G. Maw et al. / Tetrahedron Letters 42 (2001) 8387–8390
8389
precipitates before dealkylation can occur allowing its
water. The organic phase was dried over MgSO4 and
concentrated in vacuo to give the crude amino acrylate.
Purification by silica gel chromatography (petroleum ether
40–60:ethyl acetate, 4:1 as eluant) gave methyl (E)-3-
[ethyl(isopropyl)amino]-2-propenoate 6c (93%, yellow oil):
5
i
isolation. In addition, it is interesting that loss of Pr
occurs in preference to loss of Et when using H u¨ nig’s
base (entry 3, Table 1), which suggests that in this case
an S 1 reaction is involved in the iodide-mediated
N
−
1
dealkylation process. In contrast, the less nucleophilic
base, diethylaniline, did not react under the reaction
conditions employed, whereas pyridine did react result-
ing in a complex mixture of products.
wmax (film)/cm 2966, 1685, 1600, 1420, 1188, 1106, 785;
lH (300 MHz, CDCl ) 1.10–1.25 (9H, m, 3×Me), 3.12 (2H,
3
q, J 7.5, CH ), 3.50 (1H, m, J 7.5, CH), 3.65 (3H, s,
2
OCH ), 4.55 (1H, d, J 13.7, ꢀCH), 7.50 (1H, d, J 13.7,
3
ꢀ
CH); lC (75.5 MHz) 11.7 (CH ), 21.3 [CH(CH ) ], 40.0
3 3 2
(
NCH CH ), 47.0 [CH(CH ) ], 49.3 (OCH ), 82.1 (ꢀCH),
2
3
3 2
3
148.4 (ꢀCH), 169.4 (CꢀO); accurate m/z (ES+) 172.1335
+ +
9 18 2
(
100%, MH , C H NO requires m/z 172.1337).
5. All new compounds gave satisfactory NMR, IR and
HRMS data. Selected data: 6b lH (300 MHz, CDCl ) 0.9
3
6
Reported uses for amino acrylates are quite scarce;
(
6H, t, J 7.5, 2×CH ), 1.27 (4H, m, 2×CH ), 1.50 (4H, m,
3
2
there are a few examples of them being utilised in
natural product chemistry, but in each case they have
been prepared through reaction of a secondary amine
with a propiolate ester. There are also reports detailing
the preparation of trans-ammonium halides 8 as stable
2
×CH ), 3.1 (4H, bm, 2×CH ), 3.62 (3H, s, OCH ), 4.50
2 2 3
(
1H, d, J 13.2, ꢀCH), 7.40 (1H, d, J 13.2, ꢀCH); lC (75.5
MHz, CDCl ) 14.3 (CH ), 20.3 (CH ), 29.3 (CH ), 50.6
3
3
2
2
(
(
OCH ), 55.5 (CH ), 83.6 (ꢀCH), 152.1(ꢀCH), 170.5
3
2
CꢀO), 170.7 (CꢀO); 6d lH (300 MHz, CDCl ) 1.90 (4H,
3
8
compounds and their subsequent use as Diels–Alder
bm, 2×CH ), 3.10 (4H, bm, 2×CH ), 3.60 (3H, s, OCH ),
2
2
3
9
dienophiles. These salts are usually prepared by reac-
4
.45 (1H, d, J 13.1, ꢀCH), 7.60 (1H, d, J 13.1, ꢀCH); lC
tion of a quaternary ammonium chloride or bromide
with a propiolate ester under slightly milder conditions
and in these cases there were no reports of amino
acrylate formation, suggesting that elimination of
iodide leading to amino acrylate formation is a facile
process compared with loss of chloride or bromide.
(
1
75.5 MHz, CDCl ) 24.2 (CH ), 49.3 (CH ), 83.2 (ꢀCH),
3
2
2
47.7 (ꢀCH), 168.9 (CꢀO); 6e lH (300 MHz, CDCl ) 3.17
3
(
4H, t, J 7.0, 2×CH ), 3.65 (7H, m, OCH and 2×CH ),
2 3 2
4
.67 (1H, d, J 13.4, ꢀCH), 7.33 (1H, d, J 13.4, ꢀCH); lC
(
75.5 MHz, CDCl ) 47.6 (CH ), 50.3 (OCH ), 65.1 (CH ),
3 2 3 2
8
4.9 (ꢀCH), 150.8 (ꢀCH), 168.8 (CꢀO); 6f lH (300 MHz,
CDCl ) 1.15 (12H, s, 2×-(CH ) ), 3.60 (5H, bs, OCH and
3
3 2
3
To the best of our knowledge, the reaction presented
here represents an unusual example of dealkylation
from nitrogen and provides a simple, high-yielding
route to a variety of amino acrylates.
2
ꢀ
4
×CH), 4.65 (1H, d, J 13.5, ꢀCH), 7.55 (1H, d, J 13.5,
CH); lC (75.5 MHz, CDCl ) 20.5 (b, CH ), 47.0 (CH),
3
3
9.3 (OCH ), 82.1 (ꢀCH), 146.2 (ꢀCH), 169.4 (CꢀO); 6g l
3
H
(
300 MHz, CDCl ) 3.68 (3H, s, OCH ), 4.30 (4H, bs,
3
3
2
×CH ), 4.83 (1H, d, J 13.1, ꢀCH), 7.40–7.10 (10H, m,
2
ArH), 7.83 (1H, d, J 13.1, ꢀCH); lC (75.5 MHz, CDCl3)
37.6 (CH ), 51.7 (OCH ), 85.9 (ꢀCH), 126.9 (ArC), 128.8
Acknowledgements
2
3
(
ArC), 130.1 (ArC), 138.2 (ArCq), 153.2 (ꢀCH), 170.6
CꢀO); 6h lH (400 MHz, CDCl ) 1.60 (6H, bs, 3×CH ),
(
3
2
We are grateful to the EPSRC for a CASE studentship
GR/99315155) to C.T. and to Pfizer Global Research
and Development for additional funding.
3.19 (4H, bs, 2×CH ), 3.65 (3H, s, OCH ), 4.61 (1H, d, J
2
3
(
13.1, ꢀCH), 7.40 (1H, d, J 13.1, ꢀCH); lC (75.5 MHz,
CDCl ) 24.5 (CH ), 25.8 (CH ), 50.8 (OCH ), 52.0 (CH ),
3
2
2
3
2
1
2
8
(
3.6 (ꢀCH), 152.5 (ꢀCH), 170.9 (CꢀO); 8 (R =R =
3
2 4 H 2 2
CH ) , R =Me) l (400 MHz, D O) 2.18 (4H, bm, CH ),
3
.44 (3H, s, NMe), 3.78 (3H, s, OMe), 3.89 (4H, bm,
References
CH ), 6.19 (1H, d, J 9.7, ꢀCH), 6.65 (1H, d, J 9.7 Hz,
2
ꢀ
CH); lC (75.5 MHz, D O) 21.8 (CH ), 50.9 (NMe), 53.7
1
2
. (a) H e´ naff, N.; Whiting, A. Org. Lett. 1999, 1, 1137–1139;
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(
(
OMe), 68.9 (CH ), 120.3 (ꢀCH), 147.4 (ꢀCH), 164.6
(
5
2
1 2 3
CꢀO); (R =R =(CH CH ) O, R =Me) l (400 MHz,
2
2 2
H
D O) 3.53 (3H, s, NMe), 3.73 (3H, s, OMe), 3.89–4.12
2
(
8H, bm, 4×CH ), 6.32 (1H, d, J 10.4, ꢀCH), 6.58 (1H, d,
2
J 10.4, ꢀCH); lC (75.5 MHz, D O) 53.7 (NMe), 54.2
2
(
OMe), 62.1 (CH ), 64.1 (CH ), 122.0 (ꢀCH), 140.5 (ꢀCH),
2
2
1 2 3
164.3 (CꢀO); (R =R =(CH
O) 1.48 (2H, bm, CH ) 1.66–1.82 (4H, bm, CH
(3H, s, NMe), 3.37–3.46 (4H, bm, CH ), 3.74 (3H, s,
OMe), 6.24 (1H, d, J 10.4, ꢀCH), 6.43 (1H, d, J 10.4,
(75.5 MHz, D O) 20.2 (CH ), 21.3 (CH ), 53.8
), 121.0 (ꢀCH), 140.6
) , R =Me) l
(400 MHz,
2 5 H
3
929–3932.
D
2
2
), 3.40
2
3
4
. Piers, E.; Wong, T.; Coish, P. D.; Rogers, C. Can. J.
Chem. 1994, 72, 1816–1819.
2
. Representative procedure: A mixture of iodoacrylate 2
ꢀCH); l
C
2
2
2
i
(
200 mg, 0.943 mmol) and Pr NEt (314 mL, 2 equiv.) were
(NMe), 54.1 (OMe), 65.7 (CH
2
2
refluxed in dry toluene (5 ml) under argon until TLC
indicated consumption of 2. The cooled reaction was
filtered and the filtrate washed with 5% HCl and distilled
(ꢀCH), 164.8 (CꢀO).
6. (a) Pawda, A.; Price, A. T.; Zhi, L. J. Org. Chem. 1996, 61,
2283–2292; (b) Bloxham, J.; Dell, C. P. J. Chem. Soc.,