B. Alcaide, P. Almendros and J. M. Alonso
General procedure for the isomerization reaction of N-allyl amides, lac-
tams, imides, and congeners: [Cl2(Cy3P)2Ru=CHPh] (0.01 mmol) was
added in portions under argon to a solution, protected from the sunlight,
of the corresponding allylic compound (0.20 mmol) in anhydrous toluene
(6 mL), and the mixture was heated at reflux. The reaction was moni-
tored by TLC. After completion, the mixture was concentrated under re-
duced pressure, and was purified by column chromatography, eluting
with EtOAc/hexanes mixtures to give analytically pure enamide-like
compounds. Spectroscopic and analytical data for some representative
pure forms of the above enamides follow.[23]
(dd, J=9.6, 1.6 Hz, 1H), 4.83 (m, 1H), 3.89 (dd, J=11.3, 7.6 Hz, 1H),
3.50 (t, J=11.3 Hz, 1H), 2.70 (m, 1H), 1.53 (dd, J=4.4, 1.6 Hz, 1H),
1.05 ppm (d, J=7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=
173.0, 150.1, 129.7, 129.3, 123.6, 120.6, 118.5, 111.5, 62.9, 34.0, 13.1,
12.7 ppm; IR (CHCl3): n˜ =1722 cmÀ1; MS (ES): m/z (%): 217 (100)
[M+H]+, 216 (10) [M]+; elemental analysis calcd (%) for C13H16N2O
(216.3): C 72.19, H 7.46, N 12.95; found C 72.30, H 7.50, N 13.00.
General procedure for the cleavage of enamide derivatives. Preparation
of free NH-amides, lactams, imides, and congeners: Aqueous RuCl3
(0.2 mL, 3.5 mol%) and solid NaIO4 (0.4 mmol) were sequentially added
to a solution of the corresponding enamide derivative (0.20 mmol) in a
1,2-dichloroethane-water mixture (2 mL, 1:1). The reaction mixture was
stirred at room temperature until complete disappearance of the starting
material was observed (TLC), before being quenched with aqueous
Na2S2O3 and extracted with EtOAc. The organic phase was concentrated
and the resulting residue was dissolved in acetone and stirred with satu-
rated aq NaHCO3 (0.33 mL) and Na2CO3 (0.02 mmol). The mixture was
extracted with EtOAc, washed with water, dried over MgSO4, filtered,
and concentrated to give pure NH-compounds 3, 6, 9, 12, 15, and 18.
Spectroscopic and analytical data for some representative pure forms of
the above free NH-compounds follow.
(Z)-2d: From 110 mg (0.72 mmol) of 1-allyl-azepan-2-one 1d and after
column chromatography (hexanes/EtOAc 3:1) 79 mg (72%) of com-
pound (Z)-2d was obtained as a yellow oil. 1H NMR (300 MHz, CDCl3,
258C): d=6.19 (dd, J=8.4, 1.7 Hz, 1H), 5.14 (m, 1H), 3.40 (m, 2H), 2.51
(m, 2H), 1.63 (m, 6H), 1.51 ppm (dd, J=7.1, 1.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3, 258C): d=175.6, 133.7, 118.1, 51.0, 37.3, 29.9, 28.7, 23.3,
14.1 ppm; IR (CHCl3): n˜ =1652 cmÀ1; MS (ES): m/z (%): 154 (100)
[M+H]+, 153 (8) [M]+; elemental analysis calcd (%) for C9H15NO
(153.2): C 70.55, H 9.87, N 9.14; found C 70.42, H 9.83, N 9.18.
(E)-(Æ)-5d: From 150 mg (0.56 mmol) of 1-allyl-b-lactam (Æ)-4d and
after column chromatography (hexanes/EtOAc 5:1), 108 mg (72%) of
compound (E)-(Æ)-5d was obtained as
a
colorless oil. 1H NMR
NH-b-Lactam (Æ)-6a: From 87 mg (0.385 mmol) of enamide derivative
(Æ)-5a, compound (Æ)-6a (58 mg, 64%) was obtained as a colorless oil;
1H NMR (300 MHz, CDCl3, 258C): d=6.90 (s, 1H), 6.70 (m, 3H), 5.11
(d, J=4.7 Hz, 1H), 4.65 (d, J=5.7 Hz, 1H), 3.73 and 3.69 (s, each 3H),
3.16 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=168.2, 153.6,
151.2, 125.4, 113.7, 113.4, 111.1, 86.9, 58.6, 55.8, 55.7, 53.4 ppm; IR
(CHCl3): n˜ =3408, 1766 cmÀ1; MS (ES): m/z (%): 238 (100) [M+H]+, 237
(7) [M]+; elemental analysis calcd (%) for C12H15NO4 (237.3): C 60.75, H
6.37, N 5.90; found C 60.88, H 6.40, N 5.87.
(300 MHz, CDCl3, 258C): d=7.28 (m, 1H), 7.14 (m, 2H), 6.59 (m, 3H),
6.36 (m, 1H), 6.25 (m, 1H), 6.07 (dd, J=9.2, 1.7 Hz, 1H), 5.42 (d, J=
4.6 Hz, 1H), 5.30 (d, J=4.6 Hz, 1H), 4.93 (dd, J=9.2, 7.3 Hz, 1H),
1.56 ppm (dd, J=7.3, 1.7 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=
163.3, 157.2, 147.6, 143.3, 129.4 (2C), 122.4, 120.8, 115.7 (2C), 114.8,
110.9, 110.5, 81.6, 58.2, 15.1 ppm; IR (CHCl3): n˜ =1751 cmÀ1; MS (ES):
m/z (%): 208 (100) [M+H]+, 207 (9) [M]+; elemental analysis calcd (%)
for C11H13NO3 (207.2): C 63.76, H 6.32, N 6.76; found C 63.64, H 6.29, N
6.73.
NH-b-Lactam (+)-6c: From 51 mg (0.15 mmol) of enamide derivative
(+)-5c, compound (+)-6c (42 mg, 95%) was obtained as a colorless oil;
[a]D =+12.0 (c=1.0 in CHCl3); 1H NMR (300 MHz, CDCl3, 258C): d=
6.20 (s, 1H), 4.70 (d, J=4.9 Hz, 1H), 4.01 (m, 2H), 3.51 (m, 2H), 1.32
and 1.20 (s, each 3H), 0.77 (s, 9H), 0.09 and 0.01 ppm (s, each 3H);
13C NMR (75 MHz, CDCl3, 258C): d=166.2, 107.1, 76.9, 66.5, 57.7, 26.8,
25.5, 24.9, 17.8 ppm; IR (CHCl3): n˜ =3392, 1764 cmÀ1; MS (ES): m/z (%):
302 (100) [M+H]+, 301 (14) [M]+; elemental analysis calcd (%) for
C14H27NO4Si (301.5): C 55.78, H 9.03, N 4.65; found C 55.80, H 8.99, N
4.62.
Preparation of (+)-5e: From 200 mg (0.66 mmol) of 1-allyl-b-lactam (+)-
4e and after column chromatography (hexanes/EtOAc 2:1), 81 mg
(40%) of the less polar compound (E)-(+)-5e and 79 mg (39%) of the
more polar compound, its Z isomer were obtained.
(E)-(+)-5e: Colorless oil; [a]D =+184.3 (c=0.6 in CHCl3); 1H NMR
(300 MHz, CDCl3, 258C): d=7.23 (m, 2H), 6.99 (m, 3H), 6.36 (dd, J=
14.3, 1.6 Hz, 1H), 5.79 (dd, J=14.3, 6.9 Hz, 1H), 5.16 (d, J=5.4 Hz, 1H),
4.42 (m, 1H), 4.22 (m, 1H), 3.97 (m, 1H), 3.68 (m, 1H), 1.67 (dd, J=6.8,
0.6 Hz; 3H), 1.39 (s, 3H; Me), 1.27 ppm (s, 3H; Me); 13C NMR (75 MHz,
CDCl3, 258C): d=163.0, 157.4, 129.7 (2C), 122.8, 121.9, 115.9 (2C),
112.9, 109.9, 79.7, 76.9, 67.1, 61.9, 26.9, 26.8, 25.1, 15.4 ppm; IR (CHCl3):
n˜ =1753 cmÀ1; MS (ES): m/z (%):304 (100) [M+H]+, 303 (7) [M]+; ele-
mental analysis calcd (%) for C17H21NO4 (303.3): C 67.31, H 6.98, N 4.62;
found C 67.43, H 6.94, N 4.59.
NH-Bis-g-lactam (+)-12: From 20 mg (0.049 mmol) of the corresponding
enamide derivative, compound (+)-12 (14 mg, 79%) was obtained as a
orange oil; [a]D =+67.1 (c=0.8 in CHCl3); 1H NMR (300 MHz, CDCl3,
258C): d=7.21 (m, 5H), 6.70 (m, 4H), 4.78 (d, J=6.7 Hz, 1H), 4.56 (d,
J=1.7 Hz, 1H), 4.30 (d, J=5.1 Hz, 1H), 3.64 (s, 3H), 3.62 (m, 1H),
3.49 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=172.2, 171.6,
158.7, 157.5, 129.9, 129.2, 125.4, 123.1, 116.8, 115.1, 82.3, 77.6, 68.4, 60.8,
59.2, 55.9 ppm; IR (CHCl3): n˜ =3390, 1722, 1719 cmÀ1; MS (ES): m/z
(%): 409 (100) [M+H]+, 408 (11) [M]+; elemental analysis calcd (%) for
C20H20N2O5 (368.4): C 65.21, H 5.47, N 7.60; found C 65.33, H 5.44, N
7.64.
(Z)-(+)-5e: Colorless oil; [a]D =+233.0 (c=0.7 in CHCl3); 1H NMR
(300 MHz, CDCl3, 258C): d=7.24 (m, 2H), 6.97 (m, 3H), 5.96 (m, 1H),
5.18 (m, 2H), 4.42 (m, 1H), 4.10 (m, 2H), 3.68 (m, 1H), 1.73 (dd, J=7.1,
0.6 Hz, 3H), 1.39 (s, 3H), 1.14 ppm (s, 3H); 13C NMR (75 MHz, CDCl3,
258C): d=163.2, 157.4, 129.7 (2C), 122.7, 121.9, 118.7, 115.9 (2C), 115.7,
109.9, 79.4, 66.9, 61.8, 26.8, 25.1, 14.3 ppm; IR (CHCl3): n˜ =1752 cmÀ1
;
MS (ES): m/z (%): 304 (100) [M+H]+, 303 (10) [M]+; elemental analysis
calcd (%) for C17H21NO4 (303.3): C 67.31, H 6.98, N 4.62; found C 67.44,
H 6.90, N 4.65.
Compound (E)-14a: From 120 mg (0.59 mmol) of 1-allyl-acetamide 13a
Acknowledgements
and after column chromatography (hexanes/EtOAc (3:1), 85 mg (71%)
of compound (E)-14a was obtained as
a
colorless oil; 1H NMR
Support for this work by the DGI-MCYT (Project BQU2003–07793-
C02–01) is gratefully acknowledged. J. M. Alonso thanks the Universidad
Complutense de Madrid for a fellowship.
(300 MHz, CDCl3, 258C): d=7.35 (dd, J=14.3, 1.5 Hz, 1H), 6.99 (m,
2H), 6.91 (m, 2H), 4.33 (m, 1H), 3.78 (s, 3H), 1.77 (s, 3H), 1.56 ppm (dd,
J=6.7, 1.3 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=167.5, 159.1,
133.2, 129.9, 129.2, 115.1, 109.1, 55.5, 23.2, 15.1 ppm; IR (CHCl3): n˜ =
1654 cmÀ1; MS (EI): m/z (%): 205 (100) [M]+; elemental analysis calcd
(%) for C12H15NO2 (205.2): C 70.22, H 7.37, N 6.82; found C 70.10, H
7.34, N 6.78.
[1] For a pertinent review see: J. Kant, D. G. Walker in The Organic
Chemistryof b-Lactams (Ed.: G. I. Georg), Wiley-VCH, New York,
1993.
Compound (E)-17b. From 200 mg (0.926 mmol) of 2-allyl-4-methyl-1-
phenyl-pyrazolidin-3-one 16b and after column chromatography (hex-
anes/EtOAc 3:1), 174 mg (87%) of compound (E)-17b was obtained as a
orange oil; 1H NMR (300 MHz, CDCl3, 258C): d=7.20 (m, 5H), 6.35
[2] M. Suffness, Taxol Science and Applications, CRC Press, Boca
Raton, FL, USA, 1995.
[3] a) S. Escoubet, S. Gastaldi, M. Bertrand, Eur. J. Org. Chem. 2005,
3855; b) P. J. Kocienski, Protecting Groups, 3rd ed., Thieme, Stutt-
2878
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 2874 – 2879