Stereoselective formation of tertiary and quaternary carbon centers via inverse conjugate addition of carbonucleophiles to allenic esters

Article abstract of DOI:10.1016/j.tet.2010.08.002

Stereoselective inverse conjugate addition of carbonucleophiles to allenoates bearing a chiral auxiliary in the ester moiety afforded optically active α,β-unsaturated carboxylic esters bearing a new stereocenter at the δ position. The rationalization of the observed selectivity was supported by semi-empirical molecular orbital calculations.

Full text of DOI:10.1016/j.tet.2010.08.002

Tetrahedron 66 (2010) 7720e7725
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective formation of tertiary and quaternary carbon centers via inverse
conjugate addition of carbonucleophiles to allenic esters
Ana Lúcia Cardoso a, Ana Matos Beja b, Manuela Ramos Silva b, Jesús M. de los Santos c,
,
Francisco Palacios c, Paulo E. Abreu a, Alberto A.C.C. Pais a, Teresa M.V.D. Pinho e Melo a
*
a Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
b Department of Physics, University of Coimbra, 3004-516 Coimbra, Portugal
c Department of Organic Chemistry I, Faculty of Pharmacy, University of the Basque Country, Apartado 450, 01080 Vitoria, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective inverse conjugate addition of carbonucleophiles to allenoates bearing a chiral auxiliary in
Received 23 March 2010
Received in revised form 23 July 2010
Accepted 1 August 2010
Available online 7 August 2010
the ester moiety afforded optically active
the
orbital calculations.
a
,
b
-unsaturated carboxylic esters bearing a new stereocenter at
d
position. The rationalization of the observed selectivity was supported by semi-empirical molecular
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Allenoates
Carbonucleophiles
Chiral a,b-unsaturated carboxylic esters
Chiral carbon centers
Stereoselective inverse conjugate addition
1. Introduction
reported the phosphine-catalyzed CeC bond formation at the g-po-
sition of 2-butynoates with dimethyl malonate.6 Lu et al. demon-
stratedthat methyl2,3-butadienoate undergoes similaradditionwith
dimethyl malonate in the presence of 5 mol % triphenylphosphine
giving adduct (3, EWG¼CO2Me, Nu¼MeO2CCHCO2Me, Scheme 1) in
The development of efficient asymmetric methods for
carbonecarbon bond formation is an important target in modern
organic synthesis. The formation of tertiary stereogenic centers
has been widely studied and several efficient strategies are now
available. In contrast, effective approaches to the production of
quaternary stereocenters, which constitutes a challenging task,
are limited. Furthermore, several biologically active molecules
and natural compounds containing quaternary stereogenic
centers are known.1,2
good yield.7 Asymmetric version of the
g-addition of carbonucleo-
philes to 2,3-butadienoates using chiral phosphines as catalysts for
the construction of tertiary8a and quaternary centers has also been
reported.8b However, as far as we know no examples of
nucleophiles to chiral allenes have been reported.
g-addition of
In recent years, electron-deficient allenes have emerged as at-
tractive electrophiles for various synthetic purposes.3 The addition of
nucleophiles to electron-deficient allenes (1, Scheme 1), occurs at the
Nu
EWG
NuH
PR3 cat.
NuH
EWG
EWG
Nu
•
electrophilic a,b-carbonecarbon double bond to give Michael type
1
γ-adduct
3
β-adduct
2
adducts4 (2, Scheme 1) but reactivity inversion (umpolung) can be
achievedwhencatalyticamountsofphosphinesareadded(3, Scheme
1). In fact, Cristau et al. observed that the presence of phosphines
Scheme 1.
allows the nucleophilic attack at the g-carbon of methyl 2,3-buta-
dienoate (1, EWG¼CO2Me, Scheme 1) leading to
g-adducts (3,
In connection with our interest in the synthesis of allenes and
their use as building blocks in organic synthesis,4a,b,9 we now
describe a methodology to construct tertiary and quaternary
stereocenters via stereoselective inverse conjugate addition of
carbonucleophiles to allenoates bearing a chiral auxiliary in the
ester moiety (Scheme 2).
EWG¼CO2Me, Nu¼OMe, Scheme 1).5 On the other hand, Trost et al.
* Corresponding author. Tel.: þ351 239854475; e-mail address: tmelo@ci.uc.pt
(T.M.V.D. Pinho e Melo).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.002

A.L. Cardoso et al. / Tetrahedron 66 (2010) 7720e7725
7721
R1
R2
Table 2
•
OR
OR
H
Ph3P
R1
*
R3
Inverse conjugate addition of carbonucleophiles to chiral allenoate 11
O
O
R2
H
R3
Ph3P
- Ph3P
R1
R1
R2
R3
R1
R2
R3
R2
R3
Ph3P
*
CO2R
Ph3P
CO2R
Ph3P
CO2R
Entry NuH
(5 equiv)
Conditions
Product Yield %
(cis:trans)
1
2
3
4
5
6
5
PPh3 (5 mol %), 110 ꢀC, 24 h
12
85 (33:67)
89 (33:67)
62 (>98% trans)
No reaction
84 (trans)
5
5
7
7
9
PPh3 (25 mol %),a 110 ꢀC, 24 h 12
or
R =
PPh3 (10 mol %), 50 ꢀC, 24 h
PPh3 (10 mol %), 50 ꢀC, 48 h
PPh3 (10 mol %), 110 ꢀC, 24 h
PPh3 (10 mol %), 110 ꢀC, 24 h
12
13
13
14
SO2Ph
SO2Ph
Scheme 2.
75 (trans)
a
Triphenylphosphine polystyrene-supported.
2. Results and discussion
First, the reactivity of benzyl but-2,3-dienoate (4)10 toward
pronucleophiles namely ethyl 3-oxobutanoate (5), ethyl 2-oxocy-
clohexanecarboxylate (7), and 2-acetylcyclohexanone (9) was
examined (Table 1). It has been previously observed that the
selection of the appropriated temperature, additives, and phos-
phine stoichiometry is important to optimize this CeC bond-
forming reaction.8b Therefore, the inverse conjugate addition of
ethyl 3-oxobutanoate (5) to allene 4 leading to compound 6 bearing
a new tertiary center, was carried out under different reaction
conditions (entries 1e6). The condensation performed at 70 ꢀC for
5 h in the presence of 5 mol % of triphenylphosphine gave the de-
sired product with trans selectivity in 40% yield (entry 1). A better
yield (57%) was obtained carrying out the reaction at 110 ꢀC for 24 h
(entry 2). However, neither the use of additives (NaOAc/AcOH) nor
the increase of phosphine stoichiometry led to improvement. Using
the same reaction conditions compound 8 was prepared with trans
selectivity in 42% yield from allene 4 and 2-oxocyclohexane-
carboxylate 7 (entry 7). The triphenylphosphine (10 mol %) cata-
lyzed addition of 2-acetylcyclohexanone (9) to allene 4 allowed the
isolation of compounds 10-trans in 62% yield (entry 8).
buta-2,3-dienoate (11) with ethyl 3-oxobutanoate (5) carried out at
110 ꢀC for 24 h in the presence of 5 mol % of triphenylphosphine
gave the desired
g-addition product 12 in 85% yield but with
moderate trans selectivity (entry 1). A similar result was obtained
when the reaction was performed in the presence of polystyrene-
supported triphenylphosphine (entry 2). However, the addition
reaction in the presence of 10 mol % of triphenylphosphine carried
out at 50 ꢀC for 24 h gave 12 in 62% yield with high trans selectivity
(entry 3). Using pronucleophile 2-oxocyclohexanecarboxylate 7 no
reaction was observed at 50 ꢀC (entry 4) whereas the inverse con-
jugate addition of allene 11 to ethyl 2-oxocyclohexanecarboxylate
(7) at 110 ꢀC gave compound 13 in 84% yield with trans selectivity
(entry 5). Finally, the reaction of chiral allene 11 with 2-acetylcy-
clohexanone (9) allowed the synthesis of compound 14 in 75% yield
in a selective fashion (entry 6). It should be emphasized that the 1H
NMR spectra of
a,b-unsaturated carbonyl compounds 12e14
showed signals for single diastereoisomers.
The triphenylphosphine catalyzed reaction of (1R)-(ꢁ)-10-phe-
nylsulfonylisobornyl buta-2,3-dienoate 15, enantiomer of allene 11,
with pronucleophiles 5, 7, and 9 was also studied (Table 3). Using
3-oxobutanoate 5 as pronucleophile the desired product 16 was
obtained with higher trans selectivity when the reaction was
Then the behavior of optically active allene 11 was explored
(Table 2). The reaction of (1S)-(þ)-10-phenylsulfonylisobornyl
Table 1
Inverse conjugate addition of carbonucleophiles to benzyl buta-2,3-dienoate (4)
Entry
1
NuH (equiv)
Conditions
Product
Yield %
PPh3 (5 mol %), 70 ꢀC, 5 h
40 trans
2
2
5 (5)
5 (5)
PPh3 (5 mol %), 110 ꢀC, 24 h
PPh3 (5 mol %), NaOAc (0.5 equiv), AcOH (0.5 equiv),
110 ꢀC, 5 h
6
6
57 trans
57 trans
4
5 (5)
PPh3 (5 mol %), NaOAc (0.5 equiv), AcOH (0.5 equiv),
6
44 trans
110 ꢀC, 24 h
5
6
5 (5)
5 (5)
PPh3 (10 mol %), 110 ꢀC, 24 h
PPh3 (30 mol %), 110 ꢀC, 5 h
6
6
47 trans
48 trans
7
)
PPh3 (10 mol %), 110 ꢀC, 24 h
42 trans
62 trans
8 cis
8
PPh3 (10 mol %), 110 ꢀC, 24 h

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A.L. Cardoso et al. / Tetrahedron 66 (2010) 7720e7725
Table 3
Inverse conjugate addition of carbonucleophiles to chiral allenoate 15
O
O
O
O
O
O
NuH
Ph3P
(10 mol%) Nu
Toluene
•
15
Entry
O
O
CO2Et
O
SO2Ph
CO2Et
O
SO2Ph
SO2Ph
D
[α]20
= - 40
D
[α]20
= + 40
O
16
O
12
SO2Ph
SO2Ph
O
O
NuH (5 equiv)
Conditions
Product
Yield % (cis:trans)
EtO2C
CO2Et
O
1
2
3
4
5
6
5
5
5
7
7
9
70 ꢀC, 24 h
110 ꢀC, 24 h
50 ꢀC, 48 h
70 ꢀC, 24 h
110 ꢀC, 24 h
110 ꢀC, 24 h
16
16
16
17
17
18
60 (9:91)
53 (29:71)
87 (>95 trans)
43 (trans)
83 (trans)
74 (trans)
O
O
SO2Ph
D
[α]20
D
[α]20
13
= - 30
17
= + 30
O
MeOC
= - 40
COMe
O
carried out a lower temperature (entries 1e3). Compound 17 was
obtained in 43% yield carrying out the reaction of allene 15 with
pronucleophile 2-oxocyclohexanecarboxylate 7 at 70 ꢀC (entry 4)
whereas at 110 ꢀC compound 17 was isolated in 83% yield with
trans selectivity (entry 5). The addition of 2-acetylcyclohexanone
(9) to chiral allene 15 gave compound 18-trans in 74% yield (entry
O
O
O
SO2Ph
SO2Ph
D
[α]20
D
[α]20
= + 40
14
18
Scheme 3.
6). The 1H NMR spectra of
a,b-unsaturated carbonyl compounds
16e18 showed also signals for single diastereoisomers.
subsequent elimination of the phosphine affording the target
molecule 18. We concentrated on the attack of 20 to intermediate
19 leading to 21, the step where the new chiral center is generated
(Scheme 4).
The structure of (E)-(1R)-(ꢁ)-10-phenylsulfonylisobornyl 4-(2-
acetyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)but-2-enoate (18)
was determined by X-ray crystallography (Fig. 1). This allowed us to
establish the S configuration to the new chiral center. Compound 18
Figure 1. ORTEP diagram of the compound 18 with the ellipsoids drawn at the 20% probability level, for clarity reasons.
showed a positive value for the optical rotation (þ40) and the same
value with opposite sign (ꢁ40) was obtained for compound 14
indicating that these compounds are enantiomers (Scheme 3).
Therefore, we could conclude that (1R)-(ꢁ)-10-phenylsulfonyl-
isobornyl group induces selectivity leading to a new chiral center
with S configuration whereas the enantiomeric chiral auxiliary
affords a chiral center with R configuration. Furthermore, com-
pounds 12e14 and 16e18 show the same physical properties but
values for the optical rotation with opposite sign confirming that
two sets of enantiomeric derivatives were obtained (Scheme 3).
In order to be able to rationalize the stereoselectivity observed
The supermolecular structure formed by these two compounds
correspond to 105 atoms in total, and conformer generation was
deemed a necessity. As such, for each of the reagents Marvin13 was
used as the generation step of the conformers. Each conformer was
then subjected to geometry optimization using the PM614 Hamil-
tonian in MOPAC200915, resorting to the COSMO16 approach to
model the solvent. Scripts created by the authors ranked the
conformers in terms of energy and automatically performed the
calculations for all geometries.
Geometry optimization for the intermediate 19 shows that the
lowest energy conformers are not accessible from one of the sides. In
fact, the substituents of the CeC double bond hinder one of the dia-
stereofaces blocking the approach of the nucleophile (see Fig. 2 for an
example of these conformers). This is consistent with the observed
exclusive formation of (E)-(1R)-(ꢁ)-10-phenylsulfonylisobornyl (4S)-4-
(2-acetyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)but-2-enoate (18).
in the synthesis of optically active a,b-unsaturated carboxylic ester
18 semi-empirical molecular orbital calculations have been carried
out. This process involves the nucleophilic addition of triphenyl-
phosphine to 2,3-allenoate 15 giving intermediate 19, which reacts
with nucleophile 20 to produce 21, followed by proton transfer and

A.L. Cardoso et al. / Tetrahedron 66 (2010) 7720e7725
7723
the solvent is not possible, due to the fact that the Hessian calcu-
lation is not possible using the implicit solvent model and so the
nature of a stationary point cannot be assessed. Nevertheless, the
geometry of the transition state 22 is in agreement with the ste-
reochemistry outcome of the formation of the final product 18 and
corroborates the observed selectivity.
O
O
20
O
Ph3P
3. Conclusion
O
SO2Ph
19
The reaction of prochiral carbon pronucleophiles with alle-
noates bearing a chiral auxiliary in the ester moiety in the presence
of triphenylphosphine is described. Stereoselective inverse conju-
O
COMe
PPh3 O
21
gate addition was observed leading to optically active
saturated carboxylic esters compounds bearing a new stereocenter
at the position. The use of enantiomeric chiral auxiliaries led to
a,b-un-
O
Ph3P
18
d
SO2Ph
the synthesis of two sets of enantiomeric derivatives.
The structure of (E)-(1R)-(ꢁ)-10-phenylsulfonylisobornyl 4-(2-
acetyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)but-2-enoate (18)
was determined by X-ray crystallography allowing to establish the S
configuration to the new chiral center whereas the enantiomeric
chiral auxiliary, (1S)-(þ)-10-phenylsulfonylisobornyl group, affor-
ded a chiral center with R configuration. Computational studies
corroborated the rationalization of the observed selectivity.
Scheme 4.
4. Experimental section
4.1. General
1H NMR spectra were recorded on a Bruker Avance III in-
strument operating at 400 MHz. 13C NMR spectra were recorded on
a Bruker Avance III instrument operating at 100 MHz. The solvent is
deuterochloroform except where indicated otherwise. IR spectra
were recorded on a PerkineElmer 1720X FTIR spectrometer. Mass
spectra were recorded under chemical ionization (CI) or electro-
spray ionization (ESI). HRMS spectra were recorded on a Finnigan
MAT95 S instrument. Optical rotations were measured on an
Optical Activity AA-5 electrical polarimeter. Melting points were
recorded on a Reichert hot stage and are uncorrected. Flash column
chromatography was performed with Merck 9385 silica as the
stationary phase.
Figure 2. Example of a low energy conformer of 19.
The minimum energy conformers were subsequently used to
build tentative transition states, pertaining to the alternative
approximation route. The search for this transition state was
extensive, and most of the tryout geometries unsuccessful. The
putative transition state is characterized by an imaginary frequency
of 237 cmꢁ1, and this mode corresponds to the motion of the ter-
minal carbon of the double bond (Fig. 3). It is located 21 kcal/mol
above the optimized reactants in the gas phase. The calculation in
4.2. General procedure
The appropriated allene (0.5 mmol) and PPh3 (0.10 mmol %)
were dissolved in dry toluene (10 mL) followed by the dropwise
addition of the nucleophile (2.5 mmol). The reaction mixture was
stirred overnight at the designed temperature. The solvent was
evaporated off and the product purified by flash chromatography
[ethyl acetate/hexane].
4.2.1. (E)-1-Benzyl 6-ethyl 5-acetylhex-2-enedioate (6). Obtained as
an oil. IR (film) 1586, 1656, 1713 cmꢁ1 1H NMR 1.27 (CH3, t,
;
J¼7.2 Hz), 2.26 (CH3, s), 2.71e2.75 (CH2, m), 3.58 (CH, t, J¼7.3 Hz),
4.20 (CH2, q, J¼7.2 Hz), 5.16 (CH2, s), 5.92 (CH], d, J¼15.6 Hz),
6.87e6.91 (CH], m), 7.34e7.38 (5H, m, AreH); 13C NMR 14.0, 29.2,
30.2, 58.0, 61.8, 66.2, 123.4, 128.2, 128.5, 135.9, 144.8, 165.8, 168.5,
201.2. MS (ESI) m/z 304 (MHþ, 1), 213 (15), 91 (100), 68 (34); HRMS
(ESI) m/z 305.1383 (C17H21O5 [MHþ], 305.1382).
4.2.2. (E)-Benzyl 4-(1-ethoxycarbonyl-2-oxocyclohexyl)but-2-enoate
(8). Obtained as an oil. IR (film) 1497, 1654, 1714 cmꢁ1 1H NMR
;
1.21 (CH3, t, J¼7.2 Hz), 1.42e1.52 (1H, m), 1.60e1.80 (3H, m),
1.94e2.09 (2H, m), 2.45e2.51 (3H, m), 2.69e2.75 (1H, m), 4.18 (CH2,
q, J¼7.3 Hz), 5.16 (CH2, s), 5.87 (CH], d, J¼15.6 Hz), 6.92 (CH], dt,
J¼7.6, 15.6 Hz), 7.32e7.36 (5H, m, AreH); 13C NMR 14.1, 22.4, 27.4,
36.1, 37.6, 41.0, 60.6, 61.6, 66.1,124.2,128.2,128.5,136.0,144.3,165.7,
Figure 3. Geometry of the transition state 22 resulting from the attack of nucleophile
20 to intermediate 19 leading to 21. Color code: gray is carbon, red is oxygen, white is
hydrogen, yellow is sulfur and dark yellow is phosphorus.

7724
A.L. Cardoso et al. / Tetrahedron 66 (2010) 7720e7725
171.0, 206.8. MS (ESI) m/z 345 (MHþ, 100), 237 (66), 209 (27); HRMS
(ESI) m/z 345.1697 (C20H25O5 [MHþ], 345.1697).
m), 2.56e2.71 (2H, m), 2.99 (1H, d, J¼14.4 Hz), 3.56 (1H, d,
J¼14.4 Hz), 4.74e4.78 (1H, m), 5.76 (CH], d, J¼15.6 Hz), 6.61e6.69
(CH], m), 7.52e7.62 (3H, m, AreH), 7.87e7.88 (2H, m, AreH); 13
C
4.2.3. Benzyl 4-(1-acetyl-2-oxocyclohexyl)but-2-enoate (10).
NMR 19.9, 20.3, 21.5, 22.1, 26.3, 27.1, 29.7, 34.2, 36.8, 39.6, 41.6, 44.1,
49.4, 50.0, 55.2, 67.3, 77.6, 125.3, 127.8, 129.3, 133.5, 141.2, 142.7,
164.0, 205.3, 208.8.
4.2.3.1. (E)-Benzyl 4-(1-acetyl-2-oxocyclohexyl)but-2-enoate (10-
trans). Obtained as an oil. IR (film) 1653, 1700, 1718 cmꢁ1; 1H NMR
1.46e1.51 (1H, m), 1.59e1.77 (3H, m), 1.98e2.05 (1H, m), 2.10 (CH3,
s), 2.25e2.33 (1H, m), 2.46e2.51 (2H, m), 2.57e2.70 (2H, m), 5.15
(CH2, s), 5.88 (CH], d, J¼15.6 Hz), 6.78 (CH], dt, J¼7.6, 15.6 Hz),
7.35e7.36 (5H, m, AreH); 13C NMR 22.1, 26.2, 27.0, 34.1, 36.9, 41.6,
66.2, 67.3, 124.6, 127.0, 128.3, 128.6, 135.9, 143.5, 165.5, 205.1, 208.8.
4.2.6.1. (E)-(1S)-(þ)-10-Phenylsulfonylisobornyl 4-(2-acetyl-1-oxo-
1,2,3,4-tetrahydronaphthalen-2-yl)but-2-enoate (14). Obtained as
a white solid. Mp 169.4e171.0 ꢀC (from ethyl acetate/hexane). MS
(ESI) m/z 501 (MHþ, 58), 328 (4), 277 (53); HRMS (ESI) m/z 501.2306
(C28H37O6S [MHþ], 501.2310). [
a]
D
20 ꢁ40 (c 1, CH2Cl2).
4.2.3.2. (Z)-Benzyl 4-(1-acetyl-2-oxocyclohexyl)but-2-enoate (10-
cis). Obtained as an oil. IR (film) 1653, 1700, 1718 cmꢁ1
;
1H NMR
4.2.6.2. (E)-(1R)-(ꢁ)-10-Phenylsulfonylisobornyl 4-(2-acetyl-1-
oxo-1,2,3,4-tetrahydronaphthalen-2-yl)but-2-enoate (18). Obtained
as a white solid. Mp 168.7e170.1 ꢀC (from ethyl acetate/hexane).
MS (ESI) m/z 501 (MHþ, 64), 277 (100), 233 (4); HRMS (ESI) m/z
1.26e1.37 (1H, m),1.45e1.78 (3H, m),1.94e2.03 (1H, m), 2.11 (CH3, s),
2.31e2.51 (3H, m), 3.12 (1H, dd, J¼7.6, 15.6 Hz), 3.25 (1H, dd, J¼7.6,
15.6 Hz), 5.15 (CH2, s), 5.89 (CH], d, J¼11.6 Hz), 6.13 (CH], dt, J¼7.6,
11.6 Hz), 7.26e7.36 (5H, m, AreH); 13C NMR 22.1, 26.1, 27.0, 32.6, 36.9,
41.3, 65.9, 67.3, 121.7, 128.3, 128.6, 135.9, 145.0, 165.9, 207.2, 209.5.
501.2305 (C28H37O6S [MHþ], 501.2310). [
a
]
20 þ40 (c 1, CH2Cl2).
D
4.3. Crystal data for (E)-(1R)-(L)-10-phenylsulfonylisobornyl
4-(2-acetyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)but-2-
enoate (18)
4.2.4. 1-[10-Phenylsulfonylisobornyl] 6-ethyl 5-acetylhex-2-enedioate
12 and 16. IR (film) 1586, 1656, 1713 cmꢁ1 1H NMR 0.87 (CH3, s),
;
0.96 (CH3, s), 1.19e1.23 (1H, m), 1.28 (CH3, t, J¼7.1 Hz),1.73e2.05 (6H,
m), 2.29 (CH3, s), 2.75 (2H, approx. t, J¼7.1 Hz), 3.00 (1H, d,
J¼14.0 Hz), 3.56 (1H, d, J¼14.0 Hz), 3.63 (CH, t, J¼7.3 Hz), 4.22 (CH2,
q, J¼7.1 Hz), 4.80e4.83 (1H, m), 5.82 (CH], d, J¼15.5 Hz), 6.77 (CH],
dt, J¼7.1, 15.5 Hz), 7.53e7.63 (3H, m, AreH), 7.85e7.88 (2H, m,
AreH); 13C NMR 14.1, 19.9, 20.3, 21.1, 29.3, 29.4, 29.7, 30.2, 39.5, 44.1,
49.4, 49.9, 55.2, 58.1, 61.8, 77.6, 123.9, 127.7, 129.3, 133.6, 141.3, 144.0,
164.3, 168.6, 201.3.
C28H36O6S, M¼500.63, crystal dimensions 0.36ꢃ0.21ꢃ0.19 mm3,
orthorhombic, P212121, a¼8.1873(2) Å, b¼17.3020(5) Å, c¼18.8325
(5) Å, V¼2667.75(12) Å3, Z¼4, rcalcd¼1.246 g cmꢁ3
,
m
¼0.161 mmꢁ1
.
The X-ray data were collected on an Bruker APEX2 single crystal
diffractometer, at 293(3) K, using graphite-monochromated Mo K
a
radiation (l¼0.71073 Å). The structures were solved by direct
methods as implemented in SHELXS9711 and refined by full-matrix
least-squares using SHELXL97.11 54,252 reflections measured, 6419
4.2.4.1. (E)-1-[(1S)-(þ)-10-Phenylsulfonylisobornyl] 6-ethyl 5-ace-
tylhex-2-enedioate (12). Obtained as an oil. MS (ESI) m/z 491 (MHþ,
10), 277 (100),135 (55); HRMS (ESI) m/z 491.2098 (C26H35O7S [MHþ],
independent, R¼0.0399 (4486 reflections with I>2 (I)), Rw¼0.1104
s
for all reflections, GOF¼1.036, 319 parameters, non-H atoms refined
anisotropically The Flack parameter12 refined to 0.02(7).
491.2103). [
a
]
20 ꢁ40 (c 1, CH2Cl2).
D
Acknowledgements
4.2.4.2. (E)-1-[(1R)-(ꢁ)-10-Phenylsulfonylisobornyl] 6-ethyl 5-
acetylhex-2-enedioate (16). Obtained as an oil. MS (ESI) m/z 491
(MHþ, 63), 277 (22); HRMS (ESI) m/z 491.2098 (C26H35O7S [MHþ],
Thanks are due to FCT (Project: PTDC/QUI/64470/2006; Grant:
SFRH/BPD/34569/2007), COMPETE, QREN and FEDER for financial
support. We acknowledge the Nuclear Magnetic Resonance Labo-
ratory of the Coimbra Chemical Centre (www.nmrccc.uc.pt), Uni-
versity of Coimbra for obtaining the NMR data.
491.2104). [
a
]
20 þ40 (c 1, CH2Cl2).
D
4.2.5. 10-Phenylsulfonylisobornyl 4-(1-ethoxycarbonyl-2-oxocyclo-
hexyl)but-2-enoate 13 and 17. IR (film) 1447, 1653, 1711 cmꢁ1 1H
;
NMR 0.87 (CH3, s), 0.96 (CH3, s), 1.17e1.27 (3þ1H, m), 1.48e2.20
(12H, m), 2.45e2.55 (3H, m), 2.70e2.76 (1H, m), 2.99 (1H, d,
J¼14.0 Hz), 3.57 (1H, d, J¼14.0 Hz), 4.21 (CH2, q, J¼7.2 Hz),
4.75e4.78 (1H, m), 5.75 (CH], d, J¼16.0 Hz), 6.75e6.83 (CH], m),
7.49e7.64 (3H, m, AreH), 7.86e7.90 (2H, m, AreH); 13C NMR 14.2,
19.9, 20.3, 22.5, 27.1, 27.4, 29.6, 30.9, 36.2, 37.6, 39.6, 41.0, 44.0, 49.3,
49.9, 55.1, 61.6, 77.4, 124.6, 127.7, 129.3, 133.5, 141.1, 143.5, 164.2,
171.1, 206.8.
References and notes
1. (a) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003e3025; (b) Bella, M.;
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mol. Chem. 2007, 5, 873e888; (d) Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur. J.
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2. Recent selected examples on the generation of quaternary centers: (a) Du-
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4.2.5.1. (E)-(1S)-(þ)-10-Phenylsulfonylisobornyl 4-(1-ethoxycar-
bonyl-2-oxocyclohexyl)but-2-enoate (13). Obtained as an oil. MS
(ESI) m/z 531 (MHþ, 34), 277 (20), 254 (4); HRMS (ESI) m/z 531.2411
(C29H35O7S [MHþ], 531.2414). [
a
]
20 ꢁ30 (c 1, CH2Cl2).
D
4.2.5.2. (E)-(1R)-(ꢁ)-10-Phenylsulfonylisobornyl 4-(1-ethoxycar-
bonyl-2-oxocyclohexyl)but-2-enoate (17). Obtained as an oil. MS
(ESI) m/z 531 (MHþ, 100), 277 (63), 254 (12); HRMS (ESI) m/z
531.2411 (C29H35O7S [MHþ], 531.2409). [
a
]
20 ꢂ30 (c 1, CH2Cl2).
D
4.2.6. 10-Phenylsulfonylisobornyl 4-(2-acetyl-1-oxo-1,2,3,4-tetrahy-
4. For some examples see: (a) Lopes, S. M. M.; Matos Beja, A.; Ramos Silva, M.;
de los Santos, J. M.; Pinho e Melo, T. M. V. D.; Palacios, F. Tetrahedron 2009, 65,
9116e9124; (b) Pinho
dronaphthalen-2-yl)but-2-enoate 14 and 18. IR (film) 1559, 1653,
1700, 1717 cmꢁ1 1H NMR (DMSO-d6) 0.87 (CH3, s), 0.96 (CH3, s),
;
e Melo, T. M. V. D.; Cardoso, A. L.; Palacios, F.;
1.17e1.26 (1H, m), 1.48e2.04 (12H, m), 2.11 (CH3, s), 2.47e2.52 (2H,
de los Santos, J. M.; Pais, A. A. C. C.; Abreu, P. E.; Paixão, J. A.; Matos Beja, A.;

A.L. Cardoso et al. / Tetrahedron 66 (2010) 7720e7725
7725
Ramos Silva, M. Tetrahedron 2008, 64, 8141e8148; (c) de los Santos, J. M.; López,
Y.; Aparicio, D.; Palacios, F. J. Org. Chem. 2008, 73, 550e557; (d) Palacios, F.;
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hedron 2010, 66, 6078e6084.
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phosphoranylideneacetate with ketene following the general procedure
described in Ref. 9a.
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€
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