Enantioselective Synthesis of 1,3-Oxazolidin-2-imine Derivatives
J . Org. Chem., Vol. 63, No. 18, 1998 6233
bromide (10 mmol) and triethylamine (20 mmol) in dichlo-
romethane (15 mL) at 0 °C. The resulting mixture was then
washed with water and dried with anhydrous sodium sulfate.
Evaporation of the solvent gave crude carbodiimide (6) which
was distilled at reduced pressure to yield the desired unsym-
metrical carbodiimide 6. IR, NMR, MS, and analytical data
of an example unsymmetrical carbodiimide 6a are shown
below (see Supporting Information for all 6).
NMR (CDCl3) δ 14.04, 20.66, 33.84, 46.47, 60.31, 68.62, 119.07,
120.74, 122.74, 128.48, 135.53, 139.48, 150.01 ppm; MS (m/e)
244 [M]+; HRMS calcd for C15H20N2O 244.1576, found 244.1587.
Gen er a l P r oced u r e for th e Asym m etr ic P a lla d iu m -
Ca ta lyzed Cycloa d d ition Rea ction of Vin yloxir a n e w ith
Un sym m etr ica l Ca r bod iim id es. A mixture of Pd2(dba)3‚
CHCl3 (0.03 mmol), TolBINAP (0.06 mmol), and THF (5 mL)
was stirred at room temperature for 30 min. Vinyloxirane 1a
(1.5 mmol) and unsymmetrical carbodiimide 6 (1.0 mmol) were
added, and the mixture was then stirred under nitrogen at
room temperature until the conversion of the carbodiimide was
complete. The orange brown solution was subjected to rotary
evaporation, and the residue was purified by preparative silica
gel TLC using pentane/ether mixture as the developer. The
purified product was rechromatographed on preparative HPLC
in order to eliminate any residual chiral phosphine ligand. The
enantiomeric excess was calculated by determining peak area
(using a programming analytical HPLC integrator).
Sin gle-Cr ysta l X-r a y Diffr a ction Stu d y of 7g. Crystals
of 7g were obtained by purification using preparative TLC,
preparative HPLC, and recrystallization from an ether-
hexane solution. One of the crystals having a proximate
dimension of 0.2 × 0.2 × 0.2 mm was mounted on a glass
capillary. All measurements were made on a Siemens SMART
diffractometer using the ω scan mode. Cell dimensions and
an orientation matrix for data collection were obtained from
least-squares refinement using the setting angles of 8192
reflections in the range 3° < 2θ < 57° and corresponded to a
monoclinic cell with dimensions a ) 13.0399(2) Å, b ) 16.4639-
(2) Å, c )17.2130(2) Å, â ) 109.273(1). For Z ) 4 and FW )
596.85, the calculated density is 1.136 g/cm3. On the basis of
the systematic absences, the space group was determined to
be P21. The data were collected at -100 °C using the ω-2θ
scan technique to a maximum 2θ value of 57°.
N-Cycloh exyl-N ′-p h en ylca r bod iim id e (6a ) (R′ ) C6H11
,
R′′ ) C6H5): oily liquid; IR (CdN) 2116 cm-1; 1H NMR(CDCl3)
δ 1.20-2.20 (m, 10 H), 3.48 (m, 1H), 7.05-7.39 (m, 5H) 13C
NMR (CDCl3) 24.34, 25.30, 34.91, 56.61, 123.31, 124.47,
129.30, 140.88 ppm; MS (m/e) 200 [M]+, HRMS calcd for
C
13H16N2 200.1313, found 200.1291.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Cy-
cloa d d ition Rea ction of Vin yloxir a n es a n d Heter ocu -
m u len es. A mixture of Pd(PPh3)4 (0.03 mmol), PPh3 (0.06
mmol), and THF (3 mL) was stirred under nitrogen at room
temperature for 30 min. Vinyloxirane 1 (1.5 mmol) and
unsymmetrical carbodiimide 6 (1 mmol) were added to the
solution. The mixture was then stirred under nitrogen at room
temperature until the conversion of the carbodiimide was
complete (monitored by the shift of the IR absorption of the
CdN band in the free carbodiimide (∼2100 cm-1) to that of
the oxazolidine (1670-1690 cm-1)). The light yellow homo-
geneous solution was then concentrated by rotary evaporation,
and the residue was purified by silica gel TLC using pentane/
ether mixture as the developer. Melting points, IR, NMR, MS
and analytical data for selected representatives 7 and 8 are
as follows (see Supporting Information for all cases).
N -P h e n y l-3-c y c lo h e x y l-4-v i n y l-1,3-o x a z o li d i n -2-
im in e (7a ) (R ) H, R′ ) C6H11, R′′ ) C6H5): oily liquid; IR
(CdN) 1675 cm-1; 1H NMR (CDCl3) δ 0.95-2.05 (m, 10H), 3.88
(m, 2H), 4.28 (m, 2H), 5.18-5.34 (m, 2H), 5.75-5.93 (m, 1H),
6.90-7.35 (m, 5H); 13C NMR (CDCl3) δ 25.61, 25.82, 25.94,
29.55, 31.69, 54.30, 58.38, 69.54, 118.15, 121.74, 123.37,
128.35, 138.16, 148.13,152.38 ppm; MS (m/e) 270 [M]+. Anal.
Calcd for C17H22N2O: C, 75.52; H, 8.20; N, 10.36 Found: C,
75.53; H, 8.37; N, 10.38.
A total of 23988 reflections were collected. The unique set
contained only 8855 reflections. The final cycle of full matrix
least-squares refinement was based on 5999 observed reflec-
tions (I > 2.5σ(I)) and 398 variable parameters. Weights based
on counting statistics were used. The maximum and minimum
peaks on the final differences Fourier map corresponded to
0.300 and -0.400 e/a3, respectively.
N -C y c lo h e x y l-3-p h e n y l-4-v i n y l-1,3-o x a z o li d i n -2-
im in e (8a ) (R ) H, R′ ) C6H5, R′′ ) C6H11): oily liquid;
IR (CdN) 1673 cm-1
;
1H NMR (CDCl3) δ 1.10-2.00 (m,
All the calculations were performed using the NRCVAX
10H), 3.50 (m, 2H), 4.03 (dd, 1H, J ) 8.1 and 4.7 Hz),
4.42 (dd, 1H, J ) 8.1 and 8.1 Hz), 4.65 (m, 1H), 5.32
(m, 2H), 5.85 (m, 1H), 6.95-7.70 (m, 5H); 13C NMR (CDCl3)
δ 25.56, 25.76, 25.89, 29.45, 31.66, 54.18, 58.27, 69.42,
118.01, 113.64, 123.96, 141.25, 138.17, 152.29, 154.53 ppm;
MS (m/e) 270 [M]+; HRMS calcd for C17H22N2O 270.1732.
found 270.1725.
crystallographic software package.20
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for support of this research.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 6a -k , 7b-f, 7h , and 8a -i. Spectral
data of compounds 6a -k , 7a -i, and 8a -i. Text giving full
details of the X-ray structure determination of 7g including
the experimental procedure and tables of bond distances and
angles and torsion angles (75 pages). This material is con-
tained 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.
N-n -Bu tyl-3-p h en yl-4-vin yl-1,3-oxa zolid in -2-im in e (7b)
(R ) H, R′ ) C4H9, R′′ ) C6H5): oily liquid; IR (CdN) 1677
cm-1; 1H NMR (CDCl3) δ 0.95 (t, 3H), 1.28-1.65 (m, 4H), 3.17
(m, 1H), 3.99 (dd, 1H, J ) 8.12 and 7.19 Hz), 4.23 (dd, 1H, J
) 15.57 and 7.69 Hz), 4.45 (dd, 1H, J ) 7.95 and 7.95 Hz),
5.47 (m, 2H), 5.80 (m, 1H), 6.90-7.30 (m, 5H); 13C NMR
(CDCl3) δ 13.89, 20.06, 28.91, 42.52, 60.25, 69.27, 120.57,
121.89, 123.40, 128.43, 135.23, 147.94, 152.64 ppm; MS (m/e)
244 [M]+; HRMS calcd for C15H20N2O 244.1576, found 244.1567.
N-P h en yl-3-n -bu tyl-4-vin yl-1,3-oxa zolid in -2-im in e (8b)
(R ) H, R′ ) C6H5, R′′ ) C4H9): oily liquid; IR (CdN) 1697
cm-1; 1H NMR (CDCl3) δ 0.94 (t, 3H), 1.26-1.63 (m, 4H), 3.29
(m, 1H), 4.02 (dd, 1H, J ) 8.1 and 5.4 Hz), 4.45 (m, 1H), 4.66
(m, 1H), 5.29 (m, 2H), 5.81 (m, 1H), 6.97-7.59 (m, 5H); 13C
J O9804341
(20) Gabe, E. J .; Le Page, Y.; Charland, J . P.; Lee, F. L.; White, P.
S. J . Appl. Crystallogr. 1989, 22, 348-387.