Enantioselective Synthesis of Primary 1-(Aryl)alkylamines
mmol) was subjected to N-O bond cleavage. Workup and
chromatography (CHCl3-MeOH-35% NH4OH, 200:9:1) gave
as the first fraction (R)-phenylethanediol [(R)-6] (82 mg, 74%).
The second fraction gave (S)-47 (132 mg, 91%) as a pale yellow
129.4 (CH), 129.5 (CH), 130.4 (CH), 134.0 (C), 139.9 (C), 147.7
(C), 159.9 (C); EIMS m/z (relative intensity) 306 (M+[37Cl], 8),
304 (M+[35Cl], 24), 290 (100), 288 (44), 163 (65), 134 (64), 135
(55). 1‚HCl: mp 190.5-191.5 °C (EtOH). Anal. Calcd for
oil: [R]23 -14.4 (c 1.5, CHCl3)
C18H24Cl2NO: C, 63.53; H, 6.81; N, 4.12. Found: C, 63.56; H,
D
6.94; N, 4.01.
2-[(1S)-1-Am in oeth yl]p h en ol [(S)-45]. In the same man-
ner described above for the preparation of (R)-45, (S)-47 (131
mg, 0.726 mmol) was hydrolyzed. Workup and chromatogra-
phy (CHCl3-MeOH-35% NH4OH, 200:9:1) gave (S)-45 (88 mg,
N-{(1R)-1-[3-(Meth ylsu lfa n yl)p h en yl]eth yl}-3-p h en yl-
1-p r op a n a m in e (2). In the same manner described above for
the preparation of 1, 52 (20.0 mg, 0.067 mmol) was reduced
88%) as yellow cubics: [R]20 +5.3 (c 0.2, CHCl3).
to give 2 (15.3 mg, 80%) as a pale yellow oil: [R]19 +44.4 (c
D
D
0.6, CHCl3); IR (neat) 3346 cm-1; H NMR (400 MHz, CDCl3)
1
3-(2-Ch lor op h en yl)-N-[(R)-1-(3-m eth oxyp h en yl)eth yl]-
p r op a n a m id e (51). To a stirred solution of 49 (30.0 mg, 0.163
mmol) in CH2Cl2 (0.65 mL) were added dicyclohexylcarbodi-
imide (37.0 mg, 0.179 mmol) and N,N-(dimethylamino)pyridine
(2.0 mg, 0.016 mmol). Stirring was continued for 30 min at
room temperature until a white precipitate deposited; (R)-38
(24 mg, 0.163 mmol) was added, and the mixture was stirred
for an additional 10 min at the same temperature. The white
precipitate was removed by filtration through a Celite pad,
the filtrate concentrated in vacuo, and the residue purified by
chromatography (CHCl3-MeOH-concentrated NH4OH, 1600:
9:1) to give 51 (49.2 mg, 95%) as colorless needles: mp 92-
92.5 °C (CHCl3-hexane); [R]20D +45.6 (c 1.0, CHCl3); IR (KBr)
δ 1.33 (3H, d, J ) 6.6 Hz), 1.76-1.81 (2H, m), 2.45-2.66 (4H,
m), 3.71 (1H, q, J ) 6.6 Hz), 7.06-7.28 (9H, m); 13C NMR
(100.6 MHz, CDCl3) δ 15.9 (CH3), 24.4 (CH3), 32.0 (CH2), 33.7
(CH2), 47.4 (CH2), 59.4 (CH), 123.5 (CH), 124.9 (CH), 125.1
(CH), 125.8 (CH), 128.4 (CH), 128.4 (CH), 129.0 (CH), 138.5
(C), 142.3 (C), 146.7 (C); EIMS m/z (relative intensity) 286
(M+ + 1, 10), 285 (M+, 46), 271 (17), 270 (88), 180 (16), 166
(11), 152 (86), 136 (33), 117 (19), 104 (36), 91 (100), 77 (30).
(2S)-2-P h en yl-2-({[(1R)-1-p h en yl-2-p r op en yl]a m in o}-
oxy)et h a n ol [(R,S)-54] a n d (2S)-2-P h en yl-2-({[(1S)-1-
p h en yl-2-p r op en yl]a m in o}oxy)eth a n ol [(S,S)-54]. To a
stirred solution of tetravinyltin (3.22 g, 14.2 mmol) was added
a 1.06 M solution of phenyllithium in cyclohexane (41 mL, 42.6
mmol) under a N2 atmosphere at 0 °C, and the stirring was
continued for 30 min to give a 0.71 M solution of vinyllithium.
A portion of prepared vinyllithium (16.4 mL, 17.0 mmol) was
transferred via cannula into a stirring solution of 9a (1.71 g,
7.09 mmol) in toluene (71 mL) at 0 °C. After the mixture was
stirred for 5 min, another vinyllithium (24.6 mL, 25.5 mmol)
was added to the mixture at 0 °C and stirring was continued
for an additional 25 min. After addition of water (100 mL),
the organic phase was separated, and the aqueous phase was
extracted with ether (3 × 200 mL). The organic phases were
combined, washed with brine (100 mL), dried (MgSO4), and
concentrated in vacuo. Purification of the residue by chroma-
tography (hexanes-EtOAc, 3.5:1) gave as the first fraction
3286, 1640 cm-1 1H NMR (400 MHz, CDCl3) δ 1.40 (3H, d,
;
J ) 6.9 Hz), 2.49 (2H, td, J ) 7.4, 0.9 Hz), 3.08 (2H, t, J ) 7.6
Hz), 3.79 (3H, s), 5.07 (1H, quint, J ) 7.1 Hz), 5.56 (1H, br d,
J ) 7.1 Hz), 6.78-6.81 (3H, m), 7.13-7.34 (5H, m); 13C NMR
(100.6 MHz, CDCl3) δ 21.7 (CH3), 29.7 (CH2), 36.5 (CH2), 48.8
(CH3), 53.3 (CH), 112.3 (CH), 112.6 (CH), 118.5 (CH), 127.0
(CH), 127.9 (CH), 129.6 (CH), 129.8 (CH), 130.9 (CH), 133.8
(C), 138.4 (C), 144.8 (C), 159.9 (C), 170.8 (C); EIMS m/z
(relative intensity) 319 (M+[37Cl], 3), 317 (M+[35Cl], 9), 282 (16),
167 (21), 150 (21), 107 (74), 91 (41). Anal. Calcd for C18H20
-
ClNO2: C, 68.03; H, 6.34; N, 4.41. Found: C, 67.72; H, 6.33;
N, 4.25.
N-{(1R)-1-[3-(Meth ylsu lfa n yl)p h en yl]eth yl}-3-p h en yl-
1-p r op a n a m id e (52). In the same manner described above
for the preparation of 51, (R)-39 (30 mg, 0.179 mmol) was
allowed to react with 50 (27.0 mg, 0.179 mmol). Workup and
chromatography (CHCl3-MeOH-concentrated NH4OH, 1600:
9:1) furnished 52 (49.8 mg, 93%) as colorless needles (CHCl3-
hexane): mp 86-87.5 °C; [R]19D +66.9 (c 0.1, CHCl3); IR (neat)
(S,S)-54 (252 mg, 13%) as a colorless oil: [R]21 +69.7 (c 0.2,
D
CHCl3); IR (neat) 3408 cm-1
;
1H NMR (400 MHz, CDCl3) δ
3.50 (1H, m), 3.63 (1H, dd, J ) 11.8, 8.8 Hz), 4.65 (1H, d, J )
7.6 Hz), 4.70 (1H, dd, J ) 8.8, 3.0 Hz), 5.22 (2H, dd, J ) 17.6,
10.3 Hz), 5.96 (1H, ddd, J ) 17.6, 10.3, 7.6 Hz), 7.25-7.40
(10H, m); 13C NMR (100.6 MHz, CDCl3) δ 66.9 (CH2), 68.7
(CH), 86.2 (CH), 118.0 (CH2), 126.8 (CH, 2 carbons), 127.8
(CH), 127.85 (CH), 127.9 (CH), 128.2 (CH), 128.6 (CH), 128.7
(CH), 128.8 (CH), 138.6 (C), 140.2 (C); ESI m/z [M + H]+ 270;
HRMS (ESI) calcd for C17H20NO4 [M + H]+ 270.1494, found
270.1496. The second fraction afforded (R,S)-54 (1.26 g, 66%)
3285, 1641 cm-1 1H NMR (400 MHz, CDCl3) δ 1.37 (3H, d,
;
J ) 7.0 Hz), 2.45 (3H, s), 2.46 (2H, t, J ) 7.3 Hz), 2.95 (2H, t,
J ) 7.6 Hz), 5.04 (1H, quint, J ) 7.0 Hz), 5.59 (1H, br d, J )
7.1 Hz), 6.95 (1H, br d, J ) 7.7 Hz), 7.71-7.26 (8H, m); 13C
NMR (100.6 MHz, CDCl3) δ 15.9 (CH3), 21.7 (CH3), 31.8 (CH2),
38.6 (CH2), 48.6 (CH), 123.0 (CH), 124.5 (CH), 125.4 (CH),
126.3 (CH), 128.4 (CH, 2 carbons), 128.6 (CH, 2 carbons), 129.2
(CH), 138.9 (C), 140.8 (C), 143.9 (C), 171.2 (C); EIMS m/z
(relative intensity) 301 (M+ + 2, 17), 300 (M+ + 1, 26), 299
(M+, 100), 284 (3), 208 (7), 166 (10), 151 (18), 136 (5), 105 (8),
91 (12), 76 (5). Anal. Calcd for C18H21NOS: C, 72.20; H, 7.07;
N, 4.68. Found: C, 72.50; H, 7.41; N, 4.58.
as a colorless oil: [R]27 +34.3 (c 1.1, CHCl3); IR (neat) 3419
D
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.91 (1H, br s), 3.59-3.62
(1H, A part of ABX, J ) 12.1, 2.7 Hz), 3.74-3.79 (1H, B part
of ABX, J ) 12.0, 8.8 Hz), 4.59 (1H, d, J ) 7.5 Hz), 4.75 (1H,
dd, J ) 8.8, 3.0 Hz), 5.23 (1H, d, J ) 10.4 Hz), 5.30 (1H, d,
J ) 17.2 Hz), 6.10 (1H, ddd, J ) 17.2, 10.4, 7.5 Hz), 7.19-
7.30 (10H, m); 13C NMR (100.6 MHz, CDCl3) δ 67.1 (CH2), 68.6
(CH), 86.1 (CH), 117.7 (CH), 126.8 (CH), 127.9 (CH, 2 carbons),
128.0 (CH), 128.1 (CH), 128.5 (CH, 2 carbons), 128.7 (CH, 2
carbons), 138.3 (CH), 138.5 (C), 139.2 (C); EIMS m/z (relative
intensity) 271 (M+ + 2, 6), 270 (M+ + 1, 46), 149 (13), 132 (2),
103 (10), 91 (6), 77 (5). Anal. Calcd for C17H19NO2: C, 75.81;
H, 7.11; N, 5.20. Found: C, 75.77; H, 7.21; N, 5.07.
3-(2-Ch lor op h en yl)-N-[(R)-1-(3-m eth oxyp h en yl)eth yl]-
1-p r op a n a m in e (NP S R-568) (1). To a stirred solution of 51
(32.7 mg, 0.18 mmol) in CH2Cl2 (1.1 mL) was added a 0.95 M
solution of diisobutylaluminum hydride in toluene (0.22 mL,
0.21 mmol) at room temperature. After being stirred for 3 h,
the reaction was quenched by addition of saturated aqueous
NH4Cl (2 mL). The mixture was filtered through a Celite pad,
and the filtrate was concentrated in vacuo. Purification of the
residue by chromatography (CHCl3-MeOH-concentrated NH4-
(1R)-1-P h en yl-2-p r op en -1-a m in e [(R)-44]. To a stirred
solution of (R,S)-54 (1.40 g, 5.18 mmol) in a mixture of AcOH-
THF-water (3:1:1) (37 mL) was added zinc powder (8.10 g,
124 mmol) in several portions at room temperature, and
stirring was continued for 4 h at 60 °C. After addition of
concentrated NH4OH (20 mL), the mixture was stirred at room
temperature for 1 h and then inorganic material was removed
by filtration through a Celite pad. The filtrate was extracted
with CHCl3 (3 × 100 mL), dried (MgSO4), and concentrated
in vacuo. The residue was purified by chromatography (CHCl3-
MeOH-concentrated NH4OH, 500:9:1) to give as the first
OH, 1000:9:1) gave 1 (22.2 mg, 71%) as a pale yellow oil: [R]20
D
+41.9 (c 1.1, CHCl3) [lit.5b [R]20D +38.6 (c 1.1, CHCl3)]; IR (neat)
3058, 2957, 2927, 2857, 2833 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.35 (3H, d, J ) 6.6 Hz), 1.76-1.81 (2H, m), 2.50-2.59 (2H,
m), 2.70-2.77 (2H, m), 3.74 (1H, q, J ) 6.5 Hz), 3.82 (3H, s),
6.79 (1H, ddd, J ) 8.3, 2.4, 0.9 Hz), 6.89-6.90 (2H, m), 7.11-
7.33 (5H, m); 13C NMR (100.6 MHz, CDCl3) δ 24.4 (CH3), 29.8
(CH2), 30.3 (CH2), 31.4 (CH2), 47.4 (CH3), 55.3 (CH), 58.4 (CH),
112.2 (CH), 112.3 (CH), 119.1 (CH), 126.8 (CH), 127.3 (CH),
J . Org. Chem, Vol. 69, No. 17, 2004 5603