Deprotonation of oxazolinyloxiranes: Formation of substituted acyloxiranes

Article abstract of DOI:10.1002/(sici)1099-0690(199902)1999:2<409::aid-ejoc409>3.0.co;2-z

Deprotonation of oxazolinyloxiranes 1a, 1h, and 1k with sBuLi/TMEDA at - 100 °C in Et₂O furnishes oxazolinyloxiranyllithium compounds 1b, 1i, and 1I which are stable at low temperature and can be trapped with electrophiles to give substituted oxiranes 1c-1g and 1j. The reaction of 1b with aldehydes produced diastereomers syn (2a-d) and anti (3a-d). Oxiranyllithium 1i from trans-1-(4,4-dimethyl-2-oxazolinyl)-2-p-tolylepoxy-ethane (1h) was found to be configurationally stable while oxiranyllithium 1l, generated from the cis isomer 1k, was not. Oxazolinylepoxides 1d, 1j, and 1m could be deblocked to acyloxiranes 5a-e through oxazolidines 4a-e.

Full text of DOI:10.1002/(sici)1099-0690(199902)1999:2<409::aid-ejoc409>3.0.co;2-z

FULL PAPER
Deprotonation of Oxazolinyloxiranes: Formation of Substituted Acyloxiranes
Saverio Florio,*[a] Vito Capriati,[a] Serena Di Martino,[a] and Alessandro Abbotto[b]
Keywords: Deprotonation / Oxiranyloxazolines / Oxazolinyloxiranyllithium compounds / Oxazolidines / Acyloxiranes
(3a–d). Oxiranyllithium 1i from trans-1-(4,4-dimethyl-2-
Deprotonation of oxazolinyloxiranes 1a, 1h, and 1k with
sBuLi/TMEDA at –100 °C in Et2O furnishes oxazolinyl-
oxiranyllithium compounds[1] 1b, 1i, and 1l which are stable
at low temperature and can be trapped with electrophiles to
give substituted oxiranes 1c–1g and 1j. The reaction of 1b
with aldehydes produced diastereomers syn (2a–d) and anti
oxazolinyl)-2-p-tolylepoxy-ethane (1h) was found to be
configurationally stable while oxiranyllithium 1l, generated
from the cis isomer 1k, was not. Oxazolinylepoxides 1d, 1j,
and 1m could be deblocked to acyloxiranes 5a–e through
oxazolidines 4a–e.
α,β-Epoxy aldehydes and ketones are particularly attrac- be applied to epoxides bearing masked carbonyl groups as
tive intermediates to be used for synthetic purposes. Indeed, illustrated in the retrosynthetic approach of Scheme 1.
the elaboration of the epoxy moiety or the carbonyl func-
tion or both, has allowed the preparation of a number of
useful compounds such as vinyl iodides,[2] α,β-unsaturated
aldehydes,[3] butyrolactones and furanones,[4] β-lactam
antibiotics via chiral α,β-epoxyimines,[5] chiral β,γ-epoxy al-
cohols,[6aϪ6d] 1,2- and 1,3-diols,[7a] 1,2,3-triols,[7b] 1,2-cyclo-
Scheme 1. Retrosynthetic approach
hexanediols,[8] aldols,[9a] and 1,3-cyclohexanediols,[9b] hy-
droxy-substituted tetrahydrofurans,[10] 2-deoxyhexoses.[11]
In the present paper we report on a novel synthesis of
substituted acyloxiranes based on the deprotonationϪalkyl-
ationϪdeblocking sequence of certain oxiranyloxazolines.
α,β-Epoxy aldehydes and ketones are usually prepared by
oxidation of epoxy alcohols.[5,6a,9a,12,13] An alternative route
relies upon the epoxidation of α,β-unsaturated carbonyl
compounds.[7a,14aϪ14e] An asymmetric synthesis of optically
active α,β-epoxy aldehydes from α,β-unsaturated acids has
also been described.[15]
Results and Discussion
When treated with sBuLi/TMEDA in Et2O at Ϫ100°C,
the oxiranyloxazoline 1a, prepared from 2-chloromethyl-
4,4-dimethyl-2-oxazoline according to a method described
in ref.[17], underwent rapid lithiation which was complete in
a few minutes to generate 1b, which turned out to be stable
and could be trapped with Me3SiCl to give 1c. The reaction
of 1a with lithium diisopropylamide (LDA) in THF and
Me3SiCl gave a much lower yield of 1c (27%). The alkyl-
ation of 1b with MeI and allyl bromide led to compounds
1d and 1e, respectively, in good yields. Furthermore, the re-
action of 1a with sBuLi/TMEDA followed by the addition
of acetone and cyclohexanone afforded epoxy alcohols 1f
and 1g, respectively (Table 1).
The coupling reaction of 1b with acetaldehyde furnished
diastereomeric hydroxyethyl oxazolinyl epoxides 2a and 3a
as a 1.3:1 mixture (Table 2) which could be easily separated
by column chromatography. The isomer 2a, which was as-
signed the syn configuration (see below), had a less polar
character than the anti isomer 3a (∆Rf ϭ 0.37 on TLC,
petroleum ether/AcOEt, 7:3). This could be tentatively ex-
plained in terms of intramolecular hydrogen bonds between
the OH and the epoxy groups.[18] The intramolecularly as-
sociated conformation of the syn isomer 2a should be more
easily attainable than the hydrogen-bonded conformation
of the anti isomer 3a, for steric reasons. These consider-
Among the many routes to substituted epoxides now
available, one method which has not yet been fully devel-
oped is the coupling reaction of oxiranyl anions with elec-
trophiles. Such a strategy relies on the presence on the epox-
ide moiety of functional groups capable of stabilizing the
carbanionic species that can be generated by deprotonation
of simpler derivatives. Some oxiranyllithium compounds
have been reported as synthetically useful in the func-
tionalization of oxiranes.[16aϪ16i]
We have recently reported an efficient synthesis of formyl
epoxides based on the preparation of oxazolinyl epoxides
and subsequent elaboration of the oxazolinyl moiety to the
formyl group.[17] The deprotonationϪalkylation sequence
of α,β-epoxy carbonyl groups as a route to more func-
tionalized derivatives, of course, is not practicable in view of
the fact that metallating agents would attack the carbonyl
function. We envisaged that, perhaps, such a strategy could
[a]
Centro C.N.R. “M.I.S.O.”, Dipartimento Farmaco-Chimico,
`
Universita di Bari,
Via E. Orabona 4, I-70126 Bari, Italy
E-mail: florio@farmchim.uniba.it
[b]
`
Dipartimento di Scienza dei Materiali, II Universita degli Studi
di Milano Ϫ Bicocca,
Via Emanueli 15, I-20126 Milano, Italy
Eur. J. Org. Chem. 1999, 409Ϫ417
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0202Ϫ0409 $ 17.50ϩ.50/0
409

S. Florio, V. Capriati, S. Di Martino, A. Abbotto
FULL PAPER
Table 1. Deprotonation of 1a and reaction with electrophiles
energy of which (∆Hf ϭ Ϫ32.3 kcal molϪ1) matched per-
fectly that of the previously obtained minima, showing that
this structure belongs to the set of minimum-energy confor-
mations as well. Hydrogen bonding involving the epoxy
˚
unit is 2.6 A; the OϪCϪCϪO torsion angle θ (θ as defined
in Figure 1) is about 40°. An analogous partial optimization
performed for the anti isomer showed similar intramolecu-
˚
lar hydrogen bonding (2.5 A; θ ϭ 45°). However, in this
case the computed energy was higher by 2 kcal molϪ1 than
that of the anti minimum-energy conformations. In fact,
steric hindrance between the methyl group adjacent to the
OH function and both the oxazolinyl and one of the phenyl
E
Compound
Conversion (%)[a]
Yield (%)[b]
(CH3)3Si
CH3
1c
1d
> 95
> 95
69
62
70
95
62
76
67
79
˚
CH2ϭCHCH2 1e
rings (2.6Ϫ2.7 A) is the source of the decreased stability. In
(CH3)2COH
(CH2)5COH
1f
1g
other words the stabilizing term coming from a favoured
hydrogen bonding is counterbalanced by destabilizing
steric factors.
It is known that PM3 calculations predict geometries
rather successfully, but underestimate intra- and intermolec-
ular nonbonding interactions. In particular, it has been re-
[a] This value arises from the following ratio: (initial reacting moles
Ϫ residual moles)/initial reacting moles. Ϫ
material.
[b]
Based on converted
ations are supported by the infrared spectral data of the OH cently shown[21] that nonbonding intermolecular interac-
group at high dilution (5.0 · 10Ϫ3 , where intermolecular tions such as coordination bonds to molecules of solvent
hydrogen bonds are supposed not to take place). The syn are generally computed by the PM3 approach to be smaller
isomer 2a showed a broad strongly bonded OH band at by 1Ϫ5 kcal molϪ1 with respect to high-level ab initio calcu-
3411 cmϪ1. No frequence shift was observed at higher con- lations which include electron correlation. If we keep this
centrations (10Ϫ2 and 10Ϫ1 ). In contrast, the anti isomer in mind, we can expect the structures showing hydrogen
3a gave a significant sharp band at 3616 cmϪ1 ascribed to
a free OH group.[18,19] In KBr, the band at 3616 cmϪ1 of
3a was shifted to 3236 cmϪ1, while the band at 3411 cmϪ1
of 2a remained substantially unaffected.
Semiempirical calculations[20] were performed in order to
assess the preferred conformations and the relative stabilit-
ies of the syn and anti diastereoisomers 2a and 3a. Two
local minima were found for the syn isomer 2a, both show-
ing favourable hydrogen-bonding interactions. The two con-
formations differ very little in energy (heats of formation
are Ϫ33.1 and Ϫ32.4 kcal molϪ1), the relative difference
being within the usual computational error. The distance
between the hydroxy group and the epoxy oxygen atom
˚
ranges from 2.6 to 2.8 A. Two local minima have also been
found for the anti isomer 3a (∆Hf ϭ Ϫ32.5 and Ϫ32.4 kcal
molϪ1). Although their energies compare well with those of
the syn isomer, in this case the distance between the OH
group and the epoxy oxygen atom is too large (higher than
˚
3.6 A) to observe hydrogen bonding. Note that a favourable
interaction between the OH group and the oxazolinyl ring
was never observed in any of the optimized conformations
of the syn and anti isomers.
We wanted to investigate in more detail the reason for
the different behavior of the two diastereoisomers. We ap-
proached the study by performing a partial geometry opti-
mization for both the syn and anti isomers, in which an
antiperiplanar arrangement between the oxazolinyl ring
and the hydroxy group with respect to the bond linking the
two stereogenic centers was imposed. Such a situation
should favour the formation of a hydrogen bond between
the OH function and the epoxy oxygen atom. The optim-
ized structures obtained are shown in Figure 1. The compu-
tation for the syn isomer resulted in a new geometry, the diastereomers 2a and 3a
Figure 1. MinimumϪenergy conformations of the syn and anti
410
Eur. J. Org. Chem. 1999, 409Ϫ417

Deprotonation of Oxazolinyloxiranes: Formation of Substituted Acyloxiranes
FULL PAPER
bonding (all of the stable syn conformations and the par- Table 2. Reaction of 1b with aldehydes
tially optimized anti geometry) to have an absolute lower
energy than that computed. We can therefore conclude that
all of the stable syn conformations (one of which is reported
in Figure 1) involve hydrogen bonding and have a lower
energy with respect to the anti diastereoisomer. The hydro-
gen-bonded anti conformation shown in Figure 1 probably
R
Compound Conversion Overall yield dr[b]
(%)
(%)[a]
syn/anti
compares well with the other minimum-energy anti struc-
tures, where hydrogen bonding is absent, but is not particu-
larly favoured since it suffers from implicit steric interac-
tions.
CH3
2a/3a
> 95
83
> 95
83
68
65
83
70
1.3:1
1.2:1
1:1
(CH3)2CH 2b/3b
C6H5
2c/3c
2d/3d
1
Support for the above considerations came from the H-
p-Tolyl
1.8:1
NMR chemical shift analysis. In the case of the syn isomer,
which is intramolecularly hydrogen-bonded, the hydroxy
proton resonance was strongly downfield (δ ϭ 4.5 versus
2.4Ϫ2.7 for the anti isomer).[22] On the other hand, the
characteristic Ha proton (Figure 2) of the anti isomer 3a
absorbs at lower field than that of the syn isomer 2a, as
reported for similar epoxy alcohols.[23] Moreover, for the
syn isomer, the two geminal protons of the oxazoline ring
have a chemical shift difference in Hertz (∆ν) much larger
than the coupling constant (∆ν/J > 10, AX system); the anti
isomer showed two doublets with a ∆ν/J < 10 (AB system).
This probably could be due to the anisotropy of the methyl
group on the same side of the two methylene protons that
creates different magnetic environments (Figure 2). The
steric compression of the methyl group in 3a compared to
that in 2a is well reflected in the 13C-NMR spectrum: The
Me group signal in 3a appears at higher field (δ ϭ 18.27)
with respect to that in 2a (δ ϭ 19.71).[24]
[a]
[b]
Based on converted material. Ϫ
Diastereomeric ratio, deter-
mined by weighing the isolated syn and anti diastereomers after
column chromatography.
stable than the cis one. Starting trans-epoxide 1h was quan-
titavely recovered upon quenching of 1i with NH4Cl and
the reaction with MeI gave the (E)-oxirane 1j[25a,25b] (93%
yield). In contrast, lithiated intermediate 1l from the cis iso-
mer 1k furnished a mixture of the isomers 1h and 1k upon
acidic quenching in a 1.2:1 ratio (Scheme 2). This clearly
indicates that the lithiated intermediate generated from 1k
is configurationally unstable. Such a different configura-
tional stability has been reported for other oxiranyl an-
ions.[1,26a,26b]
Scheme 2. Deprotonation of oxazolinyloxiranes 1h and 1k and re-
actions with electrophiles
Figure 2. 1H-NMR chemical shift analysis of syn and anti diastere-
omers 2a and 3a
Comparable results were obtained when 1b was treated
The oxazolinyloxiranes above appear particularly useful
with other aldehydes. Indeed, the reaction with isobutyral- as they can be deblocked to formyl- and acyloxiranes (Table
dehyde, benzaldehyde, and p-tolualdehyde gave the di- 3). Indeed, treatment of oxiranyl epoxide 1d first with
astereomeric epoxy alcohols 2b and 3b, 2c and 3c, 2d and CF3SO3Me and then with PhMgBr · 2 HMPT afforded oxi-
3d, respectively (Table 2). All these compounds could be ranyloxazolidines 4a (inseparable mixture of diastereomers)
separated and characterized as in the case of 2a and 3a.
that could be elaborated in the oxazolidine moiety to fur-
It was interesting to observe that the deprotonation nish benzoyloxirane 5a. Similarly, methylation of 1d with
of trans-1-(4,4-dimethyl-2-oxazolinyl)-2-p-tolylepoxyethane CF3SO3Me followed by the addition of MeMgBr · 2 HMPT
(1h)[17] (Scheme 2) with sBuLi/TMEDA gave the oxiranyl- gave oxazolidines 4b (isolated isomers) which were sub-
lithium 1i which was configurationally stable for at least sequently deblocked to acetyloxirane 5b. In the reaction of
1 h at Ϫ100°C. At present we cannot exclude that, under 1d with cyclohexylMgCl · 2 HMPT, this Grignard reagent,
equilibrating conditions, the trans anion is much more for steric reasons, did not add to the preliminary activated
Eur. J. Org. Chem. 1999, 409Ϫ417
411

S. Florio, V. Capriati, S. Di Martino, A. Abbotto
FULL PAPER
calcium hydride. Petroleum ether refers to the 40Ϫ60°C boiling
fraction. Commercial solutions of nBuLi (as a solution in hexanes),
sBuLi (cyclohexane/hexane, 92:8 solution), CH3MgBr (3.0  solu-
tion in Et2O), PhMgBr (3.0  solution in Et2O), and (cyclohex-
yl)MgCl (2.0  solution in Et2O) from Aldrich were titrated by
using N-pivaloyl-o-toluidine prior to use.[28] All other chemicals
were of commercial grade (Aldrich) and distilled just prior to use.
2-Chloromethyl-4,4-dimethyl-2-oxazoline[29] and 2-(1-chloroethyl)-
4,4-dimethyl-2-oxazoline[30] were prepared as reported. Ϫ NMR:
Varian EM 390, Varian XL-200 (200 MHz and 50.3 MHz, for 1H
and 13C, respectively), Bruker (300 MHz for 1H). For 1H NMR,
imine π-system with CF3SO3Me, but transferred a hydride
ion to give oxazolidine 4c (substantially one diastereomer)
which was converted into formyloxirane 5c upon hydrolysis
with aqueous oxalic acid. The methylationϪadditionϪdeb-
locking sequence applied to oxiranyloxazolines 1j and 1m
afforded acetyloxiranes 5d and 5e, respectively, going
through oxazolidines 4d (inseparable mixture of dia-
stereomers) and 4e (substantially one diastereomer). In
both cases, the stereochemistry at the oxirane moiety was
perfectly preserved (Table 3).
Table 3. Deblocking of oxazolinyloxiranes 1d, 1j, and 1m to formyl- and acyloxiranes 5a؊e
Overall yield (%)[a]
Yield (%)
4a R1 ϭ R2 ϭ R3 ϭ Ph
77 ( d.r.1.5:1)[b,c]
95 ( d.r. 4:1)[b,e]
5a R1 ϭ R2 ϭ R3 ϭ Ph
69[d]
77[f]
77[a]
1d R1 ϭ R2 ϭ Ph
4b R1 ϭ R2 ϭ Ph; R3 ϭ Me
4c R1 ϭ R2 ϭ Ph; R3 ϭ H
5b R1 ϭ R2 ϭ Ph; R3 ϭ Me
1j R1 ϭ p-Tolyl; R2 ϭ H
51 (d.r. Ն 95:5)[b,g] 5c R1 ϭ R2 ϭ Ph; R3 ϭ H
1m R1 ϭ H; R2 ϭ p-Tolyl 4d R1 ϭ p-Tolyl; R2 ϭ H; R3 ϭ Me 95 (d.r. 4:1)[b,c]
5d R1 ϭ p-Tolyl; R2 ϭ H; R3 ϭ Me 40[h]
4e R1 ϭ H; R2 ϭ p-Tolyl; R3 ϭ Me 78 (d.r. Ն 95:5)[b,g] 5e R1 ϭ H; R2 ϭ p-Tolyl; R3 ϭ Me 40[h]
1
[a] Yield of isolated material. Ϫ [b] Diastereomeric ratio, determined by H-NMR analysis on the crude reaction mixture; error ± 5% of
the stated values. Ϫ [c] Inseparable mixture of diastereomers. Ϫ [d] Based on 33% conversion. Ϫ [e] Isolated diastereomeric oxazolidines;
see Experimental Section. Ϫ [f] Yield determined by 1H-NMR analysis on the crude reaction mixture.[26]
Ϫ
[g] Only one diastereomer was
1
detected by H NMR. Ϫ [h] Based on 50% conversion.
CDCl3 as solvent, δH ϭ 7.24, TMS as internal standard; for 13C
NMR, CDCl3 δC ϭ 77.0, [D6]acetone δC ϭ 20.83. Ϫ IR: Perkin
Elmer 283. Ϫ FTIR: Perkin Elmer 1600. Ϫ GC-MS spectrometry
analyses were performed with a gas cromatograph HP 5995C (di-
methylsilicon capillary column, 30 m, 0.25 mm i.d.) equipped with
a mass-selective detector operating at 70 eV (EI). Ϫ Microanalyses
were performed with a Carlo Erba Mod. 1106 C, H, N analyzer.
Melting points are uncorrected. TLC was performed on Merck sil-
ica gel plates with F-254 indicator; visualization was accomplished
by UV light (254 nm). Column chromatography was performed by
using silica gel (70Ϫ230 mesh) with petroleum ether/diethyl ether
(or AcOEt) mixtures as the eluent. A Ϫ100°C bath refers to a
mixture of liquid nitrogen and methanol; the temperature was con-
trolled with a spirit-filled low-temperature thermometer (Aldrich)
and kept at a fixed value by adding liquid nitrogen from time to
time. All reactions involving air-sensitive reagents were performed
under nitrogen in oven-dried glassware using syringe-septum cap
techniques. All products, of course, were racemates.
Finally it is worth noting that the (E)-oxiranyloxazoline
1j, as well as 1d, could also be synthesized in a single-step
sequence from the intermediate chlorohydrins (syn-6 and 8,
see Experimental Section) obtained in the reaction of 2-(1-
chloroethyl)-4,4-dimethyl-2-oxazoline[30] with LDA and p-
tolualdehyde or benzophenone, respectively, following a
procedure reported for similar systems.[17]
Scheme 3. Chlorohydrins syn-6, anti-7, 8 and 3,3-diphenylpentane-
2,4-dione 9
Preparation of Oxiranyloxazolines 1a, 1h, and 1k: These oxazolines
were prepared according to the procedure reported in ref.[17] and
showed the following data:
In conclusion, in this paper we have shown how variously
substituted oxazolinyloxiranes can be efficiently prepared
upon deprotonation of their simpler parent epoxides and
the resulting oxazolinyloxiranes can be deblocked to acyl-
oxiranes. More work is in progress to apply this method-
ology to an asymmetric synthesis of acyl epoxides.[27]
1-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-2,2-diphenylethane (1a):
Yellow oil. Ϫ 1H NMR (200 MHz): δ ϭ 0.92 (s, 3 H), 1.13 (s, 3
H), 3.59 (d, J ϭ 8.0 Hz, 1 H), 3.75 (d, J ϭ 8.0 Hz, 1 H), 4.02 (s, 1
H), 7.23-7.35 (m, 6 H), 7.43Ϫ7.48 (m, 4 H). Ϫ 13C NMR (50.3
MHz, CDCl3): δ ϭ 27.63, 27.95, 59.24, 66.30, 67.20, 79.22, 126.72,
127.86, 127.99, 128.00, 128.22, 128.30, 135.63, 138.77, 159.86. Ϫ
GC-MS (70 eV); m/z (%): 293 (58) [Mϩ], 264 (119), 238 (145), 208
(1000), 182 (109), 166 (163), 165 (823), 105 (199), 77 (211). Ϫ FTIR
(film): ν˜ ϭ 3048 cmϪ1, 2954, 1672 (CϭN), 1654, 1443, 1255, 984,
755, 696.
Experimental Section
General: Tetrahydrofuran (THF) and diethyl ether (Et2O) were
freshly distilled under nitrogen from sodium benzophenone ketyl.
TMEDA and diisopropylamine were distilled from finely powdered
(E)-1-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-2-p-tolylethane (1h):
1
Oil. Ϫ H NMR (90 MHz): δ ϭ 1.32 (s, 3 H), 1.35 (s, 3 H), 2.37
412
Eur. J. Org. Chem. 1999, 409Ϫ417

Deprotonation of Oxazolinyloxiranes: Formation of Substituted Acyloxiranes
FULL PAPER
(s, 3 H), 3.61 (d, J ϭ 1.5 Hz, 1 H), 4.04 (s, 2 H), 4.13 (d, J ϭ 1.5 (qd, 1Jq ϭ 128.8, 3Jd ϭ 1.8 Hz, CH3CϪO), 21.16 (like qt, 1Jq
ϭ
Hz, 1 H), 7.23 (s, 4 H). Ϫ GC-MS (70 eV); m/z (%): 231 (28) [Mϩ],
216 (89), 176 (149), 146 (1000), 119 (163), 91 (191), 77 (112). Ϫ IR
(film): ν˜ ϭ 2960 cmϪ1, 1655 (CϭN), 1455, 1358, 1285, 985, 810.
126.4, 3Jt
ϭ 4.4 Hz, CH3ϪAr), 27.94 (CH3CϪN), 27.99
(CH3CϪN), 59.54 , 64.00 (mainly d with fine structure, 1Jd ϭ 175.5
1
Hz, CHϪO), 67.31, 79.14 (mainly t with fine structure, Jt ϭ 149.4
Hz, CH2ϪO), 126.47, 128.37, 131.07, 137.63, 161.75 (CϭN). Ϫ
GC-MS (70 eV); m/z (%): 245 (9) [Mϩ], 146 (1000), 91 (118), 43
(177). Ϫ FTIR (film): ν˜ ϭ 2968 cmϪ1, 1674, (CϭN), 1458, 1365,
1119, 1080, 808.
(Z)-1-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-2-p-tolylethane (1k):
Oil. Ϫ H NMR (90 MHz): δ ϭ 1.04 (s, 3 H), 1.15 (s, 3 H), 2.34
(s, 3 H), 3.74 (s, 2 H), 3.83 (d, J ϭ 5.2 Hz, 1 H), 4.20 (d, J ϭ 5.2
Hz, 1 H), 7.07Ϫ7.37 (m, 4 H). Ϫ GC-MS (70 eV); m/z (%): 231
1
(25) [Mϩ], 216 (85), 176 (138), 146 (1000), 119 (155), 91 (191), 77 General Procedure for the Lithiation of the Epoxyoxazolines 1a, 1h,
(122). Ϫ IR (film): ν˜ ϭ 2960 cmϪ1, 1670 (CϭN), 1510, 1455, 1245,
1k, and Reaction with Electrophiles: The deprotonation of 1a and
the reaction with MeI are described as an example. To a solution
of 1a (200 mg, 0.68 mmol) and TMEDA (0.82 mmol, 0.12 mL) in
10 mL of dry Et2O, under N2 at Ϫ100°C, 1.26  sBuLi (0.82 mmol,
0.65 mL) was added dropwise. The resulting yellow solution of the
putative oxiranyl anion was stirred at Ϫ100°C for 2 h. MeI (0.89
mmol) in 3 mL of Et2O was then added slowly. Stirring at Ϫ100°C
was continued for 1 h. Then the reaction mixture was allowed to
warm to room temp., quenched with sat. aq. NH4Cl and extracted
with Et2O (3 ϫ 10 mL). The combined organic layers were dried
with Na2SO4 and concentrated in vacuo. The residue was purified
by column chromatography (silica gel; petroleum ether/Et2O, 1:1)
to give 1d (190 mg, 62% yield). The same eluent was also used to
purify 1c, 1e, and 1f. In the case of 1g and for diastereomeric epoxy
alcohols 2a/3a, 2b/3b, 2c/3c, 2d/3d a 7:3 petroleum ether/AcOEt
mixture as the eluent was used. Ϫ 1d could also be prepared more
conveniently through the reaction of 2-(1-chloroethyl)-4,4-di-
methyl-2-oxazoline[30] with benzophenone in the presence of LDA
likewise as described in ref.[17] The chlorohydrin 8 was purified by
column chromatography (silica gel, petroleum ether/Et2O, 7:3)
(64% yield) and subsequently cyclized quantitatively to 1d in
NaOH/iPrOH.[25b] Ϫ The new compounds showed the following
data:
975, 800.
Preparation of Oxazolinyl Epoxides 1j and 1m: These epoxides were
prepared as described in ref.[17] from 2-(1-chloroethyl)-4,4-di-
methyl-2-oxazoline.[30] Ϫ A mixture of diastereomeric chloro-
hydrins syn-6 and anti-7 (Scheme 3) (1.3:1 syn/anti ratio,[25c] 71%
overall yield) was obtained when 2-(1-chloroethyl)-4,4-dimethyl-2-
oxazoline (1 mmol) was treated with LDA (1.2 mmol) and then
with p-tolualdehyde (1.2 mmol). Chlorohydrins 6 and 7 could be
separated by column chromatography (silica gel, hexane/AcOEt,
6:4) and converted quantitatively to (E)- and (Z)-[25a,25b]oxazolinyl
epoxides 1j and 1m, respectively. The chlorohydrins and the epox-
ides showed the following data:
syn-2-Chloro-2-(4,4-dimethyl-2-oxazolin-2-yl)-1-p-tolyl-1-propanol
(6): M.p. 104Ϫ106°C (hexane/AcOEt). Ϫ 1H NMR (200 MHz):
δ ϭ 1.31 (s, 3 H), 1.33 (s, 3 H), 1.62 (s, 3 H), 2.34 (s, 3 H), 4.04 (s,
2 H), 4.93 (br s, 1 H, exchanges with D2O), 5.14 (s, 1 H), 7.12Ϫ7.16
(m, 2 H), 7.34Ϫ7.38 (m, 2 H). Ϫ 13C NMR (50.3 MHz, CDCl3):
δ ϭ 21.18, 22.00, 27.85, 28.06, 66.00, 67.50, 78.14, 79.40, 128.26,
128.63, 134.32, 137.87, 166.28. Ϫ GC-MS (70 eV); m/z (%): 246
(522) [Mϩ Ϫ Cl], 228 (242), 161 (1000), 146 (420), 120 (402), 119
(562), 91 (718), 65 (215), 55 (229), 42 (218), 41 (232). Ϫ IR (KBr):
ν˜ ϭ 3300Ϫ3100 cmϪ1 (OϪH), 1655 (CϭN), 1440, 1275, 1065, 805.
Ϫ C15H20ClNO2 (281.78): calcd. C 63.94, H 7.15, N 4.97; found C
64.05, H 7.31, N 5.23.
1-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-1-trimethylsilyl-2,2-
diphenylethane (1c): M.p. 107Ϫ109°C (isooctane). Ϫ 1H NMR (200
MHz): δ ϭ Ϫ0.11 (s, 9 H), 0.76 (s, 3 H), 0.96 (s, 3 H), 3.59 and
3.62 (2ϫ d, AB system, J ϭ 8.0 Hz, 2 H), 7.17Ϫ7.30 (m, 6 H),
7.52Ϫ7.59 (m, 4 H). Ϫ 13C NMR (50.3 MHz, CDCl3): δ ϭ Ϫ2.59,
27.67, 27.97, 62.02, 66.96, 70.62, 78.90, 126.90, 127.25, 127.53,
127.56, 127.60, 127.78, 128.00, 139.32, 139.42, 162.89. Ϫ GC-MS
(70 eV); m/z (%): 365 (159) [Mϩ], 364 (519), 350 (149), 294 (112),
280 (411), 176 (168), 166 (140), 165 (403), 77 (107), 73 (1000). Ϫ
FTIR (KBr): ν˜ ϭ 3061 cmϪ1, 2963, 1644 (CϭN), 1358 , 1293, 1244,
845, 704, 623. Ϫ C22H27NO2Si (365.55): calcd. C 72.29 H 7.44, N
3.83; found C 72.60, H 7.74, N 3.63.
anti-2-Chloro-2-(4,4-dimethyl-2-oxazolin-2-yl)-1-p-tolyl-1-propanol
(7): M.p. 117Ϫ119°C (hexane/AcOEt). Ϫ 1H NMR (200 MHz):
δ ϭ 1.23 (s, 3 H), 1.29 (s, 3 H), 1.59 (s, 3 H), 2.32 (s, 3 H), 4.03 (s,
2 H), 4.62 (br. s, 1 H, exchanges with D2O), 5.08 (s, 1 H), 7.10Ϫ7.14
(m, 2 H), 7.29-7.33 (m, 2 H). Ϫ 13C NMR (50.3 MHz, CDCl3):
δ ϭ 21.20, 23.55, 27.83, 28.04, 67.46, 68.70, 77.67, 79.42, 128.24,
128.44, 134.12, 138.12, 165.63. Ϫ GC-MS (70 eV); m/z (%): 161
(38) [Mϩ Ϫ p-C6H4CHO], 148 (222), 146 (730), 120 (756), 119
(852), 96 (761), 91 (1000), 65 (340), 63 (283). Ϫ IR (KBr): ν˜ ϭ
3300Ϫ3100 cmϪ1 (OϪH), 1640 (CϭN), 1450, 1068.
Ϫ
2-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-1,1-diphenylpropane
(1d): M.p. 103Ϫ104°C (hexane). Ϫ 1H NMR (300 MHz): δ ϭ 0.87
(s, 3 H), 1.07 (s, 3 H), 1.43 (s, 3 H), 3.54 (d, J ϭ 8.0 Hz, 1 H), 3.69
(d, J ϭ 8.0 Hz, 1 H), 7.18Ϫ7.34 (m, 6 H), 7.47Ϫ7.51 (m, 4 H). Ϫ
13C NMR (50.3 MHz, CDCl3): δ ϭ 17.63, 27.72, 27.88, 62.92,
67.29, 70.48, 79.24 (CH2ϪO), 127.14, 125.49, 127.68, 127.81,
128.26, 137.92, 138.49, 163.03 (CϭN). Ϫ GC-MS (70 eV); m/z (%):
307 (13) [Mϩ], 208 (1000), 165 (666), 105 (130), 77 (193), 43 (271).
Ϫ FTIR (KBr): ν˜ ϭ 3044 cmϪ1, 2966, 1666 (CϭN), 1444, 1294,
1100, 966, 700. Ϫ C20H21NO2 (307.39): calcd. C 78.15, H 6.89, N
4.56; found C 78.16, H 6.86, N 4.56.
C15H20ClNO2 (281.78): calcd. C 63.94, H 7.15, N 4.97; found C
64.34, H 7.44, N 5.01.
(E)-2-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-1-p-tolylpropane
1
(1j): Yellow oil. Ϫ H NMR (300 MHz): δ ϭ 1.30 (s, 6 H), 1.33 (s,
3 H), 2.32 (s, 3 H), 4.00 (s, 2 H), 4.36 (s, 1 H), 7.12Ϫ7.21 (m, 4 H).
Ϫ
13C NMR (50.3 MHz, CDCl3): δ ϭ 13.80 (q, 1Jq ϭ 128.9 Hz,
CH3CϪO), 21.17 (mainly q with fine structure, 1Jq ϭ 126.8 Hz,
CH3ϪAr), 28.26 (2 ϫ CH3CϪN), 57.47, 62.33 (mainly d with fine
structure, 1Jd ϭ 176.3 Hz, CHϪO), 65.15, 79.54 (mainly t with fine
structure, 1Jt ϭ 149.5 Hz, CH2ϪO), 126.59, 128.86, 131.22, 137.82,
164.32. Ϫ GC-MS (70 eV); m/z (%): 245 (7) [Mϩ], 146 (999), 119
(137), 91 (155), 43 (228). Ϫ FTIR (film): ν˜ ϭ 2967 cmϪ1, 1656 (Cϭ
N), 1461, 1133, 1078, 967, 811.
4-(4,4-Dimethyl-2-oxazolin-2-yl)-4,5-epoxy-5,5-diphenyl-1-pentene
1
(1e): Oil. Ϫ H NMR (300 MHz): δ ϭ 0.87 (s, 3 H), 1.05 (s, 3 H),
1.94 (ddt, J ϭ 14.8, 5.7, 1.5 Hz, 1 H), 2.85 (ddt, J ϭ 14.8, 7.9, 1.0
Hz, 1 H), 3.53 and 3.69 (2 ϫ d, AB system, J ϭ 8.0 Hz, 2 H),
5.05Ϫ5.16 (3 m, 2 H), 5.75Ϫ5.93 (m, 1 H), 7.15Ϫ7.37 (m, 6 H),
7.48Ϫ7.54 (m, 4 H). Ϫ 13C NMR (APT, 50.3 MHz, CDCl3): δ ϭ
27.62 (CH3), 27.84 (CH3), 35.98 (CH2ϪCϭ), 65.65, 67.28, 70.39,
(Z)-2-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-1-p-tolylpropane
1
(1m): Yellow oil. Ϫ H NMR (300 MHz): δ ϭ 0.94 (s, 3 H), 1.01
(s, 3 H), 1.64 (s, 3 H), 2.25 (s, 3 H), 3.62 (s, 2 H), 3.91 (s, 1 H),
7.01Ϫ7.20 (2 m, 4 H). Ϫ 13C NMR (50.3 MHz, CDCl3): δ ϭ 20.54
Eur. J. Org. Chem. 1999, 409Ϫ417
413

S. Florio, V. Capriati, S. Di Martino, A. Abbotto
FULL PAPER
76.37 (CH2ϪO), 118.36 (CH2ϭ), 127.10, 127.13, 127.53, 127.77,
syn-2-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-4-methyl-1,1-di-
1
128.30, 131.83 (CHϭ), 137.64, 138.22, 161.54 (CϭN). Ϫ GC-MS phenyl-3-pentanol (2b): Oil. Ϫ H NMR (200 MHz): δ ϭ 0.94 and
(70 eV); m/z (%): 333 (5) [Mϩ], 332 (3), 208 (1000), 165 (558), 105
(135), 77 (191), 41 (271). Ϫ FTIR (film): ν˜ ϭ 3055 cmϪ1 (OH),
1664 (CϭN), 1488, 1444, 1361, 1300, 966, 916, 750, 700, 627.
0.96 (2 ϫ d, J ϭ 6.6 Hz, 6 H), 1.05 (s, 3 H), 1.08 (s, 3 H), 1.73Ϫ1.90
(m, 1 H), 2.74 (d, J ϭ 8.7 Hz, 1 H), 3.27 (d, J ϭ 8.2 Hz, 1 H), 3.73
(d, J ϭ 8.2 Hz, 1 H), 4.1Ϫ4.3 (br. s, 1 H, exchanges with D2O),
7.20Ϫ7.37 (2 m, 6 H), 7.49Ϫ7.64 (2 m, 4 H). Ϫ 13C NMR (APT,
50.3 MHz, CDCl3): δ ϭ 18.54 (CH3ϪCH), 19.27 (CH3ϪCH),
27.75 (CH3), 27.84 (CH3), 33.37 (CHϪCHOH), 66.12, 67.75, 69.76,
76.50 (CHϪOH), 78.61 (CH2ϪO), 127.02, 127.27, 127.67, 127.90,
128.34, 137.13, 138.26, 161.91 (CϭN). Ϫ GC-MS (70 eV); m/z (%):
365 (9) [Mϩ], 322 (252), 294 (65), 208 (1000), 165 (617), 105 (223),
77 (167), 55 (242), 43 (199), 41 (248). Ϫ FTIR (film): ν˜ ϭ 3404
cmϪ1 (OH), 3056, 1644 (CϭN), 1461, 1394, 1083, 1044, 972, 750,
700, 622.
3-(4,4-Dimethyl-2-oxazolin-2-yl)-3,4-epoxy-2-methyl-4,4-diphenyl-2-
butanol (1f): M.p. 117Ϫ119°C (isooctane). Ϫ 1H NMR (200 MHz):
δ ϭ 0.85 (s, 3 H), 0.94 (s, 3 H), 1.13 (s, 3 H), 1.41 (s, 3 H), 2.55
(br. s, 1 H, exchanges with D2O), 3.51 and 3.63 (2 ϫ d, AB system,
J ϭ 8.0 Hz, 2 H), 7.15Ϫ7.35 (m, 6 H), 7.52Ϫ7.62 (2 m, 4 H). Ϫ
13C NMR (APT, 50.3 MHz, CDCl3): δ ϭ 26.96 (CH3), 27.03
(CH3), 27.47 (CH3), 27.54 (CH3), 67.22, 70.90, 71.26, 78.90
(CH2ϪO), 126.56, 126.76, 127.41, 127.71, 127.81, 128.37, 138.33,
139.42, 161.42 (CϭN). Ϫ GC-MS (70 eV); m/z (%): 351 (2) [Mϩ],
336 (1000), 294 (74), 292 (108), 208 (602), 165 (627), 105 (187), 77
(157), 59 (464). Ϫ FTIR (KBr): ν˜ ϭ 3500Ϫ3200 cmϪ1 (OH), 3061,
1667 (CϭN), 1528, 1450, 1361, 1178, 1028, 961, 906, 739. Ϫ
C22H25NO3 (351.44): calcd. C 75.19, H 7.17, N 3.98; found C
75.15, H 7.33, N 3.58.
anti-2-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-4-methyl-1,1-di-
phenyl-3-pentanol (3b): White solid, m.p. 142Ϫ144°C (isooctane).
1
Ϫ H NMR (200 MHz): δ ϭ 0.73 (s, 3 H), 0.89 and 0.92 (2 ϫ d,
J ϭ 6.6 Hz, 6 H), 1.04 (s, 3 H), 1.80Ϫ1.90 (br. s, 1 H, exchanges
with D2O), 1.91Ϫ2.08 (m, 1 H), 3.42 (d, J ϭ 7.3 Hz, 1 H), 3.65 (s,
2 H), 7.16Ϫ7.36 (m, 6 H), 7.51Ϫ7.58 (2 m, 4 H). Ϫ 13C NMR
1-(4,4-Dimethyl-2-oxazolin-2-yl)-1,2-epoxy-1-(1-hydroxy-1-cyclo-
(APT, 50.3 MHz, CDCl3):
δ ϭ 17.92 (CH3ϪCH), 19.84
1
hexyl)-2,2-diphenylethane (1g): Paste. Ϫ H NMR (200 MHz): δ ϭ
(CH3ϪCH), 27.45 (CH3), 27.73 (CH3), 31.27 (CHϪCHOH), 67.01,
68.51, 71.17, 75.35 (CHϪOH), 79.07 (CH2ϪO), 127.12, 127.19,
127.68, 127.80, 127.97, 128.28, 137.30, 138.37, 160.01 (CϭN). Ϫ
GC-MS (70 eV); m/z (%): 365 (7) [Mϩ], 322 (358), 208 (1000), 180
(132), 165 (481), 105 (164), 77 (137), 55 (134), 43 (107), 41 (113).
Ϫ FTIR (KBr): ν˜ ϭ 3605 cmϪ1 (sharp, OH free), 3250 (broad, OH
bonded), 1661 (CϭN), 1447, 1365, 1054, 977, 759, 704, 627. Ϫ
C23H27NO3 (365.47): calcd. C 75.59, H 7.45, N 3.83; found C
75.98, H 7.85, N 3.7.
0.85 (s, 3 H), 0.91 (s, 3 H), 1.16Ϫ1.55 (m, 8 H), 1.73Ϫ1.91 (m, 2
H), 2.1 (br. s, 1 H, exchanges with D2O), 3.49 and 3.61 (2 ϫ d, AB
system, J ϭ 8.0 Hz, 2 H), 7.13Ϫ7.33 (m, 6 H), 7.50Ϫ7.61 (2 m, 4
H). Ϫ 13C NMR (APT, 50.3 MHz, CDCl3): δ ϭ 21.10 (CH2), 21.29
(CH2), 25.44 (CH2), 27.50 (CH3), 27.52 (CH3), 33.71 (CH2), 34.26
(CH2), 67.19, 70.93, 71.26, 72.30, 78.73 (CH2ϪO), 126.58, 126.67,
127.31, 127.59, 127.75, 128.33, 138.65, 139.57, 161.25 (CϭN). Ϫ
GC-MS (70 eV); m/z (%): 391 (88) [Mϩ], 390 (231), 348 (156), 292
(175), 244 (255), 209 (386), 208 (591), 165 (728), 99 (1000), 81 (493),
55 (314), 41 (265). Ϫ FTIR (KBr): ν˜ ϭ 3600Ϫ3200 cmϪ1 (OH),
1640 (CϭN), 1440, 1360, 1260, 742, 700.
syn-2-(4,4-Dimethyl-2-oxazolin-2-yl)-2,3-epoxy-1,3,3-triphenyl-1-
1
propanol (2c): M.p. 140Ϫ142°C (hexane). Ϫ H NMR (300 MHz):
δ ϭ 0.90 (s, 3 H), 0.99 (s, 3 H), 3.08 (d, J ϭ 8.1 Hz, 1 H), 3.45 (d,
J ϭ 8.1 Hz, 1 H), 4.34 (s, 1 H), 5.55 (br. s, 1 H, exchanges with
D2O), 7.18Ϫ7.31 (m, 7 H), 7.35Ϫ7.40 (m, 2 H), 7.44Ϫ7.46 (m, 2
H), 7.52Ϫ7.55 (m, 2 H), 7.72Ϫ7.78 (m, 2 H). Ϫ 13C NMR (APT,
50.3 MHz, CDCl3): δ ϭ 27.56 (CH3), 27.68 (CH3), 66.93, 67.69,
71.33, 71.88 (CHϪOH), 78.35 (CH2ϪO), 125.72, 126.90, 127.21,
127.35, 127.84, 127.89, 127.93, 128.19, 128.49, 136.97, 137.93,
140.61, 161.58 (CϭN). Ϫ GC-MS (70 eV); m/z (%): 399 (58) [Mϩ],
380 (123), 292 (373), 208 (1000), 165 (807), 107 (471), 105 (308),
79 (209), 77 (378). Ϫ FTIR (KBr): ν˜ ϭ 3432 cmϪ1 (OH), 3087,
2923, 1655 (CϭN), 1450, 1383, 1044, 966, 700, 600. Ϫ C26H25NO3
(399.49): calcd. C 78.17, H 6.31, N 3.51; found C 78.51, H 6.45,
N 3.18.
syn-3-(4,4-Dimethyl-2-oxazolin-2-yl)-3,4-epoxy-4,4-diphenyl-2-
butanol (2a): M.p. 112Ϫ114°C (hexane). Ϫ H NMR (200 MHz):
1
δ ϭ 1.08 (s, 3 H), 1.14 (s, 3 H), 1.28 (d, J ϭ 6.5 Hz, 3 H), 3.28 (d,
J ϭ 8.2 Hz, 1 H), 3.27Ϫ3.37 (m overlap d at δ ϭ 3.28, CHϪO
oxazoline ring; q centered at δ ϭ 3.32 after exchange with D2O),
3.74 (d, J ϭ 8.2 Hz, 1 H), 4.58 (br. d, J ϭ 9.9 Hz, 1 H, exchanges
with D2O), 7.20Ϫ7.37 (m, 6 H), 7.44Ϫ7.62 (2 m, 4 H). Ϫ 13C NMR
(APT, 50.3 MHz, CDCl3): δ ϭ 19.71 (CH3ϪCHOH), 27.80 (CH3),
28.04 (CH3), 66.70, 67.34 (CHϪOH), 67.81, 72.12, 78.52
(CH2ϪO), 126.77, 127.19, 127.71, 127.92, 128.02, 128.39, 137.05,
138.18, 161.55 (CϭN). Ϫ GC-MS (70 eV); m/z (%): 337 (17) [Mϩ],
322 (90), 292 (63), 208 (1000), 165 (571), 105 (173), 77 (164), 45
(157). Ϫ FTIR (KBr): ν˜ ϭ 3367 cmϪ1 (OH), 2978, 1644 (CϭN),
1444, 1367, 1078, 700. Ϫ C21H23NO3 (337.42): calcd. C 74.75, H
6.87, N 4.15; found C 75.15, H 7.19, N 3.98.
anti-2-(4,4-Dimethyl-2-oxazolin-2-yl)-2,3-epoxy-1,3,3-triphenyl-1-
propanol (3c): White solid, m.p. 113Ϫ115°C (isooctane). Ϫ 1H
NMR (200 MHz): δ ϭ 0.65 (s, 3 H), 0.83 (s, 3 H), 2.5Ϫ2.8 (br. s,
1 H, exchanges with D2O), 3.30 and 3.40 (2 ϫ d, AB system, J ϭ
8.0 Hz, 2 H), 4.97 (s, 1 H), 7.17Ϫ7.41 (m, 11 H), 7.50Ϫ7.63 (2 ϫ
m, 4 H). Ϫ 13C NMR (APT, 50.3 MHz, CDCl3): δ ϭ 27.18 (CH3),
27.45 (CH3), 66.91, 68.84, 70.78, 72.42 (CHϪOH), 78.79
(CH2ϪO), 126.96, 127.29, 127.66, 127.75, 127.87, 128.18, 128.60,
137.03, 137.99, 139.15, 159.91 (CϭN). Ϫ GC-MS (70 eV); m/z (%):
399 (87) [Mϩ], 380 (140), 292 (340), 208 (1000), 165 (762), 107
(419), 105 (278), 79 (199), 77 (344). Ϫ FTIR (KBr): ν˜ ϭ 3233 cmϪ1
(broad, OH), 3056, 2967, 1661 (CϭN), 1500, 1450, 1083, 967, 739,
700. Ϫ C26H25NO3 (399.49): calcd. C 78.17, H 6.31, N 3.51; found
C 78.57, H 6.71, N 3.26.
anti-3-(4,4-Dimethyl-2-oxazolin-2-yl)-3,4-epoxy-4,4-diphenyl-2-
butanol (3a): White solid, m.p. 183Ϫ185°C (isooctane). Ϫ 1H
NMR (200 MHz: δ ϭ 0.89 (s, 3 H), 1.03 (s, 3 H), 1.33 (d, J ϭ 6.6
Hz), 2.4Ϫ2.7 (br. s, 1 H, exchanges with D2O), 3.58 (q partially
overlap AB system CH2ϪO), 3.66 and 3.69 (2 ϫ d, AB system
CH2ϪO, J ϭ 8.0 Hz, 2 H), 7.20Ϫ7.37 (m, 6 H), 7.48Ϫ7.55 (m, 4
H).
Ϫ δ ϭ 18.27
13C NMR (APT, 50.3 MHz, CDCl3):
(CH3ϪCHOH), 27.68 (CH3), 27.77 (CH3), 67.23, 69.08 (CHϪOH),
69.21, 71.13, 78.91 (CH2ϪO), 126.91, 127.03, 127.68, 127.71,
127.87, 127.98, 128.39, 137.14, 138.11, 159.79 (CϭN). Ϫ GC-MS
(70 eV); m/z (%): 337 (14) [Mϩ], 322 (145), 292 (56), 208 (999), 165
(486), 105 (125), 77 (101), 45 (65). Ϫ FTIR (KBr): ν˜ ϭ 3236 cmϪ1
(OH), 2967, 1678 (CϭN), 1444, 1294, 1128, 1106, 744, 700. Ϫ
C21H23NO3 (337.42): calcd. C 74.75, H 6.87, N 4.15; found C
74.72, H 7.14, N 3.94.
syn-2-(4,4-Dimethyl-2-oxazolin-2-yl)-2,3-epoxy-3,3-diphenyl-1-p-
1
tolyl-1-propanol (2d): M.p. 136Ϫ138°C (hexane). Ϫ H NMR (200
MHz): δ ϭ 0.94 (s, 3 H), 1.00 (s, 3 H), 2.29 (s, 3 H), 3.09 (d, J ϭ
Eur. J. Org. Chem. 1999, 409Ϫ417
414

Deprotonation of Oxazolinyloxiranes: Formation of Substituted Acyloxiranes
FULL PAPER
8.2 Hz, 1 H), 3.48 (d, J ϭ 8.2 Hz, 1 H), 4.31 (s, 1 H), 7.07Ϫ7.43 1,2-Epoxy-1,1-diphenyl-2-(2,3,4,4-tetramethyl-1,3-oxazolidin-2-yl)-
(2 m, 11 H; 10 H after exchange with D2O), 7.52Ϫ7.76 (2 m, 4 H).
13C NMR (APT, 50.3 MHz, CDCl3): δ ϭ 21.07 (CH3ϪAr),
27.60 (CH3), 27.73 (CH3), 66.98, 67.70, 71.39, 71.82 (CHϪOH),
78.32 (CH2ϪO), 125.64, 126.91, 127.24, 127.78, 127.91, 128.15,
propane (4b): Diastereomeric oxazolidines (4:1 ratio, 1H-NMR and
13C-NMR analyses) could be isolated by chromatography on silica
gel (petroleum ether/AcOEt, 9:1): 95% overall yield. Ϫ Minor Dia-
Ϫ
1
stereomer: Oil. Ϫ H NMR (300 MHz): δ ϭ 0.88 (s, 3 H), 1.02 (s,
128.47, 128.58, 136.88, 137.02, 137.54, 138.00, 161.63 (CϭN). Ϫ 3 H), 1.13 (s, 3 H), 1.18 (s, 3 H), 1.91 (s, 3 H), 3.62 (d, J ϭ 7.7 Hz,
GC-MS (70 eV); m/z (%): 413 (60) [Mϩ], 394 (106), 293 (283), 292 1 H), 3.69 (d, J ϭ 7.7 Hz, 1 H), 7.10Ϫ7.60 (3 m, 10 H). Ϫ 13C
(473), 246 (99), 230 (118), 208 (417), 165 (794), 121 (1000), 105
NMR [50.3 MHz, (CD3)2CO]: δ ϭ 18.57, 20.41, 21.72, 24.88,
(236), 93 (240), 91 (254), 77 (330). Ϫ FTIR (KBr): ν˜ ϭ 3407 cmϪ1 27.19, 75.83, 77.33, 77.96, 78.95, 98.65, 126.88, 126.98, 127.26,
(OH), 3062, 1656 (CϭN), 1449, 1390, 1048, 704, 625.
C27H27NO3 (413.51): calcd. C 78.42, H 6.58, N 3.39; found C
78.25, H 6.83, N 3.24.
Ϫ
127.94, 128.20, 128.70, 142.05. Ϫ GC-MS (70 eV); m/z (%): 322 (7)
[Mϩ Ϫ CH3], 165 (156), 128 (1000), 74 (108), 56 (208). Ϫ FTIR
(film): ν˜ ϭ 2962 cmϪ1, 1444, 1260, 1096, 1022, 799, 705. Ϫ Major
Diastereomer: White solid, m.p. 93Ϫ95°C (hexane). Ϫ 1H NMR
(300 MHz): δ ϭ 0.97 (s, 3 H), 1.04 (s, 3 H), 1.20 (s, 3 H), 1.37 (s,
3 H), 2.33 (s, 3 H), 3.28 (d, J ϭ 7.5 Hz, 1 H), 3.76 (d, J ϭ 7.5 Hz,
1 H), 7.22Ϫ7.53 (3 m, 10 H). Ϫ 13C NMR [50.3 MHz, (CD3)2CO]:
δ ϭ 18.19, 21.13, 21.42, 24.24, 60.21, 68.30, 72.41, 74.56, 77.32,
96.01, 126.44, 126.87, 127.15, 127.24, 127.93, 128.68, 142.49,
143.94. Ϫ GC-MS (70 eV); m/z (%): 322 (7) [Mϩ Ϫ CH3], 165
(156), 128 (1000), 74 (108), 56 (208). Ϫ FTIR (film): ν˜ ϭ 2921
cmϪ1, 1444, 1253, 1100, 1053, 1026, 703, 686. Ϫ C22H27NO2
(337.46): calcd. C 78.30, H 8.06, N 4.15; found C 78.14, H 8.08,
N 3.91.
anti-2-(4,4-Dimethyl-2-oxazolin-2-yl)-2,3-epoxy-3,3-diphenyl-1-p-
tolyl-1-propanol (3d): White solid, m.p. 143Ϫ145°C (hexane). Ϫ 1H
NMR (200 MHz): δ ϭ 0.66 (s, 3 H), 0.85 (s, 3 H), 2.29 (s, 3 H),
2.35Ϫ2.55 (br. s, 1 H, exchanges with D2O), 3.34 and 3.42 (2 ϫ d,
AB system, J ϭ 8.0 Hz, 2 H), 4.93 (s, 1 H), 7.04Ϫ7.41 (m, 10 H),
7.49Ϫ7.63 (2ϫ m, 4 H). Ϫ 13C NMR (APT, 50.3 MHz, CDCl3):
δ ϭ 21.15 (CH3ϪAr), 27.22 (CH3), 27.47 (CH3), 66.94, 68.94,
70.85, 72.39 (CHϪOH), 78.79 (CH2ϪO) , 127.00, 127.19, 127.65,
127.75, 128.16, 128.56, 136.14, 137.12 137.56, 138.06, 159.91 (Cϭ
N). Ϫ GC-MS (70 eV); m/z (%): 413 (37) [Mϩ], 394 (74), 293 (394),
292 (637), 246 (187), 230 (236), 208 (612), 165 (887), 121 (999), 105
(190), 93 (211), 91 (225), 77 (245). Ϫ FTIR (KBr): ν˜ ϭ 3200 cmϪ1
(OH), 3057, 2967, 1656 (CϭN), 1444, 1256, 1083, 1017, 806, 700.
Ϫ C27H27NO3 (413.51): calcd. C 78.42, H 6.58, N 3.39; found C
78.66, H 6.86, N 3.27.
1,2-Epoxy-1,1-diphenyl-2-(3,4,4-trimethyl-1,3-oxazolidin-2-yl)pro-
pane (4c): Diastereomeric ratio: Ն 95:5 Ϫ White solid, m.p.
1
118Ϫ120°C (hexane), 51% overall yield. Ϫ H NMR (200 MHz):
δ ϭ 0.81 (s, 3 H), 1.10 (s, 3 H), 1.16 (s, 3 H), 2.21 (s, 3 H), 3.49 (s,
1 H), 3.62 (s, 2 H), 7.16Ϫ7.35 (m, 6 H), 7.44Ϫ7.57 (m, 4 H). Ϫ 13C
NMR [50.3 MHz, (CD3)2CO]: δ ϭ 12.94, 16.54, 23.29, 57.80,
59.99, 68.08, 69.27, 79.36, 95.62, 127.40, 127.70, 127.77, 128.01,
128.60, 128.75, 140.39, 141.34. Ϫ GC-MS (70 eV); m/z (%): 323 (6)
[Mϩ], 165 (1063), 114 (10000), 60 (1125), 42 (1548). Ϫ FTIR (KBr):
ν˜ ϭ 2971 cmϪ1, 2865, 1495, 1447, 1069, 1018, 768 , 706. Ϫ
C21H25NO2 (323.43): calcd. C 77.98, H 7.79, N 4.33; found C
77.58, H 8.05, N 3.98.
General Procedure for the Synthesis of Oxazolidinyl Epoxides 4a؊e:
The preparation of 4a is described as an example. To a solution of
oxazolinyl epoxide 1d (468 mg, 1.52 mmol) in dry THF (3.5 mL),
under N2 at 0°C, methyl triflate (2.29 mmol, 259 µL) was added
directly. After 30 min, to the resulting N-methyloxazolinium salt a
complex of PhMgBr (3.0 , 0.55 mL) with hexamethylphosphorous
triamide[31] (HMPT, 3.34 mmol, 607 µL) in THF (2.0 mL) was
added dropwise at room temp. The reaction mixture was stirred for
50 min, then quenched with sat. aq. NH4Cl and extracted with
Et2O (3 ϫ 10 mL). The combined organic layers were dried with
Na2SO4, filtered and concentrated in vacuo. The crude product was
purified by flash chromatography (petroleum ether/Et2O, 8:2) to
give 4a (468 mg, 77% overall yield) as an inseparable 1.5:1 mixture
(E)-1,2-Epoxy-2-(2,3,4,4-tetramethyl-1,3-oxazolidin-2-yl)-1-p-tolyl-
propane (4d): Inseparable mixture of diastereomers (4:1 ratio, 1H-
and 13C-NMR analyses): oil, 95% overall yield. Ϫ 1H NMR (90
MHz), selected data: δ ϭ 0.85 (s, 3 H, major), 0.97 (s, 3 H, major),
1.13 (s, 3 H, major), 1.49 (s, 3 H, major), 2.19 (s, 3 H, major), 2.31
(s, 3 H, major), 3.43 and 3.75 (2 ϫ d, AB system, J ϭ 5.0 Hz, 2
H, minor), 3.46 and 3.74 (2 ϫ d, AB system, J ϭ 7.5 Hz, 2 H
maior), 7.07Ϫ7.32 (m, 4 H minor ϩ 4 H major). Ϫ GC-MS (70
eV); m/z (%) (minor): 260 (6) [Mϩ Ϫ CH3], 128 (1000), 86 (72), 74
(90), 56 (185). Ϫ GC-MS (70 eV); m/z (%) (minor): 260 (12) [Mϩ
Ϫ CH3], 128 (999), 86 (78), 74 (95), 56 (207). Ϫ FTIR (film) (major
ϩ minor), selected data: ν˜ ϭ 2928 cmϪ1, 1465, 1366, 1262, 1123,
1074, 750.
1
of diastereomers (checked by H- and 13C-NMR analyses). In the
case of 4c, 4d, and 4e a (8Ϫ9):(2Ϫ1) petroleum ether/Et2O mixture
was used as the eluent. The new oxazolidinyl epoxides showed the
following data:
1,2-Epoxy-1,1-diphenyl-2-(3,4,4-trimethyl-2-phenyl-1,3-oxazolidin-
2-yl)propane (4a): Waxy solid. Ϫ 1H NMR (300 MHz): δ ϭ 0.46
(s, 3 H, major), 0.79 (s, 3 H, major), 0.87 (s, 3 H, minor), 1.13 (s,
3 H, major), 1.17 (s, 3 H, minor), 1.18 (s, 3 H, minor), 1.20 (s, 3
H, minor), 2.05 (s, 3 H, major), 3.78 (d, J ϭ 7.3 Hz, 1 H, major),
3.87 (d, J ϭ 7.3 Hz, 1 H, major), 3.92 (d, J ϭ 7.5 Hz, 1 H, minor),
4.23 (d, J ϭ 7.5 Hz, 1 H, minor), 7.03Ϫ7.24 (m, 4 H major ϩ 4 H
minor), 7.30Ϫ7.41 (m, 6 H major ϩ 6 H minor), 7.47Ϫ7.68 (m, 5
H major ϩ 5 H minor). Ϫ 13C NMR [50.3 MHz, (CD3)2CO],
(major ϩ minor): δ ϭ 20.01, 20.57, 21.17, 22.42, 23.05, 24.14,
60.69, 62.23, 68.58, 70.99, 73.90, 74.29, 77.80, 78.20, 97.79, 100.75,
126.10, 126.65, 126.79, 127.10, 127.28, 127.38, 127.45, 127.83,
127.99, 128.09, 128.14, 128.50, 128.75, 128.79, 140.19, 140.49,
(Z)-1,2-Epoxy-2-(2,3,4,4-tetramethyl-1,3-oxazolidin-2-yl)-1-p-tolyl-
propane (4e): Diastereomeric ratio Ն 95:5. Ϫ Oil, 78% . Ϫ 1H
NMR (90 MHz): δ ϭ 1.10 (s, 3 H), 1.17 (s, 3 H), 1.18 (s, 3 H),
1.43 (s, 3 H), 2.36 (s, 3 H), 2.40 (s, 3 H), 3.71 (s, 2 H), 4.52 (s, 1
H), 7.22 (s, 4 H). Ϫ GC-MS (70 eV); m/z (%): 260 (2) [Mϩ Ϫ CH3],
128 (1000), 91 (46), 74 (114), 56 (228). Ϫ FTIR (film): ν˜ ϭ 2972
cmϪ1, 1517, 1467, 1366, 1263, 1135, 1076, 1045, 803.
142.06, 142.24, 143.96, 144.43. Ϫ GC-MS (70 eV); m/z (%) (minor): Deblocking of Oxazolidines 4a؊e to Acyloxiranes 5a؊e: Oxazolid-
384 (1) [Mϩ Ϫ CH3], 190 (1000), 165 (105), 105 (179), 77 (117). Ϫ ines 4a؊e were deblocked to acyloxiranes 5a؊e according to the
GC-MS (70 eV); m/z (%) (major): 384 (2) [Mϩ Ϫ CH3], 190 (1000),
procedure reported in ref.[17] With the exception of 5b (see below)
165 (128), 105 (208), 77 (143). Ϫ FTIR (KBr) (major ϩ minor): all the other acyl epoxides were purified by column chromatogra-
ν˜ ϭ 3088 cmϪ1, 2944, 1600, 1577, 1488, 1444, 1377, 1355, 1261,
phy [silica gel, petroleum ether/Et2O, (7Ϫ9):(3Ϫ1)]. The acyl epox-
1166, 1066, 744 , 700.
ides had the following data (see also Table 3):
Eur. J. Org. Chem. 1999, 409Ϫ417
415

S. Florio, V. Capriati, S. Di Martino, A. Abbotto
FULL PAPER
[8]
J. A. Molander, D. C. Shubert, J. Am. Chem. Soc. 1987, 109,
576Ϫ578.
2,3-Epoxy-2-methyl-1,3,3-triphenylpropan-1-one (5a): Oil, 69% [16
h, room temp., 1.8 equiv. (COOH)2 · 2 H2O]. Ϫ 1H NMR (300
MHz): δ ϭ 1.54 (s, 3 H), 7.05Ϫ7.10 (m, 3 H), 7.27Ϫ7.58 (m, 10
H), 7.83Ϫ7.85 (m, 2 H). Ϫ GC-MS (70 eV); m/z (%): 314 (187)
[Mϩ], 272 (153), 271 (225), 209 (69), 165 (1000), 105 (427), 77 (502),
51 (191), 43 (89). Ϫ FTIR (film): ν˜ ϭ 3060 cmϪ1, 2927, 1681(Cϭ
O), 1448, 1278, 1165,1073, 1090, 703.
[9] [9a]
G. A. Molander, G. Hahn, J. Org. Chem. 1986, 51,
2596Ϫ2599. Ϫ [9b] G. A. Molander, C. del Pozo Losada, J. Org.
Chem. 1997, 62, 2935Ϫ2943.
[10]
[11]
[12]
[13]
M. J. Begley, M. C. Bowden, P. Patel, G. Pattenden, J. Chem.
Soc., Perkin Trans. 1 1991, 1951Ϫ1958.
W. R. Roush, J. A. Straub, M. S. VanNieuwenhze, J. Org. Chem.
1991, 56, 1636Ϫ1648.
M. Shimazachi, H. Hara, K. Tsuchihashi, Tetrahedron Lett.
1987, 28, 5891Ϫ5894.
3,4-Epoxy-3-methyl-4,4-diphenylbutan-2-one (5b): A mixture of the
expected epoxy ketone 5b[32] (77%) and 3,3-diphenylpentane-2,4-
dione (9) (23%) (Scheme 3) (1H NMR and MS inspection) was
obtained when the oxazolidine 4b (diastereomers, 0.28 mmol) was
treated with an aq. (COOH)2 · 2 H2O solution (10 mL of 3.2% w/
w; temp. 60Ϫ65°C; 3 d). Attempted separation by silica gel chro-
matography of 5b and 9 failed as 5b isomerized quantitatively to 9.
Such an isomerization occurs frequently with β,β-diphenyl epoxy
ketones.[33] To our knowledge, 5b had been isolated in pure form
only by preparative gas-cromatographic analysis.[32]
G. P. Howe, S. Wang, G. Procter, Tetrahedron Lett. 1987, 28,
2629Ϫ2632.
[14] [14a]
[14b]
G. B. Payne, J. Org. Chem. 1961, 26, 250Ϫ252. Ϫ
O.
L. Chapman, T. C. Hess, J. Org. Chem. 1979, 44, 962Ϫ964. Ϫ
[14c]
E. Hasegawa, K. Ishiyama, T. Horaguchi, T. Shimizu, J.
[14d]
Org. Chem. 1991, 56, 1631Ϫ1635. Ϫ
S. M. Roberts et al.,
[14e]
J. Chem. Soc., Chem. Commun. 1997, 739Ϫ740. Ϫ
S. Wa-
tanabe, Y. Kobayashi, T. Arai, H.Sasai, M. Bougauchi, M.
Shibasaki, Tetrahedron Lett. 1998, 39, 7353Ϫ7356.
M. Hayashi, S. Terashima, K. Koga, Tetrahedron 1981, 37,
2797Ϫ2803.
[15]
[16] [16a]
2,3-Epoxy-2-methyl-3,3-diphenylpropanal (5c): Oil, 77% [32 h, room
temp., 1.0 equiv. of (COOH)2 · 2 H2O]. Ϫ 1H NMR (90 MHz):
δ ϭ 1.30 (s, 3 H), 7.11Ϫ7.59 (m, 10 H), 8.98 (s, 1 H). Ϫ GC-MS
(70 eV); m/z (%): 238 (2) [Mϩ], 237 (8), 195 (552), 165 (1000), 105
(117), 77 (266), 51 (185), 43 (257). Ϫ FTIR (film): ν˜ ϭ 3055 cmϪ1
2933, 2833, 1722 (CϭO), 1494, 1450, 1072, 1016, 766, 750, 700.
C. A. Cope, P. A. Trumbull, J. Am. Chem. Soc. 1958, 80,
2844Ϫ2849. Ϫ [16b] J. K. Crandall, L.ϪH.C. Lin, J. Am. Chem.
Soc. 1967, 89, 4526Ϫ4527. Ϫ [16c] J. K. Crandall, L.ϪH.C. Lin,
J. Am. Chem. Soc. 1967, 89, 4527Ϫ4528. Ϫ [16d] J. K. Crandall,
M. Apparu, Org. React. 1983, 29, 345Ϫ443 and references ther-
[16e]
,
ein. Ϫ
G. A. Molander, K. Mautner, J. Org. Chem. 1989,
54, 4042Ϫ4050. Ϫ [16f] G. A. Molander, K. Mautner, Pure Appl.
Chem. 1990, 62, 707Ϫ712. Ϫ [16g] N. S. Mani, C. A. Townsend,
J. Org. Chem. 1997, 62, 636Ϫ640. Ϫ [16h] A. Baramee, J. Clardy,
P. Kongsaeree, S. Rajviroongit, C. Suteerachanon, C. Thebtar-
(E)-3,4-Epoxy-3-methyl-4-p-tolylbutan-2-one (5d): Oil , 40% [2 d,
room temp., 11 equiv. of (COOH)2 · 2 H2O]. Ϫ 1H NMR (300
MHz): δ ϭ 1.62 (s, 3 H), 1.80 (s, 3 H), 2.30 (s, 3 H), 4.04 (s, 1 H),
7.08Ϫ7.38 (m, 4 H). Ϫ GC-MS (70 eV); m/z (%): 190 (686) [Mϩ],
147 (494), 119 (561), 105 (378), 104 (530), 103 (558), 91 (419), 78
(636), 43 (999). Ϫ FTIR (film): ν˜ ϭ 1716 cmϪ1 (CϭO).
anonth, Y. Thebtaranonth, J. Chem. Soc., Chem. Commun.
[16i]
1996, 1511Ϫ1512. Ϫ
P. Lohse, H. loner, P. Acklin, F.
Sternfeld, A. Pfaltz, Tetrahedron Lett. 1991, 32, 615Ϫ618.
S. Florio, V. Capriati, R. Luisi, Tetrahedron Lett. 1996, 37,
4781Ϫ4784.
[17]
[18]
That an epoxy group, through the nonbonding electrons of the
oxygen atom, is a good effective acceptor of hydrogen bonds, is
well known; see: C. R. Johnson, C. J. Cheer, J. Am. Chem. Soc.
1968, 90, 178Ϫ183.
(Z)-3,4-Epoxy-3-methyl-4-p-tolylbutan-2-one (5e): Oil, 40% [2 d,
room temp., 8 equiv. of (COOH)2 · 2 H2O]. Ϫ 1H NMR (300
MHz): δ ϭ 1.54 (s, 3 H), 2.16 (s, 3 H), 2.34 (s, 3 H), 4.14 (s, 1 H),
7.13Ϫ7.18 (m, 4 H). Ϫ GC-MS (70 eV); m/z (%): 190 (526) [Mϩ],
189 (188), 147 (404), 119 (638), 105 (361), 104 (443), 103 (493), 91
(460), 78 (601), 43 (999). Ϫ FTIR (film): ν˜ ϭ 1716 cmϪ1 (CϭO).
[19]
[20]
P. L. Kuhn, J. Am. Chem. Soc. 1952, 74, 2492Ϫ2495.
All of the structures were optimized with no symmetry con-
straints, unless otherwise stated, and using the keyword PRE-
CISE in order to meet rigorous criteria. In order to ensure that
results did not involve an artifact, we used different geometries
as starting structures in which all of the feasible conformations
were considered (i.e. presence or absence of hydrogen bonding
to the epoxy oxygen or oxazolinyl heteroatoms, steric hin-
drance). MOPAC 6.0: J. J. P. Stewart, QCPE 455, 1990. All of
the calculations were performed using the keywords PM3, EF,
and PRECISE.
A. Abbotto, A. Streitwieser, P. v. R. Schleyer, J. Am. Chem. Soc.
1997, 119, 11255Ϫ11268 and references therein.
R. J. Ouellette, K. Liptak, G. Booth, J. Org. Chem. 1967, 32,
2394Ϫ2397.
W. Adam, K. Peters, M. Renz, J. Org. Chem. 1997, 62,
3183Ϫ3189 and references therein.
Signals of carbon atoms that are sterically perturbed appear at
higher field than those of similar carbon atoms that are not
sterically crowded, as reported; D. M. Grant, B. V. Cheney, J.
Am. Chem. Soc. 1967, 89, 5315Ϫ5318.
Acknowledgments
This work was carried out under the framework of the National
Project “Stereoselezione in Sintesi Organica. Metodologie ed Ap-
plicazioni” supported by the Ministero dellЈUniversita e della
Ricerca Scientifica e Tecnologica (MURST, Rome), and by the
University of Bari and CNR (Rome).
[21]
[22]
[23]
[24]
`
[1]
For a review on oxiranyl anions see: T. Satoh, Chem. Rev. 1996,
96, 3303Ϫ3325.
[2]
H. J. Bestman, H. S. Rippel, R. Dostalek, Tetrahedron Lett.
1989, 30, 5261Ϫ5262.
[3]
A. K. Mandal, S. W. Mahajan, Tetrahedron 1988, 44,
[25] [25a]
The configuration of the two diastereomeric (E)- (1j) and
2293Ϫ2299.
(Z)-epoxides (1m) was assigned by 13C-NMR spectroscopy as
reported for similar system: C. A. Kingsbury, D. L. Durham, R.
Hutton, J. Org. Chem. 1978, 43, 4696Ϫ4700. Ϫ [25b] S. Florio, V.
Capriati, V. Russo, Gazz. Chim. Ital. 1997, 127, 587Ϫ595. Ϫ
[25c] The syn (6) and anti (7) structures of the two diastereomeric
chlorohydrins were determined by the ratios and structures of
the (E)- (1j) and (Z)-oxazolinyl epoxides (1m), respectively.
[26] [26a] A first example of a heterocyclic stabilized oxiranyllithium
had been reported by us: S. Florio, G. Ingrosso, L. Troisi, V.
Lucchini, Tetrahedron Lett. 1993, 34, 1363Ϫ1366. Ϫ [26b] Ethy-
nyl-stabilized oxiranyl anions from optically pure cis-disubsti-
tuted ethynyloxiranes were also proved to be configurationally
stable: D. Grandjean, P. Pale, J. Chuche, Tetrahedron: Asym-
metry 1993, 4, 1991Ϫ1994.
[4]
J. W. Scheeren, J. Lange, Tetrahedron Lett. 1984, 25,
1609Ϫ1612.
[5]
D. A. Evans, J. M. Williams, Tetrahedron Lett. 1988, 29,
5065Ϫ5068.
[6] [6a]
Y. Takeda, T. Matsumoto, F. Sato, J. Org. Chem. 1986, 51,
[6b]
4728Ϫ4731. Ϫ
S. Wang, G. P. Howe, R. S. Mahal, G.
[6c]
Procter, Tetrahedron Lett. 1992, 33, 3351Ϫ3354. Ϫ
T. Ka-
wakami, I. Shihata, A. Baba, H. Matsuda, J. Org. Chem. 1993,
[6d]
58, 7608Ϫ7609. Ϫ
A. T. Gillmore, S. M. Roberts, M. B.
Hursthouse, K. M. A. Malik, Tetrahedron Lett. 1998, 39,
3315Ϫ3318.
[7] [7a]
M. Takeshita, M. Miura, Y. Unuma, J. Chem. Soc., Perkin
[7b]
` `
G. Fouche (nee van Vuuren),
Trans. 1 1993, 2901Ϫ2905. Ϫ
R. M. Horak, O.-M. Cohn, J. Chem. Soc., Chem. Comm.
1993, 119Ϫ120.
[27]
A preliminary communication of this work has been published:
416
Eur. J. Org. Chem. 1999, 409Ϫ417

Deprotonation of Oxazolinyloxiranes: Formation of Substituted Acyloxiranes
FULL PAPER
S. Florio, V. Capriati, S. Di Martino, Tetrahedron Lett. 1998,
39, 5639Ϫ5642.
ide (HMPA) to a THF suspension of the corresponding oxazol-
inium salt. In this case aliphatic Grignard reagents were not
successfully formylated: A. I. Meyers, E. W. Collington, J. Am.-
Chem. Soc. 1970, 92, 6676Ϫ6678.
[28]
[29]
J. Suffert, J. Org. Chem. 1989, 54, 509Ϫ512.
´
`
P. Breton, C. Andre-Barres, Y. Langlois, Synth. Commun. 1992,
[32]
[33]
22, 2543Ϫ2554.
P. Sulmon, N. De Kimpe, N. Schamp, J.-P. Declercq, B. Tinant,
J. Org. Chem. 1988, 53, 4457Ϫ4462.
[30]
[31]
The preparation of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline
has been described in: A. Abbotto, S. Bradamante, S. Florio, V.
Capriati, J. Org. Chem. 1997, 62, 8937Ϫ8940.
F. L. M. Smeets, L. Thijs, B. Zwanenburg, Tetrahedron 1980,
36, 3269Ϫ3272.
The formylation of a Grignard reagent via 4,4-dimethyl-2-ox-
azoline was performed by A. I. Meyers et al. by adding a Grig-
nard reagent containing 2.0 equiv. of hexamethylphosphoram-
Received June 30, 1998
[O98273]
Eur. J. Org. Chem. 1999, 409Ϫ417
417