A silicon-position dependent 6-endo-trig cyclization during Tsuji-Trost alkylation

Article abstract of DOI:10.1016/j.tet.2013.08.080

Two silylated cyclohexenes products have been prepared by using a Tsuji-Trost palladium-catalyzed cyclization. It involves the generation of a cationic π-allylic palladium complex bearing a triethylsilyl group on C-3, which cyclizes via a 6-endo-trig process to afford the cyclohexene derivatives. It is also demonstrated that the position of the silyl group on the starting allylic substrate strongly influenced the reaction. It could favor either the production of the expected cyclohexenyl ring or a diene by an elimination that occurs on the silyl-substituted C-2 π-allylic palladium complex.

Full text of DOI:10.1016/j.tet.2013.08.080

Tetrahedron 69 (2013) 9398e9405
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A silicon-position dependent 6-endo-trig cyclization during
TsujieTrost alkylation
*
Jyoti Agarwal, Claude Commandeur, Max Malacria, Serge Thorimbert
ꢀ
ꢀ
UPMC Sorbonne Universites, Institut Parisien de Chimie Moleculaire, UMR CNRS 7201, 4 Place Jussieu, 75005 Paris, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 July 2013
Received in revised form 26 August 2013
Accepted 30 August 2013
Available online 5 September 2013
Two silylated cyclohexenes products have been prepared by using a TsujieTrost palladium-catalyzed
cyclization. It involves the generation of a cationic
p-allylic palladium complex bearing a triethylsilyl
group on C-3, which cyclizes via a 6-endo-trig process to afford the cyclohexene derivatives. It is also
demonstrated that the position of the silyl group on the starting allylic substrate strongly influenced the
reaction. It could favor either the production of the expected cyclohexenyl ring or a diene by an elimi-
nation that occurs on the silyl-substituted C-2
p
-allylic palladium complex.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
TsujieTrost alkylation
Cyclization
Palladium
Regioselectivity
Silicon derivatives
1. Introduction
Since the pioneering work of Hirao, it is admitted that the
presence of a silyl groups usually direct the attack of the nucleo-
philes to the distal position (relative to the silicon atom) of the
Palladium-catalyzed allylic alkylation represents one of the
most versatile protocols in organic chemistry.1 After the pioneering
work of Tsuji and Trost,2 it has been applied successfully to the
synthesis of many biological active molecules, natural products,
and other important organic skeletons.3 This alkylation occurred
palladium p-allylic cationic complex leading to the corresponding
vinyl silanes.9 Such a regioselectivity may be accounted for in terms
of steric factors, charge distribution of the allyl complex, as well as
stability of the newly formed olefinePd(0) complex. We reported
a very strong silicon effect that afforded highly chemo- and ster-
eoselective palladium-catalyzed alkylations10 that we later applied
in synthesis.11 This directing group has been used to force the 5-
endo-trig processes versus the classical 3-exo-trig but was un-
successful for the 7-endo-trig versus the 5-exo-trig ones.12 All above
facts drew our attention to study the effect of the position of a silyl
group to direct a 6-endo-trig cyclization through the palladium-
catalyzed allylation process. Considering this, we envisaged the
synthesis of silylated cyclohexene products C through the forma-
via a p-allylic palladium complex intermediate generated from the
oxidative addition of Pd(0) into allylic substrates. Steric effects
usually govern the regioselectivity of this reaction, but electronic
properties of the substituents also greatly control the nucleophilic
attack.4 Along with various applications of this protocol, many re-
ports on palladium-catalyzed cyclization have been published.5 As
well exposed by J.E. Baldwin, cyclization processes are mostly
governed by the created ring size, the hybridization of the attacked
carbon as well as the inside or outside position of the break bond in
comparison to the formed cycle.6 Thus, the angle of approach of the
tion of the
p-allylic intermediates B, which in turn, could be gen-
nucleophile on the
p-allylic complex is indicative of the feasibility
erated from the reaction of allylic acetate or carbonate precursors A
of the reaction. It has been reported that malonyl vinylepoxides, in
the presence of palladium catalyst, led to cyclobutanols in place of
cyclohexenols via a 4-exo-trig process.7 Ionic 6-endo-trig cycliza-
tions in carbon skeleton remain a challenging area and methods to
synthesize cyclohexenes are still required even after the de-
velopment of ring closing metathesis reactions.8
with Pd(0) catalyst (Scheme 1).
2. Results and discussion
We first considered the precursor C bearing one hydroxyl
function on allylic position (Scheme 1; R0¼OH). The expected
resulting cyclohexene presents the correct functionalization for the
synthesis of carbocycles of biological interest, such as Shikimic acid,
for example.
* Corresponding author. Fax: þ33 1 44 27 73 60; e-mail address: serge.thor-
imbert@upmc.fr (S. Thorimbert).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.080

J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
9399
Even if this lactone could be considered as a protection of the
hydroxyl group, this ring should be open before the final cyclization
step due to strong steric constraints. Moreover, both the THP pro-
tective group and the third ester should also be replaced. Starting
from 7, we performed the simultaneous deprotection of the pri-
mary alcohol and the decarboxylation of one of the ester. Using
a catalytic amount of p-TSA in MeOH at room temperature, we
isolated the lactone 8 in 93% yield. Transesterification of 8 was then
performed using Ti(Oi-Pr)4 in refluxing isopropanol. Delightfully,
this protocol resulted in the formation of the corresponding diol 9
with 64% yield (Scheme 4).
Scheme 1. Silylated precursor A for 6-endo-trig cyclization.
We reasoned that the precursor 1 required for the cyclization
could be prepared in few steps (hydrosilylation, acylation) via the
alkyne resulting from the addition of the propargylic alcohol 3 to
the malonyl aldehyde 2 (Scheme 2).
Scheme 4. Preparation of alkynyl diol 9.
We then performed the hydrosilylation of the triple bond of the
alkynyl diol 9 by using Et3SiH in presence of catalytic amount of
H2PtCl6 (Fig. 1).14 Surprisingly, when the reaction was performed in
i-PrOH as solvent, no hydrosilylation was noticed after one night at
50 ꢀC (Table 1, entry 1). In acetonitrile, only 20% of hydrosilylation
product was obtained with the recovery of 70% of starting material
(Table 1, entry 2). In neat conditions, the conversion was also not
completed, affording mostly degradation products (Table 1, entry
3). In all cases, no selectivity was apparent. Finally, the best result
was obtained in THF, giving the corresponding regioisomers 10 and
11 in 90% yield in a 1:1 ratio. We also tested the direct hydro-
silylation of the lactone 7 with tert-butyldimethylsilane, but this
also led to a mixture of two isomers in a 59% yield.
Scheme 2. Approach towards the cyclization precursor 1.
We observed degradation products during the condensation
step between the malonyl aldehyde 2 and the propargylic alcohol
derivative 3. It is noteworthy to mention here that the hydrogen
atom present at
a-position related to the ester groups is acidic
enough to give side reactions under the operating conditions. We
thus masked this acidic proton by replacing it with a third ester
function (Scheme 3).
Scheme 3. Preparation of triester aldehyde 6 and synthesis of lactone 7.
Fig. 1. Hydrosilylation of 9.
Thus, the allyl malonate 4 was converted into the triester 5 by
alkylation with methyl chloroformate.13 The ozonolysis of the
double bond delivered the expected aldehyde 6 in good yield over
the two steps. Our next target was the preparation of the allylic
acetate 1. For that purpose, we performed the alkylation of the al-
dehyde 6 with the lithiated anion of O-protected propargylic al-
cohol 3. The reaction was fast but the expected allylic alcohol was
not observed. In its place, we isolated in nearly quantitative yield,
the lactone 7 resulting from the intramolecular attack of the gen-
erated alkoxide ion to one of the ester functions. The more hindered
triethyl ester also delivered the corresponding lactone. To avoid the
formation of the lactone 7, we considered performing the alkylation
in the presence of Cerium (III) or Chromium (III) chlorides or with
the preformed ceric anion of 3. These conditions also led to the
formation of the heterocyclic compound 7 with comparable yields.
Table 1
Solvent screening for the hydrosilylation of 9
Entry
Solvent
Conversion (%)
Ratio 10:11
Yield (%)a
1
2
3
4
i-PrOH
CH3CN
Neat
d
d
d
30
70
100
1:1
1:1
1:1
20
20
90
THF
a
Combined isolated yield of both regioisomers.
The two regioisomers 10 and 11 were separated by flash chro-
matography, and 10 was quantitatively converted into the corre-
sponding allylic acetate 12 by using acetic anhydride and NEt3 in
CH2Cl2. It should be noted that 10,11, and 12 slowly cyclized into the

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J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
corresponding more stable lactones (see Experimental part for
characterization). Therefore, it is essential to engage them rela-
tively quickly after their preparation.
The two tetrahydropyranyl derivatives 17 and 18 could be sep-
arated by careful flash chromatography. However, it is preferable,
with these substrates, to first remove the THP group in acidic
conditions (p-TSA/MeOH)18 and then to separate the corresponding
allylic alcohols 19 and 20. Acylation of 19 delivered the expected
allylic acetate 21 in 89% yield over these two steps.19 We treated 21
with NaH followed by the palladium catalyst [prepared from
Pd(OAc)2 and phosphines, such as mono- and diphosphine (PPh3 or
dppe), phosphite or ferrocenyl ligands]. Various solvents, such as
THF, toluene, and DMF were tested for the present protocol. No
product was detected and, in all cases, the starting material 21 was
fully recovered. Under the same conditions, precursors bearing
either a trifluoroacetate or a carbonate as leaving group also did not
lead to the expected cyclohexene but degradation mostly occurred.
Given the non-reactivity of the starting material, we concluded
that under the operating conditions, degradation of the catalytic
system should be faster than the cyclization. To test this hypothesis,
we quickly heat the reaction mixture containing, the sodium anion
of 21 and the catalyst to 90 ꢀC. Gratifyingly, under these new re-
action conditions, we obtained the desired cyclization product 22. A
marked difference in reactivity was observed depending on the
ligands of the palladium (Fig. 2, Table 2).
After the synthesis of the allylic acetate precursor 12, we per-
formed the palladium-catalyzed 6-endo-trig cyclization.15 This re-
action was carried out in presence of sodium hydride followed by
the addition of 5 mol % of Pd(PPh3)4 catalyst. The reaction worked
well in THF at 65 ꢀC and we observed the consumption of the
starting material in less than 3 h. After purification, we did not
observe the formation of the expected silylated cyclohexenol 13 but
we isolated the conjugated trienic ester 15 in 42% yield. The 1H and
13C NMR indicated the presence of five vinylic protons and six vi-
nylic carbons. HRMS definitively confirmed the proposed structure
(Scheme 5).
Scheme 5. Palladium-catalyzed cyclization of 12.
We examined the formation of this compound, and hypothe-
sized that the 6-endo-trig cyclization has taken place as expected.
Indeed, we propose the formation of the desired cyclohexenol 13
followed by a dehydration reaction. The palladium complex could
eventually mediate this undesired elimination.16 The resulting
Fig. 2. Palladium-catalyzed cyclization of 21.
cyclohexadiene 14 then underwent a 6-
p retro-electrocyclization
giving the more stable conjugated triene 15.17 To validate the hy-
pothesis that the formation of compound 15 occurred through a 6-
endo-trig cyclization, and not merely a direct degradation of the
precursor 12, we decided to synthesize a simplified precursor,
which did not possesses a secondary hydroxyl function (Scheme 1,
C; R0¼H). This model, required to validate our strategy, could be
prepared by hydrosilylation of an alkyne precursor 16 previously
reported by Deslongchamps (Table 3).18
Table 2
Ligand optimization for 6-endo-trig cyclization
Entry
Ligand (L)
Time (h)
Conversion (%)
Yield (%)a
1
2
3
4
5
6
dppf
P(OPh)3
dppe
PPh3
P(OEt)3
P(Oi-Pr)3
24
24
24
24
24
2
38
42
65
n.d.
n.d.
n.d.
30
72
74
34
100
66
The introduction of the triethylsilyl group onto 16 was con-
ducted under standard H2PtCl6-catalyzed hydrosilylation. It de-
livered a mixture of two regioisomers 17 and 18 in a 2:3 ratio with
an overall yield of 90% (Scheme 6). Few organometallic complexes
were tested without real improvement. For example, when the
rhodium dimer [RhCl(cod)]2 was used the yield decreased to 74%,
whereas the platine(II) precursor PtCl2(PhCN)2 gave a slightly
better 95% yield. The use of cationic ruthenium complexes mainly
degradated the starting alkyne.
a
Isolated yield; not determined when conversion was too low.
Regardless of the ligand used, the 6-endo-trig cyclization process
has consistently held. However, the reactivities remained generally
modest and the conversions did not exceed 74% after 24 h (Table 2,
entries 1e5). The use of tri-isopropylphosphite allowed the full
conversion of the substrate 21 a significant acceleration in the re-
action rate as the starting material disappeared within 2 h. It
afforded the expected cyclohexene 22 in 66% isolated yield as well
as some unidentified degradation products (Table 2, entry 6).
We also prepared a precursor having bulkier isopropyl ester
functions. At this end, we performed the trans-esterification of
compound 19 mediated by Ti(Oi-Pr)4 in isopropanol. The expected
diisopropylic malonate was isolated in 90% yield then acylated by
using the standard conditions (Ac2O, NEt3) to provide the allylic
acetate 23 in 96% yield (Scheme 6). Using the optimized reaction
conditions (vide supra), total conversion of the starting material
was observed and the corresponding cyclohexene 24 was isolated
in a moderated 45% yield in addition to unidentified degradation
products (Scheme 7).
Scheme 6. Hydrosilylation of 16.

J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
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4. Experimental section
4.1. General
The characterization data for compounds 2, 3, 4, 5, and 16 was
previously reported. All reactions requiring anhydrous conditions
were carried out under an atmosphere of nitrogen or argon in
flame-dried glassware using standard syringe techniques. 1H NMR
spectra were recorded on 200 and 400 MHz NMR spectrometers
using CDCl3
(
d
¼7.26 ppm) as the internal reference. 13C NMR
spectra were recorded at 50 or 100 MHz using CDCl3 (
d
¼77.16 ppm)
as the internal reference. Infrared spectra were recorded on an FT-
IR spectrophotometer and signals are reported in cmꢁ1. Mass
spectra were recorded either through electrospray ionization (ESI)
or electron impact (EI) on an instrument operating at 70 eV.
Scheme 7. Preparation of precursor 23 and cyclization into 24.
4.1.1. 2-Allyl-2-methoxycarbonyl-malonic acid dimethyl ester
(5).13 At 0 ꢀC, to a suspension of NaH (60% in mineral oil) (5.85 g,
146.2 mmol, 1.5 equiv) in THF (150 mL), was added 4 (16.78 g,
97.4 mmol) and the mixture was warmed to rt and stirred during 1 h.
Then, freshly distilled ClCO2Me (20 mL, 258.0 mmol, 2.6 equiv) was
slowly added at 0 ꢀC and the solution was warmed to rt and stirred
during 2 h. The reaction mixture was diluted in diethyl ether and
washed with saturated aqueous solution of ammonium chloride and
brine, dried over MgSO4, filtered, and concentrated. Pure compound
5 (20.41 g, 88.6 mmol, 91%) was obtained as a colorless oil. 1H NMR
To demonstrate the strong influence of the position of the silyl
group during the cyclization, we also tested the allylic acetate 25.
This compound is supposed to produce a highly reactive
p-allyl
palladium complex unsuitable for cyclization (Fig. 3).11a,12b
Thus, engaged in the palladium-catalyzed reaction at room
temperature, the starting acetate 25 was recovered (Table 3, entry
1). As expected, upon heating, the diene 26 was isolated quanti-
tatively regardless of the solvent or the ligand used (Table 3, entries
2e6). We explain these results by the competition between the
unfavorable cyclization with the fast elimination on the in-
(CDCl3, 200 MHz)
d
5.95e5.77 (ddt, J¼17.2; 10.3 and 7.4 Hz, 1H,
H2C]CHCH2); 5.09 (dd, J¼17.2 and 1 Hz, 1H, HC]CHtrans); 4.99 (dd;
J¼10.3 and 1 Hz, 1H, HC]CHcis); 3.70 (s, 9H, CO2CH3); 2.78 (d,
termediate cationic p-allylic palladium complex.
J¼7.4 Hz, 2H, H2C]CHCH2). 13C NMR (CDCl3, 50 MHz)
d 166.9
(CO2CH3); 132.4 (H2C]CHCH2); 119.4 (H2C]CHCH2); 65.7
(C(CO2CH3)3); 53.1 (CO2CH3); 37.6 (H2C]CHCH2). IR (neat), cmꢁ1
:
2900; 1740; 1460; 1370; 1230. Anal. for C10H14O6
(M¼230.22 g molꢁ1): calcd (%) : C¼52.17; H¼6.13. found (%) :
C¼52.06; H¼6.32.
4.1.2. 2-Methoxycarbonyl-2-(2-oxo-ethyl)-malonic acid dimethyl es-
ter (6). In a flask without septum, ozone was added to a cold
(ꢁ78 ꢀC) solution of allyl malonate 5 (1.38 g, 6.0 mmol) in a mixture
CH2Cl2/MeOH: 3:1 (20 mL) until a persistent blue color was per-
ceived or until total disparition of S.M. was observed by TLC. Then, O3
in excess was removed by bubbling a N2 flow. Methyl sulfide
(2.15 mL, 30 mmol, 5 equiv) was added and the solution is stirred
10 min at ꢁ78 ꢀC, then slowly warmed to rt in 3 h. Me2S was re-
moved under reduced pressure using a NaClO trap. After removal of
the solvent, diethyl ether was added and the crude product, which
precipitate was filtered. Pure compound 6 (1.33 g, 5.7 mmol, 96%)
was obtained as a white powder. TLC (PE/EA¼7:3): Rf¼0.40. Mp:
Fig. 3. Palladium-catalyzed elimination into diene 26.
Table 3
Effect of ligand in palladium-catalyzed elimination
Entry
Ligand (L)
Solvent
Temp (ꢀC)
Yield (%)a
1
2
3
4
5
6
PPh3
THF
rt
n.r.
PPh3
dppe
dppe
dppe
THF
THF
Toluene
DMF
DMF
65
50
80
90
90
quant.
quant.
quant.
quant.
quant.
75 ꢀC. 1H NMR (CDCl3, 200 MHz)
CO2CH3); 3.17 (s, 2H, CH2).13C NMR (CDCl3, 50 MHz)
166.5 (CO2CH3); 62.4 (C(CO2CH3)3); 53.9 (CO2CH3); 45.5 (CH2). IR
d
9.68 (s, 1H, O]CH); 3.78 (s, 9H,
196.5 (O]CH);
P(Oi-Pr)3
d
a
Isolated yield.
(neat), cmꢁ1
: 2975; 1720; 1435; 1240. Anal. for C9H12O7
(M¼232.19 g molꢁ1): calcd (%): C¼46.56; H¼5.21. Found (%):
C¼46.68; H¼5.24.
3. Conclusion
4.1.3. 2-Oxo-5-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl]-dihydro-
furan-3,3-dicarboxylic acid dimethyl ester (7). To a solution of 3
(23.45 mL, 166.8 mmol, 1.1 equiv) in THF (250 mL), at ꢁ78 ꢀC, was
added dropwise a 2 M solution of n-BuLi (83.4 mL, 166.8 mmol,
1.1 equiv) and the mixture was stirred 30 min at this temperature.
Then, the anion was canulated onto a solution of aldehyde 6 (35.2 g,
151.6 mmol) in THF (50 mL) and the mixture warmed to rt and
stirred 2 h. Then, Et2O and NH4Cl were added. The aqueous phase
was extracted with Et2O. Combined organic layers were washed
with brine, dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude compound 7 was obtained as an
We have developed conditions allowing the preparation of
functionalized silylated cyclohexenes. The position of the vinylic
silyl group on the starting allylic substrate strongly influenced the
palladium-catalyzed cyclizations. It could favor either the pro-
duction of an open chain diene by a direct elimination on the pal-
ladium intermediate or a cyclohexenyl ring via a 6-endo-trig
process. In addition, the presence of a hydroxyl group at the allylic
position of the starting material, allowed the cyclization to proceed
smoothly. It is followed by dehydration and a 6-
rearrangement giving a conjugated trienic product.
p electrocyclic

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J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
orange oil and was directly engaged in the next step. TLC (PE/
CHCO2i-Pr); 2.45 (s br, 1H, OH); 2.13 (ddd, J¼14.7, 10.6 and 5.6 Hz,
1H, part of CH2CHOH); 1.96 (ddd, J¼14.7, 8.6 and 3.0 Hz, 1H, part of
CH2CHOH); 1.66 (s br, 1H, OH); 1.25 (d, J¼6.6 Hz, 12H,
CO2CH(CH3)2); 0.92 (t, J¼7.6 Hz, 9H, SiCH2CH3); 0.65 (q, J¼7.6 Hz,
EA¼7:3): Rf¼0.35. 1H NMR (CDCl3, 200 MHz)
5.31 (t, J¼6.9 Hz, 1H,
d
OCHCC); 4.73 (s, 1H, OCHO); 4.23 (s, 2H, CCCH2O); 3.63 (s, 6H,
CO2CH3); 3.60e3.42 (m, 2H, CH2CH2O); 2.41 (t, J¼6.9, 2H,
CH2CCO2Me); 1.73e1.50 (m, 6H, (CH2)3CHO). 13C NMR (CDCl3,
6H, SiCH2CH3). 13C NMR (CDCl3, 100 MHz)
d 168.3 (CO2i-Pr); 140.6
50 MHz)
d
168.9 (CO2Me); 154.5 (C(O)CCO2Me); 96.8 (OCHO); 83.7
(]CSi); 138.1 (]CH); 69.2 (CO2CH(CH3)2); 61.7 (CHOH); 54.8
(CH2OH); 49.1 (CH(CO2i-Pr)2); 33.3 (CH2CH(CO2i-Pr)2); 21.6
(CCCH2OCHO); 81.2 (CCCH2OCHO); 65.8 (OCHCC); 62.0 (CH2CH2O);
54.0 (CCCH2OCHO); 52.8 (CO2CH3); 47.8 (CCO2Me); 33.6
(CH2CCO2Me); 30.2 (CH2CH2CHO); 25.3 (CH2CH2CHO); 19.0
(CH2CH2O). IR (ATR), cmꢁ1: 2953; 1736; 1439; 1339; 1258; 1119;
1024; 941; 902.
(CO2CH(CH3)2); 7.2 (SiCH2CH3); 3.4 (SiCH2CH3). IR (ATR), cmꢁ1
:
3450; 2954; 2876; 1728; 1456; 1375; 1262; 1166; 1102; 1004; 721.
100: TLC (PE/EA¼7:3): Rf¼0.50. 1H NMR (CDCl3, 400 MHz)
d 5.94
(t, J¼5.1 Hz, 1H, ]CH); 5.53 (t, J¼8.6 Hz, 1H, CHOCO); 5.05 (sept,
J¼6.1 Hz, 1H, CH(CH3)2); 4.31e4.16 (m, 2H, CH2OH); 3.54 (m, 1H,
CHCO2i-Pr); 2.68e2.07 (m, 2H, CH2CHO); 1.25 (d, J¼6.1 Hz, 6H,
CO2CH(CH3)2); 0.92 (t, J¼7.6 Hz, 9H, SiCH2CH3); 0.65 (q, J¼7.6 Hz,
4.1.4. 5-(3-Hydroxy-prop-1-ynyl)-2-oxo-tetrahydro-furan-3-
carboxylic acid methyl ester (8). To a solution of crude 7 (16.35 g,
48.03 mmol) in MeOH (50 mL) was added at rt p-TSA (3.66 g,
19.2 mmol, 40%) and the mixture was stirred overnight. Then, the
solution was diluted in Et2O and a saturated aqueous solution of
NaHCO3 was added. The aqueous phase was extracted with Et2O.
Combined organic layers were washed with brine, dried over
MgSO4, filtered, and concentrated under reduced pressure. The
crude compound was purified by flash chromatography and 8
(8.92 g, 45 mmol; 93% over 2 steps from 6) was obtained as a pale
yellow oil. TLC (PE/EA¼7:3): Rf¼0.10. 1H NMR (CDCl3, 400 MHz)
6H, SiCH2CH3). 13C NMR (CDCl3, 100 MHz)
d 171.8 (CO2i-Pr); 167.4
(OC]O); 142.1 (]CH); 138.9 (]CSi); 81.3 (CHO); 70.4
(CO2CH(CH3)2); 59.9 (CH2OH); 47.7 (CH(CO2i-Pr)); 33.9 (CH2CHO);
21.7 (CO2CH(CH3)2); 7.4 (SiCH2CH3); 3.6 (SiCH2CH3). IR (ATR), cmꢁ1
:
2954; 2876; 1780; 1729; 1456; 1375; 1256; 1164; 1103; 1004; 971;
722. Anal. for C17H30O5Si (M¼342.50 g molꢁ1): calcd (%) : C¼59.62;
H¼8.83. found (%): C¼59.71; H¼8.74.
d
5.32 (t, J¼6.4 Hz, 1H, OCHCC); 4.26 (s, 2H, CH2OH); 3.77 (s, 3H,
4.3. General procedure B
CO2CH3); 3.63 (t, J¼7.4 Hz, 1H, CHCO2CH3); 2.44 (dd, J¼7.4 and
6.4 Hz, 2H, CH2CHCO2); 2.23 (s, 1H, OH). 13C NMR (CDCl3, 100 MHz)
4.3.1. 2-(5-Acetoxy-2-hydroxy-3-triethylsilanyl-pent-3-enyl)-ma-
lonic acid diisopropyl ester (12). To a solution of 10 (430 mg,
1.15 mmol), in dry CH2Cl2 (2 mL), distilled Et3N (0.4 mL, 2.8 mmol,
2.5 equiv) was added and the resulting suspension was allowed to
stir at room temperature until dissolution was completed. Freshly
distilled acetyl chloride (80 mL, 1.15 mmol, 1 equiv) was then added
dropwise at 0 ꢀC to the reaction mixture. The reaction was then
allowed to warm to room temperature and stirred overnight. The
mixture was treated with a saturated aqueous solution of NH4Cl. The
aqueous phase was extracted with CH2Cl2. The collected organic
layers werewashed with brine, dried over MgSO4, and evaporated in
vacuo. The crude product was purified by flash chromatography to
give 12 (511 mg, 1.15 mmol, quant.) as a colorless oil. TLC (Pent/
d
169.0 (CO2Me); 154.6 (C(O)CHCO2Me); 86.1 (CCCH2OH); 80.4
(CCCH2OH); 65.8 (OCHCC); 52.8 (CO2CH3); 50.5 (CH2OH); 47.8
(CHCO2Me); 33.5 (CH2CHCO2Me). IR (neat), cmꢁ1: 3499; 2958;
1755; 1441; 1268; 1027; 939.
4.1.5. 2-(2,5-Dihydroxy-pent-3-ynyl)-malonic acid diisopropyl ester
(9). To a solution of 8 (2.47 g, 12.46 mmol) in i-PrOH (20 mL) was
added, at rt, Ti(Oi-Pr)4 (3.7 mL, 12.46 mmol, 1 equiv). The mixture
was warmed to 80 ꢀC and stirred overnight. After completion of the
reaction, Et2O and a saturated aqueous solution of Na2SO4 were
added. Ti salts were filtered and the compound 9 (2.29 g, 8.0 mmol,
64%) was obtained as translucent oil. TLC (PE/EA¼5:5): Rf¼0.40. 1H
NMR (CDCl3, 400 MHz)
d
5.26 (t, J¼5.1 Hz, 1H, CHOH); 5.05 (sept,
EA¼95:5): Rf¼0.60.1H NMR (CDCl3, 400 MHz)
5.81 (t, J¼6.8 Hz,1H,
d
J¼6.1 Hz, 2H, CO2CH(CH3)2); 4.26 (d, J¼5.6 Hz, 2H, CH2OH); 3.68 (t,
J¼8.1 Hz, 1H, CH(CO2i-Pr)2); 2.88e2.46 (m, 2H, CH2CHOH); 2.24 (s
br, 2H, 2ꢂ CHOH); 1.23 (d, J¼6.1 Hz, 12H, CO2CH(CH3)2). 13C NMR
]CH); 5.54 (m, 1H, SiCCHOH); 5.05 (sept, J¼6.3 Hz, 2H,
CO2CH(CH3)2); 4.62 (m, 2H, CH2OAc); 3.51 (m, 1H, CHCO2i-Pr);
2.69e2.37 (m, 2H, CH2CHOH); 2.05 (s, 3H, OCOCH3); 1.27 (d,
J¼6.3 Hz, 12H, CO2CH(CH3)2); 0.90 (t, J¼7.8 Hz, 9H, SiCH2CH3); 0.66
(CDCl3, 100 MHz)
d 166.9 (CO2CH(CH3)2); 86.8 (CCCHOH); 80.9
(CCCH2OH); 70.4 (OCH(CH3)2); 68.3 (CCHOH); 50.6 (CH2OH); 46.7
(q, J¼7.8 Hz, 6H, SiCH2CH3). 13C NMR (CDCl3, 100 MHz)
d 171.6
(CH(CO2i-Pr)2); 33.5 (CHCH2); 21.6 (CO2CH(CH3)2). IR (ATR), cmꢁ1
:
(OCOCH3); 167.3 (CO2i-Pr); 141.7 (]CSi); 136.3 (]CH); 81.2 (CHO);
70.5 (CO2CH(CH3)2); 61.3 (CH2O); 47.7 (CH(CO2i-Pr)); 33.7
(CH2CHO); 21.8 (CO2CH(CH3)2); 21.1 (OCOCH3); 7.5 (SiCH2CH3); 3.6
(SiCH2CH3). IR (ATR), cmꢁ1: 3440; 2954; 2873; 1727; 1455; 1375;
1260; 1168; 1101; 1004; 720. Anal. for C22H40O7Si
(M¼444.63 g molꢁ1): calcd (%): C¼59.43; H¼9.07. found (%):
C¼59.69; H¼8.68.
3482; 2983; 1778; 1721; 1454; 1258; 1147; 1101; 1007.
4.2. General procedure A for hydrosilylation
Under Ar, to a solution of alkyne (1 equiv) in THF (3 M), silane
(1.2 equiv), and a 0.1 M solution of H2PtCl6, 6H2O (0.01 mol %) in
THF were added. The mixture was warmed to 50 ꢀC overnight. The
solution was filtered at room temperature over a short pad of Celite,
concentrated in vacuo, and purified by flash chromatography.
4.3.2. 5-(3-Acetoxy-1-triethylsilanyl-propenyl)-2-oxo-tetrahydro-fu-
ran-3-carboxylic acid isopropyl ester (120). The formation of this
compound (pale yellow oil) sometime occurs during acylation of 10
or when 12 was stored at rt. TLC (PE/EA¼7:3): Rf¼0.30. 1H NMR
4.2.1. 2-(2,5-Dihydroxy-3-triethylsilanyl-pent-3-enyl)-malonic acid
diisopropyl ester (10) and 5-(3-hydroxy-1-triethylsilanyl-propenyl)-
2-oxo-tetrahydro-furan-3-carboxylic acid isopropyl ester (100).
These compounds were prepared according to the general pro-
cedure A from 9 (1.88 g, 6.5 mmol) to give a mixture of two
regioisomers 10/11 in a 1/1 ratio (pale yellow oil, 2.4 g, 5.9 mmol).
10 was isolated by flash chromatography, and cyclized slowly into
100 when stored at rt. 10: TLC (PE/EA¼7:3): Rf¼0.40. 1H NMR (CDCl3,
(CDCl3, 400 MHz)
d
5.83 (t, J¼5.4 Hz,1H, ]CH); 5.54 (t, J¼6.6 Hz,1H,
CHOCO); 5.05 (sept, J¼6.1 Hz, 1H, CH(CH3)2); 4.65e4.58 (m, 2H,
CH2O); 3.57 (m, 1H, CHCO2i-Pr); 2.70e2.37 (m, 2H, CH2CHO); 2.07
(s, 3H, OCOCH3); 1.24 (d, J¼6.1 Hz, 6H, CO2CH(CH3)2); 0.90 (t,
J¼7.6 Hz, 9H, SiCH2CH3); 0.62 (q, J¼7.6 Hz, 6H, SiCH2CH3). 13C NMR
(CDCl3, 100 MHz)
d 172.5 (OCOCH); 171.6 (OCOCH3); 167.8 (CO2i-
Pr); 142.4 (]CSi); 137.1 (]CH); 81.9 (CHO); 71.2 (CO2CH(CH3)2);
62.0 (CH2O); 48.4 (CH(CO2i-Pr)); 34.5 (CH2CHO); 22.6
(CO2CH(CH3)2); 21.8 (OCOCH3); 8.2 (SiCH2CH3); 4.4 (SiCH2CH3). IR
(ATR), cmꢁ1: 2954; 2876; 1782; 1733; 1455; 1375; 1227; 1163;
400 MHz)
d
5.89 (t, J¼6.1 Hz, 1H, ]CH); 5.05 (sept, J¼6.6 Hz, 2H,
CO2CH(CH3)2); 4.53 (dd, J¼10.6 and 3.0 Hz, 1H, SiCCHOH); 4.28 (dd,
J¼6.1 and 2.0 Hz, 2H, CH2OH); 3.54 (dd, J¼8.6 and 5.6 Hz, 1H,

J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
9403
1105; 1019; 970; 722. Anal. for C19H32O6Si (M¼384.54 g molꢁ1):
calcd (%): C¼59.34; H¼8.39. Found (%): C¼59.27; H¼8.40.
stirred overnight. Then, the solution was diluted in Et2O and a sat-
urated aqueous solution of NaHCO3 was added. The aqueous phase
was extracted with Et2O. Combined organic layers were washed
with brine, dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude compound was purified by flash
chromatography to give 19 (1.07 g, 5.0 mmol, quant.) as a pale
yellow oil. NMR spectrum were identical to the described molecule.
4.4. General procedure C
4.4.1. 2-(3-Triethylsilanyl-penta-2,4-dienylidene)-malonic acid dii-
sopropyl ester (15). To a suspension of sodium hydride (19 mg,
0.475 mmol, 0.95 equiv) in THF (2 mL), was added, at 0 ꢀC, a solu-
tion of 12 (215 mg, 0.5 mmol) in THF (0.5 mL). The mixture was
warmed to rt and stirred during 10 min. Then, a beforehand made
solution of Pd(OAc)2 (6 mg, 5 mol %), PPh3 (26 mg, 20 mol %) in THF
(2 mL) was added and the mixture was warmed to reflux. After 1 h,
Et2O and NH4Cl were added and after a standard work-up, the
crude product was purified by flash chromatography and 15 (77 mg,
TLC (PE/EA¼7:3): Rf¼0.20. 1H NMR (CDCl3, 400 MHz)
d 4.18 (s, 2H,
CH2OH); 3.70 (s, 6H, CO2CH3); 3.54 (t, J¼7.1 Hz,1H, CHCO2CH3); 2.42
(s, 1H, OH); 2.27 (t, J¼7.1 Hz, 2H, CCCH2CH2); 2.05 (dt, J¼7.1 and
7.1 Hz, 2H, CH2CHCO2Me). 13C NMR (CDCl3, 100 MHz)
d 169.6
(CO2CH3); 83.9 (CCCH2OH); 80.1 (CCCH2OH); 52.7 (CO2CH3); 51.1
(CH2OH); 50.4 (CHCO2CH3); 27.6 (CCCH2CH2); 16.8 (CCCH2CH2). IR
(ATR), cmꢁ1: 3419; 2955; 1728; 1435; 1248; 1154; 1047; 1010.
0.21 mmol, 42%) was obtained as
a
colorless oil. TLC
(Pent/AE¼95:5): Rf¼0.95. 1H NMR (CDCl3, 400 MHz)
d 7.74 (d,
4.5.2. 2-(5-Hydroxy-3-triethylsilanyl-pent-3-enyl)-malonic acid di-
methyl ester (19) and 2-(5-hydroxy-4-triethylsilanyl-pent-3-enyl)-
malonic acid dimethyl ester (20). Following general procedure D,
a 2/3 mixture of 17 and 18 (53.9 g, 130 mmol) delivered two
regioisomers 19 (16.8 g, 50.8 mmol) and 20 (26.0 g, 78.7 mmol),
which were separated on silica gel.
J¼12.2 Hz, 1H, CHCCO2i-Pr); 6.68 (dd, J¼17.3 and 11.2 Hz, 1H,
CHCH2); 6.63 (d, J¼12.2 Hz, 1H, SiC]CH); 5.34 (d, J¼11.2 Hz, 1H,
CH]CHcis); 5.22 (d, J¼17.3 Hz, 1H, CH]CHtrans); 5.20 and 5.09
(2sept, J¼6.1 Hz, 2ꢂ 1H, 2ꢂ CO2CH(CH3)2); 1.31 and 1.25 (2d,
J¼6.1 Hz, 2ꢂ 6H, 2ꢂ CO2CH(CH3)2); 0.90 (t, J¼8.1 Hz, 9H, CH2CH3);
19: TLC (PE/EA¼6:4): Rf¼0.65. 1H NMR (CDCl3, 200 MHz)
d 5.89
0.69 (q, J¼8.1 Hz, 6H, CH2CH3). 13C NMR (CDCl3, 100 MHz)
d 165.4
(t, J¼6.1 Hz, 1H, ]CH); 4.21 (d, J¼6.1 Hz, 2H, CH2OH); 3.70 (s, 6H,
CO2CH3); 3.31 (t, J¼7.6 Hz, 1H, CH(CO2CH3)2); 2.05 (m, 2H,
CH2CH2CSi); 2.02 (s, 1H, OH); 1.81 (m, 2H, CH2CSi); 0.87 (t, J¼8.1 Hz,
9H, CH2CH3); 0.55 (q, J¼8.1 Hz, 6H, CH2CH3). 13C NMR (CDCl3,
and 164.5 (2ꢂ CO2CH(CH3)2); 154.4 (CCO2i-Pr); 137.6 (CHCCO2i-Pr);
135.7 (CHCH2); 132.9 (SiC]CH); 127.2 (CH]CH2); 119.8 (SiC]CH);
69.1 and 68.9 (2ꢂ CO2CH(CH3)2); 21.9 (2ꢂ CO2CH(CH3)2); 7.4
(CH2CH3); 3.3 (CH2CH3). IR (neat), cmꢁ1: 2950; 1720; 1605; 1375;
1255; 1110; 740. HRMS (IC, CH4) for [MNH4]þ 367.2305, mes.
367.2307.
50 MHz)
d 169.7 (CO2CH3); 141.8 (]CH); 139.1 (]CSi); 59.3
(CH2OH); 52.6 (CO2CH3); 51.6 (CH(CO2CH3)2); 29.1 (CH2CH2CSi);
27.9 (CH2CSi); 7.4 (CH2CH3); 2.9 (CH2CH3). IR (neat), cmꢁ1: 3446;
2954; 2911; 2874; 1736; 1437; 1268; 1158; 1005; 737. Anal. for
C16H30O5Si (M¼330.49 g molꢁ1): calcd (%) : C¼58.15; H¼9.15.
Found (%): C¼58.01; H¼9.16.
4.4.2. 2-[5-(Tetrahydro-pyran-2-yloxy)-3-triethylsilanyl-pent-3-
enyl]-malonic acid dimethyl ester (17) and 2-[5-(tetrahydro-pyran-2-
yloxy)-4-triethylsilanyl-pent-3-enyl]-malonic acid dimethyl ester
(18). These compounds were prepared according to the general
procedure A from 2-[5-(tetrahydro-pyran-2-yloxy)-pent-3-ynyl]-
malonic acid dimethyl ester 1618 (13.13 g, 44 mmol). After comple-
tion of the reaction, a 2/3 mixture of two regioisomers 17 and 18 was
obtained (16.18 g, 39 mmol). 17: TLC (PE/EA¼7:3): Rf¼0.70. 1H NMR
20: TLC (PE/EA¼6:4): Rf¼0.85.1H NMR (CDCl3, 200 MHz)
d 5.73 (t,
J¼7.1 Hz,1H, ]CH); 4.15 (s, 2H, CH2OH); 3.71 (s, 6H, CO2CH3); 3.34 (t,
J¼7.6 Hz, 1H, CH(CO2CH3)2); 2.21 (dt, J¼7.6 and 7.1 Hz, 2H,
CH2CH2CH]); 1.97 (dt, J¼7.6 and 7.1 Hz, 2H, CH2CH2CH]); 1.53 (s,
1H, OH); 0.89 (t, J¼8.2 Hz, 9H, CH2CH3); 0.60 (q, J¼8.2 Hz, 6H,
CH2CH3). 13C NMR (CDCl3, 50 MHz)
d 169.9 (CO2CH3); 142.1 (]CH);
(CDCl3, 400 MHz)
d
5.83 (t, J¼5.6 Hz,1H, ]CH); 4.53 (m, 1H, OCHO);
139.9 (]CSi); 60.4 (CH2OH); 52.7 (CO2CH3); 51.0 (CH(CO2CH3)2); 28.5
(CH2CH2CH]); 26.3 (CH2CH2CH]); 7.5 (CH2CH3); 3.2 (CH2CH3). IR
(neat), cmꢁ1: 3474; 2953; 2877; 2361; 1733; 1437; 1229 (br); 1156;
1005; 716. Anal. for C16H30O5Si (M¼330.49 g molꢁ1): calcd (%):
C¼58.15; H¼9.15. Found (%): C¼58.10; H¼9.10.
4.26 (dd, part of AB system, J¼13.0 and 5.6 Hz, 1H, ]CHCH2O); 4.06
(dd, part of AB system, J¼13.0 and 6.6 Hz,1H, ]CHCH2O); 3.68 (s, 6H,
CO2CH3); 3.45 (m, 2H, CH2CH2O); 3.30 (t, J¼7.6 Hz, 1H, CHCO2CH3);
2.12 (m, 2H, CH2CH2CSi); 1.93 (m, 2H, CH2CSi); 1.9e1.4 (m, 6H,
CH2CH2CH2CH); 0.91 (t, J¼7.6 Hz, 9H, CH2CH3); 0.56 (q, J¼7.6 Hz, 6H,
CH2CH3). 13C NMR (CDCl3,100 MHz)
d 169.6 (CO2CH3); 141.4 (]CSi);
4.5.3. 2-(5-Acetoxy-3-triethylsilanyl-pent-3-enyl)-malonic acid di-
methyl ester (21)
139.3 (]CH); 98.1 (OCHO); 66.1 (]CHCH2O); 62.4 (CH2CH2O); 52.5
(CO2CH3); 51.8 (CHCO2Me); 41.1 (OCHCH2); 30.7 (CH2CH2OCHO);
28.7 (CH2CHCO2Me); 25.6 (CH2CH2CHCO2Me); 19.6 (CH2CH2CHO);
6.6 (SiCH2CH3); 2.9 (SiCH2CH3). IR (ATR), cmꢁ1: 2953; 2923; 1739;
1436; 1228; 1151; 1070; 1003; 733.18: TLC (PE/EA¼7:3): Rf¼0.70.1H
4.5.3.1. Method A. Following general procedure B, from allylic
alcohol 19 (350 mg, 1.06 mmol). The product 21 (395 mg,
1.06 mmol) was quantitatively obtained as a colorless oil.
NMR (CDCl3, 400 MHz)
d
5.83 (t, J¼5.6 Hz, 1H, ]CH); 4.53 (m, 1H,
4.5.3.2. Method B.19 Acetic anhydride (0.45 mL, 4.8 mmol,
1.2 equiv) was added dropwise to a solution of pyranyl protected
compound 17 (1.66 g, 4 mmol) and Cu(OTf)2 (72.3 mg, 0.2 mmol,
5 mol %) in CH2Cl2 (20 mL) and was stirred at rt overnight. The
reaction mixture was diluted with CH2Cl2 and washed with sodium
bicarbonate and brine. The organic layer was dried over anhydrous
sodium sulfate and concentrated on a rotary evaporator. The crude
product was purified over silica gel by flash chromatography to
provide the pure acetate 21 (863 mg, 2.32 mmol, 58%) as a pale
OCHO); 4.30 (d, 1H, J¼11.7 Hz, 1H, part of CH2O); 3.92 (d, J¼11.7 Hz,
1H, part of CH2O); 3.68 (s, 6H, CO2CH3); 3.45 (m, 2H, CH2CH2O); 3.30
(t, J¼7.6 Hz,1H, CHCO2CH3); 2.13 (m, 2H, ]CHCH2CH2); 1.95 (m, 2H,
]CHCH2); 1.9e1.4 (m, 6H, CH2CH2CH2CH); 0.83 (t, J¼7.8 Hz, 9H,
CH2CH3); 0.55 (q, J¼7.8 Hz, 6H, CH2CH3). 13C NMR (CDCl3, 100 MHz)
d
169.8 (CO2CH3); 139.6 (]CSi); 137.1 (]CH); 98.1 (OCHO); 62.4
(CH2CH2O); 61.7 (SiCCH2O); 52.5 (CO2CH3); 51.1 (CHCO2Me); 41.1
(OCHCH2); 30.7 (CH2CH2OCHO); 30.6 (CH2CH2CHCO2Me); 26.8
(CH2CHCO2Me); 19.3 (CH2CH2CHO); 7.5 (SiCH2CH3); 3.3 (SiCH2CH3).
yellow oil. TLC (¼PE/EA): Rf¼0.95. 1H NMR (CDCl3, 400 MHz)
d 5.80
(t, J¼6.1 Hz, 1H, ]CH); 4.63 (d, J¼6.1 Hz, 2H, CH2O); 3.71 (s, 6H,
CO2CH3); 3.33 (t, J¼7.6 Hz, 1H, CH(CO2CH3)2); 2.11 (m, 2H, CH2CSi);
2.03 (s, 3H, COCH3); 1.83 (m, 2H, CH2CH2CSi); 0.91 (t, J¼7.6 Hz, 9H,
CH2CH3); 0.60 (q, J¼7.6 Hz, 6H, CH2CH3). 13C NMR (CDCl3, 100 MHz)
4.5. General procedure D
4.5.1. 2-(5-Hydroxy-pent-3-ynyl)-malonic acid dimethyl ester
(19). To a solution of 16 (1.49 g, 5.0 mmol) in MeOH (10 mL) was
added at rt p-TSA (95 mg, 0.5 mmol, 10 mol %) and the mixture was
d
171.0 (COCH3); 169.6 (CO2CH3); 142.0 (]CH); 136.0 (]CSi); 61.0

9404
J. Agarwal et al. / Tetrahedron 69 (2013) 9398e9405
(CH2O); 52.6 (CO2CH3); 51.6 (CH(CO2CH3)2); 29.0 (CH2CH2CSi); 28.0
24 (84 mg, 0.23 mmol, 45%) was obtained as a colorless oil. TLC (PE/
(CH2CSi); 21.1 (COCH3); 7.4 (CH2CH3); 2.8 (CH2CH3). IR (ATR), cmꢁ1
:
EA¼9:1): Rf¼0.90. 1H NMR (CDCl3, 400 MHz)
5.90 (t, J¼3.6 Hz, 1H,
d
2954; 2875; 1735; 1435; 1225; 1154; 1017; 717.
]CH); 4.99 (sept, J¼6.1 Hz, 2ꢂ 1H, CO2CH(CH3)2); 2.54 (d, J¼3.6 Hz,
2H,¼CHCH2); 2.05 (s, 2ꢂ 2H, ]CSiCH2CH2); 1.19 (2ꢂ d, J¼6.1 Hz,
12H, CO2CH(CH3)2); 0.86 (t, J¼7.6 Hz, 9H, SiCH2CH3); 0.51 (q,
4.5.4. 4-Triethylsilanyl-cyclohex-3-ene-1,1-dicarboxylic
acid
di-
methyl ester (22). To a solution of NaH (80 mg, 2 mmol, 1 equiv, 60%
in mineral oil) in freshly distilled and degassed DMF (0.5 mL), was
added, at 0 ꢀC, a solution of allylic acetate 21 (745 mg, 2 mmol) in
DMF (0.5 mL). The mixture was warmed to rt and stirred 15 min. In
a second flask, Pd(OAc)2 (44.9 mg, 0.2 mmol, 10 mol %) was dis-
solved in DMF (1 mL). Distilled P(Oi-Pr)3 (0.2 mL, 0.8 mmol,
40 mol %) was added dropwise. After the first drop of phosphite, the
mixture become dark but at the end of the addition it took on a pale
yellow color. The catalyst was stirred 5 min and added onto the first
mixture. The mixture was immediately warmed to 90 ꢀC (in a be-
forehand warmed oil bath). The completion of the reaction was
followed by TLC (revealed by KMnO4). After 2 h, the mixture was
filtered over Celite and silica then the DMF was evaporated under
reduced pressure (30 ꢀC under 0.5 mmHg) and the crude product
was purified by flash chromatography to give 22 (413 mg,
1.32 mmol) as a colorless oil. TLC (PE/EA¼9:1): Rf¼0.90. 1H NMR
J¼7.6 Hz, 6H, SiCH2CH3). 13C NMR (CDCl3, 100 MHz)
d 171.4
(CO2CH(CH3)2); 134.8 (]CSi); 133.7 (]CH); 68.6 (CO2CH(CH3)2);
53.0 (C(CO2i-Pr)2); 32.0 (]CHCH2); 27.8 (SiCCH2CH2); 24.7
(SiCCH2); 21.7 (CO2CH(CH3)2); 7.5 (CH2CH3); 2.5 (CH2CH3). IR (neat),
cmꢁ1: 2952; 2875; 1727; 1619; 1466; 1285; 1172; 1145; 715. Anal.
for C20H36O4Si (M¼368.58 g molꢁ1): calcd (%): C¼65.17; H¼9.84.
Found (%): C¼65.21; H¼9.69.
4.5.7. 2-(5-Acetoxy-4-triethylsilanyl-pent-3-enyl)-malonic acid di-
methyl ester (25). This compound was prepared quantitatively
following the general procedure B, from 20 (330 mg, 1 mmol). TLC
(PE/EA¼7:3): Rf¼0.95. 1H NMR (CDCl3, 400 MHz)
5.87 (t, J¼7.1 Hz,
d
1H, ]CH); 4.67 (s, 2H, CH2O); 3.76 (s, 6H, CO2CH3); 3.39 (t, J¼7.6 Hz,
1H, CH(CO2CH3)2); 2.23 (dd, J¼15.3 and 7.1 Hz, 2H, ]CHCH2); 2.06
(s, 3H, COCH3); 2.02 (dd, J¼15.3 and 7.6 Hz, 2H, CH2CH2CH]); 0.93
(t, J¼7.6 Hz, 9H, CH2CH3); 0.62 (q, J¼7.6 Hz, 6H, CH2CH3). 13C NMR
(CDCl3, 400 MHz)
d
5.89 (tt, J¼3.6 and 2.0 Hz, 1H, ]CH); 3.69 (s, 6H,
(CDCl3, 100 MHz) d 170.9 (OCOCH3); 169.7 (CO2CH3); 143.8 (]CH);
CO2CH3); 2.58 (d, J¼3.6 Hz, 2H, ]CHCH2); 2.09 (m, 2H, CH2CH2CSi);
134.4 (]CSi); 62.9 (CH2O); 52.6 (CO2CH3); 51.0 (CH(CO2CH3)2);
28.5 (CH2CH2CH]); 26.7 (CH2CH]); 21.0 (COCH3); 7.3 (CH2CH3);
3.1 (CH2CH3). IR (neat), cmꢁ1: 3459; 2954; 2911; 2875; 1739; 1436;
1231; 1156; 1021; 736. Anal. for C18H32O6Si (M¼372.53 g molꢁ1):
calcd (%): C¼58.03; H¼8.66. Found (%): C¼57.98; H¼8.77.
2.07 (m, 2H, CH2CSi); 0.86 (t, J¼7.6 Hz, 9H, CH2CH3); 0.52 (q,
J¼7.6 Hz, 6H, CH2CH3). 13C NMR (CDCl3, 100 MHz)
d 172.3 (CO2CH3);
135.0 (]CSi); 133.4 (]CH); 53.1 (CCO2CH3); 52.6 (CO2CH3); 32.2
(]CHCH2); 28.1 (]CSiCH2CH2); 24.8 (]CSiCH2); 7.4 (CH2CH3); 2.5
(CH2CH3). IR (neat), cmꢁ1: 2952; 2874; 1736; 1619; 1238; 716. Anal.
for C16H28O4Si (M¼312.48 g molꢁ1): calcd (%): C¼61.50; H¼9.03.
Found (%): C¼61.32; H¼9.11.
4.5.8. 2-(4-Triethylsilanyl-penta-2,4-dienyl)-malonic acid dimethyl
ester (26). The formation of this compound occurs when compound
25 was submitted to the palladium-catalyzed general procedure C.
4.5.5. 2-(5-Acetoxy-3-triethylsilanyl-pent-3-enyl)-malonic acid dii-
sopropyl ester (23). To a solution of 19 (330.5 mg,1 mmol) in i-PrOH
(3 mL), was added distilled Ti(Oi-Pr)4 (0.3 mL, 1 mmol, 1 equiv) and
the mixture was warmed to 80 ꢀC overnight. After completion of
the reaction, Et2O and a saturated aqueous solution of Na2SO4 were
added. Ti salts were filtered and the crude allylic alcohol (351 mg,
0.9 mmol) was obtained as a translucent oil pure enough for direct
conversion into the corresponding acetate. To a solution of allylic
alcohol (187 mg, 0.48 mmol), in dry CH2Cl2 (2.5 mL), distilled Et3N
(0.25 mL, 1.78 mmol, 3.7 equiv) was added and the resulting sus-
pension was allowed to stir at room temperature until dissolution
was completed. Acetic anhydride (70 L, 0.75 mmol, 1.5 equiv) was
added dropwise at 0 ꢀC and the reaction mixture was allowed to
warm to room temperature and stirred overnight. The mixture was
treated with a saturated aqueous solution of NH4Cl. The aqueous
phase was extracted with CH2Cl2. The collected organic layers were
washed with brine, dried over MgSO4, and evaporated in vacuo. The
crude product was purified by flash chromatography to give 23
(199 mg, 0.48 mmol, 96%) as a colorless oil. TLC (PE/EA¼7:3):
TLC (PE/EA¼7:3): Rf¼0.80. 1H NMR (CDCl3, 400 MHz)
d 6.18 (d,
J¼15.2 Hz, 1H, CH]CHCSi); 5.70 (d, J¼3.1 Hz, 1H, SiC]CHtrans); 5.59
(dt, J¼15.2 and 7.1 Hz, 1H, CH]CHC]CH2); 5.29 (d, J¼3.1 Hz, 1H,
SiC]CHcis); 3.69 (s, 6H, CO2CH3); 3.42 (t, J¼7.6 Hz, 1H, CHCO2Me);
2.63 (dd, J¼7.6 and 7.1 Hz, 2H, CH2CHCO2Me); 0.88 (t, J¼7.6 Hz, 9H,
SiCH2CH3); 0.61 (q, J¼7.6 Hz, 6H, SiCH2CH3). 13C NMR (CDCl3,
100 MHz) d 169.3 (CO2CH3); 145.5 (]CSi); 138.4 (CH]CHCSi); 128.8
(SiC]CH2); 125.9 (CH]CHCSi); 52.5 (CO2CH3); 51.9 (CHCO2Me);
32.5 (CH2CHCO2Me); 7.3 (SiCH2CH3); 2.0 (SiCH2CH3). IR (ATR), cmꢁ1
:
2952; 2924; 2874; 1737; 1435; 1228; 1151; 1003; 967.
Acknowledgements
We thank the University P. et M. Curie and the European Com-
mission for funding of this research through a PhD grant to C.C. and
a EMEA Erasmus Mundus Scholarship to J.A. The authors would like
to thank Drs B. Malezieux and L. Dechoux for fruitful discussions.
Supplementary data
Rf¼0.95. 1H NMR (CDCl3, 400 MHz)
d
5.80 (t, J¼6.1 Hz, 1H, ]CH);
5.05 (sept, J¼6.2 Hz, 2ꢂ 1H, CO2CH(CH3)2); 4.67 (d, J¼6.1 Hz, 2H,
CH2O); 3.22 (t, J¼7.6 Hz, 1H, CH(CO2i-Pr)2); 2.13 (m, 2H, CH2CSi);
2.05 (s, 3H, COCH3); 1.82 (m, 2H, CH2CH2CSi); 1.23 (d, J¼6.2 Hz, 2ꢂ
6H, CO2CH(CH3)2); 0.89 (t, J¼7.5 Hz, 9H, CH2CH3); 0.60 (q, J¼7.5 Hz,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.08.080.
References and notes
6H, CH2CH3). 13C NMR (CDCl3, 100 MHz)
d 171.0 (COCH3); 168.9
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