The Journal of Organic Chemistry
Note
3.75−3.65 (1H, m), 2.92−2.56 (3H, m), 2.19−2.09 (1H, m), 2.01−
1.94 (1H, m), 1.69−1.56 (1H, m), 1.23 (9H, s); 13C{1H} NMR (100.6
MHz, CDCl3, ppm) δ 152.2, 141.4, 118.7, 110.2, 65.9, 56.2, 54.8, 44.6,
25.0, 22.9, 22.2; optical rotation [α]20D 61.7 (c 1, CH2Cl2). Anal. Calcd
for C13H21NO3S: C, 57.54; H, 7.80; N, 5.16. Found: C, 57.30; H, 7.99;
N, 5.01.
(SS)-2-Methyl-propane-2-sulfinic acid ((4S,5R)-5-hydroxymethyl-
4,5,6,7-tetrahydro-benzo[b]thiophen-4-yl)-amide ((SS,R,S)-5f). Fol-
lowing the General Procedure A, ketimine (SS,R)−3f (500 mg, 1.75
mmol) was reduced to (SS,R,S)-5f. Crystallization from MeOH/
EtOAc/heptane (1:3:3) afforded product as a colorless needles (448
mg, 89% yield): analytical TLC on silica gel, 5:95 MeOH/CH2Cl2, Rf
= 0.26; mp 138.5−139.0 °C; IR (film, cm−1) 3411 (OH), 3207 (NH);
1H NMR (400 MHz, CDCl3, ppm) δ 7.10 (1H, d, J = 5.3 Hz), 7.07
(1H, d, J = 5.3 Hz), 4.40−4.34 (1H, m), 4.10−4.04 (1H, m), 3.88−
3.81 (1H, m), 3.70 (1H, dt, J = 11.0, 7.2 Hz), 2.86−2.80 (2H, m),
2.74−2.61 (1H, m), 2.32−2.21 (1H, m), 2.05−1.96 (1H, m), 1.65
(1H, dddd, J = 13.3, 11.0, 9.0, 6.8 Hz), 1.25 (9H, s); 13C{1H} NMR
(100.6 MHz, CDCl3, ppm) δ 138.7, 136.0, 127.7, 122.9, 66.1, 56.9,
56.4, 44.1, 25.9, 24.1, 22.9; optical rotation [α]20D 98.4 (c 1, CH2Cl2).
Anal. Calcd for C13H21NO2S2: C, 54.32; H, 7.36; N, 4.87. Found: C,
54.56; H, 7.50; N, 4.77.
lowing the General Procedure A, ketimine (SS,R)−3k (201 mg, 0.54
mmol) was reduced to (SS,R,S)-5k. Purification of the crude product
by column chromatography on silica gel using gradient elution from
2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2 afforded product as a
yellow amorphous solid (190 mg, 94% yield): analytical TLC on silica
gel, 5:95 MeOH/CH2Cl2, Rf = 0.24; mp 169.4−170.6 °C; IR (film,
1
cm−1) 3390 (OH); H NMR (400 MHz, CDCl3, ppm) δ 7.34−7.29
(3H, m), 7.27−7.22 (3H, m), 7.08 (1H, ddd, J = 8.6, 7.3, 1.6 Hz),
6.69−6.64 (1H, m), 6.63−6.57 (1H, m), 4.52−4.48 (2H, m), 4.46−
4.42 (1H, m), 3.62−3.57 (2H, m), 3.54 (1H, dd, J = 11.9, 3.4 Hz),
3.36 (1H, d, J = 2.4 Hz), 3.31−3.24 (1H, m), 2.37−2.29 (1H, m),
2.27−2.06 (1H, br s), 1.22 (9H, s); 13C{1H} NMR (100.6 MHz,
CDCl3, ppm) δ 145.3, 138.6, 131.1, 129.5, 128.8, 127.2, 126.7, 119.9,
117.0, 111.7, 62.4, 55.7, 55.2, 52.6, 46.2, 40.5, 22.9; HRMS-ESI (m/z)
calcd for C21H28N2O2S [M + H]+ 373.1944, found 373.1934; optical
rotation [α]20 −60.1 (c 1, CH2Cl2).
D
(SS)-2-Methyl-propane-2-sulfinic acid ((1S,2S)-2-hydroxymethyl-
1,2,3,4-tetrahydro-naphthalen-1-yl)-amide ((SS,S,S)-6a). Following
the General Procedure A, ketimine (SS,S)-3a (80 mg, 0.29 mmol) was
reduced to (SS,S,S)-6a. Crystallization from THF/heptane (1:1)
afforded product as a colorless prisms (64 mg, 80% yield): analytical
TLC on silica gel, 5:95 MeOH/CH2Cl2, Rf = 0.33; IR (film, cm−1)
1
3261 (OH) 3156 (NH); H NMR (400 MHz, CDCl3, ppm) δ 7.55−
(SS)-2-Methyl-propane-2-sulfinic acid ((3R,4S)-3-hydrox2ymethyl-
chroman-4-yl)-amide ((SS,R,S)-5h). Following the General Procedure
A, ketimine (SS,R)-3h (202 mg, 0.72 mmol) was reduced to (SS,R,S)-
5h. Crystallization from THF/heptane (1:1) afforded product as a
crystalline solid (193 mg, 95% yield): analytical TLC on silica gel, 5:95
MeOH/CH2Cl2, Rf = 0.28; mp 148.8−149.6 °C; IR (film, cm−1) 3375
7.52 (1H, m), 7.22−7.17 (2H, m), 7.11−7.09 (1H, m) 4.72 (1H, t, J =
4.6 Hz), 3.85−3.80 (1H, m), 3.69−3.64 (1H, m), 3.33−3.23 (1H, m),
2.89 (1H, ddd, J = 17.2, 5.9, 2.4 Hz), 2.79 (1H, ddd, J = 17.2, 11.5, 6.1
Hz), 2.07−1.99 (1H, m), 1.93−1.83 (1H, m), 1.78−1.72 (1H, m),
1.71−1.59 (1H, m), 1.22 (9H, s); 13C{1H} NMR (100.6 MHz, CDCl3,
ppm) δ 137.1, 136.8, 131.3, 129.1, 127.9, 126.8, 64.3, 56.5, 54.4, 42.4,
28.9, 23.0, 20.3; HRMS-ESI (m/z) calcd for C15H23NO2S [M + H]+
1
(OH), 3191 (NH); H NMR (400 MHz, CDCl3, ppm) δ 7.40 (1H,
dd, J = 7.7, 1.4 Hz), 7.21−7.16 (1H, m), 6.96−6.90 (1H, m), 6.82
(1H, dd, J = 8.2, 1.0 Hz), 4.46 (1H, t, J = 4.0 Hz), 4.28−4.22 (1H, dd,
J = 11.2, 2.9 Hz), 4.22−4.16 (1H, m), 3.75−3.61 (2H, m), 3.58−3.52
(1H, m), 2.60−2.45 (1H, br s), 2.35−2.27 (1H, m), 1.23 (9H, s);
13C{1H} NMR (100.6 MHz, CDCl3, ppm) δ 154.9, 130.7, 129.6,
121.5, 121.4, 117.2, 63.9, 61.2, 56.1, 50.8, 41.8, 22.8; HRMS-ESI (m/z)
calcd for C14H21NO3S [M + H]+ 284.1315, found 284.1326; optical
282.1522, found 282.1547; optical rotation [α]20 −17.3 (c 0.8,
D
CH2Cl2).
General Procedure B for Reduction of tert-Butanesulfinylke-
timines (SS,R)-3 with LiBHEt3. Sulfinylketimine (SS,R)-3 (1.0 equiv)
was dissolved in anhydrous THF (10 mL/mmol of imine 3) and
cooled to −78 °C under argon atmosphere. LiBHEt3 (1 M solution in
THF; 1.2 equiv) was added slowly at a rate to keep the temperature
below −75 °C. After stirring at −78 °C for 30 min, the mixture was
gradually warmed to room temperature and left to stir for 12 h,
whereupon it was quenched by addition of MeOH (5 mL/mmol of
starting imine 3). After stirring for 15 min, the mixture was
concentrated to dryness, and the residue was suspended in CHCl3
(5 mL/mmol of starting imine 3) and filtered through a plug of Celite.
Filtrate was dried over Na2SO4, filtered, and concentrated (rotary
evaporator). The residue was purified by column chromatography on
silica gel.
rotation [α]20 8.0 (c 1, CH2Cl2).
D
(SS)-2-Methyl-propane-2-sulfinic acid ((3R,4S)-3-hydroxymethyl-
thiochroman-4-yl)-amide ((SS,R,S)-5i). Following the General Proce-
dure A, ketimine (SS,R)-3i (199 mg, 0.67 mmol) was reduced to
(SS,R,S)-5i. Crystallization from THF/heptane (1:1) afforded product
as a crystalline solid (186 mg, 93% yield): analytical TLC on silica gel,
5:95 MeOH/CH2Cl2, Rf = 0.24; mp 157.4−158.2 °C; IR (film, cm−1)
3338 (OH); 1H NMR (400 MHz, CDCl3, ppm) δ 7.37−7.31 (1H, m),
7.17−7.03 (3H, m), 4.48 (1H, t, J = 3.1 Hz), 3.74−3.64 (1H, m),
3.62−3.53 (1H, m), 3.39 (1H, dd, J = 12.8, 3.3 Hz), 3.30−3.23 (1H,
m), 2.93 (1H, dd, J = 12.8, 4.2 Hz), 2.60−2.53 (1H, m), 2.22−2.12
(1H, m), 1.21 (9H, s); 13C{1H} NMR (100.6 MHz, CDCl3, ppm) δ
133.6, 132.4, 131.1, 128.5, 126.9, 125.1, 61.9, 55.9, 53.1, 39.3, 23.6,
(SS)-2-Methyl-propane-2-sulfinic acid ((1R,2R)-2-hydroxymethyl-
1,2,3,4-tetrahydro-naphthalen-1-yl)-amide ((SS,R,R)-7a). Following
the General Procedure B for the reduction, sulfinylketimine (SS,R)-3a
(50 mg, 0.18 mmol) was converted to (SS,R,R)-7a. Purification of the
crude product by reverse phase column chromatography using 25%
MeCN/aq. 0.1% HCOOH eluent afforded product as a colorless oil
(31 mg, 62%): analytical TLC on silica gel, 5:95 MeOH/CH2Cl2, Rf =
22.8; optical rotation [α]20 −51.7 (c 1, CH2Cl2). Anal. Calcd for
D
C14H21NO2S2: C, 56.16; H, 7.07; N, 4.68. Found: C, 56.16; H, 7.19;
N, 4.52.
(SS)-2-Methyl-propane-2-sulfinic acid ((3R,4S)-3-hydroxymethyl-
1-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-amide ((SS,R,S)-5j). Fol-
lowing the General Procedure A, ketimine (SS,R)−3j (270 mg, 0.92
mmol) was reduced to (SS,R,S)-5j. Purification of the crude product by
column chromatography on silica gel using gradient elution from 3%
MeOH/CH2Cl2 to 6% MeOH/CH2Cl2 afforded product as a yellow
oil (250 mg, 92% yield): analytical TLC on silica gel, 5:95 MeOH/
1
0.34; IR (film, cm−1) 3375 (OH) 3254 (NH); H NMR (400 MHz,
CDCl3, ppm) δ 7.33−7.28 (1H, m), 7.22−7.15 (2H, m), 7.13−7.08
(1H, m), 4.66 (1H, dd, J = 9.4, 4.5 Hz), 4.27−3.90 (2H, m), 3.82 (1H,
dd, J = 11.9, 4.1 Hz), 3.74 (1H, dd, J = 11.9, 9.2 Hz), 2.89−2.74 (2H,
m), 2.30−2.22 (1H, m), 1.79−1.72 (1H, m), 1.55 (1H, dddd, J = 13.7,
11.3, 10.3, 6.2 Hz), 1.23 (9H, s); 13C{1H} NMR (100.6 MHz, CDCl3,
ppm) δ 137.5, 136.3, 130.0, 129.1, 127.6, 126.2, 63.5, 57.2, 56.5, 40.9,
28.4, 23.0, 21.5; HRMS-ESI (m/z) calcd for C15H23NO2S [M + H]+
282.1528, found 282.1510; optical rotation [α]20D 37.8 (c 1, CH2Cl2).
(SS)-2-Methyl-propane-2-sulfinic acid ((1R,2R)-2-hydroxymethyl-
indan-1-yl)-amide ((SS,R,R)-7b). Following the General Procedure B,
ketimine (SS,R)-3b (40 mg, 0.15 mmol) was reduced to (SS,R,R)-7b.
Purification of the crude product by column chromatography on silica
gel using 6% MeOH/CH2Cl2 as eluent afforded product as a colorless
oil (30 mg, 75% yield): analytical TLC on silica gel, 5:95 MeOH/
CH2Cl2, Rf = 0.33; IR (film, cm−1) 3367 (OH), 3246 (NH); 1H NMR
(400 MHz, CDCl3, ppm) δ 7.33−7.18 (4H, m), 4.93 (1H, dd, J = 10.5,
1
CH2Cl2, Rf = 0.30; IR (film, cm−1) 3390 (OH); H NMR (400 MHz,
CDCl3, ppm) δ 7.33−7.27 (1H, m), 7.21−7.13 (1H, m), 6.73−6.66
(1H, m), 6.66−6.60 (1H, m), 4.38 (1H, s), 3.61−3.54 (2H, m), 3.48
(1H, s), 3.39−3.32 (2H, m), 3.21−3.12 (1H, m), 2.92 (3H, s), 2.32−
2.24 (1H, m), 1.22 (9H, s); 13C{1H} NMR (100.6 MHz, CDCl3,
ppm) δ 146.3, 130.9, 129.4, 120.6, 117.1, 111.6, 62.6, 55.7, 52.7, 48.1,
41.1, 39.3, 22.9; HRMS-ESI (m/z) calcd for C15H24N2O2S [M + H]+
297.1631, found 297.1622; optical rotation [α]20 −57.0 (c 1,
D
CH2Cl2).
(SS)-2-Methyl-propane-2-sulfinic acid ((3R,4S)-1-benzyl-3-hydrox-
ymethyl-1,2,3,4-tetrahydro-quinolin-4-yl)-amide ((SS,R,S)-5k). Fol-
3722
dx.doi.org/10.1021/jo500506u | J. Org. Chem. 2014, 79, 3715−3724