Tellurium in organic synthesis: A general approach to buteno- and butanolides

Article abstract of DOI:10.1016/j.tet.2012.09.074

The naturally occurring butanolides (-)-blastmycinolactol, (+)-blastmycinone, (-)-NFX-2, (+)-antimycinone as well as the four stereoisomers of the butenolide Acaterin were prepared in high enantiomeric purity using hydroxy-vinyl tellurides as starting mat

Full text of DOI:10.1016/j.tet.2012.09.074

Tetrahedron 68 (2012) 10601e10610
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Tellurium in organic synthesis: a general approach to buteno- and butanolidesq
,
a,b,
Renan S. Ferrarini a, Alcindo A. Dos Santos a , Joao V. Comasseto
*
*
~
a
~
~
Instituto de Química, Universidade de Sao Paulo, Av. Prof. Lineu Presteˇ s, 748, CxP. 26077, 05508-000 Sao Paˇ ulo, Brazil
Universidade Federal de Sao Paulo, Campus de Diadema, Instituto de Ciencias Ambientais, Químicas e Farmaceuticas, Departamento de Ciencias Exatas e da Terra, Setor de Química,
ˇ
b
~
Rua Prof. Artur Ridel, 275, CEP 09972-270, Jardim Eldorado, Diadema, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 June 2012
Received in revised form 23 July 2012
Accepted 25 July 2012
Available online 19 September 2012
The naturally occurring butanolides (ꢀ)-blastmycinolactol, (þ)-blastmycinone, (ꢀ)-NFX-2, (þ)-anti-
mycinone as well as the four stereoisomers of the butenolide Acaterin were prepared in high enantio-
meric purity using hydroxy-vinyl tellurides as starting materials.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Butenolides
Butanolides
(ꢀ)-Blastmycinolactol
(þ)-Blastmycinone
(ꢀ)-NFX-2
(þ)-Antimycinone
Acaterin
Tellurium
1. Introduction
on the poisoning of humans by these compounds, neither any illness
is associated to them. As a matter of fact, some groups have been
The organic chemistry of Te(II) compounds is well developed and
documented in books1 and review articles.2 There are many syn-
thetic transformations promoted by tellurium reagents.1,2 More re-
cently, some of these transformations, coupled to the enzymatic
kinetic resolution of tellurides bearing a secondary alcohol in their
structures, allowed the preparation of enantiomerically enriched
chiral building blocks.3 Despite the great development of the organic
chemistry of tellurium, the application of its chemistry in the syn-
thesis of bioactive molecules is very scarce.4 The reluctance of the
synthetic organic chemists to employ tellurium compounds for
synthetic purposes is probably due to old literature comments re-
garding the bad smell, instability, and the toxicity of organic tellu-
rium compounds. Presently, it is known that most organic tellurium
compounds are not bad smelling and can be manipulated in the
presence of light and air with no need for special precautions. Con-
cerning the biological activity of the organic tellurium compounds, it
must be said that to ourknowledge there is no report in the literature
underscoring the biological potential of tellurium organic com-
pounds as therapeutic agents.5 Consequently, we see no impediment
in the use of organic compounds of tellurium in total synthesis.
In this paper we present a full account of our efforts to use
tellurium based methodologies in the synthesis of optically active
buteno- and butanolides, which present biological activity. The
methodology developed in our group constitutes a new approach
to the construction of these important structural unities present in
many biologically active compounds.6 Our methodology takes ad-
vantage of the hydrotelluration of acetylenes stereoselectivity,
which gives only the Z-alkene,2a,c,7 and of the stereospecific
transformation of Z-vinylic tellurides into Z-vinyl-lithiums.2a,c,4,7e9
The target molecules chosen were (ꢀ)-Blastmycinolactol (1),
(þ)-Blastmycinone (2), (ꢀ)-NFX-2 (3), (þ)-Antimycinone (4) and
the four stereoisomers of Acaterin (5). Compounds 1e4 are hy-
drolysis products of Antimycin A3 (6) and Antimycin A1 (7), which
were isolated from Streptomyces sp. and present antifungal and
antitumor activities.10 The polyketide metabolites 1e4 present
a biological activity similar to that of the Antimycins.10 (ꢀ)-Acaterin
(5) is a metabolite of the bacteria Pseudomonas sp. A92, acting as
acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, and
is considered a promising therapeutic agent against atherosclero-
sis.11 The structures of the target molecules 1e5 are shown in
Scheme 1.
DOI of original article: 10.1016/j.tet.2012.07.088.
A publisher’s error resulted in this article appearing in the wrong issue. The article
q
isreprinted here for the reader’sconvenienceand for thecontinuityof the specialissue.
For citation purposes, please use the original publication details; Tetrahedron, 68(40),
pp. 8431e8440. DOI of original item: http://dx.doi.org/10.1016/j.tet.2012.07.088
* Corresponding authors. Tel.: þ55 11 3091 2176; fax: þ55 11 3815 5579; e-mail
address: jvcomass@iq.sup.br (J.V. Comasseto).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.074

10602
R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
a chiral intermediate in the synthesis of a butanolide 9 as in the
synthesis of 1e4. In this last hypothesis, the absolute configuration
of the carbinolic carbon should define the configuration of carbons
2 and 3, since the conjugate addition to 2-furanones leads pre-
dominantly to trans,trans systems.26 In the present case, this goal
should be met by the conjugate addition of a lithium silyl cyano-
cuprate to the butenolide 8, followed by a FlemingeTamao oxida-
tion, which occurs with retention of configuration,27 to yield
compounds 1 and 3. Compounds 1 and 3 on acylation should give
compounds 2 and 4.
2. Results and discussion
Scheme 1. Structure of the target molecules 1e5.
The starting alkynones 10a and 10b were prepared by acylation
From compounds 1e4, (ꢀ)-Blastmycinolactol (1) and
(þ)-Blastmycinone (2) received more attention from the synthetic
point of view. In general, the synthetic strategies employed to
prepare these compounds in enantiomerically enriched form were
based in chiral natural products transformations,12 enzymatic res-
olutions,13 oxidative heterocyclizations,14 Sharpless oxidations,15
use of chiral auxiliaries,16 enolates chemistry,17 and the use of
elaborate organometallics.18 Some of the problems found in the
enantioselective synthesis of these compounds are the formation of
diastereoisomeric mixtures,19 the great number of synthetic
steps,20 low global yields and the use of elaborate and expensive
starting materials. Concerning the butenolide Acaterin (5), few
synthetic studies aiming its preparation in its enantiomerically
enriched form are available.21,22 It is important to note the exis-
tence of biosynthetic assays aiming the elucidation of the bio-
synthetic mechanisms for its formation.23
of the corresponding alkyne, as shown in Eq. 1.
(1)
In the case of alkynone 10c, this procedure led to the product in
lower yield (34%). Alternatively, the protected propargyl alcohol 16,
prepared by addition of lithium acetylide to 1-octanal, followed by
protection with 2-methoxyethoxymethyl chloride (MEM-Cl), was
deprotonated with nBuLi, the resulting lithium acetylide was added
to acetaldehyde and the resulting alcohol was oxidized with Cr(VI)
(Scheme 3).
Scheme 2 shows the retrosynthesis of buteno- and butanolides
via tellurium reagents. As can be observed, the butenolides 8 can be
precursors of the butanolides 9.
Scheme 3. Preparation of alkynones 10c.
Scheme 2. Retrosynthetic analysis for 1e5.
The reaction sequence shown in Scheme 3 was performed with
the enantiomerically pure protected alcohols 16. The enantio-
merically pure alcohols (R)-15 and (S)-15 were obtained by enzy-
matic kinetic resolution of racemic 15 using NovozymeÒ 435 as the
catalyst and vinyl acetate as the acetyl donor in hexane at 32 ꢁC
(Scheme 4). The reaction conditions were optimized as shown in
Table 1.28
The starting material is an alkynone 10, commercially available
or easily prepared. The use of alkynones instead of propargyl al-
cohols as the starting material is due to the high regioselectivity of
the hydrotelluration of these compounds, in contrast to the low
regioselectivity of the hydrotelluration of propargyl alcohols.24 In
addition, the hydrotelluration of disubstituted non-activated al-
kynes does not occur.7 The alkyltelluro alcohol 12 should be ob-
tained by reduction of the telluroenone 11. The telluriumelithium
exchange reaction in vinylic tellurides is well established, being one
of the most studied reactions of organotellurium compounds.2,4,9,25
Carbonation of the vinyl-lithium 13 should give the butenolide 8.
The stereochemistry of the carbinolic carbon of 12 could be
established by an enzymatic kinetic resolution of the racemic 12,
leading to chiral building blocks (R)-13 and (S)-13. This versatility of
the methodology is important when the influence of the configu-
ration in the biological activity of the buteno- or butanolides is
being investigated, since it allows to access both stereoisomers of
the target compound. Molecules 8 can constitute the target com-
pounds, as is the case in the synthesis of Acaterin (5), or could be
Scheme 4. Enantiomerically pure (R)-15 and (S)-15 from (R,S)-15.

R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
10603
Table 1
The next step was the reduction of 11aec to the corresponding
alcohol 12. Attempts to reduce the carbonyl group of 11c in a ster-
eoselective way using N-Me-ephedrine,29 (S)-CBS-oxazobor-
olidine,30 (S)-Binol,31 and (R)-Alpineborane32 failed, leading to
decomposition or recovery of the starting material. In view of this
failure the telluroenones 11 were reduced with sodium borohy-
dride in a mixture of methanol/tetrahydrofuran (Scheme 6).
Enzymatic kinetic resolution of (R,S)-15a
Entry
Time (h)
Conv. (%)
ee (R)-15b (%)
ee (S)-18b (%)
E
1
2
3
4
5
6
7c
8
9
0.5
1
1.5
2
2.5
3
3.5
4
24
37
44
47
49
51
49
49
51
32.2
56.6
75.5
87.6
93
>99
98.2
98.6
98
>200
176
>200
>200
167
>200
>200
>200
148
96
97.8
>99
>99
98.8
95.9
94.3
94
4.5
94
a
Reaction conditions: (R,S)-15, NovozymeÒ 435, CH2]CHOAc, hexane, 32 ꢁC,
argon.
b
c
The enantiomeric excesses were determined by chiral gas chromatography.
Conditions of choice.
The best results were obtained at 3.5 h reaction time and at 49%
conversion (entry 7, Table 1). Under the optimal conditions (R)-15
was obtained in >99% ee and the acetate (S)-18 was obtained with
94.5% ee. After the separation of (R)-15 and (S)-18 by silica gel
column flash chromatography, the acetate (S)-18 was hydrolyzed
using the NovozymeÒ 435 recovered from the enzymatic kinetic
resolution of 15 shown in Scheme 4. The reaction conditions for the
hydrolysis reaction and the obtained results are shown in Table 2.
Scheme 6. Reduction of the telluroenones 11.
In order to obtain the enantiomerically enriched allyl alcohols
12a and 12b, an enzymatic kinetic resolution of (R,S)-12a and (R,S)-
12b was performed, using NovozymeÒ 435 in hexane under argon
and in the dark, as shown in Scheme 7. The alcohols (S)-12a and (S)-
12b were separated from the acetate (R)-19a and (R)-19b by silica
gel column flash chromatography.
Table 2
Hydrolysis of (S)-18a
Entry
Time (h)
ee (S)-15b
1
2
2
2.5
3
98.9
98.2
99.8
99.9
3
4c
3.5
a
Conditions: (R)-18, Na2HPO4/KH2PO4, 10 mM, pH¼7, NovozymeÒ 435, acetone,
32 ꢁC.
b
c
The enantiomeric excesses were determined by chiral gas chromatography.
Conditions of choice.
The best result was obtained at 3.5 h reaction time, and the al-
Scheme 7. Enzymatic kinetic resolution of 12a and 12b.
cohol (S)-15 was obtained in >99% ee. In Scheme 4 is presented
a summary of the whole process.
The allyl alcohols (R)-12a and (R)-12b were obtained by hy-
drolysis of the acetates (R)-19a and (R)-19b. With both enantiomers
of the telluro alcohols 12a and 12b in hands, the tellurium/lithium
exchange reaction was performed by treating them with 2 equiv of
nBuLi. The obtained dianion was treated with ultra-dry carbon
monoxide and after acidification of the reaction medium, the
butenolides 8a and 8b were obtained with the yields and enan-
tiomeric excesses shown in Scheme 8.
With the alkynones 10a, 10b, (R)-10c and (S)-10c in hands, the
hydrotelluration reaction was performed by reacting them with
a hydrotellurating mixture prepared by treating a suspension of
elemental tellurium in THF with nBuLi in hexane at 0 ꢁC followed by
addition of deoxygenated ethanol at room temperature, under ar-
gon, as shown in Scheme 5. As expected2a,7e9 only the Z isomer was
formed.
Scheme 8. Preparation of the butenolides 8a and 8b.
In the case of alcohols 12c the lactonization step was performed
with the two pairs of diastereomers following the same protocol
shown in Scheme 8, leading to the two pairs of diastereomeric
lactones 8c and 8d, which after deprotection with TiCl4 and sepa-
ration by silica gel column flash chromatography gave the four pure
stereoisomers of Acaterin in high enantiomeric purity as shown in
Scheme 9 and in Chart 1.
Scheme 5. Hydrotelluration of alkynones 10aec.

10604
R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
Table 3
1,4-Addition of silylcuprates to angelicalactone (20)
Entry
Silylchloride
Lithium
Copper salt
Yield in 21a (%)
1
Me2PhSiCl
Me2PhSiCl
tBuPh2SiCl
iPr3SiCl
Slices
CuCN
CuCN
CuCN
CuCN
CuI
20
80
59
Traces
50
2c
3
Suspensionb
Suspensionb
Suspensionb
Suspensionb
4
5
Me2PhSiCl
a
Isolated yields.
Suspension in mineral oil (30% m/m) doped with sodium.
Conditions of choice.
b
c
The chosen conditions were those shown in entry 2 of Table 3. In
this way, dilithium dimethyl(phenyl)silylcyanocuprate (22) was
used in the 1,4-addition to enones (S)-8a and (S)-8b. The addition
occurred in an anti fashion and the methyl group at the carbinol
carbon of the butenolides (S)-8a and (S)-8b defined the stereo-
chemistry at C3 of the resulting enolate, which was trapped by
a proton source to give the anti,anti three contiguous substituted
butyrolactones 23a and 23b (Scheme 11). The optical rotation of
23a and 23b agree with those found in the literature for the same
compounds.26a
A similar reaction sequence was used by Bruckner26a to prepare
23a and 23b from 8 (R¼H). The capture of the intermediate enolate
by an alkylating agent gave the products 23 in moderate yields. As
the alkyl groups are already present in 8a and 8b (R¼nBu and nHex),
by our method the capture of the enolate by a proton source
resulted in improved yields of 23a and 23b.
Scheme 9. Preparation of the four stereoisomers of Acaterin (5).
Stereoisomer
Absolute
configuration
Overall Yielda,b
[α]D
Literature21a
This work
(%)
-19.7
(c 0.61; CHCl3)
+62.6
(c 1.06; CHCl3)
-63.7
(c 0.53; CHCl3)
+19.6
(c 1.04; CHCl3)
-19.0
(c 1.0; CHCl3)
+60.1
(c 1.0; CHCl3)
-59.7
(c 1.0; CHCl3)
+20.2
(c 1.0; CHCl3)
5a
5b
5c
5d
(R,R)
(R,S)
(S,R)
(S,S)
15%
13%
14%
13%
aThe yields were calculated considering the alcohols (R)-15 and (S)-15 as starting materials.
bIn the last step the maximal yield is 50%, since a pair of diastereoisomers was separated.
Chart 1. Optical rotations of the four stereoisomers of Acaterin (5).
The chiral lactones (S)-8a and (S)-8b were employed as ad-
vanced precursors in the enantioselective synthesis of the target
molecules 1e4. For this and, a 1,4-addition of a silylcuprate to the
enones (S)-8a and (S)-8b was planed. An exploratory study to de-
termine the optimal conditions for this reaction was performed
using Angelicalactone (20) as a model compound. As shown in
Scheme 10, different silylcuprates were employed. The results are
given in Table 3.
Scheme 11. Silylcuprate 22 addition to butenolides (S)-8a and (S)-8b.
The silyl lactones 23a and 23b were submitted to the Fle-
mingeTamao oxidation27 using the conditions shown in
Scheme 12.
The best results were obtained by using protocol B, in view of
the milder reaction conditions.
The absolute configurations of compounds 1 and 3 were con-
firmed by comparing the [a]
D values of the literature26a with those
found by us.
By the sequence described above, (ꢀ)-Blastimycinolactol (1) and
(ꢀ)-NFX-2 (3) were synthesized in four steps in 23% and 20% yield,
respectively, if we consider the enantiomerically enriched
Scheme 10. 1,4-Addition of silylcuprates to Angelicalactone (20).

R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
10605
were performed using commercially available plates from Merck
(E. Merck, 5544, 0.2 mm), which were developed under ultraviolet
light (
n
¼254 nm) or iodine. Alternatively the plates were de-
veloped by vanillin in a mixture of sulfuric acid/ethanol (6% van-
illin m/v, 4% sulfuric acid and 10% water in ethanol v/v), by
a solution of p-anisaldehyde m/v, (4% sulfuric acid, 1% acetic acid in
ethanol v/v) or by an aqueous basic solution of potassium
permanganate (1% KMnO4, 2% NaOH in water m/v). The gas
chromatographic analysis (GC) were performed with Shimadzu
GC-2010 and Shimadzu GC-2014 equipments, with flame ioniza-
tion detector (FID). The carrier gas was nitrogen, or hydrogen when
chiral columns were employed. The columns employed were: J&B
Scheme 12. FlemingeTamao oxidation of 23a and 23b.
hydroxytellurides (S)-12a and (S)-12b as the starting materials, or
in 9% and 11%, respectively, if we consider the alkynones 10 as the
starting materials. The preparation of Blastmycinone (2) and Anti-
mycinone (4) was accomplished by acylation of 1 and 3, as shown in
Scheme 13.33 The enantiomeric excess of 2 and 4 were determined
by chiral gas chromatography, using racemic samples of the same
compounds for comparison, which were prepared by the same
route described above, starting from racemic hydroxytellurides 12a
and 12b. The optical rotation of the products obtained here agree
with those found in the literature.15b,34
ScientificÒ DB-35 (30 mꢂ0.25 mmꢂ0.15
m
m); SupelcoÒ Gamma
DEX 120 (30 mꢂ0.25 mmꢂ0.25
m
m); SupelcoÒ Beta DEX 110
mm). The nuclear magnetic resonance
(30 mꢂ0.25 mmꢂ0.25
spectra (1H NMR and 13C NMR) were registered with Bruker DPX-
300 (300 MHz, 1H; 75 MHz, 13C), Bruker DPX-500 (500 MHz, 1H;
125 MHz, 13C), Varian-Inova (300 MHz, 1H; 75 MHz, 13C); and
Bruker AvanceIII-200 (200 MHz, 1H; 50 MHz, 13C). In all cases tetra-
methylsilane (TMS) was used as internal standard and CDCl3 as sol-
vent. The 125Te NMR spectra were obtained with a Bruker DPX-500
(157.9 MHz, 125Te) and a Bruker AvanceII-200 (63.2 MHz, 125Te), us-
ing CDCl3 as solvent and Ph2Te2 as internal reference. The optical
rotation values were obtained with a Perkin Elmer 343 polarimeter
using 5 mm or 1 cm optical pass cuvettes. The melting points were
measured with a Buchi Melting Point B-545. The low resolution mass
spectra were obtained with a Shimadzu GCeMS-17A/QP5050A ap-
paratus. The high resolution mass spectra were obtained with
a Bruker Daltonics MicroTOF equipment. The infrared spectra were
obtained with a Bomem MB-100 spectrometer. The IUPAC names of
all compounds were obtained using a ChemDraw, version 11.0.1
software. The NMR spectra were processed using a MestreNova
software.
Scheme 13. Preparation of 2 and 4.
4.2. Enzymatic kinetic resolution of the propargyl alcohol 15
3. Conclusion
4.2.1. Typical procedure. In four 250 mL erlenmeyer flasks was
placed the propargyl alcohol 15 (20 mmol; 3.08 g in each flask) and
previously dried and deoxygenated hexane (100 mL in each flask).
Then the lipase NovozymeÒ 435 was added (0.84 g, 10,000 PLU gꢀ1
in each flask). The resulting solutions were purged with argon and
then vinyl acetate (62.5 mmol, 5.0 mL in each flask) was added. The
flasks were shacked in an orbital shaker (180 rpm) at 32 ꢁC for 3.5 h.
Then the enzyme was removed by filtration and the combined fil-
trates were concentrated under vacuum. The residue was purified
by flash silica gel column chromatography eluting with a mixture
(9:1) of hexane/ethyl acetate.
In conclusion, a general method of synthesis of enantiomerically
enriched buteno- and butanolides was developed. This method
allows the synthesis of the different enantiomers of biologically
active buteno- and butanolides, starting from a common telluride.
The versatility of this approach allowed the preparation of com-
pounds 1e5 in their enantiomerically enriched forms. Similarly,
a number of naturally occurring buteno- and butanolides could be
synthesized by the methodology described above.
4. Experimental section
4.1. General
4.2.1.1. (S)-Dec-1-yn-3-ol [(R)-15]. Colorless liquid (6.04 g, 49%);
dH(500 MHz, CDCl3) 0.88 (3H, t, J 7.0 Hz), 1.23e1.35 (8H, m),
1.41e1.48 (2H, m), 1.65e1.77 (2H, m), 2.33e2.39 (1H, m), 2.45 (1H,
d, J 5.0 Hz), 4.36 (1H, dt, J 5.0, 2.5 Hz); dC (125 MHz, CDCl3) 13.9,
22.5, 24.9, 29.12, 29.14, 31.7, 37.5, 62.2, 72.7, 85.0; nmax (liquid film)
The reagents and solvents were dried and purified according the
literature procedures.35 The THF was distilled from sodium/ben-
zophenone under nitrogen immediately before use. nBuLi was ti-
trated with isopropanol, using 1,10-phenanthroline as indicator.36
The nitrogen or argon were deoxygenated and dried. Elemental
tellurium (200 mesh), copper(I) cyanide (99%) and elemental lith-
ium (30% m/m, dispersed in mineral oil and dropped with sodium)
were purchased from Aldrich Chemical Co. The nBuLi employed was
purchased from Merck KGaA, Chemetall GmbH or Acros Organics.
The ultra-pure anhydrous carbon dioxide was purchased from Air
ProductsÒ.
3311, 2926, 2857, 1466, 1046, 1022, 654, 627 cmꢀ1; ½a D20
þ4.0 (c 3.0,
ꢃ
CHCl3, ee >99%); chiral GC-FID [SupelcoÒ Beta DEX 110 column,
carrier gas: H2, injector temperature: 275 ꢁC, detector temperature:
275 ꢁC, pressure: 100 kPa, method, isotermic: 100 ꢁC; tR: (R)-15
17.92 min; (S)-15 17.36 min; (S)-18 22.62 min and (R)-18 21.35 min;
CAS [74867-41-7].
4.2.1.2. (R)-Dec-1-yn-3-yl acetate[(S)-18]. Colorless liquid (7.68 g,
49%); dH (500 MHz, CDCl3) 0.88 (3H, t, J 7.0 Hz), 1.27e1.31 (8H, m),
1.43 (2H, quint, J 7.5 Hz), 1.74e1.79 (2H, m), 2.07 (3H, s), 2.44 (1H, d, J
2.0 Hz), 5.33 (1H, dt, J 7.0, 2.0 Hz); dC (125 MHz, CDCl3) 14.0, 20.9,
22.6, 24.8, 29.0, 29.1, 31.7, 34.5, 63.8, 73.3, 81.3, 169.9; nmax (liquid
film) 3312, 2928, 2123, 1744, 1372, 1233, 1022; HRMS (ESI): m/z
The column chromatographic separations were performed with
Acros Organics (230e400 mesh) flash silica gel. Kieselgel 60 PF254
from Merck was used in the preparative thin layer chromato-
graphic separations. The thin layer chromatographic analysis (TLC)

10606
R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
([MþNa]þ) found 219.1359. C12H20NaO2 requires 219.1361; ½a D20
ꢃ
temperature and stirred for 10 min at this temperature. The re-
action was quenched with 5% aqueous solution of HCl (20 mL), the
aqueous phase was extracted with ethyl acetate (3ꢂ40 mL) and the
combined extracts were washed with brine (50 mL) and dried with
magnesium sulfate. The solvent was removed under vacuum and
the residue was purified by silica gel flash column chromatography
eluting with a mixture (3:1) of hexane/ethyl acetate.
ꢀ54.1 (c 3.0, CHCl3, ee 94%).
4.3. Enzymatic hydrolysis of the propargyl acetate (S)-18
In four 250 mL erlenmeyer flasks was added the propargyl ac-
etate (S)-18 (10 mmol, 1.96 g in each flask) and acetone (10 mL in
each flask). Then NovozymeÒ 435 (1 g, 10,000 PLU gꢀ1) recovered
from the preceding reaction was added to each flask. To the
resulting mixture it was added Na2HPO4/KH2PO4 (10 mM, pH¼7;
100 mL in each flask). The flasks were shacked for 3.5 h at 32 ꢁC in
an orbital shaker (180 rpm). Then the enzyme was removed by
filtration. The combined filtrates were extracted with ethyl acetate
(3ꢂ70 mL), the organic phases were washed with brine (50 mL)
and dried with magnesium sulfate. The solvent was removed under
vacuum and the residue was purified by silica gel flash column
chromatography.
4.5.1.2. (5R)-5-((2-Methoxyethoxy)methoxy)dodec-3-yn-2-ol
(17a). Diastereoisomeric mixture (1:1) (4.75 g, 92%) as colorless
liquid; dH (500 MHz, CDCl3) 0,88 (3H, t, J 7.2 Hz),1.24e1.29 (16H, m),
1.39e1.50 [(10H, m), 1.43 (3H, t, J 6.6 Hz), 1.44 (3H, t, J 6.6 Hz)],
1.67e1.78 (4H, m), 3.39 (3H, s), 3.40 (3H, s), 3.57e3.59 (4H, m),
3.68e3.80 (4H, m), 4.32e4.37 (2H, m), 4.51e4.57 (2H, m), 4.74 (1H,
d, J 2.5 Hz), 4.75 (1H, d, J 2.5 Hz), 4.97 (1H, d, J 1.0 Hz), 4.98 (1H, d, J
1.0 Hz); dC (125 MHz, CDCl3) 14.1, 22.6, 24.27, 24.34, 25.3, 29.2, 31.8,
35.69, 35.72, 58.20, 58.22, 59.0, 66.4, 66.5, 67.3, 71.89, 71.91, 82.91,
82.94, 87.43, 87.47, 93.8, 93.9; nmax (liquid film) 3463, 2928, 2209,
1731, 1682, 1459, 1223, 1032 cmꢀ1; HRMS (ESI): m/z ([MþNa]þ)
4.3.1. (S)-Dec-1-yn-3-ol [(S)-15]. Colorless liquid (5.79 g, 94%); the
found 309.2030. C16H30NaO4 requires 309.2042; ½a D20
þ96.0 (c 1.0,
ꢃ
same spectral data as those described for (R)-15; ½a D20
ꢀ4.9 (c 3.0,
ꢃ
CHCl3).
CHCl3, ee >99%); CAS [74867-42-8].
4.5.1.3. (5S)-5-((2-Methoxyethoxy)methoxy)dodec-3-yn-2-ol
4.4. Protection of alcohols (R)-15 and (S)-15 with MEM-Cl
(17b). Diastereoisomeric mixture (1:1) (4.67 g, 90%) as colorless
liquid; same spectral data as for 17a. ½a D20
ꢀ99.8 (c 1.0, CHCl3).
ꢃ
4.4.1. Typical procedure. To a 150 mL round bottomed flask under
magnetic stirring, previously flame-dried and under argon, were
added the propargyl alcohol (R)-15 (39 mmol; 6.0 g), CH2Cl2
(80 mL) and diisopropylamine (57.2 mmol; 9.8 mL). The solution
was cooled to 0 ꢁC and then MEM-Cl (57.2 mmol; 6.6 mL) was
added. After 10 min the mixture was heated to room temperature
and stirred overnight. The reaction was extracted with a 5% aque-
ous solution of HCl (20 mL), the organic phase was extracted with
CH2Cl2 (3ꢂ40 mL), and the combined extracts were washed with
brine (50 mL) and the dried with magnesium sulfate. The solvent
was evaporated under vacuum and the residue was purified by
silica gel flash column chromatography eluting with a mixture (4:1)
of hexane/ethyl acetate.
4.5.2. Jones oxidation of alcohols 17
4.5.2.1. Typical procedure. To a two necked 250 mL round bot-
tomed flask equipped with magnetic stirring and a dropping fun-
nel, the alcohol 17 (18.2 mmol; 5.19 g) and diethyl ether (40 mL)
were added. The solution was cooled to 0 ꢁC and then it was slowly
added via dropping funnel the chromic acid solution prepared from
potassium dichromate (25 mmol; 7.35 g in 20 mL of water) and
sulfuric acid (89 mmol; 4.9 mL in 30 mL of water). After the addi-
tion, the reaction mixture was allowed to reach the room temper-
ature and stirred for 5 h. The mixture was then diluted with diethyl
ether (100 mL) and extracted with water (40 mL). The resulting
aqueous phase was extracted with diethyl ether (3ꢂ40 mL) and the
combined organic phases were washed with saturated solution of
NaHCO3 (50 mL) and then dried with magnesium sulfate. The sol-
vent was removed under vacuum and the residue was purified by
silica gel flash chromatography eluting with a mixture (4:1) of
hexane/ethyl acetate.
4.4.1.1. (R)-3-((2-Methoxyethoxy)methoxy)dec-1-yne [(R)-16].
Colorless liquid (7.56 g, 80%); dH (300 MHz, CDCl3) 0.88 (3H, t, J
6.6 Hz), 1.26e1.33 (8H, m), 1.44e1.51 (2H, m), 1.69e1.77 (2H, m),
2.39 (1H, d, J 2.1 Hz), 3.39 (3H, s), 3.54e3.56 (2H, m), 3.62e3.67
(1H, m), 3.74e3.80 (1H, m), 4.35 (1H, dt, J 6.6, 2.1 Hz), 4.71 (1H, d, J
7.0 Hz), 5.00 (1H, d, J 7.0 Hz); dC (75 MHz, CDCl3) 14.1, 22.7, 25.2,
29.2, 29.3, 31.8, 35.6, 59.0, 65.6, 67.2, 71.7, 73.4, 82.7, 93.2; nmax
(liquid film) 3310, 2927, 2111, 1466, 1100, 1036 cmꢀ1; HRMS (ESI):
m/z ([MþNa]þ) found 265.1769. C14H26NaO3 requires 265.1779;
4.5.2.2. (R)-5-((2-Methoxyethoxy)methoxy)dodec-3-yn-2-one
[(R)-(10c)]. Colorless liquid (4.70 g, 91%); dH (500 MHz, CDCl3) 0.88
(3H, t, J 7.2 Hz), 1.28e1.32 (8H, m), 1.45e1.48 (2H, m), 1.72e1.83 (2H,
m), 2.34 (3H, s), 3.39 (3H, s), 3.55e3.57 (2H, m), 3.66e3.70 (1H, m),
3.74e3.78 (1H, m), 4.99 (1H, t, J 6.7 Hz), 4.72 (1H, d, J 7.2 Hz), 4.95
(1H, d, J 7.2 Hz); dC (125 MHz, CDCl3) 14.1, 22.6, 25.2, 29.1, 29.2, 31.8,
32.7, 34.9, 59.0, 65.6, 67.4, 71.7, 84.7, 90.4, 93.6, 184.1; nmax (liquid
film) 2928, 2210, 1717, 1459, 1224, 1031 cmꢀ1; HRMS (ESI): m/z
½
a 2D0
ꢃ
þ106.1 (c 1.0, CHCl3).
4.4.1.2. (S)-3-((2-Methoxyethoxy)methoxy)dec-1-yne
[(S)-
16]. Colorless liquid (7.28 g, 77%); same spectral data as for (R)-16.
½
a 2D0
ꢃ
ꢀ108.4 (c 1.0, CHCl3).
([MþNa]þ) found 307.1876. C16H28NaO4 requires 307.1886; ½a D20
ꢃ
þ138.9 (c 1.0, CHCl3).
4.5. Preparation of alkynols (5R)-10c and (5S)-10c
4.5.2.3. (S)-5-((2-Methoxyethoxy)methoxy)dodec-3-yn-2-one
4.5.1. Preparation of alcohols 17
[(S)-(10c)]. Colorless liquid (4.59 g, 89%); same spectral data as for
[(R)-(10c)]. ½a D20
ꢀ145.7 (c 1.0, CHCl3).
ꢃ
4.5.1.1. Typical procedure. To a 250 mL two necks round bot-
tomed flask, under magnetic stirring, previously flame-dried under
argon, was added the MEM-ether (R)-16 or (S)-16 (21.8 mmol;
5.28 g) and THF (80 mL). The solution was cooled to ꢀ78 ꢁC and
nBuLi (22 mmol; 18.6 mL of a 1.18 mol Lꢀ1 in hexane) was added,
then the mixture was allowed to reach the room temperature and
stirred for 20 min. After this, the mixture was cooled again to
ꢀ78 ꢁC and acetaldehyde (79.7 mmol; 4.5 mL) was added. After the
addition the reaction mixture was allowed to reach the room
4.6. Hydrotelluration of alkynones 10a and 10b
4.6.1. Typical procedure. In a 250 mL two necked flask equipped
with magnetic stirring, previously flame-dried and under argon,
was added elemental tellurium (30 mmol; 4.08 g) and THF (70 mL).
The suspension was cooled to 0 ꢁC and then nBuLi (32 mmol;

R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
10607
26.7 mL of a 1.2 mol Lꢀ1 solution in hexane) was added leading to
4.8. Reduction of the enones [(R)-(11c)] and [(S)-(11c)] to the
a pale yellow solution. After 5 min the mixture was allowed to
reach the room temperature and then ethanol (72 mmol; 4.2 mL)
was added. In the following the alkynone 10a (30 mmol; 3.72 g) or
10b (30 mmol; 4.57 g) was added net. After 30 min of stirring at
room temperature, the reaction mixture was diluted with ethyl
acetate (70 mL), washed with water (20 mL) and brine (20 mL) and
the organic phase was separated and dried with magnesium sul-
fate. The solvents were evaporated in a rotatory evaporator and the
residue was purified by flash silica gel column chromatography
eluting with a mixture (20:1) of hexane/ethyl acetate.
allyl alcohols [(5R)-(12c)] and [(5S)-(12c)]
4.8.1. Typical procedure. To a 100 mL round bottomed flask equip-
ped with magnetic stirring, the enone 11c (9 mmol; 4.32 g) and THF
(30 mL) were added. The solution was cooled to 0 ꢁC and then
NaBH4 (10 mmol; 0.39 g) in methanol (10 mL) was added. The
progress of the reaction was monitored by TLC and after the con-
sumption of the starting material the mixture was diluted with
ethyl acetate (30 mL) and washed with water (30 mL). The organic
phase was extracted with ethyl acetate (2ꢂ30 mL) and the com-
bined organic phases were washed with brine (30 mL) and then
dried with magnesium sulfate. The solvents were removed in
vacuum and the residue was purified by silica gel flash column
chromatography using a mixture (4:1) of hexane/ethyl acetate.
4.6.1.1. (Z)-4-(Butyltellanyl)oct-3-en-2-one (11a). Yellow oil
(6.51 g, 70%); dH (300 MHz, CDCl3) 0.93 (3H, t, J 7.3 Hz), 0.94 (3H, t, J
7.3 Hz), 1.41 (4H, hept, J 7.3 Hz), 1.52e1.60 (2H, m), 1.70 (2H, quint, J
7.6 Hz), 2.18 (3H, s), 2.55 (2H, t, J 7.6 Hz), 2.63 (2H, t, J 7.8 Hz), 7.18
(1H, s); dC (75 MHz, CDCl3) 5.9, 13.5, 13.9, 22.2, 25.4, 29.9, 32.9, 33.4,
39.5, 127.6, 159.1, 196.2; dTe (157.9 MHz, CDCl3, Ph2Te2) 627.0; nmax
(liquid film) 2958, 2928, 2869, 1644, 1522, 1208 cmꢀ1; HRMS (ESI):
m/z ([MþNa]þ) found 335.0692. C12H22OTeNa requires 335.0630.
4.8.1.1. (5R,Z)-4-(Butyltellanyl)-5-((2-methoxyethoxy)methoxy)
dodec-3-en-2-ol [(5R)-(12c)]. Diastereomeric mixture (1:1) (3.78 g,
89%) as yellow liquid; dH (500 MHz, CDCl3) 0.80e0.85 (12H, m),
1.14e1.34 (30H, m), 1.56e1.68 (10H, m), 2.60e2.73 (4H, m); 3.32
(6H, s), 3.47e3.49 (4H, m), 3.56e3.71 (4H, m), 3.84 (1H, t, J 6.5 Hz),
3.91 (1H, dd, J 7.0, 5.5 Hz), 4.55e4.62 (4H, m), 4.68e4.69 (2H, m),
5.87 (1H, d, J 8.0 Hz), 5.90 (1H, d, J 8.0 Hz); dC (125 MHz, CDCl3) 7.08,
7.11, 13.4, 14.1, 22.6, 22.9, 23.0, 25.0, 25.5, 25.6, 29.2, 29.4, 29.42,
31.79, 31.80, 34.1, 35.8, 36.0, 59.0, 67.15, 67.18, 71.5, 71.79, 71.84,
71.9, 83.4, 84.0, 93.16, 93.25, 122.7, 123.3, 144.2, 144.9; dTe
(157.9 MHz, CDCl3, Ph2Te2) 190.5, 207.3; nmax (liquid film) 3438,
2926, 1621, 1457, 1260, 1104, 1032, 799 cmꢀ1; HRMS (ESI): m/z
4.6.1.2. (Z)-4-(Butyltellanyl)dec-3-en-2-one (11b). Yellow oil
(7.29 g, 72%); dH (300 MHz, CDCl3) 0.88e0.96 (6H, m), 1.32e1.49
(8H, m),1.51e1.61 (2H, m),1.70 (2H, quint, J 7.9 Hz), 2.18 (3H, s), 2.55
(2H, t, J 7.9 Hz), 2.62 (2H, t, J 7.9 Hz), 7.18 (1H, s); dC (75 MHz, CDCl3)
6.0,13.5,14.0, 22.6, 25.4, 28.8, 29.9, 31.4, 31.6, 32.9, 39.8,127.7,159.3,
196.3; dTe (157.9 MHz, CDCl3, Ph2Te2) 626.9; nmax (liquid film) 2957,
2928, 2857, 1644, 1521, 1359, 1202 cmꢀ1; HRMS (ESI): m/z
([MþNa]þ) found 363.0938. C14H26OTeNa requires 363.0943.
([MþNa]þ) found 497.1883.C20H40O4TeNa requires 497.1887; ½a D20
ꢃ
ꢀ23.9 (c 1.0, CHCl3).
4.7. Hydrotelluration of alkynones (S)-10c and (R)-10c
4.8.1.2. (5S,Z)-4-(Butyltellanyl)-5-((2-methoxyethoxy)methoxy)
dodec-3-en-2-ol [(5S)-(12c)]. Diastereomeric mixture (1:1) (3.78 g,
89%) as orange oil; same spectral data as for [(5R)-(12c)]; dTe
4.7.1. Typical procedure. To a two necked 250 mL round bottomed
flask equipped with magnetic stirring and previously flame-dried
under argon, it was added elemental tellurium (14.6 mmol;
1.86 g) and THF (60 mL). The suspension was cooled to 0 ꢁC and
then nBuLi (14.6 mmol; 12.4 mL of a 1.18 mol Mꢀ1 solution in
hexane) was added, leading to a pale yellow solution. After 5 min,
the mixture was allowed to reach the room temperature and then
ethanol (37.9 mmol; 2.2 mL) was added. In the following the alky-
none 10c (11.2 mmol; 3.19 g) was added. After 30 min stirring at
room temperature, the reaction mixture was diluted with ethyl
acetate (70 mL) and washed with water (20 mL), brine (20 mL) and
dried with magnesium sulfate. The solvents were removed under
vacuum and the residue was purified by silica gel flash column
chromatography eluting with a mixture (4:1) of hexane/ethyl
acetate.
(157.9 MHz, CDCl3, Ph2Te2) 191.2, 207.3; ½a D20
þ20.0 (c 1.0, CHCl3).
ꢃ
4.9. Reduction of enones 11a and 11b to the corresponding
alcohols 12a and 12b
4.9.1. Typical procedures. In
a 100 mL round bottomed flask
equipped with magnetic stirring was added the telluroenone 11a
(20 mmol, 6.19 g) and THF (35 mL). The solution was cooled to 0 ꢁC
and then a solution of NaBH4 (80 mmol; 3.12 g) in methanol
(10 mL) was slowly added. The progress of the reaction was mon-
itored by TLC and after the consumption of all of the starting ma-
terial, the mixture was diluted with ethyl acetate and washed with
water (30 mL). The aqueous phase was extracted with ethyl acetate
(2ꢂ30 mL) and the combined organic phases were washed with
brine (30 mL) and then dried with magnesium sulfate. The solvents
were removed in a rotary evaporator and the residue was purified
by flash silica gel column chromatography eluting with a mixture
(4:1) of hexane/ethyl acetate.
4.7.1.1. (R,Z)-4-(Butyltellanyl)-5-((2-methoxyethoxy)methoxy)do-
dec-3-en-2-one [(R)-(11c)]. Yellow oil (4.47 g, 84%); dH (500 MHz,
CDCl3) 0.88 (3H, t, J 7.5 Hz), 0.94 (3H, t, J 7.5 Hz), 1.27e1.46 (12H, m),
1.56e1.72 (6H, m), 2.22 (3H, s); 2.53e2.58 (1H, m), 2.65e2.71 (1H,
m), 3.39 (3H, s), 3.54 (2H, t, J 5.0 Hz), 3.61e3.65 (1H, m), 3.79e3.84
(1H, m), 4.59 (1H, dd, J 9.0, 3.5 Hz), 7.47 (1H, s); dC (125 MHz, CDCl3)
6.2, 13.5, 14.0, 22.6, 25.3, 26.0, 29.2, 29.4, 30.8, 31.8, 32.7, 37.5, 59.0,
67.4, 71.7, 79.2, 93.7, 125.8, 158.2, 196.7; dTe (157.9 MHz CDCl3,
Ph2Te2) 615.5; nmax (liquid film) 2955, 2856.7,1644.2,1524.1,1463.2,
1359.7, 1194.5, 1107.9, 1023 cmꢀ1; HRMS (ESI): m/z ([MþNa]þ)
4.9.2. (R,S)-(Z)-4-(Butyltellanyl)oct-3-en-2-ol (12a). Orange oil
(5.30 g, 80%); dH (300 MHz, CDCl3) 0.91 (6H, t, J 7.2 Hz), 1.25 (3H, d, J
6.3 Hz),1.28e1.40 (4H, m),1.48 (2H, quint, J 7.2 Hz),1.72 (2H, quint, J
7.2 Hz), 1.85 (1H, d, J 3.0 Hz), 2.32 (2H, t, J 7.2 Hz), 2.68 (2H, dt, J 7.7,
3.9 Hz), 4.56 (1H, quint, J 6.3 Hz), 5.70 (1H, d, J 7.7 Hz); dC (75 MHz,
CDCl3) 5.3, 13.4, 13.9, 21.8, 23.0, 25.1, 31.9, 34.2, 41.5, 71.7, 121.5,
140.5; dTe (157.9 MHz, CDCl3, Ph2Te2) 265.8; nmax (liquid film) 3339,
2959, 2927, 2871, 1460, 1054 cmꢀ1; HRMS (ESI): m/z ([MþNa]þ)
found 337.0782. C12H24OTeNa requires 337.0787.
found 495.1725. C20H38O4TeNa requires 495.1730; ½a D20
þ167.1 (c
ꢃ
1.0, CHCl3).
4.7.1.2. (S,Z)-4-(Butyltellanyl)-5-((2-methoxyethoxy)methoxy)do-
dec-3-en-2-one [(S)-(11c)]. Yield (4.52 g, 85%) same spectral data as
4.9.2.1. (R,S)-(Z)-4-(Butyltellanyl)dec-3-en-2-ol
oil (6.05 g, 85%); dH (300 MHz, CDCl3) 0.89 (3H, t, J 6.6 Hz), 0.92 (3H,
t, J 7.4 Hz), 1.26 (3H, d, J 6.3 Hz), 1.28e1.32 (6H, m), 1.39 (2H, quint, J
(12b). Orange
for [(R)-(11c)]. dTe (157.9 MHz, CDCl3, Ph2Te2) 617.2; ½a D20
ꢃ
ꢀ173.7 (c
1.0, CHCl3).

10608
R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
7.5 Hz), 1.67e1.77 (4H, m), 2.32 (2H, t, J 7.5 Hz), 2.68 (2H, dt, J 7.4,
4.5 Hz), 4.56 (1H, quint, J 6.4 Hz), 5.69 (1H, d, J 7.7 Hz); dC (75 MHz,
CDCl3) 5.3, 13.4, 14.1, 22.6, 23.1, 25.2, 28.5, 29.8, 31.7, 34.3, 41.9, 71.8,
121.9, 140.4; dTe(157.9 MHz, CDCl3, Ph2Te2) 265.8; nmax (liquid film)
3320, 2958, 2926, 2855, 1461, 1056 cmꢀ1; HRMS (ESI): m/z
([MþNa]þ) found 365.1092. C14H28OTeNa requires 365.1100.
with saturated solutions of NaHCO3 (30 mL) and NaCl (30 mL) and
dried with magnesium sulfate. The solvents were removed in vac-
uum and the residue was purified by flash silica gel column chro-
matography eluting with a mixture (4:1) of hexane/ethyl acetate.
4.11.1.1. (S)-3-Butyl-5-methylfuran-2(5H)-one (S)-8a. Colorless
liquid (0.39 g, 86%); dH (500 MHz, CDCl3) 0.93 (3H, t, J 7.0 Hz), 1.37
(2H, sext, J 7.5 Hz), 1.41 (3H, d, J 7.0 Hz), 1.55 (2H, quint, J 8.0 Hz),
2.26e2.29 (2H, m), 5.04 (1H, dq, J 7.0, 1.5 Hz), 7.02 (1H, d, J 1.5 Hz);
dC (125 MHz, CDCl3) 13.8, 19.2, 22.3, 24.9, 29.5, 77.5, 134.2, 149.1,
174.0; dTe (157.9 MHz, CDCl3, Ph2Te2) 2960, 2933, 1754, 1320, 1085,
4.10. Enzymatic kinetic resolution of the alcohols 12a and 12b
4.10.1. Typical procedures. In a 250 mL erlenmeyer involved in an
aluminum foil it was added the alcohol 12a (10 mmol; 3.12 g) and
previously dried and deoxygenated hexane (100 mL). Then the li-
pase NovozymeÒ 435 (1 g, 10,000 PLU gꢀ1) was added to the so-
lution, which was purged with argon. To the resulting suspension it
was added vinyl acetate (130 mmol; 12.0 mL) and the septum
stoppered flask was kept in an orbital shaker (180 rpm) at 34 ꢁC for
27 h. Then the enzyme was removed by filtration and the solvent
was removed in vacuum. The residue was then chromatographed in
a silica gel column eluting with a mixture (9:1) of hexane/ethyl
acetate.
1028; ½a 2D0
ꢃ
þ46.1 (c 1.0, CHCl3, 94% ee); chiral GC-FID [SupelcoÒ
Gamma DEX 120 column, carrier gas: H2, injector temperature:
275 ꢁC, detector temperature: 275 ꢁC, pressure: 100 kPa, method,
initial temperature: 90 ꢁC (20 min)e1 ꢁC/min; final temperature:
120 ꢁC (50 min)]; tR: (S)-8a 32.54 min and (R)-8a 34.54 min; CAS
[98587-10-1].
4.11.1.2. (S)-3-Hexyl-5-methylfuran-2(5H)-one (S)-8b. Colorless
liquid (0.44 g, 81%); dH (300 MHz, CDCl3) 0.89 (3H, t, J 6.9 Hz),
1.27e1.37 (6H, m), 1.41 (3H, d, J 6.9 Hz), 1.55 (2H, quint, J 7.5 Hz),
2.23e2.29 (2H, m), 4.99 (1H, dq, J 6.9,1.5 Hz), 7.01 (1H, d, J 1.5 Hz); dC
(75 MHz, CDCl3) 14.0, 19.2, 22.5, 35.2, 27.4, 28.9, 31.5, 77.5, 134.3,
149.0, 173.9; nmax (liquid film) 2930, 2859, 1755, 1462, 1319, 1118,
1074, 1027 cmꢀ1; HRMS (ESI): m/z ([MþNa]þ) found 183.1381.
4.10.1.1. (S,Z)-4-(Butyltellanyl)oct-3-en-2-ol [(S)-(12a)]. Orange
oil (1.06 g, 34%); same spectral data as for [(R,S)-(12a)]; ½a D20
þ6.1 (c
ꢃ
1.0, CHCl3,, 94% ee).
4.10.1.2. (R,Z)-4-(Butyltellanyl)oct-3-en-2-yl acetate [(R)-(19a)].
Orange oil (1.17 g, 33%); dH (500 MHz, CDCl3) 0.90 (3H, t, J 7.3 Hz),
0.91 (3H, t, J 7.3 Hz), 1.28 (3H, d, J 6.3 Hz), 1.32e1.42 (4H, m),
1.44e1.57 (2H, m), 1.72 (2H, quint, J 7.6 Hz), 2.01 (3H, s), 2.34 (2H, t, J
7.4 Hz), 2.69 (2H, t, J 7.7 Hz), 5.33e5.60 (1H, m), 5.67 (1H, d, J
8.0 Hz); dC (125 MHz, CDCl3) 5.3, 13.4, 13.9, 20.6, 21.3, 21.8, 25.1,
31.9, 34.2, 41.7, 75.2, 123.6, 136.4, 170.1; dTe (157.9 MHz, CDCl3,
Ph2Te2) 279.5; nmax (liquid film) 2959, 2929, 2871, 1739, 1369, 1239,
C11H19O2 requires 183.1385; ½a D20
þ42.4 (c 1.0, CHCl3, 96% ee); chiral
ꢃ
GC [SupelcoÒ Gamma DEX 120 column, carrier gas: H2, injector
temperature: 275 ꢁC, detector temperature: 275 ꢁC, pressure:
100 kPa, method, initial temperature: 90 ꢁC (20 min)e1 ꢁC/min; final
time: 120 ꢁC (50 min)]; tR: (S)-8b 62.49 min and (R)-8b 64.19 min.
4.12. Tellurium/lithium exchange reaction of alcohols 12c and
12d, followed by capture with CO2 and acidification
1044 cmꢀ1
;
HRMS (ESI): m/z ([MþNa]þ) found 379.0882.
C14H26O2TeNa requires 379.0892; ½a D20
ꢃ
þ13.5 (c 1.0, CHCl3, 96% ee).
4.12.1. Typical procedure. To a two necked 50 mL round bottomed
flask, equipped with magnetic stirring and previously flame-dried
under argon, the alcohol 12c or 12d (3 mmol; l.42 g) and THF
(15 mL) were added. The solution was cooled to ꢀ78 ꢁC and then
nBuLi (6 mmol; 4.8 mL of a 1.25 mol Lꢀ1 solution in hexane) was
slowly added. The Te/Li exchange reaction was monitored by TLC.
After the consumption of the starting material, dry CO2 was bub-
bled into the solution for 20 min. The mixture was allowed to reach
the room temperature and then an aqueous solution of HCl (25 mL)
was added. After 20 min of stirring the reaction mixture was
extracted with ethyl acetate (4ꢂ20 mL), the combined phases were
washed with saturated solution of NaHCO3 (30 mL) and brine
(30 mL) and then dried with magnesium sulfate. The solvents were
evaporated under vacuum and the residue was purified by silica gel
flash column chromatography eluting with a mixture (2:1) of
hexane/ethyl acetate.
4.10.1.3. (S,Z)-4-(Butyltellanyl)dec-3-en-2-ol [(S)-(12b)]. Orange
oil (1.12 g, 33%); same spectral data as for [(R,S)-(12b)]; ½a D20
þ9.9 (c
ꢃ
1.0, CHCl3, 96% ee).
4.10.1.4. (R,Z)-4-(Butyltellanyl)dec-3-en-2-yl acetate [(R)-(19b)].
Orange oil (1.26 g, 33%); dH (300 MHz, CDCl3) 0.86e0.93 (6H, m),
1.27e1.29 (9H, m), 1.35 (2H, sext, J 7.2 Hz), 1.50e1.54 (2H, m), 1.72
(2H, quint, J 7.6 Hz), 2.01 (3H, s), 2.32 (2H, t, J 6.4 Hz), 2.68 (2H, t, J
7.6 Hz), 5.33e5.60 (1H, m); 5.67 (1H, d, J 8.0 Hz); dC (125 MHz,
CDCl3) 5.3, 13.4, 14.0, 20.6, 21.3, 22.6, 25.1, 28.4, 29.7, 31.6, 34.1, 41.9,
75.2, 123.6, 136.3, 170.0; dTe (157.9 MHz, CDCl3, Ph2Te2) 281.7; nmax
(liquid film) 2928, 2856, 1739, 1370, 1239, 1044 ppm; HRMS (ESI):
m/z ([MþNa]þ) found 407.1205. C16H30O2TeNa requires 407.1205;
½
a 2D0
ꢃ
þ16.0 (c 1.0, CHCl3, 96% ee).
4.11. Tellurium/lithium exchange of alcohols (S)-12a and (S)-
12b and capture of the vinyl anions with carbon dioxide,
followed by acidification
4.12.1.1. 3-((R)-1-((2-Methoxyethoxy)methoxy)octyl)-5-
methylfuran-2(5H)-one (8c). Diastereoisomeric mixture (1:1)
(1.19 g, 63%) as colorless liquid; dH (500 MHz, CDCl3) 0.88 (3H, t, J
7.0 Hz), 1.27e1.45 [(13H, m), 1.43 (3H, d, J 7.0 Hz)], 1.74e1.77 (2H,
m), 3.38 (3H, s), 3.54 (2H, m), 3.64e3.77 (2H, m), 4.48 (1H, t, J
6.5 Hz), 4.71e4.77 (2H, m), 5.03e5.05 (1H, m), 7.23 (1H, s); dC
(125 MHz, CDCl3) 14.0, 19.1, 22.6, 25.0, 29.1, 31.7, 33.9, 59.0, 67.4,
71.5, 71.7, 77.5, 94.2, 134.9, 150.7,171.8; nmax (liquid film) 2928, 1755,
1456, 1319, 1200, 1025 cmꢀ1; HRMS (ESI): m/z ([MþNa]þ) found
4.11.1. Typical procedure. In a 50 mL two necked round bottomed
flask under magnetic stirring and previously flame-dried under
argon the alcohol (S)-12a (3 mmol; 0.94 g) in THF (15 mL) was
added. The solution was cooled to ꢀ70 ꢁC and then nBuLi (6 mmol;
4.8 mL of a 1.25 mol Lꢀ1 solution in hexane) was added. The Te/Li
exchange reaction was monitored by TLC. After the consumption of
the starting material dry CO2 was bubbled for 20 min. The reaction
mixture was heated to room temperature and then an aqueous
solution of HCl (25 mL) was added. After 20 min the reaction mix-
ture was extracted and the aqueous phase was washed with ethyl
acetate (4ꢂ20 mL). The combined organic phases were washed
337.1997. C17H30O5Na requires 337.1991; ½a D20
ꢀ96.8 (c 1.0, CHCl3).
ꢃ
4.12.1.2. 3-((S)-1-((2-Methoxyethoxy)methoxy)octyl)-5-
methylfuran-2(5H)-one (8d). Diastereoisomeric mixture (1:1)
(1.28 g, 68%) as colorless liquid; same spectral data as for (8c); ½a D20
ꢃ
þ102.8 (c 1.0, CHCl3).

R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
10609
4.13. Deprotection of butenolides 8c and 8d
washed with brine (30 mL) and dried with magnesium sulfate. The
solvents were removed in vacuum and the residue was purified by
silica gel flash column chromatography eluting with a mixture (9:1)
of hexane/ethyl acetate.
4.13.1. Typical procedure. To a two necked 25 mL round bottomed
flask equipped with magnetic stirring and previously flame-dried
under argon, the butenolide 8c (1 mmol; 0.31 g) and CH2Cl2
(7 mL) was added. The solution was cooled to ꢀ78 ꢁC and TiCl4
(10 mmol; 10 mL of a 1.0 mol Lꢀ1 in CH2Cl2) was slowly added. The
mixture was allowed to reach the room temperature and then
stirred for 10 h. The mixture was treated with aqueous saturated
solution of ammonium chloride (10 mL), the aqueous phase was
extracted with CH2Cl2 (2ꢂ10 mL) and the combined organic phases
were dried with magnesium sulfate. The solvent was removed un-
der vacuum and the residue was chromatographed on flash silica gel
column eluting with a mixture (1:1) of hexane/ethyl acetate to give
two fractions, consisting in (ꢀ)-Acaterin (5a) and (þ)-Acaterin (5b).
4.14.1.1. (3S,4R,5S)-3-Butyl-4-(dimethyl(phenyl)silyl)-5-
methyldihydrofuran-2(3H)-one (23a). Colorless liquid (0.48 g, 84%);
dH (500 MHz, CDCl3) 0.39 (6H, s), 0.83 (3H, t, J 7.0 Hz), 1.15e1.28
[(7H, m), 1.24 (3H, d, J 6.0 Hz)], 1.35e1.45 [(3H, m), 1.37 (1H, dd, J
12.0, 10.0 Hz)], 2.49 (1H, ddd, J 12.0, 6.5, 4.0 Hz), 4.35 (1H, dq, J 10.0,
6.5 Hz), 7.34e7.42 (3H, m), 7.44e7.52 (2H, m); dC (125 MHz, CDCl3)
ꢀ4.5, ꢀ4.4, 13.8, 22.2, 22.7, 28.0, 29.9, 35.5, 43.3, 77.4,128.2, 129.8,
133.7, 135.7, 179.4; nmax (liquid film) 2958, 2932, 2867, 1767, 1255,
1187, 1113, 1051, 839, 702 cmꢀ1; ½a D21
ꢃ
ꢀ9.7 (c 1.5, CHCl3), lit.26a
½ ꢃ
a 2D5
ꢀ9.48 (c 3.13, CHCl3); CAS [214210-35-2].
4.13.1.1. (R)-3-((R)-1-Hydroxyoctyl)-5-methylfuran-2(5H)-one;
(ꢀ)-acaterin (5a). Colorless liquid (0.109 g, 48%); dH (500 MHz,
CDCl3) 0.88 (3H, t, J 6.9 Hz),1.24e1.41 (10H, m),1.43 (3H, d, J 6.8 Hz),
1.66e1.70 (1H, m), 1.71e1.76 (1H, m), 4.48 (1H, dt, J 6.4, 1.5 Hz),
5.01e5.05 (1H, m), 7.14 (1H, s); dC (125 MHz, CDCl3) 14.0, 18.9, 22.6,
25.3, 29.2, 29.4, 31.8, 35.7, 67.2, 77.8, 136.6, 149.0, 172.5; nmax (liquid
4.14.1.2. (3S,4R,5S)-4-(Dimethyl(phenyl)silyl)-3-hexyl-5-
methyldihydrofuran-2(3H)-one (23b). Colorless liquid (0.52 g, 82%);
dH (500 MHz, CDCl3) 0.39 (6H, s), 0.86 (3H, t, J 7.0 Hz), 1.13e1.55
[(14H, m), 1.25 (3H, d, J 6.0 Hz), 1.36 (1H, dd, J 12.0, 10.0 Hz)], 2.49
(1H, ddd, J 12.0, 6.5, 4.0 Hz), 4.36 (1H, dq, J 10.0, 6.5 Hz), 7.36e7.42
(3H, m), 7.45e7.49 (2H, m); dC (125 MHz, CDCl3) 4.2, 4.1, 14.0, 22.2,
22.6, 25.8, 29.2, 30.3, 31.6, 35.6, 43.4, 77.4, 128.2, 129.9, 133.7, 135.7,
179.4; nmax (liquid film) 2956, 2929, 2857, 1767, 1255, 1186, 1113,
film) 3464, 2928, 1741, 1465 cmꢀ1; ½a D20
ꢃ
ꢀ19.0 (c 1.0, CHCl3), lit.21a
½
a 2D0
ꢃ
ꢀ19.7 (c 0.61, CHCl3); CAS [144398-20-9].
1050, 839, 702 cmꢀ1; ½a D22
ꢃ
ꢀ10.2 (c 2.0, CHCl3), lit.26a
½
a 2D2
ꢃ
ꢀ10.9 (c
4.13.1.2. (S)-3-((R)-1-Hydroxyoctyl)-5-methylfuran-2(5H)-one;
3.04, CHCl3); CAS [214210-36-3].
(þ)-Acaterin (5b). Colorless liquid (0.091 g, 40%); same spectral
data as for (5a); ½a D20
ꢃ
þ60.1 (c 1.0, CHCl3), lit.21a
½
a 2D0
ꢃ
þ62.6 (c 1.06,
CHCl3); CAS [165880-42-2].
The same procedure was repeated for the butenolide 8d, leading
to (ꢀ)-pseudo-Acaterin 1 (5c) and (þ)-pseudo-Acaterin 2 (5d).
4.15. FlemingeTamao oxidation of the lactones 23a and 23b
4.15.1. Typical procedure. To a 25 mL round bottomed flask equip-
ped with magnetic stirring were added the lactone 23a (0.76 mmol;
0.22 g), acetic acid (2 mL), potassium bromide (1.8 mmol; 0.21 g)
and anhydrous sodium acetate (2.36 mmol; 0.19 g). The resulting
mixture was cooled to 0 ꢁC and then peracetic acid (2 mL of a 30% v/
v solution in acetic acid) was slowly added. The resulting mixture
was stirred at room temperature for 2 h and then diluted with ethyl
acetate (10 mL). The mixture was treated with saturated aqueous
solution of NaI (15 mL) and with saturated solution of Na2S2O3
(20 mL), and then the aqueous phase was extracted with ethyl ac-
etate (4ꢂ10 mL). The combined organic phases were washed with
saturated aqueous solution of NaHCO3 (15 mL) and dried with
magnesium sulfate. The solvents were removed under vacuum and
the residue was purified by flash silica gel columns chromatogra-
phy, eluting with a mixture (2:1) of hexane/ethyl acetate.
4.13.1.3. (R)-3-((S)-1-Hydroxyoctyl)-5-methylfuran-2(5H)-one;
pseudo-Acaterin 1 (5c). Colorless liquid (0.102 g, 45%); same spec-
tral data as for (5a); ½a D20
ꢃ
ꢀ59.7 (c 1.0, CHCl3), lit.21a
½
a 2D0
ꢃ
ꢀ63.7 (c
0.53, CHCl3); CAS [165880-41-1].
4.13.1.4. (S)-3-((S)-1-Hydroxyoctyl)-5-methylfuran-2(5H)-one;
pseudo-Acaterin
2 (5d). Colorless liquid (0.093 g, 41%); same
spectral data as for (5a); ½a D20
ꢃ
þ20.2 (c 1.0, CHCl3), lit.21a
½
a 1D9
ꢃ
þ19.6
(c 1.04, CHCl3); CAS [165880-39-7].
4.14. 1,4-trans Selective addition of (Me2PhSi2)2Cu(CN)Li2 (22)
to -alkyl- -butenolides (S)-8a and (S)-8b
a
g
4.14.1. Typical procedure. In a 50 mL two necked round bottomed
flask equipped with magnetic stirring, previously flame-dried un-
der argon, it was placed elemental lithium doped with 0.5% sodium
(40.4 mmol; 1 g of a 30% m/m dispersion in mineral oil), which was
then washed with dry hexane (25 mL). The resulting solid was
suspended in THF (16 mL) and the suspension was cooled to 0 ꢁC. To
the suspension it was slowly added PhMe2SiCl (9.12 mmol;
1.52 mL) and the mixture was stirred at this temperature for 16 h. In
a second 100 mL round bottomed flask equipped with magnetic
stirring and previously flame-dried under argon, was added CuCN
(4.2 mmol; 0.40 g) and THF (16 mL) and then the mixture was
cooled to ꢀ70 ꢁC. The mixture of the first flask was then transferred
via cannula to the second flask containing the CuCN suspension.
After the addition was complete the mixture was heated to 0 ꢁC and
stirred at this temperature for 20 min. In the following, the mixture
was cooled to -70 ꢁC and the butenolide (S)-8a (2 mmol; 0.31 g)
was added in THF (5 mL). After 20 min stirring at ꢀ70 ꢁC the re-
action mixture was allowed to reach the room temperature and
then an aqueous saturated NH4Cl solution (10 mL) was added. The
phases were separated and the aqueous phase was washed with
diethyl ether (4ꢂ20 mL). The combined organic phases were
4.15.1.1. (3R,4R,5S)-3-Butyl-4-hydroxy-5-methyldihydrofuran-
2(3H)-one; (ꢀ)-blastmycinolactol (1). White solid (0.12 g, 93%); mp
46.3e46.6 ꢁC, lit.26a 43e44 ꢁC; dH (300 MHz, CDCl3) 0.93 (3H, t, J
7.2 Hz), 1.43e1.61 [(8H, m), 1.53 (3H, d, J 6.3 Hz)], 1.83e1.92 (2H, m),
2.56 (1H, ddd, J 8.7, 6.6, 6.0 Hz), 3.83 (1H, dd, J 8.7, 7.2 Hz), 4.20 (1H,
quint, J 6.6 Hz); dC (75 MHz, CDCl3) 13.8, 18.3, 22.7, 28.2, 28.9, 48.7,
78.9, 80.3, 176.6; nmax (KBr) 3493, 2953, 2864, 1734, 1469, 1285,
a 22
a 25
1053, 854, 652 cmꢀ1; ½ ꢃD ꢀ16.0 (c 1.0, CHCl3), lit.26a ½ ꢃD ꢀ17.1 (c
1.47, CHCl3); CAS [34867-17-9].
4.15.1.2. (3R,4R,5S)-3-Hexyl-4-hydroxy-5-methyldihydrofuran-
2(3H)-one; (ꢀ)-NFX-2 (3). White solid (0.14 g, 91%); mp
56.2e56.6 ꢁC; dH (300 MHz, CDCl3) 0.89 (3H, t, J 6.6 Hz), 1.27e1.66
[(12H, m), 1.45 (3H, d, J 6.3 Hz)], 1.81e1.92 (1H, m), 2.03 (1H, sl);
2.55 (1H, ddd, J 8.4, 7.2, 5.4 Hz), 3.84 (1H, dd, J 8.4, 7.2 Hz), 4.20 (1H,
quint, J 6.2 Hz); dC (75 MHz, CDCl3) 14.0; 18.3; 22.6; 26.7; 28.5;
29.2; 31.6; 48.7; 79.1; 79.9; 176.0; nmax (liquid film) 3439, 2951,
2849,1734,1467,1274,1187,1059, 969, 856, 653 cmꢀ1; ½a D22
ꢀ14.8 (c
ꢃ
2.0, CHCl3), lit.26a
½
a 2D5
ꢃ
ꢀ13.2 (c 2.08, CHCl3); CAS [137171-29-0].

10610
R.S. Ferrarini et al. / Tetrahedron 68 (2012) 10601e10610
Cunha, R. L. O. R. Tellurium InMingos, D. M. P., Crabtree, R. H., Eds.. Comprehensive
Organometallic Chemistry III; Elsevier: Amsterdam, 2007; Vol. 9, pp 587e648.
2. (a) Comasseto, J. V.; Barrientos-Astigarraga, R. E. Aldrichimica Acta 2000, 33, 66;
4.16. Esterification of 1 and 3 with isovaleroyl chloride
4.16.1. Typical procedure. To a 15 mL round bottomed flask under
magnetic stirring previously flame-dried over argon, it was added
(ꢀ)-blastimicinolactol (1) (0.47 mmol; 0.08 g) and pyridine
(10 mL). The mixture was cooled to 0 ꢁC and then isovaleroyl
chloride (2.43 mmol; 0.3 mL) was added. The resulting mixture was
stirred at room temperature for 6 h and then diluted with ethyl
acetate (10 mL), washed with saturated aqueous solution of CuSO4
(2ꢂ20 mL) and brine (10 mL). The organic phase was dried with
magnesium sulfate and the solvents were removed under vacuum.
The residue was purified by flash silica gel column chromatography
eluting with a mixture (9:1) of hexane/ethyl acetate.
€
(b) Petragnani, N.; Stefani, H. A. Tetrahedron 2005, 61, 1613; (c) Zeni, G.; Ludtke,
D. S.; Panatieri, R. B.; Braga, A. L. Chem. Rev. 2006, 106, 1032.
3. (a) Comasseto, J. V.; Gariani, R. A. Tetrahedron 2009, 65, 8447; (b) Dos Santos, A.
A.; Da Costa, C. E.; Princival, J. L.; Comasseto, J. V. Tetrahedron: Asymmetry 2006,
17, 2252.
4. (a) Princival, J. L.; Dos Santos, A. A.; Comasseto, J. V. J. Braz. Chem. Soc. 2010, 21,
2042; (b) Wendler, E. P.; Dos Santos, A. A. Synlett 2009, 1034.
€
5. (a) Tiekink, E. R. T. Dalton Trans. 2012, 41, 6390; (b) Ba, L. A.; Doring, M.; Jamier,
V.; Jacob, C. Org. Biomol. Chem. 2010, 8, 4203.
6. Ugurchieva, T. M.; Veselovsky, V. V. Russ. Chem. Rev. 2009, 78, 337.
7. Vieira, M. L.; Zinn, F. K.; Comasseto, J. V. J. Braz. Chem. Soc. 2001, 12, 586.
8. Barros, S. M.; Comasseto, J. V.; Berriel, J. Tetrahedron Lett. 1989, 30, 7353.
9. Tucci, F. C.; Chieffi, A.; Comasseto, J. V.; Marino, J. P. J. Org. Chem. 1996, 61, 4975.
10. (a) Yonehara, H.; Takeuchi, S. J. Antibiot., Ser. A 1958, 11, 254; (b) Kinoshita, M.;
Wada, M.; Umezawa, S. J. Antibiot. 1969, 22, 580; (c) Liu, W. C.; van Tamelen, E.
E.; Strong, F. M. J. Am. Chem. Soc. 1960, 82, 1652.
4.16.1.1. (2S,3R,4R)-4-Butyl-2-methyl-5-oxotetrahydrofuran-3-yl
3-methylbutanoate; (þ)-blastmycinone (2). Colorless liquid (0.12 g,
96%); dH (300 MHz, CDCl3) 0.92 (3H, t, J 7.2 Hz), 0.98 (6H, d, J 6.6 Hz),
1.32e1.49 [(7H, m), 1.47 (3H, d, J 6.6 Hz)], 1.61e1.68 (1H, m),
1.84e1.88 (1H, m), 2.07e2.16 (1H, m), 2.23 (2H, d, J 6.9 Hz), 2.69
(1H, dt, J 8.1, 6.0 Hz), 4.37 (1H, dq, J 6.6, 4.8 Hz), 4.95 (1H, dd, J 6.0,
4.8 Hz); dC (75 MHz, CDCl3) 13.8, 19.5, 22.3, 22.4, 25.7, 28.9, 29.0,
43.2, 46.5, 78.5, 79.4, 172.4, 175.9; nmax (liquid film) 2960, 2874,
11. Naganuma, S.; Sakai, K.; Hasumi, K.; Endo, A. J. Antibiot. 1992, 45, 1216.
12. (a) Mulzer, J.; Salii, N.; Hartl, H. Tetrahedron: Asymmetry 1993, 4, 457; (b) Suzuki,
Y.; Mori, W.; Ishizone, H.; Naito, K.; Honda, T. Tetrahedron Lett. 1992, 33, 4931;
(c) Ebata, T.; Matsumoto, K.; Yoshikoshi, H.; Koseki, K.; Kawakami, H.; Okano,
K.; Matsushita, H. Heterocycles 1993, 36, 1017.
13. (a) Sibi, M.; Gaboury, J. A. Tetrahedron Lett. 1992, 33, 5681; (b) Jacobs, H. K.;
Mueller, B. H.; Gopalan, A. S. Tetrahedron 1992, 48, 8891.
14. (a) Takahata, H. Yakugaku Zasshi 1993, 113, 737; (b) Peng, Z. H.; Woerpel, K. A.
Org. Lett. 2001, 3, 675.
15. (a) Uchiyama, H.; Kobayashi, Y.; Sato, F. Chem. Lett. 1985, 467; (b) Krishna, P. R.;
1785, 1468, 1181, 1040 cmꢀ1; ½a D22
þ11.8 (c 1.2, CHCl3, ee >97%),
ꢃ
Reddy, V. V. R.; Sharma, G. V. M. Synthesis 2004, 13, 2107.
16. (a) Yang, Y. Q.; Wu, Y. K. Chin. J. Chem. 2005, 23, 1519; (b) Sibi, M. P.; Lu, J.;
Talbacka, C. L. J. Org. Chem. 1996, 61, 7848.
lit.15b
½
a 2D0
ꢃ
þ11.0 (c 1.2, CHCl3); chiral GC-FID [SupelcoÒ Beta DEX
110 column (30 mꢂ0.25 mmꢂ0.25
mm), carrier gas: H2, injector
17. Azevedo, M. B. M.; Greene, A. E. J. Org. Chem. 1995, 60, 4940.
18. (a) Inghardt, T.; Frejd, T. Tetrahedron 1991, 47, 6483; (b) Chen, M. J.; Lo, C. Y.;
temperature: 275 ꢁC, detector temperature: 275 ꢁC, pressure:
100 kPa, method: Ti 90 ꢁC (20 min)e1 ꢁC/mineTf 120 ꢁC (100 min)]
tR: ent-(1) 111.404 min and (2) 113.182 min; CAS [27981-25-5].
ꢀ
Chin, C. C.; Liu, R. S. J. Org. Chem. 2000, 65, 6362; (c) Esteve, C.; Ferrero, M.;
Romea, P.; Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 1999, 40, 5083.
19. Nishide, K.; Aramata, A.; Kamanaka, T.; Inoue, T.; Node, M. Tetrahedron 1994, 50,
8337.
20. Chakraborty, T. K.; Chattopadhyay, A. K.; Ghosh, S. Tetrahedron Lett. 2007, 48,
1139.
4.16.1.2. (2S,3R,4R)-4-Hexyl-2-methyl-5-oxotetrahydrofuran-3-yl
3-methylbutanoate; (þ)-Antimycinone (4). Colorless liquid (0.13 g,
96%); dH (500 MHz, CDCl3) 0.88 (3H, t, J 7.0 Hz), 0.98 (6H, d, J 7.0 Hz),
1.26e1.45 (8H, m),1.47 (3H, d, J 6.5 Hz),1.59e1.67 (1H, m),1.84e1.89
(1H, m), 2.11e2.15 (1H, m), 2.23 (2H, d, J 7.0 Hz), 2.69 (1H, dt, J 8.5,
5.5 Hz), 4.36 (1H, dq, J 7.0, 5.0 Hz), 4.94 (1H, dd, J 5.5, 5.0 Hz); dC
(125 MHz, CDCl3) 13.9, 19.3, 22.2, 22.4, 25.6, 26.7, 28.8, 29.2, 31.4,
43.0, 46.4, 78.3, 79.3, 172.3, 175.8; nmax (liquid film) 2959, 2872,
21. (a) Ishigami, K.; Kitahara, T. Tetrahedron 1995, 51, 6431; (b) Anand, R. V.;
Barktharaman, S.; Singh, V. K. Tetrahedron Lett. 2002, 43, 5393.
22. (a) Hjelmgaard, T.; Persson, T.; Rasmussen, T. B.; Givskov, M.; Nielsen, J. Bioorg.
ꢁ
Med. Chem. 2003, 11, 3261; (b) Franck, X.; Figadere, B. Tetrahedron Lett. 2002, 43,
1449.
23. (a) Sekiyama, Y.; Fujimoto, Y.; Hasumi, K.; Endo, A. J. Org. Chem. 2001, 66, 5649;
(b) Sekiyama, Y.; Fujimoto, Y.; Hasumi, K.; Endo, A. Tetrahedron Lett. 1999, 40,
4223; (c) Nakano, S.; Sakane, W.; Oinaka, H.; Fujimoto, Y. Bioorg. Med. Chem.
2006, 14, 6404.
24. (a) Menezes, P. H.; Comasseto, J. V.; Oliveira, J. M.; Palmeira, D. J. J. Braz. Chem.
Soc. 2010, 21, 362; (b) Barrientos-Astigarraga, R. E.; Castelani, P.; Comasseto, J.
V.; Formiga, H. B.; Silva, N. C.; Vieira, M. L. J. Organomet. Chem. 2001, 623, 43.
25. For recent examples see: (a) Comasseto, J. V.; Dos Santos, A. A. Phosphorus,
Sulfur Silicon Relat. Elem. 2008, 183, 939; (b) Schneider, C. C.; Caldeira, H.; Gay,
B. M.; Back, D. F.; Zeni, G. Org. Lett. 2010, 12, 936; (c) Myrzayans, P. M.; Pouwer,
R. H.; Williams, C. M. Org. Lett. 2008, 10, 3861; (d) Myrzayans, P. M.; Pouwer, R.
H.; Williams, C. M.; Bernhardt, P. V. Tetrahedron 2009, 65, 8297.
1786, 1743, 1467, 1182, 1120, 1040 cmꢀ1; ½a D20
þ10.1 (c 1.5, CHCl3, ee
ꢃ
>97%), lit.26a
½
a 2D0
ꢃ
þ7.8 (c 1.75, CHCl3); chiral GC-FID [SupelcoÒ Beta
DEX 110 column (30 mꢂ0.25 mmꢂ0.25
mm), carrier gas: H2, in-
jector temperature: 275 ꢁC, detector temperature: 275 ꢁC, pressure:
100 kPa, method: Ti 90 ꢁC (20 min)e1 ꢁC/mineTf 120 ꢁC (100 min)]
tR: ent-(3) 261.365 min and (3) 263.599 min; CAS [132864-91-6].
26. (a) Berkenbusch, T.; Bruckner, R. Tetrahedron 1998, 54, 11461; (b) Fleming, I.;
Reddy, N. L.; Takaki, K.; Ware, A. C. J. Chem. Soc., Chem. Commun. 1987, 1472; (c)
Harcken, C.; Rank, E.; Bruckner, R. Chem.dEur. J. 1998, 4, 2342; (d) Krause, N.
Modern Organocopper Chemistry; Wiley-VCH: Dortmund, 2002, pp 79.
27. (a) Fleming, I.; Sanderson, P. E. J. Tetrahedron Lett. 1987, 28, 4229; (b) Fleming, I.;
Henning, R.; Parker, D. C.; Plaut, H. E.; Sanderson, P. E. J. J. Chem. Soc., Perkin
Acknowledgements
The authors thank FAPESP, CAPES and CNPq for the financial
support, Amano Pharmaceutical Co. and Novozymes Inc. are ac-
knowledged for their generous gifts of lipases. Alexandre Sardelli
Guarezemini is acknowledged for technical assistance.
ꢀ
Trans. 1 1995, 317; (c) Kurti, L.; Czako, B. Strategic Applications of Named Re-
actions in Organic Synthesis; Elsevier Academic: San Diego, 2005, pp 174.
28. Raminelli, C.; Comasseto, J. V.; Andrade, L. H.; Porto, A. L. M. Tetrahedron:
Asymmetry 2004, 15, 3117.
29. Jacquet, I.; Vigneron, J.-P. Tetrahedron Lett. 1974, 24, 2065.
30. Corey, E. J.; Link, J. O. J. Am. Chem. Soc. 1992, 114, 1906.
31. Noyori, R. Pure Appl. Chem. 1981, 53, 2315.
32. Brown, H. C.; Krishnamurthy, S. Aldrichimica Acta 1979, 12, 13.
33. A preliminary communication on the synthesis of 1e4 was published: Ferrarini,
R. S.; Dos Santos, A. A.; Comasseto, J. V. Tetrahedron Lett. 2010, 51, 6843 and
Tetrahedron Lett. 2011, 52, 2001.
34. He, Y.-T.; Yang, H. N.; Yao, Z.-J. Tetrahedron 2002, 58, 8805.
35. Perrin, D. D.; Amarego, W. L. F. Purification of Laboratory Chemicals; Pergamon:
London, 1980.
Supplementary data
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.07.088.
References and notes
1. (a) Petragnani, N.; Stefani, H. A. Tellurium in Organic Synthesis: Best Synthetic
Methods, 2nd ed.; Academic: London, 2007; (b) Comasseto, J. V.; Clososki, G. C.;
36. Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1976, 9, 165.