S. Menichetti et al. / Tetrahedron 61 (2005) 5005–5010
5009
1
IR (KBr) 1785C1740C1718 (N–C]O PthCC]O
H NMR (200 MHz, CDCl ) d: 2.37 (s, 3H), 3.01 (AB part
3
K1
1
ester) cm
C]COCH , 3H), 5.25 (s, resin-ArCH OCO, 2H); 7.70–
.
H NMR (400 MHz, CDCl ) d: 2.73 (s,
of an ABX system, JABZ13.2 Hz, 2H), 3.77 (s, 3H), 5.68 (X
part of an ABX system, JZ5.4, 2.7 Hz, 1H), 7.30–7.60 (m,
5H).
3
3
2
7
.90 (m, Phthaloyl, 4H), 13.93 (s, C]COH, 1H).
4.2.3. Immobilised oxathiin 9 from sulfenylated resin 6.
Sulfenylated resin 6 (180 mg, 0.15 mmol) was swelled in
dry CHCl (4 mL) at room temperature for 2 h, then ethyl
3
4.2.7. Thiopyran 30. To a pre-swelled sulfenylated resin 27
(160 mg, 0.12 mmol) in dry CHCl3 (4 mL) at room
temperature for 2 h, 2,3-dimethyl-1,3-butadiene (54 mg,
vinyl ether (8) (56 mg, 0.78 mmol) and Et N (33 mg,
3
0.66 mmol) and Et N (14 mg, 0.14 mmol) were added in
3
0
.32 mmol) were added in sequence and the mixture heated
sequence and the mixture heated to 60 8C for 20 h. The
general work-up afforded 154 mg of immobilised thiopyran
resin 29 which was dried and reacted with MeONa in dry
THF as described above. Evaporation of the solvent gave
thiopyran 30 (13 mg, 53%) as a colourless oil with
spectroscopic data identical of those reported in the
to 60 8C for 18 h. The general work-up afforded 164 mg of
resin 9.
IR (KBr) 1702 (s, C]O ester conjugated), 1600 (s, C]C
conjugated) cm . H NMR (400 MHz, CDCl ) d: 1.30 (bs,
OCH CH , 3H), 2.40 (s, C]COCH , 3H), 2.95–3.05 (m,
2
K1 1
3
1
9
3
3
literature.
SCH , 2H), 3.87–3.92 (m, OCH CH , 1H), 4.01–4.06 (m,
2
2
3
1
17
H NMR: (200 MHz, CDCl ) d: 1.69 (bs, 3H), 1.71 (bs,
OCH CH , 1H), 5.25 (bs, OCHO, 1H), 5.40 (s, resin-
2
3
3
ArCH OCO, 2H).
2
3H), 2.45 (AB system, 2H, JZ6.2 Hz), 3.08 (AB system,
2H, JZ16.2 Hz), 3.6 (t, 1H, JZ6.2 Hz), 3.73 (s, 3H).
4.2.4. Immobilised oxathiin 9 from resin 5: simplified
procedure. To a pre-swelled suspension of resin 5 (153 mg,
4.2.8. Immobilised monomeric thione 28. In a flat-bottom
0
1
.17 mmol) in dry DCM (2.5 mL) at room temperature for
h, PhtNSCl 1 (75 mg, 0.35 mmol) in dry DCM (1.5 mL)
PE syringe equipped with two sintered Teflon filters, resin
7 (212 mg, 0.16 mmol) was swelled in dry DCM (2 mL) at
room temperature for 1 h, then the syringe was covered with
2
and dry Et N (44 mg, 0.43 mmol) were added in succession.
3
After 20 min at room temperature vinyl ether 8 (62 mg,
0.86 mol) was introduced and the mixture heated to 60 8C
for 19 h. The general work-up afforded 170 mg of resin 9.
aluminium foil and Et N (49 mg, 0.50 mmol) was added in
3
the dark. After 2 h at room temperature the deep pink resin
obtained was washed with dry DCM, until no trace of Et N
3
was detected in the washing, transferred into a vials with dry
DCM (2 mL) and vinyl ether 8 (36 mg, 0.50 mmol) and
heated to 60 8C for 18 h. The usual work-up and cleavage
with MeONa gave cycloadduct 10 in 16% isolated yield.
4
.2.5. Resin 9 cleavage with MeONa: oxathiin 10. The
resin 9 (170 mg, 0.16 mmol) was swelled in dry THF
6 mL) at room temperature for 1 h; a solution of freshly
(
prepared MeONa 1.6 M in MeOH (0.5 mL, 0.8 mmol) was
added by syringe and the mixture kept at room temperature
for 5 h. The resin was washed with Et O (four times) and
DCM (four times), the organic solvents recollected, washed
with saturated aqueous NH Cl and brine and dried over
anhydrous Na SO . Evaporation of the solvent afforded
2
cycloadduct 10 (28 mg, 81%) as a pale yellow oil identical
to an authentic sample.
2
Acknowledgements
4
Work carried out in the framework of the National Project:
‘
4
Stereoselezione in Sintesi Organica. Metodologie ed
Applicazioni’ supported by the Ministero dell’Istruzione
della Universit a` e della Ricerca (MIUR), and by the
University of Florence. The ‘Ente Cassa di Risparmio di
Firenze’ is also acknowledged for acquisition of a 400 NMR
spectrometer.
3
1
H NMR (200 MHz, CDCl ) d: 1.25 (t, JZ7.5 Hz, 3H), 2.32
3
(
1
(
1
s, 3H), 2.76–2.94 (AB part of an ABX system, JAB
3.5 Hz, 2H), 3.64–3.76 (m, 1H), 3.73 (s, 3H), 3.84–3.96
m, 1H); 5.24 (X part of an ABX system, JZ4.0, 2.0 Hz,
H).
Z
All the above reported procedures can be considered as
representative also for the functionalization of the hydroxy-
methyl polystyrene (OH-modified Merrifield) resin, and for
all the cycloadditions described in Table 1.
References and notes
1. Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.;
Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41,
1
668–1698 and reference cited therein.
4.2.6. Cycloadduct 23 from resin 27 in DMF. To a pre-
swelled sulfenylated resin 27 (260 mg, 0.20 mmol) in dry
2. Capozzi, G.; Nativi, C.; Menichetti, S.; Rosi, A.; Valle, G.
Tetrahedron 1992, 48, 9023–9032.
DMF (1 mL) at room temperature for 2 h, phenyl vinyl
sulfide (15) (136 mg, 1.00 mmol) and Et N (21 mg,
3. Capozzi, G.; Franck, R. W.; Mattioli, M.; Menichetti, S.;
Nativi, C.; Valle, G. J. Org. Chem. 1995, 60, 6416–6426.
4. Capozzi, G.; Dios, A.; Franck, R. W.; Geer, A.; Marzabadi, C.;
Menichetti, S.; Nativi, C.; Tamarez, M. Angew. Chem., Int. Ed.
1996, 35, 777–779.
3
0
.21 mmol) were added in sequence and the mixture heated
to 60 8C for 52 h. The general work-up afforded 239 mg an
oxathiin-immobilised resin, which was dried and reacted
with MeONa in dry THF as described above. Evaporation of
the solvent gave cycloadduct 23 (16 mg, 28%) as a pale
yellow oil with spectroscopic data identical of those
5. Menichetti, S.; Nativi, C. Hetero Diels–Alder approach to
oxathiins. In Targets in Heterocyclic Systems—Chemistry and
Properties, 2003; Vol. 7, pp 108–139.
3
reported in the literature.
6. A preliminary report of this work has been presented at 21st