1866
S. Karlsson, H.-E. Högberg
SPECIAL TOPIC
13C NMR (62.9 MHz, CDCl3): d = 31.2, 33.7 (2 C), 49.1, 72.0, 83.1,
Scheme 4), the total amount of epimers in the product 9,
obtained in 72% yield, was reduced from 10% to less than
127.8, 127.9, 128.5, 137.8.
1%. Interestingly, complete epimerisation was achieved MS (EI): m/z (%) = 288 [32, (M+, Br81)], 286 [32, (M+, Br79)], 197
(12), 195 (12), 181 (10), 179 (10), 91 (100).
around C-2 and C-3 when the reaction was performed un-
der hydrogen in the presence of a hydride source such as
NaBH4.
Anal. calcd for C12H15BrOS: C, 50.2; H, 5.3. Found: C, 50.1; H, 5.3.
(2S,4S)-1-Bromo-2,4-dimethyloctane (6)
Compound 6 was prepared from (2S,4S)-2,4-dimethyloctan-1-ol,
which was obtained from the same batch prepared previously in our
laboratory5 (stereoisomeric purity >99.5%), using PPh3 and Br2 un-
der standard conditions.15 Bp 90 °C/7 mbar; [a]D25 +2.8 (c = 1.2,
CHCl3).
1H NMR (250 MHz, CDCl3): d = 0.87 (d, 3 H, J = 6.5 Hz), 0.89 (t,
3 H, J = 6.5 Hz), 1.01 (d, 3 H, J = 6.6 Hz), 1.03-1.51 (m, 9 H),
1.83-1.96 (m, 1 H), 3.30 (dd, 1 H, J = 6.2, 9.8 Hz), 3.42 (dd, 1 H, J
= 4.3, 9.8 Hz).
In conclusion, a new approach was developed for the syn-
thesis of enantiopure sex pheromone components having
the threo-3-methylalkan-2-ol unit in its backbone and was
exemplified by the preparation of 9 in 99% stereoisomeric
purity. Acetylation of this gives5 (1S,2R,6R,8S)-1,2,6,8-
tetramethyldodecyl acetate (9, OAc instead of OH), which
is an active sex pheromone component of the pine sawfly
Macrodiprion nemoralis. This new strategy should con-
stitute an efficient and useful method for the synthesis of
similar compounds e.g. the numerous threo-3-methyl-2-
alkyl esters shown to be pheromones of many pine saw-
flies.
13C NMR (62.9 MHz, CDCl3): d = 14.1, 19.4, 20.0, 23.0, 29.0, 30.0,
32.4, 36.5, 41.8, 42.5.
MS (EI): m/z (%) = 165 (100), 163 (90), 83 (75), 55 (62).
2-[(2S,4S)-2,4-Dimethyl-1-octyl]-1,3-dithiane (7)
A procedure similar to that reported by Page et al.27 was used. BuLi
(1.4 M in hexane, 2.4 mL, 3.4 mmol) was added dropwise to a
stirred solution of 1,3-dithiane (0.41 g, 3.4 mmol) in THF (15 mL)
at -20 °C. After 1 h, the solution was cooled to -78 °C and (2S,4S)-
1-bromo-2,4-dimethyloctane (6; 0.50 g, 2.3 mmol) was added. The
reaction was then allowed to reach 22 °C. After 1.5 h, the reaction
was quenched by the addition of aq sat. NH4Cl solution (25 mL) and
extracted with Et2O (75 + 25 mL). The combined organic phases
were dried (Na2SO4), filtered and concentrated. Flash column chro-
matography of the residue (EtOAc/cyclohexane, 0-5% as eluent)
followed by distillation (bp 130 °C/1 mbar) furnished 7 (0.56 g,
95%) as a colourless oil in > 99% purity (GC); [a]D25 +11.3 (c = 1.3,
hexane).
1H NMR (250 MHz, CDCl3): d = 0.85 (d, 3 H, J = 6.6 Hz), 0.88 (t,
3 H, J = 6.6 Hz), 0.90 (d, 3 H, J = 6.5 Hz), 0.93-1.53 (m, 10 H),
1.68-1.96 (m, 3 H), 2.07-2.19 (m, 1 H), 2.76-2.98 (m, 4 H), 4.10
(dd, 1 H, J = 5.4, 9.4 Hz).
13C NMR (62.9 MHz, CDCl3): d = 14.2, 20.1, 23.0, 26.2, 27.0, 29.1,
29.8, 30.3, 30.6, 36.4, 42.4, 45.0, 45.6.
All chemicals were used as received unless otherwise stated. THF
(K, benzophenone), DMPU (CaH2) and Et2O (LiAlH4) were dis-
1
tilled from the indicated drying agents. H NMR and 13C NMR
1
spectra were recorded with a Bruker DMX 250 (250 MHz H and
62.9 MHz 13C) instrument. TLC was performed on silica gel plates
(60 F254, Merck) and preparative liquid chromatography on straight
phase silica gel (Merck 60, 230-400 mesh, 0.040-0.063 mm) using
an increasing concentration of distilled EtOAc or CH2Cl2 in dis-
tilled cyclohexane as eluent. Raney nickel (W-2 type) was obtained
from Fluka and used as received. GC analyses were carried out us-
ing a capillary column EC-5, 30 m, 0.32 mm i.d., df = 0.25 mm, or a
CP-Sil 19 CB, 30 m, 0.25 mm i.d., df = 0.25 mm, carrier gas N2. The
diastereomeric purity of compound 9 was determined using a capil-
lary column EC-wax, 30 m, 0.25 mm i.d., df = 0.25 mm, carrier gas
He. The elemental analyses (C, H, N) were performed by Mikro
Kemi AB, SE-752 28 Uppsala, Sweden. Melting and boiling points
are uncorrected and the latter are given as air bath temperatures
(bath temp./mbar) in a bulb to bulb (Büchi GKR-51) distillation ap-
paratus. Optical rotations were measured with a Perkin-Elmer 241
MC polarimeter in a 1 dm cell. Mass spectra were recorded on a Sat-
urn 2000 instrument, coupled to a Varian 3800 GC instrument.
Chloromethyl (trimehylsilyl)methyl sulfide (1) was obtained from
the same batch as that used in ref. 14. Compounds 2, 3 and 4 were
prepared using the same procedure as reported by us previously14
but using (1R)-camphorsultam as the chiral auxiliary. NMR, MS
and GC analytical data for those intermediates were identical to
those reported14 for the enantiomers. Physical data: 2: [a]D25 +77.8
MS (EI): m/z (%) = 260 (100, M+), 185 (40), 119 (58).
Anal. calcd for C14H28S2: C, 64.6; H, 10.8. Found: C, 64.5; H, 11.1.
2-[(3R,4R)-(4-Benzyloxy-3-tetrahydrothienyl)methyl]-2-
[(2´S,4´S)-2´,4´-dimethyl-1´-octyl]-1,3-dithiane (8)
For the synthesis of compound 8, a procedure similar to that report-
ed by Rokach et al.28 was used. To a solution of 7 (96.5 mg, 0.37
mmol) in THF (2 mL) was added BuLi (1.6 M hexane, 0.23 mL,
0.37 mmol) at -78 °C. After 1 h the solution was slowly allowed to
reach -20 °C (1 h). After 2 h at -20 °C, the solution was recooled
to -78 °C and DMPU (0.2 mL) was added followed by the addition
of compound 5 (34.4 mg, 0.12 mmol). The reaction mixture was
slowly allowed to reach -30 °C (1 h) and then quenched by the ad-
dition of aq sat. NH4Cl solution (4 mL). The aqueous phase was ex-
tracted with EtOAc (4 × 5 mL) and the combined organic phases
were dried (Na2SO4). Concentration followed by flash column chro-
matography (EtOAc/cyclohexane, 0-5%) afforded recovered 7
(distilled, 64.0 mg, nearly 100%) in nearly 100% purity (GC) and
the desired product 8 (46.8 mg, 83%) as a colourless oil; purity
>99% (GC); [a]D25 +51.1 (c = 0.65, CHCl3).
(c = 0.58, CHCl3); mp 144-145 °C. {Lit.14 for enantiomer: [a]D
25
-76.5 (c = 0.52, CHCl3); mp 143-145 °C}. 3 [a]D25 +140.9 (c =
25
0.42, CHCl3). {Lit.14 for enantiomer: [a]D -137.3 (c = 0.66,
CHCl3)}. 4 [a]D25 +112.1 (c = 0.67, CHCl3); bp 185 °C/0.9 mbar.
{Lit.14 for enantiomer: [a]D25 -107.7 (c = 0.34, CHCl3); bp 180 °C/
1.2 mbar}.
(3R,4R)-3-Benzyloxy-4-(bromomethyl)tetrahydrothiophene (5)
Compound 5 was prepared from the corresponding alcohol 4, see
above, (stereoisomeric purity > 99%) using PPh3 and Br2 under
standard conditions.15 Bp 160 °C/0.7 mbar; [a]D25 +95.0 (c = 0.64,
CHCl3).
1H NMR (250 MHz, CDCl3): d = 2.55-3.10 (m, 5 H), 3.44 (dd, 1 H,
J = 6.5, 10.2 Hz), 3.50 (dd, 1 H, J = 5.2, 10.2 Hz), 4.01 (q, 1 H, J
= 6.4 Hz), 4.54 (d, 1 H, J = 11.7 Hz), 4.63 (d, 1 H, J = 11.7 Hz),
7.28-7.40 (m, 5 H).
1H NMR (250 MHz, CDCl3): d = 0.87 (d, 3 H, J = 6.5 Hz), 0.87-
1.05 (m, 5 H), 1.01 (d, 3 H, J = 6.5 Hz), 1.14-1.52 (m, 7 H), 1.69
(dd, 1 H, J = 6.7, 14.9 Hz), 1.76-1.97 (m, 5 H), 2.04 (dd, 1 H, J
= 2.5, 14.8 Hz), 2.58-2.90 (m, 7 H), 2.98 (dd, 1 H, J = 5.2, 10.9 Hz),
Synthesis 2000, No. 13, 1863–1867 ISSN 0039-7881 © Thieme Stuttgart · New York