316 J . Org. Chem., Vol. 67, No. 1, 2002
Notes
3-phenyl-2-propen-1-ol, cis-2-buten-1-ol, cis-2-penten-1-ol, and
cis-2-hexen-1-ol with diethylzinc and diiodomethane yielded the
corresponding cyclopropyl methanols 1, 5, 7, 8, and 9 in yields
of 60-98%.3 Cyclopropanation of allylbenzene, 4-bromo-1-
butene, and 5-bromo-1-pentene with diazoacetate in the presence
of catalytic rhodium(II) diacetate or cupric sulfate gave pure cis-
and trans-cyclopropyl carboxylates after flash chromatography
with EtOAc/hexane (20:1).2 Treatment of the above carboxylates
with LiAlH4 afforded cyclopropyl alcohols 3, 4, 6, and 11,
respectively in yields of 80-95%. The cyclopropyl alcohols 2 and
10 were obtained in yields of 72% and 40%, respectively by
LiAlH4 reduction of trans and cis-dimethylcyclopropane dicar-
boxylates,3 and monoacetylation with Ac2O/DMAP in dichlo-
romethane. Oxidation of the racemic cyclopropyl alcohols with
pyridinium chlorochromate provided the corresponding racemic
aldehydes, which were used as standards for gas chromatogra-
phy, NMR, and TLC analysis.
Mosher ester synthesis was performed as follows:3a,14 (R)-
(-)-R-methoxy-R-(trifluoromethyl)phenylacetyl chloride (1.1 equiv)
was added to a solution of alcohol (0.02 mmol), DMAP (1.2 equiv),
and triethylamine (7 equiv) in CH2Cl2. After 5 h, the mixture
was filtered through a short plug of silica gel eluted with EtOAc/
hexane (1:4) and concentrated in vacuo. The enantiomeric excess
(ee) was determined by 1H NMR through the relative integration
of the multiplets of the corresponding Mosher esters from two
enantiomers of the alcohols.
Gen er a l P r oced u r e for Ch lor op er oxid a se-Ca ta lyzed
Oxid a tion . Chloroperoxidase (1400 units/mg) was obtained from
Chirazyme, Inc. (Urbana, IL). Cyclopropylmethanol (0.3 mmol)
and CPO (0.05-0.6 µmol) were stirred vigorously with TBHP
(0.6 mmol) in the presence of 1% (v/v) of polyethylenimine5 in
5.0 mL of 50 mM sodium citrate buffer, pH 5.5. The reaction
vial was capped, and the mixture was stirred for 1 h at room
temperature. Sodium hydrosulfite was then added, and the
mixture was extracted twice with CH2Cl2. The combined organic
extracts were dried over MgSO4, and the products were purified
by flash chromatography (CH2Cl2/acetone). Quantitative gas
chromatography (GC) was performed with dodecane as an
internal standard. The conversion of the reaction was evaluated
by GC analysis using the corresponding aldehydes and alcohols
as authentic samples.
data. The absolute configuration was determined by comparing
the optical rotation with literature data.2
(1S,2R)-(-)-2-Meth yl-1-for m ylcyclopr opan e (7): 37% yield
determined by GC and 38% conversion of the racemic alcohol 5,
determined by GC analysis; 90% ee determined by chiral gas
chromatography analysis of the corresponding alcohol obtained
by LiAlH4 reduction of aldehyde 7 (chiral R-Dex column, 60 °C,
tR ) 10.8 min, minor isomer; 11.3 min, major isomer); 1H NMR
(500 MHz, CDCl3) δ 9.38 (d, J ) 6.0, 1H), 1.89-1.83 (m,1H),
1.57-1.49 (m, 1H), 1.27 (d, J ) 6.5 Hz, 3 H), 1.25-1.21 (m, 1H),
1.18-1.14 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 202.37, 28.31,
18.85, 15.94, 13.54. The absolute configuration was determined
by chiral GC analysis of the corresponding alcohol obtained by
LiAlH4 reduction of aldehyde 7.
(1R,2S)-(+)-2-Meth ylcyclop r op a n em eth a n ol (7): 60% iso-
lated yield; 37% ee determined by gas chromatography using
chiral R-Dex column (60 °C, tR ) 10.8 min, major isomer; 11.3
min, minor isomer); [R]25 +19.0° (c 0.19, CH2Cl2). 1H and 13C
D
NMR spectral data are identical to the literature data. The
absolute configuration was determined by comparing the optical
rotation with literature data.3
(1S,2R)-(-)-2-Eth yl-1-for m ylcyclop r op a n e (8): 35% iso-
lated yield; 56% conversion; 59% ee determined by gas chroma-
tography using a chiral R-Dex column (50 °C, 10 min, 50 f 90
°C, 2 °C/min; tR ) 18.6 min, major isomer; 18.9 min, minor
isomer); [R]25D -9.8° (c 0.60, CH2Cl2); 1H NMR (500 MHz, CDCl3)
δ 9.36 (d, J ) 5.5 Hz, 1H), 1.89-1.58 (m, 2H), 1.53-1.41 (m,
2H), 1.25-1.17 (m, 2H), 0.97 (t, J ) 7.5 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 202.13, 28.04, 26.84, 21.78, 14.92, 14.41. The
absolute configuration was determined by chiral GC analysis of
the corresponding alcohol obtained by LiAlH4 reduction of
aldehyde 8.
(1R,2S)-(+)-2-Eth ylcyclop r op ylm eth a n ol (8): 40% iso-
lated yield; 92% ee determined by 1H NMR analysis of MTPA
ester (4.45 ppm, major; 4.50 ppm, minor); [R]25 +29.2° (c 0.37,
D
CH2Cl2). 1H and 13C NMR spectral data match the literature
data. The absolute configuration was determined by comparing
the optical rotation with literature data.3
(1S,2R)-(-)-1-F or m yl-2-p r op ylcyclop r op a n e (9): 44% iso-
lated yield; 54% conversion; 82% ee determined by 1H NMR
analysis of MTPA ester (4.43 ppm, minor; 4.48 ppm, major);
[R]25D -13.8° (c 0.39, CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 9.34
(d, J ) 6.0 Hz, 1H), 1.88-1.83 (m, 1H), 1.67-1.31 (m, 5H), 1.26-
1.16 (m, 2H), 0.91 (t, J ) 7.5 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 202.16, 30.43, 27.94, 24.72, 23.27, 14.89, 13.91. The
absolute configuration was determined by chiral GC analysis of
the corresponding alcohol obtained by LiAlH4 reduction of
aldehyde 9.
(1S,2R)-1-F or m yl-2-p h en ylcyclop r op a n e (5): 7% yield de-
termined by GC, 8% conversion; 65% ee determined by gas
chromatography using a chiral R-Dex column (100 °C, 10 min,
100 f 150 °C, 1.5 °C/min; tR ) 38.3. min, minor isomer; 38.6
1
min, major isomer); H NMR (500 MHz, CDCl3) δ 8.66 (d, J )
7.0 Hz, 1H), 7.33-7.21 (m, 5H), 2.83 (q, J ) 8.5 Hz, 1H), 2.17-
2.10 (m, 1H), 1.88 (dt, J ) 7.5, 13.5 Hz, 1H), 1.59 (dt, J ) 5.5,
8.0 Hz, 1H).
(1R,2S)-(+)-2-P r op ylcyclop r op ylm eth a n ol (9): 42% iso-
lated yield; 93% ee determined by 1H NMR analysis of MTPA
(1R,2S)-2-P h en ylcyclop r op ylm eth a n ol (5): >90% isolated
yield; 18% ee determined by gas chromatography using a chiral
ester (4.43 ppm, major; 4.48 ppm, minor); [R]25 +27.9° (c 0.20,
D
CH2Cl2). 1H and 13C NMR spectral data match the literature
data. The absolute configuration was determined by comparing
the optical rotation with literature data.3
R-Dex column (100 °C, 10 min, 100 f 150 °C, 1.5 °C/min; tR
)
38.3. min, major isomer; 38.6 min, minor isomer).1H and 13C
NMR spectral data match literature data.3 The absolute con-
figuration was assigned on the basis of the analogue to alcohol
6.
(1S,2R)-2-Acetoxym eth yl-1-for m ylcyclopr opan e (10): 40%
isolated yield; 41% conversion; 92% ee determined by gas
chromatography using chiral R-Dex column (100 °C, tR ) 22.4
min, major isomer; 22.0 min, minor isomer); 1H NMR (500 MHz,
CDCl3) δ 9.54 (d, J ) 4.0 Hz, 1H), 4.50 (q, J ) 6.5 Hz, 1H), 3.94
(dd, J ) 9.0, 12.0 Hz, 1H), 2.12-2.05 (m, 1H), 2.04 (s, 3H), 1.91-
1.81 (m, 1H), 1.36-1.24 (m, 2H); 13C NMR (125 MHz, CDCl3) δ
200.29, 171.11, 62.66, 26.82, 21.07, 12.94.
(1S,2R)-(+)-2-Ben zyl-1-for m ylcyclop r op a n e (6): 32% iso-
lated yield, 54% conversion; 66% ee determined by 1H NMR
analysis of MTPA ester of the corresponding alcohol obtained
from LiAlH4 reduction of aldehydes 6 (4.56 ppm, major; 4.52
ppm, minor); 1H NMR (500 MHz, CDCl3) δ 9.58 (d, J ) 5.0 Hz,
1H), 7.32-7.20 (m, 5H), 2.94 (q, J ) 7.5 Hz, 1H), 2.82 (q, J )
7.5 Hz, 1H), 2.08-2.02 (m, 1H), 1.83-1.76 (h, J ) 7.5 Hz, 1H),
1.41-1.37 (m, 1H), 1.32 (dt, J ) 5.0, 8.0 Hz, 1H). The absolute
configuration was determined by 1H NMR analysis of MTPA
ester of the corresponding alcohol obtained from LiAlH4 reduc-
tion of aldehyde 6.
(1R ,2S )-(-)-2-Ac e t o x y m e t h y lc y c lo p r o p y lm e t h a n o l
(10): 57% isolated yield; 57% ee determined by 1H NMR analysis
of MTPA ester (4.53 ppm, minor; 4.48 ppm, major); [R]25D -10.0°
(c 0.55, CH2Cl2). 1H and 13C NMR spectral data match the
literature data. The absolute configuration was determined by
comparing the optical rotation with the literature data.4c
(1S,2R)-(+)-2-Br om oeth yl-1-for m ylcyclopr opan e (11): 35%
(1R,2S)-(+)-2-Ben zylcyclop r op ylm eth a n ol (6): 45% iso-
lated yield; 95% ee determined by 1H NMR analysis of MTPA
ester (4.56 ppm, minor; 4.52 ppm, major); [R]25 +15.4° (c 0.22,
1
D
isolated yield; 45% conversion; 91% ee determined by H NMR
CH2Cl2). 1H and 13C NMR spectral data match the literature
analysis of MTPA ester of the corresponding alcohol obtained
from LiAlH4 reduction of 11a (4.05 ppm, minor; 4.01 ppm,
major): [R]25D +32.0° (c 0.27, CH2Cl2). 1H and 13C NMR spectral
data match the literature data. Excess LiAlH4 reduction of
aldehyde 11 afforded alcohol 11 and alcohol 8 (∼5:1). The
absolute configuration was determined by 1H NMR analysis of
(14) (a) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969,
34, 2543-2549. (b) Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J . Am. Chem. Soc. 1982, 109, 5765-
5780.