0 Copyright 1995 American Chemical Society
Volume 14, Number 7, January 7995
Communications Mechanism of the Palladium-CatalyzedElimination of Acetic Acid from Allylic Acetates Pher G. Andersson" and Szymon Schab Department of Organic Chemistry, University of Uppsala, Box 531, S-751 21 Uppsala, Sweden Received May 31, 1994@ Summary: The mechanism of the palladium-catalyzed elimination of acetic acid from allylic acetates has been studied. It was found that this process can take place not only via conventional syn elimination of palladium hydride but also via an anti elimination pathway.
Introduction. The palladium-catalyzed elimination of acetic acid from allylic acetates was first developed by Tsujil and Trost2and has since then become a useful synthetic route to 1,3-dienes. This reaction (eq 1) has
L
1
been thought to proceed via a p-elimination from the intermediate (a-ally1)palladium complex 1, but the mechanism has never been subject to closer investigation. In this communication we present results which show that an anti elimination is an important pathway. During our development of palladium-catalyzed anAbstract published in Aduance ACS Abstracts, December 1,1994. (1)Tsuji, J.;Yamakawa, T.; Kaito, M.; Mandai, T. Tetrahedron Lett. 1978,2075. (2)Trost, B. M.; Verhoeven, T. R.; Fortunak, J. M. Tetrahedron Lett. 1979,2301. @
nulation chemistry3 we prepared some of the requisite diene starting materials via the route outlined in Scheme 1. Palladium-catalyzed elimination of HOAc from the cis-acetate 3 under standard conditions4 resulted in a 5:l mixture of the two dienes 4 and 5. During the optimization of the reaction conditions several bases were tried and it was found that sterically hindered amines favored the formation of 4. Thus, triisobutylamine gave a 7:l ratio between 4 and 5. We have now undertaken further studies of this elimination and found that the ratio of 4 and 5 can be further shifted, depending on which base is used; for example, the use of DBU resulted in a very much faster reaction rate and the ratio of 4 and 5 in the isolated product was >25:1. These findings suggest that the base is at least in part responsible for the proton abstraction, a result which stands in sharp contrast to the commonly accepted syn p-elimination mechanism in which the base does not participate in the elimination step. In order to gain further insight into the mechanism, trans-acetate 6 was synthesized via an sN2 displacement of allylic chloride 2 with sodium mal~~~~~
~
~
(3)(a) Backvall, J.E.; Andersson, P. G.; VAgberg, J. 0. Tetrahedron Lett. 1989,30,137. (b) Backvall, J.E.; Andersson, P. G. J.Am. Chem. SOC.1990,112, 3683. (c) Backvall, J. E.; Andersson, P. G.; Stone, G. B.; Gogoll, A. J. Org. Chem. 1991,56, 2988. (d) Backvall, J. E.; Andersson, P. G. J . Am. Chem. SOC.1993,114,6374. (e) Backvall, J. E.; Granberg, K. L.; Andersson, P. G.; Gatti, R.; Gogoll, A. J . Org. Chem. 1993,58,5445. (4)The acetate (1equiv) was dissolved in toluene under a nitrogen atmosphere. To this solution were added Pd(dba)z (0.02equiv), dppe (0.04equiv), and triethylamine (1.5equiv). The resulting solution was heated to reflux until the reaction was complete.
0276-733319512314-0001$09.00/0 0 1995 American Chemical Society
2 Organometallics, Vol. 14, No. 1, 1995
Communications
Scheme l a
Scheme 2. Elimination Pathways for 3 and 6
DC‘aCHY
AcO
A d
AcO
OHE2 3
3
2
[pp-’] anti I syn
Legend: Nu = 0, NR; E = C02Me; X = C1, RO, RC02; Y = RCOz a
/
Table 1. Palladium-CatalyzedElimination of Acetates 3 and 6a time (fin) 0 5 10 15 30 45 60 90 120 240 480
acetates 3 6 95.8 81.4 74.2 63.7 31.6 0
4.2 4.1 3.8 3.2 2.1 0
dienes 4
5
0 1.6 19.6 29.3 58.3 88.2
0 0.9 2.4 3.8 8.0 11.8
acetates 3 6 5.1 5.5 5.4 5.3 5.0 4.6 4.3 3.8 2.8 0.5 0
94.3 93.9 93.8 93.1 91.5 88.2 83.5 16.4 59.3 26.1 0
uCH
0 C H E z
\
4
5
anti I svn
dienes 4
5
0 0.4 0.5 1.0 1.9 4.8 7.9 12.9 23.1 46.6 62.1
0 0.2 0.3 0.6 1.6 2.4 4.3 6.9 14.8 26.2 31.9
AcO
6
Scheme 3. Trapping of the Intermediate z-Allyl Complep
The acetate 3 or 6 (1 equiv) was dissolved in toluene under a nitrogen atmosphere. To this solution were added Pd(dba)Z (0.02 equiv), dppe (0.04 equiv) and triisobutylamine(1.5 equiv). The resulting yellow solution was heated to reflux and monitored by GC until the reaction was completed.
~ n a t e .If~ the diene formation were t o proceed via p-elimination of palladium hydride, this substrate would be expected to give rise to diene 4 exclusively, since only one hydrogen would be syn to palladium in the intermediate o-allyl complexes. However, in contrast with such a prediction, a substantially greater amount of diene 5 was formed when 6 was reacted under the same conditions as 3. As mentioned above, reaction of 3 in toluene at reflux in the presence of Pd(dba)2, 1,2-bis(dipheny1phosphino)ethane(dppe) and triisobutylamine gave a 7:l mixture of 4 and 5 after 45 min (Table 1). When 6 was reacted under the same conditions, the corresponding value was 1.6:l. It is known that allylic acetates can isomerize in palladium(0)-catalyzed reactions.2 This isomerization takes place via a syn migration of acetate from palladium to carbon in the allyl intermediate t o give the stereoisomeric acetate. To ensure that this pathway was not operative here, the reactions were followed by GC, which showed that no isomerization of the starting material took place during the reaction (Table 1). Another possible isomerization pathway involves s N 2 attack by “free Pd(0)” on the (mally1)palladiumcomplex and results in a new palladium species in which the configuration at the n-allyl is now inverted.6 This isomerization is, however, known to be efficiently inhibited by the use of a bidentate phosphine ligand such A control experiment was performed in as ( 5 ) Backvall, J. E.; VBgberg, J. 0. Org. Synth. 1990,69,38.
(6)(a)Moreno-Mafias, M.; Ftibas, J.; Virgili, A. J . Org.Chem. 1988, 22, 5328. (b) Backvall, J . E., Granberg, K. L.; Heumann, A. Isr. J. Chem. 1991,31,17.(c) Granberg, K. L.; Blckvall, J. E. J . Am. Chem. Soc. 1992,114,6858.(d) Stary, I.; Zajicek, J.;Kocovsky, P. Tetrahedron 1992,48,7229. (7)The spectral data of compounds 7 and 8 were identical with those reported in the literature: Backvall, J. E.; Juntunen, S. K. J . Am. Chem. SOC.1987,109,6396.
w
x A
_I”
6 (95% trans)
1id
1
L2‘
I”
8 (94% trans)
“To a THF solution of the acetate (3 or 6) was added Pd(OAc)z 0.05 equiv) and dppe (0.10 equiv) under a n atmosphere of nitrogen. The resulting solution was heated to reflux for 1 h after which a THF solution of sodium malonate was added. After the reaction was complete, the crude product was analyzed by NMR and GC.
which the intermediate n-allyl complex was trapped with sodium malonate after 1h of reflux. Trapping the n-allyl complex derived from acetates 3 and 6, respectively, produced the correspondingbis(malonates) 7 and 8 in a highly stereospecific manner, confirming that no isomerization of the (n-ally1)palladium complex had o~curred.~ Conclusion. The above-mentioned findings strongly suggest that an anti-elimination pathway can operate in the palladium-catalyzed elimination of allylic acetates. A probable mechanism would be a base-assisted 1,2-diaxial elimination of the proton and Pd(0) from a (o-a1lyl)palladium intermediate (cf. Scheme 21, which nicely explains the effect of the base on the regiochemical outcome of the reaction.
Acknowledgment. Financial support &om the Swedish Natural Science Research Council is gratefully acknowledged. S.S. thanks the Swedish Institute for a fellowship. We are grateful to Prof. J. E. Backvall and Dr. D. Tanner for helpful discussions and to Johnson Matthey for a generous gift of palladium chloride. OM9404083
