A New Preparation of Optically Active N-Acyloxazolidinones via Ruthenium-Catalyzed Enantioselective Hydrogenation

Article abstract of DOI:10.1021/jo971733d

α-Methylene-N-acyloxazolidinones are readily prepared in three steps from propargylic alcohols via cyclic carbonates, and the enantioselective hydrogenation of the latter catalyzed by chiral (diphosphine)ruthenium complexes makes possible the obtention of both enantiomers of optically active N-acyloxazolidinones with very high enantioselectivities.

Full text of DOI:10.1021/jo971733d

1806
J . Org. Chem. 1998, 63, 1806-1809
A New P r ep a r a tion of Op tica lly Active N-Acyloxa zolid in on es via
Ru th en iu m -Ca ta lyzed En a n tioselective Hyd r ogen a tion
Pierre Le Gendre, Patrice Thominot, Christian Bruneau,* and Pierre H. Dixneuf*
Lab de Chim de Coord et Catalyse, UMR 6509, Campus de Beaulieu, Universite de Rennes I,
35042 Rennes Cedex, France
Received J uly 16, 1997
R-Methylene-N-acyloxazolidinones are readily prepared in three steps from propargylic alcohols
via cyclic carbonates, and the enantioselective hydrogenation of the latter catalyzed by chiral
(diphosphine)ruthenium complexes makes possible the obtention of both enantiomers of optically
active N-acyloxazolidinones with very high enantioselectivities.
Sch em e 1
Optically active N-acyloxazolidinones are powerful
chiral auxiliaries with widespread uses for the synthesis
of optically active molecules.1,2 Their efficiency is due to
the fact that their deprotonation at the R-carbon of the
N-acyl group gives a (Z)-enolate with high stereoselec-
tivity and that the reaction of the latter with a variety
of electrophiles leads to stereoselective C-C bond forma-
tion via alkylation,3 acylation4 and aldol reaction,5 or
C-heteroatom bond formation via halogenation,6 sulfen-
ylation,7 oxygenation,8 and amination.9 When the acyl
group contains a conjugated double bond, stereoselective
Diels-Alder cycloaddition10 and Michael addition11 can
be performed. The strength of N-acyloxazolidones is that
their chiral oxazolidinone structure, which carries the
stereochemical information, can be easily recovered and
reused.
oxazolidinones.12,13 Other synthetic processes mainly
involve epoxides generated via Sharpless epoxidation of
allylic alcohols14 or â-functionalized alcohols such as
diols,15,16 hydroxy azides,17 and hydroxy esters.18
We report here a novel route to both enantiomers of
optically active N-acyloxazolidinones with very high
optical purity, based on the enantioselective hydrogena-
tion of N-acyl-4-methylene-1,3-oxazolidin-2-ones cata-
lyzed by chiral ruthenium complexes (Scheme 1).
Optically active oxazolidinones are usually prepared
from optically active natural compound derivatives or
bifunctional substrates. Natural amino acids are sub-
strates of choice for the access to amino alcohols which
react with phosgene derivatives to give optically active
Resu lts a n d Discu ssion
P r ep a r a tion of th e N-Acyl-4-m eth ylen e-1,3-oxa zo-
lid in -2-on es. The unsaturated cyclic carbonates 1, 2 can
be selectively prepared from prop-2-yn-1-ols by catalytic
reaction with carbon dioxide,19 and it is known that they
readily react with primary amines to generate oxazoli-
(1) (a) Evans, D. A.; Bartroli, J .; Shih, T. L. J . Am. Chem. Soc. 1981,
103, 2127. (b) Evans, D. A.; Takacs, J . M., McGee, L. R.; Ennis, M. D.;
Mathre, D. J .; Bartroli, J . Pure Appl. Chem. 1981, 53, 1109. (c) Evans,
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WO 95/18112, 1995.
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T. H.; Chu, V. V.; Lin, T. C.; Wu, C. H.; Liu, L. H. Tetrahedron Lett.
1991, 32, 4959. (d) Kubota, Y.; Kodaka, M.; Tomohiro, T.; Okuno, H.
J . Chem. Soc., Perkin Trans. 1 1993, 5. (e) Imada, Y.; Mitsue, Y.; Ike,
K.; Washizuka, K. I.; Murahashi, S. I. Bull. Chem. Soc. J pn. 1996, 69,
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S.; Kondo, A.; Han, Q. Chem. Lett. 1991, 1245. (d) J ung, M. E.; J ung,
Y. H. Synlett 1995, 563. (e) Trost, B. M.; Sudhakar, A. R. J . Am. Chem.
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J . Org. Chem. 1993, 58, 2725. (c) Evans, D. A.; Bilodeau, M. T.; Somers,
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(d) Kanno, H.; Osamai, K. Tetrahedron Lett. 1995, 36, 5375.
(4) (a) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J . S.; Bilodeau,
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Am. Chem. Soc. 1986, 108, 6395. (b) Trimble, L. A.; Vederas, C. J . J .
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Am. Chem. Soc. 1987, 109, 6881. (d) Harris, J . M.; Bolessa, A. E.;
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Trans. 1 1995, 1945.
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1997, 8, 821.
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1988, 110, 1238. (b) Sugahara, T.; Iwata, T.; Yamaoka, M.; Takano, S.
Tetrahedron Lett. 1989, 30, 1821.
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Lett. 1994, 50, 1073.
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S0022-3263(97)01733-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/20/1998

Preparation of Optically Active N-Acyloxazolidinones
J . Org. Chem., Vol. 63, No. 6, 1998 1807
Ta ble 1. Hyd r ogen a tion of N-Acyloxa zolid in on es 6-10
Sch em e 2
Ca ta lyzed by (d ip h osp h in e)Ru (II) Com p lexesa
run substrate
catalyst
compoundb eec
1
2
3
4
5
6
7
6
6
6
7
8
((R)-Binap)Ru(O2CCF3)2
((S)-Biphemp)Ru(O2CCF3)2
[((R)-Binap)RuCl2]2NEt3
((R)-Binap)Ru(O2CCF3)2
((R)-Binap)Ru(O2CCF3)2
((R)-Binap)Ru((O2CCF3)2
[((R)-Binap)RuCl2]2NEt3
R-(-)-11
S-(+)-11
R-(-)-11
R-(-)-12
R-(-)-13
R-(-)-14
R-(-)-15
>99
99
99
>99
98
9
10
98
98
a
Reactions carried out in dry methanol with a substrate/catalyst
b
ratio ) 100 at 50 °C under 10 MPa hydrogen pressure. Absolute
configurations were deduced from literature data. c ee were de-
termined by high pressure liquid chromatography with a chiral
(S,S-WHELK 0-1 column eluted with a hexane-2-propanol mix-
ture.
Sch em e 3
Sch em e 4
dinones.20 Advantage can thus be taken of these carbon-
ates to produce the desired precursors N-acyloxazolidi-
nones according to Scheme 2.
Treatment of carbonates 1, 2 with ammonia at room
temperature led to the hydroxylated oxazolidinones 3 and
4 in 95% isolated yield. Subsequent treatment with an
excess of acyl chloride in refluxing dichloromethane in
the presence of a catalytic amount of p-toluenesulfonic
acid (PTSA) led to the N-acyloxazolidinones 6-9 in 86,
80, 80, and 65% yield, respectively, resulting from both
acylation of the N-H functionality and dehydration.
N-Acyloxazolidinones are commonly prepared by depro-
tonation of the parent oxazolidinones in the presence of
BuLi1a,3b,8a or Et3N21 followed by acylation with anhy-
drides or acid chlorides. Furthermore, acylation with an
optically pure acyl chloride has been used to resolve
4-methyloxazolidinone.22 By using a catalytic amount of
PTSA instead of a base, the R-methylene-N-acyloxazoli-
dinones 6-9 could be prepared in three steps from
tertiary propargylic alcohol, CO2, ammonia, and an acyl
chloride.
The N-acyloxazolidinone 10 was obtained with an
alternative synthesis involving initial introduction of the
benzoyl group by treatment of the cyclic carbonate 1 with
deprotonated benzamide to give 5 (72%), and subsequent
dehydration in the presence of PTSA (Scheme 3).
E n a n t ioselect ive H yd r ogen a t ion of N-Acyl-4-
m eth ylen e-1,3-oxa zolid in -2-on es. The N-acyloxazo-
lidinones 6-10 contain an enamide CdC, which is
expected to be enantioselectively hydrogenated in the
presence of a chiral ruthenium(II) catalyst,23 and an
oxazolidinone ring that can also act as a chelating ligand.
This consideration led us to attempt the hydrogenation
of the N-acyloxazolidinones 6-10 with chiral ruthenium
complexes containing the Binap and Biphemp optically
active diphosphine ligands.24 A typical hydrogenation
was performed from 0.2 g of unsaturated oxazolidinone,
1 mol % of ruthenium catalyst (Table 1), and 10 mL of
distilled methanol, which were introduced under inert
atmosphere into a 125 mL autoclave. The hydrogenation
was then carried out at 50 °C under 10 MPa initial
pressure of hydrogen, and the conversion was determined
by gas chromatography (Scheme 4).
Under these conditions, complete conversion of the
starting N-acyl-4-methylene oxazolidinones was obtained
after 20 h of reaction and the 1H and 13C NMR of the
reaction product showed the hydrogenated N-acyloxazo-
lidinones as the sole products, indicating that the reaction
was very selective and no cleavage of the acyl group or
ring opening took place. The pure compounds were
isolated by distillation under reduced pressure in more
than 85% yield. The enantiomeric excesses of the N-
acyloxazolidinones 6-10 were determined by high-pres-
sure liquid chromatography with a chiral (S,S)-WHELK
0-1 column eluted with a hexane-2-propanol (95/5)
mixture.
The various ruthenium catalyst precursors tested were
very efficient in terms of activity and enantioselectivity
as the amount of the minor enantiomer was always at
the limit of detection of the HPLC analysis (Table 1). The
nature of the acylating groups (acetyl, propionyl, or
benzoyl) and the nature of the substituents at C(5) had
no effect on the enantioselectivity of the hydrogenation.
The hydrogenation of the N-cyclohexyl-4-methylene-
1,3-oxazolidin-2-one, which contains no acyl group, was
not possible under our experimental conditions. The
excellent enantioselectivities obtained from acyloxazoli-
dinones might be due to the coordination of both the
exocyclic CdC double bond and the acyl NCO group to
the chiral ruthenium center. In this process, the carbonyl
group of the cyclic carbamate is probably not involved
(20) Bruneau, C.; Dixneuf, P. H. J . Mol. Catal. 1992, 74, 97.
(21) (a) Ager, D. T.; Allen, D. R.; Schaad, D. R. Synthesis 1996, 1283.
(b) Ho, G.-J .; Mathre, D. J . J . Org. Chem. 1995, 60, 2271.
(22) Ishizuka, T.; Kimura, K.; Ishibushi, S.; Kunieda, T. Chem. Lett.
1992, 991.
(23) (a) Heiser, B.; Broger, A.; Crameri, Y. Tetrahedron: Asymmetry
1991, 2, 51. (b) Kitamura, M.; Hsiao, Y., Noyori, R. Tetrahedron Lett.
1987, 28, 4829. (c) Noyori, R.; Ohta, M.; Hsiao, Y.; Kitamura, M.; Ohta,
T.; Takaya, H. J . Am. Chem. Soc. 1986, 108, 7117. (d) Kitamura, M.;
Hsiao, Y.; Ohta, M.; Tsukamoto, M.; Ohta, T.; Takaya, H.; Noyori, R.
J . Org. Chem. 1994, 59, 297. (e) Tschaen, D. M.; Abramson, L.; Cai,
D.; Desmond, R.; Dolling, U. H.; Frey, L.; Karady, S.; Shi, Y. J .;
Verhoeven, T. R. J . Org. Chem. 1995, 60, 4324.
(24) Binap: (1,1′-binaphthyl-2,2′-diyl)bis(diphenylphosphine); Bi-
phemp: (6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine).

1808 J . Org. Chem., Vol. 63, No. 6, 1998
Gendre et al.
chiral (S,S)-WELK 0-1 column (250 × 4.6 mm) eluted with a
hexane-2-propanol (95/5) mixture. Elemental analyses were
carried out by Le Service d’Analyses du CNRS at Vernaison
(France). All solvents were distilled and dried before use.
4-Hydr oxy-4,5,5-tr im eth yl-1,3-oxazolidin -2-on e (3). Am-
monia was bubbled overnight through a solution containing 9
mmol of carbonate 1 in 50 mL of ethyl acetate. After
evaporation of the solvent and washing with diethyl ether, the
cyclic carbamate 3 was isolated by filtration as a white solid
Sch em e 5
(95%): mp ) 136 °C; IR (KBr) ν 3250, 1750 cm-1 1H NMR
;
as already suggested in the enantioselective hydrogena-
tion of the similar cyclic carbonate25 and lactone struc-
tures.26
(300 MHz, CDCl3) δ 6.86 (s, 1H), 4.65 (s, 1H), 1.42 (s, 3H),
1.40 (s, 3H), 1.37 (s, 3H); 13C {1H} NMR (75 MHz, CDCl3) δ
160.20, 88.80, 88.70, 25.20, 22.80, 20.90. Anal. Calcd for C6-
H11NO3: C, 49.64; H, 7.64; N, 9.65. Found: C, 49.51; H, 7.56;
N, 9.75.
5′-Cycloh exa n esp ir o-4′-h yd r oxy-4′-m eth yl-1′,3′-oxa zo-
lid in -2′-on e (4). Under the above experimental conditions,
95% of 4 was isolated as a white solid: mp ) 174 °C; IR (KBr)
ν 3402, 1764 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.66 (s, 1H),
4.31 (s, 1H), 1.41 (s, 3H), 2.20-1.00 (m, 10H). Anal. Calcd
for C9H15NO3: C, 58.36; H, 8.16; N, 7.56. Found: C, 58.52;
H, 8.12; N, 7.88.
Gen er a l P r oced u r e for th e Acyla tion of th e Oxa zoli-
d in on es 3 a n d 4. A 7 mmol amount of 3 or 4 and 30 mmol
of acyl chloride were heated in the presence of 0.5 mmol of
p-toluenesulfonic acid in 50 mL of refluxing dichloromethane
(18 h with acetyl chloride, 48 h with propionyl chloride). The
water was removed thanks to a cartridge of calcium chloride
placed in a Soxhlet apparatus. After evaporation of the
solvent, the acyloxazolidinones were isolated by distillation
under reduced pressure or chromatography over silica gel.
N-Acet yl-5,5-d im et h yl-4-m et h ylen e-1,3-oxa zolid in -2-
on e (6). Isolated by distillation as a white solid (86%): mp )
56 °C; IR (KBr) ν 1789, 1722, 1657 cm-1; 1H NMR (300 MHz,
CDCl3) δ 5.84 (d, 1H, J ) 2.0 Hz), 4.52 (d, 1H, J ) 2.0 Hz),
2.54 (s, 3H), 1.47 (s, 6H); 13C {1H} NMR (75 MHz, CDCl3) δ
170.59, 152.63, 145.51, 93.71, 82.27, 28.08, 25.86. Anal. Calcd
for C8H11NO3: C, 56.79; H, 6.56; N, 8.27. Found: C, 56.79;
H, 6.70; N, 8.18.
It has been shown that the use as chiral auxiliary of a
5,5-symmetrically disubstituted oxazolidinone ring rather
than the corresponding unsubstituted ring was preferable
as it gave less undesirable degradation byproducts.12 It
is also noteworthy that using compound 13, containing
an alkyl group as small as a methyl attached to the
asymmetrical C(4) carbon atom, good diastereoselectivity
was observed upon alkylation with PhCH2Br/LDA.12
Clea va ge of th e Acyl Gr ou p : Syn th esis of Op ti-
ca lly Active Oxa zolid in on es. The presence of the acyl
group is required to obtain a high enantioselectivity
during the hydrogenation of the exocyclic olefinic double
bond. Subsequent deacylation is achieved by treatment
with potassium carbonate in methanol at room temper-
ature (Scheme 5). Thus, treatment of 0.16 g (0.9 mmol)
of 11 with 0.2 g (1.4 mmol) of potassium carbonate in 10
mL of anhydrous methanol at room temperature for 24
h led to the quantitative conversion to the oxazolidinone
16. After usual workup, the optically active R-(-)-4,5,5-
trimethyloxazolidin-2-one 16 was obtained in 90% yield.
([RD] ) -2.6 (c 4, CHCl3)).12
Compound 16 could have arisen from the 4-methyl-
eneoxazolidin-2-one 17 via hydrogenation; however, 17
was not accessible by direct dehydration of 3. The three-
step process involving acylation of 3, catalytic enantio-
selective hydrogenation of 6 followed by the deacylation
of 11, produced 16 in more than 70% yield and with high
enantiomeric purity.
In summary, the enantioselective hydrogenation of
N-acyl-4-methylene-1,3- oxazolidin-2-ones in the presence
of ruthenium catalysts containing an optically pure
diphosphine ligand provides a novel method for direct
access to optically active N-acyloxazolidinones of high
optical purity. This method also allows the preparation
of both enantiomers of new chiral auxiliaries sym-
metrically disubstituted at C(5) with introduction of the
chirality at the last step of the synthesis and competes
with the methods starting from natural compounds such
as (L)-amino acids. It also offers an efficient access to
optically active 4-methyloxazolidinones via cleavage of
the acyl group under mild conditions.
N-Acetyl-5′-cycloh exa n esp ir o-4′-m eth ylen e-1′,3′-oxa zo-
lid in -2′-on e (7). Isolated as a white solid after chromatog-
raphy over silica gel with a ether-pentane (3/1) mixture as
eluent (80%): mp ) 90 °C; IR (KBr) ν 1787, 1721, 1660 cm-1
;
1H NMR (300 MHz, CDCl3) δ 5.85 (d, 1H, J ) 1.9 Hz), 4.49 (d,
1H, J ) 1.9 Hz), 2.55 (s, 3H), 2.00-1.00 (m, 10H); 13C {1H}
NMR (75 MHz, CDCl3) δ 170.76, 152.86, 145.63, 93.85, 83.94,
37.06, 26.01, 24.50, 21.59. Anal. Calcd for C11H15NO3: C,
63.14; H, 7.23; N, 6.69. Found: C, 63.02; H, 7.38; N, 6.54.
N-P r op ion yl-5,5-d im eth yl-4-m eth ylen e-1,3-oxa zolid in -
2-on e (8). Isolated as a colorless liquid by chromatogaphy over
silica gel with diethyl ether as eluent (80%): IR (neat) ν 1794,
1
1723, 1652 cm-1; H NMR (300 MHz, CDCl3) δ 5.89 (d, 1H, J
) 2.5 Hz), 4.56 (d, 1H, J ) 2.5 Hz), 3.12 (q, 2H, J ) 6.9 Hz),
1.54 (s, 6H), 1.17 (t, 3H, J ) 6.9 Hz). Anal. Calcd for
C9H13NO3: C, 59.00; H, 7.15; N, 7.65. Found: C, 59.28; H,
7.34; N, 7.61.
N-P r op ion yl-5′-cycloh exa n esp ir o-4′-m et h ylen e-1′,3′-
oxa zolid in -2′-on e (9). Isolated as a white solid after chro-
matography over silica gel with diethyl ether as eluent (65%):
mp ) 98 °C; IR (KBr) ν 1787, 1719, 1655 cm-1; 1H NMR (300
MHz, CDCl3) δ 5.86 (d, 1H, J ) 1.9 Hz), 4.48 (d, 1H, J ) 1.9
Hz), 2.96 (q, 2H, J ) 7.3 Hz), 2.00-1.30 (m, 10H), 1.17 (t, 3H,
J ) 7.3 Hz); 13C {1H} NMR (75 MHz, CDCl3) δ 174.7, 152.81,
145.89, 93.67, 83.96, 37.16, 31.08, 24.55, 21.61, 8.33. Anal.
Calcd for C12H17NO3: C, 64.55; H, 7.67; N, 6.27. Found: C,
64.50; H, 7.76; N, 6.11.
N-Ben zoyl-4-h yd r oxy-4,5,5-tr im eth yl-1,3-oxa zolid in -2-
on e (5). A 1.23 g (41 mmol) amount of NaH (80% in mineral
oil) was cooled to 0 °C in 40 mL of tetrahydrofuran. A 3 g (25
mmol) amount of benzamide diluted in 20 mL of dichlo-
romethane and 3 mL (25 mmol) of carbonate 1 were added,
and the solution was stirred at room temperature for 4 h. After
treatment with a saturated NH4Cl solution, extraction with
diethyl ether, drying over MgSO4, and evaporation of the
solvent, 5 was recrystallized from diethyl ether as a white solid
Exp er im en ta l Section
Gen er a l. NMR spectra were recorded on a Bruker AC 300P
(300.13 MHz for 1H; 75.49 for 13C) spectrometer. Infrared
spectra were obtained on a Nicolet 205 FT-IR and mass spectra
were provided by Le Centre de Mesures Physiques de l’Ouest
(Rennes) on a Varian Mat 311 machine. [R]D were measured
on a Perkin-Elmer 241 MC polarimeter, and the enantiomeric
excesses were determined after separation of the enantiomers
by HPLC on a Perkin-Elmer chromatograph equipped with a
(25) Le Gendre, P.; Braun, T.; Bruneau, C.; Dixneuf, P. H. J . Org.
Chem. 1996, 61, 8453.
(26) Ohta, T.; Miyake, T.; Seido, N.; Kuniobayashi, H.; Takaya, H.
J . Org. Chem. 1995, 60, 357.

Preparation of Optically Active N-Acyloxazolidinones
(72%): mp ) 118 °C; IR (KBr) ν 3462, 1778, 1680 cm-1
J . Org. Chem., Vol. 63, No. 6, 1998 1809
;
1H
(R)-N-P r op ion yl-4,5,5-t r im et h yl-1,3-oxa zolid in -2-on e
(13):12 white solid (95%); mp ) 82 °C; IR (KBr) ν 1777, 1704
NMR (300 MHz, CDCl3) δ 7.82-7.42 (m, 5H), 4.50 (s, 1H), 1.76
(s, 3H), 1.54 (s, 3H), 1.52 (s, 3H). MS m/z ) 249 (M+).
N-Ben zoyl-5,5-d im eth yl-4-m eth ylen e-1,3-oxa zolid in -2-
on e (10). A 0.5 g (2 mmol) amount of 5 and 17 mg (5 mol %)
of p-toluenesulfonic acid were heated in refluxing toluene for
12 h in a Dean-Stark apparatus. After evaporation of toluene,
the reaction mixture was treated with a saturated NaHCO3
solution, extracted with dichloromethane, and dried over
MgSO4. The resulting solid was recrystallized from diethyl
cm-1; H NMR (300 MHz, CDCl3) δ 4.16 (q, 1H, J ) 6.6 Hz),
1
2.90-2.88 (m, 2H, J ) 16.0 and 7.3 Hz), 1.41 (s, 3H), 1.39 (s,
3H), 1.26 (d, 3H, J ) 6.6 Hz) 1.14 (t, 3H, J ) 7.3 Hz); 13C NMR
(75 MHz, CDCl3) δ 174.34 (s), 152.79 (s), 81.41 (s), 58.88 (d, J
) 147 Hz), 29.33 (t, J ) 128 Hz), 27.83 (q, J ) 128 Hz), 21.55
(q, J ) 127 Hz), 14.69 (q, J ) 128 Hz), 8.35 (q, J ) 128 Hz).
Anal. Calcd for C9H15NO3: C, 58.36; H, 8.16; N, 7.56.
Found: C, 58.07; H, 8.45; N, 7.60. [R]D -51 (c ) 0.9, CHCl3)
(ee ) 98%).
ether (26%): mp ) 132 °C; IR (KBr) ν 1778, 1764, 1662 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.69-7.42 (m, 5H), 5.55 (d, 1H,
J ) 2.6 Hz), 4.60 (d, 1H, J ) 2.6 Hz), 1.64 (s, 6H). Anal. Calcd
for C13H13NO3: C, 67.52; H, 5.67. Found: C, 67.77; H, 5.74.
Gen er a l P r oced u r e for th e Hyd r ogen a tion of N-Acyl-
oxa zolid in on es (6-10). N-Acyloxazolidinone (0.2 g) and the
ruthenium catalyst (1 mol %) were placed in a 125 mL
stainless steel autoclave. After addition of 10 mL of distilled
methanol under nitrogen, the autoclave was pressurized with
hydrogen (10 MPa) and heated at 50 °C for 18 h. The solvent
was evaporated and the hydrogenated N-acyloxazolidinone
was recovered by distillation under reduced pressure. The
conversion was determined by GC of the crude on a capillary
column coated with FFAP (30 m × 0.53 mm) and the enan-
tiomeric excess by HPLC of the isolated compound on a (S,S)-
WHELK 0-1 column (25 cm × 4.5 mm) eluted with a hexane-
2-propanol (95/5) mixture. The optical rotation was measured
with a Perkin-Elmer 241 polarimeter.
N-P r op ion yl-5′-cycloh exa n esp ir o-4′-m eth yl-1′,3′-oxa zo-
lid in -2′-on e (14): white solid (93%): mp ) 78 °C; IR (KBr) ν
1
1775, 1701 cm-1; H NMR (300 MHz, CDCl3) δ 4.18 (q, 1H, J
) 6.5 Hz), 2.90 (m, 2H), 1.90-1.30 (m, 10H), 1.25 (d, 3H, J )
6.5 Hz), 1.14 (t, 3H, J ) 7.3 Hz); 13C NMR (75 MHz, CDCl3) δ
174.44 (s), 152.85 (s), 82.69 (s), 58.00 (d, J ) 146 Hz), 36.49
(t, J ) 127 Hz), 30.52 (t, J ) 128 Hz), 29.36 (t, J ) 129 Hz),
24.91 (t, J ) 127 Hz), 22.32 (t, J ) 129 Hz), 22.00 (t, J ) 129
Hz), 13.80 (q, J ) 128 Hz), 8.40 (q, J ) 128 Hz). Anal. Calcd
for C12H19NO3: C, 63.98; H, 8.50; N, 6.22. Found: C, 63.80;
H, 8.54; N, 5.93. [R]D -53 (c ) 0.9, CHCl3) (ee ) 98%).
N-Ben zoyl-4,5,5-tr im eth yl-4-m eth ylen e-1,3-oxa zolid in -
2-on e (15): white solid (85%); mp ) 88 °C; IR (KBr) ν 1781,
1
1684 cm-1; H NMR (300 MHz, CDCl3) δ 7.59-7.30 (m, 5H),
4.20 (q, 1H, J ) 6.5 Hz), 1.43 (s, 3H), 1.36 (s, 3H), 1.32 (d, 3H,
J ) 6.5 Hz); 13C {1H} NMR (75 MHz, CDCl3) δ 170.32, 152.87,
133.64, 132.46, 129.04, 127.99, 81.92, 60.07, 27.07, 21.95,
13.99. Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.01.
Found: C, 66.73; H, 6;72; N, 5.98. [R]D -143 (c ) 2, EtOH)
(ee ) 98%).
(R)-N-Acetyl-4,5,5-tr im eth yl-1,3-oxa zolid in -2-on e (11):
white solid (87%); mp ) 42 °C; IR (KBr) ν 1764, 1703 cm-1
;
1H NMR (300 MHz, CDCl3) δ 4.10 (q, 1H, J ) 6.5 Hz), 2.44 (s,
3H), 1.36 (s, 3H), 1.34 (s, 3H), 1.21 (d, 3H, J ) 6.5 Hz); 13C
NMR (75 MHz, CDCl3) δ 170.57 (s), 152.88(s), 81.39 (s), 58.78
(d, J ) 146 Hz), 27.81 (q, J ) 125 Hz), 23.98 (q, J ) 146 Hz),
21.53 (q, J ) 124 Hz), 14.63 (q, J ) 128 Hz). Anal. Calcd for
C8H13NO3: C, 56.12; H, 7.65; N, 8.18. Found: C, 55.76; H,
7.62; N, 8.07. [R]D -20 (c ) 0.5, EtOH) (ee ) 99%).
(R)-4,5,5-Tr im eth yl-4-m eth ylen e-1,3-oxa zolid in -2-on e
(16):12 white solid (90%); mp ) 61 °C; IR (KBr) ν 3273, 1741
1
cm-1; H NMR (300 MHz, CDCl3) δ 5.94 (s, 1H), 3.62 (q, 1H,
J ) 6.5 Hz), 1.42 (s, 3H), 1.30 (s, 3H), 1.15 (d, 3H, J ) 6.5
Hz); 13C {1H} NMR (75 MHz, CDCl3) δ 159.22 (s), 83.59 (s),
57.17 (d, J ) 142 Hz), 27.22 (q, J ) 127 Hz), 21.55 (q, J ) 127
Hz), 16.16 (q, J ) 127 Hz). [R]D -2.6 (c ) 4, CHCl3) (from 11,
ee ) 99%).
(R)-N-Acetyl-5′-cycloh exa n esp ir o-4′-m eth yl-1′,3′-oxa zo-
lid in -2′-on e (12): white solid (87%); mp ) 59 °C; IR (KBr) ν
1
1777, 1702 cm-1; H NMR (300 MHz, CDCl3) δ 4.16 (q, 1H, J
) 6.5 Hz), 2.49 (s, 3H), 2.00-1.30 (m, 10H), 1.24 (d, 3H, J )
6.5 Hz); 13C NMR (75 MHz, CDCl3) δ 170.67 (s), 152.95 (s),
82.75 (s), 57.98 (d, J ) 143 Hz), 24.02 (q, J ) 129 Hz), 36.47
(t, J ) 129 Hz), 30.49 (q, J ) 129 Hz), 24.85 (t, J ) 129 Hz),
22.30 (t, J ) 129 Hz), 22.03 (t, J ) 129 Hz), 13.77 (q, J ) 128
Hz). Anal. Calcd for C11H17NO3: C, 62.54; H, 8;11; N, 6.63.
Found: C, 62.65; H, 8.20; N, 6.59. [R]D -21 (c ) 0.45, CHCl3)
(ee ) 99%).
Ackn owledgm en t. The authors thank Dr. R. Schmid
from F. Hoffmann-La Roche Ltd (Basel) for helpful
discussions and a generous gift of Biphemp ligand.
J O971733D