Chiral Auxiliary-Bearing Isocyanides as Synthons: Synthesis of Strongly Fluorescent (+)-5-(3,4-Dimethoxyphenyl)-4-[[N-[(4S) -2-oxo-4- (phenylmethyl) -2-oxazolidinyl] ] carbonyl] oxazole and Its Enantiomer

Article abstract of DOI:10.1021/jo961554g

Both (4S-(+)-3-(isocyanoacetyl)-4-(phenylmethyl)-2-oxazolidinone (R)-1 and its enantiomer (S)-1 have been synthesized as potentially useful synthons in asymmetric synthesis. Optically active (+)-5-(3,4-dimethoxyphenyl)-4-[[N-[(4S)-2-oxo-4-(phenylmethyl)-2

Full text of DOI:10.1021/jo961554g

8750
J . Org. Chem. 1996, 61, 8750-8754
Ch ir a l Au xilia r y-Bea r in g Isocya n id es a s Syn th on s: Syn th esis of
Str on gly F lu or escen t (+)-5-(3,4-Dim eth oxyp h en yl)-4-[[N-
[(4S)-2-oxo-4-(p h en ylm eth yl)-2-oxa zolid in yl]]ca r bon yl]oxa zole a n d
Its En a n tiom er
J ian S. Tang* and J ohn G. Verkade
Department of Chemistry, Gilman Hall, Iowa State University, Ames, Iowa 50011
Received August 9, 1996X
Both (4S-(+)-3-(isocyanoacetyl)-4-(phenylmethyl)-2-oxazolidinone (R)-1 and its enantiomer (S)-1 have
been synthesized as potentially useful synthons in asymmetric synthesis. Optically active (+)-5-
(3,4-dimethoxyphenyl)-4-[[N-[(4S)-2-oxo-4-(phenylmethyl)-2-oxazolidinyl]]carbonyl] oxazole (S)-2 and
its enantiomer (R)-2 obtained by treating 3,4-dimethoxybenzoyl chloride with (S)-1 and (R)-1,
respectively, in the presence of the nonionic superbase P(MeNCH2CH2)3N, have high fluorescence
quantum yields. The molecular structure of (S)-2 obtained by X-ray means is also presented.
In tr od u ction
Being both nucleophilic and electrophilic, R-metalated
isocyanides can add to polar double bonds, forming a
variety of heterocycles such as 2-oxazolines, 2-imidazo-
lines, 2-thiazolines, oxazoles, thiazoles, triazoles, imida-
zolinones, pyrroles, pyrrolines, 1,3-oxazines, and imida-
zolidinones.1 Oxazolines and oxazoles are not only
pharmaceutically interesting classes of heterocyclic com-
pounds, but they are also useful intermediates to R-amino
acids and R-acylamino acids,2 while thiazolines are key
intermediates to penicillin antibiotics and their structural
variants.1 R-Metalated isocyanides are also used for the
preparation of 1,2- and 1,3-amino alcohols, 1,2-diamines,
and 2,3-diaminoalkenoic acids.1 Recently, there has
arisen considerable interest in the asymmetric aldol
addition of isocyanide enolates to aldehydes for producing
optically active 2-oxazoline-4-carboxylates or 4-carbam-
ides which upon hydrolysis give proteinogenic or non-
proteinogenic amino acids. Moreover, considerable ef-
forts have been devoted to developing effective chiral
catalysts such as ferrocenyldiphosphine gold(I) complexes
for asymmetric aldol reactions.3 Yet, there has been no
report on the use of a chiral auxiliary-bearing isocyanide
enolate for such asymmetric syntheses. Here, we report
the synthesis of the chiral auxiliary-bearing isocyanides
(R)-1 and (S)-1. We also report the synthesis of a new
type of optically active fluorescence system, namely, (R)-2
and (S)-2 derived from (R)-1 and (S)-1, the fluorescence
quantum yields of (R)-2 and (S)-2, and the crystal
structure of (S)-2. (R)-2 and (S)-2 are potentially useful
in fluorescence-detected circular dichroism for on-column
capillary electrophoresis.4
late conjugates derived from these compounds react with
a variety of carbon and heteroatomic electrophiles with
high diastereoselection led to the development of practical
methods for asymmetric alkylation,5 acylation,6 aldol
addition,5b,7 azidation,8,9 hydrazination,10 and hydroxy-
lation.11 Similarly, R,â-unsaturated N-acyloxazolidinones
have proven to be useful dienophiles in Lewis acid-
(5) (a) Evans, D. A.; Mathre, D. J . J . Org. Chem. 1986, 50(11), 1831.
(b) Evans, D. A.; Takes, J . M.; McGee, L. R.; Ennis, M. O.; Mathre, D.
J .; Barroli, J . Pure Appl. Chem. 1981, 53, 1109. (c) Evans, D. A.; Urpi,
F.; Somers, T. C.; Clark, J . S.; Bilodeak, M. T. J . Am. Chem. Soc. 1990,
112, 8215.
(6) Evans, D. A.; Ennis, M. D.; Le, T. J . Am. Chem. Soc. 1984, 106,
11154.
(7) (a) Evans, D. A.; Bartroli, J .; Shih, T. L. J . Am. Chem. Soc. 1981,
103(8), 2127. (b) Evans, D. A.; Weber, A. G. J . Am. Chem. Soc. 1986,
108, 6757. (c) Evans, D. A.; Rieger, D. C.; Bilodeau, M. T.; Urpi, F. J .
Am. Chem. Soc. 1981, 113, 1047. (d) Evans, D. A.; Clark, J . S.;
Metternich, R.; Novack, U. T.; Sheppard, G. S. J . Am. Chem. Soc. 1980,
112(2), 867.
(8) (a) Evans, D. A.; Britton, T. C.; Ellman, J . A.; Dorow, R. L. J .
Am. Chem. Soc. 1980, 112, 4011. (b) Evans, D. A.; Ellman, J . A.; Dorow,
R. Tetrahedron Lett. 1987, 28(11), 1123.
Resu lts a n d Discu ssion
Syn th esis of Ch ir al Au xiliar y-Bear in g Isoycan ides.
The substituted oxazolidinones 3 have proven to be
versatile chiral auxiliaries for the construction of enan-
tiomerically pure substances. The observation that eno-
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) Scho¨llkopf, U. Angew Chem., Int. Ed. Engl. 1977, 16(6), 339.
(2) (a) Suzuki, M.; Iwasaki, T.; Miyoshi, M.; Okamuya, K.; Matsu-
moto, K. J . Org. Chem. 1973, 38(2), 3571. (b) Tang, J . S., Verkade, J .
G. J . Org. Chem. 1994, 59, 7793.
(3) Sawamura, M.; Ito, Y. Chem. Rev. 1992, 92, 857.
(4) (a) Christensen, P. L.; Yeung E. S. Anal. Chem. 1989, 61(3), 1345.
(b) Yeung, E. S., private communication.
(9) (a) Evans, D. A.; Britton, T. C. J . Am. Chem. Soc. 1987, 109(22),
6881. (b) Evans, D. A.; Ellman, J . A. J . Am. Chem. Soc. 1989, 111(3),
1063.
S0022-3263(96)01554-X CCC: $12.00 © 1996 American Chemical Society

Chiral Auxiliary-Bearing Isocyanides as Synthons
J . Org. Chem., Vol. 61, No. 25, 1996 8751
Sch em e 1
Sch em e 2
Sch em e 3
catalyzed Diels-Alder reactions.12 However, R in 3 has
been limited to alkyl, aryl, acyl, and isothiocyano groups.
Compound 1 (i.e., 3 with R ) NC) though not previously
reported, is potentially useful for the construction of
many types of optically active substances, in view of the
known wide range of reactivities of racemic isocyanides.1
A successful synthesis of (R)-1 reported herein is shown
schematically in Scheme 1. Its enantiomer (S)-1 was
synthesized similarly. (R)-5 and (S)-5 were prepared
from their corresponding optically pure 2-oxazolidinones
in high yields by use of a procedure previously reported
for (S)-5.7b The synthesis of (S)-6, also reported pre-
viously,7b was carried out by the reaction of (S)-5 with
sodium azide in 1:1 CH2Cl2/H2O using the phase transfer
catalyst n-Bu4NHSO4. Since NaN3-CH2Cl2 is a danger-
ously explosive mixture,13 we modified the procedure by
using DMF as the solvent and eliminating the use of a
phase transfer catalyst. In this way (R)-6 and (S)-6 were
isolated in 85-90% yields. (R)-6 and (S)-6 were conve-
niently transformed into (R)-7 and (S)-7, respectively, by
use of a modified literature procedure used previously
for the preparation of the corresponding perchlorate
salt.7b An attempt to convert [(S)-7]ClO4 to (S)-8 with
CH3CO2CHO in HCO2H, followed by treatment with Na2-
CO3/H2O, resulted in the formation of 9 and (S)-4
(Scheme 2). Apparently, neutralization of the ammonium
group in [(S)-7]ClO4 facilitated conversion of the (CO)-O
linkage to the more thermodynamically stable C(O)-N
bond. The formation of (S)-4 from [(S)-7]ClO4 suggests
that the exo-acylimide bond is labile in an alkaline
environment. An attempt to convert (R)-5 to (R)-8
directly with NaNHCHO in DMF resulted in the forma-
tion of 10 and (R)-4, suggesting the exo-acylimide bond
is also labile to the strongly nucleophilic NaNHCHO
(Scheme 3). Formation of 10 in this reaction should be
accompanied by ClCH2CONHCHO, but the latter was not
isolated. [(R)-7]CF3CO2 and [(S)-7]CF3CO2 were success-
fully converted in high yield to (R)-8 and (S)-8, respec-
tively, with CH3CO2CHO in CH2Cl2 in the presence of
pyridine. Transformation of a formamide group to an
isocyano group is well documented,14 and herein both
(R)-8 and (S)-8 were converted to the desired crystalline
(R)-1 and (S)-1 in ∼60% yield with triphosgene15 in CH2-
Cl2 in the presence of Et3N.
Before we devised the strategy shown in Scheme 1, the
method shown in Scheme 4 for the synthesis of (R)-1 was
tried unsuccessfully. Though the reaction of isocy-
anoacetyl chloride (derived from CNCH2CO2K and
[Me2NdCHCl]Cl) with amines provides isocyanoaceta-
mides in high yield,16 (R)-1 was not formed by treating
Li[(R)-4)] with CNCH2CO2K/[Me2NdCHCl]Cl in THF.
Formation of (R)-4 suggests a proton transfer from
CNCH2COCl to Li[(R)-4] due to the high acidity of the
methylene protons in CNCH2COCl. While the reaction
of Li[(R)-4] with the anhydride of hexenoic acid and tri-
methylacetic acid gives 2-hexenylacetyloxazolidine in
93% yield,7b treatment of Li[(R)-4] with CNCH2CO2C(O)-
CMe3 resulted in the formation of (R)-4, supporting the
idea of proton transfer from the acidic methylene in
CNCH2CO2(CO)CMe3 to Li[(R)-4].
Syn th esis, Qu a n tu m Yield , a n d Cr ysta l Str u ctu r e
of Op tica lly Active Oxa zoles. Optically active fluo-
rescence materials with high quantum yields and/or
strong circular dichroism signals are rare but they are
important as standards in fluorescence-detected circular
dichroism for on-column detection in capillary electro-
phoresis (FDCD-CE). This newly developed method,
widely useful in biology, medicine, and in the pharma-
ceutical industry, enjoys several advantages over tradi-
tional detection methods. In FDCD-CE, riboflavin (which
has a low quantum yield and a weak CD signal) is used
as the optically active fluorescence standard. The intro-
(10) (a) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J . F. J .
Am. Chem. Soc. 1986, 108, 6395. (b) Trinable, L. A.; Vederas, J . F. J .
Am. Chem. Soc. 1986, 108, 6397. (c) Evans, D. A.; Britton, T. C.; Dorow,
R. L.; Dellaria, J . F., J r. Tetrahedron 1988, 44(7), 5525.
(11) Evans, D. A.; McCrissey, M. M.; Dorow, R. L. J . Am. Chem.
Soc. 1985, 167(14), 4347.
(12) (a) Evans, D. A.; Chapman, K. T.; Bisaka, J . Tetrahedron Lett.
1984, 25(37), 4071. (b) Evans, D. A.; Chapman, K. T.; Bisaka, J . J .
Am. Chem. Soc. 1984, 106, 4363.
(14) Ugi, J .; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann, K.
Angew. Chem., Int. Ed. Engl. 1965, 4(6), 472.
(15) Eckert, H.; Forster, B. Angew. Chem., Int. Ed. Engl. 1987, 26-
(9), 894.
(13) Chem. Eng. News 1993, Apr 19, p 4; Oct 11, p 2; Dec 13 p 4.
(16) Hoppe, I.; Scholkopf, U. Chem. Rev. 1976, 109, 482.

8752 J . Org. Chem., Vol. 61, No. 25, 1996
Tang and Verkade
Sch em e 4
Sch em e 5
and the plane containing the two carbonyl groups (O2-
C4-N2-C5-O3) is almost perpendicular (81.7°) to the
oxazole plane.
Exp er im en ta l Section
Gen er a l. All reactions and solvent treatments were done
under a nitrogen or argon atmosphere. THF and diethyl ether
were refluxed with sodium in the presence of benzophenone
and freshly distilled. CH2Cl2, pyridine, triethylamine, and
cyclohexane were refluxed with CaH2 and freshly distilled.
Methyl alcohol and ethyl alcohol were refluxed with sodium
and then freshly distilled. Compounds 14,2b 15,2b and tri-
methyl-pro-azaphosphatrane 1217 were prepared as described
as previously. Elemental analyses were performed by Desert
Analytics. The X-ray data collection and structure solution
was carried out in the Iowa State University Molecular
Structure Laboratory. All melting points are uncorrected.
(4R)-(-)-3-(Ch lor ocetyl)-4-(p h en ylm eth yl)-2-oxa zolid i-
n on e (R)-1. (4R)-(-)-4-(phenylmethyl)-2-oxazolidinone (R)-4
(4.00 g, 0.0226 mol) and Ph3CH (15 mg, indicator) were
dissolved in dry THF (50 mL) at room temperature and then
cooled to -78 °C. To this solution was added dropwise n-BuLi
(14 mL of a 1.6 M solution in hexanes 0.023 mol, 1.0 equiv)
giving an orange solution. Chloroacetyl chloride (2.83 g,
0.0248 mol, 1.10 equiv) was added by syringe over 2 min at
-78 °C to give a yellowish solution which was stirred at -78
°C for 20 min. The dry ice-acetone bath was removed, and
the solution was stirred for 2.5 h and finally quenched with
saturated aqueous ammonium chloride (25 mL). After vola-
tiles were removed in vacuo at room temperature, the residue
was diluted with distilled water (20 mL) and extracted with
CH2Cl2 (100 mL and then 50 mL). The combined extracts were
dried with anhydrous Na2SO4 overnight and filtered. The
filtrate was concentrated at 40 °C in vacuo to give crude solid
(R)-5 (5.71 g, 100%) which was used directly for further
reactions because 1H NMR spectra indicated nearly pure
material. For analyses, 0.76 g of crude (R)-5 was recrystallized
from CH2Cl2-hexane in a freezer to give colorless crystals. The
supernatant was removed by syringe while it was still cold,
and the colorless crystals remaining weighed 0.49 g after being
dried in vacuo. Mp 74-5 °C, Rf ) 0.48 (ethyl acetate:hexane
Ta ble 1. UV Sp ectr a l, F L Sp ectr a l, a n d Qu a n tu m Yield
Da ta for (R)-2, (S)-2, 14, 15 a n d P BD
FL emission Φ (315)
compounda
solvent
EtOH
etoh
etoh
EtOH
cyclohexane
λ
maxUV λmaxFL range (nm)
nm
(S)-2
(R)-2
14
15
PBD
313
313
277
291
301
397
397
346
410
355
330-650
330-650
<300-500
326-600
0.99
0.99
b
0.30
310 to 530 0.83c
Concentration: 2.0 × 10-6 M. b The Φ value was not measured
because this compound has no UV absorption at 315 nm. c Refer-
ence 19.
a
Ta ble 2. Selected Mea n Devia tion s a n d In ter p la n a r
An gles to th e p la n e O1-N1-C1-C2-C3
mean
deviations (Å)
interplanar
angles (deg)
least-square plane
O1-N1-C1-C2-C3
C3-C4-O2-N2
C8-C9-C10-C11-C12-C13
O2-C4-N2-C5-O3
0.0052
0.0033
0.0069
0.0198
0
83.0
22.5
81.7
duction of a standard having a higher fluorescence
quantum yield and/or a stronger circular dichroism could
enhance the detection sensitivity, thereby improving
detection limits.4 For this purpose, (R)-2 and (S)-2 were
conveniently synthesized in high yields from (R)-1 and
(S)-1 by a reaction we studied previously2b (Scheme 5).
The maximum UV absorption (λUVmax) and fluores-
cence (FL) emission (λFLmax), fluorescence quantum
yields Φ, and FL emission ranges for (R)-2, (S)-2, 14, 15,
and 2-(4-biphenyl)-5-phenyl-1,3,4-oxadiazole (PBD), a
standard for Φ measurements, are summarized in Table
1. The λUVmax red-shifts from 276.8 nm for 14 to 291.0
nm for 15 as OMe groups are added to the phenyl group.
Replacement of the ester group in 15 with an 2-oxo-
oxazolidin-3-yl acyl group in (R)-2 or (S)-2, further red-
shifts λUVmax to 315.4 nm. It is interesting to note the
λFLmax red-shift from 14 to 15, the λFLmax blue-shift from
15 to (R)-2 or (S)-2, and the quantum yield increase from
Φ ) 0.30 for 15 to Φ ) 0.99 for (R)-2 or (S)-2. The high
fluorescence quantum yields suggest the potential use
of (R)-2 and (S)-2 as optically active fluorescence stan-
dards in FDCD-CE.
) 1:2). [R]25 -87.2 (CH2Cl2, c ) 0.620 g/mL). Anal. Calcd:
D
C, 56.91; H, 5.01; N, 5.80. Found: C, 56.85; H, 4.87; N, 5.39.
(4R)-(-)-3-(Azid oa cetyl)-4-(p h en yl)m eth yl-2-oxa zolid i-
n on e (R)-6. Meth od A: Although this method is less safe
The bond lengths and bond angles for (S)-2 are
unremarkable. The ground state for the five-membered
oxazole ring is essentially planar. The dimethoxyphenyl
group plane is twisted 22.5° away from the oxazole plane
F igu r e 1. Computer drawing of (S)-2 (C22H20N2O6; fw, 408.4;
monoclinic, P212121; colorless; a ) 7.863(1) Å, b ) 10.059(1)
Å, c ) 25.218(3) Å; Z ) 4; R ) 3.85%; GOF ) 1.82). Ellipsoids
are drawn at the 50% probability level.
(17) Tang, J . S.; Verkade, J . G. Tetrahedron Lett. 1993, 34(18), 2903.

Chiral Auxiliary-Bearing Isocyanides as Synthons
J . Org. Chem., Vol. 61, No. 25, 1996 8753
than method B, it is given here for completeness. To a solution
of crude (4R)-(-)-3-(chloroacetyl)-4-(phenylmethyl)-2-oxazoli-
dinone (R)-5 (7.1 g, 0.028 mol) in dry CH2Cl2 (30 mL) were
added sequentially water (30 mL), NaN3 (9.2 g, 0.14 mol, 5.0
equiv) and the phase-transfer catalyst (n-Bu)4NHSO4 (0.96 g,
0.0028 mol, 0.10 equiv). The reaction mixture was stirred
vigorously with a mechanical stirrer for 1.5 h. The organic
layer was separated, and the aqueous layer was extracted with
CH2Cl2 (100 mL). The combined organic layers were concen-
trated in vacuo, and the resulting residual brownish oil was
filtered through a short silica gel column (50 × 50 mm) using
CH2Cl2 as the eluent to give crude (R)-6 (7.1 g, 97%) as white
crystals. For analysis, 0.42 g of crude (R)-6 was recrystallized
from ethyl acetate-hexane to give 0.35 g of pure (R)-6. Mp
the mixture was rotary-evaporated at 30 °C using ice-water
as the coolant. Final evaporation was carried out under oil
pump pressure at 0.4 torr. This two-fold evaporation proce-
dure was repeated three times. The resulting oil was flash-
chromatographed on a silica gel column (50 × 50 mm) using
hexane:ethyl acetate (3:1 to 1:1) to give the product as a
colorless oil (4.85 g, 93%). Rf ) 0.29 (hexane:ethyl acetate )
1:3). [R]25 ) -86.0 (CH2Cl2, c ) 0.812 g/mL). Anal. Calcd
D
C, 59.54; H, 5.38; N, 10.68. Found: C, 59.42; H, 5.48; N, 10.23.
(4R)-(-)-3-(Isocya n oa cetyl)-4-(p h en ylm eth yl)-2-oxa zo-
lid in on e (R)-1. To a solution of (4R)-(-)-3-[(formylamino)-
acetyl]-4-(phenylmethyl)-2-oxazolidinone (0.21 g, 0.80 mmol)
in dry CH2Cl2 (27 mL) was added by syringe dry Et3N (0.21 g,
2.0 mmol, 2.5 equiv). The solution was cooled to 0 °C, and a
solution of triphosgene (0.095 g, 0.32 mmol, 1.2 equiv) which
was weighed in a hood into dry CH2Cl2 (5 mL) was added
dropwise. The reaction mixture was stirred at room temper-
ature for 24 h and filtered through a short silica gel column
with 1:1 hexane/ethyl acetate) to remove salts. The eluents
were combined and concentrated in vacuo. The residue was
flash chromatographed on a silica gel column (45 × 130 mm)
with hexane:ethyl acetate (2:1) to give colorless crystals (0.13
g, 67%). Mp 277.0-278.0 °C, Rf ) 0.62 (hexane:ethyl acetate
) 1:1). [R]25D ) -95.0 (CH2Cl2, c ) 0.500 g/mL). Anal. Calcd
C, 63.92; H, 4.95; N, 11.47. Found: C, 63.72; H, 4.88; N, 11.40.
(4S)-(+)-3-(Azid oa cetyl)-4-(p h en ylm eth yl)-2-oxa zolid i-
n on e (S)-6. The synthesis of (S)-6 was similar to that of (R)-6
using method B (overall yield from (R)-4, 90%). Rf ) 0.48
(hexane:ethyl acetate ) 2:1). [R]25D ) +93.6 (CH2Cl2, c ) 0.917
g/mL).
62-63 °C, Rf ) 0.48 (hexane:ethyl acetate ) 2:1). [R]25
)
D
-93.9 (CH2Cl2, c ) 0.917 g/mL). Anal. Calcd: C, 55.38; H,
4.65; N, 21.52. Found: C, 55.17; H, 4.68; N, 21.30.
Meth od B: To a stirred solution of crude (R)-5 (27.3 g, 0.108
mol) in DMF (100 mL) was added NaN3 (35.1 g, 0.540 mol,
5.00 equiv). After the mixture was stirred vigorously with a
mechanical stirrer for 10 min, the liquid layer changed from
colorless to brownish. The mixture was further stirred at room
temperature for 11 h and filtered through Celite in vacuo to
remove inorganic salts and then ethyl acetate (100 mL × 2)
was passed through the Celite. The filtrate was washed with
25% sodium chloride solution (300 mL). The organic phase
was separated, and the aqueous phase was extracted with
ethyl acetate (100 mL). The combined organic phases were
dried with anhydrous Na2SO4 and then concentrated in vacuo
at 35 °C. The residual oil was crystallized from ethyl acetate
and hexane (1:1) in a freezer to give (R)-6 as white crystals
(12.25 g). The supernatant was concentrated in vacuo at 25°
to 30 °C, and the residue was flash-chromatographed on a
silica gel column (45 × 150 mm) using a 2:1 ratio of CH2Cl2:
hexane as eluent to give 11.4 g of (R)-6 as a white solid. The
total yield of (R)-6 was 85%.
(4S)-(+)-3-[(F or m yla m in o)a cetyl]-4-(p h en ylm eth yl)-2-
oxa zolid in on e (S)-8. The synthesis of (S)-8 was similar to
that of (R)-8 (overall yield from (S)-6, 90%). Rf ) 0.29 (ethyl
acetate:hexane ) 3:1). [R]25 ) +86.5 (CH2Cl2, c ) 0.812
D
g/mL).
(4S)-(+)-3-(Isocya n oa cetyl)-4-(p h en ylm eth yl)-2-oxa zo-
lid in on e (S)-1. The synthesis of (S)-1 was similar to that of
(R)-1. Yield ) 53%. [R]25D ) +195.3 (CH2Cl2, c ) 0.500 g/mL).
(+)-5-(3,4-D i m e t h o x y p h e n y l)-4-[N -[(4S )-2-o x o -4-
(p h en ylm eth yl)-2-oxa zolid in yl]]ca r bon yloxa zole (S)-2.
To a stirred solution of trimethyl-pro-azaphosphatrane 1217
(0.23 g, 0.0011 mol) in dry THF (5 mL) at 0 °C was added
under nitrogen colorless crystals of (4S)-3-(isocyanoacetyl)-4-
(phenylmethyl)-2-oxazolidinone, (S)-1 (0.26 g, 0.0010 mol).
After 5 min, a colorless solution of 3,4-dimethoxybenzoyl
chloride (0.22 g, 1.1 mmol) in dry THF (5 mL) was added
dropwise to give an orange solution plus a white precipitate.
The mixture was stirred at 0 °C for 20 min and then at room
temperature for 30 min. The volatiles were removed in vacuo,
and the resulting residue was treated with water (5 mL). The
solution was then extracted with ethyl acetate (25 mL × 2).
The combined extracts were dried overnight with anhydrous
Na2SO4 and flash chromatographed on a silica gel column (25
× 130 mm) with ethyl acetate/hexane (1:1) to afford 0.39 g
(96%) of (S)-2 as colorless crystals. Rf ) 0.20 (ethyl acetate:
hexane ) 1:1). The solution was blue under UV light (254
nm). Anal. Calcd C, 64.68; H, 4.94; N, 6.86. Found: C, 64.79;
[[[(4R)-(-)-4-(P h en ylm eth yl)-2-oxooxa zolid in -3-yl]ca r -
bon yl]m eth yl]am m on iu m Tr iflu or oacetate [(R)-7]CF3CO2.
To a solution of crude (4R)-(-)-3-(azidoacetyl)-4-(phenyl-
methyl)-2-oxazolidinone (R)-6 (5.31 g, 0.0205 mol) in anhy-
drous methanol (160 mL) was added CF3CO2H (4.8 mL, 0.062
mol, 3.0 equiv), and then 10% palladium-carbon (1.30 g) was
added slowly with a spatula. The reaction flask was stoppered
with a septum, and air inside the flask was removed by
flushing with argon. The flask was then purged with hydrogen
for 10 min by bubbling hydrogen through a long needle inlet
and out via a short needle. The mixture was then stirred
under a hydrogen atmosphere (by attaching a hydrogen balloon
to a needle through the septum) for 23.5 h. The Pd/C catalyst
was filtered through Celite and was washed with methanol
(30 mL). The filtrate and washing solution were combined and
rotary-evaporated at room temperature using ice-water as a
recycling coolant. The residue was then evacuated under oil
pump pressure (0.4 torr) at room temperature to afford white
foamy particles (7.1 g, 100%) which were not further purified
but were used directly for the formylation reaction that
followed.
(4R)-(-)-3-[(F or m yla m in o)a cetyl]-4-(p h en ylm eth yl)-2-
oxa zolid in on e (R)-8. To a suspension of crude [(R)-7]CF3-
CO2 (7.2 g, 0.020 mol) in dry CH2Cl2 (100 mL) was added by
syringe CH3CO2CHO18 (20.4 g, 0.232 mol). The reaction
mixture was placed in a dessicator containing CaSO4 and the
dessicator was placed in a freezer. After 2 min a clear solution
formed which was allowed to cool to 0 °C and then dry pyridine
(18.5 g, 0.235 mol) was added by syringe over a period of 2
min. The solution was further stirred at 0 °C for 45 min and
then at room temperature for 1 h. Finally it was poured into
10% hydrochloric acid (85 mL). The organic phase was
separated and the aqueous phase was extracted with CH2Cl2
(2 × 100 mL). The combined organic phases were dried
overnight with anhydrous Na2SO4 after which volatiles were
removed at 30 °C in vacuo. To remove any acetic acid
remaining, 30 mL of ethyl acetate/toluene (1:2) was added and
H, 4.83; N, 6.72. [R]25 ) +68.9 (c ) 0.80 g/mL). Pertinent
D
UV spectral, FL spectral, and fluorescence quantum yield data
are summarized in Table 1.
(+)-5-(3,4-D i m e t h o x y p h e n y l)-4-[[N -(4R )-2-o x o -4-
(p h en ylm eth yl)-2-oxa zolid in yl]]ca r bon yl]oxa zole (R)-2.
(R)-2 was synthesized similarly. Yield, 96%; [R]25 ) -68.8
D
(c ) 0.80 g/mL). Pertinent UV spectral, FL spectral, and
fluorescence quantum yield data are summarized in Table 1.
Ultr a violet Sp ectr a , F lu or escen t Sp ectr a , a n d F lu o-
r escen ce Yield of (R)-2, (S)-2, 14, 15 a n d 2-(4-Bip h en yl)-
5-p h en yl-1,3,4-oxa d ia zole (P BD). The concentrations of (R)-
2, (S)-2, 14, 15, and PBD in cyclohexane were all 2.0 × 10-6
M. Ultraviolet spectra and absorbances were measured with
a Shimadzu UV-240 Ultra-Via spectrometer, and fluorescent
(19) Birlman, I. B., Ed. Handbook of Fluorescence Spectra of
Aromatic Molecules, 2nd ed.; Academic Press: New York, 1971; pp 291
and 306.
(18) Muramatsu, I.; Murakami, H.; Yoneda, T.; Hagitani, A. Bull.
Chem. Soc. J pn. 1965, 38(2), 244.
(20) Parker, C. A.; Rees, W. T. Analyst 1961, 85, 587.

8754 J . Org. Chem., Vol. 61, No. 25, 1996
Tang and Verkade
spectra and intensities (area integration) were measured with
a Spex FluoroMax spectrometer using 315 nm as the exciting
wavelength. Fluorescent quantum yields were calculated
using the following equation:20
absorption correction was not deemed necessary. The space
group P212121 was chosen based on systematic absences and
intensity statistics. This assumption proved to be correct as
determined by a successful direct-method solution and sub-
sequent refinement. All non-hydrogen atoms were placed
directly from the E-map. All non-hydrogen atoms were refined
with anisotropic thermal parameters. All hydrogen atoms
were refined as riding atoms with C-H distances of 0.96 Å
and individual isotropic displacement parameters. Each
methoxy group was refined torsionally in order to find the best
placement of the hydrogen atoms. Conversion was then made
to a riding atom model with group isotropic displacement
parameters. Refinement calculations were performed on a
Digital Equipment MicroVAX 3100 computer using the SHELX-
TL-Plus programs.22,23
F(1 - 10-A
o
n2
)
Φf ) Φf°
(1)
2
Fo(1 - 10-A) no
where Φf and Φf° are fluorescent quantum yields of the
specimen and the standard (PBD, Φf° ) 0.8319), respectively,
F and Fo are total fluorescent intensities of the specimen and
the standard (PBD), respectively, A and Ao are the absorbances
of the specimen and the standard (PBD) at 315 nm, respec-
tively, and ni and no are the refractive indices of the specimen
solution in ethanol and the standard (PBD) solution in
cyclohexane, respectively. Since all the solutions used were
quite dilute, the solvent refractive indices21 of pure ethanol (n
) 1.3600) and cyclohexane (no ) 1.4246) were used in the
calculations. The pertinent results are summarized in Table
1.
Ack n ow led gm en t. The authors are grateful to the
Donors of the Petroleum Research Foundation, admin-
istered by the American Chemical Society, and the
National Science Foundation for grant support of this
research.
Molecu la r Str u ctu r e of (S)-2. A crystal of the compound
was attached to the tip of a glass fiber and mounted on the
P4RA diffractometer for data collection at 295 ( 1 K. The cell
constants for the data collection were determined from reflec-
tions found from a 360° rotation photograph. High-angle cell
constants were determined from a subset of intense reflections
in the range of 35.0 to 50.0° (2θ). Lorentz and polarization
corrections were made, and a nonlinear correction based on
the decay in the standard reflections was also applied to the
data. A series of azimuthal reflections was collected. An
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
data, mass spectral molecular weights, and details of at-
tempted syntheses (7 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O961554G
(22) SHELXTL-Plus, Siemens Analtical X-ray Inc., Madison, WI.
(23) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
(21) Reichardt, C. Ed. Solvent Effects in Organic Chemistry; Verlag
Chemie, Weinheim, New York, 1979.