1
132
S. R. Hussaini and M. G. Moloney
Typical Procedure for the Reduction b-Enaminoester
To a solution of b-enaminoester (10 mmol) in absolute ethanol (150 mL) was
added sodium borohydride (40 mmol) and stirring continued for 30 min at
08C, then at room temperature for 6 h. Galacial acetic acid was then
carefully added to the mixture with stirring and cooling in an ice bath until
pH 5.0 was reached. The mixture was partitioned between CH Cl and
2
2
water. The CH Cl layer was washed with a saturated solution of NaHCO ,
3
2
2
water, and brine; dried over MgSO ; and evaporated. Silica-gel chroma-
4
tography gave the corresponding alcohol. Data for the reduction products
are as follows:
2-(2-Hydroxymethyl-pyrrolidin-5-ylidene)-3-oxo-3-phenyl-propionic acid
ethyl ester 2a. Obtained as an inseparable mixture of diastereomers.
2
1
R ¼ 0.36 (EtOAc); nmax/cm (neat) 3340, 3044, 1659, 1589, 1476; dH
f
(400 MHz, CDCl ) (major) 0.71 (3H, t, J 7.0, OCH CH ), 1.67–1.75 (1H,
3 2 3
m, C(3)HH), 2.03–2.13 (1H, m, C(3)HH), 3.08–3.18 (2H, m, C(4)H ), 3.31
2
(
1H, dd, J 11.4, 6.9, CHHOH), 3.64–3.86 (3H, m, CHHOH, OCH CH ),
2 3
4.04–4.51 (1H, m, C(2)H), 7.25–7.60 (5H, m, C H ), 11.01 (1H, br, NH);
dC (100 MHz, CDCl ) 13.5 (OCH CH ), 22.8 (C(3)), 33.0 (C(4)), 59.5
6 5
3
2
3
(
(
(
OCH CH ), 62.5 (C(2)), 64.6 (CH OH), 98.1 (NCC), 125.6, 127.6, 129.4
2 3 2
ArC), 143.5 (quaternary ArC), 169.13, 173.0 (C(5), COOC H ), 195.2
2
5
þ
þ
C H CO); m/z (APCI ) 290 (M þ H , 4%), 244 (100%). d (400 MHz,
6
5
H
CDCl ) (minor) 1.24 (3H, t, J 7.1, OCH CH ), 1.67–1.75 (1H, m, C(3)HH),
3
2
3
2.03–2.13 (1H, m, C(3)HH), 2.59–2.61 (2H, m, C(4)H ), 3.42–3.58 (2H,
m, CH OH), 3.64–3.86 (1H, m, C(2)H), 4.04–4.51 (2H, m, OCH CH ),
2
2
2
3
7.25–7.6 (5H, m, C H ), 9.47 (1H, br, NH); d (100 MHz, CDCl ) 14.6
6 5 C 3
(
OCH CH ), 23.8 (C(3)), 31.7 (C(4)), 59.1 (OCH CH ), 61.6 (C(2)), 65.1
2 3 2 3
(CH OH), 95.6 (NCC), 125.6, 128.4, 131.7 (ArC), 142.9 (quaternary ArC),
2
170.1, 170.8 (C(5), CO C H ), 195.4 (C H CO).
2 2 5 6 5
2
2
-(2-Hydroxymethyl-pyrrolidin-5-ylidene)-malonic acid diethyl ester
2
2
b. R ¼ 0.26 (3:7 Petrol (40/60): EtOAc); [a] ¼ þ19.3 (c ¼ 0.14,
f
D
2
1
CHCl ); n /cm (neat) 3416, 1644, 1567; d (400 MHz, CDCl ) 1.27
3
max
H
3
(3H, t, J 7.1, OCH CH ), 1.28 (3H, t, J 7.1, OCH CH ), 1.73–1.8 (1H, m,
2 3 2 3
C(3)HH), 2.05–2.15 (1H, m, C(3)HH), 2.78 (1H, s, OH), 3.02–3.2 (2H, m,
C(4)H ), 3.52 (1H, dd, J 11, 6.7, CHHOH), 3.71 (1H, dd, J 11, 4.0,
2
CHHOH), 3.98–4.01 (1H, m, C(2)H), 4.14–4.28 (4H, m, 2 ꢀ OCH CH ),
2
3
9
3
1
.59 (1H, br, NH); d (50 MHz, CDCl ) 14.3 (2 ꢀ OCH CH ), 23.8 (C(3)),
C
3
2
3
3.8 (C(4)), 59.6 (2 ꢀ OCH CH ), 60.4 (C(2)), 66.1 (CH OH), 87.3 (NCC),
2 3 2
þ
þ
67.8,169.7,172.7(C(5),2 ꢀ CO C H );m/z(APCI )258(M þ H ,8%),212
2
2 5
þ
(
100%);HRMS(M þ H )258.1340,C H NO requires258.1341.
1
2
20
5
N-Ethyl-2-(2-Hydroxymethyl-pyrrolidin-5-ylidene)-malonic acid diethyl
2
ester 3b. R ¼ 0.5 (95:5 EtOAc: MeOH); nmax/cm (neat) 3440, 1683,
1
f
1560; d (400 MHz, CDCl ) 1.07–1.16 (3H, m, NCH CH ), 1.22–1.30
H 3 2 3