Synthesis of Five-, Six-, and Seven-Membered Heterocycles by Intramolecular Ring Opening Reactions of 3-Oxetanol Derivatives

Article abstract of DOI:10.1021/jo971866z

Intramolecular ring opening reactions of 2-phenyl-3-oxetanols have been studied. The starting materials were prepared by the photocycloaddition of benzaldehyde and various silyl enol ethers. The intramolecular nucleophile was either incorporated into the silyl enol ether prior to the PaternoBuchi reaction (oxetanes 3,16) or was later installed by functional group interconversion (oxetanes 5, 12). With anionic heteroatom nucleophiles (O, N, S) which were attached to the carbon atom C-3 of the trimethylsilyl-protected oxetanol via an alkyl chain, a substitution at the less substituted position C-4 was observed and the corresponding heterocycles (6, 8, 13, 19) were obtained in moderate to good yields (52-91%). Upon acid catalysis a ring opening of the Boc-protected 3-oxetanol 23 to cyclic carbonates occurred. The reaction did not proceed stereospecifically and resulted in a mixture of diastereomeric products 24 and 25.

Full text of DOI:10.1021/jo971866z

1910
J . Org. Chem. 1998, 63, 1910-1918
Syn th esis of F ive-, Six-, a n d Seven -Mem ber ed Heter ocycles by
In tr a m olecu la r Rin g Op en in g Rea ction s of 3-Oxeta n ol Der iva tives
Thorsten Bach,*,† Kristian Kather,‡ and Oliver Kra¨mer†,§
Fachbereich Chemie, Philipps-Universita¨t Marburg, D-35032 Marburg, Germany, and
Organisch-Chemisches Institut, Universita¨t Mu¨nster, D-48149 Mu¨nster, Germany
Received October 9, 1997
Intramolecular ring opening reactions of 2-phenyl-3-oxetanols have been studied. The starting
materials were prepared by the photocycloaddition of benzaldehyde and various silyl enol ethers.
The intramolecular nucleophile was either incorporated into the silyl enol ether prior to the Paterno`-
Bu¨chi reaction (oxetanes 3, 16) or was later installed by functional group interconversion (oxetanes
5, 12). With anionic heteroatom nucleophiles (O, N, S) which were attached to the carbon atom
C-3 of the trimethylsilyl-protected oxetanol via an alkyl chain, a substitution at the less substituted
position C-4 was observed and the corresponding heterocycles (6, 8, 13, 19) were obtained in
moderate to good yields (52-91%). Upon acid catalysis a ring opening of the Boc-protected
3-oxetanol 23 to cyclic carbonates occurred. The reaction did not proceed stereospecifically and
resulted in a mixture of diastereomeric products 24 and 25.
Sch em e 1
In tr od u ction
Diastereomerically pure 2-aryl-3-silyloxyoxetanes A
can be readily obtained by the photocycloaddition of
aromatic aldehydes and â-unsubstituted silyl enol ethers
(Scheme 1).1 The synthetic relevance of this C-C bond-
forming reaction rests to a considerable extent on the
further use of the oxetanes by ring-opening processes.2
Two positions (C-2 and C-4) in the oxetanes A (Scheme
1) are amenable to nucleophilic attack. Ring opening
between O and C-4 leaves the relative configuration
established in the photochemical step untouched, whereas
a ring opening between O and C-2 may change the
relative configuration depending on the mechanism of the
nucleophilic displacement reaction. In terms of regiose-
lectivity, the oxetanes should behave similarly to oxiranes
(epoxides).3 An SN2 type nucleophilic substitution with
an anionic nucleophile is expected to occur at the least
substituted position (C-4).4 Precoordination of the oxet-
ane to a Lewis acid, however, may lead to a lengthening
of the bond between O and C-2, the extreme being the
formation of a carbenium ion (SN1 type reaction). In such
a distorted cyclic ether a nucleophile will attack the
carbon atom which is more loosely bound to the oxygen
atom (C-2).
opening reactions not suited to facilitate a cleavage of
the oxetane nucleus in satisfactory yields.5 Only if an
intramolecular assistance is provided either by a hydroxy
or an amino group does a clean intermolecular reaction
occur.6 As an alternative one can apply fragmentation
reactions which make use of an exocyclic substituent.1
Finally, a protected heteroatom nucleophile can be at-
tached to the oxetane and made to react intramolecularly
after deprotection or activation. In this particular case
the oxetane ring opening represents equally well a ring
closure (cyclization) to a new heterocyclic ring system.
We have attempted to realize the latter approach in order
to prepare five-, six-, and seven-membered heterocycles
stereoselectively by nucleophilic ring opening.7 Previous
work in this area has centered on the Bro¨nsted or Lewis
acid-catalyzed ring opening with oxygen nucleophiles8
and on C-C bond-forming reactions.9 Nitrogen and
sulfur nucleophiles have not yet been used for an in-
tramolecular attack.
In connection with our studies on 3-oxetanol deriva-
tives such as A, we have found most intermolecular ring
† Philipps-Universita¨t Marburg
‡ Universita¨t Mu¨nster
§ Undergraduate Research Participant (Summer 1997)
(1) Bach, T.; J o¨dicke, K.; Kather, K.; Fro¨hlich, R. J . Am. Chem. Soc.
1997, 119, 2437 and refs. cited therein.
Two different positions for the attachment of an
intramolecular nucleophile are conceivable in oxetane A.
(2) Reviews: (a) Bach, T. Liebigs Ann. 1997, 1627. (b) Bach, T. GIT
Labor-Fachzeitschrift 1997, 41, 299.
(3) Reviews: (a) Kropf, H.; Thiem, J .; Nimz, H. In Methoden der
Organischen Chemie (Houben-Weyl), 4th ed.; Kropf, H., Ed.; Thieme:
Stuttgart, 1979; Vol. VI/1a, p 338. (b) Lewars, E. G. In Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Ed.; Pergamon Press: Oxford
1984; Vol. 7, p 96.
(5) Bach, T.; J o¨dicke, K. Chem. Ber. 1993, 126, 2457.
(6) (a) Bach, T.; Kather, K. J . Org. Chem. 1996, 61, 3900. (b) Bach,
T.; Schro¨der, J . Tetrahedron Lett. 1997, 38, 3707. (c) Bach, T.; Eilers,
F.; Kather, K. Liebigs Ann. 1997, 1529.
(7) Preliminary communication: Bach, T.; Kather, K. J . Org. Chem.
1996, 61, 7642.
(4) General reviews on oxetane ring opening: (a) Searles, S. In The
Chemistry of Heterocyclic Compounds; Weissberger, A., Ed.;
Wiley-Interscience: New York, 1964; Vol. 19-2, p 983. (b) Searles, S.
In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Ed.;
Pergamon Press: Oxford, 1984; Vol. 7, p 363.
(8) (a) Corey, E. J .; Raju, N. Tetrahedron Lett. 1983, 24, 5571. (b)
Khan, N.; Morris, T. H.; Smith, E. H.; Walsh, R. J . Chem. Soc., Perkin
Trans. 1 1991, 865. (c) Itoh, A.; Hirose, Y.; Kashiwagi, H.; Masaki, Y.
Heterocycles 1994, 38, 2165.
(9) Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1984, 25, 4549
S0022-3263(97)01866-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/20/1998

Intramolecular Ring Opening of 3-Oxetanols
J . Org. Chem., Vol. 63, No. 6, 1998 1911
Sch em e 2a
isomers, i.e. the 3-trimethylsilyloxypropyl-substituted
3-oxetanol, and the disilylated diol were observed as
degradation products.
In tr a m olecu la r Atta ck of a n Alk oxid e. Alkoxides
are formed as intermediates during the removal of the
pivaloyl group as described above (Scheme 2). Upon
treatment with methyllithium in ether, the cleavage of
ester 3 occurs within 1 h at room temperature and an
intramolecular oxygen nucleophile is generated. How-
ever, we did not detect any ring-expanded heterocycles
even after extended periods of time at reflux in ether as
solvent. Due to the lability of alcohols 4, a deprotonation
with base did not appear suited as an efficient way to
form an alkoxide. Success was encountered in the case
of oxetane 3a after the solvent had been changed from
ether to dimethoxyethane (DME). The deprotection was
carried out with methyllithium at room temperature.
Subsequent heating to reflux temperature (84 °C) yielded
the desired tetrahydropyran 6a after workup (eq 1). In
a
Reagents, conditions, and yields: (a) five steps; see ref 11.
2a : 68%; 2b: 82%. (b) PhCHO, hν, 30 °C (PhH), 3a : 65% (d.r. )
88/12); 3b: 63% (d.r. ) 84/16). (c) MeLi, 25 °C (Et2O), >95%. (d)
AcSH, PPh3, DEAD, 0 °C f 25 °C (THF), 5a : 87%; 5b: 83%.
First, as depicted in Scheme 1, a nucleophile can be
connected to the carbon atom C-3 of oxetane B by a
carbon chain of variable length. Second, the oxetanol
oxygen may serve as a site to which an intramolecular
nucleophile can be attached. After deprotection of 3-si-
lyloxyoxetane A, compounds C are available by O-
alkylation or O-acylation of the intermediate oxetanol.10
We have undertaken experiments related to both cases
illustrated by B and C in Scheme 1. The results of this
study are presented in the following account.
addition, an intermolecular silyl transfer took place.
Consequently, a part of the intermediate alkoxide was
captured by the formation of the unreactive product 7
losing its nucleophilicity.
Resu lts a n d Discu ssion
Compounds B′ were identified as representative ex-
amples for oxetanes which contain an intramolecular
nucleophile. We envisaged oxygen, sulfur, and nitrogen
as synthetically relevant heteroatoms (X), the protective
group (PG) of which was to be cleaved before a possible
nucleophilic attack.
The regioselectivity of the ring opening was deduced
from the structure of tetrahydropyran 6a . MS data
revealed the expected R-cleavage of the PhCHOH frag-
ment from the heterocycle. Indeed, both significant ions
[PhCHOH+] (37%) and [M+ - PhCHOH] (19%) were
detected. The putative regioisomeric product should
readily lose a CH2OH fragment (m/z ) 31). The ion [M+
1
- 31] was not observed. In addition, H NMR spectra
recorded in DMSO-d6 exhibited a doublet and a singlet
for the OH protons. This result correlates with structure
6a , whereas the OH protons of the regioisomer would
account for a triplet and a singlet.
For all other products described below, these two
methods were routinely applied to secure the regioselec-
tivity of the nucleophilic substitution. As already men-
tioned, an attack of the nucleophile at the more acces-
sible, less substituted C-4 position was to be foreseen and
was indeed observed. With all anionic heteroatom nu-
cleophiles there were no hints pointing toward an attack
at the oxetane’s carbon atom C-2.
The ring opening of the homologue 3b turned out to
be less facile. Employing the very same conditions used
for the reaction of oxetane 3a (MeLi, DME, reflux)
resulted only in the removal of the pivaloyl group, and
alcohol 4b was isolated in 68% yield together with the
fully deprotected diol (15%). Replacing DME as solvent
with the high boiling (162 °C) diethylene glycol dimethyl
ether (diglyme) successfully induced a ring opening to
the seven-membered oxepane 6b (eq 2).
For the preparation of compounds B′ it appeared most
feasible to start from a silyl enol ether which already
bears a latent nucleophile in its side chain. In contrast
to silyl enol ethers containing an amide or hydroxy
moiety,11 the corresponding derivatives from alkylcarbo-
nyloxy-substituted alkylmethyl ketones can be readily
synthesized. We selected the pivaloyl (Piv) substituted
silyl enol ethers 2 which were prepared from the keto
esters 1 and which reacted well in the photocycloaddition
to benzaldehyde (Scheme 2). The oxetanes 3 were formed
in decent yields with good diastereoselectivities. These
compounds served as starting materials for the prepara-
tion of other oxetanes which carry a heteroatom in the
side chain. The protected thiols 5 were obtained after
selective deprotection of the pivaloyl esters 3 with me-
thyllithium in ether and subsequent Mitsunobu reac-
tion12 of alcohols 4 with thiolacetic acid.13
The free alcohols 4 are not stable and they should be
used immediately after they have been prepared. Intra-
or intermolecular migration of the TMS group occurs
upon standing. In the case of alcohol 4a , its position
(10) Bach, T.; Kather, K. J . Prakt. Chem. 1996, 338, 750.
(11) Bach, T. Liebigs Ann. 1995, 855.
(12) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Hughes, D. L. Org.
React. 1992, 42, 339.
Unfortunately, the drastic reaction conditions gave rise
to an undesired epimerization. In view of earlier obser-

1912 J . Org. Chem., Vol. 63, No. 6, 1998
Bach et al.
vations,10 it is likely that a deprotonation/protonation
sequence induced by the alkoxide is responsible for this
phenomenon. We have not been able to find milder
conditions which suppress an epimerization. A variation
of the counterion (vide infra) was not successful, either.
In tr a m olecu la r Atta ck of a Th ioa lk oxid e. The
higher nucleophilicity of sulfur as compared to oxygen
nucleophiles let us hope for a smooth ring opening of
oxetanes 5.14 Compound 5a fulfilled this hope without
any complications. Its acetyl group was removed follow-
ing the same protocol previously applied to the O-
pivaloates 3. Upon heating in DME, the resulting
thioalkoxide underwent a smooth cyclization/ring opening
to the desired thiotetrahydropyran (eq 3). After workup
the heterocyclic products proved to be a mixture of diol
8a and silyl ether 9.
synthesized several oxetanes which bear electronically
different nitrogen atoms (eq 5). The idea was to install
one protective group (R1) at nitrogen which is labile under
basic or nucleophilic conditions. The second substituent
R2 should resist removal and remain at nitrogen in the
consecutive substitution step.
Except for the hydroxamic acid derivative 11a , which
led partially to O-alkylation, the Mitsunobu reaction
proceeded cleanly and in good yields.16 To our surprise,
the 9-fluorenylmethoxycarbonyl (Fmoc) protected tolu-
enesulfonamide 11c gave the free 3-tosylaminopropyl
oxetane 12c, which in contrast to alcohols 4 can be stored
at room temperature for some time.
Following the protocol employed for the previous ring
openings, we attempted to react the nitrogen-substituted
oxetanes 12a and 12d after in situ deprotection. The
acetyl group of 12a was cleaved with methylmetal
compounds (MeLi, MeMgBr). For the trifluormethansul-
fonyl (Tf) group of 12d , LiAlH4 was used as recommended
in the literature.17 Disappointingly, no ring-opened
product was found in either case under a variety of
conditions. Instead, the decomposition of the oxetanes
was the major pathway. At elevated temperature oxet-
ane 12a was fully deprotected at the nitrogen atom and
yielded the 3-aminopropyl-substituted product.
Next, we turned to the readily availble tosylated
substrate 12c. Deprotonation of this compound should
generate an amide anion which can attack the oxetane
nucleus. Originally, we had planned the synthesis of 12c
starting from the N-Boc derivative 12b by thermal
removal of the Boc group.18 As problems were encoun-
tered for this particular substrate in this process, both
in terms of yield (55% at best) and in terms of reproduc-
ibility, we used the Fmoc-protected sulfonamide 11c for
the preparation of 12c. Sulfonamide 11c was easily
obtained from TsNCO and 9-fluorenylmethanol in anal-
ogy to Weinreb’s procedure16b (93% yield). The attempted
ring opening after deprotonation of amide 12c with
sodium (NaH) and lithium (MeLi, LDA) bases remained
unsuccessful, and none of the desired piperidine was
formed. As in the case of oxetane 5b, magnesium as
Both compounds were separated and characterized.
On the basis of MS and NMR analyses, the silyl group
in 9 is attached to the secondary and not to the tertiary
alkoxy group. In the course of the reaction a migration
must have occurred and the less congested silyl ether was
formed. Preparatively, it proved most convenient to
deprotect alcohol 9 by treating the crude product mixture
with K2CO3 in methanol and to isolate only the diol 8a .
The total yield is not deteriorated by this minor modifica-
tion and it remained high (91%).
Sulfur compound 5b was less prone to the desired ring
opening. The standard conditions (vide supra) yielded
only minor amounts of the thiooxepane 8b (16%) ac-
companied by the deprotected thiol 10 (64%). We were
pleased to find that the counterion of the thioalkoxide
can exert a beneficial influence on its nucleophilicity or,
alternatively, on the electrophilicity of the oxetane.
Methylmagnesium bromide turned out to be the reagent
of choice for the sequence acetyl cleavage/thiooxepane
formation. The yield of the desired heterocyclic product
8b rose to 54%. Compound 8b was isolated in diaste-
reomerically pure form and no epimerized product was
observed.
(15) Intermolecular ring opening by nitrogen nucleophiles: (a)
Searles, S.; Gregory, V. P. J . Am. Chem. Soc. 1954, 76, 2789. (b) Mullis,
J . C.; Weber, W. P. J . Org. Chem. 1982, 47, 2873. (c) Gassman, P. G.;
Haberman, L. M. Tetrahedron Lett. 1985, 26, 4971. (d) Chini, M.;
Crotti, P.; Favero, L.; Macchia, F. Tetrahedron Lett. 1994, 35, 761. (e)
Crotti, P.; Favero, L.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 1994,
35, 7089. (f) Meguro, M.; Asao, N.; Yamamoto, Y. J . Chem. Soc., Perkin
Trans. 1 1994, 2597.
(16) (a) 11a : Lee, B. H.; Miller, M. J . J . Org. Chem. 1983, 48, 24.
(b) 11b: Henry, J . R.; Marcin, L. R.; McIntosh, M. C.; Scola, P. M.;
Harris, G. D., J r.; Weinreb, S. M. Tetrahedron Lett. 1989, 30, 5709. (c)
11d : Bell, K. E.; Knight, D. W.; Gravestock, M. B. Tetrahedron Lett.
1995, 36, 8681.
In tr a m olecu la r Atta ck of a n Am id e. In contrast
to the chalkogen nucleophiles O and S, the nucleophilicity
of amides depends on an additional substituent not
located within the alkyl chain.15 Due to this increase in
the number of possible substitution patterns, we have
(13) Volante, R. P. Tetrahedron Lett. 1981, 22, 3119.
(14) Intermolecular ring opening by sulfur nucleophiles: (a) Searles,
S. J . Am. Chem. Soc. 1951, 73, 4515. (b) Whistler, R. L.; Luttenegger,
T. J .; Powell, R. M. J . Org. Chem. 1968, 33, 396. (c) Godziela, G.;
Tonker, T.; DuBois, M. R. Organometallics 1989, 8, 2220. (d) Xianming,
H.; Kellogg, R. M. Tetrahedron: Asymmetry 1995, 6, 1399.
(17) Hendrickson, J . B.; Bergeron, R.; Sternbach, D. D. Tetrahedron
1975, 31, 2517.
(18) Rawal, V. H.; J ones, R. J .; Cava, M. P. J . Org. Chem. 1987, 52,
19.

Intramolecular Ring Opening of 3-Oxetanols
J . Org. Chem., Vol. 63, No. 6, 1998 1913
Sch em e 3a
is prone to an elimination to benzofuran 19. The
dehydration occurred for example upon drying in vacuo.
Diol 17 was therefore always slightly contaminated with
some benzofuran 19. The tendency to eliminate water
was less pronounced in the silyl ether 18, which could
be obtained in analytically pure form.
If magnesium was used as the counterion for the
intramolecular phenoxide nucleophile, the direct forma-
tion of benzofuran 19 was the major reaction pathway.
A reasonable explanation for the different behavior of the
lithium and magnesium reagents can be based on the
migratory aptitudes of the silyl group. Silyl ether 20 was
isolated from the MeMgBr-induced ring opening at lower
temperature (rt) in ether. It is indicative of the fact that
there is no silyl migration in the intermediate alkoxide
21 if magnesium is the counterion. For lithium as
a
Reagents, conditions, and yields: (a) PivCl, NEt3, DMAP, 25
°C (CH2Cl2), 99%. (b) LDA, TMSCl, -78 °C f 25 °C (THF), 99%.
(c) PhCHO, hν, 30 °C (PhH), 37%. (d) MeLi, 25 °C f 85 °C (DME),
17: 70%; 18: 21%. (e) MeMgBr, 25 °C f 85 °C (DME), 19: 83%;
MeMgBr, 25 °C (Et2O), 19: 32%; 20: 24%. (f) K2CO3, 25 °C
(MeOH), quant.
counterion, the migration takes place and an elimination
to benzofuran 19 is prevented. As shown in a control
experiment, diol 17 does not undergo an elimination if
subjected to the reaction conditions of the MeMgBr-
initiated ring opening. Silyl ether 20 or the alkoxide 21,
however, are forced to undergo an elimination with excess
base by an E2 or E1cB pathway.
counterion proved to be a more fortitious choice. Upon
treatment of 12c with MeMgBr at ambient temperature
in DME and after subsequent heating the heterocycle 13
was generated (eq 6).
An interesting observation was made running the
reaction with MeMgBr in ether at room temperature. The
oxetane 16 used was not diastereomerically pure (dia-
stereomeric ratio d.r. ) 87/13) and the ring expansion
remained incomplete. Besides the already mentioned
silyl ether 20 (24%) and benzofuran 19 (32%), starting
material (17%) was isolated whose diastereomeric com-
position was determined to be d.r. ) 69/31. Obviously,
the major diastereoisomer 16 had reacted much faster
in the ring opening than its epimer. Indeed, since no silyl
ether diastereomeric to 20 was isolated, it appears as if
the diastereoisomer of 16 is not reactive at all. Clearly,
the phenoxide derived from 16 can react intramolecularly
in an SN2 type reaction whereas SN2 attack is hindered
in its diastereomer.
In tr a m olecu la r Atta ck of a Ca r bon a te. In the
context of recent work on the ring opening of 3-aminoox-
etanes, it was observed that N-Boc-protected 3-amino-
2-aryloxetanes undergo a stereospecific ring opening at
the C-2 position.6b Acid catalysis led to the formation
of oxazolidinones in which the configuration of the
oxetane’s former C-2 atom was inverted. The latter
result suggests a reaction course via a protonated oxetane
which is attacked by the weak intramolecular nucleophile
fast enough to avoid epimerization.
As some silylated product 14 was also detected, the
crude product mixture was completely desilylated (K2-
CO3, MeOH). With this modification the yield of piperi-
dine 13 was improved to 52%. Still, the nitrogen
nucleophiles under scrutiny cannot compete with the
sulfur nucleophile with regard to nucleophilicity and we
therefore did not attempt a ring opening/cyclization to a
seven-membered azepane.
In tr a m olecu la r Atta ck of a P h en oxid e. As a
prototypical substrate with a protected intramolecular
phenoxide we selected oxetane 16. This compound is
obtained readily from 2-hydroxyacetophenone (15) in
three steps (Scheme 3): pivaloyl protection,11 silyl enol
ether formation,5 and photocycloaddition.5 The sequence
proceeded uneventfully but, as observed earlier with
related R-aryl silyl enol ethers, the Paterno`-Bu¨chi reac-
tion is sluggish. A possible reason may be a triplet
energy transfer from the photoexcited aldehyde to the
alkene.
The ring opening of oxetane 16 occurred without any
problems. Indeed, due to the cis-arrangement of the
enolate in the aromatic side chain, this substrate is
predisposed toward an effective ring expansion. Treat-
ment of compound 16 with MeLi in DME and subsequent
reflux yielded the desired diol 17 in combination with
its monosilylated derivative 18 (Scheme 3). In analogy
to what had happened during thiotetrahydropyran for-
mation (8a /9), the TMS group migrated to the less
congested secondary alkoxy group. Desilylation (K2CO3,
MeOH) to diol 17 is facile, but it should be noted that 17
In analogy to these experiments, we hoped for an acid-
catalyzed intramolecular ring opening of oxetane 23 to
a cyclic carbonate with complete inversion of configura-
tion at C-2 (Scheme 4).19 This method, together with ring
opening reactions which occur at C-4 (retention of con-
figuration at C-2),6 would enable access to 1,2-diols with
either relative configuration starting from readily avail-
(19) For related epoxide ring opening reactions, see: (a) Minami,
N.; Ko, S. S.; Kishi, Y. J . Am. Chem. Soc. 1982, 104, 1109. (b) Corey,
E. J .; Hopkins, P. B.; Munroe, J . E.; Marfat, A.; Hashimoto, S.-i. J .
Am. Chem. Soc. 1980, 102, 7986. (c) Roush, W. R.; Brown, R. J .;
DiMare, M. J . Org. Chem. 1983, 48, 5083.

1914 J . Org. Chem., Vol. 63, No. 6, 1998
Bach et al.
Sch em e 4a
Sch em e 6
To clarify this question, we prepared the diastereo-
meric Boc-protected oxetanol 32 from the corresponding
3-silyloxyoxetane.10 By applying conditions identical to
those which induced the rearrangement of compound 23,
oxetanol 32 yielded the cyclic carbonate 25 almost
exclusively. The diastereomeric ratio of 25/24 in the
a
Reagents, conditions, and yields: (a) TFA, -20 °C f 25 °C
1
crude reaction mixture was determined to be 98/2 by H
(CH2Cl2), mixture of 24-27: 62% (ratios: 24/26 ) 46/56; 25/27 )
16/84); mixture of 28 and 29: 20% (28/29 ) 90/10).
NMR. This result is in accord with a reaction which
occurs via a direct nucleophilic substitution (path B in
Scheme 6). Only a small amount of protonated oxetane
33 undergoes ring opening to a free carbenium ion 31. A
facial diastereoselection via the carbeniumion 31 can be
ruled out as 23 and 32 yield different product ratios.
Apparently, the Boc group in 32 is situated in a way
which enables rapid attack at C-2 after protonation.
Contrary to that, the trajectory in intermediate 30 is less
favored and a ring opening to carbenium ion 31 takes
place to a larger extent.
Sch em e 5
Con clu sion a n d Ou tlook
In summary, two major routes for the ring opening of
3-oxetanols have been described. One route employs an
intramolecular heteroatom substituent attached to the
C-3 carbon atom of the oxetanol via an alkyl or aryl chain.
The ring opening is induced by formation of the anionic
heteroatom nucleophile which attacks the oxetane in an
SN2 type process at the less substituted C-4 position. By
this means tetrahydropyran 6a , thiotetrahydropyran 8a ,
thiooxepane 8b, piperidine 13, and dihydrobenzofuran
17 are accessible. The stereochemistry of the stereogenic
centers at the oxetanol’s C-2 and C-3 is retained. The
second ring opening route proceeds at the phenyl-
substituted carbon atom C-2 upon activation by acid. The
Boc-protected 3-oxetanols 23 and 32 were transformed
to the corresponding cyclic carbonates 24 and 25. As the
reaction is not stereospecific, a mixture of diastereoiso-
mers was obtained. In the case of oxetane 23, the major
product was diastereoisomer 24 (d.r. ) 85/15), whereas
oxetane 32 produced predominantly 25 (d.r. ) 98/2).
Although inversion of configuration is favored, there is
obviously a reaction pathway via a carbenium ion 31
which is responsible for partial retention. If the corre-
sponding intramolecular nucleophile was more nucleo-
philic, the partial epimerization could possibly be pro-
hibited.
able diastereomerically pure 3-silyloxyoxetanes, such as
22. Unfortunately, it turned out that the reaction is not
stereospecific. Upon treatment of oxetane 23 with trif-
luoroacetic acid (TFA) the two diastereomeric cyclic
carbonates 24 and 25 were isolated in a ratio (d.r.) of
85/15. The relative configuration of the dioxolanones was
1
deduced from H NOE studies.
Upon attempted purification by chromatography, a
rearrangement to the less substituted heterocyclic com-
pounds 26 and 27 occurred which we were not able to
suppress. Flash chromatography20 therefore delivered a
46/54 mixture of the two products 24/26 and a 16/84
mixture of 25/27 in an unseparable mixture of all four
compounds. The total yield amounted to 62%. In addi-
tion, the tert-butyl ethers 28 and 29 of alcohols 24 and
25 were isolated in a ratio which correlates roughly to
that of the parent compounds (20%, d.r. ) 90/10).
Mechanistically, one can envisage a protonated oxetane
30 as a likely intermediate (Scheme 5). Two explanations
for the observed product ratio appear plausible. If the
bond cleavage between O and C-2 is fast (path A), the
product ratio reflects the facial diastereoselection exerted
by the chiral substituent in carbenium ion 31. If the
attack of the oxygen nucleophile (path B) can compete
with the O-C bond cleavage, the product arises partially
from a direct nucleophilic displacement and partially
from an SN1 type reaction of carbenium ion 31.
Exp er im en ta l Section
Gen er a l. For general remarks, see ref 1. 13C NMR
multiplicities were obtained by DEPT experiments.
P r ep a r a tion of Silyl En ol Eth er s 2. The silyl enol ethers
(20) Still, W. C.; Kahn, M.; Mitra, A. J . J . Org. Chem. 1978, 43,
2923.
were prepared according to a known procedure from the keto

Intramolecular Ring Opening of 3-Oxetanols
J . Org. Chem., Vol. 63, No. 6, 1998 1915
esters 1.11 The analytical data for silyl enol ether 2a are given
in the reference.11
acid (609 mg, 0.6 mL) in 10 mL of THF was added dropwise.
The resulting clear solution was stirred for 1 h at 0 °C and
subsequently warmed to room temperature. After complete
consumption of the alcohol (24-48 h), the solvent was removed
in vacuo and the resulting solid was thoroughly triturated with
a 10/1 (v/v) mixture of pentane/ether. The combined organic
layers were concentrated in vacuo and the residual oil was
purified by flash chromatography (FC).
(2RS,3RS)-3-(3-E t h a n oylt h ia p r op yl)-2-p h en yl-3-[(t r i-
m eth ylsilyl)oxy]oxeta n e (5a ) was prepared from oxetane
3a according to general procedure B. Eluent (FC): CH/EtOAc
) 97/3. Yield: 1.18 g (87%). Rf ) 0.54 (CH/EtOAc ) 70/30).
IR (film): 1680 cm-1 (vs, CdO), 1245 (s, SiMe3), 980 (s, COC),
835 (vs, SiMe3). 1H NMR (CDCl3): δ -0.16 (s, 9 H), 1.72-
1.84 (m, 2 H), 1.89-2.01 (m, 1 H), 2.07-2.22 (m, 1 H), 2.35 (s,
3 H), 2.97 (t, J ) 7.0 Hz, 2 H), 4.51 (d, J ) 6.4 Hz, 1 H), 4.70
(d, J ) 6.4 Hz, 1 H), 5.43 (s, 1 H), 7.23-7.38 (m, 5 H). 13C
NMR (CDCl3): δ 1.3 (q), 23.7 (t), 29.1 (t), 30.6 (q), 39.7 (t),
77.2 (s), 81.8 (t), 92.7 (d), 126.4 (d), 127.3 (d), 127.7 (d), 138.3
(s), 195.5 (s). Anal. Calcd for C17H26O3SSi (338.536): C, 60.31;
H, 7.74. Found: C, 60.48; H, 7.66.
(2RS,3RS)-3-(4-E t h a n oylt h ia b u t yl)-2-p h e n yl-3-[(t r i-
m eth ylsilyl)oxy]oxeta n e (5b) was prepared from oxetane
3b according to general procedure B. Eluent (FC): CH/EtOAc
) 94/6. Yield: 1.17 g (83%). Rf ) 0.65 (CH/EtOAc ) 50/50).
IR (film): 1680 cm-1 (vs, CdO), 1245 (s, SiMe3), 975 (m, COC),
835 (s, SiMe3). 1H NMR (CDCl3): δ -0.23 (s, 9 H), 1.41-1.66
(m, 4 H), 1.78-1.88 (m, 1 H), 1.96-2.06 (m, 1 H), 2.26 (s, 3
H), 2.87 (t, J ) 7.1 Hz, 2 H), 4.45 (d, J ) 6.2 Hz, 1 H), 4.63 (d,
J ) 6.2 Hz, 1 H), 5.37 (s, 1 H), 7.16-7.34 (m, 5 H). 13C NMR
(CDCl3): δ 1.3 (q), 22.5 (t), 28.9 (t), 29.7 (t), 30.5 (q), 40.2 (t),
77.4 (s), 81.8 (t), 92.7 (d), 126.5 (d), 127.2 (d), 127.6 (d), 138.5
(s), 195.6 (s). Anal. Calcd for C18H28O3SSi (352.563): C, 61.32;
H, 8.01. Found: C, 61.31; H, 7.90.
Gen er a l P r oced u r e for th e In tr a m olecu la r Rin g Op en -
in g (Gen er a l P r oced u r e C). A solution of 2.4 mmol of MeLi
or MeMgBr (1.5 mL of a 1.6 M solution) in ether was added
dropwise to a stirred solution of 1.0 mmol of oxetane in 15
mL of DME at room temperature. After complete addition the
solution was stirred for another hour and subsequently heated
to reflux for the period of time indicated below. Into the hot
solution was injected 0.3 mL of a saturated aqueous NH4Cl
solution. The resulting mixture was diluted with ether and
Na2SO4 was added. After stirring for 15 min the mixture was
filtered by suction through a glass filter. The filtrate was
collected and the solvent was removed in vacuo. The crude
material was purified by flash chromatography (FC).
2,2-Dim eth ylp r op a n oic Acid 5-[(Tr im eth ylsilyl)oxy]-
5-h exen yl Ester (2b). Rf ) 0.64 (CH/EtOAc ) 70/30). IR
(film): 1720 cm-1 (vs, CdO), 1245 (s, SiMe3), 840 (vs, SiMe3).
1H NMR (acetone-d6): δ 0.19 (s, 9 H), 1.17 (s, 9 H), 1.48-1.70
(m, 4 H), 2.03-2.08 (m, 2 H), 4.00-4.06 (m, 4 H). 13C NMR
(acetone-d6): δ 0.3 (q), 24.1 (t), 27.6 (q), 28.9 (t), 36.8 (t), 39.3
(s), 64.6 (t), 90.5 (t), 159.9 (s), 178.2 (s). Anal. Calcd for
C
14H28O3Si (272.459): C, 61.72; H 10.36. Found: C, 61.87;
H, 10.29.
P r ep a r a tion of Oxeta n es 3. The oxetanes were prepared
from benzaldehyde and the corresponding silyl enol ether 2
as previously described.5,11 The analytical data for oxetane
3a are given in the reference.11
(2RS,3RS)-3-[4-(2,2-Dim et h ylp r op a n oyl)oxyb u t yl]-2-
p h en yl-3-[(tr im eth ylsilyl)oxy]oxeta n e (3b). Rf ) 0.32
(CH/EtOAc ) 90/10). IR (film): 1715 cm-1 (vs, CdO), 1240
(s, SiMe3), 980 (m, COC), 830 (s, SiMe3). 1H NMR (CDCl3): δ
-0.16 (s, 9 H), 1.22 (s, 9 H), 1.51-1.79 (m, 4 H), 1.88-1.98
(m, 1 H), 2.06-2.16 (m, 1 H), 4.13 (t, J ) 6.4 Hz, 2 H), 4.53 (d,
J ) 6.5 Hz, 1 H), 4.71 (d, J ) 6.5 Hz, 1 H), 5.45 (s, 1 H), 7.23-
7.38 (m, 5 H). 13C NMR (CDCl3): δ 1.3 (q), 19.9 (t), 27.2 (q),
28.8 (t), 38.7 (s), 40.4 (t), 64.0 (t), 77.4 (s), 81.8 (t), 92.8 (d),
126.4 (d), 127.2 (d), 127.6 (d), 138.5 (s), 178.4 (s). Anal. Calcd
for C21H34O4Si (378.583): C, 66.63; H, 9.05. Found: C, 66.64;
H, 9.17.
Gen er a l P r oced u r e for th e Dep r otection of P iva loa tes
3 (Gen er a l P r oced u r e A). A solution of 2.3 mmol of MeLi
(1.4 mL of a 1.6 M solution) in ether was added dropwise to a
stirred solution of 1.0 mmol of oxetane in 10 mL of ether at
room temperature. After complete addition, the solution was
stirred for another hour and subsequently quenched with 0.3
mL of a saturated aqueous NH4Cl solution. The resulting
mixture was diluted with ether, and Na2SO4 was added. After
stirring for 15 min the mixture was filtered by suction through
a glass filter. The filtrate was collected and the solvent was
removed in vacuo. The crude product (yield > 95%) can be
used for further transformations without purification. If
desired, it can be purified by flash chromatography.
(2RS,3RS)-3-(3-Hyd r oxyp r op yl)-2-p h en yl-3-[(tr im eth -
ylsilyl)oxy]oxeta n e (4a ) was prepared according to general
procedure A. Rf ) 0.32 (CH/EtOAc ) 50/50). IR (film): 1245
cm-1 (vs, SiMe3), 975 (s, COC), 835 (vs, SiMe3). 1H NMR
(DMSO-d6): δ -0.18 (s, 9 H), 1.47-1.64 (m, 2 H), 1.87 (ddd, J
) 14.1 Hz, J ) 10.5 Hz, J ) 5.5 Hz, 1 H), 2.02 (ddd, J ) 14.1
Hz, J ) 11.1 Hz, J ) 5.2 Hz, 1 H), 3.47 (virt q, J ≈ 5.7 Hz, 2
H), 4.45 (t, J ) 5.3 Hz, 1 H), 4.49 (d, J ) 6.7 Hz, 1 H), 4.61 (d,
J ) 6.7 Hz, 1 H), 5.41 (s, 1 H), 7.23-7.38 (m, 5 H). 13C NMR
(DMSO-d6): δ 1.6 (q), 26.7 (t), 36.7 (t), 61.0 (t), 77.6 (s), 81.2
(t), 91.9 (d), 126.8 (d), 127.3 (d), 127.7 (d), 138.9 (s). Anal. Calcd
for C15H24O3Si (280.438): C, 64.24; H, 8.63. Found: C, 64.35;
H, 8.52.
(2RS,3RS)-3-(4-Hyd r oxybu tyl)-2-p h en yl-3-[(tr im eth yl-
silyl)oxy]oxet a n e (4b ) was prepared according to general
procedure A. Rf ) 0.30 (CH/EtOAc ) 50/50). IR (film): 1245
cm-1 (vs, SiMe3), 975 (s, COC), 835 (vs, SiMe3). 1H NMR
(CDCl3): δ -0.16 (s, 9 H), 1.49-1.70 (m, 4 H), 1.85-1.95 (m,
1 H), 2.03-2.14 (m, 1 H), 2.57 (s, b, 1 H), 3.67 (t, J ) 6.3 Hz,
2 H), 4.53 (d, J ) 6.3 Hz, 1 H), 4.70 (d, J ) 6.3 Hz, 1 H), 5.46
(s, 1 H), 7.19-7.38 (m, 5 H). 13C NMR (CDCl3): δ 1.3 (q), 19.6
(t), 32.8 (t), 40.5 (t), 62.5 (t), 77.5 (s), 81.9 (t), 92.8 (d), 126.5
(d), 127.2 (d), 127.6 (d), 138.4 (s). Anal. Calcd for C16H26O3Si
(294.465): C, 65.26; H, 8.90. Found: C, 65.32; H, 8.83.
Gen er a l P r oced u r e for th e Mitsu n obu Rea ction w ith
Th iola cetic Acid (Gen er a l P r oced u r e B). An 8 mmol (1.39
g, 1.2 mL) portion of diethyl azodicarboxylate (DEAD) was
added at 0 °C to a solution of 8 mmol of triphenylphosphine
(2.10 g) in 20 mL of THF. After some time (5-50 min) the
mixture spontanously turned into a solid. (It is essential for
the success of the reaction to wait until the solidification has
occurred.) Upon warming (to 5-10 °C) the mixture could be
stirred and stirring was continued after cooling to 0 °C. At
this temperature a solution of 4 mmol of crude alcohol 4
(prepared according to procedure A) and 8 mmol of thiolacetic
(3RS,1′RS)-3-Hyd r oxy-3-(1-h yd r oxyp h en ylm eth yl)tet-
r a h yd r op yr a n (6a ). Tetrahydropyran 6a was prepared from
oxetane 4a with MeLi in DME according to general procedure
C (reflux for 6 h). Eluent (FC): CH/EtOAc ) 90/10 f 55/45.
Yield: 112 mg (54%). Mp: 130-131 °C. Rf ) 0.18 (CH/EtOAc
) 50/50). IR (KBr): 3430 cm-1 (s, OH), 3300 (s, b, OH), 1070
(vs, COC). 1H NMR (CDCl3): δ 1.32-1.55 (m, 3 H), 1.70-
1.84 (m, 1 H), 2.71 (s, b, 1 H), 2.76 (s, b, 1 H), 3.42 (ddd, J )
10.2 Hz, J ) 10.2 Hz, J ) 2.7 Hz, 1 H), 3.55 (d, J ) 11.7 Hz,
1 H), 3.72-3.81 (m, 1 H), 3.75 (d, J ) 11.7 Hz, 1 H,), 4.55 (s,
1 H), 7.26-7.38 (m, 5 H). 1H NMR (DMSO-d6): δ 1.13-1.21
(m, 1 H), 1.36-1.48 (m, 2 H), 1.58-1.71 (m, 1 H), 3.29-3.40
(m, 1 H), 3.38 (d, J ) 10.7 Hz, 1 H), 3.53-3.59 (m, 1 H), 3.55
(d, J ) 10.7 Hz, 1 H), 4.20 (s, 1 H), 4.41 (d, J ) 4.9 Hz, 1 H),
5.21 (d, J ) 4.9 Hz, 1 H), 7.18-7.36 (m, 5 H). 13C NMR
(CDCl3): δ 21.9 (t), 30.3 (t), 68.1 (t), 71.4 (s), 74.0 (t), 76.7 (d),
127.6 (d), 128.0 (d), 128.2 (d), 139.7 (s). Anal. Calcd for
C
12H16O3 (208.257): C, 69.21; H, 7.74. Found: C, 69.16; H
7.69.
(3SR,1′RS)-3-Hyd r oxy-3-(1-h yd r oxyp h en ylm et h yl)t h -
iotetr a h yd r op yr a n (8a ). Compound 8a was obtained to-
gether with its silyl derivative 9 from oxetane 5a with MeLi
in DME according to general procedure C (reflux for 3 h). After
complete desilylation,10 pure thiotetrahydropyran 8a was
isolated. Eluent (FC): CH/EtOAc ) 85/15. Yield: 204 mg
(91%). Mp: 94-95 °C. Rf ) 0.47 (CH/EtOAc ) 50/50). IR
(KBr): 3370 cm-1 (vs, OH), 3300 (b, sh, OH). 1H NMR
(CDCl3): δ 1.21 (ddd, J ) 13.8 Hz, J ) 8.8 Hz, J ) 7.4 Hz, 1

1916 J . Org. Chem., Vol. 63, No. 6, 1998
Bach et al.
H,), 1.57 (ddt, J ) 13.8 Hz, J ) 4.1 Hz, J ) 2.1 Hz, 1 H), 1.80-
1.89 (m, 2 H), 2.40-2.44 (m, 2 H), 2.69 (d, J ) 13.5 Hz, 1 H),
2.78 (d, J ) 13.5 Hz, 1 H), 4.59 (s, 1 H), 7.29-7.41 (m, 5 H).
13C NMR (CDCl3): δ 23.5 (t), 28.0 (t), 31.9 (t), 37.5 (t), 69.9
(s), 79.4 (d), 127.7 (d), 127.9 (d), 128.0 (d), 139.6 (s). Anal.
Calcd for C12H16O2S (224.317): C, 64.25; H, 7.19. Found: C,
64.31; H, 7.20.
(3SR,1′RS)-3-Hyd r oxy-3-(1-h yd r oxyp h en ylm et h yl)t h -
iooxep a n e (8b). Thiooxepane 8b was prepared from oxetane
5b with MeMgBr in DME according to general procedure C
(reflux for 5 h). Eluent (FC): CH/EtOAc ) 95/5 f 85/15.
Yield: 129 mg (54%). Mp: 111-112 °C. Rf ) 0.44 (CH/EtOAc
) 50/50). IR (KBr): 3380 cm-1 (vs, OH), 3250 (b, OH). 1H
NMR (CDCl3): δ 1.40-1.47 (m, 2 H), 1.54 (s, 1 H), 1.57-1.71
(m, 3 H), 1.92-2.04 (m, 1 H), 2.57-2.74 (m, 2 H), 2.61 (d, J )
4.3 Hz, 1 H), 2.74 (d, J ) 14.9 Hz, 1 H), 3.09 (d, J ) 14.9 Hz,
1 H), 4.59 (d, J ) 4.3 Hz, 1 H), 7.29-7.42 (m, 5 H). 13C NMR
(CDCl3): δ 21.8 (t), 31.9 (t), 34.7 (t), 36.7 (t), 40.9 (t), 78.0 (s),
78.3 (d), 127.8 (d), 127.9 (d), 128.1 (d), 140.0 (s). Anal. Calcd
for C13H18O2S (238.344): C, 65.51; H, 7.61. Found: C, 65.37;
H, 7.79.
N-9-F lu or en ylm eth yloxyca r bon yl-N-p-tolu en esu lfon a -
m id e (11c). At ambient temperature, 6 mmol of solid 9-fluo-
renylmethanol (1.18 g) was added in portions to a stirred
solution of 6 mmol of toluenesulfonyl isocyanate (1.18 g, 0.9
mL) in 6 mL of toluene. The addition was accompanied by a
moderate exotherm and a solid precipitated. After the addi-
tion was complete, the mixture was stirred for another 10 min
and it was subsequently filtered by suction through a glass
filter. The solid collected in the filter was washed thoroughly
with pentane and dried in vacuo. Yield: 2.20 g (93%). Mp:
170-171 °C. IR (KBr): 3170 cm-1 (m, b, NH), 1705 (vs, CdO).
1H NMR (acetone-d6): δ 2.42 (s, 3 H), 4.18 (t, J ) 6.7 Hz, 1
H), 4.39 (d, J ) 6.7 Hz, 2 H), 7.26 (dt, J ) 7.4 Hz, J ) 1.0 Hz,
2 H), 7.38 (t, J ) 7.4 Hz, 2 H), 7.41 (d, J ) 8.2 Hz, 2 H), 7.61
(d, J ) 7.4 Hz, 2 H), 7.82 (d, J ) 7.4 Hz, 2 H), 7.89 (d, J ) 8.2
Hz, 2 H), 10.49 (s, b, 1 H). 13C NMR (acetone-d6): δ 21.5 (q),
47.4 (d), 68.4 (t), 120.8 (d), 125.9 (d), 127.9 (d), 128.6 (d), 128.8
(d), 130.4 (d), 137.7 (s), 142.0 (s), 144.3 (s), 145.5 (s), 151.7 (s).
Anal. Calcd for C22H19NO4S (393.456): C, 67.16; H, 4.87; N,
3.56. Found: C, 67.22; H, 4.85; N, 3.72.
Gen er a l P r oced u r e for th e Mitsu n obu Rea ction w ith
Am id es 11 (Gen er a l P r oced u r e D). Triphenylphosphine
and the corresponding amide 11 were dissolved in THF, and
the solution was cooled to 0 °C. At this temperature the
alcohol 4a (prepared according to general procedure A) was
added to the stirred solution followed by dropwise addition of
DEAD. The mixture was subsequently warmed to room
temperature. After complete consumption of the alcohol (24-
48 h), the solvent was removed in vacuo and the resulting solid
was purified by flash chromatography (FC).
80/20 f 70/30. Yield: 661 mg (61%). Mp: 78-80 °C. Rf )
0.27 (CH/EtOAc ) 70/30). IR (KBr): 1240 cm-1 (s, SiMe3),
955 (m, COC), 835 (s, SiMe3). 1H NMR (CDCl3): δ -0.21 (s,
9 H), 1.57-1.67 (m, 2 H), 1.78-1.88 (m, 1 H), 2.00-2.08 (m, 1
H), 2.40 (s, 3 H), 3.03 (virt dq, J ≈ 6.9 Hz, J ) 2.8 Hz, 2 H),
4.44 (d, J ) 6.4 Hz, 1 H), 4.66 (d, J ) 6.4 Hz, 1 H), 5.06 (t, J
) 6.2 Hz, 1 H), 5.31 (s, 1 H), 7.22-7.36 (m, 7 H), 7.78 (d, J )
8.3 Hz, 2 H). 13C NMR (CDCl3): δ 1.3 (q), 21.4 (q), 23.9 (t),
37.8 (t), 43.3 (t), 77.0 (s), 81.5 (t), 92.5 (d), 126.3 (d), 127.1 (d),
127.3 (d), 127.7 (d), 129.7 (d), 137.2 (s), 138.2 (s), 143.4 (s).
Anal. Calcd for C22H31NO4SSi (433.637): C, 60.94; H, 7.21; N,
3.23. Found: C, 60.86; H, 7.10; N, 3.47.
(2RS,3RS)-N-P h en ylm eth yl-N-[3-[2-p h en yl-3-[(tr im eth -
ylsilyl)oxy]oxet a n -3-yl]p r op yl]t r iflu or om et h a n esu lfo-
n a m id e (12d ). Compound 12d was prepared from 5 mmol of
alcohol 4a (1.40 g), 5.5 mmol of triphenylphosphine (1.44 g), 5
mmol of amide 11d (1.20 g), and 5.5 mmol of DEAD (0.96 g,
0.90 mL) in 10 mL of THF according to general procedure D.
Eluent (FC): CH/EtOAc ) 90/10 f 80/20. Yield: 2.31 g (92%).
Mp: 89-90 °C. Rf ) 0.52 (CH/EtOAc ) 90/10). IR (KBr):
1245 cm-1 (s, SiMe3), 975 (m, COC), 830 (s, SiMe3). 1H NMR
(CDCl3): δ -0.22 (s, 9 H), 1.53-1.75 (m, 3 H), 1.88-1.98 (m,
1 H), 3.39 (t, J ) 7.5 Hz, 2 H), 4.34 (d, J ) 6.4 Hz, 1 H), 4.56
(s, b, 2 H), 4.63 (d, J ) 6.4 Hz, 1 H), 5.16 (s, 1 H), 7.18 (dd, J
) 7.6 Hz, J ) 1.4 Hz, 2 H), 7.23-7.43 (m, 8 H). 13C NMR
(CDCl3): δ 1.2 (q), 22.6 (t), 37.6 (t), 49.0 (t), 52.8 (t), 76.8 (s),
81.4 (t), 92.4 (d), 126.3 (d), 127.4 (d), 127.7 (d), 128.5 (d), 128.8
(d), 129.0 (s), 129.1 (d), 134.6 (s), 138.1 (s). Anal. Calcd for
C
23H30F3NO4SSi (501.635): C, 55.07; H, 6.03; N, 2.79.
Found: C, 55.03; H, 5.84; N, 2.99.
(3RS,1′RS)-3-Hyd r oxy-3-(1-h yd r oxyp h en ylm eth yl)-N-
4-tolu en esu lfon ylp ip er id in e (13). Compound 13 was pre-
pared according to general procedure C except for the fact that
3 mmol of MeMgBr (1 mL of a 3 M solution in ether) was used
(reflux for 5 h). After complete desilylation,10 pure piperidine
13 was isolated. Eluent (FC): CH/EtOAc ) 80/20 f 65/35.
Yield: 188 mg (52%). Mp: 155-156 °C. Rf ) 0.37 (CH/EtOAc
) 50/50). IR (KBr): 3500 cm-1 (s, OH), 3390 (b, OH). 1H NMR
(CDCl3): δ 1.16 (ddd, J ) 13.7 Hz, J ) 9.8 Hz, J ) 4.5 Hz, 1
H), 1.30 (dt, J ) 13.7 Hz, J ) 5.2 Hz, 1 H), 1.54-1.66 (m, 1
H), 1.70-1.84 (m, 1 H), 2.44 (s, 3 H), 2.65 (ddd, J ) 12.0 Hz,
J ) 9.1 Hz, J ) 3.6 Hz, 1 H), 2.83 (s, 1 H), 2.84 (d, J ) 11.6
Hz, 1 H), 2.88 (d, J ) 5.3 Hz, 1 H), 3.30 (dt, J ) 12.0 Hz, J )
4.8 Hz, 1 H), 3.37 (d, J ) 11.6 Hz, 1 H), 4.58 (d, J ) 5.3 Hz, 1
H), 7.27-7.36 (m, 7 H), 7.66 (d, J ) 8.1 Hz, 2 H). 13C NMR
(CDCl3): δ 20.9 (t), 21.5 (q), 31.0 (t), 46.4 (t), 53.9 (t), 71.9 (s),
76.6 (d), 127.6 (d), 127.6 (d), 128.1 (d), 128.2 (d), 129.7 (d), 133.2
(s), 139.3 (s), 143.7 (s). Anal. Calcd for
C19H23NO4S
(361.455): C, 63.14; H, 6.41; N, 3.88. Found: C, 63.21; H, 6.50;
N, 4.09.
2,2-Dim eth ylp r op a n oic Acid (2-Acetylp h en yl) Ester .
This compound was prepared from phenol 15 on a 50 mmol
scale according to a published acylation procedure.11 Yield:
10.9 g (99%). Rf ) 0.23 (CH/EtOAc ) 90/10). IR (film): 1740
cm-1 (vs, OCdO), 1680 (vs, CdO), 1590 (s, CdC). 1H NMR
(CDCl3): δ 1.38 (s, 9 H), 2.54 (s, 3 H), 7.04 (dd, J ) 8.1 Hz, J
) 1.2 Hz, 1 H), 7.29 (virt dt, J ≈ 7.6 Hz, J ) 1.2 Hz, 1 H), 7.50
(ddd, J ) 8.1 Hz, J ) 7.4 Hz, J ) 1.7 Hz, 1 H), 7.75 (dd, J )
7.6 Hz, J ) 1.7 Hz, 1 H). 13C NMR (CDCl3): δ 27.0 (q), 29.4
(q), 39.0 (s), 123.4 (d), 125.7 (d), 129.7 (d), 131.6 (s), 132.9 (d),
149.2 (s), 176.7 (s), 197.6 (s). Anal. Calcd for C13H16O3
(220.268): C, 70.89; H, 7.32. Found: C, 70.76; H, 7.43.
2,2-Dim eth ylp r op a n oic Acid 2-[1-[(Tr im eth ylsilyl)oxy]-
eth en yl]p h en yl Ester . This compound was prepared from
the corresponding ketone on a 44 mmol scale according to a
published procedure.5 Yield: 12.8 g (99%). Rf ) 0.58 (CH/
EtOAc ) 90/10). IR (film): 1740 cm-1 (vs, CdO), 1620 (m,
CdC), 1245 (s, SiMe3), 840 (vs, SiMe3). 1H NMR (acetone-d6):
δ 0.17 (s, 9 H), 1.34 (s, 9 H), 4.61 (d, J ) 0.8 Hz, 1 H), 4.62 (d,
J ) 0.8 Hz, 1 H), 7.02 (dd, J ) 7.9 Hz, J ) 1.4 Hz, 1 H), 7.23
(dt, J ) 7.6 Hz, J ) 1.4 Hz, 1 H), 7.33 (dt, J ) 7.9 Hz, J ) 1.9
Hz, 1 H), 7.50 (dd, J ) 7.6 Hz, J ) 1.9 Hz, 1 H). 13C NMR
(acetone-d6): δ 0.5 (q), 27.8 (q), 39.8 (s), 97.4 (t), 124.4 (d), 126.7
(d), 130.2 (d), 130.3 (d), 133.5 (s), 149.6 (s), 153.9 (s), 177.1 (s).
(2RS,3RS)-N-Ben zyloxy-N-[3-[2-p h en yl-3-[(t r im et h yl-
silyl)oxy]oxet a n -3-yl]p r op yl]a cet yla m id e (12a ). Com-
pound 12a was prepared from 6 mmol of alcohol 4a (1.68 g),
7.8 mmol of triphenylphosphine (2.05 g), 7.2 mmol of amide
11a (1.19 g), and 7.8 mmol of DEAD (1.36 g, 1.2 mL) in 60 mL
of THF according to general procedure D. Eluent (FC): CH/
EtOAc ) 85/15 f 80/20. Yield: 724 mg (28%). Mp: 54-56
°C. Rf ) 0.28 (CH/EtOAc ) 70/30). IR (KBr): 1635 cm-1 (m,
CdO), 1245 (s, SiMe3), 980 (m, COC), 840 (s, SiMe3). 1H NMR
(CDCl3): δ -0.16 (s, 9 H), 1.76-1.89 (m, 2 H), 1.91-2.00 (m,
1 H), 1.97 (s, 3 H), 2.12-2.22 (m, 1 H), 4.04 (dt, J ) 6.2 Hz, J
) 1.4 Hz, 2 H), 4.52 (d, J ) 6.5 Hz, 1 H), 4.71 (d, J ) 6.5 Hz,
1 H), 4.94 (s, 2 H), 5.44 (s, 1 H), 7.23-7.38 (m, 10 H). 13C
NMR (CDCl3): δ 1.3 (q), 13.7 (q), 23.0 (t), 37.2 (t), 66.3 (t),
75.7 (t), 77.3 (s), 81.8 (t), 92.8 (d), 126.5 (d), 126.5 (d), 127.3
(d), 127.6 (d), 128.2 (d), 128.2 (d), 138.4 (s), 138.4 (s), 162.6
(s). Anal. Calcd for C24H33NO4Si (427.615): C, 67.41; H, 7.78;
N, 3.28. Found: C, 67.31; H, 8.07; N, 3.30.
(2RS,3RS)-N-[3-[2-P h en yl-3-[(tr im eth ylsilyl)oxy]oxetan -
3-yl]p r op yl]-4-tolu en esu lfon a m id e (12c). Compound 12c
was prepared from 2.5 mmol of alcohol 4a (0.70 g), 7.5 mmol
of triphenylphosphine (1.97 g), 3.75 mmol of amide 11c (1.48
g), and 7.8 mmol of DEAD (1.09 g, 1.0 mL) in 35 mL of THF
according to general procedure D. Eluent (FC): CH/EtOAc )

Intramolecular Ring Opening of 3-Oxetanols
J . Org. Chem., Vol. 63, No. 6, 1998 1917
Anal. Calcd for C16H24O3Si (292.449): C, 65.71; H, 8.27.
Found: C, 65.57; H 8.54.
The dioxolanones 24-27 were obtained as a mixture of
products. Their ratio (24/25/26/27 ) 37/3/43/17) was deter-
mined by 1H NMR. The total yield amounted to 146 mg (62%).
Mp: 111-113 °C. Rf ) 0.19 and 0.15 (CH/EtOAc ) 70/30).
IR (KBr): 3490 cm-1 (vs, OH), 3260 (m, b, OH), 2950 (m, CalH),
1780 (vs, CdO). Anal. Calcd for C13H16O4 (236.267): C, 66.09;
H, 6.83. Found: C, 66.14; H, 6.95.
(4RS,5SR)-4-Hyd r oxym eth yl-4-(m eth yleth yl)-5-p h en yl-
[1,3]d ioxola n -2-on e (24). 1H NMR (CDCl3): δ 1.13 (d, J )
6.9 Hz, 3 H), 1.13 (d, J ) 6.9 Hz, 3 H), 1.47 (virt t, J ≈ 6.7 Hz,
1 H), 2.47 (sept, J ) 6.9 Hz, 1 H), 3.37 (dd, J ) 12.6 Hz, J )
7.1 Hz, 1 H), 3.43 (dd, J ) 12.6 Hz, J ) 5.7 Hz, 1 H), 5.55 (s,
1 H), 7.32-7.45 (m, 5 H). 1H NOE (CDCl3): H (5.55): Har
[2.4%], CHMe2 [3.2%], CH3 [1.3%]; CH2 (3.37 and 3.43): Har
[0.8%], Hδ5.55 [0.6%], CHMe2 [2.1%], OH [4.4%], CH3 [0.9%];
CHMe2 (2.47): Hδ5.55 [2.1%], CH3 [1.3%]. 13C NMR (CDCl3):
δ 15.9 (q), 16.5 (q), 31.5 (d), 62.7 (t), 80.7 (d), 89.9 (s), 126.3
(d), 128.8 (d), 129.3 (d), 133.4 (s), 154.2 (s).
(2RS,3RS)-3-[2-(2,2-Dim eth ylp r op a n oyl)oxyp h en yl]-2-
p h en yl-3-[(tr im eth ylsilyl)oxy]oxeta n e (16). Oxetane 16
was prepared from benzaldehyde and the corresponding silyl
enol ether on a 1.5 mmol scale according to a published
procedure5 (irradiation time: 7 h). Yield: 221 mg (37%).
Diastereomeric ratio (d.r.) ) 87:13. Mp: 88-89 °C. Rf ) 0.21
(CH/EtOAc ) 95/5). IR (KBr): 1740 cm-1 (vs, CdO), 1240 (s,
SiMe3), 980 (s, COC), 835 (vs, SiMe3). 1H NMR (CDCl3): δ
-0.44 (s, 9 H), 1.40 (s, 9 H), 4.89 (d, J ) 6.7 Hz, 1 H), 5.11 (d,
J ) 6.7 Hz, 1 H), 6.19 (s, 1 H), 7.14 (dd, J ) 8.1 Hz, J ) 1.0
Hz, 1 H), 7.27 (dt, J ) 7.6 Hz, J ) 1.0 Hz, 1 H), 7.36-7.49 (m,
5 H), 7.64-7.68 (m, 2 H). 13C NMR (CDCl3): δ 0.9 (q), 27.1
(q), 39.2 (s), 79.4 (s), 82.9 (t), 91.8 (d), 123.1 (d), 125.2 (d), 127.9
(d), 128.1 (d), 128.6 (d), 128.9 (d), 129.3 (d), 133.5 (s), 137.6
(s), 149.6 (s), 176.5 (s). Anal. Calcd for C23H30O4Si (398.573):
C, 69.31; H, 7.59. Found: C, 69.60; H, 7.78.
(3RS,1′RS)-3-Hydr oxy-3-(1-h ydr oxyph en ylm eth yl)dih y-
d r oben zofu r a n (17). Compound 17 was prepared from
oxetane 16 with MeLi according to general procedure C.
Eluent (FC): CH/EtOAc ) 80/20. The compound was not
stable (see narrative) and was not obtained in analytically pure
form. Yield: 170 mg (70%). Rf ) 0.23 (CH/EtOAc ) 70/30).
IR (film): 3400 cm-1 (s, b, OH). 1H NMR (CDCl3): δ 2.47 (d,
J ) 3.2 Hz, 1 H), 2.65 (s, 1 H), 4.28 (d, J ) 10.5 Hz, 1 H), 4.74
(d, J ) 10.5 Hz, 1 H), 4.98 (d, J ) 3.2 Hz, 1 H), 6.78 (d, J )
8.1 Hz, 1 H), 6.85 (dt, J ) 7.4 Hz, J ) 1.0 Hz, 1 H), 7.01 (ddd,
J ) 7.4 Hz, J ) 1.4 Hz, J ) 0.5 Hz, 1 H), 7.23 (ddd, J ) 8.1
Hz, J ) 7.4 Hz, J ) 1.4 Hz, 1 H), 7.28-7.33 (m, 5 H). 13C
NMR (CDCl3): δ 77.6 (d), 79.8 (t), 83.3 (s), 110.4 (d), 120.6
(d), 124.9 (d), 127.8 (d), 128.1 (d), 128.2 (s), 128.4 (d), 130.7
(d), 138.5 (s), 160.9 (s). C15H14O3 (HRMS) Calcd.: 242.0943.
Found: 242.0937.
(3RS,1′RS)-3-H yd r oxy-3-[1-[(t r im et h ylsilyl)oxy]p h e-
n ylm eth yl]d ih yd r oben zofu r a n (18). In addition to benzo-
furan 17, compound 18 was obtained from treatment of
oxetane 16 with MeLi according to general procedure C.
Eluent (FC): CH/EtOAc ) 80/20. Yield: 66 mg (21%). Rf )
0.52 (CH/EtOAc ) 70/30). IR (film): 3440 cm-1 (m, b, OH),
1240 (s, SiMe3), 835 (vs, SiMe3). 1H NMR (CDCl3): δ -0.03
(s, 9 H), 3.01 (s, 1 H), 4.26 (d, J ) 10.0 Hz, 1 H), 4.68 (d, J )
10.0 Hz, 1 H), 4.88 (s, 1 H), 6.76 (dt, J ) 8.1 Hz, J ) 0.7 Hz,
1 H), 6.79 (virt dt, J ≈ 7.2 Hz, J ) 1.0 Hz, 1 H,), 6.84 (ddd, J
) 7.4 Hz, J ) 1.9 Hz, J ) 0.7 Hz, 1 H), 7.18 (ddd, J ) 8.1 Hz,
J ) 6.9 Hz, J ) 1.9 Hz, 1 H), 7.24-7.30 (m, 5 H). 13C NMR
(CDCl3): δ 0.0 (q), 78.9 (d), 80.0 (t), 83.5 (s), 110.1 (d), 120.3
(d), 125.2 (d), 127.7 (d), 127.9 (s), 128.1 (d), 128.1 (d), 130.2
(d), 139.2 (s), 161.0 (s). Anal. Calcd for C18H22O3Si (314.456):
C, 68.75; H, 7.05. Found: C, 69.06; H, 7.12.
(1′RS)-3-(1-H yd r oxyp h en ylm et h yl)b en zofu r a n (19).
Compound 17 was prepared from oxetane 16 with MeMgBr
according to general procedure C. Eluent (FC): CH/EtOAc )
95/5 f 90/10. Yield: 186 mg (83%). Mp: 58-59 °C. Rf )
0.43 (CH/EtOAc ) 70/30). IR (KBr): 3350 cm-1 (m, b, OH).
1H NMR (CDCl3): δ 2.37 (s, b, 1 H), 6.00 (s, 1 H), 7.14 (t, J )
7.6 Hz, 1 H), 7.25 (dt, J ) 7.6 Hz, J ) 1.4 Hz, 1 H), 7.29-7.38
(m, 3 H), 7.40-7.48 (m, 5 H). 13C NMR (CDCl3): δ 69.5 (d),
111.5 (d), 120.6 (d), 122.6 (d), 123.8 (s), 124.5 (d), 126.1 (s),
126.6 (d), 128.1 (d), 128.6 (d), 142.1 (s), 142.4 (d), 155.8 (s).
Anal. Calcd for C15H12O2 (224.259): C, 80.34; H 5.39. Found:
C, 80.10; H, 5.49.
(4RS,5RS)-4-Hyd r oxym eth yl-4-(m eth yleth yl)-5-p h en yl-
[1,3]d ioxola n -2-on e (25). 1H NMR (CDCl3): δ 0.52 (d, J )
6.9 Hz, 3 H), 0.93 (d, J ) 6.9 Hz, 3 H), 1.93 (sept, 3J ) 6.9 Hz,
2
2
1 H), 3.79 (d, J ) 12.6 Hz, 1 H), 4.10 (d, J ) 12.6 Hz, 1 H),
5.89 (s, 1 H), 7.17-7.45 (m, 5 H).
(4RS,1′SR)-4-(1-Hydr oxyph en ylm eth yl)-4-(m eth yleth yl)-
[1,3]d ioxola n -2-on e (26). 1H NMR (CDCl3): δ 0.98 (d, J )
6.9 Hz, 3 H), 1.09 (d, J ) 6.9 Hz, 3 H), 2.12 (sept, J ) 6.9 Hz,
1 H,), 2.66 (d, J ) 4.3 Hz, 1 H), 4.10 (d, J ) 8.6 Hz, 1 H), 4.56
(d, J ) 8.6 Hz, 1 H), 5.00 (d, J ) 4.3 Hz, 1 H), 7.32-7.45 (m,
5 H). 13C NMR (CDCl3): δ 16.3 (q), 16.3 (q), 31.2 (d), 66.4 (t),
74.0 (d), 89.5 (s), 127.4 (d), 128.8 (d), 129.0 (d), 137.2 (s), 154.9
(s).
(4RS,1′RS)-4-(1-Hydr oxyph en ylm eth yl)-4-(m eth yleth yl)-
[1,3]d ioxola n -2-on e (27). 1H NMR (CDCl3): δ 0.92 (d, J )
6.9 Hz, 3 H), 1.00 (d, J ) 6.9 Hz, 3 H), 1.92 (sept, J ) 6.9 Hz,
1 H,), 2.37 (d, J ) 4.5 Hz, 1 H), 4.25 (d, J ) 8.6 Hz, 1 H), 4.55
(d, J ) 8.6 Hz, 1 H), 4.82 (d, J ) 4.5 Hz, 1 H), 7.30-7.47 (m,
5 H). 13C NMR (CDCl3): δ 15.9 (q), 16.0 (q), 31.2 (d), 67.1 (t),
74.8 (d), 88.5 (s), 127.8 (d), 128.6 (d), 128.7 (d), 138.1 (s), 155.1
(s).
The tert-butyl derivatives 28 and 29 were obtained as a
mixture of diastereoisomers (d.r. ) 90/10). The total yield
amounted to 56 mg (20%). Rf ) 0.55 (CH/EtOAc ) 70/30). IR
(film): 1800 cm-1 (vs, CdO). Anal. Calcd for C17H24O4
(292.374): C, 69.84; H, 8.27. Found: C, 70.11; H, 7.98.
(4RS,5SR)-4-(1,1-Dim eth yleth yloxym eth yl)-4-(m eth yl-
et h yl)-5-p h en yl[1,3]d ioxola n -2-on e (28).
1H NMR
(CDCl3): δ 0.86 (s, 9 H), 1.10 (d, J ) 6.9 Hz, 3 H), 1.13 (d, J
) 6.9 Hz, 3 H), 2.35 (sept, J ) 6.9 Hz, 1 H), 3.11 (d, J ) 9.5
Hz, 1 H), 3.18 (d, J ) 9.5 Hz, 1 H), 5.50 (s, 1 H), 7.32-7.39
(m, 5 H). 13C NMR (CDCl3): δ 16.2 (q), 16.3 (q), 26.7 (q), 32.7
(d), 60.7 (t), 73.2 (s), 82.3 (d), 88.9 (s), 127.0 (d), 128.1 (d), 128.8
(d), 134.3 (s,), 154.5 (s).
(4RS,5RS)-4-(1,1-Dim eth yleth yloxym eth yl)-4-(m eth yl-
et h yl)-5-p h en yl[1,3]d ioxola n -2-on e (29).
1H NMR
(CDCl3): δ 0.65 (d, J ) 6.9 Hz, 3 H), 0.88 (d, J ) 6.9 Hz, 3 H),
1.28 (s, 9 H), 1.88 (sept, J ) 6.9 Hz, 1 H), 3.63 (d, J ) 9.9 Hz,
1 H), 3.69 (d, J ) 9.9 Hz, 1 H), 5.75 (s, 1 H), 7.32-7.39 (m, 5
H).
(2SR,3RS)-3-[(1,1-Dim et h ylet h yloxy)ca r b on yloxy]-3-
(m eth yleth yl)-2-p h en yloxeta n e (32). Oxetane 32 was pre-
pared on a 0.95 mmol scale from the corresponding oxetanol
(182 mg) in full analogy to a previously published procedure.10
Purification (FC) with CH/EtOAc (99/1). Yield: 271 mg (97%).
Rf ) 0.72 (CH/EtOAc ) 70/30). IR (film): 1740 cm-1 (vs, CdO),
990 (s, COC). 1H NMR (CDCl3): δ 0.49 (d, J ) 6.8 Hz, 3 H),
0.82 (d, J ) 7.0 Hz, 3 H), 1.53 (s, 9 H), 2.28 (virt sept, J ≈ 6.9
Hz, 1 H), 4.60 (d, J ) 7.6 Hz, 1 H), 4.89 (d, J ) 7.6 Hz, 1 H),
6.01 (s, 1 H), 7.30-7.60 (m, 5 H). 13C NMR (CDCl3): δ 16.1
(q), 16.7 (q,), 27.7 (q), 30.6 (d), 75.7 (t,), 82.2 (s), 87.6 (s), 89.8
(d), 126.9 (d), 127.9 (d), 128.0 (d), 137.7 (s), 152.0 (s). Anal.
Calcd for C17H24O4 (292.374): C, 69.84; H, 8.27. Found: C,
69.44; H, 8.66.
Acid -Ca ta lyzed Rin g Op en in g of Oxeta n e 23. At -20
°C a solution of 1 mmol (292 mg) of oxetane 2310 in 1 mL of
CH2Cl2 was added dropwise to a solution of 2 mmol (228 mg,
160 µL) of TFA in 4 mL of CH2Cl2. After the addition was
complete the mixture was stirred at -20 °C for another 30
min and was subsequently warmed to room temperature.
According to TLC the reaction was complete after an additional
3 h. The mixture was azeotroped three times with toluene
(10 mL) in vacuo. The diastereomeric ratios 24/25 (d.r. ) 85/
15) and 28/29 (d.r. ) 90/10) were determined by 1H NMR
spectroscopy of the crude product mixture. The material was
purified by FC (Eluent: CH/EtOAc ) 95/5 f 60/40).
Acid -Ca ta lyzed Rin g Op en in g of Oxeta n e 32. The
reaction was conducted as desribed for the diastereomeric
oxetane 23. The diastereomeric ratio 24/25 (d.r. ) 2/98) was

1918 J . Org. Chem., Vol. 63, No. 6, 1998
Bach et al.
determined by 1H NMR spectroscopy of the crude product
mixture. The material was purified by flash chromatography
(FC) eluting with CH/EtOAc (95/5 f 70/30). The dioxolanones
25 and 27 were obtained as a mixture of products. Their ratio
Su p p or tin g In for m a tion Ava ila ble: Further analytical
data (NMR assignments, IR, MS) for compounds 2b, 3b, 4-6,
8, 11c, 12, 13, and 16-19 (11 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
1
(25/27 ) 34/66) was determined by H NMR. The total yield
amounted to 133 mg (56%). The tert-butyl derivative 29 was
obtained diastereomerically pure (d.r. > 98/2). Yield: 26 mg
(9%).
Ack n ow led gm en t. This work was generously sup-
ported by the Deutsche Forschungsgemeinschaft (Ba
1372/1-2) and by the Fonds der Chemischen Industrie.
J O971866Z