Asymmetric synthesis of cyclopropanes from lithiated aryloxiranes and α,β-unsaturated fischer carbene complexes

Article abstract of DOI:10.1021/jo050443r

A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes and α,β-unsaturated Fischer carbene complexes is described.

Full text of DOI:10.1021/jo050443r

Asymmetric Synthesis of Cyclopropanes from Lithiated
Aryloxiranes and r,â-Unsaturated Fischer Carbene Complexes
Vito Capriati,† Saverio Florio,*,† Renzo Luisi,† Filippo Maria Perna,† and Jose´ Barluenga‡
Dipartimento Farmaco-Chimico, Universita` di Bari, Via E. Orabona 4, I-70126 Bari, C.N.R.,
Istituto di Chimica dei Composti OrganoMetallici “ICCOM”, Sezione di Bari, Italy, and Instituto
Universitario de Quı´mica Organometa´lica “Enrique Moles”, Unidad Asociada al C.S.I.C. Julia´n Claverı´a,
8, Universidad de Oviedo, 33006 Oviedo, Spain
florio@farmchim.uniba.it
Received March 8, 2005
A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and
cyclopropanecarboxylates from lithiated aryloxiranes and R,â-unsaturated Fischer carbene com-
plexes is described.
Introduction
have recently demonstrated that some optically active
lithiated aryloxiranes1f,5 react with electrophiles in a
stereospecific manner with complete retention of config-
uration at the benzylic carbon atom. However, reactions
with aldehydes proceeded with no or very low diastereo-
selectivity at the newly created stereogenic center, as
reported for other oxiranyllithiums.1d,2
We have recently found that lithiated oxazolinyl ary-
loxiranes couple diastereoselectively with Fischer carbene
complexes6 providing cyclopropane-γ-butyrolactones and
-carboxylates.7 These results seemed to be promising for
asymmetric induction so that we decided to study the
reaction of racemic and optically active R-lithiated aryl-
oxiranes, such as styrene oxides 1,5a phenylpropylene
The utility of lithiated oxiranes as nucleophiles (e.g.,
oxiranyllithiums) has been long underestimated,1 though
they may provide the organic chemist with a very direct
way to assemble substituted epoxides. Only with the
beginning of the 1990s has the oxiranyl anion methodol-
ogy become an efficient synthetic strategy.2
Among metalated oxiranes, R-lithiated aryloxiranes
have been investigated only recently.1c,f,3,4 There are two
aspects of the chemistry of R-lithiated aryloxiranes that
make these species significantly important: the configu-
rational stability and the potential as asymmetry induc-
tors. After the seminal papers from Eisch and Galle,3 we
† Universita` di Bari.
‡ Universidad de Oviedo.
(4) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996, 52,
14361-14384.
(5) (a) Capriati, V.; Florio, S.; Luisi, R.; Salomone, A. Org. Lett. 2002,
4, 2445-2448. (b) Capriati, V.; Florio, S.; Luisi, R.; Nuzzo, I. J. Org.
Chem. 2004, 69, 3330-3335. (c) Florio, S.; Aggarwal, V. K.; Salomone,
A. Org. Lett. 2004, 6, 4191-4194.
(1) (a) Satoh, T. Chem. Rev. 1996, 96, 3303-3325. (b) Mori, Y. Rev.
Heteroatom Chem. 1997, 17, 183-211. (c) Hodgson, D. M.; Gras, E.
Synthesis 2002, 1625-1642. (d) Chemla, F.; Vrancken, E. In The
Chemistry of Organolithium Compounds; Rappoport, Z., Marek, I.,
Eds.; John Wiley & Sons: New York, 2004; Vol. 2, Chapter 18, pp
1165-1242. (e) For a special issue on oxiranyl and aziridinyl anions,
see: Florio, S., Ed. Tetrahedron 2003, 59, 9693-9864. (f) For a recent
account on R-lithiated aryloxiranes, see: Capriati, V.; Florio, S.; Luisi,
R. Synlett 2005, 9, 1359-1369.
(2) Molander, G. A.; Mautner, K. Pure Appl. Chem. 1990, 62, 707-
712.
(3) (a) Eisch, J. J.; Galle, J. E. J. Organomet. Chem. 1976, 121, C10-
14. (b) Eisch, J. J.; Galle, J. E. J. Organomet. Chem. 1988, 341, 293-
313. (c) Eisch, J. J.; Galle, J. E. J. Org. Chem. 1990, 55, 4835-4840.
(6) (a) Barluenga, J.; Santamar´ıa, J.; Toma´s, M.Chem. Rev. 2004,
104, 2259-2284. (b) Barluenga, J.; Flo´rez, J.; Fan˜ana´s, F. J. J.
Organomet. Chem. 2001, 624, 5-17. (c) Herndon, J. W. Tetrahedron
2000, 56, 1257-1280. (d) Sierra, M. A. Chem. Rev. 2000, 100, 3591-
3638. (e) Wulff, W. D. In Comprehensive Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: New
York, 1995; Vol. 12, p 470.
(7) Florio, S.; Perna, F. M.; Luisi, R.; Barluenga, J.; Fan˜ana´s, F. J.;
Rodr´ıguez, F. J. Org. Chem. 2004, 69, 9204-9207.
10.1021/jo050443r CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/29/2005
5852
J. Org. Chem. 2005, 70, 5852-5858

Asymmetric Synthesis of Cyclopropanes
SCHEME 1a
a Reagents and conditions: (i) s-BuLi/TMEDA, THF, -98 °C; (ii) NH4Cl.
TABLE 1. Preparation of Cyclopropane Carbenes 6a-k and Cyclopropanecarboxylates 9a-j
oxirane
carbene complex
R3
R1
R2
compd 6 (% yield)a
compd 9 (% yield)a
1
1
1
1
1
4a
4b
4c
4d
4e
4a
4f
Ph
H
H
6a (73)
6b (78)
6c (81)
6d (59)
9a (88)
9b (82)
9c (81)
b
p-MeOC6H4
p-ClC6H4
1-methylpyrrol-2-yl
2-furyl (Fur)
Ph
H
H
H
H
H
H
H
H
c
(R*,R*)-2
(R*,R*)-2
(R*,S*)-2
(R*,R*)-2
(R*,R*)-3d
(R*,S*)-3
1
H
Me
Me
H
6e (71)
6f (68)
6g (70)
6h (75)
6i (73)
6j (77)
6k (74)
9e (88)
p-MeC6H4
p-MeC6H4
2-furyl (Fur)
Ph
Ph
Me
H
4f
Me
H
9g (84)
4e
4a
4a
4g
Me
Ph
H
H
Ph
H
9i (83)
9j (87)
H
a Isolated yield after column chromatography. b Lactone 7c was also detected (<5%) in the crude reaction mixture; see Scheme 2 and
text. c In this case, lactone 7e was the only product isolated (48%); see Scheme 3 and text. d Reaction temperature: -60 °C.
oxides 2,5b and stilbene oxides 35c with R,â-unsaturated
The stereochemical outcome of the above reaction
might reasonably be accounted for with a diastereo-
selective nucleophilic 1,4-addition of 1-Li to 4a (similar
to that reported for â-lithiated oxazolinyloxiranes)7 lead-
ing to the lithium derivative 5a in which the appropriate
orbital alignment allows the overlap of the carbanion lone
pair on the â-carbon (with respect to the oxirane ring)
with the antibonding orbital of the oxirane C-O bond,
thus promoting cyclopropanation simultaneously with the
oxirane ring-opening. Comparable results were obtained
when 1-Li was reacted with complexes 4b and 4c to give
6b (78%) and 6c (81%), respectively (Table 1).
The addition of lithiated rac-1 to heteroaryl carbene
complexes 4d and 4e (Table 1) was also investigated. The
pyrrole carbene complex 4d reacted with 1-Li likewise
to 4a-c leading diastereoselectively to the cyclopropane
derivative 6d as the main product (59% yield) (Scheme
2). A minor compound, identified as the cyclopropane-γ-
butyrolactone 7c, likely generated by air oxidation of the
related organometallic precursor 7b, was also detected
by NMR and GC-MS in the crude reaction mixture; it
formed only in traces (<5%) and was not isolated (Scheme
2).
Fischer carbene complexes.
Results and Discussion
Treatment of rac-1 with s-BuLi/TMEDA in THF at -98
°C (10 min) produced R-lithium styrene oxide 1-Li
(Scheme 1): addition to the R,â-unsaturated tungsten
carbene complex 4a resulted in the formation of cyclo-
propane derivative 6a as the sole diastereomer upon
quenching with NH4Cl after 1 h at -98 °C and warming
to rt (73%, Table 1). The relative configuration of 6a was
deduced from 2D-NOESY correlations. Significant NOE
interactions, detected either between the two cyclopro-
pane ring protons Ha and Hb and the two ortho aromatic
ring protons Hc and Hd or between one of the two
methylenic carbinol protons and Ha, as depicted in
Scheme 1, were diagnostic of a close proximity relation-
ship. Moreover, the coupling constant value (5.8 Hz)
between Ha and Hb was in agreement with a trans
arrangement of these two protons, as analogously re-
ported for other diastereomeric cyclopropanes.8
(8) (a) Capriati, V.; Florio, S.; Luisi, R.; Rocchetti, M. T. J. Org.
Chem. 2002, 67, 759-763. (b) Vicinal coupling constants between
protons of cyclopropanes exhibit a strong dependence on the stereo-
chemistry of the two protons and depend also on the nature and the
electronegativities of the substituents, decreasing as the latter increase.
The relationship Jcis (6-12 Hz) > Jtrans (2-9 Hz) is always observed,
and there are no known exceptions (see: Pretsch, E.; Bu¨hlmann, P.;
Affolter, C. In Structure Determination of Organic Compounds, 3rd
ed.; Tables of Spectral Data; Springer Publishing: New York, 2004;
pp 176-178).
Something particularly interesting happened when we
used the Fischer carbene complex 4e. Indeed, in contrast
to 4a-d, the furyl carbene complex 4e proved to be
unreactive toward 1-Li at -98 °C. Only upon warming
to rt, after 1 h at -98 °C, did it react, leading exclusively,
through 7d (not isolated), to the cyclopropane-γ-butyro-
lactone 7e (single diastereomer) (48% yield) (Scheme 3).
J. Org. Chem, Vol. 70, No. 15, 2005 5853

Capriati et al.
SCHEME 2
SCHEME 3
SCHEME 5a
a
Reagents and conditions: (i) s-BuLi/TMEDA, THF, -98 °C;
(ii) 4a and quick warming to rt; (iii) air and sunlight.
SCHEME 4
In this context, the formation of the cyclopropane-γ-
butyrolactone 7a besides 9a in the reaction of 1-Li with
4a (Scheme 5), when the reaction mixture was warmed
to rt after 5 min from the reactants mixing, could be
similarly rationalized with the carbenoid character of
lithiated styrene oxide; indeed, it has been demonstrated
that the electrophilic character (vs the carbanionic
character) of lithiated styrene oxide tends to increase
with the temperature.5a
Lithiated phenylpropylene oxides (R*,R*)-2-Li and
(R*,S*)-2-Li5b reacted with carbenes 4a and 4f to give
cyclopropane carbenes 6e-g in good yields (Table 1). It
is worth pointing out that (R*,R*)-2-Li, in contrast to
1-Li, reacted with 4e to give 6h (75% yield, Table 1). This
different behavior might be justified considering that
lithiated phenylpropylene oxide would have a more
pronounced carbanionic character at low temperature;5b
indeed, it is known that it survives for more than 2 h at
-98 °C, whereas lithiated styrene oxide 1-Li, under the
same conditions, has a lifetime of only 30 min. It is,
therefore, reasonable that lithiated species 1-Li may
exhibit a different reactivity (carbanionic and/or car-
benoid) depending upon the electrophile and the tem-
perature. However, more work is needed to support this
mechanistic viewpoint.10
The addition of lithiated stilbene oxides (R*,R*)-3-Li
and (R*,S*)-3-Li5c to 4a resulted in the formation of
carbenes 6i (73%) and 6j (77%) (Table 1), respectively
(dr > 98:2): the relative configuration of 6i was secured
by an X-ray analysis.11 This was a clear confirmation that
the lithiated aryloxirane retains the configuration in the
Michael addition step but inverts at the R-carbon in the
oxirane ring-opening.
Also in this case, the relative configuration was estab-
lished by 2D-NOESY correlations, the He and Hf coupling
constant value (3.3 Hz) indicating a trans relationship
(Scheme 3).8b
A tentative mechanistic explanation for the formation
of 7e might be given by considering that 4e contains a
Lewis basic heteroatom and that styrene oxide 1-Li, as
reported,5a can exhibit a carbenoid character even at low
temperature! Now, assuming that lactone 7d would likely
result from a stereochemistry which puts the alkoxy
group and the metal fragment cis to each other on the
cyclopropane ring, to justify this geometry it could be
reasonable to suppose that in the presence of a prelimi-
nary coordination between the lithium and the furyl
oxygen, the π bond of 4e might act as a nucleophile
causing an SN2-like epoxide ring-opening9 (i.e., a con-
certed SN2-type pathway with backside attack of the
CdC bond at the oxirane C-O bond) according to the
transition state TS-A (transition state TS-B should be
more sterically congested and without any possibility to
chelate the lithium) to give first the alkoxide 8 and, soon
after, the lactone 7d whose formation should be the
driving force of the reaction (Scheme 4). Indeed, the furyl
cyclopropane, deriving from the protonation of alkoxide
8, was never isolated.
(10) A computational and an NMR spectroscopic study on lithiated
styrene- and phenylpropylene oxides is underway, and results will be
reported in due course.
(11) Crystallographic data for compound 6i have been deposited at
the Cambridge Crystallographic Data Centre (deposition no. CCDC-
259218). Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K. [fax:
(int.) +44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
(9) The LUMO of the carbenoid could be, in this case, a strongly
polarized σ*C-O orbital. For an exhaustive review on the electrophilic
character of carbenoids, see: Boche, G.; Lohrenz, C. W. Chem. Rev.
2001, 101, 697-756.
5854 J. Org. Chem., Vol. 70, No. 15, 2005

Asymmetric Synthesis of Cyclopropanes
SCHEME 6a
SCHEME 7a
a Reagents and conditions: (i) s-BuLi/TMEDA, THF, -98 °C;
(ii) methyl trans-cinnamate; (iii) NH4Cl.
As observed for R- and â-lithiated oxazolinyloxiranes,7
the use of complexes 4 was necessary for the formation
of cyclopropane carbenes. Indeed, lithiated racemic
styrene oxide 1-Li did not react with methylcinnamate,
and trans-phenylpropylene oxide (R*,R*)-2-Li gave a
mixture of the 1,2-addition product 10 (22% yield) and a
chromatographically separable mixture of hex-3-en-2,5-
diols 11 (35% overall yield, 2.9:1 E/Z ratio),14 which likely
originates from the carbenoid dimerization of the starting
lithiated oxirane (Scheme 7).
Finally, we could prove that the addition of lithiated
aryloxiranes to R,â-unsaturated Fischer carbene com-
plexes takes place also with â-alkyl-R,â-unsaturated
Fischer carbene complexes other than with the aryl-
substituted ones. Indeed, the addition of 1-Li to the
Fischer carbene complex 4g gave the cyclopropane de-
rivative 6k in good yield and with high diastereoselec-
tivity (74%, dr > 98:2, Table 1).
In conclusion, lithiated styrene, phenypropylene, and
stilbene oxides react diastereo- and, when optically active,
enantiospecifically with R,â-unsaturated Fischer carbene
complexes to give stereodefined tetrasubstituted cyclo-
propane carbenes and cyclopropanecarboxylates,15 which
are potentially useful intermediates in organic synthe-
sis.16 These are, to the best of our knowledge, the first
examples of optically active lithiated aryloxiranes capable
of inducing asymmetry in the coupling reaction with
prochiral substrates.
a Reagents and conditions: (i) 4a or 4c; (ii) NH4Cl; (iii) PyNO,
rt, THF, 24 h.
All of the above cyclopropane carbenes (6a-c,e,g,i,j)
could be easily oxidized to the corresponding cyclopro-
panecarboxylates (9a-c,e,g,i,j) with pyridine N-oxide
(PyNO)12 in THF (rt, 24 h) (Table 1).
Next, we studied the addition of lithiated optically
active styrene oxides (R)-1 and (S)-1 to the complex 4c:
the addition of (R)-1-Li resulted in the formation of
tetrasubstituted arylcyclopropane (1S,2S,3R)-(-)-6c (79%
yield, dr > 98/2), whereas the addition of (S)-1-Li
furnished the enantiomeric arylcyclopropane (1R,2R,3S)-
(+)-6c (81% yield, dr > 98/2) (Scheme 6). The (S)-(+)-R-
methoxy-R-trifluoromethylphenylacetyl chloride (MTPA-
Cl) was used to ascertain, via NMR,13 the enantiomeric
purity of the above-cited cyclopropanecarboxylates, by
comparing the two MTPA esters formed with those
deriving from a sample of rac-1. A cascade process
involving the stereospecific Michael addition (retention
of configuration at the R-carbon) of (R)- or (S)-1-Li to 4c
(according to that described in Scheme 1), followed by
the oxirane ring-opening-promoted cyclopropanation (in-
version of configuration at the R-carbon), might likely
explain the formation of (-)- and (+)-6c. Taking into
account the stereochemical features of the entire process,
it has been possible to determine also the absolute
configuration of all three stereocenters of these cyclopro-
pane carbenes by 2D-NOESY experiments.
Similarly, lithiated optically active phenylpropylene
oxides (R,R)-2-Li and (S,S)-2-Li5b (Scheme 6), generated
by deprotonation of (R,R)-2 and (S,S)-2, reacted smoothly
with 4a to furnish cyclopropane carbenes (1′S,1R,2R,3S)-
(-)-6e (68%) and (1′R,1S,2S,3R)-(+)-6e (70%), respec-
tively, in both cases highly enantiomerically enriched
[er > 98:2, via (S)-MTPA chloride].
The absolute configuration of the four stereocenters
was determined by 2D-NOESY experiments considering
that there is retention of configuration at the â-carbon
and inversion at the R-benzylic carbon of the starting
epoxide. Compounds (-)-/(+)-6c and (-)-/(+)-6e could be
easily oxidized with PyNO to give the corresponding
cyclopropanecarboxylates (+)-/(-)-9c, (87% yield) and (+)-
9e (85% yield) and (-)-9e (88% yield), respectively
(Scheme 6). The configuration remained unaffected.
Experimental Section
Preparation of Carbene Complexes 6a-k and Phen-
ylpropenone 10. General Procedure. A solution of s-BuLi
(1.2 mmol, 0.92 mL of a 1.3 N solution in cyclohexane), under
N2 and stirring, was added to a solution of oxirane 1, 2, or 3
(1.0 mmol) and TMEDA (3.0 mmol) in THF (6 mL) previously
cooled to -98 °C (methanol-liquid nitrogen bath) [-60 °C in
the case of (R*,R*)-3]. After 15 min [60 min for (R*,R*)-2,
(14) The Z or E configuration to diastereomeric enediols 11 could
be assigned on the basis of the methine and methyl protons chemical
shifts: 5.12 and 1.29 vs 4.31 and 1.03 δ, respectively. In fact, if bulky
substituent groups exist on the double bond gem to aromatic rings these
will adopt a twist conformation and a shielding of the protons in “cis
positions” will occur, as reported (Gaudemar, A. In Stereochemistry:
Fundamentals and Methods; Kagan, H. B., Ed.; Georg Thieme Publish-
ers: Stuttgart, 1977; Vol. 1. Determination of configurations by
spectrometric methods, pp 48-50). A PM3 semiempirical geometry
optimization of the Z and E diastereomers showed that the phenyl
ring was indeed twisted with respect to the plane of the CdC double
bond of about 86° and 73°, respectively, thus supporting the above
conclusions.
(15) For other routes to diastereomerically pure cyclopropanes, see
also: Avery, T. D.; Taylor, D. K.; Tiekink, E. R. T. J. Org. Chem. 2000,
65, 5531-5546.
(12) (a) Barluenga, J.; Bernad, P. L.; Concello´n, J. M.; Pin˜era-
Nicola´s, A.; Garc´ıa-Granda, S. J. Org. Chem. 1997, 62, 6870-6875 and
references cited therein. (b) Herndon, J. W. Coord. Chem. Rev. 2002,
248, 3-79.
(13) Seco, J. M.; Quin˜oa´, E.; Riguera, R. Chem. Rev. 2004, 104, 17-
117.
(16) (a) Reissig, H. U. Organic synthesis via cyclopropanes: prin-
ciples and applications. In The Chemistry of the Cyclopropyl Group;
Patai, S., Rappoport, Z., Eds.; John Wiley and Sons: New York, 1987;
Chapter 8. (b) Liu, H. W.; Walsh, C. T. Biochemistry of the cyclopropyl
group. In The Chemistry of the Cyclopropyl Group; Patai, S., Rappoport,
Z., Eds.; John Wiley and Sons: New York, 1987; Chapter 16.
J. Org. Chem, Vol. 70, No. 15, 2005 5855

Capriati et al.
(R*,S*)-2, (R*,R*)-3] at the above temperature, a solution of
the tungsten complex 4 (0.9 mmol) (or a solution of methyl
trans-cinnamate in the case of synthesis of 10) in THF (3 mL)
was added dropwise. The resulting mixture was stirred for 1
h, allowed to warm to rt, and quenched with saturated aqueous
NH4Cl. Then, it was poured into 20 mL of satd brine, extracted
with Et2O (3 × 15 mL), dried (Na2SO4), and concentrated in
vacuo. The crude residue was flash chromatographed (silica
gel; petroleum ether/Et2O 4/1) to give the compounds 6a-k
and 10, which showed the following data:
20.4, 41.7, 59.5, 60.6, 68.5, 71.3, 127.2, 127.3, 127.9, 128.4,
128.7, 131.7, 135.2, 136.1, 197.8 (4 × CdO), 203.4 (CdO), 324.2
(CdW); GC-MS (70 eV) m/z 280 [M+ - W(CO)5, 18], 264 (8),
220 (60), 205 (100), 192 (45), 115 (37), 77 (13); FT-IR (film,
cm-1) 3473, 3028, 2948, 2928, 2067, 1917, 1496, 1448, 1269,
1089, 755, 701. (+)-(1′S,1R,2R,3S)-6e: 70%; [R]20D ) +189 (c
1, CHCl3). (-)-(1′R,1S,2S,3R)-6e: 68%; [R]20 ) -187 (c 1,
D
CHCl3).
Pentacarbonyl{[(1′R*,1S*,2S*,3R*)-2-[1-hydroxyethyl]-
3-(4-methylphenyl)-2-phenylcyclopropyl]methoxymeth-
1
ylene}tungsten (6f): yellow oil, 68%; H NMR (500 MHz) δ
Pentacarbonyl{[(1R*,2R*,3S*)-2-hydroxymethyl-2,3-
diphenylcyclopropyl]methoxymethylene}tungsten
0.76 (d, J ) 6.5 Hz, 3 H), 1.99 (br s, exchanges with D2O, 1
H), 2.36 (s, 3 H), 3.42 (q, J ) 6.5 Hz, 1 H), 3.76 (d, J ) 6.0 Hz,
1 H), 3.93 (s, 3 H), 4.53 (d, J ) 6.0 Hz, 1 H), 7.16-7.34 (m, 9
H); 13C NMR (125 MHz) δ 20.4, 21.0, 41.6, 59.7, 60.8, 68.4,
71.3, 127.2, 127.9, 128.2, 129.3, 131.7, 132.1, 136.2, 136.9,
197.8 (4 × CdO), 203.4 (CdO), 324.4 (CdW); GC-MS (70 eV)
m/z 294 [M+ - W(CO)5, 10], 278 (11), 234 (60), 205 (100), 192
(45), 77 (13); FT-IR (film, cm-1) 3473, 3461 3032, 2948, 2928,
2066, 1917, 1448, 1263, 1080, 701.
1
(6a): yellow solid; mp 63-64 °C (Et2O), 73%; H NMR (300
MHz) δ 2.61 (br s, exchanges with D2O, 1 H), 3.52 (d, J ) 11.9
Hz, 1 H), 3.95 (d, J ) 5.8 Hz, 1 H), 3.98 (s, 3 H), 4.05 (d, J )
11.9 Hz, 1 H), 4.33 (d, J ) 5.8 Hz, 1 H), 7.33-7.46 (m, 10 H);
13C NMR (75.4 MHz, DEPT) δ 40.5 (CH), 54.9 (Cq), 59.2 (CH),
66.3 (CH2), 68.5 (CH3), 127.4 (CH), 127.6 (CH), 128.4 (2 × CH),
128.8 (2 × CH), 128.9 (2 × CH), 130.4 (2 × CH), 135.8 (Cq),
137.6 (Cq), 197.7 (4 × CdO), 204.9 (CdO), 323.3 (CdW); GC-
MS (70 eV) m/z 266 [M+ - W(CO)5, 43], 205 (100), 191 (40),
Pentacarbonyl{[(1′R*,1R*,2R*,3S*)-2-[1-hydroxyethyl]-
3-(4-methylphenyl)-2-phenylcyclopropyl]methoxymeth-
ylene}tungsten (6g): yellow solid; mp 51-52 °C (Et2O), 70%;
1H NMR (500 MHz) δ 1.20 (d, J ) 6.5 Hz, 3 H), 1.58 (br s,
exchanges with D2O, 1 H), 2.34 (s, 3 H), 3.57 (q, J ) 6.5 Hz, 1
H), 3.71 (d, J ) 5.7 Hz, 1 H), 3.98 (s, 3 H), 4.33 (d, J ) 5.7 Hz,
1 H), 7.07-7.36 (m, 9 H); 13C NMR (125 MHz) δ 21.0, 32.2,
43.0, 58.8, 59.4, 68.6, 70.3, 127.2, 127.3, 127.9, 128.5, 129.5,
132.1, 136.0, 137.1, 197.7 (4 × CdO), 203.2 (CdO), 324.
(CdW); GC-MS (70 eV) m/z 294 [M+ - W(CO)5, 11], 278 (20),
219 (100), 115 (37), 77 (13); FT-IR (film, cm-1) 3564, 3453,
3026, 2970, 2948, 2066, 1926, 1446, 1271, 1046, 763, 701. Anal.
Calcd for C25H22O7W: C, 48.57; H, 3.59. Found: C, 48.29; H,
3.40.
Pentacarbonyl{[(1′R*,1S*,2S*,3R*)-3-(2-furyl)-2-[1-hy-
droxyethyl]-2-phenylcyclopropyl]methoxymethylene}-
tungsten (6h): yellow oil, 75%; 1H NMR (500 MHz) δ 0.85 (d,
J ) 6.2 Hz, 3 H), 3.56 (d, J ) 5.2 Hz, 1 H), 3.62 (q, J ) 6.2 Hz,
1 H), 3.91 (s, 3 H), 4.40 (d, J ) 5.2 Hz, 1 H), 6.25 (d, J ) 3.1
Hz), 6.34 (dd, J ) 3.1, 1.8 Hz, 1 H), 7.22-7.37 (m, 7 H, 6 H
after exchange with D2O); 13C NMR (125 MHz) δ 20.5, 33.5,
58.1, 61.1, 68.5, 71.6, 108.0, 110.5, 127.4, 127.9, 131.6, 135.2,
142.1, 150.2, 197.6 (4 × CdO), 203.0 (CdO), 324.9 (CdW);
GC-MS (70 eV) m/z 270 [M+ - W(CO)5, 11], 195 (100), 115
(23), 91 (14), 77 (7); FT-IR (film, cm-1) 3477, 3033, 2927, 2066,
1936, 1537, 1260, 753, 700.
Pentacarbonyl{[(1′R*,1S*,2S*,3R*)-2-[hydroxy(phen-
yl)methyl]-2,3-diphenylcyclopropyl]methoxymethylene}-
tungsten (6i): yellow oil, 73%; 1H NMR (500 MHz) δ 2.12 (br
s, exchanges with D2O, 1 H), 3.77 (d, J ) 6.0 Hz, 1 H), 3.94 (s,
3 H), 4.54 (s, 1 H), 4.83 (d, J ) 6.0 Hz, 1 H), 6.05-6.07 (m, 2
H), 6.86-7.03 (m, 4 H), 7.22-7.41 (m, 9 H); 13C NMR (125
MHz) δ 42.1, 59.7, 60.0, 65.8, 68.5, 126.8, 127.1, 127.2, 127.3,
127.4, 127.5, 128.6, 128.8, 132.2, 135.1, 136.2, 140.2, 197.7 (4
× CdO), 203.5 (CdO), 324.4 (CdW); GC-MS (70 eV) m/z 342
[M+ - W(CO)5, 6], 326 (10), 281 (60), 207 (100), 191 (25), 115
(39), 77 (13); FT-IR (film, cm-1) 3404, 3028, 2928, 2067, 1916,
1494, 1365, 753, 700.
Pentacarbonyl{[(1′R*,1R*,2R*,3S*)-2-[hydroxy(phenyl)-
methyl]-2,3-diphenylcyclopropyl]methoxymethylene}-
tungsten (6j): yellow oil, 77%; 1H NMR (500 MHz) δ 3.77 (d,
J ) 6.0 Hz, 1 H), 3.89 (s, 3 H), 4.54 (s, 1 H), 4.75 (d, J ) 6.0
Hz, 1 H), 6.79 (br s, exchanges with D2O, 1 H), 6.85-6.89 (m,
2 H), 7.05-7.20 (m, 8 H), 7.32-7.57 (m, 5 H); 13C NMR (125
MHz) δ 43.8, 58.4, 60.1, 68.6, 76.5, 127.0, 127.1, 127.2, 127.5,
127.7, 127.8, 128.7, 128.8, 132.4, 135.6, 135.8, 140.2, 197.5 (4
× CdO), 203.0 (CdO), 325.0 (CdW); GC-MS (70 eV) m/z 342
[M+ - W(CO)5, 11], 326 (9), 281 (53), 207 (100), 191 (30), 115
(43), 77 (13); FT-IR (film, cm-1) 3365, 303, 2930, 2065, 1917,
1511, 1444, 756, 704.
176 (49), 115 (27), 105 (31), 91 (53), 77 (23); FT-IR (film, cm-1
)
3422, 2925, 2066, 1934, 1447, 1277, 700. Anal. Calcd for
C23H18O7W: C, 46.80; H, 3.07. Found: C, 47.14; H, 3.08.
Pentacarbonyl{[(1R*,2R*,3S*)-2-hydroxymethyl-3-
(4-methoxyphenyl)-2-phenylcyclopropyl]methoxy-
methylene}tungsten (6b): yellow solid; mp 54-55 °C (Et2O),
78%; 1H NMR (300 MHz) δ 3.11 (br s, exchanges with D2O, 1
H), 3.49 (d, J ) 11.9 Hz, 1 H), 3.81 (s, 3 H), 3.90 (d, J ) 5.9
Hz, 1 H), 3.97 (s, 3 H), 4.04 (d, J ) 11.9 Hz, 1 H), 4.24 (d, J )
5.8 Hz, 1 H), 6.96-7.04 (m, 2 H), 7.30-7.55 (m, 7 H); 13C NMR
(75.4 MHz, DEPT) δ 40.4 (CH), 51.3 (CH3), 55.0 (Cq), 59.2 (CH),
66.0 (CH2), 68.5 (CH3), 115.1 (2 × CH), 127.7 (CH), 127.9 (2 ×
CH), 128.5 (2 × CH), 129.3 (2 × CH), 135.8 (Cq), 137.6 (Cq),
156.9 (Cq), 197.7 (4 × CdO), 204.9 (CdO), 324.1 (CdW); GC-
MS (70 eV) m/z 296 [M+ - W(CO)5, 21], 235 (100), 204 (38),
115 (27), 105 (13), 91 (31), 77 (29); FT-IR (film, cm-1) 3412,
2926, 2066, 1924, 1447, 1271, 804, 703. Anal. Calcd for
C24H20O8W: C, 46.47; H, 3.25. Found: C, 46.18; H, 3.14.
Pentacarbonyl{[(1R*,2R*,3S*)-3-(4-chlorophenyl)-2-
hydroxymethyl-2-phenylcyclopropyl]methoxymeth-
ylene}tungsten (6c): yellow solid; mp 55-56 °C (Et2O), 81%;
1H NMR (300 MHz) δ 2.48 (br s, exchanges with D2O, 1 H),
3.42 (d, J ) 12.0 Hz, 1 H), 3.84 (d, J ) 6.0 Hz), 3.93 (s, 3 H),
4.05 (d, J ) 12.0 Hz, 1 H), 4.20 (d, J ) 6.0 Hz,1 H), 7.26-7.32
(m, 3 H), 7.34-7.41 (m, 6 H); 13C NMR (75.4 MHz, DEPT) δ
39.7 (CH), 54.6 (Cq), 59.2 (CH), 65.4 (CH2), 68.5 (CH3), 127.6
(CH), 128.3 (2 × CH), 128.9 (2 × CH), 130.4 (4 × CH), 130.5
(Cq), 133.3 (Cq), 137.3 (Cq), 197.6 (4 × CdO), 203.3 (CdO),
322.1 (CdW); GC-MS (70 eV) m/z 300 [M+ - W(CO)5, 1], 241
(28), 239 (84) 204 (70), 175 (100), 91 (15); FT-IR (film, cm-1
)
3406, 2067, 1916, 1494, 1447, 1277, 1089, 700. Anal. Calcd
for C23H17ClO7W: C, 44.22; H, 2.74. Found: C, 44.54; H, 2.55.
(+)-(1R,2R,3S)-6c: 81%; [R]20 ) +205 (c 1, CHCl3). (-)-
D
(1S,2S,3R)-6c: 79%; [R]20 ) - 206 (c 1, CHCl3).
D
Pentacarbonyl{[(1R*,2R*,3S*)-2-hydroxymethyl-2-
phenyl-3-(1-methyl-1H-pyrrol-2-yl)cyclopropyl]methoxy-
methylene}tungsten (6d): yellow oil, 59%; 1H NMR (300
MHz) δ 3.58-3.61 (m, 2 H), 3.63 (br s, exchanges with D2O, 1
H), 3.73 (s, 3 H), 3.94 (s. 3 H), 4.18-4.21 (m, 2 H), 6.06-6.12
(m, 2 H), 6.62-6.66 (m, 1 H), 7.28-7.41 (m, 5 H); 13C NMR
(75.4 MHz) δ 31.8, 34.2, 54.3, 59.2, 65.8, 68.6, 107.0, 108.6,
122.9, 127.5, 127.7, 128.6, 130.2, 137.3, 197.7 (4 × CdO), 203.4
(CdO), 323.1 (CdW); GC-MS (70 eV) m/z 207 (M+ - W(CO)5,
100), 190 (10), 165 (16), 103 (9), 77 (7); FT-IR (film, cm-1) 3427,
3031, 2929, 2066, 1934, 1449, 1261, 1172, 751, 700.
Pentacarbonyl{[(1′R*,1S*,2S*,3R*)-2-[1-hydroxyethyl]-
2,3-diphenylcyclopropyl]methoxymethylene}tungsten
1
(6e): yellow oil, 71%; H NMR (500 MHz) δ 0.75 (d, J ) 6.5
Hz, 3 H), 1.72 (br s, exchanges with D2O, 1 H), 3.42 (q, J )
6.5 Hz, 1 H), 3.81 (d, J ) 6.0 Hz, 1 H), 3.93 (s, 3 H), 4.57 (d,
J ) 6.0 Hz, 1 H), 7.27-7.38 (m, 10 H); 13C NMR (125 MHz) δ
Pentacarbonyl{[(1R*,2R*,3R*)-2-hydroxymethyl-3-
methyl-2-phenylcyclopropyl]methoxymethylene}-
5856 J. Org. Chem., Vol. 70, No. 15, 2005

Asymmetric Synthesis of Cyclopropanes
tungsten (6k): yellow oil, 74%; 1H NMR (400 MHz) δ 1.38 (d,
J ) 6.4 Hz, 3 H), 1.42 (br s, exchanges with D2O, 1 H), 2.60-
2.64(m, 1 H), 3.53 (d, J ) 5.2 Hz, 1 H), 3.75 (d, J ) 12.0 Hz,
1 H), 3.82 (s, 3 H), 4.25 (d, J ) 12.0 Hz, 1 H), 7.13-7.28 (m,
5 H); 13C NMR (100 MHz) δ 13.4, 31.3, 55.0, 63.1, 66.4, 68.3,
127.4, 128.3, 130.4, 138.4, 197.7 (4 × CdO), 203.5 (CdO), 324.3
(CdW); GC-MS (70 eV) m/z 204 [M+ - W(CO)5, 11], 143 (100),
115 (22), 77 (10); FT-IR (film, cm-1) 3406, 3028, 2933, 2066,
1938, 1446, 1268, 1063, 759, 700.
1-[(2R*,3R*)-3-Methyl-2-phenyloxiran-2-yl]-3-phenyl-
prop-2-en-1-one (10): white solid; mp 57-58 °C (Et2O), 22%;
1H NMR (500 MHz) δ 1.41 (d, J ) 6.0 Hz, 3 H), 3.29 (q, J )
6.0 Hz, 1 H), 6.56 (d, J ) 12.6 Hz, 1 H), 6.89 (d, J ) 12.6 Hz,
1 H), 7.26-7.42 (m, 6 H), 7.48-7.59 (m, 4 H); 13C NMR (125
MHz) δ 15.8, 62.8, 67.9, 122.8, 128.0, 128.3, 128.4, 128.5, 128.7,
128.8, 134.3, 135.4, 145.4, 194.9; GC-MS (70 eV) m/z 264 (M+,
16), 248 (21), 157 (12), 131 (100), 105 (29), 77 (25); FT-IR (film,
cm-1) 3031, 2967, 1685, 1541, 1260, 753, 702.
Preparation of Cyclopropanecarboxylates 9a-j and
Lactone 7e. General Procedure. A solution of the carbene
complex 6a-c,e,g,i,j (or the crude reaction mixture of 7b,
obtained from the reaction of 1-Li with 4e according to the
general procedure described above) (0.8 mmol) in hexane (10
mL) was subjected to air oxidation under sunlight. After 24
h, the mixture was filtered off on Celite, the solvent was
removed under reduced pressure, and the residue was purified
by column chromatography (Et2O/petroleum ether 1/4) to give
the corresponding cyclopropanecarboxylate. Alternatively, the
oxidation could be carried out with pyridine N-oxide (3 equiv)
in THF (5 mL) at rt overnight.12a
(1R*,5S*,6R*)-6-(2-Furyl)-5-phenyl-3-oxabicyclo[3.1.0]-
hexan-2-one (7e): white solid; mp 55-56 °C (Et2O), 48%; 1H
NMR (300 MHz) δ 2.80 (d, J ) 3.3 Hz, 1 H), 2.90 (d, J ) 3.3
Hz, 1 H), 4.40 (d, J ) 9.3 Hz, 1 H), 4.68 (d, J ) 9.3 Hz, 1 H),
5.87 (d, J ) 3.2 Hz, 1H), 6.16 (dd, J ) 3.2, 1.9 Hz, 1H), 7.15-
7.31 (m, 6 H), 7.31-7.56 (m, 7 H); 13C NMR (75.4 MHz, DEPT)
δ 28.7 (CH), 39.4 (CH), 45.5 (Cq), 74.7 (CH2), 107.7 (CH), 110.4
(CH), 128.1 (CH), 128.6 (2 × CH), 128.9 (2 × CH), 133.3 (Cq),
141.9 (CH), 148.1 (Cq), 170.9 (CdO); GC-MS (70 eV) m/z 240
(M+, 7), 196 (100), 195 (57), 181 (47), 91 (10), 77 (12); FT-IR
(film, cm-1) 3044, 2927, 1732, 1448, 1247, 1035, 700. Anal.
Calcd for C15H12O3: C, 74.99; H, 5.03. Found: C, 74.68; H,
4.87.
(1R*,2R*,3S*)-Methyl-2-(hydroxymethyl)-3-(4-chloro-
phenyl)-2-phenylcyclopropanecarboxylate (9c): white solid;
1
mp 48-49 °C (Et2O), 81%; H NMR (300 MHz) δ 2.03 (br s,
exchanges with D2O, 1 H), 2.49 (d, J ) 5.9 Hz, 1 H), 3.34 (d,
J ) 11.8 Hz, 1 H), 3.40 (d, J ) 5.9 Hz, 1 H), 3.55 (s, 3 H), 3.70
(d, J ) 11.8 Hz, 1 H), 7.32-7.42 (m, 9 H); 13C NMR (75.4 MHz,
DEPT) δ 29.5 (CH), 33.8 (CH), 43.6 (Cq), 51.9(CH3), 66.4 (CH2),
127.7 (CH), 128.6 (Cq), 128.8 (2 × CH), 129.7 (2 × CH), 130.5
(2 × CH), 133.0 (2 × CH), 134.2 (Cq), 138.3 (Cq), 170.7 (CdO);
GC-MS (70 eV) m/z 318 (M+ + 2, 2), 316 (M+, 6) 298 (20), 241
(31), 239 (100), 180 (65), 137 (83), (31), 91 (53), 77 (15); FT-IR
(film, cm-1) 3407, 2927, 1739, 1447, 1277, 760, 700. Anal. Calcd
for C18H17ClO3: C, 68.25; H, 5.41. Found: C, 68.48; H, 5.28.
(-)-(1R,2R,3S)-9c: 87%; [R]20 ) -41.3 (c 1, CHCl3). (+)-
D
(1S,2S,3R)-9c: 87%;, [R]20 ) +41.8 (c 1, CHCl3).
D
(1′R*,1S*,2S*,3R*)-Methyl 2-[1-hydroxyethyl]-2,3-di-
phenylcyclopropanecarboxylate (9e): colorless oil, 88%; 1H
NMR (500 MHz) δ 0.85 (d, J ) 6.5 Hz, 3 H), 1.95 (br s,
exchanges with D2O, 1 H), 2.86 (d, J ) 6.2 Hz, 1 H), 3.29 (q,
J ) 6.5 Hz, 1 H), 3.47 (d, J ) 6.2 Hz, 1 H), 3.93 (s, 3 H), 7.35-
7.52 (m, 10 H); 13C NMR (125 MHz) δ 20.2, 30.4, 35.2, 47.1,
51.9, 70.7, 127.0, 127.5, 128.0, 128.5, 128.6, 130.8, 135.0, 136.5,
171.0; GC-MS (70 eV) m/z 296 (M+, 1), 278 (48), 219 (95), 190
(100), 158 (46), 134 (47), 91 (53), 77 (22); FT-IR (film, cm-1
)
3415, 3031, 2929, 1723, 1480, 1261, 754, 702. (-)-(1′S,1R,2R,-
3S)-9e: 88%; [R]20D ) -55.0 (c 1, CHCl3). (+)-(1′R,1S,2S,3R)-
9e: 85%; [R]20 ) +54.3 (c 1, CHCl3).
D
(1′R*,1R*,2R*,3S*)-Methyl 2-[1-hydroxyethyl]-3-(4-me-
thylphenyl)-2-diphenylcyclopropanecarboxylate (9g): col-
1
orless oil, 84%; H NMR (500 MHz) δ 1.15 (d, J ) 6.5 Hz, 3
H), 2.05 (br s, exchanges with D2O, 1 H), 2.35 (s, 3 H), 2.41 (d,
J ) 6.0 Hz, 1 H), 2.74 (q, J ) 6.5 Hz, 1 H), 3.30 (d, J ) 6.0 Hz,
1 H), 3.57 (s, 3 H), 7.08-7.36 (m, 9 H); 13C NMR (125 MHz) δ
20.4, 21.1, 29.7, 35.7, 46.7, 51.8, 69.6, 127.4, 127.9, 128.8, 129.3,
131.2, 132.2, 136.1, 136.8, 171.0; GC-MS (70 eV) m/z 310 (M+,
1), 292 (41), 233 (86), 190 (100), 158 (46), 134 (42), 105 (51);
FT-IR (film, cm-1) 3421, 3036, 2973, 2941, 1716, 1478, 1261,
841, 751, 702.
(1′R*,1S*,2S*,3R*)-Methyl-2-[hydroxy(phenyl)methyl]-
2,3-diphenylcyclopropanecarboxylate (9i): white solid; mp
1
75-76 °C (Et2O), 83%; H NMR (500 MHz) δ 3.05 (d, J ) 6.1
Hz, 1 H), 3.37 (d, J ) 6.1 Hz, 1 H), 3.55 (s, 3 H), 3.79 (br s,
exchanges with D2O, 1 H), 4.40 (s, 1 H), 6.08-6.11 (m, 2 H),
6.88-6.91 (m, 2 H), 7.03-7.39 (m, 11 H); 13C NMR (125 MHz)
δ 29.7, 35.7, 47.7, 51.9, 76.4, 126.7, 127.2, 127.4, 127.5, 128.0,
128.2, 128.5, 129.0, 131.2, 135.1, 136.8, 140.3, 171.0; GC-MS
(70 eV) m/z 358 (M+, 20), 281 (42), 252 (100), 220 (89), 191
(85), 165 (33), 105 (70), 77 (64); FT-IR (film, cm-1) 3583, 3406,
2954, 2915, 1731, 1455, 1377, 1168, 1025, 754, 699.
(1R*,2R*,3S*)-Methyl-2-(hydroxymethyl)-2,3-diphenyl-
cyclopropanecarboxylate (9a): white solid; mp 45-46 °C
(Et2O), 88%; 1H NMR (300 MHz) δ 2.11 (br s, exchanges with
D2O, 1 H), 2.53 (d, J ) 5.9 Hz, 1 H), 3.30 (d, J ) 11.8 Hz, 1
H), 3.42 (d, J ) 5.9 Hz, 1 H),3.55 (s, 3 H), 3.71 (d, J ) 11.8
Hz, 1 H), 7.22-7.42 (m, 10 H); 13C NMR (75.4 MHz, DEPT) δ
29.5 (CH), 33.6 (CH), 43.5 (Cq), 51.8(CH3), 66.7 (CH2), 127.5
(CH), 127.6 (2 × CH), 128.0 (2 × CH), 128.2 (CH), 128.5 (2 ×
CH), 128.7 (2 × CH), 134.2 (Cq), 138.3 (Cq), 170.3 (CdO); GC-
MS (70 eV) m/z 282 (M+,11) 264 (25), 205 (100), 146 (43), 91
(71), 77 (32); FT-IR (film, cm-1) 3429, 2923, 1737, 1516, 1441,
753, 700. Anal. Calcd for C18H18O3: C, 76.57; H, 6.43. Found:
C, 76.78; H, 6.28.
(1′R*,1R*,2R*,3S*)-Methyl 2-[hydroxy(phenyl)methyl]-
2,3-diphenylcyclopropanecarboxylate (9j): white solid; mp
1
69-70 °C (Et2O), 87%; H NMR (500 MHz) δ 2.86 (d, J ) 6.0
Hz, 1 H), 3.03 (br s, exchanges with D2O, 1 H), 3.40 (d, J )
6.0 Hz, 1 H), 3.46 (s, 3 H), 4.27 (s, 1 H), 6.80-6.95 (m, 4 H),
7.15-7.44 (m, 9 H), 7.56-7.59 (m, 2 H); 13C NMR (125 MHz)
δ 35.4, 47.9, 51.8, 67.6, 75.5, 126.3, 127.2, 127.3, 127.4, 127.7,
128.8, 128.9, 129.0, 131.5, 135.4, 135.5, 140.9, 170.4; GC-MS
(70 eV) m/z 358 (M+, 18), 281 (32), 249 (59), 220 (55), 196 (100),
165 (30), 105 (74), 77 (63); FT-IR (film, cm-1) 3570, 3425, 3059,
2955, 2921, 1735, 1448, 1237, 1166, 1013, 756, 700.
(1R*,2R*,3S*)-Methyl-2-(hydroxymethyl)-3-(4-meth-
oxyphenyl)-2-phenylcyclopropanecarboxylate (9b): white
1
solid; mp 53-54 °C (Et2O), 82%; H NMR (300 MHz) δ 2.20
(br s, exchanges with D2O, 1 H), 2.50 (d, J ) 5.8 Hz, 1 H),
3.40 (d, J ) 5.8 Hz, 1 H), 3.44 (d, J ) 11.9 Hz, 1 H),3.55 (s, 3
H), 3.75 (d, J ) 11.9 Hz, 1 H), 3.84 (s, 3 H), 6.86-6.95 (m, 2
H), 7.31-7.56 (m, 7 H); 13C NMR (75.4 MHz, DEPT) δ 29.4
(CH), 33.6 (CH), 43.5 (Cq), 51.7(CH3), 55.2 (CH3), 66.6 (CH2),
114.0 (2 × CH), 127.5 (CH), 128.5 (2 × CH), 129.7 (2 × CH),
129.9 (2 × CH), 133.0 (Cq), 138.6 (Cq), 158.6 (Cq), 170.9 (Cd
O); GC-MS (70 eV) m/z 312 (M+, 2), 294 (30), 235 (100), 221
(42), 176 (62), 137 (83), 121 (45), 105 (31), 91 (53), 77 (15);
FT-IR (film, cm-1) 3422, 2927, 1732, 1514, 1445, 1247, 1035,
700. Anal. Calcd for C19H20O4: C, 73.06; H, 6.45. Found: C,
73.16; H, 6.49.
3,4-Diphenylhex-3-ene-2,5-diol (11). (E, major diastere-
omer): white solid; mp 102-103 °C (Et2O); 26%; Rf 0.46 (Et2O,
silica gel); 1H NMR (400 MHz) δ 1.03 (d, J ) 6.4 Hz, 6 H),
1.65 (br s, exchanges with D2O, 2 H), 4.31 (q, J ) 6.4 Hz, 2
H), 7.22-7.39 (m, 10 H); 13C NMR (100 MHz) δ 22.2, 67.5,
127.3, 128.1, 129.9, 136.3, 141.8; GC-MS (70 eV) m/z 268 (M+,
4), 250 (15), 207 (100), 178 (51), 129 (58), 91 (26); FT-IR (film,
cm-1) 3281, 2967, 2925, 1600, 1442, 1370, 1113, 1065, 748, 700.
(Z, minor diastereomer): colorless oil; 9%; Rf 0.38 (Et2O, silica
1
gel); H NMR (400 MHz) δ 1.29 (d, J ) 6.4 Hz, 6 H), 1.62 (br
s, exchanges with D2O, 2 H), 5.12 (q, J ) 6.4 Hz, 2 H), 6.93-
7.09 (m, 10 H); 13C NMR (100 MHz) δ 23.0, 67.2, 126.2, 127.4,
J. Org. Chem, Vol. 70, No. 15, 2005 5857

Capriati et al.
130.2, 138.5, 142.7; GC-MS (70 eV) m/z 268 (M+, 2), 250 (21),
207 (100), 178 (43), 129 (15), 77 (18); FT-IR (film, cm-1) 3356,
2922, 1657, 1598, 1442, 1115, 752, 700.
are also grateful to Dr. Michel Giorgi of the Centre
Scientifique Saint-Jerome, Marseille, France, for per-
forming the X-ray analysis of compound 6i.
Acknowledgment. This work was carried out under
the framework of the National Project “Stereoselezione
in Sintesi Organica. Metodologie ed Applicazioni” and
the FIRB Project “Progettazione, preparazione e valuta-
zione biologica e farmacologica di nuove molecole orga-
nizzazione quali potenziali farmaci innovativi” sup-
ported by the MIUR (Rome), by the University of Bari,
and by the Interuniversities Consortium CINMPIS. We
Supporting Information Available: General experimen-
1
tal methods; copies of H or 13C NMR spectra for compounds
6d-f,h-k, 9e,g,i,j, 10, and (E)- and (Z)-11; ORTEP view and
CIF file for compound 6i. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO050443R
5858 J. Org. Chem., Vol. 70, No. 15, 2005