=
=
3385, 3299, 3063, 2918, 1628, 1529, 1495, 1454, 1432, 1419; dH
(400 MHz, CDCl3) 2.39–2.46 (1H, m, CHH), 2.63–2.70 (1H, m,
CHH), 3.16 (1H, br s, OH), 4.16–4.18 (1H, m, CHOH), 4.38–
CH CH2), 5.74 (1H, dddd, J 7.3, 9.9, 10.2, 14.3, CH CH2);
dC (100 MHz, CDCl3) 20.1, 26.1, 38.5, 42.4, 46.0, 50.5, 66.43,
66.9, 71.6, 102.8, 118.6, 132.8, 169.7, 206.0; Found (ES): [MNa]+
308.1495, C14H23NO5 requires MNa, 308.1474.
=
4.48 (2H, m, PhCH2), 5.17 (1H, d, J 15.7, CH CHH), 5.17 (1H,
=
=
d, J 11.5, CH CHH), 5.75–5.85, (1H, m, CH CH2), 7.01 (1H,
br s, NH), 7.24–7.34 (5H, m, Ph); dC (100 MHz, CDCl3) 39.2,
43.1, 70.9, 119.4, 127.5, 127.7, 128.7, 133.2, 137.9, 172.9; Found
(ES): [M]+ 205.1095, C12H15NO2 requires M, 205.1103.
(R)-2-((S)-1-Methoxy-1-methyl-2-oxo-propoxy)-pent-4-enoic
acid methoxy-methyl-amide (57)
Allyl glycolate 39 (148 mg, 0.64 mmol) was dissolved in
THF (1 ml) and cooled to 0 C. N,O-Dimethylhydroxylamine
hydrochloride (643 mg, 6.43 mmol) was added in one portion
followed by dropwise addition of PrMgCl (2.0M solution in
◦
(R)-2-Hydroxy-pent-4-enoic acid benzyl-methyl-amide (53)
i
Allyl glycolate 39 (72.0 mg, 0.31 mmol) was dissolved in N-
methylbenzylamine (0.155 ml, 1.20 mmol) and stirred at rt for
120 h. A solution of TFA–H2O (9 : 1, 3 ml) was added and the
mixture stirred at rt for 15 min. The reaction was concentrated in
vacuo and purified by column chromatography to give the amide
as a pale brown oil (58.0 mg, 66%); [a]2D5 +21.8 (c 0.71, CHCl3);
mmax (film)/cm−1 3406, 2930, 1635, 1496, 1453; dH (500 MHz,
DMSO, 120 ◦C) 2.30–2.36 (1H, m, CHH), 2.43–2.50 (1H, m,
CHH), 2.93 (3H, s, NMe), 4.44 (1H, dd, J 6.8, 5.4, CH), 4.57
(1H, d, J 15.3, PhCHH), 4.60 (1H, d, J 15.3, PhCHH), 5.03
THF, 6.23 ml, 12.5 mmol) over 1 h using a syringe pump.
The resulting suspension was stirred for 5 h and warmed to
rt. Phosphate buffer (pH 7, 1 ml) and EtOAc (2 ml) were added
and the suspension stirred overnight at rt. The suspension was
added to H2O (10 ml) and then extracted with EtOAc (3 ×
15 ml). The combined organic layers were washed with brine
(30 ml), dried (MgSO4) and concentrated in vacuo. The residue
was purified by flash column chromatography (Et2O : petrol 1 :
1 then 1 : 2) to give the amide as a colourless oil (111 mg, 67%);
[a]D25 +29.0 (c 1.1, CHCl3); mmax (film)/cm−1 2944, 1729, 1673;
dH (400 MHz, CDCl3) 1.39 (3H, s, Me), 2.23 (3H, s, COMe),
2.40–2.47 (2H, m, CH2), 3.15 (3H, br s, NMe), 3.21 (3H, s,
OMe), 3.69 (3H, s, NOMe), 4.65 (1H, m, CH), 5.02–5.13 (2H,
=
=
(1H, d, J 10.3, CH CHH), 5.08 (1H, d, J 17.2, CH CHH),
5.80–5.89 (1H, m, CH CHH), 7.24–7.29 (3H, m, Ph), 7.33–7.36
=
(2H, m, Ph); dC (125 MHz, DMSO, 120 ◦C) 34.4, 39.1, 51.8, 68.6,
117.2, 127.5, 127.9, 128.8, 135.0, 138.0, 173.4; Found (ES): [M]+
219.1252, C13H17NO2 requires M, 219.1259.
=
=
m CH CH2), 5.77 (1H, dddd, J 7.0, 9.9, 10.2, 14.3, CH CH2);
dC (125 MHz with CryoProbe, CDCl3) 20.2, 26.0, 37.8, 50.9,
61.2, 67.9, 102.8, 118.1, 133.4, 172.6, 206.3; Found (ES): [MNa]+
282.1303, C12H21NO5 requires MNa, 282.1317.
(R)-2-Hydroxy-pent-4-enoic acid isobutyl-amide (54)
Allyl glycolate 39 (72.7 mg, 0.32 mmol) was dissolved in
isopropylamine (0.12 ml, 1.4 mmol) and stirred at rt for 120 h.
A solution of TFA–H2O (9 : 1, 3 ml) was added and the mixture
stirred at rt for 15 min. The reaction was concentrated in vacuo
and purified by column chromatography to give the amide as
a pale brown oil (47.2 mg, 68%); [a]2D5 +59.8 (c 0.44, CHCl3);
mmax (film)/cm−1 3311, 2960, 2873, 1643, 1537, 1468, 1436; dH
(400 MHz, CDCl3) 0.91 (6H, d, J 6.7, 2 × Me), 1.71–1.84 (1H, m,
Me2CH), 2.38–2.45 (1H, m, CHH), 2.62–2.68 (1H, m, CHH),
3.01–3.16 (2H, m, CH2), 3.23 (1H, br s, OH), 4.13–4.15 (1H,
References
1 For examples see: G. M. Coppola and H. F. Schuster, in a-
Hydroxy Acids in Enantioselective Synthesis, VCH, Weinheim, 1997;
Y. Murakami, Y. Oshima and Y. Yasumoto, Bull. Jpn. Soc. Sci. Fish.,
1982, 48, 69; C. N. Battershill, P. T. Northcote and L. M. West, J. Org.
Chem., 2000, 65, 445.
2 For examples see: F. A. Davis and B. C. Chen, Chem. Rev., 1992,
92, 919; T. Ooi, T. Miura, K. Takaya, H. Ichikawa and K. Maruoka,
Tetrahedron, 2001, 57, 867; W. Adam, M. Lazarus, C. R. Saha-Moller
and P. Schreier, Acc. Chem. Res., 1999, 32, 837; Z. Wang, B. La, J. M.
Fortunak, X. J. Meng and G. W. Kabalka, Tetrahedron Lett., 1998,
39, 5501; M. J. Burk, C. S. Kalberg and A. Pizzano, J. Am. Chem.
Soc., 1998, 120, 4345; I. S. Byun and Y. H. Kim, Synth. Commun.,
1995, 25, 1963; H. C. Brown, B. T. Cho and W. S. Park, J. Org. Chem.,
1986, 51, 3396; M. B. Andrus, E. J. Hicken and J. C. Stephens, Org.
Lett., 2004, 6, 2289.
=
m, CH), 5.18 (1H, d, J 11.6, CH CHH), 5.19 (1H, d J 15.6,
=
=
CH CHH), 5.75–5.86 (1H, m, CH CHH), 6.72 (1H, br s, NH);
dC (100 MHz, CDCl3) 20.0, 28.5, 39.3, 46.4, 70.8, 119.4, 133.3;
Found (ES): [M]+ 171.1256, C9H17NO2 requires M, 171.1259.
(R)-2-Hydroxy-1-pyrrolidin-1-yl-pent-4-en-1-one (55)
3 A. I. Meyers, G. Knaus and P. M. Kendall, Tetrahedron Lett., 1974,
15, 3495; D. Seebach and R. Naef, Helv. Chim. Acta, 1981, 64,
2704; D. Seebach, in Modern Synthetic Methods, Springer, Berlin,
1986, pp. 125–257; J. D’Angelo, O. Pages, J. Maddaluno, F. Dumas
and G. Revial, Tetrahedron Lett., 1983, 24, 5869; G. Helmchen and
R. Wierzchowski, Angew. Chem., Int. Ed. Engl., 1984, 23, 60; M.
Enomoto, Y. Ito, T. Katsuki and M. Yamaguchi, Tetrahedron Lett.,
1985, 26, 1343; T. R. Kelly and A. Arvanitis, Tetrahedron Lett., 1984,
25, 39; J. W. Ludwig, M. Newcomb and D. E. Bergbreiter, Tetrahedron
Lett., 1986, 27, 2731; W. H. Pearson and M. C. Cheng, J. Org. Chem.,
1986, 51, 3746; P. Renaud and D. Seebach, Angew. Chem., Int. Ed.
Engl., 1986, 25, 843; S. G. Davies and M. Wills, J. Organomet. Chem.,
1987, 328, C29; G. Cardillo, M. Orena, M. Romero and S. Sandri,
Tetrahedron, 1989, 45, 1501; P. Renaud and S. Abazi, Helv. Chim.
Acta, 1996, 79, 1696; J. W. Chang, D. P. Jang, B. J. Uang, F. L. Liao
and S. L. Wang, Org. Lett., 1999, 1, 2061; J. E. Jung, H. Ho and
H. D. Kim, Tetrahedron Lett., 2000, 41, 1793; M. T. Crimmins, K. A.
Emmitte and J. D. Katz, Org. Lett., 2000, 2, 2165; M. B. Andrus,
B. Sekhar, E. L. Meredith and N. K. Dalley, Org. Lett., 2000, 2,
3035; M. B. Andrus, B. Sekhar, T. M. Turner and E. L. Meredith,
Tetrahedron Lett., 2001, 42, 7197; R. K. Boeckman, D. J. Boehmler
and R. A. Musselman, Org. Lett., 2001, 3, 3777; M. B. Andrus,
K. G. Mendenhall, E. L. Meredith and B. Sekhar, Tetrahedron Lett.,
2002, 43, 1789; H. W. Yu, C. E. Ballard, P. D. Boyle and B. H. Wang,
Tetrahedron, 2002, 58, 7663.
Allyl glycolate 39 (72.0 mg, 0.31 mmol) was dissolved in
pyrrolidine (0.100 ml, 1.20 mmol) and stirred at rt for 120 h.
A solution of TFA–H2O (9 : 1, 3 ml) was added and the mixture
stirred at rt for 15 min. The reaction was concentrated in vacuo
and purified by column chromatography to give the amide as
a pale brown oil (50.3 mg, 75%); [a]2D5 +46.0 (c 0.25, CHCl3);
mmax (film)/cm−1 3392, 2974, 2879, 1623, 1455; dH (400 MHz,
CDCl3) 1.79–1.88 (2H, m, CH2), 1.90–1.99 (2H, m, CH2), 2.27–
2.34 (1H, m, CHH), 2.35–2.43 (1H, m, CHH), 3.31–3.67 (1H,
m, CHH), 3.40–3.49 (2H, m, CH2), 3.51–3.57 (1H, m, CHH),
3.80 (1H, br s, OH), 4.26–4.28 (1H, m, CHOH), 5.08 (1H, d,
=
=
J 9.5, CH CHH), 5.09 (1H, d, J 19.0, CH CHH), 5.78–5.89
(1H, m, CH); dC (100 MHz, CDCl3) 23.8, 25.9, 38.8, 46.0, 46.2,
69.1, 117.8, 113.2, 172.2; Found (ES): [M]+ 169.1097, C9H15NO2
requires M, 169.1103.
(R)-2-((S)-1-Methoxy-1-methyl-2-oxo-propoxy)-1-morpholin-4-
yl-pent-4-en-1-one (56)
Allyl glycolate 39 (27 mg, 0.12 mmol) was dissolved in morpho-
line (50 ll, 0.56 mmol) and stirred at rt for 48 h. The reaction
was concentrated in vacuo to yield the amide as a colourless oil
(35 mg, 100%); [a]D25 +46.7 (c 0.76, CHCl3); mmax (film)/cm−1 2968,
1729, 1640; dH (400 MHz, CDCl3) 1.41 (3H, s, Me), 2.22 (3H, s,
OCCH3), 2.48 (2H, t, J 7.3, CH2), 3.27 (3H, s, OMe), 3.55–3.71
(8H, m, 4 × CH2), 4.44 (1H, t, J 7.3, CH), 5.07–5.16 (2H, m
4 S. V. Ley, R. Downham, P. J. Edwards, J. E. Innes and M. Woods,
Contemp. Org. Syn., 1995, 2, 365.
5 R. Downham, K.-S. Kim, S. V. Ley and M. Woods, Tetrahedron Lett.,
1994, 35, 769; G.-J. Boons, R. Downham, K.-S. Kim, S. V. Ley and
M. Woods, Tetrahedron, 1994, 50, 7157.
3 6 1 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 6 0 8 – 3 6 1 7