H. Bagum et al. / Tetrahedron 75 (2019) 130561
9
m. p. 135e137 ꢀC (lit [2]. m.p. 94e100 ꢀC); 1:2 mixture of keto-enol
According to General Method D, malonamide 2c (5.38 g,
16.2 mmol) was reacted with KOtBu (2.0 g, 17.8 mmol) in THF
(0.2 M) to furnish tetramic acid 4c. Yield 84% (3.9 g); white solid, m.
tautomers. Rf (10% MeOH in EtOAc) 0.30; ½a D25
þ80.3 (c 1.0 in DCM);
ꢂ
nmax/cmꢁ1 3298 (OeH), 2963 (CeH), 2876 (CeH), 1790 (C]O), 1733
(C]O); dH (400 MHz, CDCl3): 0.84 (9H, s, C(CH3)3 (keto þ enol)),
1.22 (3H, d, J 7.2, C(7)CH3 (keto)), 1.63 (3H, s, C(7)CH3 (enol)), 3.35
p. 148e150 ꢀC; ½a D25
ꢂ
þ291.4 (c 1.0 in MeOH); nmax/cmꢁ1 3366
(OeH), 2956 (CeH), 1751 (C]O), 1650 (C]O); dH (400 MHz,
MeOD): 0.95 (9H, s, C(CH3)3), 1.66 (3H, s, C(7)CH3), 2.80 (1H, d, J
(1H, d, J 8.5, C(4)HAHB (enol)), 3.49 (1H, d, J 9.4, C(4)HAHB (keto)),
3.65 (1H, q, J 7.2, C(7)H (keto)), 3.71 (3H, s, CO2CH3 (enol)), 3.76 (3H,
s, CO2CH3 (keto)), 4.59 (1H, s, C(2)H (enol)), 4.71e4.82 (2H, m, C(4)
11.2, C(4)HAHB), 3.68 (1H, d, J 11.2, C(4)HAHB), 3.78 (3H, s, CO2CH3),
4.87 (1H, s, C(2)H); dC (100 MHz, MeOD): 4.8 (C(7)CH3), 25.6
(C(CH3)3), 32.6 (C(4)), 36.3 (C(CH3)3), 52.1 (CO2CH3), 71.2 (C(2)),
HAHB (keto þ enol)), 4.99 (1H, s, C(2)H (keto)); dC (100 MHz, CDCl3):
6.3 (C(7)CH3)(keto), 7.6 (C(7)CH3 (enol)), 24.6 (C(CH3)3 (enol)), 24.7
(C(CH3)3 (keto)), 35.1 (C(CH3)3 (enol)), 35.6 (C(CH3)3 (keto)), 49.4
79.1 (C(5)), 100.0 (C(7)), 168.6 (CO2CH3), 169.2 (C(8)), 179.4 (C(6));
m/z ([ESI]þ) 286.0 ([MþH]þ, 100%); HRMS ([ESI]þ) found 286.1105,
C
13H20NO4S ([MþH]þ) requires 286.1108.
(C(7) keto), 53.1 (CO2CH3 (keto)), 53.8 (CO2CH3 (enol)), 68.3 (C(4)
enol), 69.9 (C(4) keto), 74.2 (C(5) (enol)), 79.1 (C(5) (keto)), 96.6
2.12.9. (2R,4S,5S)-2-(tert-Butyl)-1-((R)-1-ethoxycarbonyl-1-
methylacetyl)-5-methoxycarbonyl-4-methyl-1,3-oxazolidine (7b),
(2R,4S,5S)-2-(tert-Butyl)-1-((S)-1-ethoxycarbonyl-1-methylacetyl)-
5-methoxycarbonyl-4-methyl-1,3-oxazolidine (7b’)
(C(2) keto), 98.0 (C(2) enol), 103.9 (C(7) enol), 166.9 (CO2CH3
(enol)), 168.0 (CO2CH3 (keto)), 169.2 (C(8) keto), 175.4 (C(8) enol),
181.5 (C(6) enol), 201.1 (C(6) keto); m/z ([ESI]þ) 270.2 ([MþH]þ,
60%), 292.0 ([MþNa]þ); HRMS ([ESI]þ) found 270.1333, C13H20NO5
([MþH]þ) requires 270.1336.
2.12.7. (2R,4S,5R)-1-Aza-2-(tert-butyl)-6-hydroxy-5-
methoxycarbonyl-4, 7-dimethyl-3-oxa-8-oxobicyclo[3.3.0] oct-6-
ene, 4b
According to General Method C, oxazolidine (870 mg,
4.3 mmol), DCC (969 mg, 4.7 mmol), and DMAP (37 mg, 0.3 mmol)
was reacted with ethyl a-phenyl malonic acid 6 (990 mg, 4.7 mmol)
in DCM (43 mL). The crude product was purified by flash column
chromatography (20% EtOAc in petroleum ether) to afford N-acyl
oxazolidine as a 2:1.6 mixture of diastereomers 7b and 7b’. Yield
95% (1.61 g); 2:1.6 mixture of diastereomers; colourless oil; minor
isomer 7b’ is solid for which m.p. is 84e86 ꢀC. Rf (20% EtOAc in
25
According to General Method D, malonamide 2b (853 mg,
Petrol) 0.19 þ 0.25þ0.28. Major isomer 7b: [
a
]
þ25.0 (c 1.0 in
D
t
2.6 mmol) was reacted with KOtBu (319 mg, 2.85 mmol) in BuOH
DCM); nmax/cmꢁ1 2984 (CeH), 2958 (CeH), 2872 (CeH), 1754 (C]
O), 1678 (C]O); dH (400 MHz, CDCl3) 0.96 (9H, s, C(CH3)3), 1.19 (3H,
t, J 7.1, C(10)H3), 1.22 (3H, d, J 6.4, C(4)CH3), 3.75 (3H, s, CO2CH3),
3.81 (1H, q, J 6.4, C(4)H), 4.04e4.22 (3H, m, (C(5)H þ C(9)H2), 4.58
(1H, s, (C(7)H), 5.11 (1H, s, C(2)H), 7.25e7.33 (5H, m, ArH); dC
(0.2 M) to furnish tetramic acid 4b. Yield 67% (494 mg); white solid,
m. p. 168e170 ꢀC; Rf (EtOAc) 0.30; ½a 2D5
ꢂ
þ96.1 (c 1.0 in DCM); nmax
/
cmꢁ1 3420 (OeH), 2958 (CeH), 2871 (CeH), 1755 (C]O), 1649 (C]
O); dH (400 MHz, MeOD): 0.81 (9H, s, C(CH3)3, 1.55 (6H, d, J 6.3, C(7)
CH3 þ C(4)CH3), 3.50 (1H, q, J 6.5, C(4)H), 3.60 (3H, s, CO2CH3), 4.45
(100 MHz, CDCl3): 14.0 (C(10)), 15.3 (C(4)CH3), 26.4 (C(CH3)3), 37.1
(C(CH3)3), 52.1 (CO2CH3), 59.1 (C(7)), 61.8 (C(9)), 62.2 (C(5)), 74.9
(C(4)), 96.7 (C(2)), 128.5e132.0 (ArC), 168.2 (NC]O), 168.9
(1H, s, C(2)H); dC (100 MHz, MeOD): 4.8 (C(7)CH3), 13.6 (C(4)CH3),
24.2 (C(CH3)3), 34.5 (C(CH3)3), 51.2 (CO2CH3), 73.7 (C(5)), 79.8
(C(4)), 95.8 (C(2)), 102.0 (C(7)), 167.8 (CO2CH3), 169.4 (C(8)), 181.7
(C(6)); m/z ([ESI]þ) 284.2 ([MþH]þ, 100%); HRMS ([ESI]þ) found
284.1492, C14H22NO5 ([MþH]þ) requires 284.1493.
(CO2CH3), 169.3 (CO2Et); m/z ([ESI]þ) 392.2 ([MþH]þ, 50%); HRMS
([ES]Iþ) found 392.2061, C21H30NO6 ([MþH]þ) requires 392.2068.
Diastereomer 7b’: [
a
]
D
25 ꢁ 46.0 (c 1.0 in DCM); nmax/cmꢁ1 2985
(CeH), 2957 (CeH), 2873 (CeH), 1751 (C]O), 1672 (C]O); dH
2.12.8. (2R,5R)-1-Aza-2-(tert-butyl)-6-hydroxy-5-
methoxycarbonyl-7-methyl-8-oxo-3-thiabicyclo[3.3.0] octane, 4c
(400 MHz, CDCl3) 0.84 (9H, s, C(CH3)3), 1.19 (3H, t, J 7.1, C(10)H3),
1.28 (3H, d, J 6.4, C(4)CH3), 3.50 (3H, s, CO2CH3), 4.08e4.21 (3H, m,
C(9)H2 þ C(4)H), 4.51 (1H, d, J 6.5, C(5)H), 4.68 (1H, s, C(7)H), 5.18
(1H, s, C(2)H), 7.24e7.32 (5H, m, ArH); dC (100 MHz, CDCl3): 14.1
(C(10)), 15.2 (C(4)CH3), 26.4 (C(CH3)3), 37.0 (C(CH3)3), 51.8
(CO2CH3), 59.2 (C(7)), 61.9 (C(9)), 63.5 (C(5)), 75.1 (C(4)), 96.9 (C(2)),
128.1e133.1 (ArC), 168.3 (NC]O), 168.6 (CO2CH3), 170.5 (CO2Et); m/
z ([ESI]þ) 392.2 ([MþH]þ, 50%); HRMS ([ESI]þ) found 392.2069,
C
21H30NO6 ([MþH]þ) requires 392.2068.
2.12.10. (2R,5R)-2-(tert-Butyl)-1-((R)-1-ethoxycarbonyl-1-
phenylacetyl)- and (2R,5R)-2-(tert-Butyl)-1-((S)-1-ethoxycarbonyl-
1-phenylacetyl)-5-methoxycarbonyl-1,3-thiazolidine, 7c and 7c’