Eco-Friendly and Industrially Scalable Synthesis of the Sex Pheromone of Lobesia botrana. Important Progress for the Eco-Protection of Vineyard

Article abstract of DOI:10.1021/acs.oprd.7b00206

A one-pot synthesis of the pheromone of Lobesia botrana is described. The procedure allows an efficient and economical access to this product which is used for the protection of vineyards.

Full text of DOI:10.1021/acs.oprd.7b00206

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Full Paper
Eco-Friendly and Industrially-Scalable Synthesis of the Sex Pheromone of
Lobesia botrana. An Important Progress for the Eco-Protection of Vineyard
Gerard Cahiez, Olivier Guerret, Alban Moyeux, Samuel Dufour, and Nicolas Lefevre
Org. Process Res. Dev., Just Accepted Manuscript • Publication Date (Web): 21 Aug 2017
Downloaded from http://pubs.acs.org on August 21, 2017
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Eco-Friendly and Industrially-Scalable Synthesis of the Sex Pheromone of Lobesia
botrana. An Important Progress for the Eco-Protection of Vineyard
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Gérard Cahiez,*a Olivier Guerret,b Alban Moyeux,a,c Samuel Dufour,b and Nicolas Lefevrea
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Chimie ParisTech, PSL Research University, CNRS, Institut de Recherche de Chimie Paris
(IRCP), Fꢀ75005 Paris, France.
b M2i, Route Nationale 117, Lotissement Induslacq, 64170 Lacq, France.
c Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny, France.
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ABSTRACT
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A oneꢀpot synthesis of the pheromone of Lobesia botrana is described. The procedure allows
an efficient and economical access to this product which is used for the protection of
vineyards.
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KEYWORDS: Sex pheromones, Lobesia Botrana, ironꢀcatalyzed crossꢀcoupling, dienol
phosphates, trapping of dienolates
INTRODUCTION
Pheromones1 are very promising for the ecoꢀfriendly protection of a wide range of crops such
as grape, banana, apple, etc.2 Contrary to classical pesticides, pheromones are specific to one
species of pest, other insects, and especially pollinator insects, are unaffected. Furthermore,
pheromones are biodegradable and have no effect upon human’s health.3 Those properties
make pheromones ideal candidates for modern ecoꢀfriendly crop protection.
In our continued effort to develop efficient and largeꢀscale procedures, we became interested
in developping a new industrial access to the sex pheromone of the European grapevine moth
Lobesia botrana 1.
Figure 1. Sex pheromone of the European grapevine moth Lobesia botrana: (7E,9Z)ꢀ
dodecadienꢀ1ꢀyl acetate
Despite its outstanding environmental benefits, few European countries are currently using
this pheromone for the protection of vineyards on a large scale due to its relatively high cost.4
However, in Germany or Switzerland where the government provides wine producers with
financial support, 60 to 65 % of the surface of vineyards is successfully treated with the
pheromone 1.5 In this context, it appears clearly that the search for an economically viable
synthesis of the pheromone is a preꢀrequisite for a global use.
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The current industrial process leading to the sex pheromone of Lobesia botrana is a linear and
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multiꢀstep procedure starting from a not easily accessible chlorinated alkyne (Scheme ).6
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Scheme 1. Current industrial synthesis of the pheromone of Lobesia botrana
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This relatively short synthesis requires the isolation of four intermediates, which is
economically unfavorable. Furthermore, the pheromone 1 is isolated in only 11 % yield and
75 % of isomeric purity.
Other groups7 also reported the synthesis of 1. However, all the procedures are
unattractive for an industrial production since they are too long and linear, poorly
efficient, difficult to scale-up and require expensive reagents. Moreover, all
intermediates have to be isolated.
RESULTS AND DISCUSSION
Previously, 8 we described an efficient and stereoselective ironꢀcatalyzed crossꢀcoupling
reaction between dienol phosphates9 and Grignard reagents. These results prompted us to
explore a new economical and scalable synthesis of the pheromone of Lobesia botrana using
this coupling reaction as a key step. Our project is based on a strategy described in Scheme 2;
(i) preparation of the Grignard reagent ωꢀalcoholate 4 derived from 6ꢀchlorohexanol 3, and
(ii) ironꢀcatalyzed crossꢀcoupling reaction of 4 with dienol phosphate 5a, followed by an in-
situ acylation of the resulting alcoholate 6 to give the desired pheromone 1 (Scheme 2).
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Scheme 2. Strategy for oneꢀpot synthesis of the pheromone of Lobesia botrana 1
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This project was ambitious since our goal was to perform the entire synthesis in a oneꢀpot
procedure.
Stereoselective preparation of dienol phosphate 5 from trans-2-hexenal
In 2008, our group reported a convenient method for a stereoselective preparation of dienol
phosphates (Scheme 3).9 It should be noted that the stereoisomeric purity of the C3ꢀC4 double
bond decreases when the length of the R alkyl group increases.
Scheme 3. Stereoselective synthesis of dienol phosphates
To prepare the pheromone of Lobesia botrana according to the strategy disclosed above
(Scheme 2) we needed the dienol phosphate 5 derived from transꢀ2ꢀhexenal 7 (Table 1). 7
was first treated with tꢀBuOK in a mixture of THF/NMP at ꢀ78 °C (Table 1, entry 1). The
resulting dienolate 8 was then reacted with ClP(O)(OEt)2 to give dienol phosphate 5 in 80 %
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yield (3E/3Z= 85:15).
It shoud be noted that on a large scale, ClP(O)(OEt)2 is
advantageously prepared from POCl3 and EtOH (see supporting information).
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For industrial applications, it is not very convenient to work at ꢀ78 °C. We have thus tried to
perform the enolization step at a higher temperature (Table 1). It is important to recall that the
commercial product 1 has a stereochemical purity of 75 % (1E,3Z/1E,3E= 3:1)6 Thus, it is
interesting to note that the dienol phosphate 5 can be obtained in a similar stereochemical
ratio 5a/5b= 73:24 at only ꢀ10 °C (Table 1, entry 4). On the other hand, the enolate 8 has to
be trapped with ClP(O)(OEt)2 rapidly to avoid the isomerisation of the C3ꢀC4 double bond
(Table 1, entries 4 and 5).
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Table 1. Stereoselective synthesis of dienolphosphate 5: Influence of the temperature.
Entry T
(°C) (3Z, 1Z) (3E, 1Z) (3Z, 1E) (3E, 1E)
Ratioa
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ꢀ78
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ꢀ30
ꢀ10
ꢀ10b
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<1
<1
<1
<1
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<1
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a/ Determined by GC. b/ Enolization time: 1h
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Preparation of Grignard reagent ClMgO(CH2)6MgCl
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In 1978, the group of Normant reported the preparation in good yields of alkyl Grignard
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reagents bearing an alcoholate in the ωꢀposition (Scheme 4).11 These functionalized Grignard
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reagents are readily obtained in a twoꢀstep procedure starting from an ωꢀchloroalcanꢀ1ꢀol: (i)
metallation of the alcohol with MeMgCl or iꢀPrMgCl (ii) insertion of magnesium (oxidative
addition) into the carbonꢀchlorine bond of the chloroalcoholate ClMgO(CH2)nCl. On a large
scale, the weak point of this procedure is the second step. Indeed, it is not always easy to
activate the magnesium which is added to the chloroalcoholate solution and the yield ranges
from 85 to 90%.
Scheme 4. Preparation of alkyl Grignard reagent ClMgO(CH2)nMgCl
Our search of efficiency prompted us to develop a new one-pot procedure (Scheme 5).
At first, butyl chloride reacts with two equivalents of magnesium to give BuMgCl + 1
equiv of Mg. Then, addition of chloroalcohol 2 between -10 to r.t. leads to the
quantitative formation of the magnesium alcoholate 3. By heating at reflux, this one
undergoes an oxidative addition with the second equivalent of magnesium, to give the
Grignard alcoholate 4 in 97 % yield. It should be noted that the conversion of 2 to 3 then
of 3 to 4 can be performed sequentially only by adjusting the temperature of the
reaction mixture.
Let us remark that this one-pot procedure allows to prepare ClMgO(CH2)6MgCl much
easier than the previous one depicted in Scheme 4. Indeed, the insertion of magnesium
into the C-Cl bond of 3 occurs easily since the second equivalent of magnesium present
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in the reaction mixture is already activated and very reactive. The expected Grignard
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reagent 4 was then obtained reproducibly in 97 % yield.
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Scheme 5. One-pot preparation of ClMgO(CH2)6MgCl 4
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Fe-catalyzed cross-coupling reaction between Grignard reagent 4 and dienol phosphate 5
To continue the development of our one-pot procedure, we have added at 0 °C, to the
solution of ClMgO(CH2)6MgCl 4 previously prepared (Scheme 5), a catalytic amount of
Fe(acac)3 and the dienol phosphate 512. The reaction mixture was stirred at room
temperature for 2 h and the resulting alcoholate 6 was then acylated with acetic
anhydride to give the pheromone 1 (Table 2). The first experiment was performed with
1 % of Fe(acac)3. However, we have shown that the amount of catalyst can be decreased
until 0.05 % (Table 2, entry 4). This result clearly evidences the high efficiency of iron
catalysis.
Table 2. Iron-catalyzed cross-coupling reaction between Grignard reagent 4 and dienol
phosphate 5 then acylation of 6 (one-pot procedure)
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Amount of
catalyst
(mol %)
1
Isolated
yield of 1
(%)
Entry
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Conclusions
In this article, we describe a very short and efficient one-pot synthesis of the
pheromone of Lobesia botrana. The key step of this procedure is an iron-catalyzed
cross-coupling reaction between a dienol phosphate and a Grignard reagent
alcoholate ClMgO(CH2)6MgCl. This procedure is currently used on an industrial
scale for the production of the pheromone of Lobesia botrana 10
.
EXPERIMENTAL SECTION
General. Gas Chromatography analyses (GC) were performed on a Shimadzu
Chromatograph 2010 Plus apparatus equipped with a flame ionization detector.
ꢀ Stereochemical ratio of dienol phosphates 5 was determined using a column Zebron ZBꢀ
5MS (length: 10 m, I.D.: 0.10 mm, film thickness: 0.10 ꢀm. 5 % Polysilarylene / 95 %
polydimethylsiloxane). Hydrogen was used as a carrier gas (1.07 mL/min, ratio split: 80).
Standard analysis conditions: 80 °C to 200 °C (hold 4 min), heating rate: 20 °C/min.
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ꢀ Stereochemical ratio of the pheromone 1 was determined using a column HP Innowax
(length: 30 m, I.D.: 0.25 mm, film thickness: 0.25 ꢀm). Hydrogen was used as a carrier gas
(0.73 mL/min, ratio split: 100). Standard analysis conditions: 150 °C (hold 10 min) to 200
°C (hold 7.5 min), heating rate: 20 °C/min.
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Thin layer chromatography (TLC) was carried out on silica gel plates (Carlo Erba 60 F254).
Spots were detected with UV light and revealed with a potassium permanganate solution
(KMnO4: 6 g, K2CO3: 40 g, acetic acid: 0.5 mL, water: 600 mL).
Flash chromatography was performed on silica gel columns (Carlo Erba, spherical, neutral,
40ꢀ60 ꢁm).
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1H NMR (300 MHz, CDCl3), C NMR (75 MHz, CDCl3) and P NMR (121 MHz, H3PO4
external standard) were recorded on a Brucker Avance 300 instrument. Coupling constants (J)
are given in Hz. The following abbreviations are used: s, singlet, d, doublet, t, triplet, q,
quartet, m, multiplet.
Mass spectra were recorded on a HewlettꢀPackart HP 5973 mass spectrometer via a GC/MS
coupling with a HewlettꢀPackart HP 6890 Chromatograph equipped with a capillary column
HPꢀ5MS (length: 50 m, I.D.: 0.25 mm, film thickness: 0.25 ꢀm). Ionisation was performed
by electronic impact (EI, 70 eV). Mass spectra are reported as m/z (% of relative intensity).
ESIꢀMS experiments were carried out using a LTQꢀOrbitrap XL from Thermo Scientific and
operated in positive ionization mode, with a spray voltage at 3.6 kV. Sheath and auxiliary gas
were set at a flow rate of 45 and 15 arbitrary units (a.u.), respectively. Applied voltages were
20 and 70 V for the ion transfer capillary and the tube lens, respectively. The ion transfer
capillary was held at 275 °C. Detection was achieved in the Orbitrap with a resolution set to
60,000 (at m/z 400) and a m/z range between 110ꢀ1200 in profile mode. Spectrum was
analyzed using the acquisition software XCalibur 2.1 (Thermo Fisher Scientific). The
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automatic gain control (AGC) allowed accumulation of up to 2.105 ions for FTMS scans.
Maximum injection time was set to 300 ms and 1 µscan was acquired. 5 µL was injected
using a Thermo Finnigan Surveyor HPLC system (Thermo Fisher Scientific) with a
continuous infusion of methanol at 100 µL/min.
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Purification of solvents and reagents. THF (Acros, 99.8 %, extra dry, stabilized), iron(III)
acetylacetonate (Acros, 99 %), magnesium (nonferrum metal powders GmbH, 99.8 %,
turnings, 3ꢀ4 mm), 6ꢀchlorohexanol (Acros, 95 %), 2,2ꢀbiquinoline (Alfa Aesar, 98 %), ethyl
bromide (SigmaꢀAldrich, 98 %), nꢀbutyl chloride (Acros, 99 %) acetic anhydride (Acros, 98
%), 1ꢀmethylꢀ2ꢀpyrrolidinone (Acros, 99 %, extra pure), transꢀ2ꢀhexenal, (Acros, 99 %),
phosphorus oxychloride (Acros, 99 %), ethanol (absolute, Carlo Erba, for HPLC), potassium
tertꢀbutoxide (Acros, 98 %) were used without purification. Triethylamine was dried over
potassium hydroxide and distilled under argon. Tertꢀbutyl methyl ether was distilled under
argon and stored under argon over activated 3Å molecular sieves.13
All reactions were performed under an argon atmosphere. Titration of Grignard reagents were
performed according to the procedure reported by Watson14 by using a 1 M solution of secꢀ
butyl alcohol in toluene, 1 mL of the THF solution of the Grignard reagent and 1ꢀ2 mg of 2,2ꢀ
biquinoline.
Diethyl chlorophosphate (CAS n°814-49-3)15
Preparative Procedure. In a dry fourꢀneck 250 mL roundꢀbottom flask equipped with a
mechanical stirrer, a thermometer and an argon inlet, were introduced at 20 °C triethylamine
(21.3 g, 210 mmol), tertꢀbutyl methyl ether (75 mL) and ethanol (9.67 g, 210 mmol).
Phosphorus oxychloride (15.3 g, 100 mmol) was added dropwise in 10 min via a syringe, the
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temperature was maintained below ꢀ5 °C. Then, the cooling bath was removed and the white
suspension was vigorously stirred during 5 h at 20 °C. The mixture was filtered and the solid
was rinsed with 3x100 mL of diethyl ether. The solvents were removed under vacuo. The
resulting crudez product was distilled under reduced pressure to afford 15.4 g (89 % yield) of
diethyl chlorophosphate containing 3 % of triethylphosphate.
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1
Eb3 = 51 °C (litt.:15 Eb10 = 85ꢀ87 °C). H NMR (CDCl3, 300 MHz, δ): 1.37 (6H, t, J = 6.0
Hz), 4.16ꢀ4.30 (4H, m). 13C NMR (CDCl3, 75 MHz, δ): 15.6 (d, J = 7.5 Hz), 65.7 (d, J = 6.8
Hz). 31P RMN (CDCl3, 121 MHz, δ): 4.5.
Diethyl (1E,3Z)-hexa-1,3-dienyl phosphate16
Preparative Procedure. In a dry fourꢀneck 500 mL roundꢀbottom flask equipped with a
mechanical stirrer, a thermometer and an argon inlet, were introduced at 20 °C potassium tertꢀ
butoxide (12.6 g, 110 mmol), THF (150 mL) and NMP (100 mL). The purple solution was
stirred at ꢀ10 °C and transꢀhexenal (9.81 g, 100 mmol) was added dropwise in 5 minutes at 0
°C. After 5 minutes, diethyl chlorophosphate (20 g, 110 mmol) was added dropwise in 10
minutes at ꢀ10 °C. The mixture was stirred for 30 minutes then quenched by adding 150 mL
of an aqueous solution of HCl (1 M). The aqueous layer was extracted with 3x50 mL of
diethyl ether. The combined organic layers were dried over magnesium sulphate, filtrated and
concentrated under vacuo. The product was distilled under reduced pressure to afford 19.9 g
(84 %) of a yellow oil (1E,3Z/1E,3E = 74/26). The product can alternatively be purified by
chromatography on a silica gel column using heptane/EtOAc 9:1 as eluent.
TLC, Rf = 0.53 (Heptane/EtOAc 1:1). GC: tR(3Z, 1Z) = 2.93 min, tR (3E, 1Z) = 3.01 min,
tR(3Z, 1E) = 3.14 min, tR(3E, 1E) = 3.22 min. Eb0.01 = 70 °C. 1H NMR (CDCl3, 300 MHz, δ):
0.95 (3H, t, J = 6.0 Hz), 1.32 (6H, t, J = 6.0 Hz), 2.0ꢀ2.14 (2H, m), 4.07ꢀ4.18 (4H, m), 5.39
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(1H, dt, J = 12 Hz, 6 Hz), 5.78 (1H, t, J = 12 Hz), 6.24 (1H, t, J = 12 Hz), 6.63 (1H, dd, J = 12
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Hz, 6 Hz). C NMR (CDCl3, 75 MHz, δ): 14.0, 16.0 (d, J = 6.8 Hz), 20.9, 64.3 (d, J = 6.0
Hz), 113.2 (d, J = 11.3 Hz), 121.4, 133.9, 139.1 (d, J = 6.0 Hz). 31P NMR (CDCl3, 121 MHz,
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δ): ꢀ4.5.
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Grignard reagent 4 prepared from 6-chlorohexanol17
Preparative Procedure. In a dry fourꢀneck 500 mL roundꢀbottom flask equipped with a
mechanical stirrer, a dropping funnel, a thermometer, a condenser and an argon inlet, were
introduced at 20 °C magnesium (17.8 g, 732 mmol) and THF (50 mL). Ethyl bromide (1.31 g,
12 mmol) was added instantaneously under vigorous stirring. After less than 1 min, the
mixture became greenish and the temperature rose to 28ꢀ30 °C. The reaction mixture was then
stirred at 50 °C and a solution of nꢀbutyl chloride (30.8 g, 333 mmol) in THF (200 mL) was
added dropwise in 20 to 30 min. After the end of the addition, stirring was continued for 3 h
at 45 °C. The reaction mixture was cooled to ꢀ10 °C and 6ꢀChlorohexanol (41 g, 300 mmol)
was added dropwise in 10 min via a syringe. The cooling bath was removed and the reaction
mixture was stirred for 1 h. The product was then heated to reflux for 5 hours. After cooling
to 20 °C, the expected Grignard reagent ClMgO(CH2)6MgCl was obtained in 95ꢀ97 % yield.
(7E, 9Z)-Dodecadien-1-yl acetate18
Preparative Procedure. To 82.5 mmol of ClMgO(CH2)6MgCl prepared as described above
were added , at 0 °C, THF (80 mL) and iron(III) acetylacetonate (26.5 mg, 0.1 mol%) in one
portion. To the dark mixture thus obtained was added diethyl (1E,3Z)ꢀhexaꢀ1,3ꢀdienyl
phosphate 5 (17.6 g, 75 mmol) in 10 min via a syringe. The reaction mixture was then stirred
for 2 h at 20 °C, cooled to 0 °C and acetic anhydride (14 mL, 150 mmol) was added dropwise
at 5 °C in 5 min via a syringe. After 1 h of stirring at 20 °C, 150 mL of an aqueous solution of
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HCl (1 M) was added to the reaction mixture. After decantation, the aqueous layer was
extracted with 3x20 mL of petroleum ether. The combined organic layers were dried over
magnesium sulphate, filtrated and concentrated under vacuo. The product was purified by
distillation under reduced pressure affording 14.0 g (83 %) of a slightly yellow oil
(7E,9Z/7E,9E = 74/26).
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TLC, Rf = 0.4 (100 % Petroleum ether). GC: tR(7Z, 9Z) = 13.04 min, tR(7E, 9Z) = 13.24 min,
1
tR(7Z, 9E) = 13.33 min, tR(7E, 9E) = 13.52 min. Eb0.06 = 90 °C. H NMR (CDCl3, 300 MHz,
δ): 0.98 (3H, t, J = 6.0 Hz), 1.27ꢀ1.41 (6H, m), 1.56ꢀ1.65 (2H, m), 2.02 (3H, s), 2.05ꢀ2.21
(4H, m), 4.04 (2H, t, J = 6.0 Hz), 5.29 (1H, td, J = 9.0 Hz, 6.0 Hz), 5.62 (1H, td, J = 15.0 Hz,
13
6.0 Hz), 5.89 (1H, t, J = 9.0 Hz), 6.28 (1H, dd, J = 15.0 Hz, 9.0 Hz). C NMR (CDCl3, 75
MHz, δ): 14.2, 20.88, 20.93, 25.7, 28.5, 28.7, 29.2, 32.7, 64.5, 125.6, 127.9, 131.7, 134.2,
171.0. HRMS: Calculated for C14H24O2Na: 247.1669. Found: 247.1669.
ASSOCIATED CONTENT
† Supporting Information
The supporting information is available free of charge on the ACS Publications website
at DOI:
1-H, 13-C and MS spectra.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: gerardꢀcahiez@chimieꢀparistech.fr
Author Contributions
G.C., N.L. and A.M. contributed equally to this work. O.G. and S.D. participated to fruitful
discussions.
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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We thank the fondation de la Maison de la Chimie for a grant to N. L. We thank also
the company M2i for a financial support in the framework of PHEROCHEM, a joint
laboratory between CNRS-Chimie ParisTech and M2i.
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NOTES AND REFERENCES
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(2) (a) Stockel, J.; Schmitz, V.; Lecharpentier, P.; Roehrich, R.; Torres Vila, M.; Neumann,
U.; Brustis J. M.; Pronier, V. Agronomie 1994, 2, 71. (b) Ideses, R.; Klug, J. T.; Shani, A.;
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WO 101636, 2015. d) Descoins, C.; Henrick, C. A. Tetrahedron Lett. 1972, 30, 2999.
(3) Kirsh, P. Am. J. Altern. Agric. 1988, 3, 83.
(4) Treating a one-hectare field with a regular pesticide costs between 50 and 150 €.
The biocontrol of the same surface using the pheromone costs around 250 €.
(5) http://www.agro.basf.fr/agroportal/fr/fr/cultures/la_vigne/les_insecticides4/La_confusion_
sexuelle.html. [September the 14th, 2016].
(6) Yamamoto, A.; Fukumoto, T. EP 0241335, 1987.
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(7) (a) Ujváry, I.; KisꢀTamás, A.; Novák, L. J. Chem. Ecol. 1985, 11, 113. (b) Odinokov, V.
N. Chem. Nat. Compd, 1999, 35, 260 (c) Lee, J. Y.; Choi, J. H.; Ryoo, K. S.; Kwon, Y. B.;
Hong, Y. P. Bull. Korean Chem. Soc. 2015, 36, 421. (d) Petrushkina, E. A.; Kalinin V. N.
Russ. J. Gen. Chem. 2008, 78, 1897. (e) de Figueiredo, R. M.; Berner, R.; Julis, J.; Liu, T.;
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Phys. Lipids 2001, 110, 57. (h) Alexakis, A.; Jachiet, D. Tetrahedron 1989, 45, 381. (i)
Ujváry, I.; KisꢀTamás, A.; Novák, L. J. Chem. Ecol. 1985, 11, 113. (j) Dressaire, G.;
Langlois, Y. Tetrahedron Lett. 1980, 21, 67. (k) Bestmann, H. G.; Süb, J.; Vostrowsky, O.
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(8) Cahiez, G.; Habiak, V.; Gager, O. Org. Lett. 2008, 10, 2389.
(9) Cahiez, G.; Habiak, V.; Gager, O. J. Org. Chem. 2008, 73, 6871.
(10) This synthesis was performed on a 50 kilogramme scale by our industrial partner
M2i. Dufour, S.; Guerret, O. WO 001383, 2016
(11) (a) Alexakis, A.; Cahiez, G.; Normant, J. F. Tetrahedron Lett. 1978, 23, 2030. (b)
Cahiez, G.; Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1978, 33, 3014.
(12) Same yields were obtained by using dienolphosphate 5 after purification or as a crude
product.
(13) Williams, D. B. G.; Lawton, M. J. Org. Chem. 2010, 75, 8351.
(14) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.
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(16) Dufour, S.; Guerret, O. WO 001383, 2016.
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(17) (a) Alexakis, A.; Cahiez, G.; Normant, J. F. Tetrahedron Lett. 1978, 23, 2030. (b)
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(18) Lee, J. Y.; Choi, J. H.; Ryoo, K. S.; Kwon, Y. B.; Hong, Y. P. Bull. Korean Chem. Soc.
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