J.S. Nakhla et al. / Tetrahedron 65 (2009) 6549–6570
6561
5.5.5. (þ)-(S)-N1-Allyl-N2-(4-chlorophenyl)-N1-(4-methoxy-
5.5.8. (ꢁ)-N1-Allyl-N1-benzyl-N2-phenyl-3-(4-
chlorophenyl)propane-1,2-diamine (1k)
phenyl)propane-1,2-diamine (1i)
General procedure 4 was used for the deprotection of (S)-7c
(513 mg, 1.60 mmol). This procedure afforded 318 mg (91%) of (S)-
N1-allyl-N1-(4-methoxyphenyl)propane-1,2-diamine (8c) as a yel-
low oil. This material was used without further purification. 1H
General procedure 4 was used to deprotect (ꢁ)-7e (1.08 g,
2.61 mmol). This procedure afforded 0.81 g (98%) of (ꢁ)-N1-allyl-
N1-benzyl-3-(4-chlorophenyl)propane-1,2-diamine (8e) as a clear
oil. This material was used without further purification. 1H NMR
NMR (500 MHz, CDCl3)
d
6.81 (d, J¼9.0 Hz, 2H), 6.75 (d, J¼9.0 Hz,
(400 MHz, CDCl3) d 7.22–7.19 (m, 4H), 7.16–7.13 (m, 3H), 7.05 (d,
2H), 5.86–5.79 (m, 1H), 5.14–5.11 (m, 2H), 3.90 (dd, J¼1.5, 5.0 Hz,
2H), 3.75 (s, 3H), 3.26–3.21 (m, 1H), 3.20 (d, J¼4.5 Hz, 1H), 3.00–
2.96 (m, 1H), 1.60 (s, br, 2H), 1.09 (d, J¼6.0 Hz, 3H).
J¼8.4 Hz, 2H), 5.82–5.72 (m, 1H), 5.12 (t, J¼9.8 Hz, 2H), 3.66 (d,
J¼13.2 Hz, 1H), 3.43 (d, J¼13.4 Hz, 1H), 3.14 (dd, J¼5.8, 14.0 Hz, 1H),
3.10–3.03 (m, 1H), 2.95 (dd, J¼7.6, 14.4 Hz, 1H), 2.65 (dd, J¼4.8,
13.6 Hz, 1H), 2.39–2.30 (m, 3H).
General procedure 4 was used for the N-arylation of (S)-8c
(64 mg, 0.29 mmol) with 4-bromochlorobenzene (55 mg,
0.29 mmol). This procedure afforded 65 mg (69%) of the title
compound as a yellow oil. The enantiopurity was judged to be 98%
General procedure 4 was used for the N-arylation of (ꢁ)-8e
(0.99 g, 3.14 mmol) with bromobenzene (0.49 g, 3.14 mmol). This
procedure afforded 1.00 g (81%) of the title compound as an orange
ee by chiral HPLC analysis (chiralcel OD column, 1% isopropanol/
oil. 1H NMR (400 MHz, CDCl3)
d 7.33–7.26 (m, 5H), 7.23–7.16 (m,
23
hexanes, 0.2 mL/min, RT¼59.14 min and 63.37 min), [
a
]
D þ21.46ꢀ
4H), 7.06 (d, J¼8.8 Hz, 2H), 6.71 (t, J¼7.2 Hz, 1H), 6.58 (d, J¼8.4 Hz,
2H), 5.91–5.80 (m, 1H), 5.16 (d, J¼15.6 Hz, 2H), 3.85 (s, 1H), 3.70–
3.65 (m, 1H), 3.61 (d, J¼13.2 Hz, 1H), 3.53 (d, J¼13.2 Hz, 1H), 3.15–
3.04 (m, 2H), 2.88–2.79 (m, 2H), 2.54–2.44 (m, 2H); 13C NMR
(c 0.11, CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
7.08 (d, J¼8.8 Hz, 2H),
6.83 (d, J¼9.2 Hz, 2H), 6.75 (d, J¼9.2 Hz, 2H), 6.48 (d, J¼8.8 Hz, 2H),
5.86–5.77 (m, 1H), 5.16–5.11 (m, 2H), 3.95–3.79 (m, 2H), 3.77 (s,
3H), 3.74–3.63 (m, 2H), 3.32–3.22 (m, 2H), 1.22 (d, J¼6.4 Hz, 3H);
(100 MHz, CDCl3)
d 147.7, 139.1, 137.0, 135.3, 132.0, 130.8, 129.3,
13C NMR (100 MHz, CDCl3)
d
152.5, 146.4, 143.6, 134.6, 129.2, 121.9,
129.0, 128.3, 127.1, 118.0, 117.4, 113.3, 58.6, 57.4, 56.7, 52.0, 38.2; IR
(film) 2254, 1493, 912, 742 cmꢃ1. MS (ESI) 391.1928 (391.1941 calcd
for C25H27ClN2, MþHþ).
116.9, 116.2, 114.9, 114.6, 57.8, 55.9, 55.7, 48.0, 19.5; IR (film) 3391,
2929, 1598 cmꢃ1. MS (EI) 330.1490 (330.1500 calcd for C19H23ClN2).
5.5.6. (ꢁ)-N1-Allyl-N1-(4-methoxyphenyl)-N2-phenylpropane-
1,2-diamine (1h)
5.5.9. (ꢃ)-(R)-4-{1-[Allyl(benzyl)amino]-3-(benzyloxy)-propan-2-
ylamino}benzonitrile (1l)
Diamine (ꢁ)-7c was prepared from racemic alanine using a se-
quence of transformations identical to that described above for the
synthesis of (S)-7c. General procedure 4 was then used for the N-
arylation of (ꢁ)-7c (350 mg, 1.59 mmol) with bromobenzene
General procedure 4 was used for the deprotection of (R)-7f
(3.9 g, 9.5 mmol). This procedure afforded 3.1 g (100%) of (S)-N1-
allyl-N1-benzyl-3-benzyloxypropane-1,2-diamine (8f) as a yellow
oil. This material was used without further purification. 1H NMR
(168
m
L, 1.36 mmol). This procedure afforded 308 mg (65%) of the
(400 MHz, CDCl3)
d
7.37–7.21 (m, 10H), 5.86 (dt, J¼6.0, 11.0 Hz, 1H),
title compound as a yellow oil. 1H NMR (500 MHz, CDCl3)
d
7.19 (t,
5.17–5.12 (m, 2H), 4.50 (s, 2H), 3.67 (d, J¼13.5 Hz,1H), 3.51–3.48 (m,
2H), 3.30–3.26 (m, 1H), 3.20–3.12 (m, 2H), 3.00 (dd, J¼5.4, 7.5 Hz,
1H), 2.46–2.38 (m, 2H), 1.60 (s, 2H). MS (ESI) 311.2116 (311.2123
calcd for C20H26N2O, MþHþ).
J¼7.5 Hz, 2H), 6.88–6.85 (m, 2H), 6.82–6.78 (m, 2H), 6.72 (t, J¼7 Hz,
1H), 6.62 (d, J¼8.0 Hz, 2H), 5.90–5.82 (m, 1H), 5.20–5.16 (m, 2H),
3.98–3.93 (m, 1H), 3.89–3.85 (m, 1H), 3.80–3.72 (m, 5H), 3.39–3.35
(m,1H), 3.29–3.25 (m,1H),1.27 (d, J¼6.5 Hz, 3H); 13C NMR (125 MHz,
General procedure 4 was used for the N-arylation of (S)-8f
(900 mg, 2.89 mmol) with 4-bromobenzonitrile (527 mg,
2.89 mmol). This procedure afforded 864 mg (73%) of the title
compound as an orange oil. The enantiopurity was judged to be 98%
CDCl3)
d 152.3, 147.8, 143.7, 134.6, 129.4, 117.5, 116.8, 115.9, 114.8,
113.5, 57.8, 55.9, 55.6, 47.8, 19.7; IR (film) 2929, 2341, 1601 cmꢃ1. MS
(ESI) 297.1964 (297.1967 calcd for C19H24N2O, MþHþ).
ee by chiral HPLC analysis (chiralcel AD column, 0.7% isopropanol/
5.5.7. (–)-(S)-N1-Allyl-N1-benzyl-N2-phenyl-4-methylpentane-
1,2-diamine (1j)
hexanes, 1 mL/min, RT¼24.75 min and 28.10 min), [
a]
D –25.59ꢀ (c
23
0.79, CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
7.35–7.28 (m, 12H), 6.40
General procedure 4 was used for the deprotection of (S)-7d
(1.49 g, 4.30 mmol). This procedure afforded 1.06 g (100%) of (S)-
N1-allyl-N1-benzyl-4-methylpentane-1,2-diamine (8d) as a yellow
oil. This material was used without further purification. 1H NMR
(d, J¼8.5 Hz, 2H), 5.85 (dt, J¼6.5, 10.5 Hz, 1H), 5.22–5.16 (m, 2H),
4.54 (d, J¼6.5 Hz, 1H), 4.49–4.44 (m, 2H), 3.67 (dd, J¼3.0, 9.0 Hz,
1H), 3.65–3.56 (m, 2H), 3.53–3.46 (m, 2H), 3.17–3.10 (m, 2H), 2.74
(dd, J¼7.5, 13.5 Hz, 1H), 2.60 (dd, J¼6.5, 13.5 Hz, 1H); 13C NMR
(500 MHz, CDCl3)
d
7.31–7.28 (m, 4H), 7.25–7.22 (m, 1H), 5.91–5.83
(100 MHz, CDCl3) d 151.0, 139.5, 138.0, 135.6, 133.8, 129.1, 128.6,
(m, 1H), 5.18–5.13 (m, 2H), 3.77 (d, J¼13.5 Hz, 1H), 3.40 (d,
J¼13.5 Hz, 1H), 3.23–3.19 (m, 1H), 2.96–2.91 (m, 2H), 2.34–2.31 (m,
1H), 2.27–2.23 (m, 1H), 1.75–1.68 (m, 1H), 1.53 (s, 2H), 1.15–1.06 (m,
2H), 0.89 (d, J¼6.5 Hz, 3H), 0.86 (d, J¼7.0 Hz, 3H).
128.5, 127.99, 127.90, 127.4, 120.7, 118.1, 112.7, 98.6, 73.5, 69.9, 59.3,
58.3, 54.3, 51.4; IR (film) 3365, 2211, 1606 cmꢃ1. MS (ESI) 412.2383
(412.2389 calcd for C27H29N3O, MþHþ).
Generalprocedure4 wasused fortheN-arylationof(S)-8d(1.06 g,
5.5.10. (ꢁ)-4-{2-[Benzyl(but-3-en-2-yl)amino]-ethylamino}-
benzonitrile (9)
4.30 mmol) with bromobenzene (453 ml, 4.30 mmol). Thisprocedure
afforded 1.09 g (79%) of the title compound as an yellow oil. The
enantiopurity was judged to be 99% ee by chiral HPLC analysis
General procedure 4 was used for the deprotection of (ꢁ)-7h
(1.35 g, 4.44 mmol). This procedure afforded 842 mg (93%) of
(chiralcel OJ-H column, 5% isopropanol/hexanes, 1 mL/min,
(ꢁ)-N1-benzyl-N1-(but-3-en-2-yl)ethane-1,2-diamine
(8h)
as
23
RT¼6.16 min and 8.90 min), [
a]
–44.10ꢀ (c 3.2, CH2Cl2). 1H NMR
a yellow oil. This material was used without further purification. 1H
D
(500 MHz, CDCl3)
d
7.32–7.27 (m, 4H), 7.25–7.22 (m, 1H), 7.13 (t,
NMR (300 MHz, CDCl3) d 7.39–7.19 (m, 5H), 5.94–5.82 (m,1H), 5.16–
J¼7.5 Hz, 2H), 6.65 (t, J¼7.0 Hz,1H), 6.54 (d, J¼8.0 Hz, 2H), 5.90–5.82
(m, 1H), 5.18–5.13 (m, 2H), 3.72 (d, J¼6.0 Hz, 1H), 3.63 (d, J¼13.5 Hz,
1H), 3.56 (d, J¼13.5 Hz, 1H), 3.48–3.41 (m, 1H), 3.14–3.06 (m, 2H),
2.55–2.45 (m, 2H),1.77–1.69 (m,1H),1.50–1.45 (m,1H),1.38–1.32 (m,
1H), 0.96 (d, J¼7.0 Hz, 3H), 0.88 (d, J¼6.5 Hz, 3H); 13C NMR (100 MHz,
5.03 (m, 2H), 3.65–3.53 (m, 2H), 3.34–3.25 (m, 1H), 2.72–2.61 (m,
2H), 2.60–2.44 (m, 2H), 1.21 (s, br, 2H), 1.14 (d, J¼6.9 Hz, 3H).
General procedure 4 was used for the N-arylation of (ꢁ)-8h
(681 mg, 3.33 mmol) with 4-bromobenzonitrile (606 mg,
3.33 mmol). This procedure afforded 905 mg (89%) of the title
CDCl3)
d
148.6, 139.8, 135.9, 129.4, 129.2, 128.4, 127.2, 117.8, 117.0,
compound as an orange oil. 1H NMR (300 MHz, CDCl3)
d 7.43–7.21
113.2, 59.2, 58.3, 57.8, 49.8, 43.6, 25.1, 23.3, 23.1; IR (film) 3400, 2954,
(m, 7H), 6.41 (d, J¼9.0 Hz, 2H), 5.94–5.83 (m,1H), 5.21–5.08 (m, 2H),
1601 cmꢃ1. MS (ESI) 323.2471 (323.2487 calcd for C22H30N2, MþHþ).
4.65 (s,1H), 3.66–3.52 (m, 2H), 3.39–3.30 (m,1H), 3.08–2.97 (m, 2H),