1.45 ml, 2.32 mmol), (S)-10 (500 mg, 2.36 mmol) in anhydrous
THF (5 ml) and 19 (261 mg, 0.79 mmol) in THF (5 ml) gave,
after purification by column chromatography on silica gel
(hexane–Et2O 15 : 1) 22 (518 mg, 87%) as a white foam; [α]2D4
Preparation of (1R,2S,3S)-tert-butyl 1-(N-benzyl-N-ꢁ-methyl-
benzylamino)-3-[(tert-butoxycarbonyl)methyl]indane-2-carb-
oxylate 27
Following representative procedure 1, n-butyllithium (2.5 M,
0.36 ml, 0.90 mmol), (S)-10 (192 mg, 0.91 mmol) in anhydrous
THF (5 ml) and 17 (100 mg, 0.30 mmol) in THF (5 ml) gave,
after purification by column chromatography on silica gel
(hexane–Et2O 10 : 1), 27 (134 mg, 82%) as a white foam; [α]2D3
ϩ81.4 (c 1.0, CHCl3), lit.17 [α]2D0 ϩ77.4 (c 0.94, CHCl3); δH (400
MHz, CDCl3) 1.28 (3H, d, J 6.9, C(α)Me), 1.50, 1.53 (2 × 9H, s,
CO2C(Me)3), 2.58–2.70 (2H, m, C(1Ј)H2), 3.01 (1H, app t, J 7.5,
C(2)H), 3.67 (1H, app q, J 7.2, C(3)H), 3.72 (1H, d, J 15.1,
NCHA), 3.82 (1H, d, J 15.1, NCHB), 4.18 (1H, q, J 6.9, C(α)H),
4.94 (1H, d, J 7.2, C(1)H), 7.15–7.39 (10H, m, Ph), 7.43–7.51
(4H, m, Ph).
Ϫ11.0 (c 1.0, CHCl3); νmax/cmϪ1 (KBr) 2975 (C–H), 1729 (C᎐O),
᎐
1141 (C–H); δH (400 MHz, CDCl3) 1.23 (18H, s, CO2C(Me)3),
1.31 (6H, d, J 6.9, C(α)Me), 2.56 (2H, dd, J2A,2B 14.6, J2A,3 9.7,
C(2)HA), 2.64 (2H, dd, J2B,2A 14.6, J2B,3 5.1, C(2)HB), 3.76 (4H,
app s, NCH2), 4.06 (2H, q, J 6.9, C(α)H), 4.51 (2H, dd, J3,2A 9.7,
J3,2B 5.1, C(3)H), 7.20–7.38 (19H, m, Ph), 7.48–7.50 (4H, m,
Ph), 7.70 (1H, s, Ph(2)H); δC (100 MHz, CDCl3) 16.3, 27.8,
38.8, 50.9, 57.2, 59.2, 80.1, 126.5, 126.8, 127.3, 127.8, 128.1,
140.5, 141.6, 144.2, 171.1; m/z (APCIϩ) 754 (MHϩ, 100%), 776
(MNaϩ, 10%); HRMS (CIϩ) C50H61N2O4 requires 753.4631;
found 753.4609.
Preparation of (3R,3ЈR)-di-tert-butyl benzene-1,3-bis(3-amino-
propanoate) 23
Preparation of (E )-tert-butyl 3-(2-iodophenyl)prop-2-enoate 29
n-Butyllithium (1.6 M, 11.9 ml, 19.0 mmol) was added to a
solution of tert-butyl diethylphosphonoacetate (5.0 g, 19.8
mmol) in THF (20 ml) at Ϫ78 ЊC under nitrogen. After thirty
minutes, this solution was added dropwise via a cannula to a
stirred solution of 2-iodobenzaldehyde (4.0 g, 17.2 mmol) in
THF (10 ml) at Ϫ78 ЊC and warmed to RT after stirring for
thirty minutes at Ϫ78 ЊC. After two hours, the solution was
recooled to Ϫ78 ЊC and quenched by the addition of saturated
aqueous ammonium chloride (5 ml). After warming to RT, the
solution was partitioned between brine (20 ml) and DCM
(3 × 100 ml), dried and concentrated in vacuo. Purification by
column chromatography on silica gel (hexane–Et2O 60 : 1) gave
29 (5.3 g, 93%) as a yellow oil; νmax/cmϪ1 (film) 2977 (C–H),
Pd(OH)2 on C (150 mg) was added to a solution of 22 (150 mg,
0.20 mmol) in a mixture of degassed MeOH–acetic acid (5 : 1, 5
ml) and the resultant black suspension stirred under a hydrogen
atmosphere (5 atm) for 16 hours. The reaction mixture was
filtered through a plug of Celite (eluent MeOH) and concen-
trated in vacuo. The residue was purified by column chrom-
atography on silica gel (CHCl3–MeOH 6 : 1) to give 23 (65 mg,
90%) as a colourless oil; [α]2D4 ϩ10.8 (c 1.0, CHCl3); νmax/cmϪ1
(KBr) 3438 (NH), 2975 (C–H), 1736 (C᎐O), 1159 (C–O);
᎐
δH (400 MHz, CD3CN) 1.41 (18H, s, CO2C(Me)3), 2.75 (2H, dd,
J2A,2B 16.2, J2A,3 6.6, C(2)HA), 2.85 (2H, dd, J2B,2A 16.2, J2B,3 7.5,
C(2)HB), 4.46 (2H, br s, C(3)H), 7.38–7.46 (4H, m, Ph); δC (50
MHz, CD3CN) 28.3, 43.5, 53.5, 82.5, 126.6, 127.9, 130.4, 171.7;
m/z (APCIϩ) 365 (MHϩ, 100%); HRMS (CIϩ) C20H33N2O4
requires 365.2440, found 365.2441.
1708 (C᎐O), 1637 (C᎐C); δ (400 MHz, CDCl3) 1.55 (9H, s,
᎐
᎐
H
OC(Me)3), 6.25 (1H, d, J 15.7, C(2)H), 7.04 (1H, t, J 7.6,
Ph(4)H C6H4I), 7.34 (1H, t, J 7.6, Ph(5)H C6H4I), 7.56 (1H, d,
J 7.6, Ph(6)H C6H4I), 7.83 (1H, d, J 15.7, C(3)H), 7.90 (1H, d,
J 7.6, Ph(3)H C6H4I); δC (100 MHz, CDCl3) 28.6, 81.2, 101.7,
123.4, 127.7, 128.9, 130.7, 135.9, 140.4, 147.1, 166.0; m/z
(APCIϩ) 331 (MHϩ, 10%), 348 (MNH4ϩ, 30%); HRMS (CIϩ)
C13H16IO2 requires 331.0195, found 331.0194.
Preparation of (3R,ꢁS,3ЈR,ꢁЈS)-di-tert-butyl benzene-1,4-bis[3-
(N-benzyl-N-ꢁ-methylbenzylamino)propanoate] 24
Following representative procedure 1, n-butyllithium (2.5 M,
0.72 ml, 1.81 mmol, 2.95 equiv.), (S)-10 (388 mg, 1.78 mmol,
3.0 equiv.) in anhydrous THF (5 ml) and 21 (200 mg, 0.61
mmol, 1 equiv.) in THF (5 ml) gave, after purification by
column chromatography on silica gel (hexane–Et2O 12 : 1), 24
(367 mg, 80%) as a hygroscopic white foam; [α]2D4 ϩ11.8 (c 1.0,
Preparation of (3R,ꢁS)-tert-butyl 3-(N-benzyl-N-ꢁ-methylbenz-
ylamino)-3-(2-iodophenyl)propanoate 30
Following representative procedure 1, n-butyllithium (2.5 M,
5.6 ml, 14.1 mmol), (S)-10 (3.1 g, 14.5 mmol) in anhydrous
THF (20 ml) and 29 (3.0 g, 9.1 mmol) in THF (20 ml) gave,
after purification by column chromatography on silica gel
(hexane–Et2O 12 : 1) and recrystallisation (hexane–Et2O), 30
(4.3 g, 88%) as white needles; mp 88 ЊC; C28H32INO2 requires C,
62.1; H, 6.0; N, 2.6%; found C, 62.1; H, 6.0; N, 2.5%; [α]2D4 Ϫ24.5
CHCl3); νmax/cmϪ1 (film) 2976, 2920 (C–H), 1726 (C᎐O), 1149
᎐
(C–O); δH (400 MHz, CDCl3) 1.17 (18H, s, CO2C(Me)3), 1.21
(6H, d, J 6.8, C(α)Me), 2.49–2.57 (4H, m, C(2)H2), 3.66 (4H,
app s, NCH2), 3.97 (2H, q, J 6.8, C(α)H), 4.39 (2H, dd, J3,2A 9.0,
J3,2B 6.1, C(3)H), 7.14–7.42 (24H, m, Ph); δC (100 MHz, CDCl3)
16.6, 27.8, 38.2, 50.7, 57.0, 59.2, 80.1, 126.5, 126.8, 127.8, 128.1,
140.5, 141.6, 144.2, 171.1; m/z (APCIϩ) 754 (MHϩ, 100%), 776
(MNaϩ, 10%); HRMS (CIϩ) C50H61N2O4 requires 753.4631;
found 753.4608.
(c 1.0, CHCl3); νmax/cmϪ1 (KBr) 2972 (C–H), 1717 (C᎐O), 1148
᎐
(C-O); δH (400 MHz, CDCl3) 1.18 (9H, s, CO2C(Me)3), 1.51
(3H, d, J 6.7, C(α)Me), 2.17 (1H, dd, J2A,2B 13.7, J2A,3 9.7,
C(2)HA), 2.60 (1H, dd, J2B,2A 13.7, J2B,3 5.6, C(2)HB), 3.72 (1H,
d, J 15.5, NCHA), 3.82 (1H, d, J 15.5, NCHB), 3.92 (1H, q,
J 6.7, C(α)H), 4.75 (1H, dd, J3,2A 9.7, J3,2B 5.5, C(3)H), 6.93–
6.97 (1H, m, Ph(4)H C6H4I), 7.11–7.44 (11H, m, Ph and Ph(6)H
C6H4I), 7.66–7.68 (1H, dd, J 7.9, J 1.1, Ph(5)H C6H4I), 7.81–
7.83 (1H, dd, J 7.9, J 1.1, Ph(3)H C6H4I); δC (100 MHz, CDCl3)
12.5, 27.7, 42.9, 50.5, 56.7, 66.3, 80.3, 101.7, 126.3, 126.7, 127.5,
127.8, 128.0, 128.3, 129.0, 129.8, 139.6, 142.6, 143.7, 145.2,
170.1; m/z (APCIϩ) 542.2 (MHϩ, 100%).
Preparation of (3R,3ЈR)-di-tert-butyl benzene-1,4-bis(3-amino-
propanoate) 25
Pd(OH)2 on C (Pearlman’s catalyst, 90 mg) was added to a
solution of 24 (180 mg, 0.24 mmol) in degassed MeOH and the
resultant black suspension stirred under a hydrogen atmosphere
(5 atm) for 16 hours. The reaction mixture was filtered through
a plug of Celite (eluent MeOH) and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(CHCl3–MeOH 10 : 1) to give 25 (71 mg, 81%) as a colourless
oil; [α]2D4 Ϫ9.1 (c 1.0, CHCl3); νmax/cmϪ1 (film) 2977, 2920 (C–H),
Preparation of (3R,ꢁS,E )-tert-butyl 3-[2-(3-tert-butoxy-3-
oxoprop-1-enyl)phenyl]-3-(N-benzyl-N-ꢁ-methylbenzylamino)-
propanoate 31
1726 (C᎐O), 1149 (C–O); δ (400 MHz, CDCl3) 1.42 (18H, s,
᎐
H
CO2C(Me)3), 2.00 (4H, br s, NH), 2.55–2.58 (4H, m, C(2)H2),
4.35–4.38 (2H, m, C(3)H), 7.32 (4H, app s, Ph); δC (100 MHz,
CDCl3) 28.0, 45.0, 52.3, 80.8, 126.5, 171.3; m/z (APCIϩ) 365.2
(MHϩ, 100%), 387.1 (MNaϩ, 80%); HRMS (CIϩ) C20H33N2O4
requires 365.2440, found 365.2441.
A mixture of 30 (1.75 g, 3.23 mmol), tert-butyl acrylate (0.98
ml, 6.47 mmol), PPh3 (168 mg, 0.64 mmol) and Pd(OAc)2 (70
mg, 0.32 mmol) in NEt3 (35 ml) was refluxed overnight. The
resultant mixture was filtered through Celite (eluent Et2O),
2936
J. Chem. Soc., Perkin Trans. 1, 2001, 2931–2938