6372
O. Arjona et al. / Tetrahedron Letters 44 (2003) 6369–6373
ratio could not be modified in favor of the E isomer by
Acknowledgements
prolonged heating or by adding larger amounts of thiolate
(which caused only an increase of the double addition
product, the dithioacetal). We assume, therefore, that the
Z/E equilibrium position for most RS–CHꢁCH–COOMe
adducts is nearly the above-mentioned 18:82 ratio. In sharp
contrast, for RO–CHꢁCH–COOR and R2N–CHꢁCH–
COOR, Z/E ratios of ca. 0:100 are observed (for a classical
review, see: Perlmutter, P. Conjugate Addition Reactions in
Organic Synthesis, Pergamon Press: Oxford, 1992).
5. In the absence of a base (catalyst), the reactions were much
slower and poor yields of adducts were generally obtained
after 5 h of reaction, unless the solutions were concentrated
or heated. Stereoselectivities of 90:10 or higher were usually
obtained. It is worth noting that in the base-catalyzed
additions too long reaction times were detrimental. Thus,
with DMAP a dismutation took place in some cases (e.g.
in the case of 1a, stirring for 20 h afforded a mixture of
2a, starting material 1a and dithioacetal in a 2:1:7 ratio)
and a retroaddition occurred mainly in others (e.g. in the
case of 1e, stirring for 4 days gave only a 40% of 2e with
recovery of starting material). With 20 mol% of Et3N, the
Z/E ratios decreased to 68:32 in two experiments. With
Me3P, too long reaction times caused a stereoselectivity
loss (e.g. after 20 h, a 86:14 Z/E mixture of 2a was
converted to a 75:25 mixture).
Financial support from the Ministerio de Ciencia y
Tecnolog´ıa (Grants BQU2000-0653 and PB98-1272) is
acknowledged. Thanks are also to Professor Dr.
Joaqu´ın Plumet for fruitful discussions.
References
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Jpn. 1974, 47, 2325 (addition to ArCꢀC-COR). For related
works, see: (g) Truce, W. E.; Onken, D. W. J. Org. Chem.
1975, 40, 3200; (h) Lucchi, O. D.; Lucchini, V.; Marchioro,
C.; Valle, G.; Modena, G. J. Org. Chem. 1986, 51, 1457;
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C.; Vo¨gtle, F. Org. Lett. 2000, 2, 593, and Ref. 9 therein.
For the preparation of dithioacetals, see: (l) Cossu, S.;
Lucchi, O. D.; Fabris, F.; Ballini, R.; Bosica, G. Synthesis
1996, 1481, and Refs. 5 and 6 therein; (m) Kuroda, H.;
Tomita, I.; Endo, T. Synth. Commun. 1996, 26, 1539; (n)
Kuroda, H.; Tomita, I.; Endo, T. Polymer 1997, 38, 6049.
3. Arjona, O.; Iradier, F.; Medel, R.; Plumet, J. J. Org. Chem.
1999, 64, 6090.
4. In our hands, benzenemethanethiol (1a) reacts completely,
in CH3CN at 0°C, within 15 min in the presence of 20 mol%
of Et3N or DMAP, with an equivalent amount of methyl
propynoate (HCꢀC-COOMe) to afford ca. 65:35 ratios of
the Z/E adducts (isomer Z, l 7.07 and 5.82, J=10.0 Hz;
isomer E, l 7.70 and 5.81, J=15.2 Hz). No significant
changes in these Z/E ratios were obtained by performing
the reaction of 1a and HCꢀC-COOMe in the presence of
only 1 mol% of Et3N and/or by using absolute EtOH or
THF instead of CH3CN. Without Et3N or DMAP, the
reaction was very slow (several days of reaction were
required for its completion). On the other hand, by heating
a 65:35 Z/E adduct mixture with a small amount of
benzenemethanethiolate ion (NaSCH2Ph, 10 mol%) for
few hours, a new ratio of 18:82 (Z/E) was obtained; this
6. DMAP and R3P may act as basic catalysts (B of Scheme
1), to afford intermediates 3, and/or as nucleophilic cata-
lysts (Nu), with previous conjugate addition to the triple
bond, followed by proton transfer from thiol to give
intermediate 4. Complex adduct mixtures might be
expected. However, even in the case of Nu=Me3P, which
could be prone to give byproducts arising from the attack
of RS− at position a of 4, we did not observe these
byproducts (probably because our reaction conditions are
very mild).
For ‘anomalous’ reactions of 2-alkynoates catalyzed by
Bu3P or Ph3P (a- or g-addition instead of b-addition), see:
(a) Trost, B. M.; Li, C.-J. J. Am. Chem. Soc. 1994, 116,
3167; (b) Alvarez-Ibarra, C.; Csa´ky, A. G.; Oliva, C. G.
Tetrahedron Lett. 1999, 40, 8465; (c) Liu, B.; Davis, R.;
Joshi, B.; Reynolds, D. W. J. Org. Chem. 2002, 67, 4595,
and refs. cited therein; (d) Lu, X.; Zhang, C.; Xu, Z. Acc.
Chem. Res. 2001, 34, 535; (e) Lu, C.; Lu, X. Org. Lett. 2002,
4, 4677. Also see: (f) Back, T. G.; Wehrli, D. Tetrahedron
Lett. 1995, 36, 4737, and Ref. 2c.
7. That the S-Tosvinyl group had always configuration Z
whereas the O-Tosvinyl group was a 85:15 Z/E mixture
could be confirmed by allowing 1i to react with 210 mol%
of tosylacetylene in the presence of 20 mol% of DMAP.
The O,S-diprotected derivative 5 was formed quantita-
tively and could be easily analyzed by NMR to be the
above-mentioned mixture of only two stereoisomers (the
ZZ one as the major compound).
8. The DMAP-catalyzed (largely Nu-catalyzed) protection of
phenols and catechols with alkyl propynoates is known:
Ariza, X.; Pineda, O.; Vilarrasa, J.; Shipps, G. W.; Ma, Y.;
Dai, X. Org. Lett. 2001, 3, 1399.