C. Eidamshaus, H.-U. Reissig / Tetrahedron: Asymmetry 22 (2011) 1644–1652
1649
mixture was stirred at rt for 2 h. Then water and EtOAc were added
(15 mL each) and the resulting phases were separated. The aque-
ous layer was extracted with EtOAc (3 ꢂ 10 mL) and the combined
organic layers were dried with Na2SO4, filtered, and evaporated.
The crude product was purified by flash column chromatography
on silica gel (5% MeOH in CH2Cl2 + approx. 1 vol % NEt3) to afford
column chromatography on silica gel (5% MeOH in CH2Cl2 + ap-
prox. 1 vol % NEt3) 33 mg (65%) of pure 17c as a yellow oil.
[a
]
D = ꢁ108 (c 1.50, CHCl3). 1H NMR (500 MHz, CDCl3): d = 3.75
(s, 3H, OMe), 3.83, 8.90 (2s, 2H each, PhCH2, PyrCH2), 5.66 (s, 1H,
CHPh), 6.49, 6.76 (2d, J = 2.1 Hz, 1H each, 3-H/5-H), 7.33–7.35 (m,
10H, Ph) ppm; the OH signal was not detected. 13C NMR
(126 MHz, CDCl3): d = 53.3, 54.1 (2t, PhCH2, PyrCH2), 55.2 (q,
OMe), 75.0 (d, CHPh), 105.3, 107.2 (2d, C-3/C-5), 127.0, 127.7,
128.2, 128.4, 128.5 (5d, Ph)⁄,⁄139.9, 143.2 (2s, Ph), 159.8, 162.2,
166.9 (3s, C-2/C-4/C-6) ppm; one signal (d, Ph) was not detected.
23 mg (83%) of pure 17a as a colorless oil. [
a]
D = ꢁ26.2 (c 0.4,
CHCl3). 1H NMR (400 MHz, CDCl3): d = 1.33 (d, J = 6.6 Hz, 3H,
CHMe), 3.63, 3.68 (AB system, JAB = 14.0 Hz, 1H each, PyrCH2),
3.65 (s, 3H, OMe), 3.73 (q, J = 6.6 Hz, 1H, CHMe), 5.56 (s, 1H, PhCH),
6.37, 6.56 (2 d, J = 2.2 Hz, 1H each, 3-H/5-H), 7.16–7.32 (m, 10H,
Ph) ppm; the OH signal was not detected. 13C NMR (101 MHz,
CDCl3): d = 24.1 (q, CHMe), 52.4 (t, PyrCH2), 55.2 (q, OMe), 57.7
(d, CHMe), 74.5 (d, PhCH), 105.4, 107.3 (2d, C-3/C-5), 126.8,
127.1, 127.2, 127.8, 128.50, 128.53 (6d, Ph), 159.5, 162.1, 166.8
IR (ATR):
m = 3315 (OH), 3060–2850 (@C–H, C–H), 1560 (C@C)
cmꢁ1. HRMS (ESI-TOF): Calcd for C21H23N2O2 [M+H]+: 335.1760.
Found: 335.1758.
4.2.4. (R)-{6-[((R)-20-Amino-1,10-binaphthyl-2-ylamino)-
(3s, C-2/C-4/C-6) ppm. IR (ATR):
H, C–H), 1710–1550 (C@O, C@C) cmꢁ1. HRMS (ESI-TOF): Calcd for
22H25N2O2 [M+H]+: 349.1916. Found: 349.1897.
m
= 3245 (OH), 3060–2870 (@C–
methyl]-4-methoxypyridin-2-yl}(phenyl)methanol 17d
Following the typical procedure, reaction of pyridyl aldehyde 15
(240 mg, 0.68 mmol) and (R)-1,10-binaphthyl-2,20-diamine (96 mg,
0.34 mmol) in the presence of MgSO4 in anhydrous ClCH2CH2Cl
(3.5 mL) at 50 °C provided 414 mg of the respective crude product
as a yellow oil. Reduction of the crude imine with NaBH4 (114 mg,
3.01 mmol) in EtOH (4.5 mL) afforded after flash column chroma-
tography on silica gel (hexane/EtOAc = 8:2) 55 mg (26%, 85 mg of
15 were re-isolated; yield brsm: 61%) of pure 16d as a colorless so-
C
4.2.2. (R)-{4-Methoxy-6-[((R)-1-phenylethylamino)methyl]-
pyridin-2-yl}(phenyl)methanol 17b
Following the typical procedure, reaction of pyridyl aldehyde 15
(75 mg, 0.21 mmol) and (R)-methylbenzylamine (28 mg,
0.23 mmol) in the presence of MgSO4 in CH2Cl2 (1.5 mL) afforded
70 mg of the respective crude imine as a yellow oil. Reduction of
the crude imine (64 mg, 0.14 mmol) with NaBH4 (19 mg,
0.50 mmol) in EtOH (1.5 mL) afforded 55 mg (60% over two steps)
of pure 16b as a yellow oil which was used in the next step without
further purification. Proto-desilylation of 16b (55 mg, 0.12 mmol)
with TBAF (1 M in THF, 0.12 mL, 0.12 mmol) in THF (1 mL) pro-
vided after flash column chromatography on silica gel (4% MeOH
in CH2Cl2 + approx. 1 vol % NEt3) 33 mg (80%) of pure 17b as a yel-
lid; mp 167 °C. [a]D = +73.3 (c 2.6, CHCl3). Due to the presence of
rotamers only characteristic signals are given: 1H NMR (400 MHz,
CDCl3): d = 0.00, 0.92 (2s, 6H, 9H, OTBS), 3.67 (s, 3H, OMe), 4.44
(s, 2H, PyrCH2), 5.60 (br s, 1H, CHPh), 6.56, 7.09 (2s, 1H each, 3-
H/5-H), 7.15–7.24, 7.76–7.81 (2m, 17H, BINAM, Ph) ppm. 13C
NMR (101 MHz, CDCl3): d = ꢁ4.95, 18.2, 25.8 (q, s, q, OTBS), 55.1
(q, OMe), 104.0, 105.9 (2d, C-3/C-5), 112.3, 112.5 (2s, BINAM),
114.1, 118.4 (2s, BINAM), 121.9, 122.4, 124.0, 126.0, 126.7, 126.8,
127.1, 127.7, 128.0, 128.1, 129.5 (11d, Ph, BINAM), 133.5, 134.0
(2s, BINAM), 142.6, 143.0 (2s, Ph, BINAM) ppm. IR (ATR):
low oil. [
a
]
D = ꢁ50.3 (c 2.1, CHCl3). 1H NMR (500 MHz, CDCl3):
d = 1.41 (d, J = 6.7 Hz, 3H, CHMe), 3.73 (m, 5H, OMe, PyrCH2), 3.81
(q, J = 6.7 Hz, 1H, CHMe), 5.65 (s, 1H, CHPh), 6.47, 6.66 (2d,
J = 2.4 Hz, 1H each, 3-H/5-H), 7.32–7.34 (m, 10H, Ph) ppm; the
OH signal was not detected. 13C NMR (126 MHz, CDCl3): d = 24.3
(q, CHMe), 52.7 (t, PyrCH2), 55.2 (q, OMe), 57.6 (d, CHMe), 76.7
(d, CHPh), 105.2, 107.2 (2d, C-3/C-5), 126.7, 126.9, 127.0, 127.7,
128.5 (5d, Ph)⁄, 143.3, 145.2 (2s, Ph), 159.9, 162.2, 166.8 (3s, C-2/
C-4/C-6) ppm; ⁄one signal (d, Ph) was not detected. IR (ATR):
m
= 3050–2850 (@C–H, C–H), 1600–1550 (C@C) cmꢁ1. HRMS (ESI-
TOF): Calcd for C40H44N3O2Si [M+H]+: 626.3203. Found: 626.3189.
Proto-desilylation of 16d (52 mg, 0.08 mmol) with TBAF (1 M in
THF, 0.08 mL, 0.08 mmol) in THF (0.2 mL) provided after flash col-
umn chromatography on silica gel (hexane/EtOAc = 1:1) 33 mg
(80%) of pure 17d as a colorless oil. [
a
]
D = ꢁ17.6 (c 1.7, CHCl3).
1H NMR (400 MHz, CDCl3): d = 3.64 (s, 3H, OMe), 4.46, 4.51 (AB sys-
tem, JAB = 16.8 Hz, 2H, PyrCH2), 5.56 (s, 1H, CHPh), 6.41, 6.64 (2d,
J = 2.3Hz, 1H each, 3-H/5-H), 7.05–7.27, 7.77–7.85 (2 m, 17H, BI-
NAM, Ph) ppm; the OH signal was not detected. 13C NMR
(126 MHz, CDCl3): d = 48.2 (t, PyrCH2), 55.4 (q, OMe), 74.3 (d,
CHPh), 105.9, 106.3 (2d, C-3/C-5), 112.2, 112.7, 113.9, 118.4 (4s, BI-
NAM), 122.1, 122.7, 123.7, 123.9, 126.8, 126.9, 127.8, 128.1, 128.2,
128.5, 129.7 (11d, Ph, BINAM)⁄, 133.6, 133.9 (2s, BINAM), 142.5,
142.9, 143.3 (3s, Ph, BINAM), 159.1, 161.9, 167.6 (3s, C-2/C-4/C-
6) ppm; ⁄four signals (d, Ph/BINAM) were not detected. IR (ATR):
m
= 3305 (O–H), 3080–2850 (@C–H, C–H), 1570–1500 (C@C)
cmꢁ1. HRMS (ESI-TOF): calcd for C22H25N2O2 [M+H]+: 349.1916.
Found: 349.1915.
4.2.3. (R)-{6-[(Benzylamino)methyl]-4-methoxypyridin-2-
yl}(phenyl)methanol 17c
Following the typical procedure, reaction of pyridyl aldehyde 15
(240 mg, 0.68 mmol) and benzylamine (73 mg, 0.68 mmol) in the
presence of MgSO4 in CH2Cl2 (3.5 mL) afforded 302 mg of the
respective crude imine as a pale yellow oil. Reduction of the crude
imine (302 mg, 0.67 mmol) with NaBH4 (76 mg, 2.00 mmol) in
EtOH (7 mL) afforded after flash column chromatography on silica
gel (hexane/EtOAc = 7:3 to 3:2) 73 mg (24% over two steps) of pure
m
= 3365 (O–H), 3050–2850 (@C–H, C–H), 1600–1550 (C@C)
cmꢁ1. HRMS (ESI-TOF): Calcd for C34H30N3O2 [M+H]+: 512.2333.
Found: 512.2357.
16c as yellow oil. [
a
]
D = +55.4 (c 0.7, CHCl3). 1H NMR (400 MHz,
4.2.5. (2R,3R,4S,5R,6S)-2-(Acetoxymethyl)-6-{4-(6-[(R)-(tert-
butyldimethylsiloxy)(phenyl)methyl]-4-methoxypyridin-2-yl)-
1H-1,2,3-triazol-1-yl}tetrahydro-2H-pyran-3,4,5-triyl triacetate
20
CDCl3): d = 0.03, 0.96 (2s, 6H, 9 H, OTBS), 3.76–3.85 (m, 7H, OMe,
PhCH2, PyrCH2), 5.85 (s, 1H, CHPh), 6.67, 7.02 (2d, J = 2.3Hz, 1H
each, 3-H/5-H), 7.49–7.51 (m, 10H, Ph) ppm. 13C NMR (101 MHz,
CDCl3): d = ꢁ4.89 18.3, 25.8 (q, s, q, OTBS), 53.2, 54.3 (2t, PhCH2,
PyrCH2), 55.0 (q, OMe), 77.5 (d, CHPh), 103.9, 106.7 (2d, C-3/C-5),
126.1, 126.8, 127.0, 128.0, 128.1, 128.2 (6d, Ph), 140.3, 143.9 (2s,
Ph), 160.2, 165.8, 166.8 (3s, C-2/C-4/C-6) ppm. IR (ATR):
To a solution of alkynyl pyridine 18 (84 mg, 0.24 mmol) in
CH3CN (5 mL) was added 1-azido-2,3,4,6-tetra-O-acetyl-
cose 19 (89 mg, 0.24 mmol), CuI (9 mg, 0.05 mmol), TBTA (25 mg,
0.05 mmol), and NEt3 (7 L, 0.05 mmol). The resulting mixture
a-D-glu-
l
m
= 3050–2850 (@C–H, C–H), 1595–1500 (C@C) cmꢁ1. HRMS (ESI-
was stirred at rt under an atmosphere of argon for 6.5 h. Then
water (20 mL) and EtOAc (20 mL) were added and the phases were
separated. The aqueous layer was extracted with EtOAc
(3 ꢂ 20 mL), the combined organic layers were dried with Na2SO4,
TOF): calcd for C27H37N2O2Si [M+H]+: 449.2624. Found 449.2625.
Proto-desilylation of 16c (70 mg, 0.16 mmol) with TBAF (1 M in
THF, 0.16 mL, 0.16 mmol) in THF (1.5 mL) provided after flash