The Journal of Organic Chemistry
Article
2882, 1611, 1585, 1252, 1063, 765 cm−1
;
1H NMR (300 MHz,
1H), 4.64 (d, J = 12.2 Hz, 1H), 5.01 (dd, J = 6.5, 4.6 Hz, 1H), 7.17−
7.42 (m, 9H); 13C NMR (125 MHz, CDCl3) δ 30.2, 32.4, 70.4, 82.6,
124.9, 125.1, 126.3, 127.5, 127.7, 128.3, 130.3, 138.8, 142.8, 144.0;
LC/MS (ESI) m/z 247.38 (M + Na)+; HRMS (CI) calcd for C16H15O
(M − H)+ 223.1123, found 223.1119; HPLC (Chiralcel OD column,
n-hexane:i-PrOH = 98:2, 0.5 mL/min, 254 nm) Rt (major) = 9.82 min,
Rt (minor) = 11.19 min; ee = 99%.
CDCl3) δ 1.97−2.11 (m, 3H), 4.22 (d, J = 3.9 Hz, 1H), 4.23 (dd, J =
3.0, 1.2 Hz, 1H), 4.76 (q, J = 5.1 Hz, 1H), 6.83 (d, J = 8.1 Hz, 1H),
6.90 (dt, J = 6.6, 0.9 Hz, 1H), 7.20 (dt, J = 9.0, 1.5 Hz, 1H), 7.29 (dd, J
= 7.5, 1.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 30.8, 61.9, 63.2,
117.0, 120.5, 124.3, 129.7, 129.7, 154.5; LC/MS (ESI) m/z 173.27 (M
+ Na)+; HRMS (CI) calcd for C9H11O2 (M + H)+ 151.0759, found
151.0760; HPLC (Chiralcel OD-RH column, CH3CN:H2O = 10:90,
1.0 mL/min, 225 nm) Rt (major) = 21.74 min, Rt (minor) = 26.67
min; ee = 98%.
General Procedure for the Synthesis of Chiral Benzylic Ethers
(2a−k). To a stirred mixture of chiral benzylic alcohol (1.42 mmol) in
anhydrous THF (6 mL) and DMF (1.5 mL) was added NaH (2.13
mmol, 60% in mineral oil) at 0 °C. After stirring for 30 min, CH3I or
BnBr (4.26 mmol) was added at 0 °C under N2. The reaction mixture
was stirred at room temperature for 12 h under N2. The reaction
mixture was carefully quenched with H2O (10 mL), then extracted
with EtOAc (2 × 30 mL). The organic layer was washed with brine,
dried over Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography (n-hexane/EtOAc) to afford
chiral benzylic ether.
(S)-1-(Benzyloxy)-5-methyl-2,3-dihydro-1H-indene (2f): colorless
oil; yield = 91%; Rf = 0.43 (n-hexane/EtOAc = 20/1); [α]27 −9.1 (c
D
0.5, CHCl3); IR (neat) υ 2929, 2858, 1495, 1454, 1342, 1089, 808
cm−1; 1H NMR (300 MHz, CDCl3) δ 2.08−2.18 (m, 1H), 2.28−2.39
(m, 1H), 2.34 (s, 3H), 2.74−2.84 (m, 1H), 3.03−3.14 (m, 1H), 4.58
(d, J = 11.8 Hz, 1H), 4.63 (d, J = 11.8 Hz, 1H), 5.00 (dd, J = 6.5, 4.2
Hz, 1H), 7.17−7.43 (m, 9H); 13C NMR (125 MHz, CDCl3) δ 21.3,
30.1, 32.6, 70.2, 82.4, 124.8, 125.5, 127.1, 127.3, 127.6, 128.3, 138.1,
138.9, 139.9, 144.3; LC/MS (ESI) m/z 239.45 (M + H)+; HRMS (CI)
calcd for C17H17O (M − H)+ 237.1279, found 237.1281; HPLC
(Chiralcel OD column, n-hexane:i-PrOH = 100:0, 0.5 mL/min, 225
nm) Rt (major) = 49.97 min, Rt (minor) = 54.50 min; ee = 97%.
(S)-1-(Benzyloxy)-5-bromo-2,3-dihydro-1H-indene (2g): colorless
oil; yield = 89%; Rf = 0.40 (n-hexane/EtOAc = 40/1); [α]26D −16.7 (c
1.0, CHCl3); IR (MeOH) υ 3030, 2933, 2856, 1599, 1471, 1453, 1089,
(S)-1-(Benzyloxy)-1,2,3,4-tetrahydronaphthalene (2a): colorless
oil; yield = 85%; Rf = 0.27 (n-hexane/EtOAc = 20/1); [α]26 +1.5
1
1069, 698 cm−1; H NMR (300 MHz, CDCl3) δ 2.10−2.20 (m, 1H),
D
(c 1.0, CHCl3); IR (neat) υ 2937, 2864, 1492, 1347, 1058, 740 cm−1
;
2.31−2.43 (m, 1H), 2.76−2.86 (m, 1H), 3.03−3.14 (m, 1H), 4.59 (d, J
= 11.8 Hz, 1H), 4.64 (d, J = 11.8 Hz, 1H), 4.96 (dd, J = 6.5, 4.2 Hz,
1H), 7.07−7.16 (m, 1H), 7.26−7.40 (m, 7H); 13C NMR (125 MHz,
CDCl3) δ 29.9, 32.4, 70.5, 81.8, 122.2, 126.4, 127.5, 127.6, 127.9,
128.3, 129.3, 138.4, 141.8, 146.2; LC/MS (ESI) m/z 303.08 (M +
H)+; HRMS (CI) calcd for C16H16BrO (M + H)+ 303.0385, found
303.0378; HPLC (Chiralcel OD column, n-hexane:i-PrOH = 98:2, 0.5
mL/min, 270 nm) Rt (minor) = 12.92 min, Rt (major) = 13.16 min; ee
= 98%.
1H NMR (300 MHz, CDCl3) δ 1.70−1.80 (m, 1H), 1.92−2.12 (m,
3H), 2.67−2.90 (m, 2H), 4.54 (dd, J = 8.7, 4.2 Hz, 1H), 4.60 (d, J =
11.8 Hz, 1H), 4.70 (d, J = 11.8 Hz, 1H), 7.08−7.21 (m, 3H), 7.28−
7.43 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 18.9, 27.9, 29.1, 70.2,
74.6, 125.7, 127.4, 127.8, 128.3, 129.0, 129.3, 136.7, 137.6, 138.9; LC/
MS (ESI) m/z 261.24 (M + Na)+; HRMS (CI) calcd for C17H17O (M
− H)+ 237.1279, found 237.1276; HPLC (Chiralcel OD column, n-
hexane:i-PrOH = 98:2, 0.5 mL/min, 267 nm) Rt (major) = 9.45 min,
Rt (minor) = 10.65 min; ee = 99%.
(S)-1-Methoxy-1,2,3,4-tetrahydronaphthalene (2h): colorless oil;
yield = 81%; Rf = 0.20 (n-hexane/EtOAc= 20/1); [α]26 −2.6 (c 1.0,
(S)-1-Methoxy-1-phenylethane (2b): colorless oil; yield = 87%; Rf
D
= 0.38 (n-hexane/EtOAc = 15/1); [α]26D −107.6 (c 1.0, CHCl3), lit.21
CHCl3), lit.23 [α]12 −3.5 (c 1.0, CHCl3); IR (neat) υ 2938, 1685,
D
[α]22 −117.3 (c 0.8, CH3CN); IR (neat) υ 2978, 2931, 2821, 1451,
1454, 1054, 742 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.72−1.80 (m,
1H), 1.83−1.93 (m, 1H), 1.95−2.07 (m, 2H), 2.66−2.87 (m, 2H),
3.44 (s, 3H), 4.31 (t, J = 4.2 Hz, 1H), 7.05−7.15 (m, 1H), 7.17−7.22
(m, 2H), 7.32−7.37 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 18.7,
27.4, 29.1, 56.1, 76.8, 125.6, 127.5, 128.9, 129.3, 136.6, 137.5; LC/MS
(ESI) m/z 163.29 (M + H)+; HRMS (CI) calcd for C10H11 (M −
CH3O)+ 131.0861, found 131.0862; HPLC (Chiralcel OD column, n-
hexane:i-PrOH = 98:2, 0.5 mL/min, 225 nm) Rt (major) = 10.24 min,
Rt (minor) = 11.36 min; ee = 99%.
D
1219, 1116, 701 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.43 (d, J = 6.5
Hz, 3H), 3.22 (s, 3H), 4.29 (q, J = 6.5 Hz, 1H), 7.24−7.38 (m, 5H);
13C NMR (125 MHz, CDCl3) δ 23.9, 56.4, 79.6, 126.2, 127.4, 128.4,
143.5; LC/MS (ESI) m/z 137.29 (M + H)+; HRMS (CI) calcd for
C9H11O (M − H)+ 135.0810, found 135.0811; HPLC (Chiralcel OD
column, n-hexane:i-PrOH = 99:1, 0.5 mL/min, 260 nm) Rt (major) =
7.14 min, Rt (minor) = 8.37 min; ee = 99%.
(S)-1-Benzyloxy-1-phenylethane (2c): colorless oil; yield = 85%;
Rf = 0.43 (n-hexane/EtOAc = 15/1); [α]26 −87.0 (c 1.0, CHCl3),
(S)-4-(Benzyloxy)chroman (2i): white solid; yield = 85%; Rf = 0.27
D
lit.22 [α]22 −100.6 (c 0.5, CHCl3); IR (MeOH) υ 3030, 2976, 2863,
(n-hexane/EtOAc = 20/1); [α]25 −74.5 (c 1.0, CHCl3); mp 79−80
D
D
°C; IR (neat) υ 2984, 2912, 2879, 1610, 1584, 1268, 1119, 745 cm−1
;
1452, 1097, 699 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.48 (d, J = 6.5
Hz, 3H), 4.30 (d, J = 11.8 Hz, 1H), 4.47 (d, J = 11.8 Hz, 1H), 4.53 (q,
J = 6.5 Hz, 1H), 7.24−7.37 (m, 10H); 13C NMR (125 MHz, CDCl3) δ
24.2, 70.2, 77.2, 126.3, 127.4, 127.5, 127.6, 128.3, 128.4, 138.6, 143.7;
LC/MS (ESI) m/z 213.39 (M + H)+; HRMS (CI) calcd for C15H17O
(M + H)+ 213.1279, found 213.1277; HPLC (Chiralcel OD column,
n-hexane:i-PrOH = 99.5:0.5, 0.5 mL/min, 260 nm) Rt (major) = 16.65
min, Rt (minor) = 17.29 min; ee = 99%.
1H NMR (300 MHz, CDCl3) δ 1.98−2.09 (m, 1H), 2.13−2.21 (m,
1H), 4.20−4.27 (m, 1H), 4.35 (dt, J = 11.1, 2.7 Hz, 1H), 4.47 (t, J =
3.8 Hz, 1H), 4.61 (d, J = 11.8 Hz, 1H), 4.66 (d, J = 11.8 Hz, 1H), 6.85
(t, J = 8.0 Hz, 1H), 6.87 (d, J = 7.2 Hz, 1H), 7.16−7.22 (m, 2H),
7.24−7.40 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 27.6, 62.1, 69.5,
69.9, 116.9, 119.9, 121.7, 127.6, 127.7, 128.4, 129.6, 130.6, 138.5,
154.9; LC/MS (ESI) m/z 263.33 (M + Na)+; HRMS (EI) calcd for
C16H16O2 (M)+ 240.1150, found 240.1154; HPLC (Chiralcel OD
column, n-hexane:i-PrOH = 98:2, 0.5 mL/min, 277 nm) Rt (major) =
13.25 min, Rt (minor) = 16.16 min; ee = 98%.
(S)-1-Methoxy-2,3-dihydro-1H-indene (2d): colorless oil; yield =
77%; Rf = 0.25 (n-hexane/EtOAc = 20/1); [α]26 +19.3 (c 1.0,
D
CHCl3); IR (neat) υ 2946, 2833, 1653, 1454, 1033, 674 cm−1; H
1
NMR (300 MHz, CDCl3) δ 2.03−2.14 (m, 1H), 2.27−2.39 (m, 1H),
2.77−2.86 (m, 1H), 3.00−3.13 (m, 1H), 3.41 (s, 3H), 4.81 (dd, J =
6.5, 4.2 Hz, 1H), 7.18−7.27 (m, 3H), 7.39−7.41 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ 30.1, 31.9, 56.1, 84.5, 124.9, 125.0, 126.2, 128.4,
142.5, 144.0; LC/MS (ESI) m/z 149.12 (M + H)+; HRMS (CI) calcd
for C10H11O (M − H)+ 147.0810, found 147.0806; HPLC (Chiralcel
OD column, n-hexane:i-PrOH = 99.5:0.5, 0.5 mL/min, 266 nm) Rt
(major) = 23.63 min, Rt (minor) = 27.98 min; ee = 99%.
(1R,2R)-1,2-Bis(benzyloxy)-2,3-dihydro-1H-indene (2j): colorless
oil; yield = 90%; Rf = 0.29 (n-hexane/EtOAc = 25/1); [α]25 −35.5
D
(c 1.0, CHCl3); IR (MeOH) υ 3064, 3030, 2864, 1455, 1353, 1095,
746, 698 cm−1; 1H NMR (300 MHz, CDCl3) δ 2.86 (dd, J = 15.6, 5.7
Hz, 1H), 3.32 (dd, J = 15.6, 6.9 Hz, 1H), 4.36−4.42 (m, 1H), 4.60 (d,
J = 11.8 Hz, 1H), 4.67 (d, J = 11.8 Hz, 1H), 4.76 (d, J = 11.8 Hz, 1H),
4.82 (d, J = 11.8 Hz, 1H), 5.06 (d, J = 4.6 Hz, 1H), 7.17−7.42 (m,
14H); 13C NMR (125 MHz, CDCl3) δ 36.2, 71.3, 71.5, 85.7, 86.4,
124.8, 124.8, 126.7, 127.3, 127.4, 127.5, 127.6, 128.2, 128.2, 128.3,
138.0, 138.4, 139.6, 140.3; LC/MS (ESI) m/z 353.22 (M + Na)+;
HRMS (CI) calcd for C23H21O2 (M − H)+ 329.1542, found 329.1540;
HPLC (Chiralcel OD column, n-hexane:i-PrOH = 98:2, 0.5 mL/min,
254 nm) Rt (major) = 15.82 min; ee = 99%.
(S)-1-(Benzyloxy)-2,3-dihydro-1H-indene (2e): colorless oil; yield
= 84%; Rf = 0.41 (n-hexane/EtOAc = 20/1); [α]26 −2.5 (c 1.0,
D
CHCl3); IR (neat) υ 3020, 2935, 2864, 1720, 1603, 1347, 772 cm−1
;
1H NMR (300 MHz, CDCl3) δ 2.08−2.18 (m, 1H), 2.28−2.39 (m,
1H), 2.74−2.84 (m, 1H), 3.04−3.14 (m, 1H), 4.59 (d, J = 12.2 Hz,
10015
dx.doi.org/10.1021/jo201794k | J. Org. Chem. 2011, 76, 10011−10019