2-Alkylidenesulfol-3-enes by (regio- and) stereoselective cheletropic addition of SO2 to (di)vinylallenes

Article abstract of DOI:10.1021/ol050240p

(Chemical Equation Presented) The cheletropic addition of SO₂ to divinylallenes is regioselective, taking place at the most substituted vinylallene and at the E unit if vinyl groups of opposite geometry are competing. Diastereofacial differenti

Full text of DOI:10.1021/ol050240p

ORGANIC
LETTERS
2005
Vol. 7, No. 8
1565-1568
2-Alkylidenesulfol-3-enes by (Regio-
and) Stereoselective Cheletropic
Addition of SO2 to (Di)vinylallenes
Jose´ A. Souto, Carlos Silva Lo´pez, Olalla Nieto Faza, Rosana Alvarez, and
Angel R. de Lera*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidade de Vigo,
36310 Vigo, Spain
qolera@uVigo.es
Received February 4, 2005
ABSTRACT
The cheletropic addition of SO2 to divinylallenes is regioselective, taking place at the most substituted vinylallene and at the E unit if vinyl
groups of opposite geometry are competing. Diastereofacial differentiation results from the approach of the reagent from the less-substituted
direction of the allene and from the concomitant disrotatory movement of the termini of the vinylallene to afford the sterically more congested
2-alkylidenesulfol-3-ene isomer. DFT computations confirm the regio- and the stereoselectivity of these cheletropic additions.
Thermal additions of SO2 to conjugated dienes and the
extrusions from sulfol-3-enes1 are concerted cheletropic
reactions. Woodward and Hoffmann established the preferred
approach of SO2 along a linear trajectory in a suprafacial
manner with respect to the diene part2 and the disrotatory
nature of the movement of the diene termini to afford the
cyclic sulfones3 (sulfol-3-enes). These species are useful in
organic synthesis as masked dienes,4,5 and tactics of thermal
extrusion of SO2 from a sulfol-3-ene and subsequent in-
tramolecular Diels-Alder reactions as pericyclic cascade
processes have been used in complex natural product
synthesis.6
(E,E)-hexa-2,4-diene by out,out disrotation, a rotational
selectivity likely due to steric reasons7 (Scheme 1).
As a continuation of our studies on the regio- and
torquoselective thermal electrocyclic reactions of (di)vinyl-
allenes,8 we recently focused on the cheletropic addition of
SO2 to these compounds. Although the addition of SO2 to
(4) (a) Dendralenes have been obtained by thermal extrusion of SO2 (450
°C) starting from 2-vinylsulfolenes: Fielder, S.; Rowman, D. D.; Sherburn,
M. S. Angew. Chem., Int. Ed. 2000, 39, 4331. (b) The methodology has
been adapted to solid phase: Cheng, W.; Olmstead, M. M.; Kurth, M. J.
Org. Chem. 2001, 66, 5528.
(5) Aromatic derivatives, in turn, are considered precursors of highly
reactive o-quinodimethane systems, but the temperatures required to generate
the o-xylylene are usually much higher (240 °C or greater). (a) Cava, M.
P.; Deana, A. A. J. Am. Chem. Soc. 1959, 81, 4266. (b) Cava, M. P.;
McGrady, J. J. Org. Chem. 1975, 40, 72. (c) Nicolaou, K. C.; Barnette, W.
E.; Ma, P. J. Org. Chem. 1980, 45, 1463. (d) Oppolzer, W.; Roberts, D. A.
HelV. Chim. Acta 1980, 63, 1703. (e) Durst, T.; Lancaster, M.; Smith, D.
J. H. J. Chem. Soc., Perkin Trans. 1 1981, 1846. (f) Levy, L. A.; Sashikumar,
V. P. J. Org. Chem. 1985, 50, 1760.
(6) Leonard, J.; Hague, A. B.; Knight, J. A. In Organosulfur Chemistry;
Page, P., Ed.; Academic Press: San Diego, 1998; Vol. 2, Chapter 6. For
recent examples, see: (a) Nicolaou, K. C.; Vassilikogiannakis, G.; Ma¨g-
erlein, W.; Kranich, R. Angew. Chem., Int. Ed. 2001, 40, 2482. (b) Nicolaou,
K. C.; Vassilikogiannakis, G.; Ma¨gerlein, W.; Kranich, R. Chem.sEur. J.
2001, 7, 5359.
cis-2,5-Dimethylsulfol-3-ene 1 undergoes thermal de-
sulfonylation more readily than the trans isomer 3 and yields
(1) (a) Mock, W. L. J. Am. Chem. Soc. 1966, 88, 2857. (b) McGregor,
S. D.; Lemal, D. M. J. Am. Chem. Soc. 1966, 88, 2858.
(2) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969,
8, 781.
(3) (a) Schank, K. In The Chemistry of Sulphones and Sulfoxides; Patai,
S., Rappoport, Z., Stirling, C., Eds.; John Wiley & Sons: New York, 1988.
(b) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon: Oxford,
1993.
10.1021/ol050240p CCC: $30.25
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Published on Web 03/19/2005

Simply bubbling SO2 into a solution of the (di)vinylallenes
in hexane at ambient temperature effected the consumption
of starting materials in short reaction times (less than 15 min).
(Di)vinylallenes 7-9 provided a single cheletropic SO2
adduct (Scheme 2). Signals for the diastereotopic (protected)
hydroxyalkyl methylene protons (δ 4.2-4.1 ppm for 12; δ
4.1-4.0 ppm for 13a; δ 4.0-3.9 ppm for 13b) and sulfolene
H5 atom (δ 3.80 ppm for 12; δ 3.57 ppm for 13a; δ 3.45
ppm for 13b) in the 1H NMR spectra of 12 and 13a,b were
considered diagnostic of the incorporation of SO2 at the
terminal polar diene unit.10 Compound 9, in contrast,
provided an adduct that exhibited a singlet resonating at δ
4.72 ppm, tentatively assigned to sulfolene H5, which
suggested that isomer 14 had formed instead. The alkylidene
geometry (E for 12 and 13; Z for 14, as result of the CIP
rules) was inferred from the observation of cross-correlation
signals in the NOE spectra between the C3-alkyl substituent
of the sulfolene ring and the exocyclic methyl (phenyl) group
at C2′ of 13a,b (C1′ of 12) and the corresponding cross-
correlation signals between the C1′-tBu group and H3 of 14.
In addition, the structure of the latter was secured by X-ray
analysis (Figure 1).
Scheme 1. Model Cheletropic Reactions of SO2 and Dienes
bis-allenes was reported by Skattebøl in 1973 (Scheme 1),9
the corresponding reaction with vinylallenes is unprecedented
to the best of our knowledge.
A series of (di)vinylallenes was designed (Scheme 2) to
Scheme 2. Cheletropic SO2 Addition to (Di)vinylallenes
Figure 1. X-ray structure of compound 14.
Although limited in number, the results illustrated in
Scheme 2 reveal some interesting trends:
(a) SO2 adds regioselectively to the more substituted diene
unit of divinylallenes 8a,b to afford 13a,b. Although
electronically richer due to the greater number of alkyl
substituents, other structural factors such as dominant s-cis
conformations and shorter distances between the diene
termini due to the presence of bulky groups located at the
analyze the regio- and stereoselectivity of the cheletropic
addition in order to gauge both steric and electronic effects
on reactivity. Their preparation followed the general proce-
dure previously reported,8 in which the allene is generated
by the SN2′ anti displacement of propargylic benzoates with
cuprates (see Supporting Information for details).
(10) Addition of SO2 to dienes has been shown to result in a complex
competition between a hetero Diels-Alder reaction to provide sultines
(kinetic control, occurring at -75 °C) and a cheletropic addition to afford
sulfolenes (thermodynamic control), and the competing pathways are further
tuned by the nature of the substituents on the diene. For the case at hand,
the alternative alkylidenesultines, corresponding to a formal hetero Diels-
Alder addition of SO2 to vinylallenes, were discarded on the basis of these
kinetic precedents and the X-ray structure of 14. (a) Roversi, E.; Monnat,
F.; Schenk, K.; Vogel, P.; Bran˜a, P.; Sordo, J. A. Chem.sEur. J. 2000, 6,
1858. (b) Deguin, B.; Vogel, P. J. Am. Chem. Soc. 1992, 114, 9210. (c)
Ferna´ndez, T.; Sua´rez, D.; Sordo, J. A.; Monnat, F.; Roversi, E.; Estrella,
A.; Schenk. K.; Vogel, P. J. Org. Chem. 1998, 63, 9490.
(7) (a) Mock, W. L. J. Am. Chem. Soc. 1966, 88, 2857. (b) McGregor,
S. D.; Lemal, D. M. J. Am. Chem. Soc. 1966, 88, 2858. (c) Mock, W. L.
J. Am. Chem. Soc. 1975, 97, 3666.
(8) (a) Lo´pez, S.; Rodr´ıguez, J.; Garc´ıa, J.; de Lera, A. R. J. Am. Chem.
Soc. 1996, 118, 1881. (b) de Lera, A. R.; Iglesias, B.; Lo´pez, S.; Rodr´ıguez,
J. Chem.sEur. J. 2000, 6, 4021. (c) de Lera, A. R.; Alvarez, R.; Lecea, B.;
Torrado, A.; Coss´ıo, F. P. Angew. Chem., Int. Ed. 2001, 40, 557.
(9) Skattebøl, L. J. Chem. Soc., Chem. Commun. 1973, 432.
1566
Org. Lett., Vol. 7, No. 8, 2005

internal position of the vinylallenes may play a role in the
regioselectivity.8
accurate energies. The nature of all the stationary points was
resolved through harmonic analysis. Solvent effects were
taken into account with sequential single-point calculations
at the gas-phase optimized geometries. A variation of the
conductor-like screening model (COSMO)14 method was
chosen (heptane) using the parameters proposed by Klamt.15
All the calculations were performed with the Gaussian 0316
suite of programs.
(b) Electron-withdrawing groups at the vinylallene termini
(CHO), on the other hand, inhibited the addition of SO2, and
vinylallenal 10 was recovered unchanged after 1 h at 25 °C
(at 80 °C, decomposition was observed). Electron-rich
divinylallene 11 suffered extensive decomposition under the
reaction conditions.
(c) (Z)-Vinylallenes are less reactive than the correspond-
ing E isomers. The structure of 14 confirms that the
cheletropic reaction occurred at the diene subunit of E
geometry despite being less substituted.
(d) Diastereoselectivity (or rotational selectivity on the
vinylallene) appears to be governed by steric factors. The
approach of the reagent from the less-hindered side of the
vinylallene dictates the disrotatory movement of the termini
(out,out in the enantiomers shown in Scheme 2), due to the
requirement of orbital overlap between the two reactants.
The allene axis configuration is thus transferred to the
exocyclic double-bond geometry (Scheme 3), and therefore
Transition structure geometries are highly asymmetric,
with sulfur-cumulene carbon bond lengths shorter (2.10-
2.27 Å) than the sulfur-olefin carbon counterparts (2.55-
2.69 Å). Small variations of these bond distances are
observed upon changes in the olefin geometry and the face
approach (syn/anti, see Scheme 3). Interestingly, the greatest
difference in forming bond lengths is observed with C3-
methyl-substituted vinylallenes. This effect, likely due to
back-strain, has also direct energetical implications, since
these substrates proceed through transition states that are
from 1 to 5 kcal/mol lower in energy than their unsubstituted
counterparts (see Table 1).
Scheme 3. Models of Computed Cheletropic Additions of SO2
Table 1. Gas Phase and Solution (COSMO, Heptane) Relative
Free Energies of Activation (kcal/mol, 298 K) of Models 1-4
to Vinylallenesa
gas phase
COSMO
syn
anti
syn
anti
(E)-r-1
(Z)-r-1
(E)-r-2
(Z)-r-2
(E)-r-3
(Z)-r-3
(E)-r-4
(Z)-r-4
27.37
34.15
26.33
29.06
27.54
30.37
31.03
33.97
26.63
33.59
25.10
28.40
25.47
28.78
26.55
30.61
26.38
33.04
24.42
27.28
25.63
28.33
29.25
32.82
24.99
31.99
22.79
26.05
23.63
26.89
24.18
28.88
a Note that the Z/E geometry of the olefin remains undefined in
the proposed nomenclature and will be specified along the discus-
sion.
Further inspection of Table 1 reveals the sources of
selectivity in the cheletropic additions. First, the Z geometry
of the vinyl moiety is a major contributor to the reaction
energetics. Transition structures of these isomers present even
more destabilization (2.83-6.96 kcal/mol) than that due to
allene substitution (1.45-4.91 kcal/mol). The trend of greater
if enantiopure reactants were used, the absolute configuration
of the sulfolene stereocenter would also be under the control
of the allene axial chirality.
To theoretically support the above findings and to get
further insight into the factors responsible for the regio- and
(14) Klamt, A.; Schu¨u¨rmann, G. J. Chem. Soc., Perkin Trans. 2 1993,
2, 799.
(15) Klamt, A.; Jonas, V.; Bu¨rger, T.; Lohrenz, J. C. W. J. Phys. Chem.
A 1998, 102, 5074.
the stereoselectivity, computations were carried out on
11,12
reactions of SO2
with model (E)- and (Z)-vinylallenes
(16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
revision B.02; Gaussian, Inc.: Pittsburgh, PA, 2003.
substituted at C1 and C5 (and C3). DFT was chosen due to
the satisfactory results reported in precedent studies with
dienes.13 The multilevel B3LYP/6-311++(3df,2p)//B3LYP/
6-31+(d,p) methodology was selected in order to obtain
(11) Kinetic studies revealed that the reaction of dienes is second order
in SO2, and in fact theoretical computations suggested a role for SO2 as a
Lewis acid.12 However regio- and diastereoselectivity are considered not
to be affected by the SO2 molecularity since the second SO2 molecule does
not modify the disrotatory nature of the reaction and merely acts as an
activating species for the reacting SO2 molecule.
(12) Ferna´ndez, T.; Sordo, J. A.; Monnat, F.; Deguin, B.; Vogel, P. J.
Am. Chem. Soc. 1998, 120, 13276.
(13) Monnat, F.; Vogel, P.; Rayo´n, V. M.; Sordo, J. A. J. Org. Chem.
2002, 67, 1882.
Org. Lett., Vol. 7, No. 8, 2005
1567

due to the sulfur dioxide addition proceeding with disrotation
of the diene termini in the direction that maximizes the orbital
overlap with the sulfur center. As a consequence, the E
substituent of the alkene rotates toward the approaching SO2
(see Scheme 4).
Scheme 4. Activation Barriers (kcal/mol) of the Two Alternate
Approaches in the Cheletropic Addition of SO2 to Model
Divinylallene (E)-r-3 and Their Corresponding Products (Gas
Phase, COSMO Values in Italics)
In summary, adducts of SO2 and vinylallenes have been
isolated and characterized. Structural studies and computa-
tional analysis confirm that the cheletropic reactions are
stereoselective and favor the approach that avoids steric
interactions with the substituents on the allene acccompanied
by the out,out disrotation of the termini carbons. Moreover,
cheletropic additions of SO2 to (E,E)-divinylallenes select
the more substituted diene unit, whereas with (Z,E)-divinyl-
allenes, the addition proceeds on the E terminus, a regio-
selectivity trend that is confirmed by DFT computations on
model systems.
Acknowledgment. We are grateful to the European
Commission (“Anticancer Retinoids”, QLK3-2002-02029),
the Spanish Ministerio de Ciencia y Tecnolog´ıa (Grant
SAF2004-07131, Ramo´n y Cajal Research Contract to R.A.
and FPU fellowship to C.S. and O.N.), FEDER and the Xunta
de Galicia (Grant PGIDIT02PXIC30108PN) for financial
support. We also thank Dr. Jose´ Garc´ıa Rey for the synthesis
of 11.
destabilization of the Z-anti relative to the E-syn approach
along the R2 series (Me, C(Me)CH2, tBu) shows reversal only
t
for the bulkier Bu substituent. Thus, in divinylallenes with
E and Z vinyl geometries, the addition of sulfur dioxide will
occur preferentially at the E unit, in keeping with the
experimental findings (see Scheme 2). Moreover, the dif-
ference in activation barriers between the anti and syn
approaches is enhanced by solvation (modeled through a
dielectric continuum). The differences computed with the
COSMO method confirm that facial selectivity in vinyl-
allenes can be achieved with substituents of moderate size
(1.63 kcal/mol with methyl in (E)-r-2 already accounts for
94:6 facial selectivity at 25 °C, whereas more than 5 kcal/
mol ensures a 99.9:0.01 ratio even at 250 °C in (E)-r-4).
Once the facial selectivity is attained, the Woodward-
Hoffmann rules ensure the stereoselectivity of the reaction,
Supporting Information Available: Typical experimen-
tal procedures for the synthesis of all compounds and their
physical and spectroscopic data; X-ray structural data of
compound 14 (CIF); and final SCF energies, geometries, and
number of imaginary frequencies. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL050240P
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Org. Lett., Vol. 7, No. 8, 2005