198
C. Agami et al. / Tetrahedron 57 (2001) 195±200
at 2108C, of a solution of commercially organolithium
(2.8 mmol) to a suspension of CuI (1.4 mmol) in diethyl
ether). The reaction was allowed to reach room temperature
within 1 h and the mixture was stirred at rt for 2 h. An
aqueous solution saturated with ammonium chloride
(15 mL) was added and the reaction mixture was extracted
with CH2Cl2 (2£20 mL). After evaporation the residue was
chromatographed (EtOAc/MeOH).
2-one 4f. To a solution of 2 (1 g; 6.21 mmol) in methanol
(60 mL) was added, at room temperature, ethyl crotonate
(3.54 mL; 31 mmol). After 12 h at re¯ux, ethanol was
evaporated under reduced pressure and the residue is chro-
matographed on silica gel (MeOH/EtOAc: 10/90) to afford
product 4f as a white solid (0.357 g; 1.55 mmol, yield 25%).
[a]2D0183 (c 1.0, CHCl3). MS-CI/NH3: 231 (M1H1, 100).
Mp: 1628C. NMR 1H (CDCl3, 250 MHz): 0.74 (d, 3H,
J6.6 Hz), 2.30 (dd, 1H, J8.75±15.9 Hz), 2.59 (dd, 1H,
J6.5±15.9 Hz), 3.71 (m, 1H), 4.11 (m, 1H), 4.28 (m, 1H),
4.90 (m, 1H), 7.37 (m, 5H). NMR 13C (CDCl3, 62.5 MHz):
20.2, 38.4, 49.5, 62.9, 73.6, 126.8, 128.5, 129.5, 137.7,
168.7, 178.5.
2.2.1. (4S,40S)-4-(2-Imino-4-phenyl oxazolidin-3-yl)-
pentan-2-one 4a. (86%). [a]2D01119 (c1, CHCl3). MS-
1
CI/NH3: 231 (M1H1, 100). H NMR (250 MHz, CDCl3):
1.20 (d, J6.4 Hz, 3H), 2.35 (dd, J15.9, 6.6 Hz, 1H), 2.59
(dd, J15.9, 6.9 Hz, 1H), 3.39±3.44 (m, 1H), 4.32 (dd,
J8.9, 6.3 Hz, 1H), 4.81 (t, J8.9 Hz, 1H), 5.03 (dd,
J8.6, 6.2 Hz, 1H), 7.22±7.39 (m, 5H). 13C NMR
(63 MHz, CDCl3): 17.2, 37.1, 45.5, 60.3, 73.2, 126.9,
128.6, 129.7, 135.5, 167.2, 178.1.
2.3. General procedure for the a-alkylation
To a solution of compound 4 (1 mmol) in THF (10 mL) was
added, at 2108C, LiHMDS (1.1 mL of a 1 M solution in
THF, 1.1 mmol) and after 15 min, at 2108C, methyl iodide
(0.09 mL, 1.5 mmol) was added. The reaction mixture was
stirred 2 h at 2108C and further quenched by a saturated
NH4Cl aqueous solution and extracted with CH2Cl2
(2£20 mL). After evaporation, the residue was chromato-
graphed (EtOAc/MeOH).
2.2.2. (3S,5R)-5-Butyl-3-phenyl-2,3,5,6-tetrahydro oxazolo
[3,2-a] pyrimidin-7-one 4b. (93%). [a]2D01109 (c 0.5,
CHCl3). MS-CI/NH3: 273 (M1H1, 100). NMR 1H (CDCl3,
250 MHz): 0.69 (t, 3H, J7.0 Hz), 1.10 (m, 2H), 1.39 (m,
2H), 1.69 (m, 2H), 2.33 (dd, 1H, J5.5±16.0 Hz), 2.50 (dd,
1H, J7.0±16.0 Hz), 3.21 (m, 1H), 4.26 (dd, 1H, J6.0±
9.0 Hz), 4.75 (t, 1H, J9.0 Hz), 4.90 (dd, 1H, J6.0±
9.0 Hz), 7.14±7.34 (m, 5H). NMR 13C (CDCl3, 62.5 MHz):
13.7, 22.3, 26.5, 30.8, 34.4, 49.3, 60.6, 73.2, 126.7, 129.7,
135.8, 167.3, 178.1.
2.3.1. (3S,5S,6S)-5,6-Dimethyl-3-phenyl-2,3,5,6-tetrahy-
dro oxazolo [3,2-a] pyrimidin-7-one 6a. (88%). [a]D20
162 (c 0.8, CHCl3). HRMS: calc for C14H16O2N2
1H1245.1290, obs245.1290. NMR 1H (CDCl3,
250 MHz): 1.14 (d,3H, J6.6 Hz), 1.19 (d, 3H,
J6.6 Hz), 2.29 (quint, 1H, J6.6 Hz), 3.03 (quint, 1H,
J6.6 Hz), 4.33 (q, 1H, J6.3±8.9 Hz), 4.84 (t, 1H,
J8.9), 5.02 (q, 1H, J6.3±8.9 Hz), 7.31 (m, 5H). NMR
13C (CDCl3, 62.5 MHz): 14.8, 16.7, 40.9, 51.7, 60.2, 73.0,
126.8, 128.4, 129.5, 135.5, 165.9, 181.4.
2.2.3. (3S,5S)-5-Vinyl-3-phenyl-2,3,5,6-tetrahydro oxazolo
[3,2-a] pyrimidin-7-one 4c. (75%). NMR 1H (CDCl3,
250 MHz): 2.55 (dd, 1H, J5.7±16.0 Hz), 2.73 (dd, 1H,
J7.0±16.0 Hz), 3.80 (m, 1H), 4.90 (m, 1H), 4.92 (m,
1H), 5.03 (dd, 1H, J17.1±1.2 Hz), 5.28 (dd, 1H,
J10.0±1.2 Hz), 5.70 (m, 1H), 3.35 (m, 5H).
2.2.4. (3S,5R)-3,5-Diphenyl-2,3,5,6-tetrahydro oxazolo
[3,2-a] pyrimidin-7-one 4d. (81%). Mp: 908C [a]D20
196 (c 0.5, CHCl3). MS-CI/NH3: 293 (M1H1, 100).
NMR 1H (250 MHz, CDCl3): 2.67 (dd, 1H, J7.4±
16.2 Hz), 2.85 (dd, 1H, J7.1±16.2 Hz), 4.25 (dd, 1H,
J7.1±7.4 Hz), 4.40 (dd, 1H, J5.8±8.8 Hz), 4.59 (dd,
1H, J5.8±8.8 Hz), 4.80 (t, 1H, J8.8 Hz), 7.03 (m, 5H),
7.32 (m, 5H). NMR 13C (62.5 MHz, CDCl3): 37.6, 54.4,
60.7, 73.1, 126.8, 127.1, 129.1, 129.4, 129.6, 129.8, 135.4,
137.0, 167.7, 177.4.
2.3.2. (3S,5S,6S)-5-butyl-6-methyl-3-phenyl-2,3,5,6-
tetrahydro oxazolo [3,2-a] pyrimidin-7-one 6b. (96%).
[a]2D0195 (c 0.2, CHCl3). MS-CI/NH3: 287 (M1H1,
100). NMR 1H (CDCl3, 250 MHz): 0.81 (t, 3H,
J6.7 Hz), 1.08 (d, 3H, J7.2 Hz), 1.22 (m, 4H), 1.50
(m, 2H), 2.46 (qd, 1H, J3.5±7.2 Hz), 2.90 (m, 1H), 4.36
(dd, 1H, J6.9±8.9 Hz); 4.88 (t, 1H, J8.9 Hz), 5.01 (dd,
1H, J6.9±8.9 Hz), 7.32 (m, 5H). NMR 13C (CDCl3,
62.5 MHz): 13.6, 16.5, 22.4, 26.1, 29.8, 38.1, 55.6, 60.4,
73.1, 127.1, 129.4, 129.6, 135.4, 165.8, 182.0.
2.2.5. (3S)-3-Phenyl-2,3,5,6-tetrahydro oxazolo [3,2-a]
pyrimidin-7-one 4e. To a solution of 2 (1 g; 6.21 mmol)
in ethanol (60 mL) was added, at room temperature, methyl
acrylate (0.87 mL; 9.3 mmol). After 12 h at re¯ux, ethanol
was evaporated under reduced pressure and the residue is
chromatographed on silica gel (MeOH/EtOAc: 10/90) to
afford product 4e as a white solid (1.02 g; 4.71 mmol,
yield 76%). [a]2D0193 (c 0.6, CHCl3). Mp: 1838C. MS-
2.3.3. (3S,6S)-6-Methyl-3-phenyl-2,3,5,6-tetrahydro oxazolo
[3,2-a] pyrimidin-7-one 6e. (35%). [a]2D0160 (c 0.6, CHCl3).
HRMS: calc for C13H14O2N21H1231.1134, obs231.1128.
NMR 1H (CDCl3, 250 MHz): 1.23 (d, 3H, J6.9 Hz), 2.84 (m,
1H), 2.88(dd, 1H, J9.2±11.7 Hz), 3.36(dd, 1H), 4.46(m, 1H,),
4.91 (m, 2H), 7.35 (m, 5H). NMR13C (CDCl3, 62.5M Hz): 14.6,
33.5, 45.5, 62.9, 73.5, 127.0, 129.6, 129.7, 135.3, 167.2, 181.4.
1
CI/NH3: 217 (M1H1, 100). NMR H (250 MHz, CDCl3):
2.3.4. (3S,5R,6R)-5,6-Dimethyl-3-phenyl-2,3,5,6-tetrahy-
dro oxazolo [3,2-a] pyrimidin-7-one 6f. (35%).
[a]2D0134 (c 0.2, CHCl3). MS-CI/NH3: 245 (M1H1,
100). NMR 1H (CDCl3, 250 MHz): 0.78 (d, 3H,
J7.2 Hz), 1.18 (d, 3H, J7.2 Hz), 2.27 (quint, 1H,
J7.2 Hz), 3.33 (quint, 1H, J7.2 Hz), 4.33 (m, 1H,),
4.84 (m, 2H,), 7.29 (m, 5H,). NMR 13C (CDCl3,
2.57 (t, 2H, J8.3 Hz), 3.16 (m, 1H), 3.27 (m, 1H), 4.33 (m,
1H), 4.86 (m, 2H), 7.33 (m, 5H). NMR 13C (62.5 MHz,
CDCl3): 29.4, 39.3, 63.2, 73.5, 127.0, 129.6, 129.8, 135.1,
168.3, 178.1.
2.2.6. (4R,40S)-4-(2-Imino-4-phenyl oxazolidin-3-yl)-pentan-