Preparation of Optically Active Tertiary Alcohols
J . Org. Chem., Vol. 62, No. 13, 1997 4357
with NaN3 (59 mg, 9.2 mmol) in refluxing MeOH/H2O (10:1)
2-Meth ylen e-4-p h en yl-3-bu tyn -1-ol (52). The iodo com-
pound (S)-16 (152 mg, 0.5 mmol; >97% ee) was treated with
acetone (20 mL) by the catalysis of CuSO4 (2 g) and p-TsOH
(2 grains) at 25 °C for 4 h to give the corresponding acetonide
(S)-51 (136 mg, 78%). The acetonide in THF (4 mL) was
treated Bu2Cu(CN)Li2 (6 mL of 0.33 M solution in THF) at
-78 °C for 2 h to give 52 (49 mg, 80%): oil; IR (neat) 3358,
solution (11 mL) for 2 h to give (S)-38 (160 mg, 75%): oil; [R]24
D
+58.22 (c 7.5, EtOH; S-isomer, >97% ee).
The azido compound (S)-38 (95 mg, 0.44 mmol) was treated
with PPh3 (126 mg, 0.48 mmol) in MeCN (10 mL) at 23 °C for
5 h to give 39 (54 mg, 71%; 56% ee favoring the R-isomer):
oil; [R]25D -12.5 (c 0.68, EtOH; 56% ee favoring the R-isomer);
HPLC (Chiralcel OD, 2-propanol/hexane (10:90), 1 mL/min)
tR 13.6 min (S-isomer), 15.0 min (R-isomer); IR (neat) 3282,
1
2205 cm-1; H NMR (200 MHz, CDCl3 ) δ 7.36-7.29 (2H, m),
7.22-7.16 (3H, m), 5.49-5.46 (2H, m), 4.11 (2H, s), 2.18 (1H,
br s, OH); 13C NMR (50 MHz, CDCl3) δ 131.5, 131.1, 128.3,
128.2, 122.6, 120.2, 90.6, 87.0, 65.0; MS m/ z (rel intensity)
158 (100, M+); HRMS calcd for C11H10O (M+) 158.0731, found
158.0722.
2-Meth yl-1,2,5-p en ta n etr iol (53). The diol (S)-45 (220
mg, 1 mmol; >97% ee) was subjected to hydrogenation by the
catalysis of Pd/C (5%, 100 mg) in EtOH at 25 °C for 15 h to
give (S)-533 (55 mg, 40%): oil; 13C NMR (50 MHz, acetone-d6)
δ 72.5, 70.3, 63.2, 35.9, 27.8, 24.1.
1
2240 cm-1; H NMR (200 MHz, CDCl3) δ 7.42-7.37 (2H, m),
7.27-7.22 (3H, m), 3.55 (2H, s), 3.42 (3H, s), 2.20 (1H, br s),
1.96 (1H, br s); 13C NMR (50 MHz, CDCl3) δ 131.7, 128.1, 128.0,
122.3, 89.1, 80.3, 75.9, 59.0, 32.0, 29.3; MS m/ z (rel intensity)
187 (5, M+), 155 (100); HRMS calcd for C12H13O1N (M+)
187.0997, found 187.0992.
1-Meth oxy-2,3-d ip h en yl-2-p r op a n ol (41). The oxirane
(S)-14 (450 mg, 3 mmol; >97% ee) was treated with NaH (750
mg, 30 mmol) and Me2SO4 (mL, 3.3 mmol) in THF (15 mL) at
23 °C for 1 h to give (S)-1-(methoxymethyl)-1-phenyloxirane
40 (501 mg, 99%). The ether (S)-40 (487 mg, 2.97 mmol) was
treated with PhLi (2.96 mL of 3 M solution in cyclohexane/
Et2O) and CuCN (400 mg, 4.45 mmol) in THF (3 mL) at -78
°C and then at 0 °C for 1.5 h to give (S)-41 (632 mg, 88%): oil;
[R]30D -26.3 (c 0.05, EtOH; S-isomer, >97% ee); IR (neat) 3450
5-(2,2,4-Tr im eth yl-1,3-d ioxola n -4-yl)-4-p en tyn -2-ol (54).
The acetonide (S)-48 (212 mg, 1 mmol; >97% ee) was treated
with MeLi (1 mL, 1.6 M of hexane solution) in THF (5 mL) at
.
25 °C for 2 h. The mixture was cooled to -78 °C, and BF3 OEt2
(0.13 mL, 1 mmol) was added. After 10 min, 1-methyloxirane
(116 mg, 2 mmol) was added. The mixture was stirred for 30
min, and the reaction was quenched by addition of Et3N and
saturated NaHCO3. The mixture was extracted with EtOAc.
The combined extracts were dried (Na2SO4) and filtered. The
filtrate was concentrated and chromatographed on a SiO2
column by elution with EtOAc/hexane (20:80) to give (S)-54
(160 mg, 81%): oil; [R]25D -9.44 (c 9.0, CHCl3; S-isomer, >97%
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.34-6.78 (10H, m) 3.66
(1H, d, J ) 9.2 Hz), 3.60 (1H, d, J ) 9.2 Hz), 3.38 (3H, s, OCH3),
3.13 (2H, s, CH2Ph), 2.83 (1H, s, OH); MS m/ z (rel intensity)
242 (1, M+), 91 (100); HRMS calcd for C16H18O2 (M+) 242.1306,
found 242.1300.
3-(H yd r oxym et h yl)-1-p h en yl-1-h ep t a d ecyn -3-ol (43).
The iodo compound (S)-16 (151 mg, 0.50 mmol; >97% ee) was
treated with NaH (125 mg, 5 mmol) and t-BuMe2SiCl (0.75
mL of 1 M THF solution) in THF (5 mL) at 25 °C for 3 h to
give a silyl ether (S)-42 (127 mg, 88%). The silyl ether was
treated with dodecylmagnesium bromide (6 mL of 1 M THF
solution) in THF at 0 °C for 2 h to give a crude product. The
product was subsequently treated with Bu4NF (172 mg, 0.66
1
ee); IR (neat) 3424, 2236 cm-1; H NMR (200 MHz, CDCl3) δ
4.05 (1H, d, J ) 8.1 Hz), 3.91-3.82 (1H, m), 3.70 (1H, d, J )
8.1 Hz), 2.35 (1H, br s, OH), 2.31 (2H, d, J ) 5.9 Hz), 1.48
(3H, s), 1.46 (3H, s), 1.33 (3H, s), 1.18 (3H, d, J ) 6.2 Hz); 13
C
NMR (50 MHz, CDCl3) δ 110.4, 84.5, 80.4, 75.7, 73.7, 66.1,
29.1, 26.9, 26.9, 26.1, 22.2; MS m/ z (rel intensity) 183 (51,
M+ - CH3), 72 (100); HRMS calcd for C10H15O3 (M+ - CH3)
183.1021, found 183.1019.
mmol) in THF (10 mL) to give (S)-43 (110 mg, 70%): oil; [R]23
D
-32.1 (c 2.0, EtOH; S-isomer, >97% ee); IR (neat) 3338, 2240
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.42-7.39 (2H, m), 7.30-
7.27 (3H, m), 3.74 (1H, d, J ) 11.0 Hz), 3.57 (1H, d, J ) 11.0
Hz), 2.25 (2H, br s), 1.73-1.54 (4H, m), 1.22 (22H, br s), 0.85
(3H, t, J ) 6.8 Hz); 13C NMR (75 MHz, CDCl3) δ 131.7, 128.5,
128.2, 122.5, 89.5, 85.4, 72.3, 69.7, 37.9, 31.9, 29.7, 29.6, 29.5,
29.3, 24.1, 22.6, 14.1; MS m/ z (rel intensity) 341 (3), 327 (100,
M+ - CH2OH); HRMS calcd for C23H35O2 (M+ - CH2OH)
327.2687, found 327.2692.
5-(2,2,4-Tr im eth yl-1,3-d ioxola n -4-yl)p en ta n -2-on e (55).
The alcohol (S)-54 (289 mg, 1.45 mmol; >97% ee) was treated
with pyridinium dichromate (1.36 g, 3.62 mmol) in the pres-
ence of molecular sieves (4 Å) in CH2Cl2 at 25 °C for 4 h. The
mixture was filtered and rinsed with Et2O. The filtrate was
concentrated to give a crude product, which was subjected to
hydrogenation (1 atm) by the catalysis of Pd/C (5%, 150 mg)
in EtOAc (15 mL) at 25 °C for 4 h to give (S)-55 (176 mg, 61%;
>97% ee): oil; IR (neat) 2981, 1707 cm-1; 1H NMR (200 MHz,
CDCl3) δ 3.75 (1H, d, J ) 8.3 Hz), 3.66 (1H, d, J ) 8.3 Hz),
2.42 (2H, t, J ) 6.9 Hz), 2.10 (3H, s), 1.67-1.39 (4H, m), 1.35
(3H, s), 1.34 (3H, s), 1.24 (3H, s); MS m/ z (rel intensity) 200
(1, M+), 185 (45), 72 (100); HRMS calcd for C11H20O3 (M+)
200.1412, found 200.1432.
4-Bu tyl-2-(h yd r oxym eth yl)-2,3-d eca d ien -1-ol (44). The
iodo compound (S)-20 (99 mg, 0.32 mmol) in THF (1.5 mL)
was treated with Bu2Cu(CN)Li2 (3 mL of 0.43 M solution in
THF) at -78 °C for 1 h and then at 0 °C for an additional 1 h
to give 44 (46 mg, 60%): oil; IR (neat) 3352, 1955 (allene) cm-1
;
1H NMR (200 MHz, CDCl3) δ 4.16 (4H, s), 1.99-1.92(6H, m, 2
CH2, 2 OH), 1.39-1.24 (12H, m) 0.89-0.81 (6H, m); 13C NMR
(50 MHz, CDCl3) δ 196.5, 109.9, 105.6, 62.7, 32.8, 32.5, 31.7,
30.0, 28.9, 27.8, 22.6, 22.3, 13.9, 13.8; MS m/ z (rel intensity)
240 (3, M+), 109 (100); HRMS calcd for C15H28O2 (M+)
240.2089, found 240.2089.
(1S,5R)-(-)-Frontalin (2). Compound (S)-55 (176 mg, 0.88
mmol; >97% ee) was treated with HCl (10 N, 0.5 mL) in Et2O
(2 mL) at 25 °C for 15 h. After addition of NaHCO3, Na2SO4
and Et2O, the mixture was filtered. The solvent was evapo-
rated, the residue was distilled (Kugelrohr, 95-100 °C, 100
mmHg) to give (1S,5R)-frontalin (76 mg, 60%; >97% ee). [R]23
D
2-Meth yl-1,2-h exa n ed iol (50). The diol (S)-46 (487 mg,
2.83 mmol; >97% ee) was treated with acetone (20 mL) by the
catalysis of CuSO4 (6 g) and p-TsOH (2 grains) at 25 °C for 4
h to give the corresponding acetonide (S)-48 (483 mg, 80%):
-52.5 (c 2.0, Et2O) [lit.28 [R]22 -52.8 (c 1.64, Et2O). 1H NMR
D
(200 MHz, CDCl3) δ 3.92 (1H, d, J ) 6.3 Hz), 3.45 (1H, d, J
)6.3 Hz), 1.26-2.02 (6H, m), 1.44 (3H, s), 1.34 (3H, s).
oil; [R]25 -5.21 (c 2.5, CHCl3; S-isomer, >97% ee). The
D
Ack n ow led gm en t. We thank the National Science
Council for financial support (Grant No. NSC84-2113-
M002-010).
acetonide (S)-48 (200 mg, 0.9 mmol; >97% ee) was treated with
MeLi (0.89 mL of 1.5 M of hexane solution) at 25 °C for 2 h.
EtI (0.4 mL, 0.9 mmol) and HMPA (1 mL) were added. The
mixture was stirred at 25 °C for 18 h to give a crude product
49 (57 mg). The product was subjected to hydrogenation by
the catalysis of Pd/C (5%, 100 mg) and p-TsOH (catalytic
amount) in MeOH (10 mL) at 25 °C for 10 h to give (S)-50 (19
Su p p or tin g In for m a tion Ava ila ble: Additional experi-
mental procedures, spectral data, and authentic NMR spectra
of new compounds (64 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
mg, 43%): oil; [R]25 -4.8 (c 0.95, CHCl3; S-isomer, >97% ee)
D
(lit.27 [R]25 -3.0 (c 0.7, CHCl3)).
D
(28) Sugai, T.; Kakeya, H.; Ohta, H. J . Org. Chem. 1990, 55, 4643.
J O970236U