Metal-dependent modulation of diastereoselectivity in the Barbier-type crotylation of (R)-cyclohexylideneglyceraldehyde

Article abstract of DOI:10.1016/j.tetasy.2009.08.013

The diastereoselectivity of the Barbier-type crotylation of (R)-cyclohexylideneglyceraldehyde could be tuned by changing the metal atom and solvent. The Ga-mediated reaction in [bmim][Br] produced the best diastereoselectivity, furnishing the all-anti pro

Full text of DOI:10.1016/j.tetasy.2009.08.013

Tetrahedron: Asymmetry 20 (2009) 1957–1961
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Metal-dependent modulation of diastereoselectivity in the Barbier-type
crotylation of (R)-cyclohexylideneglyceraldehyde
*
Dibakar Goswami, Angshuman Chattopadhyay, Subrata Chattopadhyay
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 June 2009
Accepted 18 August 2009
Available online 14 September 2009
The diastereoselectivity of the Barbier-type crotylation of (R)-cyclohexylideneglyceraldehyde could be
tuned by changing the metal atom and solvent. The Ga-mediated reaction in [bmim][Br] produced the
best diastereoselectivity, furnishing the all-anti product in good yield.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Based on our own experience, aldehyde 1 appeared well-suited
as a versatile chiral template for this purpose. We were particularly
The development of simple and efficient strategies is a highly
desirable goal in organic synthesis. Despite impressive progress,1a
this remains a very dynamic and challenging area in asymmetric
synthesis.1b,c The most practical method is aimed at producing
the target compounds via a reliable route utilizing inexpensive
and readily available materials. Over the past several years, we
have found cyclohexylideneglyceraldehyde 1 as an extremely ver-
satile, easily available and inexpensive chiral template for various
enantioselective transformations. Many of these have also been
used for the synthesis of a diverse array of bioactive compounds.
The cyclohexylidene moiety of the aldehyde 1 provides consider-
able steric bias in the addition of organometallics to its aldehyde
function, and also ensures easy separation of the resultant
epimeric carbinols by normal column chromatography.
interested in expanding the substrate-controlled strategy, since the
alcohol stereomers, obtained by crotylation of 1 are functionally
sufficiently enriched for elaboration to various target compounds.4
Hence, for the present work, we attempted the reaction using var-
ious metals, and solvents under varying reaction conditions lead-
ing to the development of an efficient asymmetric crotylation
strategy of 1 with Ga in [bmim][Br] (Scheme 1). The studies also re-
vealed that the diastereoselectivity of Barbier-type crotylation of 1
can be efficiently tuned by judicious choice of metal and solvent.
2. Results and discussion
The initial motivation for the present work stems from our pre-
vious observation that the stereochemistry of crotylation of 1 can
be tuned by changing the metals, and perhaps using different med-
ia. For example, while the Zn-mediated crotylation of 1 in wet THF
proceeded with modest anti-selectivity to furnish the diastereo-
meric alcohols 2a–c in a 2.4:33.1:64.5 ratio,5a when the reaction
was carried out with In/H2O, compounds 2b and 2c were obtained
in a ꢀ1:1 ratio.5b Admittedly, the diastereoselectivity of both the
protocols was unimpressive. This prompted us to study the diaste-
reoselectivity of the reaction by changing the metals (Mg, In, Ga
and Sb) and solvents (organic, aqueous and a room temperature io-
nic liquid, [bmim][Br]). The results are summarized in Table 1.
With Mg in ethereal solvents, practically no selectivity was ob-
tained, and the compounds 2a–c were produced almost in equal
amounts (Table 1, entries 1 and 2). The use of Sb in aqueous THF
or H2O gave a similar diastereoselectivity, but poor yields, and re-
quired an additional metal activator (KF) (Table 1, entries 3 and 4).
The In-mediated reaction proceeded well in H2O, but not in THF
(Table 1, entries 5–8), resulting in the preferential formation of
2b and 2c in a ꢀ1:1 ratio, as the major products. On the other hand,
the Ga-mediated reaction in THF produced the products in poor
Asymmetric allylation/crotylation of aldehydes2a is one of the
most extensively studied processes for carbon–carbon bond forma-
tion, driven in part by the versatility of the homoallylic alcohols as
synthetic intermediates.2b,c The crotylation reaction is valued more
as it generates two new stereogenic centres. Different approaches
involving various metals, crotylating agents and solvents have
been explored to address issues such as regio-, diastereo- and
enantioselectivities.3a–e The asymmetric version of crotylation is
accomplished by incorporating a chiral auxiliary in the substrate
and/or the reagent. While the design and synthesis of the required
chiral auxiliary provide adequate challenge, the efforts are often
very taxing, and at times frustrating. Furthermore, syntheses of
the sterically robust chiral auxiliaries may require several steps,
and involve expensive reagents. It was envisaged that a method
based on using a natural chiral pool-derived template might pro-
vide a suitable alternative for the designated transformation.
* Corresponding author. Fax: +91 22 25505151.
E-mail address: schatt@barc.gov.in (S. Chattopadhyay).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.08.013

1958
D. Goswami et al. / Tetrahedron: Asymmetry 20 (2009) 1957–1961
O
O
O
i
+
O
+
O
O
O
O
OH
2c
CHO
OH
2a
OH
2b
1
Scheme 1. Reagents: (i) Crotyl bromide/metal/additive/solvent.
Table 1
Steric course of the crotylation of 1 with different metals and solventsa
Entry
Crotyl bromide (equiv)
Metal (equiv)
Solvent
Additive
Time (h)
Yieldb (%)
2a:2b:2cc
1
2
3
4
5
6
7
8
9
3.0
3.0
2.5
2.5
3.0
1.2
3.0
3.0
4
Mg (5.0)
Mg (5.0)
Sb (5.0)
Sb (5.0)
In (5.0)
In (2.0)
In (5.0)
In (5.0)
Ga (2.5)
Ga (2.5)
In (2.0)
Ga (1.0)
Et2O
THF
H2O–THF (1:1)
H2O
H2O
H2O
H2O
THF
H2O
—
—
8
8
74
35
37
48
75
72
72
0
38.1:33.2:28.7
29.0:26.1:44.9
30.6:40.8:28.6
40:47.7:12.2
4.0:52.2:43.8
3.7:52.3:44.0
3.7:52.3:44.0
—
KF (2 M)
KF (2 M)
12
14
14
14
14
12
—
10
4
5
—
LiCl + KId
LiCl + KId
—
—
0
—
10
11
12
3.5
1.2
1.2
THF
[bmim][Br]
[bmim][Br]
KI + LiCld
55
81
82
5:35:60
9.3:13.4:77.3
3:5:92
—
—
a
b
c
The reactions were carried out on a 2 mmol scale.
Total yield of the diastereomeric mixtures.
Based on the yields of isolated individual diastereomers.
d
The reaction was carried out in the presence of 1.0 equiv of each of the additives.
yields even under metal activation and resulted in a modest 2c/2b
selectivity (Table 1, entry 10), as observed with Zn. The inability of
Ga to carry out the reaction in H2O (Table 1, entry 9) is consistent
with the fact that Ga requires thermal or ultrasonic activation,6
while we carried out the reactions at room temperature.
as 3b/c is known9 to produce the 2,3-syn carbinols almost exclu-
sively, the configuration of alcohol 2d would be (2R,3R), and hence,
the 2,3-stereochemistry of its progenitor 2c would be (2R,3S).
To establish the C-4 configuration of 2c, it was converted into the
corresponding benzoate derivative 4 by treatment with BzCN in the
presence of Et3N. Deacetalization of 4 with aqueous trifluoroacetic
acid (TFA) in CH2Cl2 afforded diol 5. Treatment of 5 with tert-butyl-
diphenylsilyl chloride (TBDPSCl) in the presence of Et3N in CH2Cl2
furnished the mono silylated compound 6. Its ozonolysis under
Consequently, we explored the In- and Ga-mediated reactions
in [bmim][Br] as the RTIL. So far, the hydrophobic RTILs are gener-
ally used in Barbier-type reactions,7 while the simplest of them,
[bmim][Br] is unexplored. We used [bmim][Br], since it possesses
high hydrophilicity and water-mimicking properties that are ideal
for the Barbier-type allylation. The In-mediated crotylation in
[bmim][Br] proceeded with an improved diastereoselectivity
namely,. 2a:2b:2c ꢀ9:13.5:77.5 (Table 1, entry 11). The selectivity
of 2a:2b:2c could be improved to 3:5:92 by carrying out the reac-
tion with Ga-metal (Table 1, entry 12). Additionally, the yields
were also very good in both these cases, and the reaction could
be accomplished much faster with almost stoichiometric amounts
of the reagents. In other solvents, the results were significantly
inferior, even with a large excess of the reagents and prolonged
reaction time. Surprisingly, the Zn-mediated crotylation of 1 did
not take place in [bmim][Br]. Compounds 2a–2c could be sepa-
rated by column chromatography and characterized by their
NMR spectra.5a,b
Initially the stereochemistry of each of the diastereomers was
identified by comparing the pattern of the signals in the region
of d 3.3–4.2 of their 1H NMR spectra with those reported8a,b for
the corresponding isopropylidene derivatives. For further confir-
mation, compounds 2b and 2c were oxidized separately with
pyridinium chlorochromate (PCC) to give the respective ketones
3b and 3c. Following our own method,9 ketone 3b was reduced
with K-Selectride to furnish the corresponding alcohol, which
showed identical NMR spectra to that of 2a. This confirmed that
compounds 2a and 2b were C-3 epimers. The K-Selectride reduc-
tion of the ketone 3c, however, furnished the other diastereomeric
alcohol 2d, as revealed by its 1H NMR spectrum.4d Since the
K-Selectride reduction of the glyceraldehyde-derived ketones such
alkaline condition10 directly produced the
c-lactone 7c (Scheme
2). The 1H NMR resonance of the –CH(OBz) proton appeared at d
5.96 (dd, J = 13.6, 2.2 Hz). The coupling constant values established
the syn- and anti-relationships of H-4 (containing the OBz group)
with its two neighbouring protons, H-3 and H-5.11 This revealed
the absolute stereochemistry of 7c as (3R,4S,5R), and hence that
of 2c as (2R,3S,4S). For determining the configuration of 2b, it was
converted to the lactone 7b in a similar manner. The 1H NMR cou-
pling constant values of its CH(OBz) proton revealed it to have a
(3S,4S,5R)-configuration, confirming the stereochemistry of its pre-
cursor, 2b as (2R,3S,4R). Hence, compound 2a must possess a
(2R,3R,4R)-configuration as it is the C-3 epimer of 2b.
It is worth mentioning that earlier, better stereocontrol in croty-
lation was accomplished with reagents such as crotyltrifluorosi-
lane,3c,d and crotyltrifluoroborates3e which need to be
synthesized separately. In that light, the present approach, using
inexpensive and commercially available reagents such as crotyl
bromide, [bmim][Br] and Ga and the widely used chiral template,
1 provides a simple and convenient strategy for asymmetric croty-
lation. Incidentally, this is the first application of a hydrophilic RTIL
in the Barbier-type allylation. Amongst the imidazole-based RTILs,
[bmim][Br] is least expensive and possesses negligible vapour
pressure, providing additional advantages for the process. The
homoallylic alcohols 2a–c have many desirable attributes of being
versatile synthons in view of their small-carbon frameworks with
high functional density that can be selectively manoeuvred for var-
ious target compounds. Especially the structural moiety possessing

D. Goswami et al. / Tetrahedron: Asymmetry 20 (2009) 1957–1961
1959
ii
O
O
i
2a
O
O
OH
2b
O
3b
O
O
i
ii
O
O
O
O
OH
O
3c
OH
2c
2d
OH
O
vi
O
iii
iv
O
RO
O
TBDPS
2c
2b
O
OBz
5 R = H
BzO
7c
OBz
v
6 R = TBDPS
4
O
O
TBDPS
O
BzO
7b
Scheme 2. Reagents and conditions: (i) PCC/NaOAc/CH2Cl2; (ii) K-Selectride/THF/ꢁ78 °C; (iii) BzCN/Et3N/CH2Cl2; (iv) aqueous TFA/CH2Cl2; (v) TBDPSCl/imidazole/CH2Cl2; (vi)
O3/NaOH/MeOH–CH2Cl2/ꢁ15 °C.
the adjacent asymmetric centres, bearing a hydroxyl group and
methyl branching is a common structural element of many polyke-
The stereoselectivity is considered to be the outcome of the ori-
entation of the R group. This explains the preferential formation
of 2c in the crotylation of 1. However, the effect of the metal
and solvent on the diastereoselectivity of the reactivity is
unclear. A large number of other factors such as the nature of
the metal,16a–c nature of the counter ion and aggregation state
of the nucleophiles17a–c may be involved in dictating this diaste-
reoselectivity and any more detailed rationalization would, at
best, be speculative.
tide metabolites such as octalactins
A and B, tylosin and
leucomycins.12a,b
Although an a- or a b-oxygenation in carbonyl compounds is re-
ported to be the most effective for chelation to metals,13 aldehyde
1 predominantly gave 4,5-anti-diols with both In and Ga. The ob-
served diastereoselectivity in the coupling indicated that due to
the bulky cyclohexanedioxy group, chelation control was not oper-
ational. The results are consistent with our previous results with
Zn and can be rationalized by the Felkin–Anh model.14
3. Conclusion
The 3,4-diastereoselectivity of the reaction involving c-substi-
tuted (Me) allylic metal reagents and aldehydes may, in princi-
ple, involve a series of cyclic transition states, wherein the
allylmetal reagent coordinates intramolecularly to the oxygen
atom of the carbonyl group (Scheme 3). The formation of TS1
and/or TS2 leads to the syn-adduct, while the anti-product is ob-
tained from TS3 and/or TS4. Given that no other intramolecular
chelation operates for this reaction, the transition state TS3 lead-
ing to the 3,4-anti-adduct is most favourable from the steric
point of view, because both Me and R (cyclohexylidene) groups
adopt equatorial positions, and the allylic-metal exists as the
E-form, irrespective of the geometry of the starting bromide.15
In conclusion, we have disclosed that by careful choice of me-
tal and solvent, the stereochemical profile of the Barbier-type
crotylation of the aldehyde 1 can be tuned. Of particular interest
is the combination of Ga/[bmim][Br], which ensured a very fast
reaction with stoichiometric amounts of the reagents, without
any additional metal activation (chemical, thermal or ultrasonic).
The reaction provides functionalized chiral homoallylic alcohols
with high yield and diastereoselectivity. To the best of our knowl-
edge, this is the first report of the Barbier-type allylation in a
hydrophilic RTIL.
R
R
H
H
H
H
R
R
O
H
O
O
O
R'
H
R'
M
M
M
M
R'
H
R'
H
TS1
TS2
TS4
TS3
Scheme 3.

1960
D. Goswami et al. / Tetrahedron: Asymmetry 20 (2009) 1957–1961
(d, J = 6.8 Hz, 3H), 1.38–1.62 (m, 10H), 2.14 (br s, 1H), 2.21–2.28
4. Experimental
(m, 1H), 3.62–3.71 (m, 1H), 3.78–3.84 (m, 2H), 4.02–4.14 (m, 1H),
4.93–5.12 (m, 2H), 5.68–5.84 (m, 1H); 13C NMR: d 12.5, 17.4, 24.1,
25.4, 35.3, 35.8, 41.2, 65.4, 74.7, 75.6, 109.2, 114.1, 138.8. Anal. Calcd
for C13H22O3: C, 68.99; H, 9.80. Found: C, 69.12; H, 9.91.
4.1. General experimental details
All the chemicals (Fluka and Lancanster) were used as received.
Other reagents were of AR grade. Unless otherwise mentioned, the
organic extracts were dried over anhydrous Na2SO4. The IR spectra
as thin films were scanned with a Jasco model A-202 FT-IR spectro-
photometer. The 1H NMR (200 MHz) and 13C NMR (50 MHz) spec-
tra were recorded with a Bruker Ac-200 spectrometer using CDCl3
as the solvent. The optical rotations were recorded with a Jasco DIP
360 digital polarimeter.
4.7. (2R,3S,4S)-1,2-Cyclohexylidenedioxy-4-methylhex-
5-en-3-ol 2c
Colourless thick oil;
½
a 2D4
ꢃ
¼ þ2:4 (c 1.17, CHCl3), {lit.5a
½
a 2D3
ꢃ
¼ þ2:6 (c 2.05, CHCl3)}; IR: 3408, 1657, 997 cmꢁ1
;
1H NMR:
d 1.07 (d, J = 6.6 Hz, 3H), 1.40–1.59 (m, 10H), 2.07 (br s, 1H),
2.20–2.43 (m, 1H), 3.53–3.58 (m, 1H), 3.82–4.06 (m, 3H), 5.0–
5.12 (m, 2H), 5.71–5.91 (m, 1H); 13C NMR: d 12.7, 16.4, 23.9,
25.1, 34.8, 36.2, 40.7, 65.1, 71.7, 74.8, 109.1, 115.9, 139.8. Anal.
Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 69.12; H, 9.91.
4.2. General method for crotylation of 1 via Grignard route
To a stirred solution of 1 (1.70 g, 0.01 mol) in THF (25 mL) was
slowly injected the Grignard reagent [prepared from crotyl bro-
mide (4.10 g, 0.03 mol) and Mg-turnings (1.20 g, 0.05 mol)] in
Et2O or THF (40 mL). After stirring for 12 h, the reaction was
quenched with aqueous saturated NH4Cl (2 mL). The organic layer
was separated and the aqueous portion was extracted with Et2O
(2 ꢂ 15 mL). The combined organic extracts were washed with
brine (1 ꢂ 5 mL), and dried. Solvent removal in vacuo and column
chromatography of the residue afforded the pure alcohols 2a–c.
4.8. (2R,4R)- and (2R,4S)-1,2-Cyclohexylidenedioxy-4-methyl-5-
hexen-3-one 3b and 3c
To a cooled (0 °C) and stirred solution of PCC (1.6 g, 5.0 mmol)
and NaOAc (0.3 g) in CH2Cl2 (10 mL) were added 2b and 2c
(1.0 g, 4.42 mmol) in CH2Cl2 (10 mL). After stirring the reaction
mixture for 3 h, it was diluted with dry Et2O (80 mL), and the
supernatant was filtered through a pad of silica gel. The eluate
was concentrated in vacuo and the residue was subjected to col-
umn chromatography (silica gel, 0–15% EtOAc/hexane) to give 3b
and 3c. Compound 3b: Yield 0.74 g (75%); colourless thick oil;
4.3. General procedure for Barbier-type crotylation of 1 in H2O
or THF
a 2D4
ꢃ
¼ þ10:2 (c 1.56, CHCl3); IR: 1741 cmꢁ1
;
1H NMR: d 1.04 (d,
Finely divided metal powder (In or Sb or Ga) was added to a
mixture of 1 (5.0 g, 0.029 mol) and crotyl bromide (equivalents
specified in Table 1) in H2O (30 mL) or THF (30 mL) and the mix-
ture was magnetically stirred for the time specified in Table 1.
The mixture was filtered and worked-up to isolate pure 2a–c as
mentioned above. For the reaction with Sb, an aqueous solution
of KF (5–6 mL, 2 M) was also added into the reaction mixture.
The In-mediated reaction was also carried out in the presence of
LiCl and KI (1.0 equiv each).
½
J = 7.6 Hz, 3H), 1.41–1.63 (m, 10H), 3.62–3.75 (m, 1H), 3.85–4.05
(m, 2H), 4.43 (dd, J = 5.8 and 7.4 Hz, 1H), 4.82–5.07 (m, 2H),
5.64–5.84 (m, 1H); 13C NMR: d 14.7, 23.4, 23.6, 24.7, 34.2, 35.3,
46.0, 65.5, 78.4, 110.9, 116.8, 136.2, 209.7. Compound 3c: Yield
0.78 g (79%); colourless thick oil; ½a D24
ꢃ
¼ þ5:9 (c 1.08, CHCl3), (lit.4d
½
a 2D2
ꢃ
¼ þ5:7 (c 1.12, CHCl3)); IR: 1740 cmꢁ1
;
1H NMR: d 1.01 (d,
J = 7.0 Hz, 3H), 1.32–1.54 (m, 10H), 3.41–3.62 (m, 1H), 3.78–3.91
(m, 1H), 3.97–4.21 (m, 1H), 4.35–4.48 (m, 1H), 4.85–5.05 (m,
2H), 5.72–5.96 (m, 1H); 13C NMR: d 13.9, 22.8, 23.1, 25.0, 34.6,
35.8, 46.2, 63.3, 76.5, 110.7, 116.9, 135.8, 205.4.
4.4. Typical procedure for the metal-mediated crotylation
reactions in [bmim][Br]
4.9. (3S,4S,5R)-4-Benzoyloxy-5,6-cyclohexylidenedioxy-3-
methyl-1-hexene 4
A mixture of the metal (In or Ga) and crotyl bromide (quantities
specified in Table 1) in [bmim][Br] (3 mL/mmol) was stirred at
room temperature for 0.5 h, followed by the addition of aldehyde
1. The reaction mixture was stirred at room temperature for 4–
5 h. After completion of the reaction (cf. TLC), the mixture was ex-
tracted with Et2O (3 ꢂ 10 mL), the ether extract was evaporated in
vacuo and the residue was purified by column chromatography
(silica gel, 0–15% EtOAc/hexane) to give 2a–c.
To a well stirred and cooled (0 °C) solution of 2c (1.1 g,
4.86 mmol) and Et3N (0.74 g, 7.3 mmol) in CH2Cl2 (25 mL) was
added a solution BzCN (0.76 g, 5.83 mmol) in CH2Cl2 (10 mL) over
40 min. Afterthe completionof thereaction (cf. TLC, 2 h) thereaction
mixture was poured into water, the organic layer was separated and
the aqueous layer was extracted with CHCl3 (2 ꢂ 15 mL). The com-
bined organic extracts were washed with water (2 ꢂ 10 mL) and
brine (1 ꢂ 5 mL), and dried. Solvent removal in vacuo followed by
column chromatography (silica gel, 5–15% EtOAc/hexane) of the res-
4.5. (2R,3R,4R)-1,2-Cyclohexylidenedioxy-4-methylhex-
5-en-3-ol 2a
idue gave 4. Yield 1.52 g (95%); colourless oil; ½a D24
¼ þ14:2 (c 1.47,
ꢃ
Colourless thick oil; ½a D24
ꢃ
¼ þ45:9 (c 1.81, CHCl3), {lit.5a
½
a 2D3
ꢃ
¼
CHCl3); IR: 1722, 995, 920 cmꢁ1 1H NMR (CDCl3): d 1.07 (d,
;
þ47:1 (c 1.4, CHCl3)}; IR: 3408, 1648, 990 cmꢁ1; 1H NMR: d 1.09 (d,
J = 6.8 Hz, 3H), 1.33–1.58 (m, 10H), 2.22–2.30 (m, 1H), 2.68 (br s,
1H), 3.31–3.39 (m, 1H), 3.71–3.76 (m, 1H), 3.93–4.15 (m, 2H),
4.98–5.08 (m, 2H), 5.68–5.84 (m, 1H); 13C NMR: d 12.4, 16.9, 23.9,
25.1, 35.0, 36.2, 41.3, 65.7, 74.6, 75.4, 109.6, 112.8, 139.6. Anal. Calcd
for C13H22O3: C, 68.99; H, 9.80. Found: C, 68.81; H, 9.95.
J = 7.0 Hz, 3H), 1.31–1.43 (m, 8H), 1.58–1.67 (m, 2H), 2.65–2.75 (m,
1H) 3.83–3.90 (m, 1H), 3.95–4.03 (m, 1H), 4.20–4.26 (m, 1H), 5.06–
5.18 (m, 2H), 5.26 (dd, J = 4.0 and 6.6 Hz, 1H), 5.77–5.87 (m, 1H),
7.38–7.54 (m, 3H), 7.99–8.04 (m, 2H). 13C NMR (CDCl3): d 16.9,
23.8, 25.0, 34.9, 36.1, 39.8, 65.9, 74.9, 76.7, 109.6, 116.3, 128.3,
129.6, 129.9, 132.9, 138.4, 165.8. Anal. Calcd for C20H26O4: C,
72.70; H, 7.93. Found: C, 72.72; H, 8.12.
4.6. (2R,3S,4R)-1,2-Cyclohexylidenedioxy-4-methylhex-
5-en-3-ol 2b
4.10. (2R,3S,4S)-3-Benzoyloxy-4-methyl-5-hexene-1,2-diol 5
Colourless thick oil; ½a D24
ꢃ
¼ þ29:8 (c 1.40, CHCl3), {lit.5a
½
a 2D3
ꢃ
¼
To a stirred and cooled (0 °C) solution of 4 (1.4 g, 4.24 mmol) in
CH2Cl2 (25 mL) was added aqueous TFA (10 mL) in portions. After
þ29:65 (c 1.45, CHCl3)}; IR: 3400, 1651, 995 cmꢁ1; 1H NMR: d 1.09

D. Goswami et al. / Tetrahedron: Asymmetry 20 (2009) 1957–1961
1961
stirring the mixture for 2.5 h, when the reaction was complete (cf.
4.13. (3S,4S,5R)-(4-Benzoyloxy-3-methyl-5-(tert)-
TLC), NaHCO3 was added to decompose the excess TFA, followed by
water, and the mixture was extracted with CHCl3 (2 ꢂ 10 mL). The
combined organic extracts were washed with water (2 ꢂ 10 mL)
and brine (1 ꢂ 5 mL), and dried. Removal of the solvent in vacuo
followed by column chromatography (silica gel, 5% CHCl3/MeOH)
of the residue afforded 5. Yield 0.92 g (86%); colourless thick oil;
butyldiphenylsilyloxymethyl) dihydro-2(3H)-furanone 7b
Colourless oil; ½a D24
¼ þ21:1 (c 0.721, CHCl3); IR: 1739, 1692
ꢃ
cmꢁ1 1H NMR: d 0.93 (d, J = 6.4 Hz, 3H), 1.17 (s, 9H), 2.92–2.98
;
(m, 1H), 3.78–3.88 (m, 2H), 4.61–4.67 (m, 1H), 5.84 (dd, J = 12.2
and 9.7 Hz, 1H), 7.29–7.37 (m, 4H), 7.48–7.75 (m, 9H), 7.95–8.02
(m, 2H). Anal. Calcd for C19H28O5Si: C, 62.61; H, 7.74. Found: C,
62.75; H, 7.62.
½
a 2D4
ꢃ
¼ þ7:5 (c 1.04, CHCl3); IR: 3411, 1724, 995, 920 cmꢁ1
;
1H
NMR (CDCl3): d 0.98 (d, J = 7.0 Hz, 3H), 2.86–2.96 (m, 3H), 3.56–
3.71 (m, 2H), 3.76–3.84 (m, 1H), 5.01 (dd, J = 2.8 and 8.6 Hz, 1H),
5.13–5.25 (m, 2H), 5.77–5.88 (m, 1H), 7.40–7.58 (m, 3H), 7.99–
8.04 (m, 2H); 13C NMR (CDCl3): d 17.4, 38.5, 62.6, 70.7, 76.7,
116.8, 128.5, 129.3, 129.8, 133.5, 138.1, 167.2. Anal. Calcd for
C14H18O4: C, 67.18; H, 7.25. Found: C, 67.32; H, 7.09.
References
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Wiley: New York, 1994.
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Wong, K. Y.; Chan, T. H. Green Chem. 2002, 4, 161–164; (c) Law, M. C.; Cheung,
T. W.; Wong, K. Y.; Chan, T. K. J. Org. Chem. 2007, 72, 923–929.
4.11. (3S,4S,5R)-4-Benzoyloxy-6-(tert)-butyldiphenylsilyloxy-3-
methyl-1-hexene 6
A cooled (0 °C) solution of 5 (0.8 g, 3.2 mmol), TBDPSCl (0.89 g,
3.2 mmol) and imidazole (0.26 g, 3.84 mmol) in CH2Cl2 (20 mL)
was stirred for 4 h. Water (15 mL) was added to the mixture, which
was extracted with CHCl3 (2 ꢂ 10 mL). The combined organic ex-
tracts were washed with water (2 ꢂ 10 mL) and brine (1 ꢂ 5 mL),
dried and concentrated in vacuo. The residue was subjected to col-
umn chromatography (silica gel, 5–15% EtOAc/hexane) to afford 6.
Yield 1.25 g (80%); colourless oil; ½a D24
¼ þ7:9 (c 0.971, CHCl3); IR:
ꢃ
3450, 1726, 997, 924 cmꢁ1 1H NMR (CDCl3): d 1.01 (d, J = 6.8 Hz,
;
3H), 1.09 (s, 9H), 1.12 (br s, 1H), 2.66–2.70 (m, 1H), 3.00–3.35
(m, 2H), 3.81–4.12 (m, 1H), 5.03 (dd, J = 2.4 and 7.8 Hz, 1H),
5.21–5.29 (m, 2H), 5.82–5.98 (m, 1H), 7.25–7.38 (m, 4H), 7.46–
7.84 (m, 9H), 7.98–8.02 (m, 2H); 13C NMR (CDCl3): d 17.4, 19.1,
37.7, 63.5, 72.1, 75.9, 116.6, 127.2, 127.5, 128.5, 129.3, 130.4,
133.5, 138.3, 171.2. Anal. Calcd for C30H36O4Si: C, 73.73; H, 7.43.
Found: C, 73.61; H, 7.59.
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108, 3422–3434.
4.12. (3R,4S,5R)-(4-Benzoyloxy-3-methyl-5-(tert)-
butyldiphenylsilyloxymethyl) dihydro-2(3H)-furanone 7c
9. Dhotare, B.; Salaskar, A.; Chattopadhyay, A. Synthesis 2003, 2571–2575.
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J. F.; Collum, D. B. J. Am. Chem. Soc. 1998, 120, 2028–2038; (b) McGarrity, J. F.;
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Williard, P. G. J. Am. Chem. Soc. 2000, 122, 12542–12546.
Ozone was bubbled for 20 min through a solution of 6 (1 g,
2.03 mmol) and methanolic NaOH (1.5 mL, 2.5 M) in CH2Cl2
(20 mL) at ꢁ78 °C. After stirring the mixture for 3 h at the same
temperature, it was diluted with CHCl3 and water, and brought
to room temperature. The organic layer was separated and the
aqueous layer was extracted with CHCl3. The combined organic ex-
tracts were washed with water and brine, and dried. Removal of
solvent in vacuo followed by chromatographic purification (silica
gel, 5–15% CHCl3/MeOH) afforded 7c. Yield 0.72 g (72%); colourless
oil; ½a 2D4
ꢃ
¼ þ16:3 (c 0.884, CHCl3); IR: 1742, 1695 cmꢁ1; 1H NMR: d
0.91 (d, J = 6.8 Hz, 3H), 1.14 (s, 9H), 3.40–3.50 (m, 1H), 3.90–4.20
(m, 2H), 4.63–4.70 (m, 1H), 5.96 (dd, J = 13.6 and 2.2 Hz, 1H),
7.27–7.37 (m, 4H), 7.44–7.81 (m, 9H), 7.97–8.01 (m, 2H). Anal.
Calcd for C19H28O5Si: C, 62.61; H, 7.74. Found: C, 62.77; H, 7.91.