β sulfinyl α,β-unsaturated carbonyl compounds from enantiomerically pure sulfenic acids

Article abstract of DOI:10.1021/jo015595a

The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology for the synthesis of β-sulfinyl αβ-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording (R_s,E)- and (S_s,E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure form after simple column chromathography. (R_s,E)-3- [(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen1-one (6_Ra) was involved as a heterodiene in inverse-electron-demanding Diels-Alder reactions with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore, the addition of methylmagnesium iodide to the carbonyl moiety of 6_Ra demonstrated that the chiral sulfur atom exerts a remote stereocontrol in this reaction if assisted by the hydroxy group being part of the isoborneol substituent.

Full text of DOI:10.1021/jo015595a

J . Org. Chem. 2001, 66, 4845-4851
4845
â-Su lfin yl r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s fr om
En a n tiom er ica lly P u r e Su lfen ic Acid s
Maria C. Aversa,* Anna Barattucci, Paola Bonaccorsi,* Placido Giannetto, and
Manuela Policicchio
Dipartimento di Chimica organica e biologica, Universita` degli Studi di Messina,
Salita Sperone 31 (vill. S. Agata), 98166 Messina, Italy
aversa@imeuniv.unime.it
Received February 27, 2001
The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology
for the synthesis of â-sulfinyl R,â-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were
generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording
(RS,E)- and (SS,E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and
3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure
form after simple column chromathography. (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-
1-one (6Ra ) was involved as a heterodiene in inverse-electron-demanding Diels-Alder reactions
with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl
auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore,
the addition of methylmagnesium iodide to the carbonyl moiety of 6Ra demonstrated that the chiral
sulfur atom exerts a remote stereocontrol in this reaction if assisted by the hydroxy group being
part of the isoborneol substituent.
Sch em e 1
In tr od u ction
Although the addition of sulfenic acids to unsaturated
bonds has been chiefly used for demonstrating the
existence of such unstable species as intermediates in
organic and biological processes,1,2 some intrinsic syn-
thetic features justify the interest devoted to this reac-
tion; for instance, it allows easy introduction of a sulfinyl
group into a suitably unsaturated substrate. The addition
of sulfenic acids to alkenes or alkynes is a concerted
reaction in which the nature of the unsaturated bond,
on one hand, and the structural features of the sulfenic
acid, on the other, play a relevant role, the former on
the regioselectivity and the latter on the total yield of
the addition, since stabilizing effects of the sulfenic acid
structure, such as high steric demands and/or intra-
molecular hydrogen bonding, could prevent its self-
condensation to give thiosulfinate.
Sch em e 2
Recently, we have reported the synthesis of enantio-
merically pure alkylsulfinylbuta-1,3-dienes 1, which was
based on the site selective addition of chiral sulfenic acids
R*SOH, generated in situ from suitable precursors, to
the triple bond of enynes 2 (Scheme 1).3 Dienes 1 have
been obtained in good yield with high regio- and stereo-
selectivities. Accordingly, we envisaged that the addition
of sulfenic acids, such as 3 and 4, to the triple bond of
compounds 5 (Scheme 2) would give an easy access to
R,â-unsaturated carbonyl compounds bearing an enan-
(1) Hogg, D. R. In The chemistry of sulphenic acids and their
derivatives; Patai, S., Ed.; J ohn Wiley & Sons: Chichester, 1990; pp
361-402.
(2) Van den Broek, L. A. G. M.; Delbressine, L. P. C.; Ottenheijm,
H. C. J . In The chemistry of sulphenic acids and their derivatives; Patai,
S., Ed.; J ohn Wiley & Sons: Chichester, 1990; pp 701-721.
(3) (a) Aversa, M. C.; Barattucci,A.; Bonaccorsi, P.; Giannetto, P.;
J ones, D. N. J . Org. Chem. 1997, 62, 4376-4384. (b) Aversa, M. C.;
Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolo`, F. J . Org. Chem.
1999, 64, 2114-2118.
tiomerically pure â-sulfoxide moiety. Good stereocontrol
in the formation of C-C bonds has been observed when
the starting products combine the reactivity of the R,â-
unsaturated carbonyl function with the capability of the
10.1021/jo015595a CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/19/2001

4846 J . Org. Chem., Vol. 66, No. 14, 2001
Aversa et al.
Ta ble 1. P r od u cts Obta in ed fr om Ad d ition of Su lfen ic
Acid s 3 a n d 4 to Oxoa lk yn es 5 (Sch em e 2)
sulfinyl group as chiral auxiliary. In particular, nucleo-
philic additions of organometallic reagents to R-sulfinyl
R,â-unsaturated carbonyl compounds have been exten-
sively investigated, and it has been shown that the high
level of stereocontrol observed in these reactions comes
from a favored chelation of the metal atom to both the
sulfinyl and carbonyl oxygen atoms.4 R-Sulfinyl R,â-
unsaturated carbonyl compounds have also given good
stereochemical results when involved as either hetero-
dienes5 or dienophiles6 in stereoselective Diels-Alder
(DA) cycloadditions.
total
R*SOH R1C(O)C)CH time (h) yield (%) products (ratio)
3
3
3
5a
5b
5c
3
2
6.5
60
60
95
6Ra /6Sa (67:33)
6Rb/6Sb (75:25)
6Rc/6Sc/8Rc/8Sc
(54:35:7:4)
4
4
5a
5b
0.75
1
80
95
7Ra /7Sa (25:75)
7Rb/7Sb (20:80)
The sterical requirements of the camphor skeleton in
sulfenic acids 3 and 4 favor their addition to the triple
bond of compounds 5 (see the Introduction), giving rise
to the good to high yields observed in their reactions
(Table 1). The isoborneol and bornyl residues, directly
linked to the sulfinyl moiety, are structurally analo-
gous: they essentially differ in the presence or absence
of the hydroxy function that allows the formation of a
stabilizing intramolecular hydrogen bonding with the
sulfoxide oxygen atom. Some unexpected and undesired
reactions of the hydroxy function previously observed10
(see below) drove us to synthesize both isoborneol and
bornyl â-sulfinyl R,â-unsaturated carbonyl compounds for
studying their behavior in subsequent reactions.
In this paper, we mainly describe a new method for
the facile obtainment in high yields of enantiomerically
pure â-sulfinyl R,â-unsaturated carbonyl compounds,
which are potentially as useful substrates as the corre-
sponding R-sulfinyl substituted products since they pos-
sess several reactive sites for nucleophilic and electro-
philic attacks and can act as synthetic equivalents of
acetylene dienophiles in DA reactions.7 In addition, we
discuss the results of reactions in which our enantiopure
â-sulfinyl R,â-unsaturated ketones are involved as nu-
cleophile acceptors and their use as heterodienes in
concerted cycloadditions with electron-rich dienophiles.
Resu lts a n d Discu ssion
The addition of intermediates 3 and 4 to the triple bond
of 1-phenyl-2-propyn-1-one (5a ) and 3-butyn-2-one (5b)
was completely regioselective, leading to â-sulfinyl R,â-
unsaturated ketones 6 or 7. When methyl propiolate (5c)
was involved in the reaction under study, R-sulfinyl R,â-
unsaturated esters 8 were obtained together with â-sul-
finyl enones 6,11 with the latter representing the major
products of the reaction (Table 1).12 This outcome is easily
understood if one considers the regioselectivity of the
addition sulfenic acid/unsaturated bond which is strictly
related to the chemical nature of substituents linked to
the reacting unsaturation.13
The results obtained (Table 1) prompted us to envisage
the possibility of modulating the direction of attack of
the sulfenic acid 3 to the triple bond of ynone 5a . By
transforming its carbonyl function into a dithioketal
moiety showing a such reduced electron-withdrawing
capacity, the formation of only R-sulfinyl R,â-unsaturated
ketone derivatives may occur. We only partially suc-
ceeded in putting this idea into practice. When sulfenic
acid 3 was reacted with the ethynyl dithioketal 1114 in
toluene solution (Scheme 3), then equal amounts of the
sulfur epimeric mixtures ïf â-sulfinyl and R-sulfinyl R,â-
Syn t h esis of t h e E n a n t iom er ica lly P u r e â-Su l-
fin yl r,â-Un sa t u r a t ed Ca r b on yl Com p ou n d s 6-8.
Sulfenic acids 3 and 4 were generated by thermolysis
(toluene, 110 °C) of suitable precursors and trapped in
situ by the oxoalkynes 5 (Scheme 2). Precursors of 3 and
4 were â-cyanosulfoxides 9 and 10, synthesized from
readily available members of the chiral pool.3 3-Butyn-
2-one (5b) and methyl propiolate (5c) are commercially
available, and 1-phenyl-2-propyn-1-one (5a ) was easily
obtained from 1-phenyl-2-propyn-1-ol.8
The addition of sulfenic acids 3 and 4 to oxoalkynes 5
gave sulfur epimeric mixtures of sulfinyl R,â-unsaturated
carbonyl compounds 6-8. The mixtures were separable
by simple column chromatography, easily leading to
enantiomerically pure compounds 6, 7, and 8Rc. The ester
8Sc was obtained in too low yield to be isolated. Moderate
to good diastereoselectivities have been observed in all
the performed experiments. The sulfur configuration in
the obtained products was assigned on the basis of
previously observed stereochemical outcome of the sulfen-
ic acid/enyne additions in the synthesis of alkyl sulfinyl
butadienes 1.3,9 The obtained results are detailed in Table
1.
(9) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.;
Nicolo`, F.; Rizzo, S. Tetrahedron: Asymmetry 1999, 10, 3907-3917.
(10) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.; Gian-
netto, P.; Nicolo`, F. J . Chem. Soc., Perkin Trans. 2 1997, 273-277.
(11) (a) Davis, F. A.; Friedman, A. J .; Nadir, U.K. J . Am. Chem.
Soc. 1978, 100, 2844-2852. (b) De Lucchi, O.; Lucchini, V.; Marchioro,
C.; Valle, G.; Modena, G. J . Org. Chem. 1986, 51, 1457-1477, 1989,
54, 3245.
(12) Epimeric esters 6Rc and 6Sc had been previously synthesized
(see ref 11b) by Michael addition of (1S)-10-mercaptoisoborneol onto
methyl propiolate, followed by stereocontrolled m-CPBA oxidation of
the sulfide. Our procedure appears to be less diastereoselective, but
our yields are higher. Moreover, we obtain only (E)-isomers, owing to
the stereospecific cis-addition of the sulfenic acid 3 onto the propiolate
5c.
(4) Posner, G. H.; Mallamo, J . P.; Hulce, M.; Frye, L. L. J . Am. Chem.
Soc. 1982, 104, 4180-4185. Posner, G. H.; Switzer, C. J . Am. Chem.
Soc. 1986, 108, 1239-1244. Posner, G. H.; Weitzberg, M.; Hamill, T.
G.; Asirvatham, E.; Cun-Heng, H.; Clardy, J . Tetrahedron 1986, 42,
2919-2929. Posner, G. H. Acc. Chem. Res. 1987, 20, 72-78.
(5) Hayes, P.; Dujardin, G.; Maignan, C. Tetrahedron Lett. 1996,
37, 3687-3690. Hayes, P.; Maignan, C. Tetrahedron: Asymmetry 1999,
10, 1041-1050.
(6) Garc´ıa Ruano, J . L.; Carretero, J . C.; Carren˜o, M. C.; Mart´ın
Cabrejas, L. M.; Urbano, A. Pure Appl. Chem. 1996, 68, 925-930.
Carretero, J . C.; Garc´ıa Ruano, J . L.; Mart´ın Cabrejas, L. M. Tetra-
hedron: Asymmetry 1997, 8, 2215-2225.
(7) (a) Girodier, L. D.; Rouessac, F. P. Tetrahedron: Asymmetry 1994,
5, 1203-1206. (b) Arai, Y.; Suzuki, A.; Masuda, T.; Masaki, Y.; Shiro,
M. J . Chem. Soc., Perkin Trans. 1 1995, 2913-2917. (c) Arai, Y.;
Masuda, T.; Masaki, Y.; Shiro, M. J . Chem. Soc., Perkin Trans. 1 1996,
759-762. (d) Solladie´, G.; Carren˜o, M. C. In Organosulphur Chemistry.
Synthetic Aspects; Page, P. C. B., Ed.; Academic Press: New York,
1995; Chapter 1, pp 1-47.
(8) Heasley, V. L.; Shellhamer, D. F.; Chappell, A. E.; Cox, J . M.;
Hill, D. J .; McGovern, S. L.; Eden, C. C.; Kissel, C. L. J . Org. Chem.
1998, 63, 4433-4437.
(13) J ones, D. N.; Cottam, P. D.; Davies, J . Tetrahedron Lett. 1979,
4977-4980.
(14) We obtained in low yield the not yet known 2-ethynyl-2-phenyl-
1,3-dithiane (11) [1H NMR: δ 7.5-7.3 (m, ArH), 2.80 (m, H2-4, 6), 2.75
(s, CHd), 2.05 (m, H2-5)] by the reaction of commercial ethynylmag-
nesium bromide with in situ generated 2-chloro-2-phenyl-1,3-dithiane,
following the synthetic strategy described by: Andersen, N. H.;
Denniston, A. D.; McCrae, D. A. J . Org. Chem. 1982, 47, 1145-1146.

Enantiopure Sulfinyl Ketones and Esters
J . Org. Chem., Vol. 66, No. 14, 2001 4847
Sch em e 3
Sch em e 4
unsaturated dithioketals 12 and 13 were obtained. These
could be further transformed into their corresponding
R,â-unsaturated ketones. The mixture of compounds 12
and 13 was separated by column chromatography, and
the products were identified by H NMR spectroscopy15
1
Reaction of 6Ra with 14, performed in refluxing 1,2-
dichloroethane for 43 h, led to (4S,6R,RS)-4-[(1S)-
isoborneol-10-sulfinyl]-5,6-dihydro-2-phenyl-6-phenylthio-
4H-pyran (16, 20% yield) as the only cycloadduct of the
reaction among four possible diastereoisomers, together
with (1R,3R,4S,7S)-2-oxa-1-phenyl-3,7-diphenylthiobicyclo-
[2.2.2]oct-5-ene (17, 10% yield) and an almost 1:1 mixture
of diastereomeric sulfoxides 18 (15% total yield). The
fused compound 17 is the product of a second DA reaction
of phenyl vinyl sulfide (14), used in large excess, onto
the diene intermediate 19, which was generated from 16
by elimination of (1S)-isoborneol-10-sulfenic acid (3)
under the reaction conditions. The isolation of sulfoxides
18 confirmed the mechanistic pathway proposed in
Scheme 4 since they are products of the trapping of
sulfenic acid 3 by vinyl sulfide 14. The structure and
relative configuration of 17 are suggested on the basis
of diagnostic 1H NMR data, such as the resonance pattern
of H2-8, where both geminal protons are each coupled
with two vicinal protons (H-4 and H-7). Moreover, the
J 3,5 ) 2.6 Hz is regarded as an indication of M (or W)
relationship between the two protons involved. Taking
into account the detection of only one cycloadduct in the
reaction mixture, and its partial conversion to 17, verified
during the 1H NMR monitoring of the reaction, it appears
well-grounded that the DA reaction (6Ra + 14) occurred
with complete endo and facial diastereoselection, the
dienophile 14 approaching the (1Re,2Re,3Si) face of the
diene 6Ra in its A conformation. Following this assump-
tion, the atom C-6, which is (R) configured in compounds
16 and 19, maintains its (R) configuration in compound
17, where it is indexed as C-3. Thus the absolute
configuration (1R,3R,4S,7S) is assigned to compound 17.
but were not fully characterized. This approach (Scheme
3) was of little use from a practical point of view, because
R-sulfinyl 13 were formed together with â-sulfinyl de-
rivatives 12, and the literature reports several efficient
methodologies for obtaining enantiomerically pure R-sulfi-
nyl R,â-unsaturated ketones in moderate to good yields.7d,16
On the contrary, to the best of our knowledge, no
stereoselective syntheses of chiral acyclic â-sulfinyl R,â-
unsaturated ketones such as 6 and 7 (Scheme 2) have
been reported up to now.
Asym m etr ic Diels-Ald er Rea ction s of â-Su lfin yl
r,â-Un sa tu r a ted Keton es w ith Electr on -Rich Di-
en op h iles. As part of our study on stereoselective DA
reactions involving sulfinyl butadienes,3,9,16b we were
interested in investigating the reactivity of enantiomeri-
cally pure â-sulfinyl R,â-unsaturated ketones in such
cycloadditions. A considerable amount of work has been
reported on their use as dienophiles.7d â-Sulfinyl R,â-
unsaturated ketones can, in principle, however, act as
heterodienes in inverse-electron-demanding DA reac-
tions, giving a straightforward access to functionalized
and enantiopure pyranoid systems.17
Readily available phenyl vinyl sulfide (14) and ethyl
vinyl ether (15) were tested as electron-rich dienophiles
toward (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-
propen-1-one (6Ra ) in several attempted experiments
before obtaining the results depicted in Scheme 4.
(15) Meaningful 1H NMR parameters are as follow. (RS,E)-2-[2-
[(1S)-isobor n eol-10-su lfin yl]vin yl]-2-p h en yl-1,3-d it h ia n e (12R ):
δ 7.09 (AB d, J 1′′, 14.7, H-2"), 6.19 (AB d, H-1′′), 4.09 (dd, J 2′, 7.7
2′′
3′
and 3.1, H-2′), 3.26 and 2.42 (AB system, J 10′A,
13.2, H2-10′), 1.10
10′B
(s, H3-8′), 0.83 (s, H3-9′). (SS,E)-2-[2-[(1S)-isobor n eol-10-su lfin yl]-
vin yl]-2-p h en yl-1,3-d ith ia n e (12S): δ 7.00 (AB d, J 1′′, 2′′ 14.7, H-2"),
6.20 (AB d, H-1′′), 4.05 (dd, J 2′, 7.7 and 3.5, H-2′), 3.33 and 2.52 (AB
3′
system, J 10′A,
14.1, H2-10′), 1.12 (s, H3-8′), 0.83 (s, H3-9′). (RS)-2-
10′B
[1-[(1S )-isob or n e ol-10-su lfin yl]vin yl]-2-p h e n yl-1,3-d it h ia n e
(13R): δ 6.39 and 5.96 (split AB system, J 2′′A, 1.5, H2-2′′), 4.11 (dd,
2′′B
J 2′, 7.7 and 3.8, H-2′), 3.11 and 2.85 (AB system, J 10′A,
13.1, H2-
10′B
3′
10′), 1.07 (s, H3-8′), 0.84 (s, H3-9′). (SS)-2-[1-[(1S)-isobor n eol-10-
su lfin yl]vin yl]-2-p h en yl-1,3-d ith ia n e (13S): δ 6.47 and 6.03 (split
AB system, J 2′′A,
1.4, H2-2′′), 4.09 (m, H-2′), 3.50 and 2.71 (AB
14.1, H2-10′), 1.12 (s, H3-8′), 0.83 (s, H3-9′).
2′′B
system, J 10′A,
10′B
(16) (a) Alexandre, C.; Belkadi, O.; Maignan, C. Synthesis 1992,
547-548. (b) Aranda, M. T.; Aversa, M. C.; Barattucci, A.; Bonaccorsi,
P.; Carren˜o, M. C.; Cid, M. B.; Garc´ıa Ruano, J . L. Tetrahedron:
Asymmetry 2000, 11, 1217-1225.
(17) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.;
Giannetto, P.; Panzalorto, M. Tetrahedron: Asymmetry 1997, 8, 2989-
2995.
When ethyl vinyl ether (15) was reacted with 6Ra , only
the condensed compound 20 was isolated in 15% yield.
Long reaction times and moderate to low yields ob-
served in these DA cycloadditions (Scheme 4) addressed

4848 J . Org. Chem., Vol. 66, No. 14, 2001
Aversa et al.
Sch em e 5
number of reports demonstrated that a chiral sulfoxide
substituent can control diastereofacial selectivity in
nucleophile additions, the facial discrimination observed
in our addition could not be easily explained by the
presence of the sulfinyl chiral auxiliary, which was far
away from the reactive site. A highly diastereoselective
1,4-conjugate addition of organoaluminum reagents to
R-sulfinyl R,â-unsaturated carbonyl compounds was re-
cently reported19 where a hydroxy group in the substrate
assisted the organoaluminum reagent in the nucleophile
transfer. Following the idea that some kind of assistance
could be analogously exerted by the hydroxy function of
the isoborneol sulfinyl moiety in the ketone 6Ra , we
decided to react methylmagnesium iodide with (RS,E)-3-
[(1S-exo)-2-bornylsulfinyl]-1-phenyl-2-propen-1-one (7Ra )
under the same conditions as the first experiment. The
lack of diastereoselectivity observed in this 1,2-addition
(Scheme 5) indicated that the hydroxy group in the
skeleton of the chiral auxiliary was responsible for the
facial diastereoselection observed when 6Ra underwent
the nucleophilic addition. Methylmagnesium iodide was
also reacted with (E)-3-[(1S)-isoborneol-10-sulfonyl]-1-
phenyl-2-propen-1-one (24), readily prepared by m-CPBA
oxidation of the corresponding sulfinyl propenone 6Ra ,
and the addition gave compounds 25 and 26 in almost
equal amounts (Scheme 5). Thus, the stereogenic sulfur
appears to be essential in the promotion of a significant
facial discrimination during the nucleophilic addition
onto the carbonyl moiety. Sulfone 25 was also obtained
by oxidizing the sulfoxide 22.
our efforts toward the use of Lewis acid catalysis in the
cycloaddition of (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-
phenyl-2-propen-1-one (6Ra ) with phenyl vinyl sulfide
(14). The presence of Lewis acids (LiClO4 suspended in
CH2Cl2, TiCl4, ZnCl2, or BF3‚Et2O) favored in all cases
polymerization of the dienophile 14, decomposition of the
â-sulfinyl R,â-unsaturated ketone 6Ra , and formation of
diastereomeric mixtures of 2-oxa-4-thiatricycloundecane
4-oxides 21, arising from intramolecular 1,4-conjugate
addition of the isoborneol hydroxy function onto the R,â-
unsaturated ketone moiety.10,18 The reaction of (RS,E)-3-
[(1S-exo)-2-bornylsulfinyl]-1-phenyl-2-propen-1-one (7Ra )
with phenyl vinyl sulfide (14) resulted in extensive
polymerization when performed in the presence of LiC-
lO4.
â-Su lfin yl r,â-Un sa tu r a ted Keton es a s Nu cleo-
p h ile Accep tor s in 1,2-Ad d ition s. Freshly prepared
methylmagnesium iodide (3.5 equiv) was added to (RS,E)-
3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one
(6Ra ) at - 78 °C in diethyl ether. This reaction led to
compounds 22 and 23 coming from the exclusive nucleo-
phile 1,2-addition to the carbonyl moiety (Scheme 5).
Epimers 22 and 23 were obtained in a 70:30 ratio and
are separable by column chromatography. Although a
These results provided the basis for a tentative ratio-
nalization of the stereochemical outcome of the addition
(MeMgI + 6Ra ). The observed diastereoselection can be
explained taking into account different conformations of
the â-sulfinyl R,â-unsaturated ketone 6Ra around the
C(3)-S bond. Conformations B and C can be regarded
as almost equally populated and favored among others,
owing to (i) the s-trans arrangement of the SO bond with
respect to the vicinal unsaturation, a feature often
observed in compounds possessing the vinylsulfoxide
moiety,3b,20 (ii) the isoborneol residue in close proximity
to the carbonyl function, so allowing magnesium interac-
tion with both carbonyl and isoborneol oxygen atoms, as
depicted in Figure 1 for 6Ra in its B conformation. In
this chelated conformation, the nucleophile approachs the
substrate from the less sterically congested Re face,
whereas, in the C conformation, the position and struc-
tural features of the isoborneol group could allow mag-
nesium/oxygen atoms interactions in both sides with
respect to the sulfinyl R,â-unsaturated carbonyl plane,
so eluding any kind of diastereotopic differentiation.
Recently, Node et al.21 described an asymmetric tandem
Michael addition/Meerwein-Pondorf-Verley reduction
(18) TiCl4 (0.4 equiv) was added to a solution of (RS,E)-3-[(1S)-
isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6Ra ) (1 equiv) and
phenyl vinyl sulfide (14) (2 equiv) in CH2Cl2 at - 20 °C. After
spontaneous reaching of the room temperature and stirring for 7 days
under argon, the solvent was removed in a vacuum and the mixture
chromatographed on silica gel (petrol/ethyl acetate 99: 1 as eluant),
giving (1R,4R,6S,9R)-11,11-dimethyl-2-oxa-3-benzoylmethyl-4-thia-
tricyclo[6.2.1.01,6]undecane 4-oxides 21A and 21B in enantiomerically
pure forms. Here, some meaningful 1H NMR parameters are reported.
21A, more mobile C-3 epimer, 15% yield: δ 4.80 (dd, J 1′A, 7.0, J 1′B,
(19) Carren˜o, M. C.; Pe´rez Gonza´lez, M.; Ribagorda M. J . Org. Chem.
1996, 61, 6758-6759.
3
3
5.0, H-3), 3.58 (dd, J 1, 7.8 and 3.2, H-1), 3.26 (AB dd, J 1′A,
HA-1′), 3.07 (AB d, J 5A, 14.1, HA-5), 3.17 (AB dd, HB-1′), 2.75 (AB d,
13.6,
10
1′B
(20) Adams, H.; Bailey, N. A.; J ones, D. N.; Aversa, M. C.; Bonac-
corsi, P.; Giannetto, P. Acta Crystallogr. 1995, C51, 1357-1359. Aversa,
M. C.; Barattucci, A.; Bonaccorsi, P.; Bonini, B. F.; Giannetto, P.; Nicolo`,
F. Tetrahedron: Asymmetry 1999, 10, 3919-3929.
5B
HB-5), 1.31 (s, H3-12), 0.91 (s, H3-13). 21B, less mobile C-3 epimer,
20% yield: δ 5.32 (dd, J 1′A, 3 7.5, J 1′B, 3 4.4, H-3), 3.67 (dd, J 1, 10 7.9 and
3.3, H-1), 3.50 (AB dd, J 1′A,
16.5, HA-1′), 3.18 (AB d, J 5A,
14.2,
1′B
5B
HA-5), 3.15 (AB dd, HB-1′), 2.75 (AB d, HB-5), 1.32 (s, H3-12), 0.91 (s,
(21) Node, M.; Nishide, K.; Shigeta, Y.; Shiraki, H.; Obata, K. J .
Am. Chem. Soc. 2000, 122, 1927-1936.
H3-13).

Enantiopure Sulfinyl Ketones and Esters
J . Org. Chem., Vol. 66, No. 14, 2001 4849
as internal standard; J values are given in Hz; the assignments
are supported by attached proton test (APT) and homodecou-
pling experiments. Protons and carbon nuclei, marked with
(′), pertain to isoborneol or bornyl moieties, but to benzoyl-
methyl substituent for compounds 21 only. The symbol (′′)
identifies aromatic nuclei in compounds 6-8 and vinyl nuclei
in compounds 12 and 13. Mass spectra were measured by FAB
(m-nitrobenzyl alcohol as matrix). Optical rotations were
measured in CHCl3 solutions. All reactions were monitored
by TLC on commercially available precoated plates (silica gel
60 F 254), and the products were visualized with acidic vanillin
solution. Silica gel 60, 230-400 mesh, was used for column
chromatography. Petrol refers to light petroleum, bp 30-40
°C. Elemental analyses were performed by REDOX, Milano,
Italy.
Su lfin yl Ester s a n d Keton es 6-8. Gen er a l P r oced u r e.
A solution of the carbonyl compound 5 (4.5 mmol) and
sulfoxides 9 or 10 (3 mmol) in toluene (5 mL) was maintained
at reflux temperature. When the reaction appeared complete
by TLC, the solvent was removed under reduced pressure and
the reaction mixture was separated by column chromatogra-
phy. Some experimental details are reported in Table 1. The
relative amounts of the products obtained were evaluated by
1H NMR.
F igu r e 1. Nucleophilic approach of MeMgI to the chelated B
conformation of 6Ra .
of R,â-unsaturated ketones via the formation of a chelated
adduct that highly resembles the one depicted in Figure
1. When the sulfone 24 undergoes nucleophilic attack
from Grignard reagent, four conformations D-G have
to be regarded as almost equally populated, that is D and
E analogous to B, and F and G analogous to C. Following
the previously discussed rationale, F and G allow mag-
nesium/oxygen atom interactions in both sides with
respect to the sulfinyl R,â-unsaturated carbonyl plane (no
tangible diastereoselection), and if D offers the less
sterically congested Re face to the nucleophilic approach,
the equally populated conformation E suffers the attack
from the Si face of the carbonyl plane (again no tangible
diastereoselection).
Rea ction of 1-P h en yl-2-p r op yn -1-on e8 (5a ) w ith 3-[(1S)-
Isobor n eol-10-su lfin yl]p r op a n en itr iles 9.3a The following
epimers were obtained by elution with petrol containing ethyl
acetate (10-15%) and are reported in order of elution from
the column.
(RS,E)-3-[(1S)-Isobor n eol-10-su lfin yl]-1-ph en yl-2-pr open -
1-on e (6Ra ): oil; 40% yield; [R]23D -101.4 (c 0.015); 1H NMR δ
8.10 (m, H-2′′,6′′), 7.83 (AB d, J 2,3 14.5, H-3), 7.74 (AB d, J 2,3
14.5, H-2), 7.7-7.5 (m, H-3′′-5′′), 4.17 (dd, J 2′,3′ 7.9 and 4.2,
H-2′), 3.31 and 2.67 (AB system, J 10′A,10′B 13.3, H2-10′), 1.9-
1.6 (m, H2-3′,5′,6′, H-4′), 1.10 (s, H3-8′), 0.87 (s, H3-9′); 13C NMR
δ 186.9 (C-1), 149.0 (C-3), 136.5 (C-1′′), 134.0 (C-2), 129.0 and
128.9 (C-2′′-6′′), 77.3 (C-2′), 55.2 (C-10′), 51.6 (C-1′), 48.5 (C-
7′), 45.1 (C-4′), 38.6 (C-3′), 30.8 and 27.1 (C-5′,6′), 20.5 and
19.8 (C-8′,9′). Anal. Calcd for C19H24O3S: C, 68.64; H, 7.28.
Found: C, 68.32; H, 7.30.
Con clu sion s
(SS,E)-3-[(1S)-Isobor n eol-10-su lfin yl]-1-ph en yl-2-pr open -
1-on e (6Sa ): oil; 20% yield; 1H NMR δ 8.10 (m, H-2′′,6′′), 7.84
and 7.82 (AB system, J 2,3 14.6, H-2,3), 7.7-7.5 (m, H-3′′-5′′),
4.10 (dd, J 2′,3′ 7.8 and 3.7, H-2′), 3.58 and 2.67 (AB system,
Enantiopure alkanesulfenic acids can fulfill a relevant
role in the stereoselective synthesis of usable sulfinyl
substituted substrates: in this paper, we have described
an easy access to â-sulfinyl R,â-unsaturated carbonyl
compounds by their addition to ynones. The pericyclic
mechanism of the reaction guarantees good stereochem-
ical control. The structural nature of the sulfenic acids
allows the obtainment in high yields of products easily
separable by column chromatography in enantiopure
form.
The synthesized â-sulfinyl R,â-unsaturated ketones
have shown their low capability as heterodienes in
inverse-electron-demanding DA reactions, but the sulfi-
nyl group has appeared once again as a very good chiral
auxiliary in controlling the stereochemical outcome of
these cycloadditions. Moreover, the unsaturated sub-
strates 6 and 7 have confirmed their expected value as
nucleophile acceptors giving useful stereochemical results
in 1,2-addition of Grignard reagents: the chiral sulfur
atom exerts a remote stereocontrol if assisted by the
hydroxy group being part of the isoborneol substituent.
Further, â-sulfinyl R,â-unsaturated ketones with similar
structural characteristics could be prepared from readily
available starting products, such as enantiopure methyl
mandelate (Scheme 1).3a
J
10′A,10′B 14.1, H2-10′), 1.9-1.6 (m, H2-3′,5′,6′, H-4′), 1.14 (s, H3-
8′), 0.86 (s, H3-9′); 13C NMR δ 186.7 (C-1), 149.9 (C-3), 136.5
(C-1′′), 133.0 (C-2), 129.0 and 128.9 (C-2′′-6′′), 76.4 (C-2′), 53.1
(C-10′), 52.8 (C-1′), 49.3 (C-7′), 44.8 (C-4′), 39.9 (C-3′), 29.7 and
27.5 (C-5′,6′), 20.5 and 20.1 (C-8′,9′). Anal. Calcd for C19H24
-
O3S: C, 68.64; H, 7.28. Found: C, 68.74; H, 7.21.
Rea ction of 5a w ith 3-[(1S-exo)-2-Bor n ylsu lfin yl]p r o-
p a n en itr iles 10.3b The following epimers were obtained by
elution with petrol/ethyl acetate 95:5 and are reported in order
of elution from the column.
(RS,E)-3-[(1S-exo)-2-Bor n ylsu lfin yl]-1-p h en yl-2-p r op en -
1-on e (7Ra ): oil; 20% yield; 1H NMR δ 8.05 (m, H-2′′,6′′), 7.73
(AB d, J 2,3 14.5, H-3), 7.69 (AB d, J 2,3 14.5, H-2), 7.6-7.5 (m,
H-3′′-5′′), 2.81 (dd, J 2′,3′ 9.4 and 6.6, H-2′), 2.3-1.2 (m, H2-
3′,5′,6′, H-4′), 1.17 (s, H3-10′), 1.05 (s, H3-8′), 0.90 (s, H3-9′);
13C NMR δ 187.1 (C-1), 150.7 (C-3), 136.6 (C-1′′), 133.7 (C-2),
128.9, 128.8, 127.9 (C-2′′-6′′), 70.7 (C-2′), 50.2 (C-1′), 47.4 (C-
7′), 45.1 (C-4′), 39.0 and 27.2 (C-5′,6′), 28.1 (C-3′), 20.2 and
19.8 (C-8′,9′), 13.5 (C-10′). Anal. Calcd for C19H24O2S: C, 72.11;
H, 7.64. Found: C, 72.13; H, 7.60.
(SS,E)-3-[(1S-exo)-2-Bor n ylsu lfin yl]-1-p h en yl-2-p r op en -
1-on e (7Sa ): oil; 60% yield; 1H NMR δ 8.06 (m, H-2′′,6′′), 7.83
(AB d, J 2,3 14.5, H-3), 7.80 (AB d, J 2,3 14.5, H-2), 7.6-7.5 (m,
H-3′′-5′′), 2.81 (dd, J 2′,3′ 9.2 and 6.8, H-2′), 1.9-1.2 (m, H2-
3′,5′,6′, H-4′), 1.28 (s, H3-10′), 1.05 (s, H3-8′), 0.93 (s, H3-9′);
13C NMR δ 187.1 (C-1), 148.3 (C-3), 136.5 (C-1′′), 133.8 (C-2),
129.3, 128.9, 128.8 (C-2′′-6′′), 73.1 (C-2′), 50.0 (C-1′), 47.7 (C-
7′), 44.8 (C-4′), 38.7 and 26.7 (C-5′,6′), 31.5 (C-3′), 20.1 and
19.4 (C-8′,9′), 13.6 (C-10′). Anal. Calcd for C19H24O2S: C, 72.11;
H, 7.64. Found: C, 72.00; H, 7.34.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
at 300 and 75 MHz, respectively, in CDCl3 solutions with TMS

4850 J . Org. Chem., Vol. 66, No. 14, 2001
Aversa et al.
Rea ction of 3-Bu tyn -2-on e (5b) w ith 9. The following
epimers were obtained by elution with petrol/CHCl3 50:50 and
are reported in order of elution from the column.
J 10′A,10′B 14.1, H2-10′), 1.8-1.1 (m, H2-3′,5′,6′, H-4′), 1.11 (s, H3-
8′), 0.84 (s, H3-9′); 13C NMR δ 164.2 (C-1), 150.5 (C-3), 125.6
(C-2), 76.3 (C-2′), 53.0 and 52.6 (C-1′,10′), 52.3 (OMe), 49.2 (C-
7′), 44.7 (C-4′), 40.0 (C-3′), 31.7 and 27.5 (C-5′,6′), 20.4 and
20.1 (C-8′,9′). Anal. Calcd for C14H22O4S: C, 58.72; H, 7.75.
Found: C, 58.71; H, 7.63.
Rea ction of 6Ra w ith P h en yl Vin yl Su lfid e (14). A
solution of heterodiene 6Ra (100 mg, 0.3 mmol) and dienophile
14 (0.24 mL, 1.8 mmol) in 1,2-dichloroethane (2.5 mL) was
maintained at reflux temperature. When the reaction appeared
complete by TLC (after 43 h), the solvent was removed under
reduced pressure and the reaction mixture was separated by
column chromatography, eluting with petrol containing 15-
20% ethyl acetate. The isolated products are reported in order
of elution from the column.
(RS,E )-4-[(1S)-Isob or n e ol-10-su lfin yl]-3-b u t e n -2-on e
(6Rb): oil; 45% yield; 1H NMR δ 7.47 (AB d, J 3,4 14.9, H-4),
6.97 (AB d, J 3,4 14.9, H-3), 4.12 (dd, J 2′,3′ 7.7 and 3.6, H-2′),
3.27 and 2.59 (AB system, J 10′A,10′B 13.2, H2-10′), 2.39 (s, H3-
1), 1.9-1.2 (m, H2-3′,5′,6′, H-4′), 1.09 (s, H3-8′), 0.85 (s, H3-9′);
13C NMR δ 194.5 (C-2), 147.4 (C-4), 132.1 (C-3), 77.2 (C-2′),
55.0 (C-10′), 51.6 (C-1′), 48.5 (C-7′), 45.1 (C-4′), 38.5 (C-3′), 30.7
and 27.1 (C-5′,6′), 29.7 (C-1), 20.5 and 19.8 (C-8′,9′); MS m/z
271 (M + 1, 33), 149 (92), 135 (100), 55 (87). Anal. Calcd for
C
14H22O3S: C, 62.19; H, 8.20. Found: C, 62.12; H, 8.30.
(SS,E)-4-[(1S)-Isobor n eol-10-su lfin yl]-3-bu ten -2-on e (6Sb):
oil; 15% yield; 1H NMR δ 7.56 (AB d, J 3,4 15.0, H-4), 6.95 (AB
d, J 3,4 15.0, H-3), 4.06 (dd, J 2′,3′ 7.4 and 3.6, H-2′), 3.51 and
2.60 (AB system, J 10′A,10′B 14.1, H2-10′), 2.39 (s, H3-1), 1.9-1.2
(m, H2-3′,5′,6′, H-4′), 1.12 (s, H3-8′), 0.85 (s, H3-9′); 13C NMR δ
194.5 (C-2), 148.4 (C-4), 132.1 (C-3), 76.4 (C-2′), 53.1 (C-10′),
52.6 (C-1′), 49.2 (C-7′), 44.7 (C-4′), 40.1 (C-3′), 31.8 and 27.5
(C-5′,6′), 29.6 (C-1), 20.4 and 20.1 (C-8′,9′); MS m/z 271 (M +
1, 29), 149 (55), 135 (56), 55 (100). Anal. Calcd for C14H22O3S:
C, 62.19; H, 8.20. Found: C, 61.81; H, 8.25.
1-[(1S)-Isobor n eol-10-su lfin yl]eth yl ph en yl su lfides (18)
(about equal amounts of two diastereomers): oil; 15% yield;
1H NMR δ 7.5-7.3 (m, ArH), 4.21 (q) and 3.96 (q) (J vic 7.3,
H-1), 4.04 (dd, J 2′,3′ 8.1 and 3.9, H-2′), 3.07 and 2.68, and 2.96
and 2.89 (two AB systems, J 10′A,10′B 12.7, H2-10′), 1.8-1.4 (m,
H2-3′,5′,6′, H-4′), 1.70 (d) and 1.63 (d) (J vic 7.3, H3-2), 1.11 (s)
and 1.01 (s) (H3-8′), 0.85 (s) and 0.74 (s) (H3-9′). Anal. Calcd
for C18H26O2S2: C, 63.88; H, 7.75. Found: C, 63.95; H, 7.65.
(1R,3R,4S,7S)-2-Oxa -1-p h en yl-3,7-d ip h en ylth iobicyclo-
Rea ction of 5b w ith 10. The following epimers were
obtained by elution with petrol/Et2O 70:30 and are reported
in order of elution from the column.
1
[2.2.2]oct-5-en e (17): oil; 10% yield; H NMR δ 7.9-7.3 (m,
ArH), 6.02 (AB ddd, J 3,5 2.6, J 4,5 3.7, J 5,6 10.0, H-5), 5.73 (AB
ddd, J 4,6 0.9, J 6,7 3.2, H-6), 4.4-4.2 (m, H-3,4), 4.00 (ddd,
J 7,8A(trans) 6.0, J 7,8B(cis) 9.2, H-7), 2.20 (AB ddd, J 4,8A 3.5, J 8A,8B
13.7, HA-8), 2.08 (AB ddd J 4,8B 4.6, HB-8). Anal. Calcd for
(RS,E)-4-[(1S-exo)-2-Bor n ylsu lfin yl]-3-bu ten -2-on e (7Rb):
oil; 19% yield; 1H NMR δ 7.43 (AB d, J 3,4 14.8, H-4), 6.88 (AB
d, J 3,4 14.8, H-3), 2.74 (dd, J 2′,3′ 9.4 and 6.6, H-2′), 2.36 (s, H3-
1), 2.3-1.2 (m, H2-3′,5′,6′, H-4′), 1.13 (s, H3-10′), 1.01 (s, H3-
8′), 0.89 (s, H3-9′); 13C NMR δ 194.8 (C-2), 149.0 (C-4), 131.5
(C-3), 70.7 (C-2′), 50.2 (C-1′), 47.3 (C-7′), 45.1 (C-4′), 39.0 and
28.0 (C-5′,6′), 29.7 (C-1), 27.1 (C-3′), 20.2 and 19.7 (C-8′,9′),
13.5 (C-10′); MS m/z 255 (M + 1, 4), 149 (5), 137 (100), 81 (66),
55 (40). Anal. Calcd for C14H22O2S: C, 66.11; H, 8.72. Found:
C, 66.07; H, 8.65.
(SS,E)-4-[(1S-exo)-2-Bor n ylsu lfin yl]-3-bu ten -2-on e (7Sb):
oil; 76% yield; 1H NMR δ 7.55 (AB d, J 3,4 14.9, H-4), 6.94 (AB
d, J 3,4 14.9, H-3), 2.74 (dd, J 2′,3′ 9.0 and 6.8, H-2′), 2.36 (s, H3-
1), 1.9-1.2 (m, H2-3′,5′,6′, H-4′), 1.25 (s, H3-10′), 1.02 (s, H3-
8′), 0.92 (s, H3-9′); 13C NMR δ 194.9 (C-2), 147.5 (C-4), 132.5
(C-3), 73.1 (C-2′), 50.0 (C-1′), 47.7 (C-7′), 44.9 (C-4′), 38.8 and
26.8 (C-5′,6′), 31.5 (C-3′), 29.7 (C-1), 20.1 and 19.4 (C-8′,9′),
13.7 (C-10′); MS m/z 255 (M + 1, 4), 149 (4), 137 (100), 81 (78),
55 (52). Anal. Calcd for C14H22O2S: C, 66.11; H, 8.72. Found:
C, 66.32; H, 8.75.
Rea ction of Meth yl P r op iola te (5c) w ith 9. The following
products were obtained by elution with petrol containing ethyl
acetate (10-20%) and are reported in order of elution from
the column.
Met h yl (RS)-2-[(1S)-isob or n eol-10-su lfin yl]-2-p r op e-
n oa te (8Rc): oil; 6% yield; 1H NMR δ 6.96 and 6.70 (AB
system, J 3A,3B 0.4, H2-3), 4.14 (split dd, J 2′,3′ 7.9 and 3.7, H-2′),
3.87 (s, OMe), 3.00 and 2.98 (AB system, J 10′A,10′B 12.8, H2-
10′), 1.9-1.2 (m, H2-3′,5′,6′, H-4′), 1.06 (s, H3-8′), 0.83 (s, H3-
9′). Anal. Calcd for C14H22O4S: C, 58.72; H, 7.75. Found: C,
58.67; H, 7.80.
C
25H22OS2: C, 74.61; H, 5.51. Found: C, 74.32; H, 5.61.
(4S,6R,RS)-4-[(1S)-Isobor n eol-10-su lfin yl]-5,6-d ih yd r o-
2-p h en yl-6-p h en ylth io-4H-p yr a n (16): oil; 20% yield; 1H
NMR δ 7.6-7.2 (m, ArH and H-3), 5.65 (dd, J 5,6 7.1 and 3.2,
H-6), 3.98 (dd, J 2′,3′ 8.1 and 4.2, H-2′), 3.63 and 2.35 (AB
system, J 10′A,10′B 13.0, H2-10′), 3.4-1.4 (m, H2-3′,5,5′,6′, H-4,4′),
1.12 (s, H3-8′), 0.83 (s, H3-9′); MS m/z 469 (M + 1, 11), 189
(10), 161 (21), 159 (47), 154 (100), 123 (42), 77 (26), 55 (16).
Anal. Calcd for C27H32O3S2: C, 69.20; H, 6.89. Found: C, 69.42;
H, 6.50.
(1S*,3R*,4R*,7R*)-3,7-Dieth oxy-2-oxa -1-p h en ylbicyclo-
[2.2.2]oct-5-en e (20). A solution of heterodiene 6Ra (70 mg,
0.21 mmol) and ethyl vinyl ether (15) (0.12 mL, 1.26 mmol) in
CH2Cl2 (2.5 mL) was maintained at reflux temperature. When
the reaction appeared complete by TLC (after 12 days), the
solvent was removed under reduced pressure and the reaction
mixture purified by column chromatography. Elution with
petrol/ethyl acetate 88:12 afforded compound 20 (15% yield)
as an oil: 1H NMR δ 8.1-7.5 (m, ArH), 5.98 (AB ddd, J 3,5 2.7,
J
4,5 3.9, J 5,6 9.9, H-5), 5.67 (AB ddd, J 4,6 0.9, J 6,7 3.9, H-6), 4.4-
4.1 (m, H-3,4,7), 3.63 and 3.41 (m, OCH2), 2.16 (AB ddd, J 4,8A
3.3, J 7,8A(trans) 4.4, J 8A,8B 13.5, HA-8), 1.97 (AB ddd J 4,8B 4.6,
J 7,8B(cis) 9.3, HB-8), 1.10 (t, J vic 7.0, Me). Anal. Calcd for
C
17H22O3: C, 74.41; H, 8.09. Found: C, 74.56; H, 8.00.
Rea ction of 6Ra w ith Meth ylm a gn esiu m Iod id e. MeMgI
(4 mmol in 3.5 mL of anhydrous Et2O), freshly prepared22 and
titrated with salicylaldehyde phenylhydrazone,23 was added
dropwise at - 78 °C to a solution of 6Ra (380 mg, 1.15 mmol)
in anhydrous Et2O (3.5 mL), maintained under stirring and
argon atmosphere. The reaction mixture was slowly brought
to room temperature (over ca. 1 h), and a saturated solution
of NaH2PO4 (4 mL) was added. The crude product was
extracted with Et2O (3 × 3 mL) and the combined organic
layers were dried over Na2SO4. Evaporation of the solvent
under reduced pressure gave an oily residue which was
purified by column chromatography eluting with petrol/ethyl
acetate 80:20. The isolated (RS,E)-4-[(1S)-isoborneol-10-sul-
finyl]-2-phenyl-3-buten-2-ols (70% total yield, 22/23 70:30) are
reported in order of elution from the column.
Meth yl (RS,E)-3-[(1S)-isobor n eol-10-su lfin yl]-2-p r op e-
n oa te (6Rc): oil; 51% yield; [R]22D -107.6 (c 0.008); 1H NMR δ
7.64 (AB d, J 2,3 14.9, H-3), 6.71 (AB d, J 2,3 14.9, H-2), 4.11 (dd,
J
J
2′,3′ 8.0 and 4.3, H-2′), 3.83 (s, OMe), 3.27 and 2.59 (AB system,
10′A,10′B 13.1, H2-10′), 1.9-1.2 (m, H2-3′,5′,6′, H-4′), 1.08 (s, H3-
8′), 0.85 (s, H3-9′); 13C NMR δ 164.2 (C-1), 149.7 (C-3), 125.9
(C-2), 77.0 (C-2′), 55.0 (C-10′), 52.5 (OMe), 51.6 (C-1′), 48.5 (C-
7′), 45.1 (C-4′), 38.6 (C-3′), 30.8 and 27.2 (C-5′,6′), 20.5 and
19.9 (C-8′,9′); MS m/z 287 (M + 1, 59), 137 (68), 135 (100).
Anal. Calcd for C14H22O4S: C, 58.72; H, 7.75. Found: C, 58.62;
H, 7.74.
Met h yl (SS)-2-[(1S)-isob or n eol-10-su lfin yl]-2-p r op e-
n oa te (8Sc), only picked out in the reaction mixture by typical
1H NMR signals, i.e., δ 6.97 and 6.72 (two br s, H2-3).
Meth yl (SS,E)-3-[(1S)-isobor n eol-10-su lfin yl]-2-p r op e-
(S ,R S ,E )-4-[(1S )-Isob or n e ol-10-su lfin yl]-2-p h e n yl-3-
bu ten -2-ol (22): oil; 49% yield; [R]22D - 100.8 (c 0.002); 1H NMR
δ 7.5-7.3 (m, ArH), 6.75 (AB d, J 3,4 14.7, H-4), 6.58 (AB d, J 3,4
n oa te (6Sc): oil; 33% yield; [R]22 +75.2 (c 0.011); 1H NMR δ
D
(22) Kruse, C. G.; Wijsman, A.; van der Gen, A. J . Org. Chem. 1979,
44, 1847-1851.
(23) Love, B. E.; J ones, E. G. J . Org. Chem. 1999, 64, 3755-3756.
7.72 (AB d, J 2,3 15.0, H-3), 6.68 (AB d, J 2,3 15.0, H-2), 4.07 (dd,
J
2′,3′ 7.6 and 3.7, H-2′), 3.83 (s, OMe), 3.51 and 2.59 (AB system,

Enantiopure Sulfinyl Ketones and Esters
J . Org. Chem., Vol. 66, No. 14, 2001 4851
14.7, H-3), 4.08 (dd, J 2′,3′ 8.0 and 4.3, H-2′), 3.19 and 2.44 (AB
system, J 10′A,10′B 13.2, H2-10′), 1.8-1.1 (m, H2-3′,5′,6′, H-4′), 1.74
(s, H3-1), 1.08 (s, H3-8′), 0.83 (s, H3-9′); 13C NMR δ 145.2 (C-4),
145.0 (C-1"), 130.7 (C-3), 128.9, 127.9, and 125.3 (C-2“-6”), 77.2
(C-2′), 74.8 (C-2), 55.6 (C-10′), 51.7 (C-1′), 48.4 (C-7′), 45.3 (C-
4′), 38.7 (C-3′), 31.0 and 27.4 (C-5′,6′), 30.0 (C-1), 20.7 and 20.1
(C-8′,9′). Anal. Calcd for C20H28O3S: C, 68.93; H, 8.10. Found:
C, 68.62; H, 8.30.
m-CPBA oxidation of sulfoxide 6Ra , following the previously
reported procedure,3a and submitted, without isolation,24 to
nucleophile addition: thus, a solution of 24 (178 mg, 0.51
mmol) in Et2O (1.5 mL) was reacted with 1.22 mmol of MeMgI
in Et2O (1 mL) following the procedure reported above. The
elution of the chromatographic column with petrol/ethyl
acetate 90:10 afforded (E)-4-[(1S)-isoborneol-10-sulfonyl]-2-
phenyl-3-buten-2-ols (50% total yield, 25/26 57:43) which are
reported in order of elution from the column.
(R ,R S,E )-4-[(1S )-Isob or n e ol-10-su lfin yl]-2-p h e n yl-3-
1
bu ten -2-ol (23): oil; 21% yield; H NMR δ 7.5-7.3 (m, ArH),
(S,E)-4-[(1S)-Isobor n eol-10-su lfon yl]-2-p h en yl-3-bu ten -
2-ol (25): low melting solid; 28% yield; [R]24 - 65.8 (c 0.047);
6.74 (AB d, J 3,4 14.7, H-4), 6.62 (AB d, J 3,4 14.7, H-3), 4.12 (dd,
J 2′,3′ 8.1 and 4.1, H-2′), 3.23 and 2.47 (AB system, J 10′A,10′B 13.3,
H2-10′), 1.8-1.1 (m, H2-3′,5′,6′, H-4′), 1.79 (s, H3-1), 1.12 (s,
H3-8′), 0.85 (s, H3-9′). Anal. Calcd for C20H28O3S: C, 68.93; H,
8.10. Found: C, 69.00; H, 8.45.
D
1H NMR δ 7.5-7.3 (m, ArH), 7.11 (AB d, J 3,4 14.8, H-4), 6.75
(AB d, J 3,4 14.8, H-3), 4.13 (m, H-2′), 3.41 and 2.86 (AB system,
J 10′A,10′B 13.6, H2-10′), 1.8-1.3 (m, H2-3′,5′,6′, H-4′), 1.79 (s, H3-
1), 1.07 (s, H3-8′), 0.82 (s, H3-9′): 13C NMR δ 152.5 (C-4), 143.4
(C-1′′), 128.8, 128.0, and 125.0 (C-2“-6”), 127.3 (C-3), 76.2 (C-
2′), 74.1 (C-2), 54.2 (C-10′), 50.7 (C-1′), 49.1 (C-7′), 44.1 (C-4′),
39.0 (C-3′), 30.7 and 27.4 (C-5′,6′), 28.9 (C-1), 20.5 and 19.8
(C-8′,9′). Anal. Calcd for C20H28O4S: C, 65.90; H, 7.75. Found:
C, 66.22; H, 7.81. The same product was obtained by m-CPBA
oxidation of sulfoxide 22.3a
(S,RS,E)- a n d (R,RS,E)-4-[(1S-exo)-2-Bor n ylsu lfin yl]-2-
p h en yl-3-bu ten -2-ols (27) a n d (28). A solution of 7Ra (200
mg, 0.63 mmol) in Et2O (1.4 mL) was reacted with 0.76 mmol
of MeMgI in Et2O (0.63 mL) following the procedure reported
above. Compounds 27 and 28 were isolated (75% total yield,
27/28 50:50) by elution with petrol containing ethyl acetate
1
(20 to 25%). More mobile epimer: oil; 37% yield; H NMR δ
(R,E)-4-[(1S)-Isobor n eol-10-su lfon yl]-2-p h en yl-3-bu ten -
2-ol (26): low melting solid; 21% yield; 1H NMR δ 7.5-7.3 (m,
ArH), 7.10 (AB d, J 3,4 14.8, H-4), 6.74 (AB d, J 3,4 14.8, H-3),
4.13 (m, H-2′), 3.43 and 2.85 (AB system, J 10′A,10′B 14.1, H2-
10′), 1.8-1.3 (m, H2-3′,5′,6′, H-4′), 1.79 (s, H3-1), 1.07 (s, H3-
8′), 0.80 (s, H3-9′). Anal. Calcd for C20H28O4S: C, 65.90; H, 7.75.
Found: C, 65.85; H, 7.81.
7.5-7.3 (m, ArH), 6.67 (AB d, J 3,4 14.9, H-4), 6.49 (AB d, J 3,4
14.9, H-3), 2.62 (dd, J 2′,3′ 9.6 and 6.5, H-2′), 2.3-1.2 (m, H2-
3′,5′,6′, H-4′), 1.73 (s, H3-1), 1.04 (s, H3-10′), 1.00 (s, H3-8′), 0.87
(s, H3-9′); 13C NMR δ 145.0 (C-1"), 144.0 (C-4), 131.8 (C-3),
128.5, 127.5, and 125.1 (C-2′′-6′′), 74.6 (C-2), 71.1 (C-2′), 49.9
(C-1′), 47.4 (C-7′), 39.2 and 27.3 (C-5′,6′), 29.6 (C-1), 28.5 (C-
3′), 20.2 and 19.9 (C-8′,9′), 13.7 (C-10′). Anal. Calcd for
C
20H28O2S: C, 72.25; H, 8.50. Found: C, 72.27; H, 8.88. Less
Ack n ow led gm en t. This work was carried out under
the auspices of the National Project “Stereoselezione in
Sintesi Organica, Metodologie ed Applicazioni” sup-
ported by the Ministero dell’Universita` e della Ricerca
Scientifica e Tecnologica, Rome. Financial support from
the University of Messina is also acknowledged.
1
mobile epimer: oil; 37% yield; H NMR δ 7.5-7.3 (m, ArH),
6.66 (AB d, J 3,4 14.8, H-4), 6.50 (AB d, J 3,4 14.8, H-3), 2.65 (dd,
J 2′,3′ 9.3 and 6.7, H-2′), 2.4-1.2 (m, H2-3′,5′,6′, H-4′), 1.73 (s,
H3-1), 1.01 (s, H3-10′), 1.00 (s, H3-8′), 0.87 (s, H3-9′); 13C NMR
δ 145.0 (C-1"), 144.0 (C-4), 131.6 (C-3), 128.5, 127.5, and 125.0
(C-2′′-6′′), 74.7 (C-2), 71.0 (C-2′), 49.8 (C-1′), 47.4 (C-7′), 39.1
and 27.3 (C-5′,6′), 29.7 (C-1), 28.4 (C-3′), 20.2 and 19.9 (C-8′,9′),
13.7 (C-10′). Anal. Calcd for C20H28O2S: C, 72.25; H, 8.50.
Found: C, 71.98; H, 8.41.
m -CP BA Oxid a tion of 6Ra a n d Rea ction of th e Ob-
t a in ed (E)-3-[(1S)-Isob or n eol-10-su lfon yl]-1-p h en yl-2-
p r op en -1-on e (24) w ith Meth ylm a gn esiu m Iod id e. The
sulfone 24 was obtained in almost quantitative yield by
J O015595A
(24) 1H NMR characterization of sulfone 24: δ 8.02 (m, H-2′′, 6′′),
7.93 (AB d, J 2, 14.9, H-3), 7.44 (AB d, H-2), 7.7-7.5 (m, H-3′′-5′′),
3
4.19 (dd, J 2′, 7.9 and 4.2, H-2′), 3.56 and 2.98 (AB system, J 10′A,
3′
10′B
13.6, H2-10′), 1.9-1.2 (m, H2-3′, 5′, 6′, H-4′), 1.09 (s, H3-8′), 0.85 (s,
H3-9′).