unprotected hydroxyl compound 3c reacted to provide the
allylic diol 4c in >50% yield. In each case, the diastereo-
selectivity was modest at best, providing a 2:1 ratio of syn
and anti stereoisomers. It appears that the reactivity of these
substrates is subject to both the electronic and steric nature
of the allylic functionality. To test the electronic effect of
the acetoxy-protecting group, a competition study was carried
out between allylic acetate 1a and allylic alcohol 1c. A 1:1
mixture of each vinyl halide was subjected to the coupling
conditions with hydrocinnamaldehyde (0.5 equiv). The ratio
of products (2a/2c) was greater than 10:1. Therefore, the lack
of reactivity of protected substrates 3a and 3b relative to
free hydroxyl 3c must be attributed to steric effects.
Table 1. Coupling Reactions between Vinyl Halides and
Aldehydes
We fully expect the allylic acyloxy products 2 to be ideal
substrates for subsequent carbon-carbon bond formation
particularly through Pd(0)-mediated reactions, Scheme 3.
Scheme 3
alcohol products.4 As can be seen from Table 1, 2-bromoallyl
acetate 1a reacts efficiently with a variety of aromatic and
aliphatic aldehydes to afford the resulting allylic alcohols in
good yield, typically on the order of 80-90%. Coupling to
aromatic aldehydes tended to produce lower yields of the
desired product presumably due to the decreased stability
of these products under the reaction conditions. Elimination
does not appear to compete with the aldehyde coupling
pathway, although products arising from elimination of
acetate (allene) would not be isolable due to volatility. To
quantify the potentially small degree of elimination that may
be occurring, we chose to explore the related coupling
reaction using 2-bromoallyl benzoate 1b (entry 6). The
coupling proceeded efficiently yielding the corresponding
allylic alcohol in 77% yield. Unreacted vinyl bromide was
easily recovered. Moreover, we were unable to detect any
benzoic acid, a product of elimination, under careful analysis
of the crude reaction mixture.
Tamaru has recently developed conditions for the conversion
of electrophilic π-allylpalladium species to allylic nucleo-
philes using diethylzinc.5 The proposed mechanism involves
a transmetalation step between the π-allylpalladium and
diethylzinc to form an allylzinc species, the presumed active
allylating agent.
In fact, exposure of allylic benzoate 5 to these conditions
in the presence of either benzaldehyde or cyclohexanecar-
boxaldehyde efficiently provided alcohol 6 with fair 1,4
stereoinduction (75:25 syn/anti). Previous work from Mulzer6
and Paquette7 have shown selectivities that range from 5:1
to 99:1 for coupling reactions using similar allylic chromium
and indium reagents generated from the corresponding allylic
bromides.
In an attempt to induce stereoselectivity in the newly
formed chiral center, we have explored coupling reactions
with substrates containing an allylic stereogenic center. Much
to our surprise, vinyl iodide 3a did not react even under
forcing conditions, Scheme 2. In contrast, allylic ether 3b
did react with hydrocinnamaldehyde to provide the product
diol 4b, albeit in low (15-20%) yield. Moreover, the
The successful application of the Nozaki-Hiyama-Kishi
coupling of 2-bromoallyl acetate to aldehydes represents a
practical, ambient temperature alternative to allyl alcohol
(4) Stamos, D. P.; Sheng, X. C.; Chen, S. S.; Kishi, Y. Tetrahedron Lett.
1997, 62, 6355-6358.
Scheme 2
(5) (a) Yasui, K., Goto, Y.; Yajima, T.; Taniseki, Y.; Fugami, K.; Tanaka,
A.; Tamaru, Y. Tetrahedron Lett. 1993, 34, 7619-7622. (b) Tamaru, Y.;
Tanaka, A.; Yasui, K., Goto, S.; Tanaka, S. Angew. Chem., Int. Ed. Engl.
1995, 43, 787-789. (c) Shimizu, M.; Kimura, M.; Tanaka, S.; Tamaru, Y.
Tetrahedron Lett. 1998, 39, 609-612.
(6) Maguire, R. J.; Mulzer, J.; Bats, J. W. J. Org. Chem. 1996, 61, 6936-
6940.
(7) Paquette, L. A.; Bennett, G. D.; Chhatriwalla, A.; Isaac, M. B. J.
Org. Chem. 1997, 62, 3370-3374.
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Org. Lett., Vol. 1, No. 3, 1999