PAPER
Rhodium-Catalyzed Synthesis of a-Amido- and a-Carboxylic-b-Ketoesters
2237
(3n) was found to be unstable in normal silica and was therefore pu-
rified using iatrobeads.
2-(2-Chloroacetylamino)-3-oxobutyric Acid Ethyl Ester (3g)
1H NMR: d = 7.66 (d, J = 3.6 Hz, 1 H, NH), 5.19 (d, J = 6.4 Hz, 1
H, CH), 4.26 (dq, J = 7.0, 1.5 Hz, 2 H, CH2), 4.07 (s, 2 H, CH2Cl),
2.38 (s, 3 H, COCH3), 1.29 (t, J = 7.1 Hz, 3 H, CH3).
2-Benzoylamino-3-oxobutyric Acid Ethyl Ester (3a)
1H NMR: d = 7.79 (d, J = 7.3 Hz, 2 H, ArH), 7.32–7.48 (m, 4 H,
ArH, NH), 5.39 (d, J = 6.4 Hz, 1 H, CH), 4,22 (dq, J = 7.2, 3.0 Hz,
2 H, CH2), 2.38 (s, 3 H, COCH3), 1.24 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR: d = 197.4, 165.9, 165.2, 63.1, 62.8, 42.0, 27.9, 13.9.
HRMS: m/z calcd for C8H12ClNNaO4: 244.0353; found: 244.0348.
13C NMR: d = 198.5, 166.6, 165.9, 132.7, 131.8, 128.4 (2 × C),
127.1 (2 × C), 63.3, 62.4, 27.8, 13.7.
Benzoic Acid 1-Ethoxycarbonyl-2-oxopropyl Ester (3h)
1H NMR: d = 8.10 (dd, J = 8.4, 1.3 Hz, 2 H, ArH), 7.55–7.62 (m, 1
H, ArH), 7.45 (t, J = 7.7 Hz, 2 H, ArH), 5.69 (s, 1 H, CH), 4.28 (q,
J = 7.1 Hz, 2 H, CH2), 2.40 (s, 3 H, COCH3), 1.29 (t, J = 7.1 Hz, 3
H, CH3).
HRMS: m/z calcd for C13H15NNaO4: 272.0899; found: 272.0891.
2-[(Naphthalene-1-carbonyl)amino]-3-oxobutyric Acid Ethyl
Ester (3b)
13C NMR: d = 197.6, 164.9, 164.4, 133.7, 129.9, 128.4, 128.3, 78.0,
62.4, 27.2, 13.9.
1H NMR: d = 8.37 (d, J = 8.1 Hz, 1 H, ArH), 7.93 (d, J = 8.3 Hz, 1
H, ArH), 7.86 (d, J = 7.3 Hz, 1 H, ArH), 7.71 (d, J = 7.0 Hz, 1 H,
ArH), 7.50–7.60 (m, 2 H, ArH), 7.41–7.48 (m, 1 H, ArH), 7.23 (d,
J = 6.3 Hz, 1 H, NH), 5.54 (d, J = 6.5 Hz, 1 H, CH), 4.32 (dq, J =
7.1, 5.4 Hz, 2 H, CH2), 2.48 (s, 3 H, COCH3), 1.34 (t, J = 7.2 Hz, 3
H, CH3).
HRMS: m/z calcd for C13H14NaO5: 273.0739; found: 273.0745.
Naphthalene-1-carboxylic Acid 1-Ethoxycarbonyl-2-oxopropyl
Ester (3i)
1H NMR: d = 8.94 (d, J = 8.7 Hz, 1 H, ArH), 8.40 (dd, J = 7.3, 1.2
Hz, 1 H, ArH), 8.06 (d, J = 8.2 Hz, 1 H, ArH), 7.89 (d, J = 8.1 Hz,
1 H, ArH), 7.63 (ddd, J = 8.5, 6.9, 1.2 Hz, 1 H, ArH), 7.49–7.58 (m,
2 H, ArH), 5.84 (s, 1 H, CH), 4.34 (q, J = 7.1 Hz, 2 H, CH2), 2.46
(s, 3 H, COCH3), 1.34 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR: d = 198.7, 169.3, 166.2, 133.9, 133.0, 131.5, 130.4,
128.6, 127.6, 126.7, 125.9, 125.5, 124.9, 64.0, 63.1, 28.5, 14.3.
HRMS: m/z calcd for C17H17NNaO4: 322.1055; found: 322.1046.
2-(3,4-Difluorobenzoylamino)-3-oxobutyric Acid Ethyl Ester
(3c)
1H NMR: d = 7.66 (ddd, J = 10.6, 7.5, 2.2 Hz, 1 H, ArH), 7.54–7.59
(m, 1 H, ArH), 7.42 (d, J = 6.4 Hz, 1 H, NH), 7.13–7.22 (m, 1 H,
ArH), 5.38 (d, J = 6.5 Hz, 1 H, CH), 4.23 (dq, J = 7.2, 2.6 Hz, 2 H,
CH2), 2.39 (s, 3 H, COCH3), 1.26 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR: d = 197.7, 165.7, 164.6, 134.4, 133.7, 131.3, 131.2,
128.6, 128.1, 126.3, 125.4, 124.9, 124.4, 78.2, 62.5, 27.4, 13.9.
HRMS: m/z calcd for C17H16NaO5: 323.0895; found: 323.0894.
3,4-Dichlorobenzoic Acid 1-Ethoxycarbonyl-2-oxopropyl Ester
(3j)
1H NMR: d = 8.16 (s, 1 H, ArH), 7.92 (d, J = 8.3 Hz, 1 H, ArH), 7.54
(d, J = 8.4 Hz, 1 H, ArH), 5.71 (s, 1 H, CH), 4.30 (q, J = 7.1 Hz, 2
H, CH2), 2.41 (s, 3 H, COCH3), 1.30 (t, J = 7.1 Hz, 3 H, CH3).
1
13C NMR: d = 198.3, 165.8, 164.6, 152,6 (dd, JCF = 254.9 Hz,
2JCF = 12.9 Hz), 150.0 (dd, 1JCF = 250.3 Hz, 2JCF = 13.1 Hz), 129.8
(dd, 3JCF = 5.0 Hz, 4JCF = 3.5 Hz), 123.8 (dd, 3JCF = 7.3 Hz, 4JCF
=
3.7 Hz), 117.3 (d, 2JCF = 17.8 Hz), 117.0 (d, 2JCF = 18.9 Hz), 63.4,
62.7, 27.9, 13.8.
13C NMR: d = 196.8, 164.0, 163.2, 138.5, 133.1, 131.8, 130.7,
129.0, 128.2, 78.3, 62.7, 27.3, 13.9.
HRMS: m/z calcd for C13H13F2NNaO4: 308.0710; found: 308.0726.
HRMS: m/z calcd for C13H12Cl2NaO5: 340.9959; found: 340.9967.
2-(2-Ethoxybenzoylamino)-3-oxobutyric Acid Ethyl Ester (3d)
1H NMR: d = 9.30 (d, J = 5.4 Hz, 1 H, NH), 8.15 (dd, J = 7.9, 1.9
Hz, 1 H, ArH), 7.42 (ddd, J = 8.6, 7.5, 1.9 Hz, 1 H, ArH), 7.02 (dt,
J = 7.5, 0.9 Hz, 1 H, ArH), 6.96 (d, J = 8.3 Hz, 1 H, ArH), 5.41 (d,
J = 5.7 Hz, 1 H, CH), 4.28 (q, J = 7.1 Hz, 2 H, CH2), 4.20 (q, J = 7.0
Hz, 2 H, CH2), 2.42 (s, 3 H, COCH3), 1.61 (t, J = 7.0 Hz, 3 H, CH3),
1.30 (t, J = 7.1 Hz, 3 H, CH3).
4-Nitrobenzoic Acid 1-Ethoxycarbonyl-2-oxopropyl Ester (3k)
1H NMR: d = 8.26–8.31 (m, 4 H, ArH), 5.76 (s, 1 H, CH), 4.31 (q,
J = 7.1 Hz, 2 H, CH2), 2.43 (s, 3 H, COCH3), 1.33 (t, J = 7.1 Hz, 3
H, CH3).
13C NMR: d = 196.4, 163.8, 163.2, 150.9, 133.7, 131.1 (2 × C),
123.6 (2 × C), 78.5, 62.8, 27.4, 13.9.
13C NMR: d = 198.8, 166.2, 164.8, 157.5, 133.3, 132.1, 120.8,
119.9, 112.1, 64.8, 64.1, 62.4, 28.0, 14.6, 14.0.
HRMS: m/z calcd for C13H13NNaO7: 318.0590; found: 318.0599.
4-Methoxybenzoic Acid 1-Ethoxycarbonyl-2-oxopropyl Ester
(3l)
HRMS: m/z calcd for C15H19NNaO5: 316.1161; found: 316.1160.
1H NMR: d = 8.04 (d, J = 8.8 Hz, 2 H, ArH), 6.91 (d, J = 8.8 Hz, 2
H, ArH), 5.65 (s, 1 H, CH), 4.27 (q, J = 7.1 Hz, 2 H, CH2), 3.83 (s,
3 H, OCH3), 2.39 (s, 3 H, COCH3), 1.28 (t, J = 7.1 Hz, 3 H, CH3).
2-(2-Nitrobenzoylamino)-3-oxobutyric Acid Ethyl Ester (3e)
1H NMR: d = 8.02 (d, J = 8.3 Hz, 1 H, ArH), 7.67 (dt, J = 7.5, 1.7
Hz, 1 H, ArH), 7.58 (dt, J = 7.5, 1.5 Hz, 2 H, ArH), 7.14 (d, J = 6.2
Hz, 1 H, NH), 5.42 (d, J = 6.5 Hz, 1 H, CH), 4.28 (dq, J = 7.1, 1.9
Hz, 2 H, CH2), 2.43 (s, 3 H, COCH3), 1.31 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR: d = 198.0, 164.6 (2 × C), 163.9, 132.1 (2 × C), 120.5,
113.7 (2 × C), 77.9, 62.3, 55.3, 27.2, 13.9.
13C NMR: d = 198.0, 165.8, 165.5, 146.3, 133.6, 131.5, 130.9,
128.8, 124.5, 63.3, 62.8, 28.0, 13.9.
HRMS: m/z calcd for C14H16NaO6: 303.0845; found: 303.0847.
2-Benzoylamino-4-chloro-3-oxobutyric Acid Ethyl Ester (3n)
1H NMR: d = 7.79–7.83 (m, 2 H, ArH), 7.50–7.54 (m, 1 H, ArH),
7.41–7.46 (m, 2 H, ArH), 7.38 (d, J = 5.7 Hz, 1 H, NH), 5.59 (d,
J = 6.4 Hz, 1 H, CH), 4.57 (s, 2 H, CH2Cl), 4.28 (q, J = 7.1 Hz, 2 H,
CH2), 1.29 (t, J = 7.1 Hz, 3 H, CH3).
HRMS: m/z calcd for C13H14N2NaO6: 317.0750; found: 317.0747.
2-Acetylamino-3-oxobutyric Acid Ethyl Ester (3f)
1H NMR: d = 6.90 (d, J = 5.6 Hz, 1 H, NH), 5.19 (d, J = 6.7 Hz, 1
H, CH), 4.18 (dq, J = 7.1, 1.1 Hz, 2 H, CH2), 2.30 (s, 3 H, COCH3),
1.99 (s, 3 H, COCH3), 1.23 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR: d = 193.9, 167.0, 165.3, 132.7, 132.3, 128.6 (2 × C),
127.2 (2 × C), 63.2, 60.2, 47.5, 13.9.
13C NMR: d = 198.7, 169.9, 166.0, 63.0, 62.5, 28.0, 22.5, 13.8.
HRMS: m/z calcd for C13H14ClNNaO4: 306.0509; found: 306.0504.
HRMS: m/z calcd for C8H13NNaO4: 210.0742; found: 210.0732.
Synthesis 2005, No. 13, 2234–2238 © Thieme Stuttgart · New York