believe that, due
to its electrophilic character,26 the metal atom of the
Grignard reagent, coordinates with both the oxygen atom
of the epoxide and of the aryloxy group creating an electro-
nic de®ciency on the non-cyclopropylic carbon of the
epoxide ring. At this point the oxaspiropentane undergoes
a ring expansion to the corresponding cyclobutanones 9a,b,
which then react with the Grignard reagents to give the ®nal
cyclobutanols (Scheme 3).
Strong support for this hypothesis is given by the fact that
the cyclobutanols 3b±7b are also obtained, in the same
diastereoisomeric ratio, by reaction of the corresponding
Grignard reagents with cyclobutanone 9b. This reaction
represents an unprecedented example of the use of Grignard
reagents to trigger the ring expansion of oxaspiropentanes to
cyclobutanones.
If the ®nal target is a tertiary cyclobutanol, this approach
saves one reaction step in comparison with the usual
Scheme 4.

A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
4557
ment between Hc and Hb (3.39 and 3.48 ppm, AB q) and the
aromatic proton Ha (7.28±7.30 ppm) of (E)-4b. (Fig. 1).
To obtain information regarding the stereoselectivity of this
ring expansion using Grignard reagents we decided to use a
chiral oxaspiropentane. For this purpose we prepared the
oxaspiropentane 11 by peracid oxidation of (S)-4-cyclopro-
pylidenemethyl-2,2-dimethyl-1,3-oxadiolane 10 (easily
obtained by the Wittig reaction of cyclopropylidenetriphenyl-
phosphorane with (R)-2,3-O-isopropylideneglyceraldehyde28
under McMurry's conditions).29 The oxaspiropentane 11 was
obtained as a 70:30 mixture of the expected epoxides, (2R)-
and (2S)-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-oxaspiro-
pentanes 11a and 11b (Scheme 5).
Figure 1.
methods, that allow the synthesis of the ®nal product by ®rst
preparing the cyclobutanone using either protonic acids or
lithium salts (Scheme 4).
Despite the not particularly high chiral induction, the two
diastereoisomers were easily separated by column chroma-
tography (light petroleum/diethyl ether 10:1) and this
constitutes an advantage for their synthetic exploitation.
In these cases the stereochemistry of the epoxide carbon
involved in the migration is normally inverted, and Trost
and coworkers have clearly demonstrated1,15±18 that the
stereospeci®city of the rearrangement strongly depends on
the type of acid used. In this way, changing from protonic
acids to the Lewis acidic cations of lithium or europium, the
transformation of the oxaspiropentane generates the relative
diastereoisomeric cyclobutanones with increasing levels of
stereospeci®city. Using the oxaspiropentanes 2a,b we can
say nothing about the stereoselectivity of the ring expan-
sion, although it appears that the attack of the intermediate
cyclobutanone is occurring with moderate diastereo-
selectivity, probably as a consequence of a chelation of
the magnesium with the oxygen atom of the ether group.
This chelation leads to preferential attack of the cyclo-
butanone from the same side of the ether group to give
cyclobutanols with the E geometry, except in the case of
methyl magnesium iodide, that gives the corresponding
cyclobutanol 6b with practically no stereoselectivity. The
stereochemical assignments of the geometric isomers of the
cyclobutanols were made on the basis of the differences in
the chemical shifts of the methyl and the methylene hydro-
gens, determined by the well known shielding effects
exerted by the phenyl group on cis-located groups in a
four membered ring system, and on the opposite effect
exerted by an hydroxy group.27 These assignments have
been con®rmed by the presence of a de®nite NOE enhance-
1
The structures have been assigned on the basis of their H
NMR and the stereochemistry is based on the coupling
constant of the doublets of the epoxidic CH in the two
diastereoisomers.30±32 As a matter of fact the syn stereo-
chemistry has been assigned to the major component of
the mixture (Jˆ5.1 Hz) while the anti has been assigned
to the minor one (Jˆ6.3 Hz). The stereochemical assign-
ment was further corroborated by the transformation of
the oxaspiropentane 11a into the aziridine 16 where the
Cx±Cy bond is inserted in a conformationally blocked
structure, through the sequence indicated in Scheme 6.
The oxaspiropentane 11a has been regioselectively and
stereospeci®cally33±36 opened by reaction with sodium
azide to give the azido alcohol 12, with inversion of con-
®guration, that has been protected with benzyl bromide to
give the benzyl ether 13. Subsequently, 13 has been opened
with tri¯uoroacetic acid and the primary alcoholic group of
14 has been protected as a TBDPS ether to give 15. Final
transformation of 15 into the aziridine 16 has been carried
out with PPh3/THF37 at re¯ux for 7 h. The resulting
aziridine 16 shows a coupling constant of 6.5 Hz for the
protons of the aziridinic ring, a value that is characteristic
of a syn con®guration,37±39 that is further con®rmed by the
appearance of a de®nite NOE enhancement between the two
Scheme 5.

4558
A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
Scheme 6. i: NaN3/MeOH-H2O(8:1), NH4Cl, 808C, 12 h. ii: NaH, BnBr, n-Bu4NI, imidazole(cat)THF, 08Cˆ.508C. iii: TFA.Dioxane:H2O-10:1, rt, 48 h.
iv: TBDPSCl, DMAP, imidazole, CH2Cl2, rt, 20 h. v: PPh3, THF, 658C, 7 h.
above mentioned hydrogens. As the transformation of the
oxaspiropentane 11b into the aziridine entails two steps that
occur with inversion of con®guration,40 it follows that both
the aziridine 16 and the oxaspiropentane 11a should have
the same syn con®guration.
However it was not possible to obtain pure 18 due to the
fragility of the oxadiolane ring. As a matter of fact, when
examined by glc-mass spectrometry, the products were
always accompanied by small amounts of cyclobutanols
deprotected at the oxadiolane ring that could not be
separated from the protected ones. This result tentatively
demonstrates that the transformation induced by Grignard
reagents of oxaspiropentanes into cyclobutanones is stereo-
speci®c. The attack of the Grignard reagent on the carbonyl
of the intermediate cylobutanones occurs with low
selectivity in the case of derivatives 9a,b giving mixtures
of Z and E derivatives, but with remarkably high stereo-
selectivity in the case of the intermediate 17 leading to the
corresponding Z cyclobutanols 18a±d where the stereo-
chemistry of the three stereocentres is completely
controlled. This assignment is further con®rmed by NOE
enhancement as shown in Fig. 2.
Once we con®rmed the oxaspiropentane con®guration, we
treated it with a set of Grignard reagents to transform it into
the corresponding cyclobutanols 18a±d and into cyclo-
propanol 19 in the case of benzyl magnesium chloride
(Scheme 7).
During this reaction the chiral epoxidic centre of the oxa-
spiropentane 11a is transformed into the chiral C2 centre of
the intermediate cyclobutanone 17, and a new stereocentre
is created by reaction of the Grignard reagent on the
carbonyl group to generate the tertiary cyclobutanol. As
the stereocentre of the glyceraldehyde derivative is stereo-
chemically stable towards the Grignard reagents,41,42 we
should expect a maximum of four diastereoisomers. In this
case we were only able to ®nd evidence for the presence of
one diastereoisomer of the expected cyclobutanols 18.
The trans selective addition normally observed for the
nucleophilic addition to a carbonyl group of a substituted
cyclobutanone43,44 is explained by the fact that it occurs at
the requisite angle of attack45 (uˆ1108) from the exo face of
Scheme 7.

A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
4559
avoiding non-bonded repulsions present in the axial confor-
mation, while the lack of stereoselectivity with derivatives
9a,b is explainable on the basis that both the methyl and the
aryloxymethylene groups can occupy the equatorial position
in conformations of comparable energy.
Finally, as both the oxaspiropentanes 2a,b and 11a,b carry
an ether function we decided to check if the presence of the
oxygen atom of the ether function was important in the ring
expansion induced by Grignard reagents. For this purpose
we prepared the oxaspiropentane 21 by m-CPBA oxidation
of the known cyclopropylidene derivative 2046 and reacted
it with p-tolylmagnesium bromide (Scheme 9).
Figure 2.
In this case the corresponding tertiary cyclobutanol 22 was
also obtained in good yields, with the cis geometry being
determined by the presence of a NOE enhancement between
the hydrogen Hc (2.51±2.62 ppm) and the aromatic protons
Ha and Hb (7.30±7.32 ppm). This result is a clear indication
that even an oxaspiropentane lacking a second oxygen atom
can undergo ring expansion to a cyclobutanone, giving a
tertiary cyclobutanol as the ®nal product.
its most stable conformation, that is the one carrying the
substituent in the pseudo equatorial position (Scheme 8).
This observation is in agreement with the result we obtained
in the case of the intermediate 17, where it will be the large
oxadiolane ring which remains in the equatorial position,
Scheme 8.
Scheme 9.

4560
A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
Conclusions
(s, 3H), 1.57±1.66 (m, 1H), 2.14±2.35 (m, 2H), 2.79±2.88
(m, 1H), 2.92 (br s, 1H), 4.02, 4.30 (AB q, 2H, Jˆ9.3 Hz),
6.92±7.54 (m, 10H). 13C NMR (CDCl3) d:21.69, 25.13,
30.89, 46.99, 72.71, 80.63, 114.68, 121.09, 126.21,
127.12, 128.09, 129.52, 143.53, 158.81. MS m/z: 250
(M1218(,1)), 175 (66), 148 (17), 133 (50), 105 (100),
94 (52), 77 (40). Anal. Calcd for C18H20O2: C, 80.56; H,
7.51. Found: C, 80.36; H, 7.40.
A new use of Grignard reagents has been found, as catalysts
for the ring expansion of oxaspiropentanes to cyclobutanols,
through the intermediacy of cyclobutanones. The reaction
represents a shortcut for the synthesis of cyclobutanols by
using cyclopropyl derivatives. Furthermore, the complete
stereocontrol in the ring expansion and, with aldehyde
derivatives, in the attack on the carbonyl group, allows the
easy synthesis of cyclobutanols whilst controlling the
stereochemistry of several stereogenic centres. Application
of this reaction to the synthesis of natural products is
currently under investigation and the results will be
presented in due course.
(E)-2-Methyl-1-(4-methylphenyl)-2-(phenoxymethyl)
cyclobutanol (4b). Yield: 67%. Pale yellow oil. H NMR
1
(CDCl3) d: 1.47 (s, 3H), 1.84±1.90 (m, 2H), 2.13±2.23 (m,
1H), 2.26 (br s, 1H), 2.31 (s, 3H), 2.75±2.84 (m, 1H), 3.39,
3.48 (AB q, 2H, Jˆ9.0 Hz), 6.73±7.42 (m, 9H). 13C NMR
(CDCl3) d: 18.52, 20.95, 25.07, 30.68, 47.47, 73.17, 78.95,
114.39, 120.30, 125.67, 128.79, 129.06, 136.95, 139.56,
159.10. MS m/z: 265 (M1217(,1)), 189 (80), 161 (10),
134 (51), 119 (100), 91 (40). Anal. Calcd for C19H22O2: C,
80.22; H, 7.85. Found: C, 80.30; H, 7.65.
Experimental
Reagent-grade commercially available reagents and
solvents were used. Analytical TLC plates and silica gel
were purchased from Merck. IR spectra were recorded on
a Perkin±Elmer 1310 grating spectrophotometer using NaCl
plates. 1H and 13C NMR spectra were recorded on a Varian
VXR-300 spectrometer with tetramethylsilane as internal
reference; d values are given in ppm and J values in Hz.
Mass spectra were obtained at 70 eV with a Hewlett-
Packard 5989A mass spectrometer. Optical activity was
determined on a Perkin±Elmer 241 polarimeter with a
path length of 1 dm. Concentrations are given in g/100 ml.
Microanalyses were carried out on a Carlo Erba 1106
Elemental Analyzer. Analytical data of products 2a, 2b,
3a, 7b, 8, 9b have previously reported.24
(Z)-2-Methyl-1-(4-methylphenyl)-2-(phenoxymethyl)
cyclobutanol (4b). Yield: 17%. Pale yellow oil. (Discern-
ible data from mixture of E/Z 4b): 1H NMR (CDCl3) d: 0.84
(s, 3H), 0.81±0.98 (m, 1H), 1.54±1.62 (m, 1H), 2.24±2.32
(m, 2H), 2.26 (s, 3H), 2.35 (br s, 1H), 4.00, 4.25 (AB q, 2H,
Jˆ9.3 Hz), 6.68±7.43 (m, 9H). 13C NMR (CDCl3) d: 21.05,
21.73, 25.18, 30.80, 46.90, 72.68, 80.54, 114.68, 121.01,
126.16, 128.79, 129.51, 136.69, 140.67, 158.89. MS m/z:
267 (M1215(,1)), 189 (71), 161 (11), 134 (47), 119
(100), 91 (34).
(E)-2-Methyl-2-(phenoxymethyl)-1-vinylcyclobutanol
(5b). Yield: 61%. Pale yellow oil. 1H NMR (CDCl3) d: 1.35
(s, 3H), 1.61±1.67 (m, 2H), 2.08±2.16 (m, 1H), 2.21±2.28
(m, 2H; one is D2O exchangeable), 3.68, 3.77 (AB q, 2H,
Jˆ9.0 Hz), 5.11 (dd, 1H, 3Jˆ10.8 Hz, 2Jˆ1.3 Hz), 5.28 (dd,
1H, 3Jˆ17.4 Hz, 2Jˆ1.3 Hz), 6.12 (dd, 1H, Calcd
General method for the synthesis of 2a, 2b
To a stirred solution of 1a or 1b (0.017 mol) in dichloro-
methane (80 ml) at 08C, m-CPBA (0.017 mol) was added
portion wise. After stirring for 20 h at room temperature, the
solution was ®ltered and treated several times with a satu-
rated solution of sodium bicarbonate. The organic phase
was dried (Na2SO4) and after ®ltration evaporated under
vacuum. The remaining oil was chromatographed on a silica
gel column (light petroleum/diethyl ether 5:1) to give the
puri®ed product in 75±90% yields.
3
Jˆ17.4 Hz, Jˆ10.8 Hz), 6.84±7.27 (m, 5H). 13C NMR
(CDCl3) d: 18.42, 23.95, 30.62, 46.80, 73.01, 76.92,
112.83, 114.48, 120.51, 129.25, 139.82, 159.08. MS m/z:
218 (M1(,1)), 148 (8), 133 (86), 94 (95), 77 (10), 55
(100). Anal. Calcd for C14H18O2: C, 77.03; H, 8.31.
Found: C, 77.22; H, 7.95.
(Z)-2-Methyl-2-(phenoxymethyl)-1-vinylcyclobutanol
(5b). Yield: 29%. Pale yellow oil. 1H NMR (CDCl3) d: 1.10
(s, 3H), 1.46±1.56 (m, 1H), 1.92±2.01 (m, 1H), 2.13±2.33
(m, 2H), 2.65 (br s, 1H), 3.98, 4.15 (AB q, 2H, Jˆ9.0 Hz),
5.18 (dd, 1H, 3Jˆ10.6 Hz, 2Jˆ1.5 Hz), 5.31 (dd, 1H,
3Jˆ17.4 Hz, 2Jˆ1.5 Hz), 6.09 (dd, 1H, 3Jˆ17.4 Hz,
3Jˆ10.6 Hz), 6.93±7.32 (m, 5H). 13C NMR (CDCl3) d:
20.52, 24.17, 31.31, 46.49, 73.09, 78.01, 112.45, 114.60,
121.01, 129.39, 140.45, 158.69. MS m/z: 218 (M1(,1)),
148 (8), 133 (31), 94 (100), 77 (6), 55 (94). Anal. Calcd
for C14H18O2: C, 77.03; H, 8.31. Found: C, 77.30; H, 8.10.
Analytical data of cyclobutanols 3b±6b
Following the reported general method24 cyclobutanols 3a,
3b±7b and cyclopropanol 8 were prepared.
(E)-2-Methyl-2-(phenoxymethyl)-1-phenylcyclobutanol
(3b). Yield: 56%. Pale yellow oil. 1H NMR (CDCl3) d: 1.47
(s, 3H), 1.84±1.91 (m, 2H), 2.16±2.25 (m, 1H), 2.81 (br s,
1H), 2.78±2.87 (m, 1H), 3.26, 3.36 (AB q, 2H, Jˆ9.3 Hz),
6.59±7.44 (m, 10H). 13C NMR (CDCl3) d: 18.52, 25.01,
30.68, 47.50, 73.06, 79.01, 114.34, 120.32, 125.76,
127.35, 128.05, 129.06, 142.49, 158.99. MS m/z: 250
(M1218(,1)), 175 (71), 148 (18), 133 (62), 105 (100),
94 (48), 77 (41). Anal. Calcd for C18H20O2: C, 80.56; H,
7.51. Found: C, 80.30; H, 7.60.
(E)-1,2-Dimethyl-2-(phenoxymethyl) cyclobutanol (6b).
Yield: 36%. Pale yellow oil. H NMR (CDCl3) d: 1.33 (s,
1
3H), 1.38 (s, 3H), 1.50±1.57 (m, 2H), 1.88±1.96 (m, 2H;
one is D2O exchangeable), 2.04±2.18 (m, 1H), 3.74, 3.88
(AB q, 2H, Jˆ9.3 Hz), 6.88±7.30 (m, 5H). 13C NMR
(CDCl3) d: 18.60, 23.61, 29.69, 33.42, 46.00, 72.99,
74.38, 114.48, 120.60, 129.37,159.18. MS m/z: 206
(Z)-2-Methyl-2-(phenoxymethyl)-1-phenylcyclobutanol
(3b). Yield: 19%. Pale yellow oil. 1H NMR (CDCl3) d: 082

A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
4561
(M1(,1)), 148 (5), 133 (26), 94 (100), 77 (5), 55 (40). Anal.
Calcd for C13H18O2: C, 75.69; H, 8.80. Found: C, 75.22; H,
8.95.
[a]2D5ˆ125.82 (c 10, CHCl3),1H NMR (CDCl3), d: 0.92±
1.18 (m, 4H), 1.38 (s, 3H), 1.46 (s, 3H), 3.57 (d, 1H,
Jˆ5.1 Hz), 4.00±4.13 (m, 3H);13C NMR (CDCl3), d:
1.69, 2.90, 25.32, 26.53, 57.88, 58.62, 66.43, 75.88,
109.70. MS m/z: 155 (M1215 (16)), 101 (6), 72 (26), 55
(35), 43 (100). Anal. Calcd for C9H14O3: C, 63.51; H, 8.29.
Found: C, 63.80; H, 8.10.
(Z)-1,2-Dimethyl-2-(phenoxymethyl) cyclobutanol (6b).
Yield: 44%. Pale yellow oil. H NMR (CDCl3) d: 1.12 (s,
1
3H), 1.33 (s, 3H), 1.37±1.49 (m, 1H), 1.81±2.01 (m, 2H),
2.13±2.21 (m, 1H), 2.75 (br s, 1H), 3.99, 4.07 (AB q, 2H,
Jˆ9.0 Hz), 6.92±7.31 (m, 5H). 13C NMR (CDCl3) d: 19.40,
23.96, 24.38, 34.62, 46.07, 73.45, 75.52, 114.66, 121.08,
129.47, 158.89. MS m/z: 206 (M1(,1)), 148 (4), 133
(20), 94 (100), 77 (4), 55 (33). Anal. Calcd for C13H18O2:
C, 75.69; H, 8.80. Found: C, 75.52; H, 8.65.
(2S)-2-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-oxaspiro-
pentane (11b). White waxy solid. Yield: 21%.
1
[a]2D5ˆ23.58 (c 3, CHCl3), H NMR (CDCl3), d: 0.91±
1.15 (m, 4H), 1.38 (s, 3H), 1.46 (s, 3H), 3.56 (d, 1H,
Jˆ6.3 Hz), 3.76±4.07 (m, 2H), 4.12±4.19 (m, 1H); 13C
NMR (CDCl3), d: 1.82, 1.93, 25.33, 26.62, 55.91, 59.22,
65.41, 76.90, 110.00. MS m/z: 155 (M1215 (10)), 101
(4), 83 (7), 72 (13), 55 (25), 43 (100). Anal. Calcd for
C9H14O3: C, 63.51; H, 8.29. Found: C, 63.65; H, 8.40.
2-[(4-Methoxyphenoxy)methyl]-2-methylcyclobutanone
(9a). A solution of 2a (1 g, 4.5 mmol) in dichloromethane
(10 ml) was treated with LiI (0.30 g, 0.22 mmol, 5 mol%)
and re¯uxed for 24 h. The mixture was washed repeatedly
with brine and then dried over Na2SO4. Evaporation of
dichloromethane left an oil that was puri®ed by chromato-
graphy on silica gel column (light petroleum/diethyl ether
3:1) to give 0.87 g of the expected cyclobutanone as a white
solid, m.p. 448C. Yield: 87%. 1H NMR (CDCl3) d: 1.26 (s,
3H), 1.78±1.88 (m, 1H), 2.35±2.43 (m, 1H), 3.00±3.18
(m,2H), 3.75 (s, 3H), 3.77±3.98 (AB q, 2H, Jˆ9.0 Hz),
6.81 (s, 4H). 13C NMR (CDCl3): 17.49, 21.47, 43.05,
54.98, 63.68, 70.83, 114.09, 115.15, 152.45, 153.65,
212.35. IR (nujol, cm21): 1785. MS m/z: 220 (M1 (12)),
124 (100), 109 (23), 95 (5), 69 (19). Anal. Calcd for
C13H16O3: C, 70.89; H, 7.32. Found: C, 71.06; H, 7.40.
1-{(S)-Azido [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl] methyl}
cyclopropanol (12). The oxaspiropentane 11a (2 g,
13 mmol) was dissolved in 50 ml of methanol/water (8:1)
together with sodium azide (4.2 g, 65 mmol) and ammo-
nium chloride (1.4 g, 26 mmol). The solution was stirred
at 808C (external oil bath temperature) for 6 h. The reaction
mixture was then poured onto brine and extracted with
dichloromethane. After drying and evaporation of the
solvent the residue was chromatographed on a silica gel
column with a 5:1 light petroleum/diethyl ether mixture,
to obtain 2 g of pure product as an oil. Yield: 74%.
1
[a]2D5ˆ222.0 (c 4, CHCl3); H NMR (CDCl3), d: 0.61±
0.92 (m, 4H), 1.40 (s, 3H), 1.48 (s, 3H), 2.88 (d, 1H,
Jˆ6.9 Hz), 3.37 (br s, 1H), 3.89±4.14 (m, 2H), 4.41±4.48
(m, 1H). 13C NMR (CDCl3), d: 12.14, 12.51, 25.34, 26.34,
56.69, 66.17, 68.16, 77.35, 109.93. IR (neat, cm21): 3440,
2100. MS m/z: 198 (M1215 (4)), 155 (2), 113 (5), 101 (45),
43 (100). Anal. Calcd for C9H15N3O3: C, 50.68; H, 7.09; N,
19.71. Found: C, 50.95; H, 7.10; N, 19.45.
(S)-4-Cyclopropylidene-2,2-dimethyl-1,3-oxadiolane (10).
To a stirred suspension of pentane washed sodium hydride
(60% in oil, 8 g, 0.2 mol) in dry tetrahydrofuran (80 ml),
(3-bromopropyl) triphenylphosphonium bromide (46.4 g,
0.1 mol) was added under an argon atmosphere. After
adding few drops of absolute ethanol the solution was
kept at 708C (external oil bath). After 6 h at this temperature
(R)-2,3-O-isopropylideneglyceraldehyde (6.4 g, 0.05 mol)
dissolved in THF (10 ml) together with TDA-1 (1.6 g,
5 mmol), was added dropwise. The solution was kept at
the same temperature for 14 h and then poured onto brine
after cooling. The aqueous phase was repeatedly extracted
with diethyl ether and then the organic phase was dried over
Na2SO4. After evaporation of the solvent the viscous residue
was washed several times with light petroleum while stir-
ring manually with a glass rod. Evaporation of the light
petroleum gave an oil that after puri®cation by column chro-
matography on a silica gel column (light petroleum/diethyl
ether 10:1) left 5.4 g of the pure product as a colourless oil.
Yield: 70%. [a]D20ˆ113.7 (c 4, CH2Cl2), 1H NMR (CDCl3),
d: 1.07±1.16 (m, 4H), 1.38 (s, 3H), 1.43 (s, 3H), 3.67 (m,
1H), 4.09 (m, 1H), 4.70 (m, 1H), 5.82 (m, 1H); 13C NMR
(CDCl3), d: 1.91, 2.19, 25.91, 26.76, 69.13, 76.72, 108.97,
116.02, 127.92. MS m/z: 139 (M1215 (10)), 109 (22), 96
(16), 72 (27), 43 (100). Anal. Calcd for C9H14O2: C, 70.10;
H, 9.15. Found: C, 69.90; H, 9.00.
(4S)-4-{(S)-Azido [1-(benzyloxy) cyclopropyl] methyl}-
2,2-dimethyl-1,3-dioxolane (13). A suspension of sodium
hydride (2.2 g of a 65% dispersion in mineral oil, 59 mmol)
in anhydrous tetrahydrofuran (35 ml) was treated at 508C
with a solution of benzyl bromide (4.8 g, 28 mmol) also in
anhydrous tetrahydrofuran (5 ml). A solution of 12 (5 g,
23.4 mmol) in anhydrous tetrahydrofuran (10 ml) was then
added dropwise over 1 h, and the reaction mixture was kept
at this temperature for 18 h. After cooling, the reaction
mixture was treated carefully with water to destroy the
excess of sodium hydride. Dilution with diethyl ether and
evaporation of the washed (water) organic solution afforded
the crude benzyl ether which was chromatographed on a
silica gel column with a 1:1 mixture of light petroleum/
diethyl ether to give 3.5 g of pure oily product. Yield:
1
50%. [a]2D7ˆ219.7 (c 9, CHCl3); H NMR (CDCl3), d:
0.73±0.98 (m, 4H), 1.36 (s, 3H), 1.43 (s, 3H), 3.21 (d, 1H,
Jˆ8.4 Hz), 3.89±4.15 (m, 2H), 4.35±4.42 (m, 1H), 4.49,
4.74 (AB q, 2H, JABˆ11.7 Hz), 7.23 (m, 5H). 13C NMR
(CDCl3), d: 9.81, 13.25, 25.54, 26.79, 62.06, 66.55, 69.00,
71.15, 77.72, 109.45, 127.30, 127.63, 128.38, 138.03. IR
(neat, cm21): 2100. MS m/z: 288 (M1215 (,1)), 174 (4),
147 (3), 101 (15), 91 (100). Anal. Calcd for C16H21N3O3:
C, 63.33; H, 6.98; N, 13.86. Found: C, 63.50; H, 6.90; N,
13.45.
Following the method used for the synthesis of 2a, 2b the
oxaspiropentanes 11a, 11b have been prepared.
(2R)-2-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-oxaspiro-
pentane (11a). Colourless liquid. Yield: 49%.

4562
A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
(2S,3S)-3-Azido-3-[1-(benzyloxy) cyclopropyl]-1,2-pro-
panediol (14). To a solution of the protected azido alcohol
13 (2.5 g, 8.2 mmol) in dioxane/water (1:1, 40 ml),
tri¯uoroacetic acid (1.7 ml) was slowly added under
magnetic stirring. After 48 h the reaction mixture was
diluted with dichloromethane and the organic phase was
washed with sodium bicarbonate and brine. After drying
(Na2SO4) and evaporation of the solvent, the crude reaction
mixture was chromatographed (ethyl acetate/light petro-
leum 1:1) on a silica gel column previously deactivated
with methanol/water (95:5) and then with methanol.
1.24 g of pure product were obtained as a clear oil. Yield:
C29H35NO2Si: C, 76.10; H, 7.71; N, 3.06. Found: C,
76.51; H, 7.63; N, 3.10.
Synthesis of cyclobutanols 18a±d and cyclopropanol 19
18a±d and 19 have been prepared and puri®ed by following
the same procedure described for 3a, 3b±7b and 8. NMR
data of 18 a-d, 19 were obtained from compounds contain-
ing 5±10% of cyclobutanols deprotected at the oxadiolane
ring.
(1S,2S)-2-[(4S)-2,2-Dimethyl-1,3-dioxolan-4yl]-1-phenyl-
cyclobutanol (18a). Yield: 90%. Colourless oil. H NMR
1
57%. [a]2D7ˆ232.0 (c 2, CHCl3); H NMR (CDCl3), d:
1
0.80±1.17 (m, 4H), 2.92 (br s, 2H), 3.23 (d, 1H,
Jˆ6.9 Hz), 3.74±3.86 (m, 2H), 4.00±4.06 (m, 1H), 4.55,
4.87 (AB q, 2H, JABˆ11.4 Hz), 7.28 (m, 5H). 13C NMR
(CDCl3), d: 10.14, 12.66, 62.13, 62.90, 69.18, 71.58,
72.82, 127.41, 127.81, 128.48, 137.58. IR (neat, cm21):
3440, 2100. MS m/z: 220 (M1243 (,1)), 146 (2), 118
(100), 104 (2), 91 (95). Anal. Calcd for C13H17N3O3:
C, 59.30; H, 6.51; N, 15.96. Found: C, 59.66; H, 6.60; N,
15.81.
(CDCl3), d: 1.25 (s, 3H), 1.31 (s, 3H), 1.68±1.88 (m, 2H),
2.20±2.42 (m, 2H), 2.75 and 2.78 (dt 1H Jˆ8.7, 8.1 Hz),
3.50±3.60 (m, 1H), 3.60 (br s, 1H), 3.96±4.02 (m, 1H),
4.39±4.44 (m, 1H), 7.10±7.60 (m, 5H). 13C NMR
(CDCl3), d: 16.97, 25.31, 26.61, 33.26, 46.92, 67.10,
75.56, 77.71, 108.95, 125.01, 126.68, 127.90, 146.84. MS
m/z: 233 (M1215 (2)), 190 (12), 162 (12), 145 (28), 120
(63), 43 (100).
(1S,2S)-2-[(4S)-2,2-Dimethyl-1,3-dioxolan-4yl]-1-(4-methyl-
phenyl) cyclobutanol (18b). Yield: 90%. Colourless oil. 1H
NMR (CDCl3) 1.33 (s, 3H), 1.38 (s, 3H), 1.70±1.93(m, 2H),
2.25±2.40 (m, 2H), 2.32 (s, 3H), 2.78 and 2.81 (dt, 1H
Jˆ8.0, 8.7 Hz), 3.35 (br s, 1H), 3.59±3.65(m, 1H), 4.00±
4.09 (m, 1H), 4.42±4.56 (m, 1H), 7.10±7.39 (m, 4H); 13C
NMR (CDCl3), d: 16.97, 20.90, 25.42, 26.74, 33.40, 47.06,
67.42, 76.04, 77.82, 109.25, 125.01, 128.79, 136.50, 143.93.
MS m/z: 247 (M1215 (,1)), 204 (7), 159 (23), 119 (100),
105 (8), 91 (33).
(1S,2S)-1-Azido-1-[1-(benzyloxy) cyclopropyl]-3-{[tert-
butyl (diphenyl) silyl]oxy}±2-propanol (15). A solution
of the diol 14 (1.6 g, 6 mmol) in dry dichloromethane
(30 ml) was treated with Et3N (0.72 g, 7 mmol), t-butyl
diphenylsilyl chloride (1.8 g, 6.5 mmol) and DMAP
(0.029 g, 0.24 mmol) and stirred at room temperature for
24 h. The reaction mixture was diluted with water and
extracted with dichloromethane. The combined organic
extracts were dried (Na2SO4), concentrated in vacuo and
chromatographed on a silica gel column (ethyl acetate/
light petroleum 4:1) to yield 2.6 g of a pure oil. Yield:
(1S,2S)-2-[(4S)-2,2-Dimethyl-1,3-dioxolan-4yl]-1-(4-¯uoro-
phenyl) cyclobutanol (18c). Yield: 65%, colourless oil; 1H
NMR (CDCl3), d: 1.35 (s, 3H), 1.37 (s, 3H), 1.84±1.91 (m,
2H), 2.33±2.44 (m, 2H), 2.70±2.82 (m, 1H), 3.01 (br s, 1H),
3.60±3.65 (m, 1H), 4.02±4.55 (m, 1H), 4.46±4.55 (m, 1H),
6.99±7.52 (m, 4H); 13C NMR (CDCl3), d: 17.15, 25.51,
26.86, 33.64, 47.33, 67.59, 76.22, 77.55, 109.37,114.79,
115.08, 143.02, 163.45. MS m/z: 251 (M1215 (,1)), 209
(,1), 191 (3), 163 (26), 123 (100), 109 (7), 95 (20).
1
86%. [a]2D7ˆ23.9 (c 13, CHCl3); H NMR (CDCl3): d:
0.80±1.11 (m, 4H), 1.06 (s, 9H), 2.79 (d, Jˆ4.2 Hz, 1H),
3.36 (br s, 1H), 3.72±3.91 (m, 2H), 4.10±4.16 (m, 1H), 4.52,
4.82 (AB q, Jˆ11.4 Hz 2H), 7.19±7.73 (m, 15H). 13C NMR
(CDCl3): dˆ10.47; 12.63; 19.24; 26.89; 62.71; 64.28;
68.09; 71.29; 73.11; 127.37; 127.80; 128.40; 129.89;
132.84; 133.00; 135.53; 137.97. IR (neat, cm21): 3440,
2100. MS m/z: 416 (M1285 (,1)), 241 (14), 199 (20),
163 (24), 91 (100). Anal. Calcd for C29H35N3 O3Si: C,
69.43; H, 7.03; N, 8.38. Found: C, 69.60; H, 7.10; N, 8.73.
(1R,2S)-2-[(4S)-2,2-Dimethyl-1,3-dioxolan-4yl]-1-vinyl-
cyclobutanol (18d). Yield: 60%, colourless oil. H NMR
1
(2R,3S)-2-[1-(Benzyloxy)
cyclopropyl]-3-({[tert-butyl
(CDCl3), d: 1.35 (s, 3H), 1.40 (s, 3H), 1.70±1.84 (m, 2H),
2.06±2.28 (m, 2H), 2.37±2.48 (m, 1H), 3.17 (br s, 1H),
3.58±3.66 (m, 1H), 4.02±4.08 (m, 1H), 4.41±4.48 14 (m,
1H), 5.05 (dd, 1H Jˆ10.8, 1.2 Hz), 5.27 (dd, 1H Jˆ17.4,
1.2 Hz), 6.09 (dd, 1H Jˆ10.8, 17.4 Hz). 13C NMR (CDCl3):
dˆ16.46, 25.53, 26.99, 32.27, 46.57, 67.59, 73.94, 75.97,
76.38, 109.19, 111.24, 143.67. MS m/z: 183 (M1215 (,1)),
109 (35), 99 (40), 70 (70), 55 (100).
(diphenyl) silyl]oxy} methyl) aziridine (16). To a stirred
solution of triphenylphosphine (1.3 g, 5.1 mmol) in dry
tetrahydrofuran (20 ml) the product 15 (2.6 g, 5.1 mmol)
was added. After re¯uxing for 7 h the mixture was diluted
with water (30 ml) and extracted with dichloromethane. The
combined organic extracts were dried (Na2SO4), concen-
trated in vacuo and chromatographed on a silica gel column
(ethyl acetate/light petroleum 1:4) to yield 1.6 g (62%) of a
pure oil. [a]2D7ˆ24.5 (c 30, CHCl3), H NMR (CDCl3), d:
1
1-{(1S)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-phenyl-
ethyl cyclopropanol (19). Yield: 90%. White crystals, mp
123±1248C. 1H NMR (CDCl3), d 0.01±0.07 (m, 1H), 0.28±
0.36 (m, 1H), 0.53±0.60 (m, 1H), 0.64±0.71 (m, 1H), 1.26±
1.33 (m, 1H), 1.40 (s, 3H), 1.49 (s, 3H), 2.57 (brs, 1H),
2.89±3.09 (AB q, 1H, Jˆ13.8 Hz), 2.91±3.06 (AB q, 1H,
Jˆ13.8 Hz), 3.84±3.91 (m, 1H), 4.06±4.11 (m, 1H), 4.42±
4.48 (m, 1H), 7.10±7.27 (m, 5H). 13C NMR (CDCl3)ˆ2.54;
13.48; 25.23; 26.47;32.82; 49.51; 56.91; 67.14; 78.08;
0.58±0.99 (m, 4H), 1.05 (s, 9H), 2.37 (dt, 1H, Jˆ6.0,
4.5 Hz), 2.48 (br s, 1H), 2.58 (d, 1H, Jˆ6.0 Hz), 3.79±
3.84 (m, 1H), 3.97±4.01 (m, 1H), 4.43, 4.64 (AB q, 2H,
Jˆ11.4), 7.30±7.62 (m, 15H); 13C NMR (CDCl3), d:
10.24, 11.26, 19.17, 26.84, 34.59, 37.95, 60.37, 63.25,
69.94, 127.47, 127.54, 128.17, 129.53, 133.63, 135.55,
135.60, 138.59. MS m/z: 458 (M1215 (,1)), 288 (7), 240
(60), 188 (20), 162 (21), 91 (100). Anal. Calcd for

A. M. Bernard et al. / Tetrahedron 56 (2000) 4555±4563
4563
10. Makosza, M.; Wawrzyniewicz, M. Tetrahedron Lett. 1969,
4569.
108.92; 125.93; 128.23; 129.28; 140.72. MS m/z: 247
(M1215 (2)), 204 (26), 187 (13), 161 (21), 131 (33), 91
(100).
11. Dammann, R.; Braun, M.; Seebach, D. Helv. Chim. Acta 1976,
59, 2821.
12. Hiyama, T.; Takehara, S.; Kitatani, K.; Nozaki, H.
Tetrahedron Lett. 1974, 3295.
2-Heptyl-1-oxaspiro[2.2] pentane (21). To a well stirred
suspension of potassium ¯uoride (318 mg, 5.5 mmol) in dry
dichloromethane (8 ml), was added m-CPBA (552 mg,
3.2 mmol) and the resulting suspension was stirred at
room temperature for 1 h. Then a solution of 20 (500 mg,
3.2 mmol) dissolved in 8 ml of dry dichloromethane was
added at room temperature and the reaction was stirred for
1 h. The mixture was ®ltered through a layer of silica gel
and the solvent evaporated under vacuum. The residue was
puri®ed by column chromatography on silica gel using light
petroleum/diethyl ether 5:1 as eluent. Yield: 90%, colour-
less oil. 1H NMR (CDCl3), dˆ0.85 1.12 (m, 7H), 1.20±1.82
(m, 12H), 3.45 (t, 1H, Jˆ6 Hz). 13C NMR (CDCl3):
dˆ13.96; 16.80; 22.54; 25.72; 26.95; 29.03; 29.32; 29.48;
31.70; 44.26; 60.53. MS m/z: 168 (M1 (1)), 150 (3), 124 (2),
112 (10), 98 (100), 84 (33), 70 (30). Anal. Calcd for
C11H20O: C, 78.51; H, 11.98. Found: C, 78.32; H, 12.07.
13. Wiechert, R. Angew. Chem., Int. Ed. Engl. 1970, 9, 27; Angew.
Chem. 1970, 82, 219.
14. Johnson, C. R.; Katekar, G. F.; Huxol, R. F.; Janiga, E. R.
J. Am. Chem. Soc. 1971, 93, 71.
15. Bogdanowicz, M. J.; Trost, B. M. Tetrahedron Lett. 1972, 887.
16. Bogdanowicz, M. J.; Trost, B. M. J. Am. Chem. Soc. 1973, 95, 289.
17. Bogdanowicz, M. J.; Trost, B. M. J. Am. Chem. Soc. 1973, 95,
5311.
18. Trost, B. M.; Scudder, P. H. J. Am. Chem. Soc. 1977, 99, 7601.
19. Trost, B. M.; Kurozumi, S. Tetrahedron Lett. 1974, 1929.
20. Salaun, J.; Conia, J. M. J. Chem. Soc., Chem. Commun. 1971,
1579.
21. Chevtchouk, T.; Ollivier, J.; Salaun, J. Tetrahedron:
Asymmetry 1997, 8, 1011.
22. Johnson, C. R. Acc. Chem. Res. 1973, 6, 341.
23. Trost, B. M. Acc. Chem. Res. 1974, 7, 85.
24. Preliminary communication: Bernard, A. M.; Floris, C.;
Frongia, A.; Piras, P. P. Synlett 1998, 668.
25. Bernard, A. M.; Piras, P. P. Synlett 1997, 585.
26. Raston, C. L.; Salem, G. In The Chemistry of the Metal±
Carbon Bond; Hartley, F. R., Ed.; Wiley: New York, 1987; pp
4±159.
(Z)-2-Heptyl-1-(4-methylphenyl) cyclobutanol (22). The
synthesis of 22 was carried out by following the same pro-
cedure described for cyclobutanols 18. Colourless oil.
1
Yield: 78%. H NMR (CDCl3), dˆ0.87 (t, Jˆ6.3 Hz, 3H),
1.25 (m, 10H), 1.42±1.63 (m, 2H), 1.71±1.86 (m, 1H),
1.88±2.00 (m, 1H), 2.04 (br s, 1H), 2.08±2.19 (m, 1H),
2.24±2.41 (m, 1H), 2.31 (s, 3H), 2.51±2.62 (m, 1H),
7.11±7.32 (m, 4H). 13C NMR (CDCl3): dˆ14.04; 20.93;
21.84; 22.61; 26.99; 29.26; 29.31; 29.78; 31.82; 34.11;
45.75; 78.62; 124.68; 128.88; 136.39; 144.39. MS m/z:
260 (M1 (4)), 232 (4), 157 (1), 134 (100), 119 (45), 91
(22). Anal. Calcd for C18H28O: C, 83.02; H, 10.84. Found:
C, 83.32; H, 11.06.
27. Miller, D. D.; Hsu, Fu-L.; Salman, K. N.; Patil, P. N. J. Med.
Chem. 1978, 19, 180.
28. Schmid, C. R.; Bryant, J. D.; Dowlatzedah, M.; Phillips, J. L.;
Prather, D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C. S. J. Org.
Chem. 1991, 56, 4056.
29. Stafford, J. A.; McMurry, J. E. Tetrahedron Lett. 1988, 29,
2531.
30. Horton, D.; Hughes, J. B.; Thomson, J. K. J. Org. Chem. 1968,
33, 728.
31. Mihelich, E. D. Tetrahedron Lett. 1979, 4729.
32. Yang, Z.; Zhou, W. Tetrahedron 1995, 51, 1429.
33. Rao, A. S.; Paknikar, S. K.; Kirtane, J. K. Tetrahedron 1983,
39, 2323.
Acknowledgements
Á
Financial support from the Ministero dell'Universita e della
Ricerca Scienti®ca e Tecnologica, Rome, and by the
University of Cagliari (National Project `Stereoselezione
in Sintesi Organica. Metodologie ed Applicazioni') and
from C.N.R. (Italy) is gratefully acknowledged. One of us
(A. Frongia) gratefully acknowledges ®nancial support
from the Regione Autonoma of Sardinia (Grant no. 178,
art. 37 L.R. 2/94)
34. Crotti, P.; Ferretti, M.; Macchia, F.; Stoppioni, A. J. Org.
Chem. 1984, 49, 4706.
35. Chini, M.; Crotti, P.; Macchia, F. Tetrahedron Lett. 1990, 31,
5641.
36. Zamboni, R.; Rocach, J. Tetrahedron Lett. 1983, 24, 331.
37. Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 297.
38. Shaw, K. J.; Luly, J. R.; Rapoport, H. J. Org. Chem. 1985, 50,
4515.
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