G. Desimoni et al. / Tetrahedron 57 -2001) 10203±10212
10211
20
white crystals: mp 222±2238C; [a]D 1252.0 *c0.5 in
the ligand separated ®rst and the products mixture was
submitted to the previously described HPLC analysis. The
adducts 3 can be isolated from a reaction run on 1.00 mmol
scale by column chromatography on silica gel 230±400
mesh *cyclohexane/AcOEt 3:7 as eluant) and, depending
on the diastereomeric composition of the reaction mixture,
pure 3a,b or this in admixture with 3c,d was isolated. The
chloroform); IR *Nujol) n 3410, 1690 cm21 1H N MR
;
*300 MHz, CDCl3, 258C, TMS): d 5.60 *d, 3J*H,H)
3
4.5 Hz, 2H; CHCl), 5.70 *dd, J*H,H)4.5, 9.5 Hz, 2H;
3
CHN), 7.1±7.3 *m, 20H), 8.05 *t, J*H,H)7.5 Hz, 1H;
4H pyridine), 8.35 *d, 3J*H,H)7.5 Hz, 2H; 3,5H pyridine),
3
8.78 *d, J*H,H)9.5 Hz, 2H; NH); 13C NMR *75.5 MHz,
1
CDCl3) d 58.6, 67.0, 125.4, 127.8, 128.0, 128.1, 128.3,
128.6, 135.6, 136.8, 139.3, 148.4, 162.2. Elemental analysis
calcd *%) for C35H29Cl2N3O2 *594.5): C 70.71, H 4.92, N
7.07; found C 70.56, H 5.04, N6.98.
anti-3a,b has H NMR *300 MHz, CDCl3, 258C, TMS): d
1.09 *d, 3J*H,H)6.9 Hz, 3H; Me), 2.45±2.55 *m, 1H;
3
CHMe), 2.85 *dd, J*H,H)7.35, 16.9 Hz, 1H; CHCO),
3
3.15 *dd, J*H,H)5.9, 16.9 Hz, 1H; CHCO), 4.00±4.05
*m, 2H; NCH2), 4.40±4.45 *m, 2H; OCH2), 5.02 *ddd,
3
4.2.6. 2,6-Bis[ꢀ4R,5R)-diphenyl-1,3-oxazolin-2-yl]pyridine
ꢀ7a). To a suspension of 9a *0.89 g, 1.5 mmol) in ethanol
*20 mL), an aqueous solution of 2NNaOH *10 mL) was
added and the mixture was re¯uxed untill the starting
product disappeared *about 3 hÐTLC, eluant cyclo-
hexane/ethyl acetate *7:3)). The hot suspension was ®ltered
and the white solid, washed with water, gave pure 7a
*0.59 g, yield 75%). It crystallised from ethyl acetate as
3J*H,H)1.5, 2.0, 6.4 Hz, 1H; 50H), 6.15 *dd, J*H,H)
3
2.0, 5.8 Hz, 1H; 30H), 7.59 *dd, J*H,H)1.5, 5.8 Hz, 1H;
40H). This spectrum is in accordance with that reported in
the literature for 3a.13b Some absorptions can be assigned to
the syn-3c,d, H NMR *300 MHz, CDCl3, 258C, TMS) d
1
0.94 *d, 3J*H,H)7.0 Hz, 3H; Me), 2.60±2.70 *m, 1H;
CHMe), 2.90 *dd, 1H; CHCO), 5.18±5.20 *m, 1H; 50H),
3
6.18 *dd, J*H,H)3.7, 5.8 Hz, 1H; 30H), 7.47 *dd,
white crystals: mp 201±2028C; [a]D 141.4 *c0.5 in
3J*H,H)1.5, 5.8 Hz, 1H; 40H).
20
20
chloroform) *7b, [a]D 241.4); HPLC analysis using a
Chiralpak AD column with hexane/2-propanol *2:1) as
eluant *0.7 mL min21), retention time 16.9 min *7b, same
4.3. Mukaiyama±Michael reaction between 1 and 2
carried out with different enantiomeric purity of the
catalyst from lanthanium tri¯ate and 7
conditions, retention time 13.8 min); IR *Nujol)
n
1
1660 cm21; H NMR *300 MHz, CDCl3, 258C, TMS): d
3
3
5.35 *d, J*H,H)8.5 Hz, 2H; CHN), 5.55 *d, J*H,H)
3
8.5 Hz, 2H; CHO), 7.3±7.5 *m, 20H), 8.00 *t, J*H,H)
From reactions carried out following the general procedure
described earlier but with mixtures of 7a/7b having known
enantiomeric purities of 100, 80, 60, 40 and 20%, 3a was
obtained with ee of $99.5, 72, 60, 43 and 20%, respectively.
The relationship between the eeproduct and eeligand was linear
*r0.993).
3
9.5 Hz, 1H; 4H pyridine), 8.42 *d, J*H,H)9.5 Hz, 2H;
3,5H pyridine); 13C NMR *75.5 MHz, CDCl3) d 78.9,
89.9, 126.1, 126.5, 126.8, 127.8, 128.5, 128.7, 137.3,
139.7, 141.2, 147.0, 162.9; elemental analysis calcd *%)
for C35H27N3O2 *521.6): C 80.59, H 5.22, N8.06; found C
80.66, H 5.13, N8.15.
4.3.1. X-Ray data collection and processing of the ꢀ1:1)
7b/lanthanium tri¯ate complexꢀ11). Lanthanum tri¯ate
*0.039 g, 0.066 mmol) was added to a solution of 7b
*0.035 g, 0.066 mmol) in acetonitrile *0.5 mL) at ambient
temperature. The colourless solution was let aside for 1
week then toluene was added until incipient turbidity.
Within 1 week colourless crystals of 11 separated that
4.2.7. General procedure for the enantioselective
Mukaiyama±Michael reaction between 1 and 2. *E)-3-
Crotonoyl-1,3-oxazolidin-2-one *2) *0.039 g, 0.25 mmol),
the chiral ligand box *4, 5) or pybox *6, 7) *0.013 mmol),
the inorganic perchlorate or tri¯ate *0.013 mmol) and, when
required, the molecular sieves *0.040 g) were added to
anhydrous CH2Cl2 *0.5 mL) at ambient temperature in a
rubber septum sealed vial, and the mixture was stirred and
then cooled at 08C. After 1 h *trimethylsilyloxy)furan *1)
*0.047 g50 mL, 0.30 mmol) was added with a micro-
syringe and stirring at 08C was continued for 3 days. The
reaction was decomposed in water, extracted with CH2Cl2
and dried. If TLC *cyclohexane/ethyl acetate 6:4 as eluant)
showed some unreacted starting product 2, the yield of the
1
were ®ltered: mp about 2008C after softening; H N MR
*300 MHz, CD3CN, 258C, TMS): d 5.62 *d, 3J*H,H)
3
7.8 Hz, 2H; CHN), 5.79 *d, J*H,H)7.8 Hz, 2H; CHO),
3
7.4±7.5 *m, 20H), 8.41 *d, J*H,H)8.5 Hz, 1H; 3H pyri-
dine), 8.42 *d, 3J*H,H)6.8 Hz, 1H; 30H pyridine), 8.52 *dd,
3J*H,H)6.8, 8.5 Hz, 1H; 4H pyridine); 13C NMR reported
in Table 3.
1
reation *Tables 1 and 2) was determined by H NMR from
X-Ray data were obtained on an Enraf±Nonius CAD4
diffractometer. Calculations were performed with the
WinGX-97 software.34 The structure was solved by direct
methods *SIR92)35 and re®ned by full-matrix least-squares
using SHELXL-9736 with anisotropic displacement para-
meters for all non-hydrogen atoms. Hydrogen atoms were
inserted in calculated positions with isotropic displacement
parameters proportional to those of their neighbouring
atoms. Atomic scattering factors were taken from
International Tables for X-rayCrystallography .37 Diagrams
of the molecular structures were produced by the ORTEP
program.38 Crystallographic data have been deposited with
the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-156651.
the ratio 3:2, taking the methyl doublets at 1.09, 0.94 and
1.95 d to determine 3a,b and 3c,d vs 2, respectively. In each
case the standard analysis of the reaction mixture was
performed by HPLC analysis using a Chiralpak AD column
with hexane/2-propanol *2:1) as eluant *0.5 mL min21). The
average retention times, 68 and 75 min for *R,R) anti-3a and
*S,S) anti-3b, respectively; 57 and 82 min for syn-3c,d,
largely depend from the small variations of the solvents
and were checked on the products of a reaction run under
non-enantioselective conditions *literature: 42.5 and
49.6 min for 3a and 3b, respectively).13b When the ligand
was 7, to avoid its large absorption, the CH2Cl2 residue was
chromatographed on silica gel *cyclohexane/AcOEt 3:7),