The Journal of Organic Chemistry
Article
135.4, 135.3, 132.2, 128.6−128.1 (15C), 127.2, 116.3, 68.9, 68.6, 57.4,
52.6, 36.1; HRMS (ESI) calcd for C28H26N2O6Na [M + Na]+
509.1689, found 509.1692.
7.15−7.04 (m, 3H), 6.05 (s, 1H), 4.91 (dd, J = 8.7 Hz, J = 4.1 Hz,
1H), 3.74 (s, 3H), 3.34−3.07 (m, 2H), 2.29 (s, 3H), 1.56 (s, 9H), 1.14
(s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.2, 155.8, 151.7, 135.5,
135.4, 133.2, 129.8, 127.7, 126.8, 125.4, 111.9, 82.5, 81.7, 56.8, 52.5,
36.5, 28.2 (3C), 27.5 (3C), 20.0; FTIR (neat) cm−1 3047, 2974, 2931,
1736, 1712, 1365, 1298, 1242, 1148, 730, 694; HRMS (ESI) calcd for
C23H32N2O6Na [M + Na]+ 455.2158, found 455.2155; [α]20D = −38.3
(c 0.5, CHCl3) for 93% ee. Enantiomeric excess of 6d has been
determined by HPLC analysis employing a chiral OD-H column
(heptane/2-propanol, 95:5, 1.0 mL/min), tR = 6.36 min for the major
enantiomer and tR = 10.16 min for the minor enantiomer.
1,2-Dibenzyl 3-Methyl (5Z)-5-Benzylidenepyrazolidine-1,2,3-tri-
carboxylate (E-4a). The compound was purified by preparative
thin-layer chromatography (pentane/ethyl acetate, 85:15) and was
1
obtained as a colorless oil. Rf 0.25 (pentane/ethyl acetate, 85:15); H
NMR (300 MHz, CDCl3) δ 7.44−7.16 (m, 15H), 7.04 (s, 1H), 5.33
(d, J = 12.6 Hz, 1H), 5.27 (d, J = 12.6 Hz, 1H), 5.21 (d, J = 12.6 Hz,
1H), 5.17 (d, J = 12.6 Hz, 1H), 5.12 (dd, J = 7.0 Hz, J = 3.5 Hz, 1H),
3.62 (s, 3H), 3.33−3.20 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
170.1, 156.5, 154.3, 136.2, 135.9, 135.5, 133.8, 128.7−128.0 (14C),
126.9, 114.7, 68.9, 68.4, 58.6, 52.8, 34.5; FTIR (neat) cm−1 3061,
3032, 2951, 1715, 1486, 1387, 1286, 1210, 1067, 1025, 911, 751, 694;
HRMS (ESI) calcd for C28H26N2O6Na [M + Na]+ 509.1689, found
509.1685.
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(4-tert-Butylbenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6e). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a 85:15 mixture of colorless oils 6e(A)/
1
7e(B). Rf 0.30 (pentane/ethyl acetate, 85:15); H NMR (300 MHz,
1,2-Dibenzyl 3-Methyl 6-Phenyl-3,4-dihydropyridazine-1,2,3-tri-
carboxylate (5a). The compound was purified by preparative thin-
layer chromatography (pentane/ethyl acetate, 85:15) and was
CDCl3) δ meaningful data: 7.45 (d, J = 8.4 Hz, 1H, A), 7.27 (d, J = 8.4
Hz, 1H, A), 5.98 (s, 1H, A), 5.45−5.35 (m, 1H, B), 5.28−5.20. (m,
1H, B), 4.85 (dd, J = 8.7 Hz, J = 4.9 Hz, 1H; A), 3.74 (s, 3H, A), 3.19−
3.09 (m, 2H, A), 2.75−2.50 (m, 2H, B), 1.59 (s, 3H, A), 1.30 (s, 9H,
A), 1.20 (s, 9H, A); 13C NMR (75 MHz, CDCl3) δ 171.2, 155.7,
152.1, 149.8, 133.3, 132.4, 127.9 (2C), 124.8 (2C), 114.7, 82.4, 81.9,
56.7, 52.6, 36.4, 34.5, 31.2 (3C), 28.2 (3C), 27.5 (3C); FTIR (neat)
cm−1 2970, 2931, 2868, 1739, 1716, 1356, 1290, 1152; HRMS (ESI)
calcd for C26H38N2O6Na [M + Na]+ 497.2628, found 497.2628.
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(4-Fluorobenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6f). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a colorless oil. Rf 0.24 (pentane/ethyl
acetate, 85:15); 1H NMR (300 MHz, CDCl3) δ 7.50 (dd, J = 8.5 Hz, J
= 5.5 Hz, 2H), 6.94 (app t, J = 8.8 Hz, 2H), 5.97 (s, 1H), 4.85 (dd, J =
8.7 Hz, J = 4.6 Hz, 1H), 3.74 (s, 3H), 3.25−3.05 (m, 2H), 1.54 (s,
9H), 1.26 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.1, 161.5 (1C, J
= 247 Hz), 155.5, 152.0, 132.8 (J = 1.8 Hz), 132.3 (J = 3.4 Hz), 129.7
(J = 7.8 Hz, 2C), 114.8 (2C, J = 21 Hz), 113.7, 82.5, 82.2, 56.7, 52.8,
36.4, 28.2 (3C), 27.7 (3C); FTIR (neat) cm−1 3056, 2982, 1740, 1715,
1503, 1364, 1262, 1221, 1151, 1017, 853, 740, 698; HRMS (ESI) calcd
1
obtained as a colorless oil. Rf 0.16 (pentane/ethyl acetate, 8:2); H
NMR (300 MHz, CDCl3) δ 7.40−6.90 (m, 15H), 5.51 (t, J = 4.1 Hz,
1H), 5.30−5.20 (m, 5H), 3.64 (s, 3H), 2.90−2.55 (m, 2H); HRMS
(ESI) calcd for C28H26N2O6Na [M + Na]+ 509.1689, found 509.1690.
1,2-Di-tert-butyl 3-Methyl (5Z)-5-Benzylidenepyrazolidine-1,2,3-
tricarboxylate (6a). The compound was purified by preparative thin-
layer chromatography (pentane/ethyl acetate, 85:15) and was
obtained as a colorless oil. Rf 0.37 (pentane/ethyl acetate, 85:15);
1H NMR (300 MHz, CDCl3) δ 7.55 (d, J = 7.4 Hz, 2H), 7.28 (app t, J
= 7.4 Hz, 2H), 7.18 (t, J = 7.3 Hz, 1H), 6.02 (s, 1H), 4.89 (dd, J = 8.4
Hz, J = 4.6 Hz, 1H), 3.76 (s, 3H), 3.26−3.11 (m, 2H), 1.57 (s, 9H),
1.24 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.3, 155.7, 152.1,
136.3, 133.1, 128.3 (2C), 128.0 (2C), 126.9, 114.8, 82.6, 82.1, 56.8,
52.7, 36.6, 28.2 (3C), 27.7 (3C); FTIR (neat) cm−1 2977, 2931, 1731,
1711, 1363, 1304, 1151; HRMS (ESI) calcd for C22H30N2O6Na [M +
Na]+ 441.2002, found 441.2003; [α]20 = −73 (c 1, CHCl3) for 93%
D
ee. Enantiomeric excess of 6a has been determined by HPLC analysis
employing a chiral OD-H column (heptane/2-propanol, 95:5, 1.0 mL/
min), tR = 7.23 min for the major enantiomer and tR = 8.49 min for the
minor enantiomer.
for C22H29N2O6FNa [M + Na]+ 459.1907, found 459.1908; [α]20
−73.5 (c 1, CHCl3) for 93% ee.
=
D
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(4-Methylbenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6b). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a colorless oil. Rf 0.29 (pentane/ethyl
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(4-Methoxybenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6g). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate, 8:2)
and was obtained as a colorless oil. 6g proves to be rather unstable and
decomposes slowly in chloroform-d solution. Rf 0.23 (pentane/ethyl
1
acetate, 85:15); H NMR (300 MHz, CDCl3) δ 7.42 (d, J = 7.9 Hz,
1
2H), 7.06 (d, J = 7.9 Hz, 2H), 5.97 (s, 1H), 4.85 (dd, J = 8.7 Hz, J =
4.6 Hz, 1H), 3.74 (s, 3H), 3.30−3.12 (m, 2H), 2.32 (s, 3H), 1.54 (s,
9H), 1.26 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.4, 155.9, 152.3,
136.7, 133.4, 132.3, 128.7 (2C), 128.3 (2C), 115.0, 82.5, 82.1, 56.8,
52.7, 36.6, 28.3 (3C), 27.8 (3C), 21.4; FTIR (neat) cm−1 3056, 2986,
1744, 1711, 1421, 1368, 1266, 1147, 894, 739, 702; HRMS (ESI) calcd
acetate, 85:15); H NMR (300 MHz, CDCl3) δ 7.47 (d, J = 8.7 Hz,
2H), 6.80 (d, J = 8.7 Hz, 2H), 5.96 (s, 1H), 4.83 (dd, J = 8.7 Hz, J =
4.9 Hz, 1H), 3.80 (s, 3H), 3.74 (s, 3H), 3.23−3.01 (m, 2H), 1.54 (s,
9H), 1.28 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.4, 158.6, 152.4,
131.4, 130.8, 129.6 (2C), 128.9, 114.8, 113.5 (2C), 82.5, 82.1, 56.9,
55.4, 52.7, 36.5, 28.3 (3C), 27.9 (3C); FTIR (neat) cm−1 3048, 2974,
2923, 2848, 1735, 1708, 1692, 1511, 1365, 1294, 1242, 1140, 1025;
HRMS (ESI) calcd for C23H32N2O7Na [M + Na]+ 471.2107, found
471.2106.
for C23H32N2O6Na [M + Na]+ 455.2158, found 455.2156; [α]20
−61.3 (c 1, CHCl3) for 93% ee.
=
D
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(3-Methylbenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6c). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a colorless oil. Rf 0.29 (pentane/ethyl
1,2-Di-tert-butyl 3-Methyl 6-(4-Methoxyphenyl)-3,4-dihydropyr-
idazine-1,2,3-tricarboxylate (7g). The compound was purified by
preparative thin-layer chromatography (pentane/ethyl acetate, 85:15)
to afford 7g as a colorless oil which proves to be unstable in
1
acetate, 85:15); H NMR (300 MHz, CDCl3) δ 7.36−7.30 (m, 2H),
1
7.16 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 5.98 (s, 1H), 4.89
(dd, J = 8.7 Hz, J = 4.6 Hz, 1H), 3.75 (s, 3H), 3.24−3.10 (m, 2H),
2.32 (s, 3H), 1.56 (s, 9H), 1.26 (s, 9H); 13C NMR (75 MHz, CDCl3)
δ 171.3, 155.9, 152.2, 137.3, 136.2, 132.9, 128.9, 127.9, 127.8, 125.6,
114.8, 82.5, 82.1, 56.7, 52.7, 36.7, 28.3 (3C), 27.8 (3C), 21.6; FTIR
(neat) cm−1 3047, 2974, 2931, 1736, 1712, 1365, 1298, 1242, 1148,
730, 694; HRMS (ESI) calcd for C23H32N2O6Na [M + Na]+ 455.2158,
chloroform-d solution. Rf 0.35 (pentane/ethyl acetate, 8:2); H NMR
(300 MHz, CDCl3) δ 7.55−7.30 (m, 2H), 6.84 (app d, J = 8.7 Hz,
2H), 5.35 (t, J = 5.6 Hz, 1H), 5.25−5.15 (m, 1H), 3.81 (s, 3H), 3.74
(s, 3H), 2.77−2.63 (m, 1H), 2.55 (dt, J = 18.2 Hz, J = 3.6 Hz, 1H),
1.54 (s, 9H), 1.22 (s, 9H).
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(3-Methoxybenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6h). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a colorless oil. Rf 0.34 (pentane/ethyl
found 455.2156; [α]20 = −46.2 (c 1, CHCl3) for 93% ee.
D
1,2-Di-tert-butyl 3-Methyl (5Z)-5-(2-Methylbenzylidene)-
pyrazolidine-1,2,3-tricarboxylate (6d). The compound was purified
by preparative thin-layer chromatography (pentane/ethyl acetate,
85:15) and was obtained as a colorless oil. Rf 0.27 (pentane/ethyl
1
acetate, 85:15); H NMR (300 MHz, CDCl3) δ 7.19−7.13 (m, 2H),
7.07 (br s, 1H), 6.76−6.70 (m, 1H), 5.98 (s, 1H), 4.86 (dd, J = 8.7 Hz,
J = 4.6 Hz, 1H), 3.78 (s, 3H), 3.73 (s, 3H), 3.25−3.05 (m, 2H), 1.54
(s, 9H), 1.25 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.3, 159.6,
1
acetate, 85:15); H NMR (300 MHz, CDCl3) δ 7.58−7.43 (m, 1H),
I
dx.doi.org/10.1021/jo302320v | J. Org. Chem. XXXX, XXX, XXX−XXX