J 4.7, CH NH ), 5.80 (1H, ddt, J 17.1, 10.3 and 5.7, CH ᎐CH ),
J 6.5, CHCH3); δC 175.4 (NC᎐O), 172.1 (OC᎐O), 134.4
᎐ ᎐
᎐
2
2
5.57 (1H, br d, J 8.1, CHNH ), 5.18–5.12 (2H, m, CH ᎐CH),
(CH᎐CH ), 116.1 (CH᎐CH ), 80.7 [C(CH ) ], 41.6 (CH N),
᎐ ᎐
2 2 3 3 2
᎐
2
4.00–3.92 (2H, m, CH2N), 3.70–3.64 (1H, m, CHN), 2.88 (1H,
dd, J 13.4 and 8.4, PhCH2), 2.61 (1H, dd, J 13.4 and 6.8,
PhCH2), 2.31–2.26 (1H, m, CHCO), 2.10 (1H, dd, J 14.4 and
11.1, CH2CHN), 1.26 (1H, dd, J 14.4 and 3.7, CH2CHN), 1.19
[3H, s, C(CH3)2], 1.16 [3H, s, C(CH3)2], 1.09 (3H, d, J 6.8,
CHCH3), 0.87 (3H, d, J 6.4, CHCH3); δC (125 MHz) 178.4 and
39.2 (CH2CO2), 36.9 (CHCH3), 27.8 [C(CH3)3], 17.5
(CHCH3); m/z (APCIϩ) 250 (10%, MNaϩ), 172 (60%,
MHϩ Ϫ C4H8), 154 (100%, MHϩ Ϫ C4H10O).
Preparation of (2S)-N-phenylmethyl-2-[(tert-butoxycarbonyl)-
methyl]propionamide (S)-14
175.6 (C᎐O), 139.8 (Ph: C ), 133.9 (CH ᎐CH), 129.0 and
᎐
᎐
2
ipso
To 12 (0.150 g, 0.505 mmol) at room temperature was added
neat benzylamine (0.324 g, 3.028 mmol) via pipette. The reac-
tion mixture was stirred at room temperature for 48 hours and
then partitioned between dichloromethane (30 ml) and aqueous
hydrochloric acid (10%, 30 ml) and further extracted with
dichloromethane (2 × 30 ml). The combined organic portions
were washed with brine, dried (magnesium sulfate), filtered and
concentrated in vacuo to afford a colourless oil. This material
was purified by flash chromatography on silica gel [diethyl
ether–petroleum ether (1 : 1) then ethyl acetate (100%)] eluting
first the less polar title compound (S)-14 (0.134 g, 96%) as a
colourless oil which crystallised on standing, followed by the
more polar pyrrolidinone (R)-1 (0.059 g, 92%) as a colourless
solid.
128.3 (Ph: C), 126.2 (Ph: Cpara), 116.6 (CH ᎐CH), 45.4
᎐
2
(CH2CHN), 43.7 (CHCH3), 42.4 (CHN), 42.1 (CH2N), 40.8
[C(CH3)2], 40.6 (PhCH2), 29.5 (CH3CHN), 23.1 and 22.3
[C(CH3)2], 17.3 (CHCH3); m/z (APCIϩ) 353 (15%, MNaϩ), 331
(100%, MHϩ), 168 (6%), 128 (10%); [Found (CI, NH3): MHϩ,
331.23917. C20H31N2O2 MHϩ requires, 331.23855].
1
A H NMR (300 MHz, CDCl3) chiral shift experiment with
Eu(hfc)3 showed the ee of (S)-7 to be >96%.
Preparation of (2S)-N-methoxy-N-methyl-2-phenylmethyl-
propionamide (S)-11
To a stirred suspension of N,O-dimethylhydroxylamine hydro-
chloride (0.098 g, 1.10 mmol) in dichloromethane (1 ml) at 0 ЊC
was added cautiously trimethylaluminium (0.55 ml, 1.10 mmol)
via syringe. The resultant colourless solution (effervescence
ceased after 5 minutes) was stirred at 0 ЊC for 15 minutes and
room temperature for 45 minutes.
(S)-14; mp 45–46 ЊC; [α]2D3 Ϫ7.1 (c 0.68, CHCl3) (Found: C,
69.41; H, 8.47; N, 4.84. C16H23NO3 requires C, 69.29; H, 8.36;
N, 5.05%); νmax(film)/cmϪ1 3302br s (N–H), 1729s (OC᎐O),
᎐
1651s (NC᎐O) and 1546s; δ 7.34–7.22 (5H, m, Ph), 6.16 (1H,
᎐
H
A solution of 3 (0.137 g, 0.50 mmol) in dichloromethane (0.5
ml) was then added dropwise via cannula to the aluminium
amide solution. The reaction mixture was stirred at room tem-
perature for 22 hours and under reflux for 3 hours, cooled to
0 ЊC and subsequently quenched with aqueous sulfuric acid
(1 M). The acidic (pH 1) aqueous layer was diluted with distilled
water (20 ml) and extracted with dichloromethane (3 × 20 ml).
The combined organic portions were washed with brine (20 ml),
dried (magnesium sulfate), filtered and concentrated in vacuo to
yield a crude yellow oil. This material was purified by flash
chromatography on silica gel [ethyl acetate–petroleum ether
(1 : 2) then ethyl acetate (100%)] eluting first the less polar title
compound (S)-11 (0.060 g, 79%) as a colourless oil followed by
the more polar pyrrolidinone (R)-1 (0.043 g, 93%) as a colour-
less solid.
br s, NH ), 4.49–4.36 (2H, m, PhCH2), 2.76–2.64 (2H, m,
CHCH3 and CH2CO2), 2.35–2.25 (1H, m, CH2CO2), 1.41 (9H,
s, C(CH3)3), 1.19 (3H, d, J 6.5, CHCH3); δC (50 MHz) 175.5
(NC᎐O), 172.2 (OC᎐O), 138.8 (Ph: Cipso), 128.7, 127.8 and 127.4
᎐
᎐
(Ph: C), 80.7 [C(CH3)3], 43.3 (PhCH3), 39.3 (CH2CO2), 37.0
(CHCH3), 27.9 [C(CH3)3], 17.6 (CHCH3); m/z (APCIϩ) 300
(12%, MNaϩ), 222 (100%, MHϩ Ϫ C4H8).
Preparation of (2S)-N-(4-methoxyphenylmethyl)-2-[(tert-
butoxycarbonyl)methyl]propionamide (S)-15
To 12 (0.150 g, 0.505 mmol) at room temperature was added
neat p-methoxybenzylamine (0.415 g, 3.029 mmol) via pipette.
The reaction mixture was stirred at room temperature for 48
hours and then partitioned between dichloromethane (30 ml)
and aqueous hydrochloric acid (10%, 30 ml) and further
extracted with dichloromethane (2 × 30 ml). The combined
organic portions were washed with brine (20 ml), dried
(magnesium sulfate), filtered and concentrated in vacuo to
afford a colourless oil. This material was purified by flash
chromatography on silica gel [diethyl ether–petroleum ether
(1 : 1) then ethyl acetate (100%)] eluting first the less polar
title compound (S)-15 (0.139 g, 89%) as a colourless oil
followed by the more polar pyrrolidinone (R)-1 (0.060 g, 94%)
as a colourless solid.
11; [α]2D2 ϩ60.7 (c 0.755, CHCl3) (Found: C, 69.55; H, 8.59; N,
6.75. C12H17NO2 requires C, 69.54; H, 8.27; N, 6.76%); νmax
(film)/cmϪ1 1662s (NC᎐O); δH 7.27–7.16 (5H, m, Ph), 3.47 (3H,
᎐
s, CH3O), 3.13 (4H, br s, CH3N and CHCH3), 3.03 (1H, dd,
J 13.2 and 7.8, PhCH2), 2.61 (1H, dd, J 13.1 and 6.8, PhCH2),
1.15 (3H, d, J 6.7, CHCH3); δC (50 MHz) 177.4 (C᎐O), 140.4
᎐
(Ph: Cipso), 129.3 and 128.5 (Ph: C), 126.3 (Ph: Cpara), 61.3
(CH3O), 39.8 (PhCH2), 37.5 (CHCH3), 32.1 (CH3N), 17.2
(CHCH3); m/z (APCIϩ) 208 (100%, MHϩ), 119 (20%, C9H11ϩ).
(S)-15; [α]2D3 Ϫ8.5 (c 0.685, CHCl3); νmax(film)/cmϪ1 3303br s
Preparation of (2S)-N-vinylmethyl-2-[(tert-butoxycarbonyl)-
methyl]propionamide (S)-13
(N–H), 1732s (OC᎐O), 1652s (NC᎐O) and 1544s; δH 7.26–7.12
᎐
᎐
(2H, m, Ar), 6.82–6.78 (2H, m, Ar), 6.30 (1H, br s, NH ), 4.33
(1H, dd, J 15.1 and 5.8, CH2N), 4.28 (1H, dd, J 15.1 and 9.4,
CH2N), 3.74 (3H, s, CH3O), 2.71–2.59 (2H, m, CHCH3 and
CH2CO2), 2.30–2.20 (1H, m, CH2CO2), 1.38 [9H, s, C(CH3)3],
To neat 12 (0.150 g, 0.505 mmol) at room temperature was
added neat allylamine (0.173 g, 3.028 mmol) via pipette. The
reaction mixture was stirred at room temperature for 48 hours
before the excess amine was removed in vacuo to afford a pale
yellow oil. This material was purified by flash chromatography
on silica gel [diethyl ether–petroleum ether (1 : 1) then ethyl
acetate (100%)] eluting first the title compound (S)-13 (0.109 g,
1.14 (3H, d, J 6.5, CHCH ); δ (50 MHz) 175.4 (NC᎐O), 172.2
᎐
3
C
(OC᎐O), 159.1 and 130.8 (Ph: Cipso), 129.2 and 114.1 (Ph: C),
᎐
80.8 [C(CH3)3], 55.2 (CH3O), 42.8 (CH2N), 39.3 (CH2CO2),
37.0 (CHCH3), 27.9 [C(CH3)3], 17.7 (CHCH3); m/z (APCIϩ)
330 (10%, MNaϩ), 308 (16%, MHϩ), 252 (100%, MHϩ Ϫ C4H8),
136 (6%), 121 (17%); [Found (CI, NH3): MHϩ, 308.18633.
C17H25NO4 MHϩ requires, 308.18618].
95%) as
a colourless oil followed by the more polar
pyrrolidinone (R)-1 (0.062 g, 97%) as colourless crystals.
(S)-13; [α]2D3 ϩ0.6 (c 0.67, CHCl3) (Found: C, 63.04; H, 9.69;
N, 6.09. C12H21NO3 requires C, 63.41; H, 9.31; N, 6.16%);
νmax(film)/cmϪ1 3301br s (N–H), 1732s (OC᎐O), 1652s (NC᎐O)
᎐
᎐
Preparation of (3S)-3-methyl-1-vinylmethylpyrrolidine-2,5-dione
(S)-1922
and 1547s; δH 5.90–5.75 (2H, m, NH and CH᎐CH ), 5.17 (1H,
᎐
2
d, J 17.1, CH᎐CH ), 5.11 (1H, d, J 10.2, CH᎐CH ), 3.88–3.84
᎐
᎐
2
2
(2H, m, CH2N), 2.74–2.61 (2H, m, CHCH3 and CH2CO2),
2.34–2.24 (1H, m, CH2CO2), 1.42 [9H, s, C(CH3)3], 1.17 (3H, d,
To (S)-13 (0.057 g, 0.251 mmol) in a 5 ml round bottom flask
was added TFA (3 ml) neat via pipette. The mixture was left
1874
J. Chem. Soc., Perkin Trans. 1, 2002, 1869–1876