(400 MHz, CDCl3) 1.47 (9H, s, OC(CH3)3), 3.36 (1H, dd, J
11.5, 10.1, C(2)HA), 3.59 (1H, dd, J 11.5, 8.4, C(2)HB), 3.86
(1H, m, C(3)H), 5.61 (1H, dd, J 5.9, 2.8, C(4)H), 6.25 (1H,
dd, J 5.9, 2.5, C(5)H); dC (100 MHz, CDCl3) 28.0 (OC(CH3)3),
33.1 (C(2)), 53.9 (C(3)), 81.4 (OC(CH3)3), 120.7 (C(4)), 128.7
1067s, 975s, 963s, 848s, 831s; dH (400 MHz, CDCl3) 1.55 and
1.60 (2 × 9H, 2 × s, (2 × OC(CH3)3), 6.55 (1H, dd, J 3.3, 1.6,
C(4)H), 7.17 (1H, dd, J 3.3, 2.2, C(5)H), 7.74 (1H, dd, J 2.2, 1.6,
C(2)H); dC (100 MHz, CDCl3) 27.9 and 28.2 (2 × OC(CH3)3),
80.3 and 84.8 (2 × OC(CH3)3), 112.0 (C(4)), 120.3 (C(3)), 121.2
t
+
(C(5)), 171.2 (CO2 Bu); m/z (GCMS, CI+) 204 (MNH4 , 15),
187 (MH+, 100%); HRMS, found 187.0789; C9H15O2S (MH+)
requires 187.0793.
t
t
(C(5)), 124.3 (C(2)), 148.2 (NCO2 Bu), 163.5 (C(3)CO2 Bu);
m/z (GCMS, CI+) 268 (MH+, 15), 212 (MH+ − C4H8, 100%);
HRMS, found 268.1541; C14H22NO4 (MH+) requires 268.1549.
Preparation of tert-butyl N-tert-butyloxycarbonyl-(3RS,4RS)-
4-(N,N-dibenzylamino)tetrahydropyrrole-3-carboxylate 33
Preparation of tert-butyl (3R,4R,aS)-4-(N-benzyl-N-a-methyl-
benzylamino)tetrahydrofuran-3-carboxylate 37, tert-butyl
(3S,4R,aS)-4-(N-benzyl-N-a-methylbenzylamino)tetrahydro-
furan-3-carboxylate 36, di-tert-butyl (3S,4R,3S,4S,aS)-4-
(N-benzyl-N-a-methylbenzylamino)tetrahydro-[3,3]-bifuranyl-
3,4-dicarboxylate 38 and tert-butyl (3S,4R,3S,4R,aS,aS)-
4-(N-benzyl-N-a-methylbenzylamino)-3-[4-(N-benzyl-N-
a-methylbenzylamino)-2-oxotetrahydrofuran-3-ylmethyl]-
tetrahydrofuran-3-carboxylate 39
Following general procedure 2, n-BuLi (1.6 M, 0.74 ml,
1.19 mmol), dibenzylamine (234 mg, 1.19 mmol) in THF
(8 ml) and 21 (200 mg, 0.74 mmol) in THF (2 ml) gave,
after quenching with NH4Cl (aq, sat, 10 ml), (3RS,4RS)-33
in >98% d.e. Purification by flash chromatography on silica gel
(5→10→20% EtOAc/n-pentane) gave (3RS,4RS)-33 (141 mg,
41%) as a pale yellow crystalline solid; m.p. 61–63 °C; mmax
(CHCl3) 3009m, 2980m, 2933m, 1722s, 1687s, 1411s, 1368s,
1145s, 778s, 741s; dH (400 MHz, CDCl3, rotameric at 298 K)
1.44/1.47 and 1.53/1.56 (18H, 4 × s, 2 × OC(CH3)3), 3.24 (1H,
m, C(3)H), 3.37 (1H, dd, J 10.1, 6.7, C(5)HA), 3.41–3.52 (1.5H,
m, C(2)HA and C(4)H), 3.58 and 3.75 (2 × 1H, AB system,
JAB 13.6, N(CH2Ph)2) overlays 3.58 (0.5H, m, C(4)H), 3.65
and 3.74 (2 × 1H, AB system, JAB 13.9, N(CH2Ph)2) overlays
3.72–3.79 (2H, m, C(2)HB and C(5)HB), 7.22–7.34 (10H, m,
Ph); dH (400 MHz, d8-toluene, 363 K) 1.45 and 1.46 (2 × 9H,
2 × s, 2 × OC(CH3)3), 2.90 (1H, m, C(3)H), 3.28 (1H, dd, J 11.0,
7.5, C(2)HA), 3.32 (2H, br, C(5)H2), 3.64 (4H, br, N(CH2Ph)2),
3.81–3.86 (2H, br, C(2)HB and C(4)H), 7.01–7.27 (10H, m,
Ph); dC (100 MHz, CDCl3, rotameric at 298 K) 28.2/28.3 and
28.4/28.5 (2 × OC(CH3)3), 46.5 and 47.1 (C(5)), 47.5 (C(3)),
47.9 and 48.2 (C(2)), 55.0 and 55.4 (N(CH2Ph)2), 61.1 and 62.9
(C(4)), 79.3/79.5 and 81.0/81.1 (2 × OC(CH3)3), 127.0, 127.1,
127.9, 128.1, 128.8 and 129.0 (o-, m-, p-Ph), 138.5/138.6 (ipso-
Following general procedure 2, n-BuLi (2.5 M, 3.76 ml,
9.40 mmol), (S)-N-benzyl-N-a-methylbenzylamine (1.99 g,
9.40 mmol) in THF (50 ml) and 18 (1.00 g, 5.88 mmol) in THF
(10 ml) gave, after quenching with NH4Cl (aq, sat, 20 ml), the
adducts 37:36:38:39 in a 4:47:2:47 ratio. Purification by
flash chromatography on silica gel (2→4→6→8→10→20→40%
EtOAc:n-pentane) gave the products: (3R,4R,aS)-37 as a white
crystalline solid (67 mg, 3%); m.p. 68–70 °C; [a]D24 +67.7 (c1.5,
CHCl3); mmax (KBr) 3011m, 2980s, 2935m, 2872m, 1718s, 1369s,
1149s; dH (400 MHz, CDCl3) 1.30 (3H, d, J 6.9, C(a)Me), 1.39
(9H, s, OC(CH3)3), 2.94 (1H, app q, J 8.0, C(3)H), 3.65 (1H, app
t, J 8.5, C(2)HA), 3.77 (1H, m, C(5)HA), 3.85–3.91 (2H, m, C(4)H
and C(5)HB) overlays 3.85 (2H, app s, NCH2Ph), 4.06 (1H, app
t, J 8.5, C(2)HB), 4.15 (1H, q, J 6.8, C(a)H), 7.21–7.47 (10H,
m, Ph); dC (100 MHz, CDCl3) 16.3 (C(a)Me), 28.0 (OC(CH3)3),
50.1 (C(3) and NCH2Ph), 58.0 (C(a)H), 63.3 (C(4)), 70.7 (C(2)
and C(5)), 80.7 (OC(CH3)3), 126.8 (p-Ph), 127.7, 128.1, 128.3
and 128.3 (o, m-Ph), 141.2 and 143.7 (ipso-Ph), 172.6 (CO2tBu);
m/z (APCI+) 382 (MH+, 30), 381 (M+, 50), 326 (MH+ − C4H8,
15), 222 (30), 221 (100%); HRMS, found 382.2381; C24H32NO3
(MH+) requires 382.2382; (3S,4R,aS)-36 as a white crystalline
solid (694 mg, 31%); m.p. 84–86 °C; [a]D24 −48.0 (c 1.5, CHCl3);
elemental analysis, found C, 75.4; H, 8.1; N, 8.2%; C24H31NO3
requires C, 75.6; H, 8.2; N, 3.8%; mmax (KBr) 3029w, 3010m,
2980s, 2936w, 1721s, 1369s, 1153s; dH (400 MHz, CDCl3) 1.40
(3H, d, J 6.9, C(a)Me), 1.54 (9H, s, OC(CH3)3), 3.16 (1H, td, J
7.7, 4.8, C(3)H), 3.55–3.64 (2H, m, C(4)H and C(5)HA), 3.61 and
4.03 (2 × 1H, AB system, JAB 14.8, NCH2Ph), 3.83 (1H, app t, J
7.8, C(5)HB), 3.92 (1H, dd, J 8.8, 7.8, C(2)HA), 4.11 (1H, dd, J
8.8, 4.8, C(2)HB), 4.23 (1H, q, J 6.9, C(a)H), 7.23–7.40 (10H, m,
Ph); dC (100 MHz, CDCl3) 16.3 (C(a)Me), 28.2 (OC(CH3)3), 49.3
(C(3)), 51.9 (NCH2Ph), 57.7 (C(a)H), 63.4 (C(4)), 69.7 (C(5)),
70.1 (C(2)), 81.0 (OC(CH3)3), 126.7 and 127.0 (p-Ph), 128.0,
128.1 and 128.2 (o-, m-Ph), 141.1 and 141.8 (ipso-Ph), 171.7
(CO2tBu); m/z (APCI+) 382 (MH+, 70), 381 (M+, 60), 326 (MH+–
C4H8, 65), 325 (M+–C4H8, 100), 222 (45), 221 (100%); HRMS,
found 382.2372; C24H32NO3 (MH+) requires 382.2382; 38 as a
white crystalline solid (32 mg, 2%); m.p. 82–84 °C; [a]D24 −38.0
(c 0.25, CHCl3); mmax (KBr) 3011m, 2980s, 2936m, 2889m, 1721s,
1369s, 1153s; dH (400 MHz, CDCl3) 1.15 (3H, d, J 6.9, C(a)Me),
1.42 and 1.46 (2 × 9H, 2 × s, 2 × OC(CH3)3), 2.81–2.90 (2H, m,
C(3)H and C(4)H), 3.51 (1H, dd, J 7.4, 5.3, C(4)H), 3.60 (2H,
app d, J 7.0, C(5)H2), 3.66 (1H, dd, J 8.8, 6.3, C(2)HA), 3.80
(1H, d, J 9.8, C(2)HA) overlays 3.82 (1H, m, C(2)HB), 3.87 and
4.00 (2 × 1H, AB system, JAB 14.5, NCH2Ph), 3.95 (1H, dd, J 9.8,
7.6, C(5)HA), 4.07–4.12 (2H, m, C(a)H and C(5)HB), 4.27 (1H,
d, J 9.8, C(2)HB), 7.46–7.51 (10H, m, Ph); dC (100 MHz, CDCl3)
15.0 (C(a)Me), 28.0 and 28.2 (2 × OC(CH3)3), 47.6 (C(3)), 49.6
(C(4)), 51.4 (NCH2Ph), 57.5 (C(a)H), 60.3 (C(3)) 64.8 (C(4)),
69.1 (C(5)), 71.1 (C(5)), 71.8 (C(2)), 73.9 (C(2)), 81.0 and 81.9
(2 × OC(CH3)3), 126.7 and 126.9 (p-Ph), 128.0, 128.2, 128.4 and
128.5 (o-, m-Ph), 140.4 and 143.9 (ipso-Ph), 170.4 and 172.8
t
t
Ph), 154.2/154.4 (NCO2 Bu), 170.7/171.2 (C(3)CO2 Bu); dC
(100 MHz, d8-toluene, 363 K) 28.3 and 28.6 (2 × OC(CH3)3),
48.2 (C(4), N(CH2Ph)2, C(5) and C(2)), 56.0 (C(3)), 78.7 and
80.5 (2 × OC(CH3)3), 127.1, 127.7, 127.8, 128.0, 128.1, 128.3,
128.5, 128.9, 129.0 and 129.4 (o-, m-, p-Ph), 137.4 and 139.4
t
t
(ipso-Ph), 154.1 (NCO2 Bu), 178.0 (C(3)CO2 Bu); m/z (APCI+)
467 (MH+, 100), 466 (M+, 95), 411 (MH+ − C4H8, 40), 410
(M+ − C4H8, 75%); HRMS, found 467.2908; C28H39N2O4
(MH+) requires 467.2910. Also isolated was the deconjugated
adduct tert-butyl N-tert-butyloxycarbonyl-2,3-dihydropyrrole-
3-carboxylate 34 (44 mg, 22%) as a white solid; m.p. 58–60 °C;
mmax (KBr) 3026w, 3009m, 2982s, 2933m, 1726s, 1697s, 1413s,
1369s, 1139s, 888m; dH (400 MHz, d8-toluene, rotameric at
298 K) 1.32/1.33 and 1.39/1.41 (18H, 4 × s, 2 × OC(CH3)3),
3.33–3.37 (0.5H, m, C(3)H), 3.40–3.44 (0.5H, m, C(3)H)
overlays 3.47 (0.5H, t, J 11.3, C(2)HA), 3.66 (0.5H, t, J 11.6,
C(2)HA), 4.21 (0.5H, dd, J 9.4, 4.7, C(2)HB), 4.31 (0.5H, dd, J
11.7, 6.6, C(2)HB), 4.86 (1H, dd, J 4.2, 2.6, C(4)H), 6.47 (0.5H,
m, C(5)H), 6.77 (0.5H, m, C(5)H); dH (500 MHz, d8-toluene,
363 K) 1.33 and 1.40 (2 × 9H, 2 × s, 2 × OC(CH3)3), 3.42 (1H,
m, C(3)H), 3.63 (1H, t, J 11.5, C(2)HA), 4.16 (1H, dd, J 11.5,
6.5, C(2)HB), 4.86 (1H, dd, J 4.0, 3.0, C(4)H), 6.59 (1H, br,
C(5)H); dC (100 MHz, d8-toluene, rotameric at 298 K) 28.1/28.3
and 28.4/28.6 (2 × OC(CH3)3), 47.7 (C(2)), 48.3/49.5 (C(3)),
80.2 and 80.8 (2 × OC(CH3)3), 105.6/105.7 (C(4)), 131.8/12.1
t
t
(C(5)), 151.8/152.8 (NCO2 Bu), 171.2/171.3 (C(3)CO2 Bu); dC
(125 MHz, d8-toluene, 363 K) 28.0 and 28.3 (2 × OC(CH3)3),
47.8 (C(2)), 48.7 (C(3)), 79.8 and 80.4 (2 × OC(CH3)3), 105.3
t
t
(C(4)), 131.8 (C(5)), 151.2 (NCO2 Bu), 170.8 (C(3)CO2 Bu);
m/z (GCMS, CI+) 270 (MH+, 10%), 214 (MH+ − C4H8, 20), 170
(100%); HRMS, found 270.1703; C14H24NO4 (MH+) requires
270.1705; and the aromatised adduct tert-butyl N-Boc pyrrole-
1,3-dicarboxylate 35 (22 mg, 11%) as a white crystalline solid;
m.p. 70–72 °C; mmax (KBr) 3028m, 3009m, 2983s, 2935m, 1749s,
1703s, 1561s, 1496s, 1389s, 1369s, 1289s, 1254s, 1147s, 1100s,
2 7 7 2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 7 6 3 – 2 7 7 6