D.F.Schneider, M.S.Viljoen / Tetrahedron 58 )2002) 5307±5315
5313
CHaHb), 1.44 #qdd, J12.4, 3.1 and 1.2 Hz, 1H, CHaHb),
1.49±1.62 #m, 2H, CHCHaHb), 1.86 #`d quint.', J11.9and
2.6 Hz, 1H, CHaHb), 2.04±2.14 #m, 2H, CHCHaHb), 2.33
#d sept., J1.1 and 6.5 Hz 1.4 Hz, 1H, CH#CH3)2), 2.40
#ddd, J12.9, 3.1 and 2.3 Hz, 1H, CHaHb); dC 14.37 #q,
CH3), 19.36 #q, CH3), 19.62 #q, CH3), 28.93 #t, CH2),
32.78 #d, CH), 35.13 #t, CH2), 44.92 #d, CH), 45.41 #t,
CH2), 46.61 #d, CH), 213.59#s, .CvO); M1, 154.1356.
Calcd for C10H18O: M, 154.1357. Elution with ether±
petroleum ether #2:3) subsequently produced a mixture of
the four diastereomeric carvomenthols #19)±#22) #0.65 g,
21%), bp 1158C #air-bath temp.)/15 mmHg, with similar
gas chromatographic retention times and 13C NMR spectra
as the antipodal set of diastereomers #15)±#18). The mass
spectral data of the diasteomers #19)±#22) were also in total
agreement with those exhibited by the carvomenthols #15)±
#18) as depicted in Section 3.1.1.
73%) as a colourless oil, bp 658C/20 mmHg #lit.17 1778C/
20
732 mmHg); [a]D 260.3 #c10, CHCl3);17 dH 0.87 #d,
J4.1 Hz, 3H, CH3), 0.89#d, J4.1 Hz, 3H, CH3), 1.19±
1.26 #m, 2H, CH2), 1.36±1.49#m, 2H, 2 £CH), 1.63 #ddd,
J3.3, 2.6 and 1.3 Hz, 3H, CH3), 1.65±1.77 #m, 2H, CH2),
1.78±2.03 #m, 2H, CH2), 5.38 #tq, J4.3 and 1.3 Hz, 1H,
vCH); dC 19.71 #q, CH3), 20.02 #q, CH3), 23.48 #q, CH3),
26.53 #t, CH2), 28.00 #t, CH2), 30.85 #t, CH2), 32.31 #d, CH),
40.05 #d, CH), 120.00 #s, vC,), 133.94 #s, vC,). Gas
chromatographic analysis of the distillate as in Section 3.1.3
likewise revealed the presence of trace quantities of the
corresponding 4S-diastereomers of cis- and trans-4-isopro-
penyl-1-methylcyclohexane as well as cis- and trans-p-
menthane.
3.2. Hydroboration/oxidation of ꢀ4R)-ꢀ1)-p-menthene
ꢀ24)
3.1.3. Regioselective reduction of ꢀ4R)-ꢀ1)-limonene
ꢀ23). Zinc dust #100 g, 1.53 mol) was activated by stirring
with two aliquots of aqueous hydrochloric acid #10%,
2£50 cm3), ®ltered, successively washed with water and
acetone, dried under vacuum and used instantly. To an ef®-
ciently stirred suspension of activated zinc dust #12.0 g,
183.6 mmol) and nickel chloride hexahydrate #10.0 g,
42.1 mmol) in a mixture of water #30 cm3) and 2-methoxy-
ethanol #30 cm3), #4R)-#1)-limonene #23) #5.10 g,
37.4 mmol) was added and the resulting reaction mixture
stirred for 9h at 50 8C. The reaction mixture was then
®ltered, diluted with saturated ammonium chloride
#50 cm3), extracted with ether #2£40 cm3) and the residue
from the dried #MgSO4) ether extract treated with a second,
freshly prepared portion of the reducing agent as above for
an additional 4 h at 508C. The reaction mixture was worked
up as above and the residue from the ether extract fraction-
ally distilled to yield )4R)-)1)-p-menthene #24) #3.36 g,
65%) as a colourless oil, bp 608C/22 mmHg #lit.16 174±
Boron tri¯uoride etherate #1.06 g, 7.5 mmol) in ether
#15 cm3) was added dropwise to a stirred mixture of lithium
borohydride #0.50 g, 23.0 mmol) and #4R)-#1)-p-menthene
#24) #7.75 g, 56.2 mmol) in ether #50 cm3) during 50 min at
208C. Stirring was maintained for an additional 2 h where-
upon the unreacted lithium borohydride was destroyed by
the addition of water #5 cm3). Aqueous chromic acid
#46 cm3), prepared from sodium dichromate dihydrate
3
#11.0 g, 36.9mmol), sulphuric acid #98%, 8 cm ) and
water, was then introduced to the reaction mixture during
15 min at room temperature and the resulting dark green
mixture stirred for a further 110 min at 308C. After separa-
tion of the ether layer, celite #10 g) was added to the aqueous
layer, the resulting suspension ®ltered and the ®ltrate
extracted with ether. The combined ether layers were
washed with saturated, aqueous sodium chloride
#2£40 cm3) and the residue from the dried #MgSO4) ether
extract fractionally distilled to yield a gas chromatographi-
cally determined 8:5 mixture of )2R,5R)-)1)-carvo-
menthone #13) #3.35 g, 39%) and )2S,5R)-)1)-
carvomenthone #14) #2.07 g, 24%) as a colourless oil, bp
20
1768C); [a]D 174 #c10, EtOH);6 dH 0.87 #d,
J4.1 Hz, 3H, CH3), 0.89#d, J4.1 Hz, 3H, CH3), 1.19±
1.26 #m, 2H, CH2), 1.36±1.49#m, 2H, 2 £CH), 1.63 #ddd,
J3.3, 2.6 and 1.3 Hz, 3H, CH3), 1.65±1.77 #m, 2H, CH2),
1.78±2.03 #m, 2H, CH2), 5.38 #tq, J4.3 and 1.3 Hz, 1H,
vCH); dC 19.71 #q, CH3), 20.02 #q, CH3), 23.48 #q, CH3),
26.53 #t, CH2), 28.00 #t, CH2), 30.85 #t, CH2), 32.31 #d, CH),
40.05 #d, CH), 120.00 #s, vC,), 133.94 #s, vC,). Gas
chromatographic analysis #7% Carbowax on Chromosorb B,
column temp. 1008C, inlet pressure 80 kPa N2) of the distil-
late revealed the presence of very small quantities of a 1:1
diastereomeric mixture of cis- and trans-4-isopropenyl-1-
methylcyclohexane #26) and #27) #80 mg, 1.5%) as well as
cis- and trans-p-menthane #28) and #29) #81 mg, 1.5%).
908C/10 mmHg, with
a speci®c optical rotation of
20
[a]D 19.9 #neat) #chiral TM-b-CD OV 1701-OH
column, temp. prog. 40±1208C at the rate of 1.78C/min,
¯ow rate 50 cm3 H2/sec).
3.3. Hydroboration/oxidation of ꢀ4S)-ꢀ2)-p-menthene
ꢀ30)
The hydroboration of #4S)-#2)-p-menthene #30) #6.63 g,
48.0 mmol) in ether #40 cm3) was performed as in Section
3.2 by treatment with lithium borohydride #0.45 g,
20.7 mmol) and boron tri¯uoride etherate #1.20 g,
7.2 mmol) in ether #40 cm3). The intermediate organo-
borane was oxidized by treatment with aqueous chromic
acid #131 cm3), prepared from sodium dichromate dihydrate
#9.55 g, 32.05 mmol), sulphuric acid #98%, 7.0 cm3) and
water, during 15 min at room temp. After stirring for an
additional 2 h at re¯ux the reaction mixture was worked
up, fractionally distilled and gas chromatographically
analyzed as in Section 3.2 to yield a 12:13 mixture of
#2R,5S)-#2)-carvomenthone #10) #2.14 g, 29%) and
)2S,5S)-)2)-carvomenthone #11) #2.34 g, 32%) as a colour-
less oil, bp 968C/12 mmHg, with a speci®c optical rotation
3.1.4. Regioselective reduction of ꢀ4S)-limonene ꢀ25). To
an ef®ciently stirred suspension of activiated zinc dust
#12.0 g, 183.6 mmol) and nickel chloride hexahydrate
#10.0 g, 42.1 mmol) in a mixture of water #30 cm3) and
2-methoxyethanol #30 cm3), #4S)-#2)-limonene #25)
#5.10 g, 7.4 mmol) was added and the resulting reaction
mixture stirred for 5 h at 508C. The reaction mixture was
then worked up, the product treated with an additional
portion of the reducing agent as above and ®nally extracted
as in Section 3.1.3. Fractional distillation of the residue from
the ether extract yielded #4S)-#2)-p-menthene #30) #3.76 g,
20
of [a]D 223.8 #c10, EtOH).