The Journal of Organic Chemistry
Article
8.1, 8.1 Hz, 1H), 3.76 (dd, J = 8.2, 7.0 Hz, 1H), 4.02 (dd, J = 8.2, 6.5
Hz, 1H), 4.00−4.14 (m, 2H), 4.19 (ddd, J = 7.0, 6.5, 5.7 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 14.0 (CH3), 25.3 (CH3), 26.4 (CH3),
28.0 (CH3), 33.6 (CH2), 45.9 (CH), 60.1 (CH), 60.8 (CH2), 64.4
(CH), 67.4 (CH2), 74.9 (CH), 81.2 (C), 109.4(C), 172.2(C),
172.7(C); HRMS(ESI+) m/z [M + Na]+ calcd for C17H29NO6Na
366.1887, found 366.1896; m/z [M + H]+ calcd for C17H30NO6
344.2068, found 344.2082.
(2S,4R,5R)-4-tert-Butyl 2-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxo-
lan-4-yl]pyrrolidine-2,4-dicarboxylate (exo-2a′-M). According to
the general procedure for copper(I) acetate catalyzed 1,3-dipolar
cycloadditions described above, 898 mg (91% yield) of exo-2a′-M was
obtained after column chromatography (eluent: Et2O): colorless oil;
[α]D = −22.9 (c 1.19, CHCl3); IR (neat) 3363, 1727; H NMR
(CDCl3, 400 MHz) δ 1.33 (s, 3H), 1.41 (s, 9H), 1.43 (s, 3H), 2.11
(ddd, J = 13.0, 9.5, 6.7 Hz, 1H), 2.34 (ddd, J = 13.0, 8.4, 7.2 Hz, 1H),
2.41−2.50 (bs, 1H), 2.62 (ddd, J = 9.5, 7.8, 7.2 Hz, 1H), 3.28 (dd, J =
7.8, 5.2 Hz, 1H), 3.70 (s, 3H), 3.79 (dd, J = 8.3, 6.9 Hz, 1H), 3.84 (dd,
J = 8.4, 6.7 Hz, 1H), 4.02 (dd, J = 8.3, 6.5 Hz, 1H), 4.18 (ddd, J = 6.9,
6.5, 5.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 25.2 (CH3), 26.3
(CH3), 28.0 (CH3), 34.4 (CH2), 46.7 (CH), 52.1 (CH3), 59.3 (CH),
64.4 (CH), 66.7 (CH2), 77.0 (CH), 81.1 (C), 109.3 (C), 172.7(C),
174.0(C); HRMS(ESI+) m/z [M + Na]+ calcd for C16H27NO6Na
352.1731, found 352.1736; m/z [M + H]+ calcd for C16H28NO6
330.1911, found 330.1932.
21
1
(2R,4R,5S)-2-tert-Butyl 4-Ethyl 5-[(S)-2,2-Dimethyl-1,3-dioxolan-
4-yl]pyrrolidine-2,4-dicarboxylate (endo-2b-m). According to the
general procedure for silver acetate catalyzed 1,3-dipolar cyclo-
additions described above, 62 mg (6% yield) of endo-2b-m (dr =
80/20) was obtained after column chromatography (first eluent:
Et2O/hexanes, 9:1, second eluent: Et2O, third eluent: Et2O/acetone,
1
9:1): H NMR (CDCl3, 400 MHz) 1.26 (t, J = 7.1 Hz, 3H), 1.30 (s,
3H), 1.38 (s, 3H), 1.46 (s, 9H), 2.15 (ddd, J = 13.5, 8.0, 6.7 Hz, 1H),
2.55 (ddd, J = 13.4, 8.7, 8.0 Hz, 1H), 3.06 (ddd, J = 8.0, 6.9, 6.7 Hz,
1H), 3.26 (dd, J = 8.9, 6.9 Hz, 1H), 3.71 (dd, J = 8.7, 8.0 Hz, 1H), 3.83
(dd, J = 8.2, 6.1 Hz, 1H), 4.03 (ddd, J = 9.0, 6.1, 6.1 Hz, 1H), 4.09−
4.17 (m, 3H).
(2S,4S,5S)-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4-
(phenylsulfonyl)pyrrolidine-2-carboxylate (endo-2c-M). According
to the general procedure for silver acetate catalyzed 1,3-dipolar
cycloadditions described above, 664 mg (60% yield) of endo-2c-M was
obtained after column chromatography (first eluent: Et2O, second
(2S,4R,5R)-2-tert-Butyl 4-Ethyl 5-[(S)-2,2-Dimethyl-1,3-dioxolan-
4-yl]pyrrolidine-2,4-dicarboxylate (exo-2b-M). According to the
copper(I) acetate catalyzed multicomponent [C + NC + CC]
coupling reaction described above, 792 mg (77% yield) of exo-2b-M
was obtained after column chromatography (eluent: Et2O/hexanes,
eluent: Et2O/acetone, 9:1): white solid, mp = 208 °C dec; [α]21
=
D
+34.3 (c 1.11, CHCl3); IR (Nujol) 3354, 1735; 1H NMR (CDCl3, 400
MHz) δ 1.36 (s, 3H), 1.44 (s, 3H), 2.16 (ddd, J = 14.2, 8.8, 8.1 Hz,
1H), 2.37 (ddd, J = 14.2, 7.2, 6.0 Hz, 1H), 2.86−2.95 (bS, 1H), 3.46
(dd, J = 8.5, 6.3 Hz, 1H), 3.53 (ddd, J = 8.0, 6.3, 6.0 Hz, 1H), 3.74 (s,
3H), 3.80 (dd, J = 8.8, 7.2 Hz, 1H), 3.89 (dd, J = 8.9, 5.6 Hz, 1H), 4.35
(dd, J = 8.9, 6.5 Hz, 1H), 4.82 (ddd, J = 8.5, 6.5, 5.6 Hz, 1H), 7.53−
7.59 (m, 2H), 7.62−7.68 (m, 1H), 7.83−7.87 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 24.8 (CH3), 26.9 (CH3), 32.0 (CH2), 52.3
(CH3), 58.5 (CH), 64.2 (CH), 65.3 (CH), 68.1 (CH2), 75.0 (CH),
109.4 (C), 128.4 (CH), 129.3 (CH), 133.9 (CH), 138.7(C), 172.4
(C); HRMS(ESI+) m/z [M + Na]+ calcd for C17H23NO6SNa
392.1138, found 392.1143; m/z [M + H]+ calcd for C17H24NO6S
370.1319, found 370.1325.
9:1): colorless oil; [α]22 = −28.4 (c 1.07, CHCl3); IR (neat) 3296,
D
1730; 1H NMR (CDCl3, 400 MHz) δ 1.23 (t, J = 7.2 Hz, 3H), 1.33 (s,
3H), 1.42 (s, 9H), 1.43 (s, 3H), 2.06 (ddd, J = 13.1, 9.7, 6.7 Hz, 1H),
2.36 (ddd, J = 13.1, 8.6, 7.4 Hz, 1H), 2.44−2.56 (bs, 1H), 2.70 (ddd, J
= 9.7, 8.0, 7.4 Hz, 1H), 3.27 (dd, J = 8.0, 4.4 Hz, 1H), 3.71 (dd, J = 8.6,
6.7 Hz, 1H), 3.82 (dd, J = 8.3, 6.9 Hz, 1H), 4.02 (dd, J = 8.3, 6.6 Hz,
1H), 4.12 (q, J = 7.1 Hz, 2H), 4.22 (ddd, J = 6.9, 6.6, 4.4 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 14.1 (CH3), 25.2 (CH3), 26.3 (CH3),
27.9 (CH3), 34.8 (CH2), 45.9 (CH), 60.2 (CH), 60.8 (CH2), 64.4
(CH), 66.7 (CH2), 76.3 (CH), 81.3 (C), 109.3 (C), 172.7 (C), 173.6
(C); HRMS(ESI+) m/z [M + Na]+ calcd for C17H29NO6Na 366.1887,
found 366.1888; m/z [M + H]+ calcd for C17H30NO6 344.2068, found
344.2092.
(2S,4R,5S)-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4-
(phenylsulfonyl)pyrrolidine-2-carboxylate (exo-2c-M). According to
the general procedure for copper(I) acetate catalyzed 1,3-dipolar
cycloadditions described above, 897 mg (81% yield) of exo-2c-M was
obtained after column chromatography (eluent: Et2O): white solid,
mp = 117 °C; [α]21D = −19.6 (c 1.06, CHCl3); IR (Nujol) 3292, 1740;
1H NMR (CDCl3, 400 MHz) δ 1.31 (s, 3H), 1.43 (s, 3H), 1.96 (ddd, J
= 13.9, 10.5, 9.0 Hz, 1H), 2.48 (ddd, J = 13.9, 7.5, 4.4 Hz, 1H), 2.53−
2.63 (bs, 1H), 3.58 (ddd, J = 10.5, 6.3, 4.4 Hz, 1H), 3.69 (s, 3H),
3.73−3.79 (m, 1H), 3.83−3.90 (m, 1H), 3.93 (dd, J = 8.4, 6.3 Hz,
1H), 4.02 (dd, J = 8.4, 6.8 Hz, 1H), 4.29 (ddd, J = 6.8, 6.3, 3.0 Hz,
1H), 7.55−7.61 (m, 2H), 7.64−7.70 (m, 1H), 7.89−7.93 (m, 2H); 13C
NMR (CDCl3, 100 MHz) δ 24.8 (CH3), 26.1 (CH3), 33.6 (CH2),
52.3 (CH3), 59.3 (CH), 60.9 (CH), 65.3 (CH), 66.6 (CH2), 75.8
(CH), 109.6 (C), 128.4 (CH), 129.4 (CH), 134.0 (CH), 138.3 (C),
172.8 (C); HRMS(ESI+) m/z [M + Na]+ calcd for C17H23NO6SNa
392.1138, found 392.1157; m/z [M + H]+ calcd for C17H24NO6S
370.1319, found 370.1354.
(2S,4S,5R)-4-tert-Butyl 2-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxo-
lan-4-yl]pyrrolidine-2,4-dicarboxylate (endo-2a′-M). According to
the general procedure for silver acetate catalyzed 1,3-dipolar
cycloadditions described above, 444 mg (45% yield) of endo-2a′-M
was obtained after column chromatography (first eluent: Et2O, second
eluent: Et2O/acetone, 9:1): colorless oil; [α]22 = −28.8 (c 1.08,
D
1
CHCl3); IR (neat) 3307, 1741; H NMR (CDCl3, 400 MHz) δ 1.31
(s, 3H), 1.40 (s, 9H), 1.41 (s, 3H), 2.21−2.30 (m, 2H), 2.52−2.65 (bs,
1H), 2.78 (ddd, J = 6.9, 6.9, 5.3 Hz, 1H), 3.19 (dd, J = 6.9, 6.9 Hz,
1H), 3.72 (s, 3H), 3.72−3.81 (m, 2H), 4.08 (dd, J = 8.3, 6.5 Hz, 1H),
4.18 (ddd, J = 6.5, 6.5, 6.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ
25.2 (CH3), 26.5 (CH3), 27.9 (CH3), 33.5 (CH2), 46.7 (CH), 52.1
(CH3), 59.2 (CH), 64.8 (CH), 67.5 (CH2), 75.5 (CH), 81.3 (C),
109.4 (C), 171.7 (C), 173.5 (C); HRMS(ESI+) m/z [M + Na]+ calcd
for C16H27NO6Na 352.1731, found 352.1740; m/z [M + H]+ calcd for
C16H28NO6 330.1911, found 330.1920.
(2R,4R,5S)-4-tert-Butyl 2-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxo-
lan-4-yl]pyrrolidine-2,4-dicarboxylate (endo-2a′-m). According to
the general procedure for silver acetate catalyzed 1,3-dipolar
cycloadditions described above, 89 mg (9% yield) of endo-2a′-m
was obtained after column chromatography (first eluent: Et2O, second
(2S,4S,5R)-4-Ethyl 2-Methyl 5-[(S)-2,2-Dimethyl-1,3-dioxolan-4-
yl]-2-methylpyrrolidine-2,4-dicarboxylate (endo-2d-M). According
to the general procedure for silver acetate catalyzed 1,3-dipolar
cycloadditions described above, 661 mg (70% yield) of endo-2d-M was
obtained after column chromatography (first eluent: Et2O/hexanes,
4:1, second eluent: Et2O): white solid; mp = 52 °C; [α]22D = −34.5 (c
1.19, CHCl3); IR (Nujol) 3311, 1729; 1H NMR (CDCl3, 400 MHz) δ
1.22 (t, J = 7.2 Hz, 3H), 1.29 (s, 3H), 1.38 (s, 3H), 1.41 (s, 3H), 1.86
(dd, J = 13.6, 7.6 Hz, 1H), 2.65 (dd, J = 13.6, 4.3 Hz, 1H), 2.93 (ddd, J
= 7.6, 6.7, 4.3 Hz, 1H), 3.02−3.18 (bs, 1H), 3.36 (dd, J = 6.7, 6.4 Hz,
1H), 3.73 (dd, J = 8.1, 7.0 Hz, 1H), 3.74 (s, 3H), 4.02 (dd, J = 8.1, 6.4
Hz, 1H), 4.02−4.11 (m, 2H), 4.14 (ddd, J = 7.0, 6.4, 6.4 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 14.0 (CH3), 25.2 (CH3), 26.5 (CH3),
28.1 (CH3), 40.4 (CH2), 46.6 (CH), 52.3 (CH3), 60.8 (CH2), 63.4
(CH), 65.2 (C), 67.4 (CH2), 75.3 (CH), 109.4 (C), 172.6 (C), 176.5
(C); HRMS(ESI+) m/z [M + Na]+ calcd for C15H25NO6Na 338.1574,
eluent: Et2O/acetone, 9:1): colorless oil; [α]22 = −0.5 (c 1.11,
D
CHCl3); IR (Nujol) 3288, 1736, 1712; 1H NMR (CDCl3, 400 MHz) δ
1.25 (s, 3H), 1.33 (s, 3H), 1.37 (s, 9H), 2.08 (ddd, J = 13.4, 7.5, 5.8
Hz, 1H), 2.30 (ddd, J = 13.4, 9.0, 8.0 Hz, 1H), 2.75−3.00 (bs, 1H),
2.92 (ddd, J = 8.0, 6.9, 5.8 Hz, 1H), 3.14 (dd, J = 8.7, 6.9 Hz, 1H), 3.68
(s, 3H), 3.72−3.77 (m, 2H), 3.99−4.10 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ 25.4 (CH3), 26.6 (CH3), 27.8 (CH3), 33.9 (CH2), 46.8
(CH), 52.1 (CH3), 59.6 (CH), 65.2 (CH), 68.4 (CH2), 75.1 (CH),
80.8 (C), 109.1 (C), 172.3 (C), 173.5 (C); HRMS(ESI+) m/z [M +
Na]+ calcd for C16H27NO6Na 352.1731, found 352.1720; m/z [M +
H]+ calcd for C16H28NO6 330.1911, found 330.1890.
F
dx.doi.org/10.1021/jo401967a | J. Org. Chem. XXXX, XXX, XXX−XXX