6
Tetrahedron
ACCEPTED MANUSCRIPT
8.0 Hz, 2H), 2.46 (s, 3H), 3.79-3.92 (m, 1H), 3.88 (dd, J1 = 7.5
7.36 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H); 13C NMR (125
Hz, J2 = 10.0 Hz, 1H), 4.04 (dd, J1 = 3.0 Hz, J2 = 10.0 Hz, 1H),
4.89-5.04 (m, 2H), 5.79 (tdd, J1 = 7.0 Hz, J2 = 10.0 Hz, J2 = 17.0
Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ = 21.6, 25.1, 28.7, 28.9, 29.2, 32.6,
33.7, 69.4, 74.0, 114.2, 127.9, 129.9, 132.6, 139.0, 145.0; HRMS
(EI) m/z 326.1578 (326.1552 calcd for C17H26O4S, M+); HPLC
analysis, CHIRALPAK AD-H (hexane/2-propanol = 90/10, 0.5
mL/min, 254 nm), tR = 29 (R) and 41 (S) min.
MHz, CDCl3) δ = 21.5, 22.4, 22.6, 27.7, 30.2, 38.3, 69.9, 70.6,
71.0, 127.9, 129.8, 132.7, 144.9, 170.3; HRMS (EI) m/z
343.1581 (343.1579 calcd for C17H27O5S, M++H); HPLC
analysis, CHIRALPAK AS-H (hexane/2-propanol = 90/10, 0.5
mL/min, 254 nm), tR = 18 (R) and 22 (S) min.
4.2.16. (R)-2-Hydroxy-6-methylheptyl tosylate (11)
24
[α]D = –6.5 (c 1.5, CHCl3) (94% ee); IR (neat) 3528, 2953,
1597, 1458, 1360, 1190, 1098, 966, 814, 667 cm-1; 1H NMR (300
MHz, CDCl3) δ = 0.85 (d, J=6.5 Hz, 6H), 1.00-1.57 (m, 7H),
2.23 (brs, 1H), 2.45 (s, 3H), 3.77-3.92 (m, 1H), 3.87 (dd, J1 = 7.0
Hz, J2 = 10.0 Hz, 1H), 4.03 (dd, J1 = 3.0 Hz, J2 = 10.0 Hz, 1H),
7.35 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H); 13C NMR (125
MHz, CDCl3) δ = 21.6, 22.4, 22.9, 27.7, 32.8, 38.6, 69.4, 73.9,
127.9, 129.9, 132.6, 145.0; HRMS (EI) m/z 300.1376 (300.1395
calcd for C15H24O4S, M+); HPLC analysis, (CHIRALPAK AD-
H, hexane/2-propanol = 90/10, 0.5 mL/min, 254 nm), tR = 25 (R)
and 33 (S) min.
4.2.13. (S)-2-Acetoxy-6-methylhept-6-enyl tosylate (8)
26
[α]D = –5.2 (c 2.8, CHCl3) (42% ee), IR (neat) 2966, 1742,
1450, 1366, 1236, 1177, 1098, 953, 816, 669 cm-1; 1H NMR (300
MHz, CDCl3) δ = 1.22-1.75 (m, 4H), 1.67 (s, 3H), 1.89-2.10 (m,
2H), 1.98 (s, 3H), 2.45 (s, 3H), 3.97-4.20 (m, 2H), 4.62 (s, 1H),
4.70 (s, 3H), 4.85-5.08 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.78 (d,
J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ = 20.8, 21.6, 22.1,
22.7, 29.6, 37.1, 69.9, 70.7, 110.4, 127.9, 129.8, 132.7, 144.8,
144.9, 170.3; HRMS (EI) m/z 340.1363 (340.1344 calcd for
C17H24O5S, M+).
The absolute configuration of 11 was confirmed to be R by
comparing the optical rotation sign with that of the authentic
sample (R)-11 mentioned above in 4.2.14.
Under an argon atmosphere, to a solution of (S)-8 (39.7 mg,
0.117 mmol) in THF (0.9 mL) was added DIBAL-H (0.47 mL,
1.0 M toluene solution) at –78 °C. After the mixture was stirred
overnight at –78 °C, the reaction was quenched with 0.1 M
phosphate buffer (pH 6.5). After the addition of 2 M HCl to the
mixture, the products were extracted with CH2Cl2 (x3), and the
combined organic layer was washed with brine, then dried over
Na2SO4. After evaporation in vacuo, the residue was purified by
preparative TLC (hexane/AcOEt = 2/1) to give (S)-9 as a
colorless oil (30.0 mg, 86%). The ee of (S)-8 was determined by
HPLC analysis (CHIRALPAK AD-H (hexane/2-propanol =
90/10, 0.5 mL/min, 254 nm), tR = 27 (R) and 37 (S) min) of the
resulting (S)-9.
4.2.17. (S)-(Z)-2-Acetoxdec-3-enyl tosylate (12)
24
[α]D = +3.4 (c 1.1, CHCl3) (64% ee); IR (neat) 2926, 1742,
1364, 1233, 1177, 980, 816, 664 cm-1; H NMR (500 MHz,
1
CDCl3) δ = 0.88 (t, J=7.0 Hz, 3H), 1.19-1.38 (m, 8H), 1.98 (s,
3H), 1.98-2.13 (m, 2H), 2.46 (s, 3H), 4.04 (dd, J1 = 4.0 Hz, J2 =
10.5 Hz, 1H), 4.06 (dd, J1 = 7.0 Hz, J2 = 10.5 Hz, 1H), 5.22 (tdd,
J1 = 1.5 Hz, J2 = 9.0 Hz, J3 = 10.5 Hz, 1H), 5.64 (dtd, J1 = 1.0
Hz, J2 = 7.5 Hz, J3 = 10.5 Hz, 1H), 5.65-5.72 (m, 1H), 7.35 (d, J
= 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3) δ = 14.1, 21.0, 21.7, 22.6, 28.0, 28.9, 29.2, 31.6, 67.6,
70.1, 122.3, 128.0, 129.8, 132.9, 137.5, 145.0, 169.8; HRMS
(EI) m/z 326.1515 (326.1552 calcd for C17H26O4S, M+); HPLC
analysis, (CHIRALCEL OJ-H, hexane/2-propanol = 96/4, 0.5
mL/min, 254 nm), tR = 23 (R) and 25 (S) min.
4.2.14. (R)-2-Hydroxy-6-methylhept-6-enyl tosylate (9)
25
[α]D = –7.6 (c 1.7, CHCl3) (96% ee); IR (neat) 3528, 2940,
1647, 1458, 1358, 1177, 1098, 964, 891, 814, 667 cm-1; 1H NMR
(300 MHz, CDCl3) δ = 1.31-1.79 (m, 4H), 1.69 (s, 3H), 1.84-
2.20 (m, 2H), 2.45 (s, 3H), 3.75-3.97 (m, 2H), 3.97-4.15 (m,
1H), 4.64 (s, 1H), 4.70 (s, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.80 (d,
J = 8.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ = 21.6, 22.2,
23.1, 32.1, 37.4, 69.3, 73.9, 110.3, 128.0, 129.9, 132.6, 145.0;
HRMS (EI) m/z 298.1280 (298.1239 calcd for C15H22O4S, M+).
HPLC analysis conditions of 9 were already mentioned above in
4.2.13.
4.2.18. (R)-(Z)-2-Hydroxydec-3-enyl tosylate (13)
24
[α]D = –2.4 (c 0.9, CHCl3) (99% ee), IR (neat) 3447, 2926,
1597, 1362, 1177, 1098, 970, 814, 665 cm-1;1H NMR (500 MHz,
CDCl3) δ = 0.88 (t, J = 7.0 Hz, 3H), 1.19-1.39 (m, 8H), 1.94-
2.10 (m, 3H), 2.46 (s, 3H), 3.90 (dd, J1 = 8.0 Hz, J2 = 10.5 Hz,
1H), 3.98 (dd, J1 = 3.0 Hz, J2 = 10.5 Hz, 1H), 4.65-4.72 (m, 1H),
5.26 (tdd, J1 = 1.5 Hz, J2 = 8.5 Hz, J3 = 10.5 Hz, 1H), 5.60 (dtd,
J1 = 1.0 Hz, J2 = 7.5 Hz, J3 = 10.5 Hz, 1H), 7.36 (d, J = 8.0 Hz,
2H), 7.81 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ =
14.1, 21.7, 22.6, 28.0, 28.9, 29.3, 31.6, 66.1, 73.1, 125.7, 128.0,
129.9, 132.7, 136.0, 145.1. HRMS (EI) m/z 308.1459 (308.1446
calcd for C17H24O3S, M+–H2O); HPLC analysis, (CHIRALPAK
AD-H, hexane/2-propanol = 90/10, 0.5 mL/min, 254 nm), tR =
23 (R) and 31 (S) min.
To a solution of 9 (34.9 mg, 0.117 mmol), which was
obtained by the enzymatic reaction, in EtOH (2 mL) was added
10 % Pd-C (26.1 mg) at room temperature, then the solution was
degassed under reduced pressure. Under a hydrogen atmosphere,
the mixture was stirred overnight at room temperature. After
filtration with AcOEt and evaporation in vacuo, the residue was
purified by preparative TLC (hexane/AcOEt = 2/1) to give the
corresponding alcohol 11 as a colorless oil (20.4 mg, 58%);
[α]D25 = –7.4 (c 2.0, CHCl3). The absolute configuration of 9 was
confirmed to be R by comparing the optical rotation sign of the
resulting 11 to that of the authentic sample ((R)-11, [α]D25 = –7.5
(c 2.3, CHCl3)) synthesized from (S)-glycidol (see
Supplementary data for details).
To a solution of (Z)-13 (55.0 mg, 0.168 mmol), which was
obtained by the enzymatic reaction, in EtOH (2.5 mL) was added
10 % Pd-C (25.8 mg) at room temperature, then the solution was
degassed under reduced pressure. Under a hydrogen atmosphere,
the mixture was stirred overnight at room temperature. After
filtration with AcOEt and evaporation in vacuo, the residue was
purified by preparative TLC (hexane/AcOEt = 2/1) to give 2-
hydroxydecyl tosylate (14) as a colorless oil (28.7 mg, 51%);
4.2.15. (S)-2-Acetoxy-6-methylheptyl tosylate (10)
27
[α]D24 = –10.0 (c 1.0, CHCl3) (84% ee); IR (neat) 2955, 1742,
[α]D = +1.7 (c 2.9, EtOH) ; IR (neat) 3547, 2926, 2853, 2363,
1597, 1458, 1366, 1238, 1179, 1096, 953, 916, 669 cm-1; H
1595, 1470, 1348, 1175, 1096, 957, 893, 843, 818, 675 cm-1; H
1
1
NMR (500 MHz, CDCl3) δ = 0.83 (d, J = 7.0 Hz, 6H), 1.03-1.33
(m, 4H), 1.37-1.66 (m, 3H), 1.98 (s, 3H), 2.45 (s, 3H), 4.04 (dd,
J1 = 5.0 Hz, J2 = 10.5 Hz, 1H), 4.10 (dd, J1 = 3.5 Hz, J2 = 10.5
Hz, 1H), 4.95 (ddt, J1 = 3.5 Hz, J2 = 5.0 Hz, J3 = 9.5 Hz, 1H),
NMR (500 MHz, CDCl3) δ = 0.88 (d, J = 6.5 Hz, 3H), 1.20-1.33
(m, 12H), 1.35-1.46 (m, 2H), 2.06 (d, J = 4.5 Hz, 1H), 2.46 (s,
3H), 3.80-3.87 (m, 1H), 3.88 (dd, J1 = 7.0 Hz, J2 = 9.5 Hz, 1H),
4.04 (dd, J1 = 2.5 Hz, J2 = 9.5 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H),