Synthesis of all four stereoisomers of 5-hydroxy-4-methyl-3-heptanone using plants and oyster mushrooms

Article abstract of DOI:10.1016/j.tet.2009.08.049

All four possible stereoisomers of 5-hydroxy-4-methyl-3-heptanone were synthesized from common achiral reagents using fast, straightforward organic synthesis, including the use of whole tissue of Daucus carota, Solanum melongena, and Pleurotus ostreatus.

Full text of DOI:10.1016/j.tet.2009.08.049

Tetrahedron 65 (2009) 8697–8701
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of all four stereoisomers of 5-hydroxy-4-methyl-3-heptanone using
plants and oyster mushrooms
a
a,b,
*
Bj o¨ rn Bohman , C. Rikard Unelius
a
School of Pure and Applied Natural Sciences, University of Kalmar, SE-391 82 Kalmar, Sweden
The New Zealand Institute for Plant & Food Research Limited, Canterbury Research Centre, Lincoln, 7608, New Zealand
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 March 2009
Received in revised form 5 August 2009
Accepted 20 August 2009
Available online 25 August 2009
All four possible stereoisomers of 5-hydroxy-4-methyl-3-heptanone were synthesized from common
achiral reagents using fast, straightforward organic synthesis, including the use of whole tissue of Daucus
carota, Solanum melongena, and Pleurotus ostreatus.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Sitophilure
Plants
Mushrooms
Enantioselective, b-Hydroxyketone
1. Introduction
had to be synthesized. We also wanted to obtain the remaining three
stereoisomers for tests of synergetic or inhibitory effects.
(
4R,5S)-5-Hydroxy-4-methyl-3-heptanone ((4R,5S)-1a), known
Numerous routes to the various stereoisomers of 5-hydroxy-4-
as Sitophilure (Fig. 1), has been found to be an aggregation phero-
methyl-3-heptanone (1a and 2a) have been reported over the last
3
mone for Sitophilus weevils, such as the rice weevil Sitophilus oryzae
decades. For example Mori and Ebata have prepared all possible
1
3g
and the maize weevil Sitophilus zeamais. One of the anti isomers of
isomers from methyl (R)-3-hydroxypentanoate
and more
this compound, (4S,5S)-2a, was found to be a compound specific to
males, when volatile emissions from individuals of the lucerne
weevil Sitona discoideus were analyzed, in order to attempt the
recently new biocatalytic routes have been presented, among some
are: Pilli’s and Riatto’s preparation of (þ)-Sitophilure from methyl-
3
b
3-oxopentanoate using S. cerevisiae and the preparation of the
2
identificationof itssex pheromone. To be able to determinewhether
same compound by Kalaitzakis et al. utilizing isolated NADPH-de-
3
f
(
4S,5S)-2a was in fact a pheromone for this species, the compound
pendent ketoreductases. Our approach is based on the well
known fact that diastereoselectivity of aldol additions of aldehydes
to ketones can be directed by the choice of base in combination
with added Lewis acids. We wanted to obtain the stereochemically
pure isomers of 1a and 2a by utilizing diastereoselective aldol ad-
ditions in combination with purifications by a common, commer-
cially available lipase, whole tissue of vegetables and mushrooms,
and column chromatography. By combining these methods, in-
expensive and commercially available achiral reagents could be
used to prepare substances highly enantioselectively with relative
ease. Our aim of this project was to obtain the two syn isomers:
(
4R,5S)-1a and (4S,5R)-1a as well as the two anti isomers: (4R,5R)-
a and (4S,5S)-2a as four separate samples in an isomeric purity
greater than 95%.
2
Figure 1. Starting materials and target compounds.
2. Results and discussion
*
Corresponding author. Tel.: þ46 708101514; fax: þ46 480446262.
E-mail address: rikard.unelius@hik.se (C.R. Unelius).
In order to evaluate the relationship between stereochemistry
and bioactivity, a synthesis of all four possible stereoisomers of
0
040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.08.049

8698
B. Bohman, C.R. Unelius / Tetrahedron 65 (2009) 8697–8701
5
-hydroxy-4-methyl-3-heptanone ((4R,5S)-1a, (4S,5R)-1a, (4R,5R)-
purity was achieved by a lipase-mediated transacetylation with
5
2
a, and (4S,5S)-2a) was carried out. These syntheses consisted of 11
Amano PS-D lipase and vinyl acetate. The main product (4S,5R)-1b
6
steps (Figs. 1 and 2) and total yields of the individual isomers
was enriched further by column chromatography, taking advan-
ranged from 6 to 23%. The crude syn products 1a and anti products
tage of the partial separation found for the two diastereomers on
silica gel. The remaining alcohol was predominantly (4R,5S)-1a,
which was treated with lipase a second time, then acetylated and
subjected to chromatography. The two acetate esters (4R,5S)-1b and
(4S,5R)-1b were hydrolyzed selectively by the means of whole plant
2
a of 5-hydroxy-4-methyl-3-heptanone were synthesized by the
aldol addition between 3-pentanone (3) and n-propanal (4).
Transesterification using lipase Amano PS-D from Pseudomonas
cepacia gave further enrichment of one pair of enantiomers and
column chromatography on silica gel gave partial separation of the
two pairs of diastereomers. Finally, the choice of plant tissue in the
stereoselective hydrolysis of the acetate esters 1b and 2b formed by
the lipase further enhanced the isomeric purity of the final
products.
7
tissue of eggplant Solanum melongena, yielding (4R,5S)-1a and
(4S,5R)-1a in >95% isomeric purity.
Compound (4R,5R)-2a was synthesized via a Mg(II)-mediated
aldol addition between 3 and 4, selectively forming the anti iso-
8
mers. The initial aldol product, formed by an LDA reaction in THF,
Compounds (4R,5S)-1a and (4S,5R)-1a, the two syn isomers,
were derived from 3 and 4, where the selectivity for the syn pro-
2
was treated with MgBr -etherate at low temperature followed by
warming to rt, thus converting the syn product to a predominantly
anti product. Analogously as for the syn products, a further in-
crease in isomeric purity was achieved by a lipase-mediated
ducts was achieved by formation of a titanium enolate from TiCl
4
4
and diisopropylethylamine. Further enhancement of the isomeric
O
O
+
H
3
4
LDA
(iPr) NEt
2
Mg(II)
Ti(IV)
O
OH
O
OH
O
OH
O
OH
(4S,5S)-2a
(4R,5R)-2a
(4S,5R)-1a
(4R,5S)-1a
3
5 %
35 %
45 %
45 %
1
) Amano PS
Vinyl OAc
2) MPLC
1) Amano PS
Vinyl OAc
2) MPLC
O
OAc
O
OAc
O
OH
(
4R,5R)-2b
(
4S,5R)-1b
(4R,5S)-1a
76 %
9
4 %
92 %
1
2
) Carrot
) MPLC
1) Eggplant
2) MPLC
1) Amano PS
Vinyl OAc
2) MPLC
O
OH
O
OH
O
OH
(
4R,5R)-2a
5 %
(
4S,5R)-1a
95 %
(4R,5S)-1a
89 %
9
1
) Ac O
2) MPLC
2
Pyridine
O
O
O
OH
O
OAc
Oyster
5
mushroom
(
4S,5S)-2a
(4R,5S)-1b
95 %
86 %
1
) Amano PS
Vinyl OAc
2) MPLC
1) Eggplant
2) MPLC
O
OH
O
OH
(
4S,5S)-2a
(4R,5S)-1a
96 %
95 %
Figure 2. Synthesis of all four stereoisomers of 5-hydroxy-4-methyl-3-heptanone.

B. Bohman, C.R. Unelius / Tetrahedron 65 (2009) 8697–8701
8699
transacetylation followed by chromatography of the acetate
4R,5R)-2b. The selective hydrolysis of this ester was performed
using whole tissue of carrot Daucus carota yielding the product
with a BPX-70 column (30 mꢀ0.25 mm, i.d.ꢀ0.25
m
m, SGE Aus-
(
tralia). Enantioselective GC was performed with an HP 5890 GC
m, J &
fitted with a CYCLOSILB column (30 mꢀ0.25 mm, i.d.ꢀ0.25
m
(
4R,5R)-2a in 95% isomeric purity.
W Scientific, USA). Column chromatography on silica gel (Merck 60,
0.040–0.063 mm) was carried out using a Separo medium pressure
Compound (4S,5S)-2a was synthesized by a regio- and enan-
6
tioselective reduction of the diketone 5 by the means of whole
tissue of oyster mushrooms Pleurotus ostreatus. The crude product
was purified by chromatography and subjected to a lipase trans-
acetylation. The enriched hydroxyketone was isolated from the
formed acetate esters by chromatography yielding (4S,5S)-2a in
liquid chromatography (MPLC) system. The column inner
diameter was 15, 20, or 25 mm and gradient elution was applied,
using cyclohexane and increasing amounts of ethyl acetate. All
chemicals used as starting materials in the syntheses, were used as
delivered from Sigma–Aldrich (Sweden), and Alfa Aesar (Germany).
Anhydrous solvents were used and reactions were carried out un-
der nitrogen when appropriate.
9
5% isomeric purity. In theory this stereoisomer could have been
prepared by a similar method as for (4R,5S)-1a, using rac-2a instead
of rac-1a as starting material, but our method for preparation of
(
4S,5S)-2a is shorter.
It is important to note that the hydrolysis of the acetates 1b and
4.2. Synthesis of syn 5-hydroxy-4-methyl-3-heptanone (1a)
2
b proceeded smoothly to the b-hydroxyketones 1a and 2a when
In dichloromethane (20 mL), while stirring, 3-pentanone (3)
the whole tissue of carrot and eggplant was used. This is in stark
contrast to our attempts to execute chemical hydrolysis under
alkaline standard conditions, which instantly yielded the elimina-
tion product 4-methyl-4-heptene-3-one. We also tried chemical
hydrolysis under acidic conditions, as well as various commercial
lipases (lipase B from Candida antarctica and Amano PS-D from
Pseudomonas cepacia), esterase (Pig liver esterase), and protease
(
ꢁ
0.43 g, 5.0 mmol) was dissolved and the solution was cooled to
80 C. Titanium tetrachloride (0.60 mL, 5.5 mmol) was added
ꢂ
dropwise. After 5 min, diisopropylethylamine (1.02 mL, 6.0 mmol)
was added dropwise and the mixture was stirred for 1.5 h at the
same temperature. Propanal (4) (0.44 mL, 6.0 mmol) was added
dropwise and stirring was continued for 1.5 h under the same
4
conditions. NH Cl (satd, aq, ca. 20 mL) was added, the cooling bath
(
Subtilisin A) in attempts to hydrolyze and alcoholyze 1b and 2b
was removed, and water (ca. 10 mL) and diethyl ether (ca. 20 mL)
were added. The aqueous phase was separated and extracted with
diethyl ether (ca. 2ꢀ20 mL), the combined organic phases were
without success.
The regio- and enantioselective reduction of the diketone 5 to
(
4S,5S)-2a by the use of oyster mushrooms (or other mushrooms) is
washed with brine (ca. 3ꢀ20 mL), dried over MgSO
4
, and the sol-
an attractive alternative to the use of baker’s yeast. Although ex-
vents were removed in vacuo, yielding the product 1a as a slightly
yellow oil of 98% purity (0.62 g, 90% syn, 84% yield). GC–MS:
cellent enantioselectivity and reasonable yields have been reported
9
for reductions of
b
-diketones by baker’s yeast, other authors report
1
26(15), 97(14), 86(37), 70(18), 69(11), 59(16), 57(100), 55(15). For
much lower yields (10–15%) of the anti product (>96% di-
NMR see individual isomers.
astereomeric purity, no enantiomeric purity given) for the re-
10
duction using 5 as substrate. In our laboratory the yields and
stereoselectivity of this reaction were substantially lower than
those reported above, while in experiments using oyster mush-
rooms we have obtained a crude product containing 82% of the
desired enantiomer in 95% chemical purity and 40% yield, without
any use of commercial lipases (unpublished data).
4
.3. Synthesis of anti 5-hydroxy-4-methyl-3-heptanone (2a)
Diisopropylamine (12.6 mL, 90 mmol) was dissolved in THF
ꢂ
(200 mL) and cooled to 0 C. Butyllithium (2.0 M in pentane,
3
2
0.0 mL, 60 mmol) was added slowly while stirring and after
ꢂ
0 min at rt, the mixture was cooled to ꢁ70 C. 3-Pentanone (3)
(5.16 g, 60 mmol) was added slowly and stirring was continued for
3
. Conclusions
3
0 min, whereafter propanal (4) (3.83 g, 66 mmol) was added. At
the same temperature, after 20 min, MgBr $OEt (19.4 g, 76 mmol)
was added in one portion. After continued stirring for 5 min, the
mixture was allowed to reach rt and after another 3 h NH Cl (satd,
2
2
We have described methods of stereoselective synthesis and
separation, such as aldol addition, lipase transesterification, and
column chromatography as well as ester hydrolysis mediated by
plants and mushrooms. When these methods were employed in-
dividually they gave moderate isomeric purity of certain isomers of
4
aq, ca. 200 mL) was added followed by diethyl ether (ca. 100 mL)
and water (ca. 50 mL). The aqueous phase was extracted with
diethyl ether (ca. 3ꢀ50 mL) and then the combined organic phases
5
-hydroxy-4-methyl-3-heptanone 1a and 2a but when combined
were washed with brine (ca. 2ꢀ50 mL) and dried over MgSO
4
. The
all stereoisomers of 1a and 2a could be prepared from common
achiral starting materials in good enantiomeric and diastereomeric
purity.
solvents were removed in vacuo yielding the product 2a as a yellow
oil of 54% purity (8.78 g, 71% anti). Yield: 55%. After purification by
MPLC 4.35 g product of 89% purity was collected, to be used for the
next step. For GC–MS see 1a and for NMR see individual isomers.
4
4
. Experimental
.1. General
4.4. Synthesis of 4-methyl-3,5-heptanedione (5)
For all synthesized compounds H NMR and 13C NMR spectra of
1
To acetone (250 mL), 3,5-heptanedione (12.8 g, 0.098 mol) and
potassium carbonate (oven dried, 12.8 g, 0.094 mol) were added at
rt while stirring. After 15 min, iodomethane (7.8 mL, 0.12 mol) was
added dropwise. The solution was heated to reflux overnight. After
16 h, the heating was discontinued and at rt diethyl ether (ca.
200 mL) was added and stirring was continued for 30 min. Solids
were filtered off and the remaining solution was concentrated in
vacuo to yield 5 as a yellow oil of 90% purity (14.8 g), containing
some residue of solvent. The product was used as such in the fol-
CDCl solutions were recorded at 500 MHz and 125 MHz, using
3
a Varian Unity spectrometer. Chemical shifts were expressed in
ppm in relation to tetramethylsilane, multiplicity (s, singlet; d,
doublet; t, triplet; q, quintet and m, multiplet), coupling constants
(
Hz), and number of protons. The starting materials employed were
obtained from commercial suppliers and used without further
purification. All vegetables and mushrooms were obtained from the
local supermarket. Mass spectra were obtained with an HP 6890GC
interfaced to an HP 5973 mass selective detector, in electron impact
mode (70 eV), with helium as the carrier gas. The GC was equipped
11
3f
lowing steps. GC–MS and NMR corresponded to literature data.
1
GC–MS: 142(5), 114(5), 113(8), 86(45), 57(100). H NMR d: 3.68

8700
B. Bohman, C.R. Unelius / Tetrahedron 65 (2009) 8697–8701
(
q, 1H, J¼7.1 Hz), 2.49 (m, 4H), 1.31 (d, 3H, J¼7.1 Hz), 1.04 (t, 6H,
4.7. Synthesis of (4R,5R)-5-hydroxy-4-methyl-3-heptanone
((4R,5R)-2a)
13
J¼7.2 Hz); C NMR
d: 207.9, 60.5, 35.0, 13.1, 7.8 ppm.
4
.5. Synthesis of (4R,5S)-5-hydroxy-4-methyl-3-heptanone
Compound anti-2a [1.80 g, 12.5 mmol (sum of enantiomers),
70% anti] was mixed with vinyl acetate (7.2 g, 84 mmol) and Amano
PS-D lipase (1.80 g) was added. The mixture was incubated at 25 C/
(
(4R,5S)-1a)
ꢂ
Compound syn-1a [0.60 g, 4.2 mmol (sum of isomers), 90% syn]
120 rpm in a shaking water bath. After two days the lipase was
filtered off and rinsed with dichloromethane. The solvents were
removed in vacuo and the product was isolated from the remaining
starting material and enriched by repetitive MPLC (three times)
yielding a fraction of 426 mg (4R,5R)-2b of 94% isomeric purity
was mixed with vinyl acetate (2.0 g, 23.2 mmol) and Amano PS-D
ꢂ
lipase (0.60 g) was added. The mixture was incubated at 25 C/
1
20 rpm in a shaking water bath. After 4 days the lipase was filtered
off and rinsed with dichloromethane. The solvents were removed
in vacuo and the enriched alcohol was isolated from the formed
acetate by MPLC yielding a fraction of 331 mg of 76% enantiomeric
purity. This product (331 mg, 2.3 mmol) was treated again with
Amano PS-D lipase (0.30 g) in vinyl acetate (1.0 g, 11.6 mmol) under
the same conditions for 8 days. Analogous work-up and MPLC
yielded 225 mg (75%) of (4R,5S)-1a of 89% isomeric purity.
y
(36% ).
The acetate (4R,5R)-2b (426 mg, 2.3 mmol) was mixed with
water (300 mL). Carrot D. carota (90 g) was cut into thin slices
(ca. 3 mm) and added to the mixture, which was incubated in an
ꢂ
open container at 25 C/120 rpm in a shaking water bath for 64 h.
The biological tissue was filtered off and rinsed with water (ca.
4ꢀ100 mL). The remaining aqueous solution was extracted with
diethyl ether (ca. 3ꢀ50 mL), washed with brine (ca. 50 mL), dried
The crude product (4R,5S)-1a (225 mg, 1.6 mmol) was treated
with acetic anhydride (4.05 g, 40 mmol) in pyridine (11.0 g,
1
39 mmol) at rt overnight. Then the mixture was poured on ice and
extracted with pentane (ca. 3ꢀ15 mL), washed with CuSO (10%, aq)
until no change in color was observed (ca. 50 mL), water (ca. 15 mL)
and brine (ca. 15 mL), and dried over MgSO . The solvents were
4
over MgSO , and concentrated in vacuo to yield 240 mg crude
4
product. This product was subjected to MPLC and a fraction of
85 mg (4R,5R)-2a was isolated in 95% isomeric purity and 98%
chemical purity. Overall yield from 3-pentanone: 6%. 1H NMR
d:
4
removed in vacuo to yield a colorless product (234 mg). This
product was purified by repetitive MPLC (two times) to yield the
ester (4R,5S)-1b in 95% isomeric purity (178 mg, some solvent
residue remaining).
3.62 (m, 1H), 2.40–2.70 (m, 3H), 1.58 (m, 1H), 1.41 (m, 1H), 1.13 (d,
13
3H, J¼7.2 Hz), 1.05 (t, 3H, J¼7.2 Hz), 0.98 (t, 3H, J¼7.4 Hz); C NMR
d: 217.1, 75.2, 50.8, 36.3, 27.8, 14.5, 10.1, 7.8 ppm. For MS see syn-1a.
The acetate (4R,5S)-1b (178 mg, including solvent residue) was
mixed with water (150 mL). Eggplant S. melongena (70 g) was cut
into thin slices (c. 5 mm) and added to the mixture, which was
4.8. Synthesis of (4S,5S)-5-hydroxy-4-methyl-3-heptanone
((4S,5S)-2a)
ꢂ
incubated in an open container at 25 C/120 rpm in a shaking water
4-Methyl-3,5-heptanedione 5 [1.20 g, 7.6 mmol (calcd from 90%
purity)] was mixed with water (1.8 L). Oyster mushrooms P.
ostreatus (600 g) were cut into thin slices (c. 5 mm) and added to
the mixture, which was incubated in six open 250 mL Pyrex bottles
bath for 14 h. The eggplant tissue was filtered off and rinsed with
water (ca. 4ꢀ60 mL). The remaining aqueous solution was extrac-
ted with diethyl ether (ca. 5ꢀ50 mL), washed with water (ca.
ꢂ
2
ꢀ50 mL) and brine (ca. 50 mL), dried over MgSO
4
, and concen-
at 25 C/120 rpm in a shaking water bath for 72 h. The biological
trated in vacuo to yield 53 mg crude product. This product was
material was filtered off and rinsed with water (ca. 4ꢀ250 mL). The
subjected to MPLC and 42 mg of (4R,5S)-1a was isolated in 96%
remaining aqueous solution was extracted with diethyl ether (ca.
isomeric purity and 98% chemical purity. Overall yield from
3ꢀ200 mL), washed with brine (ca. 200 mL), dried over MgSO , and
4
1
3
-pentanone: 12%. H NMR
d: 3.82 (m, 1H), 2.45–2.60 (m, 3H), 1.52
concentrated in vacuo to yield 1.27 g crude product. This product
(
0
1
m, 1H), 1.38 (m, 1H), 1.13 (d, 3H, J¼7.2 Hz), 1.06 (t, 3H, J¼7.2 Hz),
was subjected to MPLC and a fraction of 287 mg of (4S,5S)-2a was
isolated in 86% isomeric purity and 96% chemical purity.
13
.95 (t, 3H, J¼7.4 Hz); C NMR
d: 217.2, 72.8, 49.5, 35.3, 27.1, 10.6,
0.1, 7.8 ppm. For MS see syn-1a.
The crude product (4S,5S)-2a (287 mg, 2.0 mmol) was mixed
with vinyl acetate (1.0 g, 12 mmol) and Amano PS-D lipase (0.20 g)
ꢂ
4
.6. Synthesis of (4S,5R)-5-hydroxy-4-methyl-3-heptanone
was added. The mixture was incubated at 25 C/120 rpm in
(
(4S,5R)-1a)
a shaking water bath. After 4 days the lipase was filtered off and
rinsed with dichloromethane. The solvents were removed in vacuo
and the enriched alcohol was isolated from the formed ester by
MPLC yielding a fraction of 253 mg (4S,5S)-2a of 95% isomeric pu-
rity. Total yield from 3,5-heptanedione: 23%.
Compound syn-1a [0.60 g, 4.2 mmol (sum of isomers), 90% syn]
was mixed with vinyl acetate (2.0 g, 23.2 mmol) and Amano PS-D
lipase (0.30 g) was added. The mixture was incubated at 25 C/
ꢂ
120 rpm in a shaking water bath. After 4 days the lipase was filtered
off and rinsed with dichloromethane. The solvents were removed
in vacuo, the product was isolated from the remaining starting
material and enriched by repetitive MPLC (two times) yielding
a fraction of 185 mg (47%) (4S,5R)-1b in 92% isomeric purity.
The acetate (4S,5R)-1b (185 mg, 0.99 mmol) was mixed with
water (150 mL). Eggplant (S. melongena, 70 g) was cut into thin
slices (ca. 5 mm) and added to the mixture, which was incubated in
Acknowledgements
This work was supported by the University of Kalmar, Sweden
and the FRST-funded programme LINX0304 Ecosystem Bio-
Protection, New Zealand.
References and notes
ꢂ
an open container at 25 C/120 rpm in a shaking water bath for
2
4
0 h. The biological tissue was filtered off and rinsed with water (ca.
ꢀ50 mL). The remaining aqueous solution was extracted with
1. Schmuff, N. R.; Phillips, J. K.; Burkholder, W. E.; Fales, H. M.; Chen, C.-W.; Roller, P. P.;
Ma, M. Tetrahedron Lett. 1984, 25, 1533.
2. Unelius, C. R.; Wee, S. L.; McNeill, M.; Daly, J.; Bunn, B. J.; Gibb, A. R.; Bohman, B.;
diethyl ether (ca. 3ꢀ30 mL), washed with water (ca. 2ꢀ30 mL) and
Suckling, D. M. In preparation.
brine (ca. 30 mL), dried over MgSO
yield 61 mg crude product. This product was subjected to MPLC and
2 mg (4S,5R)-1a was isolated in 95% isomeric purity and 98%
4
, and concentrated in vacuo to
4
y
Yields calculated from the amount of (4R,5R)-2a present in the racemic starting
material, i.e., the yield obtained if (4S,5S)-2a would have been retrieved from the
chemical purity. Overall yield from 3-pentanone: 12%. For spectral
data see (4R,5S)-1a.
reaction mixture.

B. Bohman, C.R. Unelius / Tetrahedron 65 (2009) 8697–8701
8701
3
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