Diastereoselective Synthesis of syn-Alkanetriols from a Glyceral Derivative via K-Selectride Reduction: Application to the Synthesis of a Pheromone of the Sugarcane Weevils

Article abstract of DOI:10.1055/s-2003-42422

K-selectride reduction of commercially available D-mannitol derived ketones 2b-i produced the corresponding alcohols 3b-i in good yields and with absolute syn-selectivity in almost all the cases. It was proposed that the bulky cyclohexylidene moiety of 3

Full text of DOI:10.1055/s-2003-42422

PAPER
2571
Diastereoselective Synthesis of syn-Alkanetriols from a Glyceral Derivative via
K-Selectride Reduction: Application to the Synthesis of a Pheromone of the
Sugarcane Weevils
S
ynthesis of Syn
-
h
A
lkanetriolsaskar Dhotare, Avinash Salaskar, Angshuman Chattopadhyay*
Bio-organic Division, Bhabha Atomic Research Centre, Mumbai-400085, India
E-mail: achat@apsara.barc.ernet.in
Received 30 July 2003; revised 8 August 2003
Stereodifferentiating reduction of prochiral ketones to
Abstract: K-selectride reduction of commercially available D-
mannitol derived ketones 2b–i produced the corresponding alcohols
3b–i in good yields and with absolute syn-selectivity in almost all
the cases. It was proposed that the bulky cyclohexylidene moiety of
produce chiral carbinols are well documented in the liter-
ature. In this regard, various chiral auxiliaries have been
developed for hydride transfer4,5 or catalytic hydrogena-
3 has a significant role in favoring the reduction with K-selectride tion.6 In addition, the reduction can also be carried out en-
zymatically.7 However, the reagent controlled methods, in
via Felkin–Anh model. Subsequently, one of the reduction product
3c has been exploited to synthesize the pheromone I of sugarcane
weevil.
general, do not provide the aliphatic carbinols in apprecia-
ble enantiomeric excess. Moreover, many auxiliaries are
expensive and/or have to be prepared via multiple steps.
From this perspective, the substrate-controlled strategy as
Key words: K-selectride, reduction, syn-alkanetriols, selectivity,
Felkin–Anh model
used in the present investigation was appealing as the pro-
tocol is easy, can be carried out with commercially avail-
Enantiomeric preparation of carbinols is a useful task in
organic synthesis, as chiral carbinols are present in a large
array of natural and unnatural compounds, and also act as
precursors for various other bioactive compounds such as
lactones, macrolides, furans, spiroketals, amines, hetero-
cycles, etc. Moreover, the hydroxyl functionality is ame-
nable to versatile synthetic maneuvers, which have been
facilitated due to the development of various protecting as
well as deprotecting groups of hydroxyls that can be oper-
ated selectively under varied conditions.1
able reducing agents, and does not require chiral
auxiliaries. Indeed, the substrate-controlled strategy has
been extensively used in recent years for the reduction of
- and -oxygenated ketones with various hydrides, viz.
ZnBH4,8 K-selectride,9 L-selectride,10 polymer bound silyl
hydride,11 etc.
Recently, we observed12 that K-selectride can reduce the
ketone 2a with exclusive syn-selectivity. We now wish to
investigate the viability of this strategy for a general syn-
thesis of syn-alkynols starting from D-mannitol. Hence,
the present study was conducted using the same hydride
and a series of ketones 2b–i. The required ketones were
prepared via addition of suitable Grignard reagents to 1
and subsequent oxidation of the resultant carbinols with
pyridinium chlorochromate (PCC).13 In almost all the cas-
es, the reduction (Scheme 1) proceeded smoothly at –78
°C furnishing the syn-alcohols 3b–i in excellent yields
within 2–2.5 hours. The results of the study are presented
in Table 1. Reductions of 2b–d and 2f–i were found to be
absolute syn-selective, as evident from the 1H NMR spec-
tra of the crude products. Interestingly, in the reduction of
2e, a little amount of the anti-alcohol 4e was also formed
as a minor product. The anti-product had a lower Rf com-
pared to the major syn-isomer (TLC) and could be easily
isolated by standard column chromatography. The syn-al-
cohols 3b–d were identified from their reported spectral
data.2a,f Compounds 3e–g were also identified from the
their 1H NMR spectra which showed characteristic CHO
and CH2O resonances in the region between = 3.5 and
4.2 as observed by us earlier for similar syn-carbinols.2a
Likewise, the 1H NMR spectra of syn-aromatic carbinols,
3h and 3i show two distinguishable multiplets at = 3.78
(2 H), 4.23 (1 H) and a doublet at 4.55 (1 H, J = 7.7 Hz)
for the carbinol methylene and methine protons.
Chiral secondary carbinols can be prepared by the addi-
tion of organometallics to aldehydes, and reduction of ke-
tones, wherein the enantioselectivity can be controlled by
an external chiral auxiliary (reagent control) or those
present in the substrates (substrate control). Recently, we
developed2a–c simple routes for the synthesis of several 1-
alkylglycerols. Our strategies were based on metal-medi-
ated addition of several organic halides to easily ac-
cessible (R)-2,3-cyclohexylideneglyceraldehyde (1).2a
Subsequently, some of the functionally rich product
carbinols with their existing stereochemistry were ex-
ploited by us to prepare various molecules such as deoxy-
sugars,2c,d sugar modified nucleosides,2e insect
pheromones,2f etc. This strategy has also been utilized by
others3 for the synthesis of bioactive molecules. However,
our organometalation-strategies proceeded with moderate
to excellent anti-selectivity. We now turned our attention
to prepare several syn-alkylglycerols staring from the
same substrate in connection with our ongoing synthetic
program.
SYNTHESIS 2003, No. 16, pp 2571–2575
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Advanced online publication: 07.10.2003
DOI: 10.1055/s-2003-42422; Art ID: Z11503SS
© Georg Thieme Verlag Stuttgart · New York

2572
B. Dhotare et al.
PAPER
Scheme 1 i) RMgBr, THF; ii) PCC, CH2Cl2; iii) K–selectride, THF,
–78 °C
Table 1 Results of the K-Selectride Mediated Reduction of 2b–i
Entry
Ketone
R
Yield (%) of
Carbinola
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
CH2=CHCH2
Et
95
89
90
89
87b
90
88
85
83
Scheme 2
n-Bu
n-C5H11
n-C10H21
n-C12H25
n-C14H29
Ph
regarding the isolation of the products and exploitation of
their functionalities. The partial protection in the internal
(R,R)-1,2-diols ensures versatile manipulation of each of
their hydroxyl groups. The use of partially protected
chiral 1,2-diols for the synthesis of complex biomolecules
is well known.16a,b Application of the above strategy on
readily available (S)-117 would provide the corresponding
(S,S)-diols. It is well known that these internal diols are el-
2g
2h
2i
4-MeC6H4
egantly
accessible
via
Sharpless
asymmetric
hydroxylation18a,b of internal (E)-olefins, however the en-
suing products, generally require further protection/
deprotection of their two free hydroxyls in careful manner
for their subsequent use. It is worth mentioning that Roush
et al.19a and Sato et al.19b have reported syn selective ally-
lation and alkylation, respectively, of glyceraldehydes de-
rivatives, but it is now evident that our strategy is
amenable to easy preparation of both allylation,12 and
alkylation products with excellent steroselectivity.
a Only syn-carbinols were obtained.
b In this case, the product was a mixture syn/anti in 91.7:8.3 ratio.
This high syn-selectivity in the reaction suggests that the
approach of hydride ion of K-selectride towards the carbo-
nyl takes place via Felkin–Anh model.14 Diastreoselection
of the hydride attack on the carbonyl group is primarily
governed by the conformationally strained five membered
1,3-dioxolane ring at its - and -positions in the sub-
strates. Between the two possible conformations (OC1
and OC2) (Scheme 2) in the Felkin–Anh model, the hy-
dride addition takes place via OC1 only, as it is thermody-
namically more favorable due to its having minimum
gauche interaction giving rise to syn-selectivity. The
bulky cyclohexyl group in 2 and the isopropyl group in the
selectride possibly prevent chelation of the K+ ion with the
-alkoxy and the carbonyl functionality of the substrates.
Consequently, the possibility of an -chelation controlled
reduction15 is feeble. This is corroborated by the fact that
reduction of a sterically uncrowded 2,3-epoxyketone with
the same reagent has been reported to proceed with abso-
lute anti-selectivity.9b Presumably, in this case, the ab-
sence of any bulky moiety in the substrate allowed the
reduction to proceed under chelation control. Thus, this
can be treated as a good example of substrate controlled
acyclic stereoselection for K-selectride reduction of ke-
tones.
Having established the above syn-selective reductive pro-
tocol, it was of interest to use it in total synthesis. This was
accomplished by converting one of the carbinols, 3c to
(2R)-2-methyloctan-4-ol (I), a male produced aggregation
pheromone component of the sugarcane weevils from
Curculiondae species, Metamasius hemipterus, Spheno-
phorus levis and Rhabdoscelus obscurus.20 Thus, benzy-
lation of 3c and subsequent acid hydrolysis of its acetal
function afforded the diol 5. Its periodate cleavage pro-
duced the aldehyde 6 which on Wittig olefination with the
phosphonium salt 7 afforded 8. This on hydrogenation af-
forded I (Scheme 3) with concomitant debenzylation. The
spectral and chiroptical data of I were in conformity with
those reported in literature.20
IR spectra were recorded on a Perkin-Elmer spectrophotometer
model 837. The NMR spectra were scanned with a Bruker Ac-200
(200 MHz) instrument in CDCl3 using TMS as internal standard.
Optical rotations were measured with a Jasco DIP-360 polarimeter.
Starting materials are commercially available and were used with-
out further purification, unless otherwise mentioned. The organic
extracts were dried over Na2SO4.
Thus, we have developed a facile and simple strategy to
generate fictionalized syn-alcohols. The presence of the
cyclohexylidene moiety provides operational advantage
Synthesis 2003, No. 16, 2571–2575 © Thieme Stuttgart · New York

PAPER
Synthesis of syn-Alkanetriols
2573
Scheme 3 Reagents and conditions: i) NaH, BnBr, THF; ii) TFA, H2O, CH2Cl2; iii) NaIO4, aq MeCN; iv) NaH, DMSO, Me2CHPPh3Br (7),
THF; v) H2, Pd-C, EtOH
Ketones 2b–i; General Procedure
(2R)-1,2-O-Cyclohexylidenepentadeca-3-one (2f)
Yield: 7.4 g (72%); [ ]D22 +21.52 (c = 0.38, CHCl3).
IR (film): 2921, 1715, 1463, 1369, 1160, 1099 cm–1.
1H NMR: = 0.87 (t, J = 6.4 Hz, 3 H), 1.24 (m, 20 H), 1.40–1.60
(m, 10 H), 2.60 (t, J = 7.2 Hz, 2 H), 3.95 (dd, J = 8.5, 5.6 Hz, 1 H),
4.17 (t, J = 8.6 Hz, 1 H), 4.41 (dd, J = 8.1, 5.6 Hz, 1 H).
Following the procedure reported earlier,2a a solution of 1 (5.1 g, 30
mmol) in THF (60 mL) was added to the respective Grignard re-
agent prepared from suitable bromide (75 mmol) and Mg (1.92 g,
80 mmol) in THF (100 mL). The product obtained after usual work-
up,2a was taken in CH2Cl2 (60 mL) and added to a stirred suspension
of PCC (9.7 g, 45 mmol) in CH2Cl2 (60 mL) at 0 °C. After stirring
the mixture for 3 h, when the reaction was over (TLC monitoring),
anhyd Et2O (100 mL) was added to the mixture. The supernatant
layer was filtered through a pad of silica gel, which was subsequent-
ly eluted with Et2O. The combined Et2O extracts were concentrated
in vaccuo and the residue was purified by chromatography (silica
gel, 0–10% EtOAc–hexane) to obtain pure 2.
Anal. Calcd for C21H38O3: C, 74.51; H, 11.31. Found: C, 74.28; H,
11.51.
(2R)-1,2-O-Cyclohexylideneheptadeca-3-one (2g)
Yield: 8.16 g (74%); [ ]D22 +5.06 (c = 3.75, CHCl3).
IR (film): 2923, 1715, 1468, 1369, 1163, 1097 cm–1.
1H NMR: = 0.87 (t, J = 6.2 Hz, 3 H), 1.25 (m, 24 H), 1.40–1.60
(m, 10 H), 2.66 (t, J = 7.2 Hz, 2 H), 3.96 (dd, J = 7.7, 5.6 Hz, 1 H),
4.19 (t, J = 8.1 Hz, 1 H), 4.38 (dd, J = 7.8, 5.6 Hz, 1 H).
(2R)-1,2-O-Cyclohexylidenepent-3-one (2b)
Yield: 4.34 g, (73%); [ ]D22 +8.24 (c = 1.2, CHCl3).
IR (film): 2921, 1715, 1466, 1369, 1162, 1097 cm–1.
Anal. Calcd for C23H42O3: C, 75.36; H, 11.55. Found: C, 75.08; H,
11.34.
1H NMR: = 1.0 (t, J = 6.4 Hz, 3 H), 1.40–1.60 (m, 10 H), 2.58 (q,
J = 6.8 Hz, 2 H), 3.95 (dd, J = 7.7, 5.6 Hz, 1 H), 4.19 (t, J = 7.8 Hz,
1 H), 4.43 (dd, J = 7.3, 5.6 Hz, 1 H).
(2R)-1,2-O-Cyclohexylidene-3-phenylpropan-3-one (2h)
Yield: 5.2 g (70%); [ ]D22 +1.56 (c = 0.255, CHCl3).
IR (film): 3100, 2862, 1695, 1607, 1448, 1368, 925 cm–1.
Anal. Calcd for C11H18O3: C, 66.64; H, 9.15. Found: C, 66.88; H,
9.34.
1H NMR: = 1.40–1.60 (m, 10 H), 4.28 (m, 2 H), 5.25 (t, J = 6.5
Hz, 1 H), 7.43–7.58 (m, 3 H), 7.99–8.02 (m, 2 H).
(2R)-1,2-O-Cyclohexylidenehept-3-one (2c)
Yield: 4.82 g (71%); [ ]D22 +2.0 (c = 1.1, CHCl3).
IR (film): 2920, 1715, 1466, 1370, 1162, 1097 cm–1.
Anal. Calcd for C15H18O3: C, 73.15; H, 7.36. Found: C, 73.41; H,
7.17.
1H NMR: = 0.92 (t, J = 6.2 Hz, 3 H), 1.23–1.38 (m, 4 H), 1.40–
1.60 (m, 10 H), 2.62 (t, J = 7.7 Hz, 2 H), 3.96 (dd, J = 7.7, 5.6 Hz,
1 H), 4.18 (t, J = 7.8 Hz, 1 H), 4.43 (dd, J = 7.1, 5.6 Hz, 1 H).
(2R)-1,2-O-Cyclohexylidene-3-(4 -methylphenyl)propan-3-one
(2i)
Yield: 5.5 g (71%); [ ]D22 +32.07 (c = 0.53, CHCl3).
Anal. Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 68.78; H,
9.54.
IR (film): 3080, 2861, 1694. 1607, 1448, 1369, 925 cm–1.
1H NMR: = 1.40–1.60 (m, 10 H), 2.40 (s, 3 H), 4.26 (m, 2 H), 5.23
(t, J = 6.5 Hz, 1 H), 7.24 (d, J = 5.4 Hz, 2 H), 7.88 (d, J = 8 Hz, 2 H).
(2R)-1,2-O-Cyclohexylidenoct-3-one (2d)
Yield: 5.2 g (72%); [ ]D22 +14.77 (c = 0.93, CHCl3).
IR (film): 2920, 1717, 1466, 1371, 1162, 1097 cm–1.
Anal. Calcd for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.59; H,
7.88.
1H NMR: = 0.95 (t, J = 6.2 Hz, 3 H), 1.23–1.37 (m, 6 H), 1.40–
1.60 (m, 10 H), 2.57 (t, J = 7.7 Hz, 2 H), 3.96 (dd, J = 7.7, 5.6 Hz,
1 H), 4.19 (t, J = 8.1 Hz, 1 H), 4.43 (dd, J = 7.8, 5.6 Hz, 1 H).
K-Selectride-Mediated Reduction of 2b–i; General Procedure
To a cooled (–78 °C) and stirred solution of the ketone 2b–i (15
mmol) in THF (75 mL) was added a solution of K-selectride (30 mL,
30 mmol, 1 M) in 0.5 h. The mixture was stirred at –78 °C for an
additional 2 h, gradually brought to r.t., and treated successively
with H2O and EtOAc. The organic layer was separated and the
aqueous layer was extracted with EtOAc. The combined organic ex-
tracts were washed with brine, dried, and concentrated in vacuo.
Column chromatography of the residue (silica gel, 0–15% EtOAc–
hexane) afforded the respective syn-isomers as the sole products.
Only for entry 5, the major syn-isomer 3e could be easily separated
from the minor anti-isomer 4e.
Anal. Calcd for C14H24O3: C, 69.96; H, 10.06. Found: C, 69.75; H,
9.80.
(2R)-1,2-O-Cyclohexylidenetrideca-3-one (2e)
Yield: 6.9 g (74%); [ ]D22 +22.5 (c = 0.12, CHCl3).
IR (film): 2923, 1715, 1466, 1369, 1162, 1101 cm–1.
1H NMR: = 0.92 (t, J = 6.5 Hz, 3 H), 1.30 (m, 16 H), 1.40–1.60
(m, 10 H), 2.65 (t, J = 7.5 Hz, 2 H), 4.00 (dd, J = 8.4, 5.6 Hz, 1 H),
4.22 (t, J = 7.9 Hz, 1 H), 4.46 (dd, J = 7.7, 5.7 Hz, 1 H).
Anal. Calcd for C19H34O3: C, 73.50.64; H, 11.04. Found: C, 73.68;
H, 11.32.
(2R,3R)-1,2-O-Cyclohexylidenetridecane-3-ol (3e)
Yield: 3.75 g (80%); Rf 0.72 (10% EtOAc–hexane); [ ]D +7.5
22
(c = 0.12, CHCl3).
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2574
B. Dhotare et al.
PAPER
IR (film): 3450, 1460, 1380, 1345, 1295, 1179, 1115, 1060, 955
cm–1.
1H NMR: = 0.87 (t, J = 6.2 Hz, 3 H), 1.28 (m, 18 H), 1.40–1.60
(m, 10 H), 2.2 (br s, D2O exchangeable, 1 H), 3.46 (m, 1 H), 3.70
(m, 1 H), 3.90–4.10 (m, 2 H).
THF (30 mL) was added to the stirred mixture at 50 °C. After stir-
ring for an additional 0.5 h, H2O was added to the mixture. The or-
ganic layer was separated and the aqueous layer was extracted with
H2O. The combined organic extracts were washed with H2O, brine,
and dried. Removal of the solvent afforded the O-benzylated com-
pound in almost quantitative yield. This was dissolved in 90% aq
CF3CO2H (15 mL) at 0 °C and the mixture was stirred at the same
temperature for 4 h until the disappearance of the benzylated com-
pound (TLC monitoring). The mixture was extracted with CHCl3,
the organic extract was washed with 10% aq NaHCO3, H2O, and
brine. Solvent removal under reduced pressure, followed by column
chromatography of the residue (silica gel, 0–5% MeOH in CHCl3)
afforded pure 5 (0.990 g, 56%); [ ]D22 –11.04 (c = 0.059, CHCl3).
Anal. Calcd for C19H36O3: C, 73.30; H, 11.61. Found: C, 73.55; H,
11.34.
(2R,3S)-1,2-O-Cyclohexylidenetridecane-3-ol (4e)
Yield: 0.340 g (7%); Rf 0.66 (10% EtOAc–hexane); [ ]D22 +4.21
(c = 0.83, CHCl3).
IR (film): 3450, 1460, 1380, 1350, 1295, 1179, 1120, 1060, 955
cm–1.
1H NMR: = 0.86 (t, J = 6.2 Hz, 3 H), 1.26 (m, 18 H), 1.40–1.60
IR (film): 3405, 3108, 1496 cm–1.
1H NMR: = 0.95 (t, J = 6.2 Hz, 3 H), 1.37 (m, 6 H), 1.65 (br s, D2O
exchangeable, 2 H), 3.49 (m, 1 H), 3.60–3.72 (m, 3 H), 4.48 (d,
J = 11.7 Hz, 1 H), 4.68 (d, J = 11.7 Hz, 1 H), 7.35 (m, 5 H).
(m, 10 H), 1.90 (br s, D2O exchangeable, 1 H), 3.70–4.20 (m, 4 H).
Anal. Calcd for C19H36O3: C, 73.30; H, 11.61. Found: C, 73.44; H,
11.87.
Anal. Calcd for C14H22O3: C, 70.56; H, 9.30. Found: C, 70.75; H,
9.55.
(2R,3R)-1,2-O-Cyclohexylidenepentadecane-3-ol (3f)
Yield: 4.56 g (90%); [ ]D22 +7.44 (c = 0.83, CHCl3).
(2R)-Benzyloxyhexanal (6)
To a solution of 5 (0.952 g, 4 mmol) in 60% aq MeCN (20 mL) was
added NaIO4 (1.71 g, 8 mmol) in one portion. The mixture was
stirred at r.t for 1 h and filtered. The residue was washed with
CHCl3. The combined organic extracts were washed with H2O,
brine, and dried. Solvent removal under reduced pressure, followed
by filtration of the residue through a short pad of silica gel eluting
with 20% EtOAc in hexane to afford 6 (0.668 g, 81%) which was
found to be unstable on standing, and hence was used immediately
for the next step; [ ]D22 +19.59 (c = 0.087, CHCl3).
IR (film): 3450, 1460, 1380, 1345, 1295, 1179, 1115, 1060, 955
cm–1.
1H NMR: = 0.87 (t, J = 6.2 Hz, 3 H), 1.26 (m, 20 H), 1.40–1.60
(m, 10 H), 2.20 (br s, D2O exchangeable, 1 H), 3.46 (m, 1 H), 3.70
(m, 1 H), 3.90–4.10 (m, 2 H).
Anal. Calcd for C21H40O3: C, 74.07; H, 11.84. Found: C, 74.28; H,
12.08.
(2R,3R)-1,2-O-Cyclohexylideneheptadecane-3-ol (3g)
Yield 4.84 g, (88%); [ ]22D 19.35 (c = 0.062, CHCl3).
IR (film): 3058, 2715, 1731 cm–1.
1H NMR: = 0.90 (t, J = 7 Hz, 3 H), 1.26–1.47 (m, 4 H), 1.64–1.71
(m, 2 H), 3.75 (m, 1 H), 4.52 (d, J = 11.7 Hz, 1 H), 4.68 (d, J = 11.7
Hz, 1 H), 7.36 (m, 5 H), 9.66 (d, J = 2.1 Hz, 1 H).
IR (film): 3450, 1460, 1380, 1345, 1295, 1179, 1115,1060, 955
cm–1.
1H NMR (CDCl3): = 0.86 (t, J = 6.2 Hz, 3 H), 1.26 (m, 22 H),
1.40–1.60 (m, 10 H), 2.30 (br s, D2O exchangeable), 3.46 (m, 1 H),
3.70 (m, 1 H), 3.90-4.10 (m, 2 H).
(4R)-2-Methyl-4-benzyloxyoct-2-ene (8)
To a solution of Na-dimsyl [prepared by heating pentane-washed
NaH (50% suspension in oil, 0.192 g, 4 mmol) and DMSO (30 mL)
at 70 °C], was added isopropylphosphonium bromide (7; 1.62 g, 4.2
mmol) was added at r.t. and the mixture stirred for 1 h. The resulting
red solution was cooled to 0 °C and to this was added a solution of
6 (0.522 g, 3.2 mmol) in THF (20 mL). The mixture was stirred at
0 °C for 1 h, and at r.t. overnight. It was treated with excess H2O and
extracted with hexane. The organic extract was washed with H2O,
brine, and dried. Removal of solvent under reduced pressure afford-
ed a residue which on chromatography (silica gel, 0–15% Et2O in
hexane) afforded 8 (0.522 g, 70%); [ ]D22 +15.14 (c = 0.53, CHCl3).
Anal. Calcd for C23H44O3: C, 74.95; H, 12.03. Found: C, 74.78; H,
12.22.
(2R,3R)-1,2-O-Cyclohexylidene-3-phenylpropane-3-ol (3h)
Yield: 3.15 g (85%); [ ]D22 –7.5 (c = 0.8, CHCl3).
IR (film): 1693, 1607, 925 cm–1.
1H NMR: = 1.4–1.6 (m, 10 H), 3.0 (br s, D2O exchangeable), 3.78
(m, 2 H), 4.23 (m, 1 H), 4.55 (d, J = 7.8 Hz, 1 H), 7.39 (m, 5 H).
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.68; H, 8.
30.
IR (film): 3063, 3029, 1673, 1028, 994 cm–1.
1H NMR: = 0.91 (t, J = 6.2 Hz, 3 H), 1.28–1.41 (m, 6 H), 1.62 (s,
3 H), 1.77 (s, 3 H), 3.96–4.07 (m, 1 H), 4.35 (d, J = 12 Hz, 1 H),
4.55 (d, J = 12 Hz, 1 H), 5.09 (d, J = 9.24 Hz, 1 H), 7.31 (m, 5 H).
(2R,3R)-1,2-O-Cyclohexylidene-3-(4 -methylphenyl)propane-3-
ol (3i)
Yield: 3.25 g (83%); [ ]D22 –20.08 (c = 0.747, CHCl3).
Anal. Calcd for C16H24O: C, 82.70; H, 10.41. Found: C, 82.55; H,
10.55.
IR (film): 1694, 1607, 925 cm–1.
1H NMR: = 1.40–1.60 (m, 10 H), 2.39 (s, 3 H), 2.80 (br s, D2O
exchangeable, 1 H), 3.78 (m, 2 H), 4.23 (m, 1 H), 4.55 (d, J = 7.8
Hz, 1 H), 7.39 (m, 4 H).
(4R)-2-Methyloctan-4-ol (I)
Following a standard procedure, a solution of 8 (0.522 g) in EtOH
(30 mL) was hydrogenated in the presence of 10% Pd-C catalyst
(100 mg) using a Paar apparatus. The mixture was filtered and the
filtrate was concentrated under reduced pressure. The residue was
taken in Et2O. The organic layer was washed with H2O, brine and
then dried. Solvent removal and column chromatography of the res-
idue (silica gel, 0–15% EtOAc–hexane) afforded I (200 mg, 78%);
[ ]D22 –10.9 (c = 1.4, CHCl3) {Lit.20 [ ]D22 –10.4 (c = 0.5, CHCl3)}.
Anal. Calcd For C16H22O3: C, 73.25; H, 8.45. Found: C, 73.48; H,
8.19.
(2R,3R)-3-O-Benzylheptane-1,2-diol (5)
To a stirred suspension of pentane-washed NaH (0.360 g, 50% sus-
pension in oil, 0.0075 mol) in THF (50 mL) was added dropwise 3c
(1.71 g, 0.0075 mol) in THF (30 mL) in 0.5 h. The mixture was gen-
tly heated to 50 °C for 1 h. Benzyl bromide (1.29 g, 0.0075 mol) in
IR (film): 3350, 2966, 2830, 1468, 1368, 1026 cm–1.
Synthesis 2003, No. 16, 2571–2575 © Thieme Stuttgart · New York

PAPER
Synthesis of syn-Alkanetriols
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1H NMR: = 0.90 (d, J = 6.4 Hz, 3 H), 0.92 (d, J = 6.4 Hz, 3 H),
1.29 (m, 11 H), 1.70–1.76 (m, 1 H), 2.05 (br s, 1 H), 3.60–3.78 (m,
1 H).
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Acknowledgment
We are thankful to Mrs Sunita Gamre for preparing the compound
2g for us. We also thank Dr. Subrata Chattopadhyay for his valuable
discussion regarding this work.
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Synthesis 2003, No. 16, 2571–2575 © Thieme Stuttgart · New York