E.T. Choi et al. / Tetrahedron 64 (2008) 1515e1522
1519
were added an amine (1.2 equiv), TBAI (1.0 equiv), and DIEA
(1.2 equiv). The resulting reaction mixture was stirred at room
temperature for 24 h. The solvent in mixture was evaporated
and the crude product was purified by column chromatography
on silica gel. The substituted products were obtained in 85%
yield with 99:1 dr (with benzhydrylamine), 43% yield with
90:10 dr (with (R)-a-methylbenzylamine), in 89% yield with
81:19 dr (with benzylamine), in 40% yield with 81:19 dr
(with (S )-a-methylbenzylamine), in 79% yield with 91:9 dr
(with 9-fluorenamine), in 80% yield with 85:15 dr (with 1-
naphthylamine), and in 93% yield with 99:1 dr (with dibenzyl-
amine), respectively.6 To a solution of product in THF (0.5 M)
was added BH3eTHF (1.0 M, 5.0 equiv), and the mixture was
refluxed for 12 h. The reaction was quenched by adding
MeOH (0.5 mL) under ice-water cooling, and the solvents
were evaporated. Aqueous 5% HCl (2 mL) was added to the
residue, and the mixture was refluxed for 1 h. The reaction
mixture was basified with K2CO3, saturated with NaCl, and
extracted with CHCl3 (5 mLꢁ3). The combined organic ex-
tracts were dried with anhydrous MgSO4, filtered, and concen-
trated in vacuo. Chromatographic separation on silica gel
afforded the ligands with >99:1 dr.
(dd, J¼12.5 and 3.5 Hz, 1H), 2.23 (m, 1H), 1.89e1.58 (m,
4H); 13C NMR (CDCl3, 100 MHz) 142.7, 140.9, 128.9,
128.8, 128.5, 127.9, 127.8, 127.3, 65.7, 64.3, 63.2, 61.2,
54.8, 51.7, 27.7, 24.2. HRMS calcd for C20H27N2O
(Mþþ1): 311.2123, found: 311.2149.
4.1.4. N-[(R)-N-((S )-1-Phenylethyl)-2-amino-2-
phenylethyl]-(S )-prolinol (7)
A pale yellow oil was obtained in 49% yield. H NMR
1
(CDCl3, 400 MHz) 7.33e7.17 (m, 10H), 3.67 (dd, J¼11.1
and 3.7 Hz, 1H), 3.50 (m, 2H), 3.41 (dd, J¼11.2 and 3.1 Hz,
1H), 3.30 (br, 1H), 2.90 (t, 1H), 2.74 (m, 1H), 2.60 (m, 1H),
2.30 (dd, J¼12.5 and 3.1 Hz, 1H), 2.05 (m, 1H), 1.90e1.60
(m, 4H), 1.33 (d, J¼6.8 Hz, 3H); 13C NMR (CDCl3,
100 MHz) 145.8, 143.0, 128.9, 128.8, 127.9, 127.7, 127.3,
127.0, 65.5, 64.2, 62.9, 59.1, 55.2, 54.6, 27.8, 25.0, 24.2.
HRMS calcd for C21H29N2O (Mþþ1): 325.2280, found:
325.2251. [a]2D0 ꢂ125.5 (c 0.1, CHCl3).
4.1.5. N-[(R)-N-(9H-Fluoren-9-yl)-2-amino-2-phenylethyl]-
(S )-prolinol (8)
A colorless oil was obtained in 66% yield. 1H NMR
(CDCl3, 400 MHz) 7.63e7.13 (m, 13H), 4.73 (s, 1H), 4.24
(dd, J¼10.8 and 3.6 Hz, 1H), 3.58 (dd, J¼11.1 and 3.5 Hz,
1H), 3.34 (dd, J¼11.1 and 3.6 Hz, 1H), 2.98 (m, 4H), 2.57
(m, 1H), 2.43 (dd, J¼12.5 and 3.5 Hz, 1H), 2.25 (m, 1H),
1.83e1.50 (m, 4H); 13C NMR (CDCl3, 100 MHz) 147.2,
146.8, 142.9, 141.0, 140.6, 128.9, 128.4, 128.2, 128.1,
127.8, 127.7, 127.3, 125.9, 125.8, 120.3, 119.9, 65.7, 64.4,
63.7, 61.0, 59.8, 54.7, 27.6, 24.2. HRMS calcd for
C26H29N2O (Mþþ1): 385.2280, found: 385.2254.
4.1.1. N-((R)-N-Diphenylmethyl-2-amino-2-phenylethyl)-
(S )-prolinol (2)
A colorless oil was obtained in 70% yield. 1H NMR
(CDCl3, 400 MHz) 7.31e7.11 (m, 15H), 4.62 (s, 1H), 3.60
(m, 2H), 3.45 (dd, J¼11.0 and 4.0 Hz, 1H), 3.12 (br, 1H),
2.94 (t, J¼12.1 Hz, 1H), 2.77 (m, 1H), 2.54 (m, 1H), 2.34
(dd, J¼12.5 and 3.2 Hz, 1H), 2.04 (m, 1H), 1.80e1.63 (m,
4H); 13C NMR (CDCl3, 100 MHz) 140.5, 138.6, 129.6,
129.3, 128.7, 128.5, 127.7, 127.4, 65.4, 62.8, 61.4, 57.1,
55.1, 54.5, 28.3, 24.4. Anal. Calcd for C26H30N2O: C, 80.79;
H, 7.82; N, 7.25. Found: C, 80.77; H, 8.00; N, 7.51. [a]D20
ꢂ75.5 (c 0.1, CHCl3).
4.1.6. N-[(R)-N-(1-Naphthyl)-2-amino-2-phenylethyl]-(S )-
prolinol (9)
A colorless oil was obtained in 57% yield. 1H NMR
(CDCl3, 400 MHz) 8.05e7.10 (m, 11H), 6.27 (d, J¼8.0 Hz,
1H), 5.80 (br, 1H), 4.43 (dd, J¼11.2 and 3.6 Hz, 1H), 3.73
(dd, J¼10.8 and 4.0 Hz, 1H), 3.58 (dd, J¼10.7 and 2.8 Hz,
1H), 3.07 (m, 2H), 2.66 (m, 2H), 2.31 (m, 2H), 1.95e1.58
(m, 4H); 13C NMR (CDCl3, 100 MHz) 143.7, 142.8, 134.7,
129.2, 129.1, 127.8, 127.0, 126.8, 126.2, 125.5, 124.8,
120.7, 118.1, 107.2, 65.4, 63.8, 63.2, 58.0, 54.3, 27.9, 24.2.
HRMS calcd for C23H27N2O (Mþþ1): 347.2123, found:
347.2107.
4.1.2. N-[(R)-N-((R)-1-Phenylethyl)-2-amino-2-
phenylethyl]-(S )-prolinol (5)
A pale yellow oil was obtained in 63% yield. H NMR
1
(CDCl3, 400 MHz) 7.33e7.16 (m, 10H), 3.84 (dd, J¼10.5
and 3.4 Hz, 1H), 3.78 (q, J¼6.5 Hz, 1H), 3.61 (dd, J¼11.0
and 3.4 Hz, 1H), 3.41 (dd, J¼11.0 and 4.9 Hz, 1H), 3.21 (m,
1H), 3.00 (br, 1H), 2.97 (dd, J¼12.7 and 10.8 Hz, 1H), 2.68
(m, 1H), 2.52 (dd, J¼12.8 and 3.5 Hz, 1H), 2.36 (q,
J¼8.2 Hz, 1H), 1.90e1.60 (m, 4H), 1.36 (d, J¼6.6 Hz, 3H);
13C NMR (CDCl3, 100 MHz) 146.4, 143.4, 128.8, 128.7,
127.6, 127.5, 127.1, 127.0, 65.8, 64.8, 63.6, 60.5, 55.8, 55.3,
27.9, 24.6, 22.5. HRMS calcd for C21H29N2O (Mþþ1):
325.2280, found: 325.2309.
4.1.7. N-((R)-N,N-Dibenzyl-2-amino-2-phenylethyl)-(S )-
prolinol (10)
A colorless oil was obtained in 68% yield. 1H NMR
(CDCl3, 400 MHz) 7.42e7.18 (m, 15H), 3.89 (m, 1H), 3.87
(d, J¼13.6 Hz, 2H), 3.57 (dd, J¼10.7 and 3.5 Hz, 1H), 3.40
(dd, J¼12.8 and 8.7 Hz, 1H), 3.32 (dd, J¼10.7 and 2.1 Hz,
1H), 3.15 (d, J¼13.6 Hz, 2H), 2.80 (br, 1H), 2.79 (m, 1H),
2.62 (dd, J¼12.8 and 5.5 Hz, 1H), 2.56 (m, 1H), 2.03 (q,
J¼8.6 Hz, 1H), 1.81e1.58 (m, 4H); 13C NMR (CDCl3,
100 MHz) 144.8, 144.2, 142.9, 129.0, 128.9, 128.7, 128.4,
127.9, 127.8, 127.7, 127.5, 127.1, 65.3, 64.0, 63.5, 62.9,
59.3, 54.6, 27.9, 24.2. Anal. Calcd for C27H32N2O: C, 80.96;
4.1.3. N-((R)-N-Benzyl-2-amino-2-phenylethyl)-(S )-
prolinol (6)
A colorless oil was obtained in 69% yield. 1H NMR
(CDCl3, 400 MHz) 7.39e7.25 (m, 10H), 3.75 (m, 2H), 3.63
(dd, J¼11.1 and 3.5 Hz, 1H), 3.51 (d, J¼13.6 Hz, 1H), 3.42
(dd, J¼11.1 and 4.2 Hz, 1H), 3.01 (m, 1H), 2.92 (dd,
J¼11.3 and 12.3 Hz, 1H), 2.76 (br, 1H), 2.62 (m, 1H), 2.43