Allylic Alcohols-Dioxaborolane Ligand Cyclopropanation
J. Am. Chem. Soc., Vol. 120, No. 46, 1998 11951
mL). The two layers were separated, and the aqueous layer was
extracted with ether (2 × 10 mL). The combined organic layers were
washed with 10% aqueous HCl (10 mL) and then transferred into an
Erlenmeyer flask. A solution containing 30 mL of 2.5 M aqueous
NaOH and 3 mL of 30% aqueous H2O2 was added in one portion, and
the resulting biphasic solution was vigorously stirred for 30 min. The
two layers were then separated, and the organic layer was successively
washed with 10% aqueous HCl (10 mL), saturated aqueous Na2SO3
(10 mL), saturated aqueous NaHCO3 (10 mL), and brine (10 mL), dried
over Na2SO4, filtered, and concentrated under reduced pressure. The
crude residue was purified by flash chromatography on silica gel (5%
EtOAc/hexanes) to afford the desired cyclopropylmethanol 11 (98.1
mg, 83%) as a pale yellow liquid: Rf 0.15 (20% EtOAc/hexanes); [R]D
(100 MHz, CDCl3) δ 131.4, 124.7, 64.0, 41.1, 26.3, 25.7, 25.5, 20.0,
17.73, 17.68, 17.1. The enantiomeric excess (93%) was evaluated by
relative integration of the signals at -73.60 ppm (major) and -73.65
ppm (minor) of 19F NMR of the corresponding Mosher ester.
8-[(1R,2R)-2,2-dimethylcyclopropyl]-6-methyl-5(E)-octen-2-ol (33).
To a solution of alcohol (-)-29 (155 mg, 0.69 mmol) in anhydrous
dichloromethane (7 mL) at 0 °C was added fresly distilled triethylamine
(200 µL, 1.38 mmol), followed by fresly distilled methanesulfonyl
chloride (96 µL, 1.24 mmol). The resulting mixture was stirred for 90
min at 0 °C. Then ether (20 mL) was added, and the organic layer
was washed with saturated aqueous NaHCO3 (15 mL), water (15 mL)
and brine (15 mL), dried over MgSO4, and concentrated under reduced
pressure. The crude mesylate was used without any purification in
the next step.
1
+63.7 (c 1.92, CHCl3); H NMR (300 MHz, CDCl3) δ 3.61 (dd, J )
12, 6 Hz, 1H), 3.53 (dd, J ) 12, 7 Hz, 1H), 2.30-2.24 (m, 1H), 1.59-
1.48 (m, 2H), 1.06-0.98 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
64.7, 25.3, 14.4, -18.2; HRMS calcd for C4H7OI 197.95416, found
To a solution of the mesylate (209 mg, 0.69 mmol) in dry THF (25
mL) at 0 °C was slowly added a solution of 1.0 M in THF of Super
Hydride (6.9 mL, 6.9 mmol) over a 15 min period. The resulting
mixture was stirred at 0 °C for 2 h. The reaction was quenched with
water (10 mL); then 2.5 M aqueous NaOH (10 mL) was added followed
by 30% aqueous H2O2 (10 mL). The mixture was washed with ethyl
acetate (2 × 30 mL), and the combined organic layers were succesively
washed with saturated aqueous NaHCO3 (20 mL), water (20 mL), and
brine (20 mL), dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by flash chromatography on silica
gel (10% EtOAc/hexanes) to produce the title product 33 (112 mg,
77%): Rf 0.31 (20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3) δ
5.20-5.07 (m, 1H), 3.80 (sextuplet, J ) 6 Hz, 1H), 2.12-1.99 (m,
4H), 1.61 (s, 3H), 1.53-1.40 (m, 2H), 1.37-1.31 (m, 2H), 1.18 (d, J
) 6 Hz, 3H), 1.02 (s, 3H), 1.00 (s, 3H), 0.48-0.32 (m, 2H), -0.14 (t,
J ) 5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 135.9, 123.6, 67.8,
40.1, 39.10, 39.05, 28.4, 27.5, 24.3, 23.3, 19.8, 19.5, 15.9, 15.2; HRMS
calcd for C14H27O 211.2062, found 211.2052.
1
197.95352. The enantiomeric excess (90% ee) was evaluated by H
NMR (400 MHz, CDCl3) by the relative integration of the multiplets
at 4.36 ppm (major) and 4.28 ppm (minor) of the corresponding Mosher
ester.
(-)-(1S,2R)-2-Ethylcyclopropylmethanol (14) (Procedure D). The
cyclopropanation of (Z)-2-pentenol (38 mg, 0.44 mmol) was performed
according to procedure B with a standard workup but, here, dioxaboro-
lane ligand 22 was used instead of 1. 1H NMR analysis of the crude
showed >98% conversion, and the residue was purified by flash
chromatography on silica gel (5-10% EtOAc/hexanes) to produce the
desired cyclopropylmethanol 14 (30 mg, 60%) (87% ee) (higher yields
were obtained if the volatile alcohol was converted into its correspond-
ing benzoate derivative, see below): Rf 0.18 (20% EtOAc/hexanes);
[R]D -27.9 (c 0.62, CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.67 (dd,
J ) 11, 7 Hz, 1H), 3.59 (dd, J ) 11, 7 Hz, 1H), 1.50-1.24 (m, 3H),
1.15-1.07 (m, 1H), 1.02 (t, J ) 7 Hz, 3H), 0.90-0.80 (m, 1H), 0.71
(td, J ) 8, 5 Hz), -0.03 (dd, J ) 10, 5 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 62.8, 21.6, 18.0, 17.8, 14.2, 9.03.
The cyclopropanation of (Z)-2-pentenol (38 mg, 0.44 mmol) was
also performed according to procedure A. The crude cyclopropyl-
methanol was directly converted to the corresponding benzoate ester:
the cyclopropylmethanol was diluted in dichloromethane (5 mL), and
then pyridine (50 µL, 0.60 mmol) and benzoyl chloride (60 µL, 0.55
mmol) were added. The mixture was stirred for 8 h and diluted with
ethyl acetate (10 mL). The organic layer was successively washed
with 10% aqueous HCl (5 mL), saturated aqueous NaHCO3 (5 mL),
and brine (5 mL), dried over MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash chromatography
on silica gel (20% EtOAc/hexanes) to produce the desired cyclopro-
pylmethyl ester derivative (82 mg, 90%): [R]D -29.8° (c 1.56, CHCl3).
The enantiomeric excess (93%) was evaluated by 1H NMR (400 MHz,
CDCl3) by the relative integration of the multiplets at 4.45 ppm (major)
and 4.50 ppm (minor) of the corresponding Mosher ester.
(+)-(1S,2R)-2-Methyl-2-(4-methyl-3(E)-pentenyl)cyclopropyl]-
methanol (25). To a solution of diethylzinc (100 µL, 0.98 mmol) in
anhydrous dichloromethane (1.6 mL) and dry DME (100 µL, 0.98
mmol) at 0 °C was added dropwise diiodomethane (160 µL, 1.95 mmol)
over 2 min. The resulting clear mixture was stirred for 15 min at 0 °C
and then added to solution containing geraniol 24 (100 mg, 0.61 mmol)
and dioxaborolane 1 (193 mg, 0.71 mmol) in anhydrous CH2Cl2 (1.2
mL). The clear solution was stirred for 15 min at that temperature
and then warmed to room temperature and stirred for 2 h. Saturated
aqueous NH4Cl (5 mL) was added, and the mixture was washed with
ethyl acetate (3 × 20 mL). The combined organic layers were
successively washed with 10% aqueous HCl (15 mL), 2.5M aqueous
NaOH (2 × 15 mL), and brine (15 mL), dried over MgSO4, and
concentrated under reduced pressure. The crude residue was purified
by flash chromatography on silica gel (20% EtOAc/hexanes) to afford
the desired cyclopropylmethanol 22 (95 mg, 87%) as a colorless oil:
Rf 0.15 (20% EtOAc/hexanes); [R]D +2.16 (c 5.83, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 5.15-5.09 (m, 1H), 3.69 (dd, J ) 11, 7 Hz, 1H),
3.46 (dd, J ) 11, 8 Hz, 1H), 2.15-2.06 (m, 2H), 1.68 (s, 3H), 1.60 (s,
3H), 1.42-1.35 (m, 1H), 1.18-1.11 (m, 1H), 1.07 (s, 3H), 0.95-0.87
(m, 1H), 0.50 (dd, J ) 9, 5 Hz, 1H), 0.13 (t, J ) 5 Hz, 1H); 13C NMR
(-)-8-[(1R,2R)-2,2-Dimethylcyclopropyl]-6-methyl-5(E)-octen-2-
one or (-)-Noranthoplone (34). To a solution of alcohol 33 (70 mg,
0.33 mmol) in anhydrous dichloromethane (0.66 mL) was added NMO
(60 mg, 0.50 mmol), followed by TPAP (6 mg, 0.017 mmol). The
resulting mixture was stirred for 30 min at room temperature and then
concentrated under reduced pressure. The residue was purified by flash
chromatography on silica gel (10% EtOAc/hexanes) to produce (-)-
noranthoplone (34) (69 mg, >99%): Rf 0.63 (20% EtOAc/hexanes);
1
[R]D -8.80 (c 1.80, CHCl3) [lit.24 [R]D -10.5 (c 0.56, CHCl3)]; H
NMR (300 MHz, CDCl3) δ 5.20-5.07 (m, 1H), 2.44 (t, J ) 8 Hz,
2H), 2.25 (q, J ) 8 Hz, 2H), 2.10 (s, 3H), 2.01 (t, J ) 8 Hz, 2H), 1.60
(s, 3H), 1.42-1.32 (m, 2H), 1.02 (s, 3H), 1.00 (s, 3H), 0.45-0.38 (m,
1H), 0.33 (dd, J ) 9, 5 Hz, 1H), -0.15 (t, J ) 5 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 208.6, 136.6, 122.2, 43.6, 40.0, 29.7, 28.3, 27.5,
24.3, 22.3, 19.8, 19.5, 15.9, 15.2; HRMS calcd for C14H25O 209.1905,
found 209.1899.
(+)-(E)-1-[(1S,2S)-2-Hydroxymethylcyclopropyl]-2-phenyleth-
ene (36). To a solution of diethylzinc (190 µL, 1.87 mmol) in an-
hydrous dichloromethane (4 mL) and dry DME (195 µL, 1.87 mmol)
at -10 °C was added dropwise diiodomethane (300 µL, 3.76 mmol)
over 2 min. This clear colorless solution was stirred 10 min at -10
°C. Then a solution of the dioxaborolane 1 (202 mg, 0.75 mmol) in
anhydrous dichloromethane (1 mL) was added, followed by a solution
of the dienic alcohol 35 (100 mg, 0.624 mmol) in anhydrous
dichloromethane (1 mL). The clear solution was stirred for 2 h at that
temperature. Saturated aqueous NH4Cl (2 mL) was slowly added
followed by 10% aqueous HCl (5 mL). The mixture was diluted with
ether (20 mL) and extracted. The organic layer was successively
washed with saturated aqueous Na2SO3, 2 M aqueous NaOH containing
30% aqueous H2O2, saturated aqueous NH4Cl, and brine, dried over
MgSO4, and concentrated under reduced pressure. The crude residue
was purified by flash chromatography on silica gel (20% EtOAc/
hexanes) to afford the desired cyclopropylmethanol 36 (91.5 mg, 84%)
as a colorless oil: Rf 0.33 (20% EtOAc/hexanes); [R]D +99.3 (c 1.03,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.32-7.25 (m, 4H) 7.22-
7.16 (m, 1H), 6.47 (d, J ) 16 Hz, 1H), 5.80 (dd, J ) 16, 9 Hz, 1H),
3.57 (d, J ) 7 Hz, 2H), 1.65 (s (br), 1H), 1.55-1.49 (m, 1H), 1.33-
1.26 (m, 1H), 0.79 (t, J ) 7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
137.4, 132.9, 128.5, 127.9, 126.7, 125.6, 66.0, 23.3, 20.3, 12.1; The