An efficient and general method for resolving cyclopropene carboxylic acids

Article abstract of DOI:10.1016/j.tet.2003.12.042

A general method is described for the resolution of cycloprop-2-ene carboxylic acids via diastereomeric N-acyloxazolidines prepared from enantiomerically pure oxazolidinones. Although a number of oxazolidinones were shown to resolve cyclopropene carboxylic acids, the oxazolidinones of S-phenylalaninol, S-phenylglycine and (1S,2R)-cis-1-amino-2-indanol are optimal in terms of resolving power and cost effectiveness. Separations were performed using simple flash chromatography, and because there is typically a large difference in R_f values it is possible to separate gram quantities of pure diastereomers in a single chromatogram. The cycloprop-2-ene carboxylic acids that can be resolved include those that are substituted at the 1-position by H, Ph, α-naphthyl, CO₂Me, CH₂OMOM, and trans-styryl; alkene substituents include Me, n-alkyl, Ph and tethered alkynes. Remarkably, 2-methyl-3-propylcycloprop-2-ene carboxylic acid can also be resolved with ease. The relative configurations of four diastereomerically pure oxazolidines were determined by X-ray crystallography. Reduction of the N-acyloxazolidinones with LiBH₄ give enantiomerically pure derivatives of 3-hydroxymethylcyclopropene that react with either MeMgCl or vinylMgCl and catalytic CuI to give enantiomerically pure products of syn-addition.

Full text of DOI:10.1016/j.tet.2003.12.042

Tetrahedron 60 (2004) 1803–1816
An efficient and general method for resolving cyclopropene
carboxylic acidsq
†
Lian-an Liao, Fan Zhang, Ni Yan, James A. Golen and Joseph M. Fox
*
Brown Laboratories, Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
Received 10 November 2003; revised 15 December 2003; accepted 15 December 2003
Abstract—A general method is described for the resolution of cycloprop-2-ene carboxylic acids via diastereomeric N-acyloxazolidines
prepared from enantiomerically pure oxazolidinones. Although a number of oxazolidinones were shown to resolve cyclopropene carboxylic
acids, the oxazolidinones of S-phenylalaninol, S-phenylglycine and (1S,2R)-cis-1-amino-2-indanol are optimal in terms of resolving power
and cost effectiveness. Separations were performed using simple flash chromatography, and because there is typically a large difference in Rf
values it is possible to separate gram quantities of pure diastereomers in a single chromatogram. The cycloprop-2-ene carboxylic acids that
can be resolved include those that are substituted at the 1-position by H, Ph, a-naphthyl, CO2Me, CH2OMOM, and trans-styryl; alkene
substituents include Me, n-alkyl, Ph and tethered alkynes. Remarkably, 2-methyl-3-propylcycloprop-2-ene carboxylic acid can also be
resolved with ease. The relative configurations of four diastereomerically pure oxazolidines were determined by X-ray crystallography.
Reduction of the N-acyloxazolidinones with LiBH4 give enantiomerically pure derivatives of 3-hydroxymethylcyclopropene that react with
either MeMgCl or vinylMgCl and catalytic CuI to give enantiomerically pure products of syn-addition.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
cyclopropenation represents a significant advance, there are
a number of challenges that must be addressed before
cyclopropene carboxylic acids can be generally useful as
chirons.24 Most importantly, the enantioselective reactions
that have been described so far have been restricted to those
that utilize unsubstituted diazoacetates or N,N-dimethyl-
diazoacetamide. Reactions that produce enantiomerically
enriched cyclopropenes with quaternary centers are
unknown. Furthermore, when applied to internal alkynes
the chiral catalysts produce cyclopropenes with very low
enantiomeric excess.9 Because of renewed interest in the
development of stereoselective reactions of cyclopro-
penes,6,25–29 including that of our own group,30 we sought
to develop a simple and inexpensive procedure for obtaining
numerous derivatives of cyclopropene carboxylic acids in
enantiomerically pure form. For example, facially selective
carbometallation (Scheme 1)30 and hydrometallation
reactions27 are powerful new methods for preparing diverse
types of cyclopropane products from common chiral
precursors. The multicomponent nature of such reactions
makes them attractive for complex molecule synthesis and
drug discovery. However, before the present work was
undertaken, there was no general method for obtaining the
enantiomerically pure starting materials. We show here that
a variety of cycloprop-2-ene carboxylic acids can be
resolved through conversion to diastereomeric N-acyl-
oxazolidinones and separated by column chromatography
to provide gram quantities of diastereomerically pure
cyclopropenes. The method is notably general and reliable,
and it significantly enhances the value of the processes in
Although the unusual reactivity of cyclopropenes makes
them interesting tools for synthesis,1 –7 methods that
produce enantiomerically enriched cyclopropenes are
rare.8–18 Racemic cyclopropenecarboxylic esters19,20 can
be prepared easily and in quantity by the reactions of
stabilized diazo compounds with alkynes,21 and the groups
of Doyle and Mu¨ller have described enantioselective
versions of the process using chiral-catalysts.9–14,17,22,23
For intermolecular catalytic asymmetric cyclopropenation
reactions, excellent enantioselectivities have been obtained
for the reactions of propargylethers ($94% ee) acetals
(88–95% ee) and amines ($97% ee) with diazoacetates or
N,N-dimethyldiazoacetamide using [MEPY]4Rh2.9,10,17
High selectivity could also be achieved in the enantio-
selective cyclopropenation of t-butylacetylene (89% ee) or
the diastereoselective cyclopropenation of 1-hexyne (86%
de with d-menthyldiazoacetate).9
Although the Doyle/Mu¨ller system for enantioselective
q Supplementary data associated with this article can be found in the online
version at doi: 10.1016/S0040-4020(03)02036-2
Keywords: Cyclopropene; Enantiomerically pure oxazolidione.
*
Corresponding author. Tel.: þ1-302-831-0191; fax: þ1-302-831-6335;
e-mail address: jmfox@udel.edu
To whom inquires regarding X-ray crystallography should be addressed.
†
Current Address: Department of Chemistry and Biochemistry, University
of Massachusetts Dartmouth, North Dartmouth, MA 02747-2300, USA.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.042

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L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
Scheme 1.
Scheme 1 and new reactions of chiral cyclopropenes that are
under development.
Table 1. Synthesis of cyclopropene carboxylic acids
2. Results and discussion
A rational starting point for the resolution of cyclopropene
carboxylic acids was via diastereomeric esters, because
Kass and co-workers had previously shown that dia-
stereomeric-l-menthyl 2-phenyl-3-t-butyl-1-trimethylsilyl-
cyclopropene carboxylates were separable by MPLC.18
Accordingly, we reacted a number of enantiomerically pure
alcohols with acid chloride 1, but disappointingly none of
the diastereomeric esters were separable by TLC (Fig. 1).
Figure 1. Attempted resolution of diastereomeric esters.
Given the lack of success in these screening efforts, further
work was preceded by computational screening of various
auxilaries using molecular mechanics. Based on these
models, it was surmised that chiral oxazolidinones would
be excellent resolving groups for cyclopropene carboxylic
acids because of the difference in the relative orientations of
the alkene and oxazolidinone substituents for the dia-
stereomers (Fig. 2). The models assumed that the preferred
conformations of the N-acyloxazolidinones would place the
carbonyls in an anti orientation,31 and that like other
cyclopropylcarbonyl compounds32 the cyclopropene and
the attached carbonyl would align in an s-cis conformation.
Another possibility is that materials would separate readily
because the carbonyl oxygens of the acyloxazolidinone
could chelate to the hydrated surface of silica. Again,
because the carbonyls would be held in the same plane, the
diastereomers would have distinct shapes and should
separate readily.
Figure 2. Conformations of diastereomeric oxazolidinones.

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1805
the commercially available oxazolidinones that were
surveyed, the best auxilaries in terms of resolving ability
and cost effectiveness are those from (S)-phenylalaninol,
(S)-phenylglycinol and (1R,2S)-1-amino-2-indanol (Table 2).
Regarding the use of stoichiometric quantities of these
auxilaries, we note that all three oxazolidinones are
commercially available and inexpensive if purchased in
quantity. (S)-Benzyloxazolidinone and (S)-phenyloxazo-
lidinone cost ca. 85 cents/gram when purchased in bulk,
and (1R,2S)-1-amino-2-indanol can be purchased for ca.
$2.50 per gram.35 We also note that large scale preparations
have been reported for all three oxazolidinones.36–39
Scheme 2.
Cycloprop-2-ene carboxylic acids were synthesized by
Rh2(OAc)4 catalyzed reaction of appropriate diazo com-
pounds with alkynes20 followed by saponification33
(Table 1). All but one of the cyclopropenes in Table 1
was easily prepared and purified in good yield and in
multigram quantities. The exception was 2i, which could
still be made easily on a 0.5 g scale even though it was
produced in only 19% yield. For the cyclopropenes that
were derived from malonate, hydrolysis was selective and
gave monoacids34 3g and 3h in 86 and 82% yields,
respectively. DIBAL reduction of 2g was less selective
but still gave the monoalcohol in 52% yield (Scheme 2). Of
In the optimized procedures for preparing the N-acyloxazo-
lidinones, the cycloprop-2-ene carboxylic acid was allowed
to react with either pivaloyl chloride or adamantoyl
chloride, and the resulting mixed anhydride was combined
either with the oxazolidinone and Et3N/LiCl40/cat. DMAP41
Table 2. Resolution of cyclopropene carboxylic acids
a Yields in parentheses refer to those obtained using (S)-phenyloxazolidine as the resolving group.
b
Rx¼Rf(fast)/Rf(slow).
c For compounds with unassigned absolute stereochemistry, the designations ‘fast’ and ‘slow’ refer to the relative speed with which the diastereomers elute by
chromatography.
d
For these examples, the lithium salt of the oxazolidinone was used instead of Et3N/DMAP.

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L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
or directly with the lithium salt of the oxazolidinone.42,43
1-Adamantoyl chloride has not been used previously for the
synthesis of N-acyloxazolidinones. In most cases, we found
adamantoyl chloride to be superior to pivaloyl chloride
because minor amounts of N-pivaloyloxazolidinones were
usually formed with the latter reagent. The use of slightly
more hindered adamantoyl chloride ameliorates the
selectivity issue. The addition of a catalytic amount of
DMAP was necessary in order to obtain both diastereomeric
products in good yield. For example, although mixed
anhydride 4c (formed in situ) reacts cleanly at rt to give
5c(Rcy,Rox) in the absence of DMAP, 5c(Scy,Rox) is formed
in less than 10% yield. Both diastereomers were formed at
equal rates when DMAP was added.41 Obviously, the
former process of distinguishing the enantiomers of 4a–k
by kinetic resolution is of interest—optimization of that
process is underway and will be the subject of a future
manuscript.
structures are displayed in Scheme 3; their diastereomers
5c(Scy,Rox) and 5a-Ph(Rcy,Rox) are displayed in the
Supporting Information. The reduction of the N-acyloxazo-
lidinones in Scheme 3 gave 3-hydroxymethylcyclopropenes
(R)-(2)-6 and (S)-(2)-7 that were enantiomerically pure
within the detection limits (ee .99%) of our analysis by
chiral HPLC.
The enantiomerically pure 3-hydroxymethylcyclopropenes
that were prepared in this manner were subjected to facially
selective Cu-catalyzed additions of Grignard reagents as
shown in Scheme 4.30 In each case, the addition occurred
with high facial selectivity and with complete preservation
of enantiomeric purity.
The notable feature about using oxazolidinones to resolve
cycloprop-2-ene carboxylic acids is the generality of the
method for structurally varied cyclopropenes. This is true
even when the alkene substituents are very similar in terms
of sterics (example 5j of Table 2). For the 11 pairs of
diastereomers 5a–k, it was never necessary to test more
than two auxilaries in order to find a suitable resolving
agent. Furthermore, the syntheses are straightforward and
separations were carried out using simple flash chroma-
tography to provide significant amounts of diastereo-
Scheme 4.
merically pure material. For example,
a single
3. Conclusions
chromatograph (column diameter¼1.500) afforded 1.5 g of
5a(Scy,Sox) and an equal amount of 5a(Rcy,Sox). Using this
as a calibration point with respect to the amount of material
that can be purified quickly, it is useful to quantitatively
compare the resolving abilities of oxazolidinone auxilaries
toward different cyclopropene carboxylic acids via their Rx
values.44 As shown in Table 2, the separations for most of
the N-acyloxazolidinones is excellent (Rf difference .15%),
and even in the worst case (5b), 0.7 g of each pure
diastereomer was obtained after two chromatograms (first
column diameter¼1.500; second column diameter¼100).
A method has been described for the resolution of cyclo-
prop-2-ene-carboxylic acids via diastereomeric N-acyl-
oxazolidines prepared from enantiomerically pure oxazo-
lidinones. The method is remarkably general, and can be
used to resolve significant quantities of cyclopropenes even
when the alkene substituents are very similar. The relative
configurations of four diastereomerically pure oxazolidines
were established by X-ray crystallography. Reduction of the
N-acyloxazolidinones with LiBH4 give enantiomerically
pure derivatives of 3-hydroxymethylcyclopropene that react
with either MeMgCl or vinylMgCl and catalytic CuI to give
enantiomerically pure products of syn-addition.
X-ray crystallography revealed the absolute configurations
of four of the diastereomers from Table 2. Two of those
4. Experimental
4.1. General
All reactions were carried out in nitrogen atmosphere in
glassware that was flame-dried under vacuum and cooled
under nitrogen. GC analyses were performed using either an
HP5 or HP1 column and a FID detector. Pentane, toluene,
THF, ether and CH2Cl2 were dried with columns packed
with activated neutral alumina. Alternatively, solvents were
distilled from Na/benzophenone or CaH2 (for CH2Cl2).
Triethylamine was distilled from CaH2. Copper(I)iodide
(98%) was purchased from Acros. Ethyl diazoacetate (90%
purity), Propyne, 1,7-Octadiyne, phenylacetylene, 1-hexyne,
1-octyne, Pivaloyl chloride and 1-adamantoyl chloride
were purchased from Aldrich (we recommend that the
purity of 1-adamantoyl chloride be verified by 13C NMR
Scheme 3.

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1807
prior to use). (S)-phenyloxazolidione, (S)-benzyloxazolidi-
none and (1S,2R)-1-amino-2-indanol were purchased from
Chemicrea Inc., Tokyo, JAPAN. (3aS)-cis-Tetrahydro-2H-
indeno[1,2-d]oxazol-2-one was prepared according to the
literature precedent39 from (1S,2R)-1-amino-2-indanol, and
(3aR)-cis-Tetrahydro-2H-indeno[1,2-d]oxazol-2-one was
purchased from Aldrich. Rh2(OAc)4 was purchased from
Pressure Chemical Co. Chromatography was performed on
silica gel (ICN SiliTech 32-62D, 60 A). For H NMR, the
abbreviation ‘app’ stands for apparent (e.g., ‘app d’¼
apparent doublet). For 13C NMR, multiplicities were
distinguished using an APT pulse sequence: typical
methylene and quaternary carbons appear ‘up’ (u); methine
and methyl carbons ‘down’ (dn). Exceptions are methine
carbons of alkynes and cyclopropenes, which usually have
the same phase as ‘normal’ methylenes and quaternary
carbons.45 Yields in this paper refer to isolated yields
(average of 2 runs) of compounds estimated to be .95%
pure by 1H, 13C NMR. Diastereomer purities were
determined using normal phase silica HPLC columns, and
enantiomeric excesses were determined by HPLC using
CHIRACEL OD, OJ or AD columns, or by GC using
Chiraldex G-TA or B-PH columns. All HPLC runs were
preformed at a rate of 1.0 mL/min.
was allowed to stir for 1 h and then filtered through celite,
concentrated, and chromatographed (eluting with 3–10%
ethyl acetate in hexane) to give the corresponding
cyclopropene derivative.
4.2.1. Methyl 1,2-diphenylcycloprop-2-ene-1-carboxyl-
ate (2c). The general procudure for cyclopropenation with
methyl phenyldiazoacetate47 (1.76 g, 10 mmol) and phenyl-
acetylene (3.06 g, 30 mmol) gave 1.85 g (7.40 mmol, 73%)
of 2c, a pale yellow oil. A similar experiment that started
with 5.0 g methyl phenyldiazoacetate gave 2c in 71% yield.
1H NMR (CDCl3, 400 MHz, d): 7.62–7.59 (m, 2H), 7.41–
7.35 (m, 5H), 7.30–7.26 (m, 2H), 7.20 (m, 2H), 3.70 (s,
3H); 13C NMR (CDCl3, 100 MHz, d): 175.1(u), 140.9(u),
130.1(dn), 130.0(dn), 128.9(dn), 128.3(dn), 128.1(dn),
125.6(dn), 125.4(u), 117.3(u), 100.4(u), 52.3(dn), 33.6(u);
IR (DCM, cm21): 3211, 2916, 1766, 1721, 1506, 1213;
HRMS-CI(NH3) m/z: [Mþ], calcd for C17H14O2, 250.0630;
found, 250.0643.
1
˚
4.2.2. Methyl 2-butyl-1-phenylcycloprop-2-ene-1-carb-
oxylate (2d).48 The general procedure for cyclopropenation
with methyl phenyldiazoacetate47 (1.76 g, 10 mmol) and
1-hexyne (2.46 g, 30 mmol) gave 1.64 g (7.1 mmol, 71%)
of 2d, a colorless oil. A similar experment that started with
3.0 g of methyl phenyldiazoacetate gave 2d in 72% yield.
1H NMR (CDCl3, 400 MHz, d): 7.25–7.28 (m, 4H), 7.16–
7.21 (m, 1H), 6.64 (t, J¼1.5 Hz, 1H), 3.66 (s, 3H), 2.54 (app
dt, J¼7.4, 1.4 Hz, 2H), 1.58–1.53 (app quintet, J¼7.4 Hz,
2H), 1.37–1.31 (m, 2H), 0.89–0.85 (t, J¼7.4 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, d): 176.1(u), 141.8(u), 128.3(dn),
128.1(dn), 126.3(dn), 121.0(u), 97.0(u), 52.0(dn), 33.1(u),
28.9(u), 24.2(u), 22.3(u), 13.8(dn); IR (neat, cm21): 3131,
2959, 1719, 1494, 1222, 1023; HRMS-CI(NH3) m/z:
[MþH], calcd for C15H19O2, 231.1385; found, 231.1396.
The synthesis of 2a has been reported previously.30,46
4.1.1. Ethyl 2-methylcycloprop-2-ene-1-carboxylate (2b).
A 250 mL 3-neck flask was charged with Rh2(OAc)4
(256 mg, 0.58 mmol) and 100 mL CH2Cl2. The flask was
sealed with three rubber septa, connected to an oil bubbler,
and purged with N2. The solution was then sparged (using a
long needle) with propyne gas for 10 min. The addition of
propyne was then ceased and the outlet to the oil bubbler
was removed and replaced by a balloon filled with propyne.
A solution of ethyl diazoacetate (6 mL, 90% purity
(Aldrich), 51.3 mmol) in 4 mL CH2Cl2 was added over
the course of 7 h via syringe pump. About once an hour, the
balloon was emptied and refilled with propyne. After the
addition was complete, the mixture was filtered through a
pad of silica gel, concentrated (care should be taken not to
distil away the product), and then chromatographed on silica
gel (5% ether in pentane). Not all of the solvent from the
chromatography was removed because of the volatility of
the product. 1H NMR analysis of the colorless solution
(9.03 g) indicated that it contained ca. 5.3 g (42.0 mmol,
82%) of 2b, 2.6 g of ether and 1.2 g of pentane. This
solution was used for the preparation of 3b without further
purification. A similar experiment gave 2b in 77% yield. 1H
NMR (CDCl3, 400 MHz, d): 6.34 (m, J¼1.3 Hz, 1H), 4.12–
4.15 (m, 2H), 2.16–2.17 (d, J¼1.3 Hz, 3H), 2.11–2.12 (d,
J¼1.6 Hz, 1H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3,
90 MHz, d): 176.5 (u), 111.6(u), 94.6(u), 60.1(u), 20.0(dn),
14.3(dn), 10.5(dn); IR (neat, cm21): 3135, 2975, 1809,
1729, 1251, 1186; HRMS-CI(NH3) m/z: [MþH], calcd for
C7H11O2, 127.0759; found, 127.0753.
4.2.3. Methyl 1-phenyl-2-(hexyn-5-yl)-cycloprop-2-ene-
1-carboxylate (2e). A 100 mL flask was charged with
Rh2(OAc)4 (22 mg, 0.05 mmol), 50 mL CH2Cl2 and
1,7-octadiyne (2.00 g, 2.50 mL, 18.46 mmol). A solution
of methyl phenyldiazoacetate (1.62 g, 9.23 mmol) in 10 mL
CH2Cl2 was added via syringe pump at a rate of 0.7 mL/h at
rt. The crude mixture was filtered through a pad of silica,
concentrated and then chromatographed (the eluent was 5%
ethyl acetate in hexane) to give 1.37 g (5.39 mmol, 58%) of
the title compound as a colorless oil. A similar experiment
also gave 2e in 58% yield. 1H NMR (CDCl3, 400 MHz, d):
7.31–7.24 (m, 4H), 7.22–7.18 (m, 1H), 6.71 (t, J¼1.4 Hz,
1H), 3.68 (s, 3H), 2.58 (dt, J¼7.3, 1.4 Hz, 2H), 2.14–2.18
(app dt, J¼7.0, 2.7 Hz, 2H), 1.93 (t, J¼2.7 Hz, 1H), 1.76–
1.65 (m, 2H), 1.60–1.51 (m, 2H); 13C NMR (CDCl3,
90 MHz, d): 175.9(u), 141.6(u), 128.2(dn), 128.0(dn), 126.3
(dn), 120.6(u), 97.4(u), 84.0(u), 68.6(u), 52.0(dn), 33.0(u),
27.7(u), 25.8(u), 24.0(u), 18.0(u); IR (neat, cm21): 3289,
2947, 1718, 1224, 1021, 701, 647; HRMS-CI(NH3) m/z:
[MþH], calcd for C17H19O2, 255.1385; found, 255.1391.
4.2. General procedures for cyclopropenation
4.2.4. Methyl 2-phenyl-1-(a-naphthyl)cycloprop-2-ene-
1-carboxylate (2f). The general procudure for cyclopro-
penation with methyl (a-naphthyl)diazoacetate49 (1.13 g,
5.0 mmol) and phenylacetylene (1.53 g, 15 mmol) gave
843 mg (2.81 mmol, 56%) of 2f, a pale yellow oil. A similar
experiment with 2.0 g of (a-naphthyl)diazoacetate gave a
A solution of the diazoacetate (10 mmol) in 20 mL CH2Cl2
was added at rt via syringe pump (0.5–1.0 mL/h) to a stirred
mixture of Rh2(OAc)4 (0.10 mmol) and alkyne (30 mmol).
After the syringe pump addition was complete, the mixture

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L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
55% yield of 2f. 1H NMR (CDCl3, 400 MHz, d): 8.17
(dd, J¼7.9, 0.6 Hz, 1H), 7.86 (dd, J¼7.5, 0.5 Hz, 1H),
7.77–7.74 (m, 3H), 7.56–7.42 (m, 7H), 7.36–7.32 (m, 1H),
3.66 (s, 3H); 13C NMR (CDCl3, 90 MHz, d): 176.5(u),
139.3(u), 134.2 (u, 2 carbons), 132.9(u), 130.5(dn),
130.3(dn), 129.5(dn), 129.4(dn), 128.4(dn), 126.6(dn),
126.3(u), 126.2(dn), 126.1(dn), 125.1(dn), 118.9(u),
104.0(u), 53.0(dn), 33.2(u); IR (CH2Cl2, cm21): 3065,
2951, 1720, 1596, 1506, 1222, 1093; HRMS-CI(NH3) m/z:
[Mþ], calcd for C21H16O2, 300.1150; found, 300.1130.
J¼7.1 Hz, 2H), 2.41–2.37 (m, 2H), 2.06 (t, J¼1.5 Hz, 3H),
2.03 (s, 1H), 1.62–1.56 (m, 2H), 1.26 (t, J¼7.1 Hz, 3H),
0.95–0.99 (t, J¼7.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz,
d): 177.4(u), 106.6(u), 102.2(u), 60.2(u), 26.8(u), 23.1(dn),
20.7(u), 14.8(dn), 14.2(dn), 10.2(dn); IR (neat, cm21): 2961,
2935, 1721, 1457, 1367, 1335, 1241, 1179, 1179, 1044;
HRMS-CI(NH3) m/z: [MþH], calcd for C10H17O2,
169.1229; found, 169.1236.
4.3. General procedures for ester saponification
4.2.5. Dimethyl 2-butylcycloprop-2-ene-1,1-dicarboxyl-
ate (2g).26 The general procudure for cyclopropenation with
dimethyl diazomalonate (3.33 g, 21.08 mmol) and a solu-
tion of Rh2(OAc)4 (56 mg, 0.13 mmol) and 1-hexyne
(6.93 g, 84.3 mmol) in CH2Cl2 (20 mL) gave 3.2 g
(15.10 mmol, 72%) of the title compound as pale yellow
oil. The spectral data were in accord those reported
previously.26 1H NMR (CDCl3, 400 MHz, d): 6.35 (t, J¼
1.4 Hz, 1H), 3.72 (s, 6H), 2.55 (dt, J¼1.4, 7.3 Hz, 2H), 1.58
(m, 2H), 1.39 (m, 2H), 0.92 (t, J¼7.3 Hz); 13C NMR
(CDCl3, 100 MHz, d): 172.3 (u), 114.9 (u), 93.8 (u), 52.6
(dn), 32.8 (u), 28.8 (u), 24.1 (u), 22.6 (u), 14.1 (dn).
Aqueous KOH (30 mL of an 8.5% solution) was added to a
100 mL round bottomed flask that contained the cycloprop-
2-ene-1-carboxylate (17.8 mmol), and 30 mL MeOH. The
mixture was stirred overnight at the indicated temperature,
concentrated to remove the bulk of the MeOH, acidified to
pH 1–3 with conc. HCl, extracted (4£30 mL CH2Cl2), dried
(Na2SO4) filtered, and concentrated. The residue was
chromatographed on silica gel (20–40% ethyl acetate in
hexane) to provide the cycloprop-2-ene-1-carboxylic acid.
4.3.1. 2-Hexylcycloprop-2-ene-1-carboxylic acid (3a).
The general procedure for ester saponification conducted
at rt with 2a (3.2 g, 16.4 mmol) gave 2.55 g (15.1 mmol,
92%) of 3a as a clear oil. A similar experiment with 1.0 g of
4.2.6. Dimethyl 2-phenylcycloprop-2-ene-1,1-dicarboxyl-
ate (2h). The general procudure for cyclopropenation with
dimethyl diazomalonate(6.64 g, 40.0 mmol) and a solution
of Rh2(OAc)4 (106 mg, 0.24 mmol) and phenylacetylene
(21.4 g, 210.0 mmol) in CH2Cl2 (80 mL) gave 6.5 g
(28.0 mmol, 67%) of the title compound as pale yellow
solid, mp 70.5–71.5 (lit50 67–708). The spectral data were
in accord with those reported previously.50 1H NMR
(CDCl3, 400 MHz, d): 7.64 (m, 2H), 7.45 (m, 3H), 6.90
(s, 1H), 3.72 (s, 6H); 13C NMR (CDCl3, 100 MHz, d):
171.2, 130.6, 130.4, 128.9, 123.9, 112.2, 95.2, 52.4, 32.8.
1
2a gave 3a in 90% yield. H NMR (CDCl3, 400 MHz, d):
6.31 (m, 1H), 2.48–2.52 (m, 2H), 2.12 (d, J¼1.5 Hz, 1H),
1.61–1.55 (m, 2H), 1.38–1.25 (m, 6H), 0.88 (t, J¼6.8 Hz,
3H); 13C NMR (CDCl3, 100 MHz, d): 183.7(u), 115.4(u),
93.6(u), 31.6(u), 28.9(u), 26.7(u), 25.1(u), 22.7(u), 19.7(dn),
14.2(dn); IR (neat, cm21): 3510, 2973, 1698, 1425, 1273,
1125; HRMS-CI(NH3) m/z: [MþH], calcd for C10H17O2,
169.1229; found, 169.1230.
4.3.2. 2-Methyl-cycloprop-2-ene-1-carboxylic acid (3b).
The general procedure for ester saponification with 2b
[1.50 g (2.55 g of a ,59% mixture in Et2O/pentane),
11.9 mmol] was conducted at 0 8C during the addition of
KOH and subsequently at rt. The yield was 1.08 g
(110 mmol, 92%) of 3b, a colorless oil. A similar
experiment gave 3b in 91% yield. 1H NMR (CDCl3,
400 MHz, d): 6.34 (m, 1H), 2.17 (d, J¼1.3 Hz, 3H), 2.11 (d,
J¼1.5 Hz, 1H); 13C NMR (CDCl3, 90 MHz, d): 183.1(u),
111.2(u), 94.2(u), 19.8(dn), 10.4(dn); IR (neat, cm21): 2977,
1813, 1700, 1423, 1283, 1248, 1121, 711; HRMS-CI(NH3)
m/z: [MþH], calcd for C5H7O2, 99.0446; found, 99.0451.
4.2.7. Methyl 2-hexyl-1-trans-styrylcycloprop-2-ene-1-
carboxylate (2i). The general procedure for cyclopropena-
tion with methyl (E)-2-diazo-4-phenyl butenoate51 (2.12 g,
10.5 mmol), 1-octyne (4.63 g, 42 mmol) and Rh2(OAc)4
(28 mg, 0.063 mmol) gave 0.54 g (20%) of the title
compound as pale yellow oil. A similar experiment that
started with 240 mg of methyl (E)-2-diazo-4-phenyl
butenoate gave 2i in 18% yield. 1H NMR (CDCl3,
360 MHz, d): 7.40–7.17 (m, 6H), 6.33 (t, J¼1.2 Hz, 1H),
6.05 (d, J¼16.2 Hz, 1H), 3.73 (s, 3H), 2.52 (app dt, J¼7.2,
1.1 Hz, 2H), 1.61 (m, 2H), 1.30–1.60 (m, 6H), 0.90 (t, J¼
6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz, d): 176.1 (u),
137.7 (u), 131.8 (dn), 128.4 (dn), 127.9 (dn), 127.1 (dn),
126.8 (dn), 116.9 (u), 93.3 (u), 52.1(dn), 31.6 (u), 30.6 (u),
29.0 (u), 27.1 (u), 23.7 (u), 22.7 (u), 14.2 (dn); IR (CCl4,
cm21): 3025, 2952, 2931, 2360, 2336, 1722, 1244, 1226,
1060, 964, 765; HRMS-CI (NH3) m/z: [MþH] calcd for
C19H24O2, 285.1854; found, 285.1849.
4.3.3. 1,2-Diphenylcycloprop-2-ene-2-carboxylic acid
(3c). The general procedure for ester saponification
conducted at 35 8C with 2c (3.0 g, 12.0 mmol) gave 2.58 g
(10.9 mmol, 91%) of 3c as a white solid, mp 136–138 8C. A
similar experiment with 730 mg of 2c gave 3c in 88% yield.
1H NMR (CDCl3, 400 MHz, d): 7.63–7.59 (m, 2H), 7.43–
7.36 (m, 5H), 7.28–7.24 (m, 2H), 7.19–7.15 (m, 2H); 13C
NMR (CDCl3, 90 MHz, d): 180.6(u), 140.4(u), 130.6(dn),
130.4(dn), 129.3(dn),128.8(dn), 128.5(dn), 127.1(dn),
125.4(u), 117.3(u), 100.2(u), 33.5(u); IR (KBr, cm21):
3589, 3033, 2868, 1787, 1664, 1496, 1409, 1222, 1099;
HRMS-CI(NH3) m/z: [Mþ], calcd for C16H12O2, 236.0837;
found, 236.0833.
4.2.8. Ethyl 2-propyl-3-methyl-cycloprop-2-ene-1-carb-
oxylate (2j). The general procedure for cyclopropenation
with ethyl diazoacetate (2.53 g, 2.3 mL, 20 mmol) in
2.7 mL CH2Cl2 and a solution of 2-hexyne (2.46 g,
3.4 mL, 30 mmol) and Rh2(OAc)4 (88 mg, 0.2 mmol) in
150 mL CH2Cl2 gave 2.60 g (15.5 mmol, 78%) of the title
compound as a colorless oil. A similar experiment gave 2j in
4.3.4. 2-Butyl-1-phenylcycloprop-2-ene-1-carboxylic
acid (3d). The general procedure for ester saponification
1
76% yield. H NMR (CDCl3, 400 MHz, d): 4.10–4.15 (q,

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1809
conducted at rt with 2d (3.0 g, 13.0 mmol) gave 2.48 g
(11.5 mmol, 88%) of 3d as a clear oil. A similar experiment
with 520 mg of 2d gave 3d in 85% yield. 1H NMR (CDCl3,
400 MHz, d): 7.30–7.19 (m, 5H), 6.64 (app t, J¼1.6 Hz,
1H), 2.56–2.52 (m, 2H), 1.59–1.56 (m, 2H), 1.32–1.30 (m,
2H), 0.86 (t, J¼7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz,
d): 181.9(u), 140.8(u), 128.8(dn), 128.3(dn), 126.4(dn),
120.7(u), 96.3(u), 29.2(u), 28.7(u), 24.2(u), 22.2(u),
13.7(dn); IR (neat, cm21): 3513, 2953, 1696, 1605, 1506,
1245, 1046; HRMS-CI(NH3) m/z: [MþH], calcd for
C14H17O2, 217.1229; found, 217.1229.
23.7 (u), 22.5 (u), 14.0 (dn); IR (neat, cm21): 3147, 2955,
2874, 2360, 2095, 1749, 1668, 1435, 1315, 1065, 850;
HRMS-CI m/z [MþH] calcd for C10H15O4, 199.0970;
found, 199.0963.
4.3.8. 2-Phenylcycloprop-2-ene-1,1-dioic acid mono-
methyl ester (3h). The procedure was identical to that
used to prepare 3g, except that 2h (4.00 g, 17.25 mmol),
KOH (0.97 g, 17.25 mmol), MeOH (40 mL), water (10 mL)
were used. The protocol gave 3.14 g (83%) of the title
compound as a pale yellow solid, mp 88–89 8C. Addition-
ally, unchanged 2h (0.40 g, 10%) was recovered. A similar
experiment that started with 9.5 g of 2h gave 3h in 85%
4.3.5. 1-Phenyl-2-(5-hexynyl)-cycloprop-2-ene-1-carb-
oxylic acid (3e). The general procedure for ester saponifica-
tion with 2e (1.29 g, 5.10 mmol) was conducted at 0 8C
during the addition of KOH and subsequently at rt. The
yield was 1.06 g (4.42 mmol, 87%) of 3e, a colorless oil. A
1
yield. H NMR (CDCl3, 400 MHz, d): 7.52–7.46 (m, 5H),
6.75 (s, 1H), 3.75 (s, 3H); 13C NMR (CDCl3, 100 MHz, d):
177.2 (u), 172.5 (u), 131.5 (dn), 130.8 (dn), 129.5 (dn),
122.9 (u), 108.6 (u), 92.4 (u), 53.9 (dn), 31.3 (u); IR (neat,
cm21): 3164, 3054, 2987, 2958, 2685, 2361, 2055, 1756,
1675, 1441, 1420, 1317, 1264, 1071, 705; Anal. Calcd for
C12H10O4: C, 66.05; H, 4.62. Found: C, 65.76; H, 4.60.
1
similar experiment also gave 3e in 87% yield. H NMR
(CDCl3, 400 MHz, d): 7.30–7.27 (m, 4H), 7.23–7.18 (m,
1H), 6.70 (t, J¼1.5 Hz, 1H), 2.59 (app dt, J¼7.3 Hz, 1.5 Hz,
2H), 2.16 (app dt, J¼6.9 Hz, 2.6 Hz, 2H), 1.93 (t, J¼2.7 Hz,
1H), 1.77–1.70 (m, 2H), 1.61–1.50 (m, 2H); 13C NMR
(CDCl3, 90 MHz, d): 182.0(u), 140.7(u), 128.4(dn),
128.0(dn), 126.5(dn), 120.2(u), 96.7(u), 83.9(u), 68.6(u),
32.7(u), 27.7(u), 25.7(u), 24.0(u), 18.0(u); IR (neat, cm21):
3312, 2944, 1688, 1254, 804, 744, 696, 633; HRMS-
CI(NH3) m/z: [MþH], calcd for C16H17O2, 241.1229;
found, 241.1226.
4.3.9. 2-Hexyl-1-trans-styrylcycloprop-2-ene-1-carb-
oxylic acid (3i). A mixture of 2i (0.42 g, 1.48 mmol),
MeOH (4 mL) and 2 N KOH (aq) (6 mL) was stirred at
50 8C for 3 h. The mixture was extracted with ether
(3£5 mL), and the aqueous layer was acidified with 10%
HCl (aq) and extracted with ether (3£10 mL). The organics
were combined, washed with water and brine, dried
(Na2SO4), filtered and concentrated to give 370 mg (93%)
of 3i as a pale yellow oil. A similar experiment that started
4.3.6. 2-Phenyl-1-(a-naphthyl)cycloprop-2-ene-1-carb-
oxylic acid (3f). The general procedure for ester saponifica-
tion conducted at 50 8C with 2f (3.00 g, 10.0 mmol) gave
2.38 g (8.32 mmol, 83%) of 3f as a pale yellow solid, mp
126–129 8C. A similar experiment with 1.20 g of 2f gave 3f
1
with 0.58 g of 2i gave 3i in 96% yield. H NMR (CDCl3,
400 Hz, d): 7.37–7.18 (m, 6H), 6.31 (app t, J¼1.4 Hz, 1H),
6.03 (d, J¼16.1 Hz, 1H), 2.52 (app dt, J¼7.3, 1.4 Hz, 2H),
1.61 (m, 2H), 1.40–1.26 (m, 6H), 0.87 (t, J¼7.0 Hz, 3H);
13C NMR (CDCl3, 100 MHz, d): 182.7 (u), 137.8 (u), 131.1
(dn), 128.9 (dn), 128.3 (dn), 127.4 (dn), 126.5 (dn), 116.6
(u), 92.8 (u), 31.9 (u), 30.6 (u), 29.3 (u), 27.3 (u), 23.9 (u),
23.0 (u), 14.5 (dn); IR (CCl4, cm21): 3026, 2957, 2931,
2860, 2360, 2335, 1686, 1419, 1289, 1264, 964, 803, 746;
HRMS-CI, m/z: [M] calcd for C18H22O2, 270.1620; found,
270.1614.
1
in 85% yield. H NMR (CDCl3, 360 MHz, d): 8.22 (app d,
J¼8.3 Hz, 1H), 7.90–7.86 (app dd, J¼8.3, 1.1 Hz, 1H),
7.78–7.76 (m, 3H), 7.58–7.45 (m, 7H), 7.34 (dd, J¼8.3,
7.2 Hz, 1H); 13C NMR (CDCl3, 90 MHz, d): 181.6(u),
138.0(u), 133.8(u), 132.1(u), 130.1(dn), 129.9(dn),
129.0(dn), 128.8(dn), 128.1(dn),126.1(dn), 125.9(dn),
125.8(u), 125.7(dn), 125.5(dn), 124.6(dn), 118.1(u),
102.9(u), 32.3(u); IR (KBr, cm21): 3556, 3036, 2928,
1703, 1600, 1503, 1247, 1019; HRMS-CI(NH3) m/z: [Mþ],
calcd for C20H14O2, 286.0994; found, 286.0984.
4.3.10. 2-Propyl-3-methyl-cycloprop-2-ene-1-carboxylic
acid (3j). The general procedure for ester saponification
with 2j (0.888 g, 5.28 mmol) was conducted at 0 8C during
the addition of KOH and subsequently at rt. The procedure
gave 0.711 g (5.08 mmol, 96%) of 3j as a colorless oil. A
similar experiment gave 3j in 98% yield. 1H NMR (CDCl3,
400 MHz, d): 2.41–2.37 (m, 2H), 2.06 (app t, J¼1.5 Hz,
3H), 2.02 (s, 1H), 1.64–1.55 (m, 2H), 0.96 (t, J¼7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, d): 184.4(u), 106.2(u),
101.8(u), 26.8(u), 22.9(dn), 20.7(u), 14.2(dn), 10.1(dn); IR
(neat, cm21): 2962, 2628, 1691, 1420, 1286, 1236, 1123;
HRMS-CI(NH3) m/z: [MþH], calcd for C8H13O2,
141.0916; found, 141.0920.
4.3.7. 2-Butylcycloprop-2-ene-1,1-dioic acid monomethyl
ester (3g). A solution of 2g (5.04 g, 23.8 mmol) in 50 mL
methanol was added dropwise to a solution of KOH (1.33 g,
23.8 mmol) in 15 mL water that was cooled in an ice bath.
The reaction mixture was allowed to stir rt for 2 d, at which
point it was concentrated to remove MeOH and diluted with
20 mL water. Three extractions with ether (3£10 mL)
removed unchanged 2g (0.82 g, 16%). The remaining
aqueous layer was acidified with 10% HCl (aq) and
extracted with ether (3£20 mL). The organics were
combined, sequentially washed with water and brine,
dried (Na2SO4), filtered and concentrated to give 3g
(3.90 g, 83%) as a pale yellow oil. A similar experiment
that started with 1.27 g of 2g gave 3g in 88% yield. 1H NMR
(CDCl3, 400 MHz, d): 6.17 (app t, J¼1.5 Hz, 1H), 3.76
(s, 3H), 2.52 (m, 2H), 1.58 (m, 2H), 1.40 (m, 2H), 0.92 (t,
J¼7.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz, d): 178.1 (u),
173.2 (u), 110.6(u), 89.9(u), 53.6 (dn), 31.2 (u), 28.7 (u),
4.3.11. Methyl 2-butyl-1-hydroxymethylcycloprop-2-
ene-1-carboxylate. A 250 mL round bottomed flask con-
taining a solution of 2g (3.27 g, 15.4 mmol) in 40 mL THF
was cooled in an ice bath, and a solution of DIBAL
(30.3 mmol; 60.6 mL of a 0.5 M solution in pentane) was
added dropwise via an additional funnel. The mixture was
stirred for 1 h and then quenched with water, acidified with

1810
L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
10% HCl (aq) and extracted with ether (3£20 mL). The
organic phase was washed with water and brine, dried over
Na2SO4, filtered, and concentrated. Chromatography (10%
ethyl acetate in hexanes) gave 1.48 g (8.04 mmol, 56%) of
the title compound, a colorless oil. Additionally, 0.84 g of
2g (26%) was recovered. A similar experiment with 5.50 g
of 2g gave the title compound in 57% yield. 1H NMR
(CDCl3, 400 MHz, d): 6.43 (t, J¼1.2 Hz, 1H), 3.74 (m, 2H),
3.63 (s, 3H), 2.52 (bs, 1H), 2.48 (app dt, J¼1.2, 7.1 Hz, 2H),
1.53 (m, 2H), 1.36 (m, 2H), 0.88 (t, J¼7.4 Hz); 13C NMR
(CDCl3, 100 MHz, d): 176.8 (u), 119.9 (u), 97.3 (u), 67.3
(u), 51.8 (dn), 31.1 (u), 29.0 (u), 24.6 (u), 22.3 (u), 13.8 (dn);
IR (CH2Cl2, cm21): 2958, 2934, 2873, 1703, 1458, 1436,
1387, 1288, 1190, 1162, 1087, 1020, 975, 832, 791; HRMS-
CI, m/z: [M] calcd for C10H16O3, 184.1099; found,
184.1096.
4.4. General procedures for resolution
A stirred solution of the cycloprop-2-ene-1-carboxylic acid
(1 equiv.) in THF (50 mL/mmol acid) was cooled to
230 8C. Triethylamine (3.5 equiv.) and adamantoyl chloride
(1.05 equiv.) were added sequentially and stirring was
continued at 230 8C for 1 h. Lithium chloride (5.0 equiv.),
the appropriate oxazolidinone (1.1 equiv.) and DMAP
(0.1 equiv.) were then added and the cold bath was
removed. The mixture was allowed to gradually rise to rt
while stirring continued overnight. The solvents were
removed and the residue was partitioned between ether
and water. The aqueous layer was extracted twice with
ether, and the combined organics were dried (Na2SO4),
filtered, and concentrated. Chromatography separated the
diastereomeric products.
4.3.12. Methyl 2-butyl-1-(methoxymethoxymethyl)cyclo-
prop-2-ene-1-carboxylate. To a dry 25 mL round bottomed
flask was added methyl 2-butyl-1-hydroxymethylcyclo-
prop-2-ene-1-carboxylate (1.48 g, 8.04 mmol), N,N-diiso-
propylethylamine (1.25 g, 9.65 mmol), and CH2Cl2
(15 mL). The flask was swept with nitrogen and then cooled
in an ice bath. Methyl chloromethylether (970 mg,
12.06 mmol) was added via syringe, and the ice bath was
removed. The mixture was allowed to stir at rt for 5 h.
Concentration and chromatography (20% ethyl acetate in
hexanes) gave 1.64 g (91%) of the title compound, a pale
yellow oil. A similar experiment that started with 0.41 g of
the starting alcohol gave the title compound in 90% yield.
1H NMR (CDCl3, 400 MHz, d): 6.43 (app t, J¼1.3 Hz), 4.60
(s, 2H), 3.84 (d, J¼10.3 Hz, 1H), 3.67 (d, J¼10.3 Hz, 1H),
3.63 (s, 3H), 3.33 (s, 3H), 2.48 (app dt, J¼7.4, 1.5 Hz), 1.54
(m, 2H), 1.36 (m, 2H), 0.89 (t, J¼7.3 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 176.3 (u), 119.5 (u), 97.5 (u), 96.7
(u), 71.9 (u), 55.4 (dn), 52.2 (dn), 29.5 (u), 29.3 (u), 24.9 (u),
22.6 (u), 14.1 (dn); IR (CH2Cl2, cm21): 2952, 2934, 2874,
1715, 1466, 1288, 1243, 1149, 1104, 1046, 799; HRMS-CI
m/z: [M2OMe] calcd for C12H20O4, calcd, 197.1178;
found, 197.1169.
4.4.1. (4S)-4-Benzyl-3-[(1R)-2-hexylcycloprop-2-en-1-oyl]-
oxazolidinone [5a(Rcy,Sox)] and (4S)-4-benzyl-3-[(1S)-2-
hexylcycloprop-2-en-1-oyl]oxazolidinone [5a(Scy,Sox)].
The general procedure for resolution using (S)-benzyl-
oxazolidinone (390 mg, 2.2 mmol) and 3a (336 mg
2.0 mmol) gave 298 mg (0.91 mmol, 91%) of 5a(Scy,Sox)
and 301 mg (0.92 mmol, 92%) of 5a(Rcy,Sox) after chroma-
tography with a gradient (5–15%) of ethyl acetate in
hexane. 5a(Scy,Sox) eluted first. The Rf difference in
MTBE:toluene:hexane (1:1:2) was 27%. A similar experi-
ment with 890 mg of 3a gave 5a(Scy,Sox) in 92% yield and
5a(Rcy,Sox) in 90% yield.
The absolute configuration of 5a(Scy,Sox) was determined
by reduction with LiBH4, which gave (S)-(2)-7 in 85%
yield. The same alcohol was obtained in 81% yield
from LiBH4 reduction of crystallographically characterized
5a-Ph(Scy,Rox).
Similarly, the absolute configuration of 5a(Rcy,Sox) was
determined by reduction with LiBH4, which gave (R)-(þ)-7
in 75% yield. The same alcohol was obtained in 83% yield
from LiBH4 reduction of crystallographically characterized
5a-Ph(Rcy,Rox).
4.3.13. 1-Methoxymethoxymethyl-2-butylcycloprop-2-
ene-1-carboxylic acid (3k). A mixture of methyl 2-butyl-
1-(methoxymethoxymethyl)cycloprop-2-ene-1-carboxylate
(1.64 g, 7.20 mmol), MeOH (8 mL) and 2 N KOH (aq)
(10 mL) was stirred at 50 8C under nitrogen for 3 h. The
mixture was extracted with ether (3£5 mL). The aqueous
phase was acidified with 10% HCl (aq) and extracted
with ether (3£10 mL). The combined organics were washed
with water and brine, dried over Na2SO4, filtered, and
concentrated to give 1.44 g (94%) of the title compound
as a pale yellow oil. A similar experiment that started
with 420 mg of the ester gave the title compound in 96%
yield. 1H NMR (CDCl3, 400 MHz, d): 6.45 (app t, J¼
1.3 Hz, 1H), 4.63 (s, 1H), 3.85 (d, J¼10.4 Hz, 1H), 3.69 (d,
J¼10.4 Hz, 1H), 3.35 (s, 3H), 2.52 (app dt, J¼1.6, 7.3 Hz,
2H), 1.57 (m, 2H), 1.40 (m, 2H), 0.92 (t, J¼7.3 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, d): 182.6 (u), 119.0(u), 97.0 (u),
96.7(u), 71.5 (u), 55.5(dn), 29.3 (u), 29.2(u), 24.8(u),
22.6(u), 14.1(dn); IR (neat, cm21): 3135, 2934, 2875,
2572, 2059, 1803, 1585, 1415, 1295, 1150, 1105, 917; Anal.
Calcd for C11H18O4: C, 61.66; H, 8.47. Found: C, 61.45; H,
8.58.
1
5a(Scy,Sox): A semisolid. [a]2D3¼þ1058 (c 1.00, THF). H
NMR (CDCl3, 400 MHz, d): 7.18–7.32 (m, 5H), 6.28 (m,
1H), 4.67–4.62 (m, 1H), 4.22–4.13 (m, 2H), 3.43 (d, J¼
1.1 Hz, 1H), 3.29 (dd, J¼10.1, 3.2 Hz, 1H), 2.73 (dd, J¼9.8,
3.5 Hz, 1H), 2.52–2.47 (m, 2H), 1.62–1.55 (m, 2H), 1.38–
1.23 (m, 6H), 0.88–0.85 (t, J¼6.7 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 177.5(u), 154.5(u), 136.0(u),
129.9(dn), 129.3(dn), 127.6(dn), 114.6(u), 92.6(u), 66.7
(u), 56.1(dn), 38.5 (u), 31.9 (u), 29.2 (u), 27.2(u), 25.3 (u),
22.9 (u), 20.4(dn), 14.5(dn); IR (CCl4, cm21): 3031, 2958,
1777, 1688, 1363, 1209; HRMS-CI(NH3) m/z: [Mþ], calcd
for C20H25NO3, 327.1834; found, 327.1826.
1
5a(Rcy,Sox): A semisolid. [a]2D3¼þ468 (c 1.03, THF). H
NMR (CDCl3, 400 MHz, d): 7.33–7.18 (m, 5H), 6.26 (m,
1H), 4.67–4.62 (m, 1H), 4.22–4.13 (m, 2H), 3.43 (d, J¼
1.4 Hz, 1H), 3.27 (dd, J¼10.0, 3.3 Hz, 1H), 2.77 (dd, J¼9.6,
3.7 Hz, 1H), 2.55–2.51(m, 2H), 1.62–1.57(m, 2H), 1.38–
1.26(m, 6H), 0.86 (t, J¼5.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz, d): 177.0(u), 154.0(u), 135.5(u), 129.4(dn),
128.9(dn), 127.2(dn), 113.9(u), 92.4(u), 66.3(u), 55.7(dn),

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1811
38.0(u), 31.5(u), 28.8(u), 26.8(u), 24.9(u), 22.5(u), 20.0(dn),
14.0(dn); IR (CCl4, cm21): 3051, 2957, 1784, 1590, 1361,
1205; HRMS-CI(NH3) m/z: [Mþ], calcd for C20H25NO3,
327.1834; found, 327.1826.
2.77–2.71 (m, 1H), 2.18 (d, J¼1.3 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 177.3(u), 154.5(u), 136.0(u),
129.9(dn), 129.3(dn), 127.7(dn), 110.5(u), 93.4(u),
66.8(u), 56.1(dn), 38.5(u), 20.7(dn), 10.8(dn); IR (KBr,
cm21): 3140, 2921, 1762, 1687, 1491, 1357, 1214, 1103,
769, 714; HRMS-CI(NH3) m/z: [MþH], calcd for
C15H16NO3, 258.1130; found, 258.1118.
4.4.2. (4R)-3-[(1S)-2-Hexylcycloprop-2-en-1-oyl]-4-phenyl-
oxazolidinone [5a-Ph(Scy,Rox)] and (4R)-3-[(1R)-2-hexyl-
cycloprop-2-en-1-oyl]-4-phenyloxazolidinone [5a-Ph
(Rcy,Rox)]. The general procedure for resolution using
(R)-phenyloxazolidinone (1.44 g, 8.8 mmol) and 3a (1.35 g,
8.0 mmol) gave 1.165 g (3.72 mmol, 93%) of 5a-Ph(Rcy,
Rox) and 1.153 g (3.68 mmol, 92%) of 5a-Ph(Scy,Rox) after
chromatography with a gradient of 5–15% ethyl acetate in
hexane. 5a-Ph(Rcy,Rox) eluted first. Relative configurations
for both diastereomers were determined by X-ray crystal-
lography of crystals that were grown from ethyl acetate/
hexane. A similar experiment with 356 mg of 3a gave 5a-
Ph(Rcy,Rox) in 92% yield and 5a-Ph(Scy,Rox) in 92% yield.
5b(slow): White solid, mp¼73–75 8C. [a]D¼þ1128 (c
1
1.00, THF). H NMR (CDCl3, 400 MHz, d): 7.31–7.18(m,
5H), 6.28 (m, 1H), 4.65–4.64 (m, 1H), 4.20–4.14 (m, 2H),
3.43 (d, J¼1.6 Hz, 1H), 3.27 (dd, J¼10.0, 3.3 Hz, 1H),
2.81–2.75 (m, 1H), 2.19 (d, J¼1.3 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 177.3(u), 154.5(u), 136.0(u),
129.9(dn), 129.3(dn), 127.7(dn), 110.2(u), 93.8(u),
66.8(u), 56.1(dn), 38.5(u), 20.7(dn), 10.9(dn); IR (KBr,
cm21): 3135, 2975, 1772, 1679, 1375, 1189, 736, 701;
HRMS-CI(NH3) m/z: [MþH], calcd for C15H16NO3,
258.1130; found, 258.1143.
5a-Ph(Rcy,Rox): White needles, mp 50.5–52.5 8C.
1
[a]2D3¼21688 (c 1.00, THF). H NMR (CDCl3, 400 MHz,
4.4.4. Preparation of 5c(Rcy,Rox) and 5c(Scy,Rox). The
general procedure for resolution using (3aR)-cis-tetrahydro-
2H-indeno[1,2-d]oxazol-2-one (385 mg, 2.20 mmol) and 3c
(472 mg, 2.0 mmol) gave two diastereomers after chroma-
tography with a gradient of 10–20% ethyl acetate in hexane.
5c(Scy,Rox) (353 mg, 0.90 mmol, 90%) eluted first, followed
by 5c(Rcy,Rox) (358 mg, 0.91 mmol, 91%). Relative con-
figurations for both diastereomers were determined by
X-ray crystallography of crystals that were grown from
acetone/hexane. The Rf difference in MTBE:toluene:hexane
(1:1:2) was 22%. A similar experiment that started with
95 mg of 3c gave 5c(Scy,Rox) in 90% yield and 5c(Rcy,Rox)
in 93% yield.
d): 7.34–7.28 (m, 5H), 6.13 (m, 1H), 5.42 (dd, J¼4.7,
4.0 Hz, 1H), 4.68 (app t, J¼8.7 Hz, 1H), 4.27 (dd, J¼4.8,
4.1 Hz, 1H), 3.41 (d, J¼1.5 Hz, 1H), 2.45–2.43 (m, 2H),
1.55–1.53 (m, 2H), 1.32–1.24 (m, 6H), 0.86 (t, J¼6.9 Hz,
3H); 13C NMR (CDCl3, 100 MHz, d): 176.9(u), 154.7(u),
139.7(u), 129.5(dn), 129.0(dn), 126.5(dn), 114.4(u),
92.5(u), 70.5(u), 58.4(dn), 31.9(u), 29.2(u), 27.1(u),
25.3(u), 22.9(u), 20.6(dn), 14.5(dn); IR (CCl4, cm21):
3056, 2931, 1766, 1695, 1363, 1241, 1204, 1071; HRMS-
CI(NH3) m/z: [MþH], calcd for C19H24NO3, 314.1756;
found, 314.1762.
5a-Ph(Scy,Rox): White needles, mp 83–86 8C. [a]2D3¼2738
1
(c 1.05, THF). H NMR (CDCl3, 400 MHz, d): 7.34–7.27
5c(Scy,Rox): White crystals, mp 73–75 8C. [a]2D3¼23788 (c
1.00, THF). 1H NMR (CDCl3, 400 MHz, d): 7.78–7.75 (m,
2H), 7.65–7.63 (m, 1H), 7.43–7.30 (m, 4H), 7.27–7.17(m,
8H), 5.99 (d, J¼6.8 Hz, 1H), 5.26–5.23 (m, 1H), 3.35–3.30
(m, 2H); 13C NMR (CDCl3, 100 MHz, d): 174.5(u),
151.9(u), 141.5(u), 140.0(u), 139.5(u), 130.6(dn),
130.3(dn), 130.2(dn), 129.5(dn), 129.2(dn), 128.6(dn),
128.5(dn), 127.8(dn), 126.8(dn), 126.5(u), 125.6(dn),
121.8(u), 101.5(u), 78.5(dn), 63.8(dn), 38.4(u), 37.3(u); IR
(KBr, cm21): 3057, 2921, 1782, 1768, 1595, 1192; HRMS-
CI(NH3) m/z: [Mþ], calcd for C26H19NO3, 393.1365;
found, 393.1352.
(m, 5H), 6.19 (m, 1H), 5.42 (dd, J¼4.8, 3.8 Hz, 1H), 4.68
(app t, J¼8.8 Hz, 1H), 4.26 (dd, J¼5.0, 3.8 Hz, 1H), 3.43 (d,
J¼1.6 Hz, 1H), 2.39–2.34 (m, 2H), 1.39–1.37 (m, 2H),
1.24–1.16(m, 6H), 0.84 (t, J¼6.8 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 176.8(u), 154.7(u), 139.8(u),
129.5(dn), 128.9(dn), 126.3(dn), 114.2(u), 92.5(u),
70.5(u), 58.4(dn), 31.8(u), 29.1(u), 27.0(u), 25.2(u),
22.9(u), 20.4(dn), 14.5(dn); IR (CCl4, cm21): 3021, 2926,
1775, 1692, 1382, 1195; HRMS-CI(NH3) m/z: [Mþ], calcd
for C19H23NO3, 313.1834; found, 313.1826.
4.4.3. Diastereomers of (4S)-4-benzyl-3-(2-methylcyclo-
prop-2-en-1-oyl)oxazolidinone: 5b(fast) and 5b(slow).
The general procedure for resolution using (S)-benzyloxa-
zolidinone (1.38 g, 7.80 mmol) and 3b (0.637 g, 6.5 mmol)
gave 0.732 g (2.85 mmol, 88%) of 5b(fast) (the dia-
stereomer that elutes more quickly) and 0.740 g
(2.88 mmol, 89%) of 5b(slow) (the diastereomer that elutes
more slowly). The chromatography eluent was 1:1:1:8
MTBE:CH2Cl2:toluene:hexane. A second chromatograph
of the ‘mixed’ fractions was required. The Rf difference in
MTBE:toluene:hexane (1:1:2) was 6%. A similar experi-
ment gave 5b(fast) in 89% yield and 5b(slow) in 86% yield.
5c(Rcy,Rox): White crystals, mp 96–98 8C. [a]2D3¼þ448
1
(c 1.03, THF). H NMR (CDCl3, 400 MHz, d): 7.89–7.86
(m, 1H), 7.80–7.77(m, 2H), 7.43–7.34 (m, 4H), 7.29–7.13
(m, 8H), 5.97 (d, J¼7.0 Hz, 1H), 5.29–5.26 (m, 1H), 3.37–
3.35 (m, 2H); 13C NMR (CDCl3, 100 MHz, d): 174.2(u),
152.0(u), 141.4(u), 140.1(u), 139.5(u), 130.6(dn),
130.4(dn), 130.3(dn), 129.2(dn), 128.6(dn), 128.5(dn),
127.7(dn), 126.6(dn), 126.5(dn), 126.3(u), 125.7(dn),
122.3(u), 101.1(u), 78.6(dn), 63.6(dn), 38.5(u), 36.6(u); IR
(KBr, cm21): 3037, 2906, 1787, 1760, 1595, 1195; HRMS-
CI(NH3) m/z: [Mþ], calcd for C26H19NO3, 393.1365;
found, 393.1352.
5b(fast): White solid, mp¼96–98.5 8C. [a]2D3¼þ2018 (c
1.00, THF). 1H NMR (CDCl3, 400 MHz, d): 7.31–7.19 (m,
5H), 6.30 (m, 1H), 4.65–4.62 (m, 1H), 4.20–4.14 (m, 2H),
3.44 (d, J¼1.4 Hz, 1H), 3.29 (dd, J¼10.1, 3.2 Hz, 1H),
4.4.5. Preparation of 5d(fast) and 5d(slow). The general
procedure for resolution using (3aS)-cis-tetrahydro-2H-
indeno[1,2-d]oxazol-2-one (385 mg, 2.20 mmol) and 3d

1812
L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1
(432 mg, 2.00 mmol) gave 328 mg (0.88 mmol, 88%) of
5d(fast) (the diastereomer that elutes more quickly) and
332 mg (0.89 mmol, 89%) of 5d(slow) (the diastereomer
that elutes more slowly). Chromatography was performed
with a gradient of 10–20% ethyl acetate in hexane. The Rf
difference in MTBE:toluene:hexane (1:1:2) was 11%.
5e(slow): A semisolid. [a]2D3¼þ14.88 (c 1.00, THF). H
NMR (CDCl3, 400 MHz, d): 7.78 (d, J¼7.4 Hz, 1H), 7.37–
7.32 (m, 2H), 7.28–7.26 (m, 1H), 7.19–7.15 (m, 2H), 7.13–
7.10 (m, 1H), 7.03–7.01 (m, 2H), 6.83 (app t, J¼1.3 Hz,
1H), 5.96 (d, J¼7.0 Hz, 1H), 5.27–5.23 (m, 1H), 3.40–3.28
(m, 2H), 2.68–2.64 (m, 2H), 2.12 (app dt, J¼7.1, 2.8 Hz,
2H), 1.91 (t, J¼2.7 Hz, 1H), 1.72–1.68 (m, 2H), 1.68–1.51
(m, 2H); 13C NMR (CDCl3, 90 MHz, d): 174.8(u), 151.4(u),
142.2(u), 139.6(u), 139.1(u), 129.8(dn), 128.1(dn),
128.0(dn), 127.1(dn), 125.9(dn), 125.8(dn), 125.2(dn),
123.6(u), 100.4(u), 84.1(u), 78.0(dn), 68.4(u), 63.0(dn),
38.1(u), 35.5(u), 27.8(u), 26.0(u), 24.1(u), 18.0(u); IR
(CCl4, cm21): 3313, 2931, 1792, 1684, 1359, 1191, 810,
735, 634; HRMS-CI(NH3) m/z: [MþH], calcd for
C26H24NO3, 398.1756; found, 398.1776.
5d(fast): A semisolid. [a]2D3¼21718 (c 1.0, THF). 1H NMR
(CDCl3, 400 MHz, d): 7.70 (d, J¼7.6 Hz, 1H), 7.34–7.12
(m, 6H), 7.05–7.02 (m, 2H), 6.76 (t, J¼1.5 Hz, 1H), 5.95–
5.90 (d, J¼6.9 Hz, 1H), 5.22–5.21 (m, 1H), 3.34–3.31 (m,
2H), 2.62–2.60 (m, 2H), 1.57–1.56 (m, 2H), 1.36–1.34 (m,
2H), 0.87 (t, J¼7.3 Hz, 3H); 13C NMR (CDCl3, 90 MHz, d):
175.5(u), 151.8(u), 142.8(u), 140.1(u), 139.5(u), 130.2(dn),
128.4(dn), 128.4(dn), 127.8(dn), 126.4(dn), 126.3(dn),
125.6(dn), 124.0(u), 100.7(u), 78.4(dn), 63.5(dn), 38.5(u),
36.2(u), 29.5(u), 24.9(u), 22.7(u), 14.2(dn); IR (KBr, cm21):
3054, 2912, 1789, 1695, 1267; HRMS-CI(NH3) m/z: [Mþ],
calcd for C24H23NO3, 373.1678; found, 373.1674.
4.4.7. Preparation of 5f(fast) and 5f(slow). The general
procedure for resolution using (3aS)-cis-tetrahydro-2H-
indeno[1,2-d]oxazol-2-one (385 mg, 2.20 mmol) and 3f
(572 mg, 2.0 mmol) gave 399 mg (0.90 mmol, 90%) of
5f(fast) (the diastereomer that elutes more quickly) and
390 mg (0.88 mmol, 88%) of 5f(slow) (the diastereomer
that elutes more slowly). Chromatography was performed
with a gradient of 10–20% ethyl acetate in hexane. The Rf
difference in MTBE:toluene:hexane (1:1:2) was 20%. A
similar experiment that started with 115 mg of 3f gave
5f(fast) in 89% yield and 5f(slow) in 90% yield.
1
5d(slow): A semisolid. [a]D¼210.48 (c 1.01, THF). H
NMR (CDCl3, 400 MHz, d): 7.79 (dd, J¼7.0, 1.1 Hz, 1H),
7.36–7.33 (m, 2H), 7.26 (d, J¼7.1 Hz, 1H), 7.19–7.15 (m,
2H), 7.12–7.10 (m, 1H), 7.03–7.01(m, 2H), 6.79 (t, J¼
1.3 Hz, 1H), 5.96 (d, J¼7.0 Hz, 1H), 5.25–5.22 (m, 1H),
3.34–3.31 (m, 2H), 2.65–2.61 (m, 2H), 1.57–1.53 (m, 2H),
1.35–1.29 (m, 2H), 0.84 (t, J¼7.4 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 175.4(u), 151.9(u), 142.8(u),
140.1(u), 139.6(u), 130.2(dn), 128.5(dn), 128.4(dn),
127.6(dn), 126.3(dn), 126.2(dn), 125.6(dn), 124.4(u),
100.4(u), 78.4(dn), 63.4(dn), 38.5(u), 36.0(u), 29.4(u),
24.7(u), 22.7(u), 14.1(dn); IR (KBr, cm21): 3055, 2933,
1786, 1693, 1202; HRMS-CI(NH3) m/z: [Mþ], calcd for
C24H23NO3, 373.1678; found, 373.1674.
5f(fast): A pale yellow semisolid. [a]2D3¼þ38.78 (c 0.95,
THF). 1H NMR (CDCl3, 400 MHz, d): 8.38–8.35 (m, 1H),
7.81–7.75 (m, 3H), 7.72–7.69 (m, 2H), 7.54 (s, 1H), 7.50
(dd, J¼6.0, 1.2 Hz, 1H), 7.41–7.35 (m, 6H), 7.26–7.24 (m,
1H), 7.17–7.11 (m, 2H), 5.80 (d, J¼7.0 Hz, 1H), 5.03–4.99
(m, 1H), 3.22 (dd, J¼17.7, 6.6 Hz, 1H), 3.06 (app d, J¼
17.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz, d): 177.4(u),
152.2(u), 140.3(u), 138.7(u), 138.0(u), 134.0(u), 132.6(u),
130.3(2 carbons, dn), 130.2(dn), 129.3(dn), 129.2(dn),
128.7(dn), 128.3(dn), 128.2(dn), 128.2(dn), 126.8(u),
126.5(dn), 126.0(dn), 125.7(dn), 125.4(dn), 124.4(dn),
121.8(u), 104.1(u), 78.7(dn), 64.4(dn), 38.4(u), 37.5(u); IR
(CH2Cl2, cm21): 3029, 2926, 1784, 1676, 1362, 1265, 1190;
HRMS-CI(NH3) m/z: [Mþ], calcd for C30H21NO3,
443.1521; found, 443.1503.
4.4.6. Preparation of 5e(fast) and 5e(slow). The general
procedure for resolution was followed using (3aS)-cis-
tetrahydro-2H-indeno[1,2-d]oxazol-2-one
(84 mg,
0.48 mmol), 3e (96 mg, 0.40 mmol), triethylamine
(142 mg, 0.2 mL, 1.4 mmol), 1-adamantoyl chloride
(98 mg, 0.44 mmol), LiCl (84 mg, 2.0 mmol) and DMAP
(5 mg, 0.04 mmol). Chromatography (the eluent was 5%
ethyl acetate in hexane) gave 70 mg (0.18 mmol, 88%) of
5e(fast) (the diastereomer that elutes more quickly) and
68 mg (0.17 mmol, 86%) of 5e(slow) (the diastereomer that
elutes more slowly). A similar experiment gave 5e(fast) in
92% yield and 5e(slow) in 92% yield. The Rf difference in
MTBE:toluene:hexane (1:1:2) was 14%.
5f(slow): A pale yellow solid, mp 78–80 8C. [a]2D3¼þ8.78
1
(c 1.07, THF). H NMR (CDCl3, 400 MHz, d): 8.27 (d,
J¼8.4 Hz, 1H), 7.90–7.87 (m, 2H), 7.78–7.81(m, 1H),
7.74–7.76(d, J¼7.6 Hz, 1H), 7.69–7.71(d, J¼8.1 Hz, 1H),
7.62(s, 1H), 7.51–7.53(dd, J¼6.1, 1.1 Hz, 1H), 7.32–
7.41(m, 5H), 7.26–7.28(m, 1H), 7.15–7.21(m, 2H), 5.74–
5.75(d, J¼6.6 Hz, 1H), 4.94–4.98(m, 1H), 3.10–3.23(m,
2H); 13C NMR (CDCl3, 100 MHz, d): 177.1(u), 152.1(u),
140.1(u), 139.0(u), 138.3(u), 134.0(u), 132.4(u), 130.39
(dn), 130.33(dn), 130.2(dn), 129.3(dn), 129.3(dn),
128.7(dn), 128.4(dn), 128.4(dn), 128.2(dn), 126.9(u),
126.5(dn), 125.9(dn), 125.7(dn), 125.4(dn), 124.3(dn),
120.2(u), 105.5(u), 79.1(dn), 65.1(dn), 38.0(u), 37.2(u); IR
(CCl4, cm21): 3029, 2924, 1785, 1680, 1362, 1262, 1190;
HRMS-CI(NH3) m/z: [Mþ], calcd for C30H21NO3,
443.1521; found, 443.1503.
5e(fast): A semisolid. [a]2D3¼þ1888 (c 0.98, THF). 1H NMR
(CDCl3, 400 MHz, d): 7.72 (d, J¼7.4 Hz, 1H), 7.36–7.26
(m, 3H), 7.23–7.19 (m, 2H), 7.16–7.14 (m, 1H), 7.06–7.04
(m, 2H), 6.82 (app s, 1H), 5.95 (d, J¼6.9 Hz, 1H), 5.25–
5.21(m, 1H), 3.40–3.28 (m, 2H), 2.66 (t, J¼7.2 Hz, 2H),
2.18 (app dt, J¼7.0, 2.6 Hz, 2H), 1.95–1.94 (m, 1H), 1.77–
1.73 (m, 2H), 1.61–1.55 (m, 2H); 13C NMR (CDCl3,
90 MHz, d): 174.9(u), 151.4(u), 142.2(u), 139.7(u), 139.0(u),
129.8(dn), 128.1(2 carbons, dn), 127.3(dn), 126.0(2 carbons,
dn), 125.2(dn), 123.2(u), 100.7(u), 84.1(u), 78.0(dn),
68.5(u), 63.1(dn), 38.0(u), 35.8(u), 27.9(u), 26.0(u),
24.3(u), 18.1(u); IR (CCl4, cm21): 3313, 2933, 1793, 1683,
1359, 1297, 1190, 767, 697; HRMS-CI(NH3) m/z: [MþH],
calcd for C26H24NO3, 398.1756; found, 398.1769.
4.4.8. Diastereomers of (4S)-4-benzyl-3-(2-butyl-1-meth-
oxycarbonyl-cycloprop-2-en-1-oyl)oxazolidinone:

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1813
5g(fast) and 5g(slow). A solution of 3g (204 mg,
1.03 mmol) and triethylamine (1.42 mmol) in 10 mL THF
was stirred in a 25 mL flask and cooled in a bath of dry ice/
acetone. Pivaloyl chloride (124 mg, 1.03 mmol) was added
via syringe, and the solution was stirred at 278 8C for 5 min
and then warmed to 0 8C for 1 h. The mixture was once
again cooled in the dry ice/acetone bath.
Chromatography (20% MTBE in Petroleum Ether) gave
5h(fast) (81 mg, 0.21 mmo1, 86%) and 5h(slow) (84 mg,
0.22 mmo1, 89%). The Rf difference in MTBE:petroleum
ether (1:1) was 45%. A similar experiment with 1.62 g of 3h
gave 5h(fast) in 81% yield and 5h(slow) in 79% yield.
1
5h(fast): A semisolid. [a]2D3¼þ137.9 (c 1.00, THF). H
NMR (CDCl3, 400 MHz, d): 7.76 (m, 2H), 7.45(m, 3H),
7.32–7.18 (m, 5H), 7.00 (s, 1H), 4.71 (m, 1H), 4.30–4.21
(m, 1H), 3.70 (s, 3H), 3.35 (dd, J¼13.4, 3.2 Hz, 1H), 2.81
(dd, J¼13.4, 9.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz, d):
172.0 (u), 170.8 (u), 154.0 (u), 135.6 (u), 131.04 (dn),
130.97 (dn), 129.9(dn), 129.37 (dn), 129.32(dn), 127.8,
(dn), 124.9 (u), 114.5 (u), 97.0 (u), 67.0 (u), 55.7 (dn), 52.9
(dn), 38.0 (u), 36.6(u); IR (CH2Cl2, cm21): 3154, 3066,
3031, 2953, 2359, 2338, 2274, 1784, 1739, 1718, 1695,
1387, 1354, 1312, 1214, 1111, 1083, 766; HRMS-CI m/z
[M] calcd for C22H19NO5, 377.1263; found, 377.1259.
In a separate 10 mL flask, a solution of (S)-benzyloxazo-
lidinone (273 mg, 1.55 mmol) in 4 mL THF, cooled in a
bath of dry ice/acetone. n-BuLi (1.5 mL of a 2.5 M solution
in hexanes, 1.55 mmol) was added dropwise. This solution
was stirred at 278 8C for 0.5 h, and then transferred via
cannula to the 25 mL flask that contained the mixed
anhydride. The reaction mixture was stirred at 278 8C for
5 min then warmed to 0 8C for 0.5 h. The reaction was
carefully quenched with water, and 2 mL of 1% HCl was
added. Three extracts with ether (3£20 mL) were combined
and washed with water and brine, dried (Na2SO4), filtered
and concentrated. Chromatography (20% MTBE in petro-
leum ether) gave 5g(fast) (171 mg, 0.48 mmol, 93%) and
5g(slow) (169 mg, 0.47 mmol, 92%). The Rf difference in
MTBE:petroleum ether (4:6) was 40%. A similar experi-
ment with 1.00 g of 3g gave 5g(fast) in 92% yield and
5g(slow) in 91% yield.
5h(slow): A semisolid. [a]2D3¼222.2 (c 1.00, THF). 1H
NMR (CDCl3, 400 MHz, d): 7.78 (m, 2H), 7.45(m, 3H),
7.24–7.17 (m, 5H), 7.00 (s, 1H), 4.68 (m, 1H), 4.26–4.20
(m, 2H), 3.71 (s, 3H), 3.35 (dd, J¼13.6, 3.3 Hz, 1H), 2.91
(dd, J¼13.6, 9.1 Hz, 1H); 13C NMR (CDCl3, 100 MHz, d):
172.0 (u), 170.7 (u), 154.0 (u), 135.6 (u), 131.04 (dn),
131.02 (dn), 129.95(dn), 129.34 (dn), 129.31(dn), 127.7
(dn), 124.9 (u), 114.4 (u), 97.1 (u), 67.0 (u), 55.7 (dn), 52.9
(dn), 37.9 (u), 36.5(u); IR (CH2Cl2, cm21): 3154, 3065,
3031, 2953, 2359, 2322, 2283, 1784, 1739, 1719, 1694,
1390, 1355, 1311, 1214, 1112, 1083, 768; HRMS-CI m/z
[M] calcd for C22H19NO5, 377.1263; found, 377.1256.
1
5g(fast): Colorless oil. [a]2D3¼þ48.68 (c 1.00, THF). H
NMR (CDCl3, 400 MHz, d): 7.36–7.21 (m, 5H), 6.53 (app
t, J¼1.4 Hz, 1H), 4.68 (m, 1H), 4.24–4.19 (m, 2H), 3.69 (s,
3H), 3.38 (dd, J¼13.5, 3.4 Hz, 1H), 2.80 (dd, J¼13.5,
9.8 Hz, 1H), 2.61 (m, 2H), 1.63 (m, 2H), 1.41 (m, 2H), 0.93
(t, J¼7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz, d): 172.7
(u), 171.7 (u), 153.8 (u), 135.7 (u), 129.9 (dn), 129.3 (dn),
127.7 (dn), 117.3 (u), 95.4 (u), 66.8 (u), 55.5 (dn), 52.6 (dn),
38.0 (u), 35.7 (u), 29.1 (u), 24.5 (u), 22.6 (u), 14.1 (dn); IR
(CCl4, cm21): 3153, 3055, 2958, 2933, 2873, 2359, 2332,
1785, 1734, 1716, 1695, 1436, 1387, 1310, 1261, 1214, 789,
756, 703; HRMS-CI m/z [M] calcd for C20H23NO5,
357.1576; found, 357.1580.
4.4.10. Diastereomers of (4S)-4-benzyl-3-(2-hexyl-1-
trans-styryl-cycloprop-2-en-1-oyl)oxazolidinone: 5i(fast)
and 5i(slow). The general procedure for resolution was
followed using 3i (108 mg, 0.4 mmol), 1-adamantoyl-
chloride (84 mg, 0.42 mmol), Et3N (202 mg, 2.0 mmol),
LiCl (85 mg, 2.0 mmol), DMAP (5 mg, 0.04 mmol),
(S)-benzyloxazolidione (75 mg, 0.42 mmol) and THF
(30 mL). Chromatography (10% MTBE in Petroleum
Ether) gave 5i(fast) (64 mg, 0.15 mmol, 73%) and
5i(slow) (63 mg, 0.15 mmol, 73%) of the title compounds
as pale yellow oils. The purities of 5i(fast) and 5i(slow)
were estimated by 1H NMR to be .95 and .96%,
respectively. The Rf difference in toluene:MTBE:petroleum
ether (2:1:2) was 17%. A similar experiment with 1.62 g of
3i gave 5i(fast) in 73% yield and 5i(slow) in 73% yield.
1
5g(slow): Colorless oil. [a]2D3¼þ56.88 (c 1.00, THF). H
NMR (CDCl3, 400 MHz, d): 7.34–7.21 (m, 5H), 6.52 (t,
J¼1.1 Hz, 1H), 4.67 (m, 1H), 4.25–4.19 (m, 2H), 3.68 (s,
3H), 3.32 (dd, J¼13.5, 3.2 Hz, 1H), 2.83 (dd, J¼13.5,
9.5 Hz, 1H), 2.62 (m, 2H), 1.66 (m, 2H), 1.43 (m, 2H), 0.94
(t, J¼7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz, d): 172.7
(u), 171.6 (u), 153.8 (u), 135.7 (u), 129.9 (dn), 129.3 (dn),
127.7 (dn), 117.2 (u), 95.6 (u), 66.8 (u), 55.5 (dn), 52.6 (dn),
37.9 (u), 35.6 (u), 29.0 (u), 24.4 (u), 22.6 (u), 14.1 (dn); IR
(CCl4, cm21): 3153, 3058, 2958, 2933, 2873, 2363, 2321,
1785, 1734, 1717, 1693, 1436, 1387, 1312, 1251, 1213, 701;
HRMS-CI m/z [M] calcd for C20H23NO5, 357.1576; found,
357.1561.
5i(fast): A pale yellow oil. [a]2D3¼þ32.38 (c 1.00, THF). 1H
NMR (CDCl3, 400 MHz, d): 7.32–7.16 (m, 10H), 6.71 (t,
J¼1.3 Hz, 1H), 6.55 (d, J¼16.0 Hz, 1H), 6.18 (d, J¼
16.0 Hz, 1H), 4.73 (m, 1H), 4.23–4.15 (m, 2H), 3.34 (dd,
J¼13.4, 3.3 Hz, 1H), 2.79 (dd, J¼13.4, 9.3 Hz, 1H), 2.58
(m, 2H), 1.64 (m, 2H), 1.40–1.26 (m, 6H), 0.87 (t, J¼
7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, d): 176.1 (u),
153.0 (u), 137.7 (u), 135.6 (u), 132.7 (dn), 129.9 (dn), 129.4
(dn), 128.9 (dn), 128.3 (dn), 127.8 (dn), 127.4 (dn), 126.5
(dn), 123.0 (u), 98.6 (u), 66.8 (u), 55.6 (dn), 38.2 (u), 35.1
(u), 31.9 (u), 29.3 (u), 27.4 (u), 25.1 (u), 23.0 (u), 14.5 (dn);
IR (CH2Cl2, cm21): 3054, 2957, 2931, 2859, 2305, 1786,
1687, 1600, 1448, 1388, 1351, 1259, 1215, 1076, 959, 896,
757, 713; HRMS-CI, m/z: [MþNa]: calcd for C28H31NO3,
452.2226; found, 452.2218.
4.4.9. Diastereomers of (4S)-4-benzyl-3-(2-phenyl-1-
methoxycarbonyl-cycloprop-2-en-1-oyl)oxazolidinone:
5h(fast) and 5h(slow). The procedure was identical to that
used to resolve 3g, except that adamantoyl chloride (99 mg,
0.5 mmol) was used in place of pivaloyl chloride. The other
materials were used in the following quantities: 3h (109 mg,
0.5 mmol), Et3N (61 mg, 0.084 mL, 0.6 mmol), THF
(7 mL), (S)-benzyloxazolidinone (233 mg, 0.75 mmol),
n-BuLi (0.3 mL of a 2.5 M solution in hexane, 0.75 mmol).

1814
L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
5i(slow): A pale yellow oil. [a]2D3¼þ42.6 (c 1.00, THF). 1H
NMR (CDCl3, 400 MHz, d): 7.31–7.16 (m, 10H), 6.68 (app
s, 1H), 6.45 (d, J¼16.1 Hz, 1H), 6.20 (d, J¼16.1 Hz, 1H),
4.62 (m, 1H), 4.18–4.13 (m, 2H), 3.37 (dd, J¼13.3, 3.1 Hz,
1H), 2.84 (dd, 1H), 2.62 (app t, J¼7.2 Hz, 2H), 1.64 (m,
2H), 1.40–1.26 (m, 6H), 0.88 (t, J¼6.7 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, d): 175.6 (u), 152.8 (u), 137.8 (u), 135.8
(u), 132.9 (dn), 130.0 (dn), 129.4 (dn), 128.9 (dn), 128.4
(dn), 127.8 (dn), 127.5 (dn), 126.5 (dn), 123.1 (up), 99.7 (u),
66.7 (u), 56.1 (dn), 38.1 (u), 34.7 (u), 32.0 (u), 29.4 (u), 27.4
(u), 25.1 (u), 23.1 (u), 14.6 (dn); IR (CH2Cl2, cm21): 3054,
2958, 2931, 2858, 2305, 1788, 1686, 1600, 1385, 1350,
1270, 1076, 959, 909, 756, 710; HRMS-CI, m/z: [MþNa]:
calcd for C28H31NO3, 452.2226; found, 452.2187.
0.17 mmol, 86%) and 5k(slow) (65 mg, 0.17 mmol, 86%).
The Rf difference in MTBE:petroleum ether (4:6) was 40%.
A similar experiment gave 5k(fast) in 91% yield and
5k(slow) in 90% yield.
1
5k(fast): A pale yellow oil. [a]D¼þ10.9 (c 1.0, THF). H
NMR (CDCl3, 400 MHz, d): 7.34–7.20 (m, 5H), 6.78 (app
t, J¼1.2 Hz, 1H), 4.65–4.60 (m, 1H), 4.63 (s, 2H), 4.21 (m,
1H), 4.14 (m, 1H), 4.06 (d, J¼11.3 Hz, 1H), 3.57 (d, J¼
11.3 Hz, 1H), 3.36 (m, 1H), 3.34 (s, 3H), 2.71 (dd, J¼13.3,
9.7 Hz, 1H), 2.55 (app dt, J¼1.0, 7.4 Hz, 2H), 1.60 (m 2H),
1.39 (m, 2H), 0.92 (t, J¼7.3 Hz, 3H); 13C NMR (CDCl3,
100 MHz, d): 176.1 (u), 153.6 (u), 135.8 (u), 129.8 (dn),
129.3 (dn), 127.7 (dn), 123.3 (u), 100.1 (u), 96.4 (u), 72.9
(u), 67.0 (u), 55.67 (dn), 55.66(dn), 38.3 (u), 33.5 (u), 29.4
(u), 25.5 (u), 22.7 (u), 14.2 (dn); IR (CCl4, cm21): 2956,
2930, 2875, 2228, 1784, 1691, 1605, 1454, 1386, 1350,
1215, 1150, 971; Anal. Calcd for C21H27NO5: C, 67.54; H,
7.29; N, 3.75. Found: C, 67.26; H, 7.27; N, 3.68.
4.4.11. Diastereomers of (4S)-4-phenyl-3-[2-methyl-3-
propylcycloprop-2-en-1-oyl]oxazolidinone: 5j(fast) and
5j(slow). The general procedure for resolution was fol-
lowed using 3j (400 mg, 2.86 mmol), 1-adamantoylchloride
(622 mg, 3.14 mmol), Et3N (1.01 g, 1.4 mL, 10 mmol),
LiCl (600 mg, 14.3 mmol), DMAP (5 mg, 0.04 mmol),
(S)-phenyloxazolidinone (75 mg, 0.42 mmol) and THF
(30 mL). Chromatography (10% MTBE in hexane) gave
5j(fast) (378 mg, 1.33 mmol, 93%) and 5j(slow) (0.375 g,
1.32 mmol, 92%). A similar experiment gave 5j(fast) in
92% yield and 5j(slow) in 93% yield. The Rf difference in
MTBE:toluene:hexane (1:1:2) was 28%.
5k(slow): A pale yellow oil. [a]D¼þ31.5 (c 1.0, THF). 1H
NMR (CDCl3, 400 MHz, d): 7.32–7.20 (m, 5H), 6.72 (app
t, J¼1.2 Hz, 1H), 4.63 (s, 2H), 4.63–4.60 (m, 1H), 4.21 (m,
1H), 4.16 (m, 1H), 3.80 (s, 2H), 3.34 (s, 3H), 3.34 (dd, J¼
13.4, 3.2 Hz, 1H), 2.80 (dd, J¼13.4, 9.5 Hz, 1H), 2.62 (m,
2H), 1.65 (m, 2H), 1.40 (m, 2H), 0.94 (t, J¼7.3 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, d): 175.6 (u), 153.4 (u), 135.8 (u),
129.9 (dn), 129.3 (dn), 127.7 (dn), 123.9 (u), 101.5 (u), 96.4
(u), 73.1 (u), 67.0 (u), 56.1 (dn), 55.7(dn), 38.1 (u), 33.0 (u),
29.5 (u), 25.5 (u), 22.7 (u), 14.2 (dn); IR (CCl4, cm21):
2957, 2930, 2874, 2232, 1787, 1690, 1604, 1454, 1386,
1350, 1213, 1150, 971; Anal. Calcd for C21H27NO5: C,
67.54; H, 7.29; N, 3.75. Found: C, 67.67; H, 7.47; N, 3.76.
5j(fast): White solid, 66.5–68 8C. [a]2D5¼þ1438 (c 1.0,
THF). 1H NMR (CDCl3, 400 MHz, d): 7.37–7.29 (m, 5H),
5.44 (dd, J¼8.7, 4.0 Hz, 1H), 4.69 (app t, J¼8.7 Hz, 1H),
4.26 (dd, J¼8.8, 3.9 Hz, 1H), 3.35 (s, 1H), 2.39–2.34 (m,
2H), 1.95 (m, 3H), 1.61–1.54 (m, 2H), 0.95 (t, J¼7.4 Hz,
3H); 13C NMR (CDCl3, 90 MHz, d): 177.2(u), 154.9(u),
140.0(u), 129.5 (dn), 128.9(dn), 126.3(dn), 105.3(u),
100.7(u), 70.4(u), 58.4(dn), 26.8(u), 23.5(dn), 20.9(u),
14.3(dn), 10.0(dn); IR (KBr, cm21): 3034, 2964, 1907,
1775, 1686, 1453, 1375, 1305, 1189, 1093, 765, 699;
HRMS-CI(NH3) m/z: [MþH], calcd for C17H20NO3,
286.1443; found, 286.1453.
4.5. General procedures for reduction
A solution of the cycloprop-2-en-1-oyl oxazolidinone
(1.0 mmol) in THF (30 mL) was cooled in an ice bath.
Methanol (32 mg, 40 mL, 1.0 mmol) and LiBH4(4.0 mmol,
2.0 mL of a 2.0 M solution in THF) were added sequen-
tially. The ice bath was removed, and stirring was continued
for 4 h while the mixture warmed to rt. The reaction was
quenched by NH4Cl (aq) and extracted with ether
(3£30 mL). The organics were combined, dried (Na2SO4),
filtered, concentrated, and chromatographed (10–30%
ethyl acetate in hexane) to provide the 3-hydroxymethyl-
cycloprop-1-ene.
5j(slow): White solid, 43–46.5 8C. [a]D¼þ1328 (c 1.0,
THF). 1H NMR (CDCl3, 400 MHz, d): 7.36–7.26 (m, 5H),
5.45 (dd, J¼8.7, 3.9 Hz, 1H), 4.69 (app t, J¼8.8 Hz, 1H),
4.26 (dd, J¼8.8, 4.0 Hz, 1H), 3.35 (s, 1H), 2.29–2.25 (m,
2H), 2.03–2.04 (t, J¼1.5 Hz, 3H), 1.43–1.37 (m, 2H), 0.83
(t, J¼7.4 Hz, 3H); 13C NMR (CDCl3, 90 MHz, d): 176.7(u),
154.4(u), 139.5(u), 129.0(dn), 128.4(dn), 125.9(dn),
104.8(u), 100.1(u), 70.0(u), 58.0(dn), 26.1(u), 23.0(dn),
20.3(u), 13.7(dn), 9.6(dn); IR (KBr, cm21): 3030, 2960,
1772, 1685, 1451, 1376, 1303, 1182, 1106, 166, 705;
HRMS-CI(NH3) m/z: [MþH], calcd for C17H20NO3,
286.1443; found, 286.1453.
4.5.1. (3S)-(2)-1-Hexyl-3-hydroxymethylcycloprop-1-
ene [S-(2)-7]. The general procedure for reduction with
5a(Scy,Sox) (327 mg, 1.0 mmol) gave 131 mg (0.85 mmol,
85%). The general procedure with 5a-Ph(Scy,Rox) (313 mg,
1.0 mmol) gave 131 mg product, 85%. A similar experiment
with 800 mg of 5a(Scy,Sox) gave S-(2)-7 in 86% yield. The
specific rotation of the colorless oil was [a]D¼234.38 (c
1.03, THF). Analysis by HPLC (CHIRACEL OD using 15%
IPA in hexane) showed the material to be of .99% ee.
Other spectral data were identical to those reported for the
racemate.30
4.4.12. Diastereomers of (4S)-4-benzyl-3-(2-butyl-1-
methoxymethoxymethyl-cycloprop-2-en-1-oyl)oxazolidi-
none: 5k(fast) and 5k(slow). The general procedure
for resolution was followed using 3k (86 mg, 0.4 mmol),
1-adamantoylchloride (83 mg, 0.42 mmol), Et3N (202 mg,
0.28 mL, 2.0 mmol), LiCl (85 mg, 2.0 mmol), DMAP
(5 mg, 0.04 mmol), (S)-benzyloxazolidinone (75 mg,
0.42 mmol) and THF (30 mL). Chromatography (20%
MTBE in petroleum ether) gave 5k(fast) (64 mg,
4.5.2. (3R)-1,3-Diphenyl-3-hydroxymethylcycloprop-1-
ene [R-(2)-6] and (3S)-1,3-diphenyl-3-hydroxymethyl-
cycloprop-1-ene [S-(1)-6]. The general procedure for

L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
1815
group. Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1987;
pp 1224–1339.
reduction with 5c(Rcy,Rox) (320 mg, 0.81 mmol) gave
163 mg (91%) of R-(2)-6, a semisolid, [a]D¼218.98 (c
1.1, THF). A similar experiment with 250 mg of 5c(Rcy,Rox)
gave R-(2)-6 in 86% yield. Analysis by HPLC
(CHIRACEL OD using 15% IPA in hexane) showed the
material to be of .99% ee. 1H NMR (CDCl3, 400 MHz, d):
7.58–7.56 (m, 2H), 7.39–7.26 (m, 8H), 7.19–7.21(m, 1H),
4.29–4.33(m, 1H), 4.21–4.25(m, 1H); 13C NMR (CDCl3,
100 MHz, d): 145.2(u), 130.1(dn), 129.9(dn), 129.3(dn),
128.7(dn), 127.6(u), 126.9(dn), 126.3(dn), 123.0(u),
105.4(u), 68.1(u), 32.8(u); IR (CCl4, cm21): 3595, 3282,
2875, 1717, 1508, 1265, 1065; HRMS-CI(NH3) m/z:
[MþH] calcd for C16H13O, 221.0966; found, 221.0960.
2. Baird, M. S. Top. Curr. Chem. 1988, 144, 137.
3. Baird, M. S.; Schmidt, T.; 4th ed. Carbocyclic three-
membered ring compounds, de Meijere, A., Ed.; Georg
Thieme: Stuttgart, 1996; Vol. E17a, pp 114–255.
4. Baird, M. S.; Bushby, R. J.; Schmidt, T.; 4th ed. Carbocyclic
three-membered ring compounds, de Meijere, A., Ed.; Georg
Thieme: Stuttgart, 1996; Vol. E17d, pp 2695–2860.
5. Hopf, H. Carbocyclic three-membered ring compounds, de
Meijere, A., Ed.; Georg Thieme: Stuttgart, 1996; Vol. E17d,
pp 2745–2746.
6. Nakamura, M.; Isobe, H.; Nakamura, E. Chem. Rev. 2003,
103, 1295.
7. Padwa, A.; Fryxell, G. E. Advances in strain in organic
chemistry, Halton, B., Ed.; Jai: Greenwich, CT, 1991; Vol. 1.
8. York, E. J.; Dittmar, W.; Stevenson, J. R.; Bergman, R. G.
J. Am. Chem. Soc. 1973, 95, 5680.
Similarly, reduction of 5c(Scy,Rox) (320 mg, 0.81 mmol)
gave 160 mg (89%) of S-(þ)-6, [a]D¼þ18.78 (c 1.0, THF),
.99% ee. A similar experiment with 200 mg of 5c(Scy,Rox)
gave R-(þ)-6 in 85% yield
9. Doyle, M. P.; Protopopova, M.; Mu¨ller, P.; Ene, D.; Shapiro,
E. A. J. Am. Chem. Soc. 1994, 116, 8492.
4.5.3. (1)-1-Butyl-3-hydroxymethyl-3-phenylcycloprop-
1-ene [(1)-9]. The general procedure for reduction with
5d(fast) (373 mg, 1.0 mmol) gave 167 mg (0.83 mmol,
83%) of (þ)-9, a colorless oil. A similar experiment that
started with 500 mg of 5d(fast) gave (þ)-9 in 82% yield.
Analysis by HPLC (CHIRACEL OD using 15% IPA
in hexane) showed the material to be of .99% ee. [a]D¼
þ23.18 (c 1.0, THF). Other spectral data were identical to
those reported for the racemate.30
10. Mu¨ller, P.; Imogai, H. Tetrahedron: Asymmetry 1998, 9, 4419.
11. Doyle, M. P.; Ene, D. G.; Forbes, D. C.; Pillow, T. H. Chem.
Commun. 1999, 1691.
12. Timmons, D. J.; Doyle, M. P. J. Organomet. Chem. 2001, 617,
98.
13. Doyle, M. P.; Hu, W. Tetrahedron Lett. 2000, 41, 6265.
14. Doyle, M. P.; Hu, W. H. Synlett 2001, 1364.
¨
15. Schollkopf, U.; Hupfeld, B.; Ku¨per, S.; Egert, E.; Dyrbusch,
M. Angew. Chem., Int. Ed. Engl. 1988, 27, 433.
16. Baird, M. S.; Fitton, H. L.; Clegg, W.; McCamley, A. J. Chem.
Soc., Perkin Trans. 1 1993, 321.
4.5.4. (1S,2S)-(2)-1-Hexyl-2-hydroxymethyl-1-vinylcyclo-
propane [(1S,2S)-(2)-8] was prepared from (S)-(2)-7 in
the same way as the racemate.30 Gas Chromatography on
a Chiraldex B-PH column showed the material to be of
.99% ee. The injection temperature for the GC was 120 8C.
The GC oven temperature was increased from 708 to 908 at a
rate of 1.0 8C/min, from 90 8C to 110 8C at 0.2 8C/min, and
then from 110 8C to 150 8C at 5.0 8C/min. The product is a
clear oil, [a]D¼23.08 (c 1.0, THF). Other spectral data were
identical to those reported for the racemate.30
17. Imogai, H.; Bernardinelli, G.; Granicher, C.; Moran, M.;
Rossier, J. C.; Muller, P. Helv. Chim. Acta 1998, 81, 1754.
18. Arrowood, T. L.; Kass, S. R. J. Am. Chem. Soc. 1999, 121,
7272.
19. Diaz-Requejo, M. M.; Mairena, M. A.; Belderrain, T. R.;
Nicasio, M. C.; Trofimenko, S.; Perez, P. J. Chem. Commun.
2001, 1804. and references cited therein.
20. Petiniot, N.; Anciaux, A. J.; Noels, A. F.; Hubert, A. J.;
Teyssie, P. H. Tetrahedron Lett. 1978, 14, 1239.
21. Protopopova, M. N.; Shapiro, E. A. Russ. Chem. Rev. (Engl.
Transl.) 1989, 58, 667.
4.5.5. (1)-1a-Butyl-2b-hydroxymethyl-1b-methyl-2a-
phenylcyclopropane (1)-10]. Was prepared from (þ)-(9)
in the same way as the racemate.30 Gas Chromatography
with a Chiraldex B-PH column showed the material to be of
.99% ee. The injection temperature for the GC was 120 8C.
The GC oven temperature was increased from 908 to 1108 at
a rate of 1.0 8C/min, from 110 8C to 140 8C at 0.5 8C/min,
and then from 140 8C to 150 8C at 1.0 8C/min. The product
is a clear oil, [a]D¼þ7.88 (c 1.0, THF). Other spectral data
were identical to those reported for the racemate.30
22. The report that a chiral Cu-catalyst also gives non-racemic
cyclopropenes seems to be in error, based on the reported
NMR spectra: Cho, D.-J.; Jeon, S.-J.; Kim, H. S.; Cho, C.-S.;
Shim, S.-C.; Kim, T.-J. Tetrahedron: Asymmetry 1999, 10,
3833.
23. Doyle, M. P.; Ene, D. G.; Peterson, C. S.; Lynch, V. Angew.
Chem., Int. Ed. 1999, 38, 700.
24. Hanessian, S. Pure Appl. Chem. 1993, 65, 1189.
25. Baird, M. S.; Huber, F. A. M.; Clegg, W. Tetrahedron 2001,
57, 9849.
26. Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc.
2003, 125, 7198.
Acknowledgements
27. Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc.
2002, 124, 11566.
The project described was supported by NIH Grant Number
P20 RR017716-01 from the COBRE Program of the
National Center for Research Resources.
28. Araki, S.; Shiraki, F.; Tanaka, T.; Nakano, H.; Subburaj, K.;
Hirashita, T.; Yamamura, H.; Kawai, M. Chem. Eur. J. 2001,
7, 2784.
29. Boger, D. L.; Zhu, Y. J. Org. Chem. 1994, 59, 3453. and
references therein.
References and notes
30. Liao, L.-a.; Fox, J. M. J. Am. Chem. Soc. 2002, 124, 14322.
31. For representative crystal structures of N-acyloxazolidnones,
1. Halton, B.; Banwell, M. G. In The chemistry of the cyclopropyl

1816
L. Liao et al. / Tetrahedron 60 (2004) 1803–1816
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