Facile approach towards the synthesis of homochiral functionalised alcohols from 4-O-[(tert)-butyldimethylsilyl]2,3-O-cyclohexylidene-L-threose of (L)-(+)-tartaric acid origin

Article abstract of DOI:10.1016/S0957-4166(98)00282-1

(L)-(+)-Diethyl tartarate 2 has been transformed into the aldehyde 6. Grignard additions to 6 take place with moderate diastereoselectivity giving predominant formation of the anti products 8a-e. However, in each case the diastercoalcohols are easily sepa

Full text of DOI:10.1016/S0957-4166(98)00282-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2715–2723
Facile approach towards the synthesis of homochiral
functionalised alcohols from 4-O-[(tert)-butyldimethylsilyl]-
2,3-O-cyclohexylidene-L-threose of (L)-(+)-tartaric acid origin
Angshuman Chattopadhyay ∗ and Bhaskar Dhotare
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai-400085, India
Received 16 June 1998; accepted 15 July 1998
Abstract
(L)-(+)-Diethyl tartarate 2 has been transformed into the aldehyde 6. Grignard additions to 6 take place with
moderate diastereoselectivity giving predominant formation of the anti products 8a–e. However, in each case
the diastereoalcohols are easily separable by column chromatography giving rise to the formation of a series of
functionalised homochiral alcohols 7 and 8. On the other hand Zn mediated allylation and propargylation of 6
in the presence of water proceeded efficiently with almost absolute (>99%) stereoselective formation of versatile
functionalised homoallylic 8d and homopropargylic 8e alcohols respectively. © 1998 Elsevier Science Ltd. All
rights reserved.
1. Introduction
Recent years have witnessed a tremendous upsurge in the synthesis of optically active compounds
of biological relevance. In this endeavour, the chiron approach1 which deals with the exploitation of
suitably functionalised chiral building blocks, has drawn considerable attention. These chirons on careful
functional and stereochemical manipulation generate the basic structural units that are present in the
target molecules. For such operations a major prerequisite is the availability of suitably functionalised
chirons in enantiomerically pure form. Any polyfunctional chiron is said to have good synthetic potential
if its functional groups are amenable for chemical as well as stereochemical manipulation independently
of each other. One convenient approach to prepare such chiral intermediates bearing contiguous stereo-
centres, is based on the stereodifferentiating addition2–4 of simple or functionalised organometallics to
α- and/or β-alkoxy3a–j or other heterosubstituted3k–m acyclic carbonyls. Consequently, there has been a
considerable amount of recent interest in understanding the acyclic stereochemistry involved during such
∗
Corresponding author.
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00282-1

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organometallations.2–4 The advantage for choosing acyclic carbonyls lies with the possible stereochem-
ical flexibility for the addition of a given nucleophile which can be achieved by changing metal, solvent
or other additives. However, from a synthetic viewpoint an organometallation which is associated with
a very high stereoselectivity is always desirable. In the case of poor or moderately selective addition
each of the resulting diastereoalcohols needs to be isolated in pure form from the product mixture
without being derivatised as this may not be compatible with the subsequent reactions. Usually for a
polyhydroxylated carbonyl substrate, choosing the right combination of O-protecting groups, means that
each of the hydroxyl functionalities of the resulting diastereoalcohols after organometallation become
amenable for selective manipulation. In view of these facts, there is always scope for the development
of an operationally simple procedure for the preparation of polyoxygenated chirons with hydroxyls
versatilely and stably protected.
During our ongoing programme on the synthesis of bioactive compounds, we have developed5 a
convenient synthesis of a chemically stable (R)-2,3-cyclohexylideneglyceraldehyde 1 of (D)-mannitol
origin. Subsequently 1 has been treated with several Grignard reagents5 under anhydrous conditions
and also subjected to Barbier type allylation, crotylation and propargylation6 in the presence of water,
following Luche’s procedure,7 to synthesise a series of homochiral functionalised alcohols which have
good potential as functionalised chirons. We observed that the presence of stable cyclohexylidene
functionality generates hydrophobicity in 1 and the product alcohols giving rise to an operational
advantage during the organometallations of 1 in the presence of water and also allowing acid treatment
which is required to facilitate the work up after the reactions in some cases. We have subsequently
utilised three of these addition products of 1 as useful chirons to develop facile routes for the synthesis of
coriolic acid,5 LTB4 and 2,3-dideoxy-3-substituted sugar modified nucleosides8 which have significant
6
biological importance.
We report here the synthesis of another useful aldehyde 6 which has been prepared from commercially
available (L)-(+)-diethyl tartarate 2 and discuss our study on some simple organometallations of 6.
This has been initiated with a view to developing an easy approach for the synthesis of a series of
homochiral alcohols bearing additional stereogenic centres compared to those generally preparable
from 1. Incidentally, several reports9–11 are available regarding the organometallation of several other
aldehydes similar to 6 originating from 2 bearing different O-protecting groups. We also present here a
comparative survey of our investigation with those done by others.
2. Results and discussion
To obtain 6, 2 was first ketalised on treatment with cyclohexanone following a standard procedure, to
give 3 in high yield. Compound 3, without being purified further by chromatography, was directly treated
with LiAlH4 to afford the diol 4. Monosilylation of the C2-symmetric diol 4 has been performed easily to
give 5 in good yield. Oxidation of the purified alcohol 5 has been found to be effected smoothly using a
recently reported method12 to give the aldehyde 6. The formation of 6 was confirmed by IR and 1H-NMR
spectra of the residue after usual extraction and solvent removal of the oxidation product. Though not
very stable, the aldehyde 6 was sufficiently pure (TLC) and could be used for further reaction without
any purification.
Compound 6 was subjected to a number of Grignard additions (as shown in Scheme 1). In all
cases, the reaction proceeded smoothly producing the desired products with good yield. In each case
the reaction was associated with the formation of a major amount of anti alcohols 8 and a minor but
appreciable amount of the syn alcohols 7 of the diastereoisomers which were easily separable by column

A. Chattopadhyay, B. Dhotare / Tetrahedron: Asymmetry 9 (1998) 2715–2723
2717
1
chromatography (SiO2). The H-NMR spectra chemical shifts of the CHO and CH2O of the alcohols
show two distinguishable patterns of multiplets with a broad one in the region of δ 3.5–4.25 for all
the syn products 7a–e and a compact one in the region of δ 3.6–4.0 for the anti products 8a–e for five
protons. However in order to establish the absolute configuration of the stereogenic centre, formed by
the organometallation, 8b, one of the anti products was chosen as a representative example. This was
sequentially subjected to benzoylation and then deketalization (CF3COOH/water) at low temperature.
Finally NaIO4 cleavage of the resulting diol 9 afforded 10, the coriolic acid synthon whose spectral and
optical data were in accordance with those already reported by us.5
Scheme 1.
The advantages of this approach are the operational simplicity during the preparation of 6 and its good
reactivity towards the practically viable Grignard additions, which are followed by easy isolation and
separability of the diastereoalcohols 7 and 8. Here, the moderate selectivity of the Grignard additions
has been exploited to make both the diastereoalcohols 7 and 8 available on a preparative scale with high
enantiopurity (see Table 1). As in the case for 1 and its addition products,5,6 the poor water solubility
and relative functional stability of 6, 7 and 8 due to the presence of cyclohexylidene moiety, also add
advantages to the entire operation. Reports are available10 for Grignard addition to the corresponding
1-O-benzyl-2,3-bis-(methoxymethyl) derivative which gives predominantly the syn product. In their case
the addition is associated with an α-chelate model4b whereas in our case the predomonancy of the
anti products suggests that the addition takes place in accordance with the Felkin–Anh model.4h,i It is
generally observed that Grignard addition to α-OMOM-carbonyls gives rise to syn products4b However
this requires handling of highly toxic MOMCl which is unwarranted for practical purposes. Similar to

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A. Chattopadhyay, B. Dhotare / Tetrahedron: Asymmetry 9 (1998) 2715–2723
Table 1
Organometallation of 6
our case, the anti selectivity of Grignard addition was reported for a 2,3-O-isopropylidene derivative11
corresponding to 6. Hence it can be concluded that the stereochemical flexibility during the Grignard
additions of (L)-threose can be achieved by changing the O-protecting groups.
The efficacy of our approach is further established by the possible isolation of both the diastereomers of
the homoallylic 7d and 8d and homopropargylic 7e and 8e alcohols which are rich with diverse function-
alities. It should be recalled that Mukaiyama’s group9 have investigated varied types of organometallation
of a 2,3-O-isopropylidene derivative of DET origin. Allylation of their aldehyde with diallyltin in anhy-
drous medium afforded the homoallylated alcohols with a syn:anti ratio of 1:9 which were then separated
by flash chromatography. They subsequently utilised the purified anti isomer as a useful building block
for stereoselective synthesis of a number of diversely functionalized monosaccharides. However, in the
two cases9,11 the presence of the isopropylidene moiety in the aldehydes is likely to restrict their use
under all conditions due to its greater affinity to be hydrolysed in a mild acidic environment during a
reaction or work up causing difficulty in selective manipulation of the hydroxyl groups of their products.
The enormous synthetic potential of versatilely functionalised allylated9 and propargylated products
(entries d and e) led us to explore the viability of a more practical approach for their preparation. In
view of this, 6 was subjected to Barbier type allylation and propargylation in the presence of water
using Luche’s procedure.7 Both the reactions were carried out following similar experimental conditions
as reported by us earlier in the case of 1.6 To our satisfaction, in both the cases using excess Zn and
bromide, compound 6 was found to be reacted completely producing the desired homoallylic (entry d ii)
and homopropargylic alcohols (entry e ii) in appreciable yield. The isolation of the product was facilitated
during work up by treating the filtrate with acid to dissolve the suspended turbid material without
affecting the stable cyclohexylidene moiety. The reactions were associated with a high improvement
of stereoselectivity showing almost total formation (>99%) of anti products 8d and 8e. This was evident
1
from the TLC and the spectral pattern in the region of δ 3.5–4.0 in the H-NMR of the crude residue
after the usual extraction and solvent removal under reduced pressure. Furthermore, any syn isomer
could not be isolated by us after column chromatography. In this case the propargylation proceeded with
the formation of a negligible amount (<1.5%) of the allene compound which was also evident from the
1H-NMR spectrum of the residue (entry e ii).
In conclusion, 6 can be considered to be an easily accessible and effective precursor for the practical
synthesis of a variety of functionalised diastereoalcohols whose contiguous stereocentres make them
useful chiral building blocks for the synthesis of bioactive molecules. Moreover considering all the
operational advantages associated with 6 viz. its relatively easy preparation without handling any toxic
materials, functional stability, sufficiently good reactivity even in the presence of water, separability of

A. Chattopadhyay, B. Dhotare / Tetrahedron: Asymmetry 9 (1998) 2715–2723
2719
the diastereoisomers of its organometallated products by simple means like column chromatography etc.,
it has apparently an edge over the other reported aldehydes9–11 of the same origin 2 from a practical
viewpoint. Using the same reaction protocol with the commercially available enantiomer of 2, the
enantiomeric series of polyoxygenated chirons can be achieved with equal ease.
3. Experimental section
Chemicals used as starting materials are commercially available and were used without further purific-
ation unless otherwise mentioned. The IR spectra were recorded with a Perkin–Elmer spectrophotometer
model 837. The PMR spectra were scanned with a Brucker AC-200 (200 MHz) instrument in CDCl3. The
optical rotations were measured with a Jasco DIP-360 polarimeter. The organic extracts were desiccated
over Na2SO4.
3.1. (2S,3S)-2,3-Cyclohexylidene-butan-1,2,3,4-tetrol 4
A solution of diethyl (L)-tartarate 2 (30.9 g, 0.15 mol), cyclohexanone (16 g, 0.16 mol) and PTS (∼100
mg) in benzene (200 ml) was refluxed in a Dean–Stark apparatus for 6 h with continuous removal of
water. The reaction was monitored with TLC and stopped when the starting material had been consumed.
The solution was washed with 10% aqueous Na2CO3 and water and dried. Solvent removal under reduced
pressure afforded the residue containing diester 3 in almost quantitative yield. It was taken in THF (100
ml). The solution was added dropwise to a cooled suspension of LiAlH4 (8 g, 0.21 mol) in THF (100 ml)
over a period of 2 h. The mixture was refluxed for another 2 h. Saturated aqueous solution of Na2SO4
was added dropwise to decompose the excess hydride. The mixture was filtered and the precipitate was
washed with CHCl3. Solvent removal under reduced pressure and column chromatography of the residue
20
(silica gel, 0–5% MeOH in CHCl3) afforded the diol 4. Yield: 23.5 g (77.5%); [α]D −5.27 (c 2.2,
1
CHCl3); IR (film): 3462, 1466, 1363, 1064, 837; H-NMR (CDCl3) δ 1.5–1.6 (m, 10H), 2.7 (bs, D2O
exchangeable, 2H), 3.6–4.2 (m, 6H). Anal. calcd For C10H18O4: C, 59.38; H, 8.97. Found: C, 59.19; H,
9.18.
3.2. (2S,3S)-2,3-Cyclohexylidene-4-silyloxybutane-1,2,3-triol 5
To a stirred mixture of 4 (10.1 g, 0.05 mol) and imidazole (5.1 g, 0.075 mol) in CH2Cl2 (100 ml)
was added tert-butyldimethylsilyl chloride (7.53 g, 0.05 mole) in portions over a period of 1.5 h. It was
stirred for 2 h more and poured into water. After the usual extraction and solvent removal, the residue
was chromatographed over SiO2 column (0–20% EtOAc in petroleum ether) to afford 5. Yield: 11.8 g
(74.7%); [α]D20 +3.54 (c 3.9, CHCl3); IR (film) 3484, 2855, 1474, 1369, 1256, 1011, 950, 845; 1H-NMR
(CDCl3) δ 0.06 (s, 6H), 0.88 (s, 9H), 1.5–1.6 (m, 10H), 2.9 (bs, D2O exchangeable, 1H), 3.6–4.2 (m,
6H). Anal. calcd for C16H32O4Si: C, 60.71; H, 10.19. Found: C, 60.87; H, 10.28.
3.3. 4-O-[(tert)-Butyldimethylsilyl]-2,3-O-cyclohexylidene-L-threose 6
A mixture of 5 (3.16 g, 0.01 mol), DMSO (1.8 ml, 0.025 mol) and P2O5 (3.5 g, 0.025 mol) in CH2Cl2
(25 ml) was stirred at room temperature for 4 h. Triethylamine (5.6 ml, 0.04 mol) was added to it. The
mixture was stirred for 2 h more, cooled with ice–water and treated with 5% aqueous HCl (15 ml). The
organic layer was washed successively with water and brine and dried. Solvent removal under reduced

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A. Chattopadhyay, B. Dhotare / Tetrahedron: Asymmetry 9 (1998) 2715–2723
pressure gave the residue (2.7 g, 84.6%) containing the aldehyde 6. As the aldehyde was found to be
sufficiently pure but unstable on long standing, it was immediately used as such for the next step without
being purified further. IR (film): 2855, 2720, 1735, 1474, 1369, 1256, 1120, 1011, 950, 845, 800; the
1
pertinent signals and their relative intensity in H-NMR (CDCl3) δ 0.06 (s, 6H), 0.88 (s, 9H), 1.5–1.6
(m, 10H), 3.7–4.4 (m, 4H), 9.8 (d, J=1.5 Hz, 1H).
3.4. General procedure for the preparation of 7 and 8
To a stirred solution of Grignard reagent at −50°C, prepared by treating halide (0.025 mol) with a
suspension of Mg (720 mg, 0.03 g equiv.) in the required solvent (60 ml) (as shown in Table 1), was
added 6 (3.14 g, 0.01 mol) in THF (30 ml) over a period of 1 h. The mixture was stirred at −50°C for
3 h and at room temperature overnight to ensure completion of the reaction. Saturated aqueous NH4Cl
was added followed by extraction with ether. The organic layer was washed with water and brine, dried,
and evaporated under reduced pressure with 0–20% ethyl acetate in hexane resulting in the separation of
pure 7 and 8. In all the cases the minor syn isomer 7 was eluted first followed by the major anti isomer 8.
The Rf values on the TLC (16 cm plate) of all the isomers have been indicated.
3.5. 1-[(tert-Butyldimethylsilyl)oxy]-2,3-O-cyclohexylidene-octane-2,3,4-triol 7a and 8a
3.5.1. Minor (2S,3S,4R)-isomer 7a
20
Yield 901 mg (25.5%); Rf 0.63 (20% EtOAC/hexane); [α]D −3.33 (c 0.9, CHCl3); IR (film) 3461,
1
2857, 1463, 1363, 1254, 837; H-NMR (CDCl3) δ 0.06 (s, 6H), 0. 87 (s, 9H overlapped with a t, J=6
Hz, 3H), 1.24 (bs, 1H, D2O exchangeable), 1.3–1.4 (m, 6H), 1.5–1.6 (m, 10H), 3.5–4.25 (m, 5H). Anal.
calcd for C20H40O4Si: C, 64.46; H, 10.82. Found: C, 64.57; H, 10.62.
3.5.2. Major (2S,3S,4S)-isomer 8a
20
Yield 2.16 mg (57.9%); Rf 0.53 (20% EtOAC/hexane); [α]D −1.17 (c 1.08, CHCl3); IR (film) 3455,
2858, 1463, 1363, 1253, 837; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0. 87 (s, 9H overlapped with a t, J=6 Hz,
3H), 1.3–1.4 (m, 6H), 1.5–1.6 (m, 10H), 3.06 (bs, 1H, D2O exchangeable), 3.6–4.0 (m, 5H). Anal. calcd
for C20H40O4S: C, 64.46; H, 10.82. Found: C, 64.63; H, 10.59.
3.6. 1-[(tert-Butyldimethylsilyl)oxy]-2,3-O-cyclohexylidene-nonane-2,3,4-triol 7b and 8b
3.6.1. Minor (2S,3S,4R)-isomer 7b
20
Yield 877 mg (22.7%); Rf 0.66 (20% EtOAC/hexane); [α]D −5.79 (c 1.06, CHCl3); IR (film) 3464,
1
2857, 1464, 1365, 1256, 837; H-NMR (CDCl3) δ 0.06 (s, 6H), 0.87 (s, 9H overlapped with a t, J=6
Hz, 3H), 1.3–1.4 (m, 8H), 1.5–1.6 (m, 10H), 2.35 (bs, 1H, D2O exchangeable), 3.5–4.25 (m, 5H). Anal.
calcd for C21H42O4Si: C, 65.23; H, 10.95. Found: C, 65.34; H, 10.72.
3.6.2. Major (2S,3S,4S)-isomer 8b
20
Yield 2.18 mg (56.7%); Rf 0.57 (20% EtOAC/hexane); [α]D −1.15 (c 1.06, CHCl3); IR (film) 3464,
2858, 1463, 1366, 1256, 837; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0. 87 (s, 9H overlapped with a t, J=6 Hz,
3H), 1.3–1.4 (m, 8H), 1.5–1.6 (m, 10H), 3.06 (bs, 1H, D2O exchangeable), 3.6–4.0 (m, 5H). Anal. calcd
for C21H42O4Si: C, 65.23; H, 10.95. Found: C, 65.37; H, 10.89.

A. Chattopadhyay, B. Dhotare / Tetrahedron: Asymmetry 9 (1998) 2715–2723
2721
3.7. 1-[(tert-Butyldimethylsilyl)oxy]-2,3-O-cyclohexylidene-tetradecane-2,3,4-triol 7c and 8c
3.7.1. Minor (2S,3S,4R)-isomer 7c
20
Yield 865 mg (18.9%); Rf 0.71 (20% ether/hexane); [α]D +2.46 (c 3.6, CHCl3); IR (film) 3464,
2857, 1464, 1365, 1256, 837; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0.9 (s, 9H overlapped with a t, J=6 Hz,
3H), 1.3–1.4 (m, 18H), 1.5–1.6 (m, 10H), 2.5 (bs, 1H, D2O exchangeable), 3.5–4.25 (m, 5H). Anal. calcd
for C26H52O4Si: C, 68.36; H, 11.48. Found: C, 68.57; H, 11.62
3.8. Major (2S,3S,4S)-isomer 8c
20
Yield 2.64 mg (57.9%); Rf 0.64 (20% ether/hexane); [α]D +14.07 (c 2.6, CHCl3); IR (film) 3464,
2858, 1463, 1366, 1256, 837; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0. 9 (s, 9H overlapped with a t, J=6 Hz,
3H), 1.3–1.4 (m, 18H), 1.5–1.6 (m, 10H), 3.06 (bs, 1H, D2O exchangeable), 3.6–4.0 (m, 5H). Anal. calcd
for C26H52O4Si: C, 68.36; H, 11.48. Found: C, 68.63; H, 11.69.
3.9. 1-[(tert-Butyldimethylsilyl)oxy]-2,3-O-cyclohexylidene-6-heptene-2,3,4-triol 7d and 8d
3.9.1. Minor (2S,3S,4R)-isomer 7d
20
Yield 807 mg (22.6%); Rf 0.72 (20% EtOAc/hexane); [α]D −5.14 (c 1.56, CHCl3); IR (film) 3453,
1
3082, 2857, 1640, 1364, 1254, 1004, 941, 911, 837; H-NMR (CDCl3) δ 0.06 (s, 6H), 0.88 (s, 9H),
1.5–1.6 (m, 10H), 2.2–2.5 (m, 2H), 2.9 (bs, 1H, D2O exchangeable), 3.5–4.25 (m, 5H), 5.0–5.1 (m, 2H),
5.7–5.9 (m, 1H). Anal. calcd for C19H36O4Si: C, 64.0; H, 10.18. Found: C, 63.89; H, 10.26.
3.9.2. Major (2S,3S,4S)-isomer 8d
Yield 2.17 mg (60.9%); Rf 0.65 (20% EtOAc/hexane); [α]D +9.09 (c 1.68, CHCl3); IR (film) 3455,
3074, 2857, 1640, 1471, 1365, 1253, 1004, 941, 911, 837; H-NMR (CDCl3) δ 0.06 (s, 6H), 0.88 (s,
20
1
9H), 1.5–1.6 (m, 10H), 2.2–2.5 (m, 2H), 2.75 (bs, 1H, D2O exchangeable), 3.6–4.0 (m, 5H) 5.0–5.1 (m,
2H), 5.7–5.9 (m, 1H). Anal. calcd for C19H36O4Si: C, 64.0; H, 10.18. Found: C, 63.77; H, 10.19.
3.10. 1-[(tert-Butyldimethylsilyl)oxy]-2,3-O-cyclohexylidene-6-heptyne-2,3,4-triol 7e and 8e
3.10.1. Minor (2S,3S,4R)-isomer 7e
20
Yield 522 mg (14.7%); Rf 0.63 (20% EtOAc/hexane); [α]D −3.7 (c 3.06, CHCl3); IR (film) 3440,
3310, 2857, 1369, 1254, 950, 845; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0.90 (s, 9H), 1.5–1.6 (m, 10H), 2.05
(t, J=1.5 Hz, 1H), 2.4–2.6 (m, 2H), 3.05 (bs, 1H, D2O exchangeable), 3.5–4.25 (m, 5H). Anal. calcd for
C19H34O4Si: C, 64.36; H, 9.66. Found: C, 64.56; H, 9.82.
3.10.2. Major (2S,3S,4S)-isomer 8e
20
Yield 2.26 mg (63.9%); Rf 0.57 (20% EtOAc/hexane); [α]D +3.57 (c 1.06, CHCl3); IR (film) 3445,
3300, 2857, 1471, 1365, 1253, 847; 1H-NMR (CDCl3) δ 0.06 (s, 6H), 0. 88 (s, 9H), 1.5–1.6 (m, 10H),
2.05 (t, J=1.5 Hz, 1H), 2.4–2.6 (m, 2H), 2.9 (bs, 1H, D2O exchangeable), 3.6–4.0 (m, 5H). Anal. calcd
for C19H34O4Si: C, 64.36; H, 9.66. Found: C, 64.27; H, 9.51.

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3.11. General procedure for allylation and propargylation of 6
To a cooled (10°C) and well-stirred mixture of 6 (4.7 g, 0.015 mol), Zn dust (2 g, 0.03 mol for
allylation; 3.4 g, 0.052 mol for propargylation) and bromide (3.63 g for allylation, 0.03 mol; 5.4 g
for propargylation, 0.045 mol) in THF (50 ml) was added a saturated aqueous solution of NH4Cl (1
ml) in portions over a period of 0.5 h. The reaction started vigorously soon after the addition of the
first portion of the salt solution. The mixture was stirred for 4 h more for allylation or 6 h more for
propargylation till the complete disappearance of the aldehyde (TLC). The mixture was filtered and
washed with EtOAc. The organic layer was washed with 5% HCl to dissolve the suspended turbid
material, then successively with 10% NaHCO3, water and dried. Solvent removal under reduced pressure
and column chromatography of the residue (silica gel, 0–20% EtOAc in petroleum ether) afforded 8d
(3.9 g, 73.8%) for allylation and 8e (3.8 g, 71.7%) for propargylation.
3.12. (2S)-2-Benzoyloxyheptanal 10
To a solution of 8b (965 mg, 0.0025 mol) in THF (15 ml) containing pyridine (3 ml) at 0°C was added
benzoyl chloride (0.9 ml, 0.0075 mol) dropwise over a period of 30 min. After stirring the mixture for 2
h at 0°C and 2 h more at room temperature, it was poured into water and extracted with ether. The usual
work up and solvent removal under reduced pressure afforded the residue benzoate. This was mixed with
90% aqueous trifluoroacetic acid (10 ml), stirred for 3 h at −70°C, and diluted with CHCl3 and water.
The aqueous layer was extracted with CHCl3. The combined organic layer was washed successively
with 2% NaHCO3 and water until neutral. Solvent removal under reduced pressure gave the residue
diol 9. To a stirred solution of this diol in 60% aqueous acetonitrile (15 ml), was added NaIO4 (1.0 g).
The white precipitate started separating, then the mixture was stirred for 30 min more and filtered. The
precipitate was washed with CHCl3. The combined organic layer was washed with water and brine, and
dried. Solvent removal under reduced pressure afforded the residue which was chromatographed (silica
20
gel, 0–10% EtOAc in hexane) to furnish pure 10 (306 mg, 53.1%). Its spectral and optical data [α]D
−31.2 (c 1.44, CH2Cl2); were found to be identical with those previously reported5 by us [α]D −31.1
20
(c 1.41, CH2Cl2).
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