9
608
J . Org. Chem. 1998, 63, 9608-9609
P a lla d iu m Ca ta lyzed Alk yla tion w ith Allylic
Aceta tes u n d er Neu tr a l Con d ition s
Sch em e 1
Giuliano Giambastiani and Giovanni Poli*
Dipartimento di Chimica Organica “Ugo Schiff” and Centro
CNR di Studio per la Chimica e la Struttura dei Composti
Eterocicli e loro Applicazioni, Via G. Capponi 9, I-50121,
Firenze, Italy
Sch em e 2
Received August 10, 1998
The palladium catalyzed allylic alkylation of soft nucleo-
philes represents one of the most useful organic transforma-
tions.1 During our recent studies in palladium-catalyzed
intramolecular allylic alkylations of activated carboxamides,2
we noticed that small amounts of cyclization product could
be intriguingly attained even in the absence of the enolizat-
3
ing system BSA/AcOK (cat.). In order to shed light on this
intriguing result, we decided to examine simple intermo-
lecular reactions either in the presence of BSA/AcOK cat.
(
1
method A) or under base-free conditions (method B) (Scheme
).
4
When methyl nitroacetate was added to cinnamyl acetate
the allylic alkylation proceeded only under base-free condi-
5
tions (Table 1, entries 1-3). A similar trend was observed
in the addition of sulfonyl nitromethane to cinnamyl acetate
(
entries 6 and 7). When bis(phenylsulfonyl)methane was
reacted with cinnamyl acetate or geranyl acetate, adducts
ca or 3cb were respectively obtained with either method
entries 8-11). Methyl (phenylsulfonyl)acetate and ethyl
6
7
has ample precedents with allylic carbonates, phenoxides,
8
and oxiranes, since the pKa values of the alcoholic species
generated therefrom, i.e., of the conjugated acid of the
displaced group, are unequivocally much higher than those
of the active methylenes. On the other hand, a similar
reasoning cannot be applied to allylic acetates.
3
(
acetoacetate behaved analogously (entries 14-17). Malono-
nitrile afforded exclusively the diallylated adduct 4fa with
method A, whereas base-free conditions gave the monoal-
lylated product 3fa as the only new product (entries 18 and
+
-
The addition of 1 mol equiv of n-Bu4N AcO to a CDCl3
solution of the disulfone 1c or ethyl acetoacetate caused the
immediate and total disappearance of their respective me-
thylene singlets in the 1H NMR spectra. When the same
experiment was repeated with the less acidic diethyl mal-
onate, such an effect was totally absent. This result suggests
that the acetate anion can readily engage in deprotonation
substrates of suitable pKa value to give rapidly equilibrating
species. The reaction appears also to be dramatically de-
pendent on the nature of the phosphine used. Thus, when a
bis-coordinating phosphine such as BINAP9 or DPPE was
used instead of PPh3 as the ancillary ligand, the reaction
between methyl nitroacetate and the acetate 2a resulted
seriously or totally inhibited, respectively (entries 4 and 5).
The results so far obtained may be well rationalized accord-
ing to the mechanistic path shown in Scheme 2.
1
9). High proportions, or even exclusive formation, of the
diallylated adduct were also obtained with Meldrum’s acid
and barbituric acid under base-free conditions (entries 20-
2
malonate and cinnamyl acetate took place only in the
presence of the BSA/AcOK catalytic system (entries 24 and
2
new method can be reasonably accounted for by assuming
that the leaving group displaced from the allylic system is
capable of acting as the deprotonating species. Such an event
3). The condensation between the less acidic diethyl
5). The results of Table 1 suggest that the success of this
*
To whom correspondence should be addressed. E-mail: poli@
risc1.chimorg.unifi.it.
1) (a) Hegedus L. S. In Organometallics in Synthesis; Schl o¨ sser, M., Ed.;
Wiley: New York, 1994; Chapter 5, pp 385-459. (b) Tsuji, J . Palladium
Reagents and Catalysts; Wiley: New York, 1995. (c) Heck, R. F. Palladium
Reagents in Organic Synthesis; Academic Press: New York, 1985. (d) Frost,
C. G.; Howarth, J .; Williams, J . M. J . Tetrahedron: Asymmetry 1992, 3,
(
Oxidative addition of (Ph3P)2Pd(0) onto the allylic acetate
generates first a cationic π-allyl palladium complex. Coun-
terion exchange between the acetate and the nucleophile
anion at the π-allyl palladium complex (I f II, Scheme 2)
can then take place.10 The above-mentioned inhibition by
BINAP or DPPE suggests that such a process may pass
through competitive coordination at the metal center be-
tween the nucleophiles and the phosphines, at least for those
1
089. (e) Harrington P. J . In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995;
Vol. 12, Chapter 8.2, pp 798-903. (f) Moreno-Ma n˜ as, M.; Pleixats, R. Adv.
Heterocycl. Chem. 1996, 66, 73.
(2) Poli, G.; Giambastiani, G.; Pacini, B.; Porcelloni, M. J . Org. Chem.
1
998, 63, 804.
(
(
3) Trost, B. M.; Murphy, D. J . Organometallics 1985, 4, 1143.
4) To the best of our knowledge, we could find only two nonrationalized
precedents of Pd(0)-catalyzed allylic alkylations using allylic acetates in
the absence of bases. (a) Moreno-Ma n˜ as, M.; Prat, M.; Ribas, J .; Virgili, A.
Tetrahedron Lett. 1988, 29, 581. (b) Atkins, K. E.; Walker, W. E.; Manyik,
R. M. Tetrahedron Lett. 1970, 11, 3821.
(6) Tsuji, J .; Minami, I. Acc. Chem. Res. 1987, 20, 140.
(7) Tsuji, J .; Okumoto, H.; Kobayashi, Y.; Takahashi, T. Tetrahedron Lett.
1981, 22, 1357.
(8) Tsuji, J .; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981, 22, 2575.
(9) Wagaw, S.; Rennels, R. A.; Buchwald, S. L. J . Am. Chem. Soc. 1997,
119, 8451.
a
(5) Sources of the pK values reported in Table 1. (Phenylsulfonyl)-
nitromethane, barbituric acid, malononitrile, Meldrum’s acid, bis(phenyl-
sulfonyl)methane, ethyl acetoacetate, diethyl malonate: (a) Bordwell, F.
G. Acc. Chem. Res. 1988, 21, 456. Ethyl nitroacetate: (b) Hashida, Y.;
Kobayashi, M.; Matsui, K. Bull. Chem. Soc. J pn. 1971, 44, 2506. (c) Pearson,
R. G.; Dillon, R. L. J . Am. Chem. Soc. 1953, 75, 2439. The pK
methyl phenylsulfonyl acetate and of ethyl nitroacetate in DMSO have been
estimated.
a
values of
(10) In a recent example of palladium-catalyzed C-Mitsunobu condensa-
tion a similar palladium complex has been postulated: Shing, T. K. M.; Li,
L.-H.; Narkunan K. J . Org. Chem. 1997, 62, 1617.
1
0.1021/jo981599c CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/08/1998