On the Nature of the Catalytic Palladium-Mediated Elimination of Allylic Carbonates and Acetates To Form 1,3-Dienes

Full text of DOI:10.1021/ja962313t

5956
J. Am. Chem. Soc. 1997, 119, 5956-5957
several reaction conditions, including those commonly employed
for the preparative reactions. For example, treatment of 6b with
0.1 equiv of [Pd(OAc)2, 10 PPh3, dioxane, 100 °C]2 affords a
5.4 ( 0.6:1 ratio of 9:10 and 0.1 equiv of [Pd(PPh3)4, THF, 65
°C]3 affords a 6.9 ( 0.6:1 mixture.10,11
On the Nature of the Catalytic Palladium-Mediated
Elimination of Allylic Carbonates and Acetates To
Form 1,3-Dienes
James M. Takacs,* Edward C. Lawson, and Francis Clement
Department of Chemistry, UniVersity of Nebraska-Lincoln
Lincoln, Nebraska 68588-0304
ReceiVed July 8, 1996
The palladium-catalyzed elimination of allylic alcohol deriva-
tives to form 1,3-dienes is a well-known synthetic transforma-
tion. In conjunction with studies on the telomerization of 1,3-
butadiene Smutny reported what may be the earliest preparative
procedure, the (Ph3P)4Pd-catalyzed elimination of an octadienyl
phenyl ether to 1,3,7-octatriene.1 In the late 1970s Tsuji2 and
Trost3 introduced popular variants of the reaction, employing
an allylic acetate as the substrate. More recently, it was reported
that allylic carbonates react under yet milder conditions,4
particularly using the very efficient 1:1 Pd(OAc)2:PBu3 catalyst
system introduced by Tsuji and co-workers.5 This latter catalyst
system shows unusual regioselectivity in the elimination of
certain cyclic allylic carbonates6 and should be considered the
current method of choice for the palladium-catalyzed elimination
of allylic alcohol derivatives.
We became interested in the details of this reaction as a result
of other studies in our labs7 and prepared allylic carbonate 1a
and two isotopically labeled derivatives (i.e., 1b and 1c).
Palladium-catalyzed elimination of 1a under the Tsuji conditions
(0.10 equiv of [Pd(OAc)2/PBu3], THF, 25 °C, 12 h) affords
4-methyl-2,4-heptadiene (2) as a 1.3:1 mixture of isomers about
the trisubstituted double bond. The 13C-labeled derivative 1b
affords a similar mixture of heptadienes, wherein the 13C-label
is roughly equally distributed between C(2) and C(6). The
distribution of the 13C label is consistent with the reaction
proceeding via a symmetric intermediate such as 3. The
deuterated derivative 1c affords dienes 4 and 5 in greater than
a 5:1 ratio, indicating a large preference for the loss of hydrogen
over deuterium under these conditions.
The reaction of 6 presumably proceeds via the formation of
η3-allylpalladium intermediates 7 and 8, which may interconvert
under the reaction conditions. Figure 1 illustrates three possible
pathways (A-C) for the formation of dienes 9 and 10 from 7
and 8. The generally accepted mechanism (pathway A) involves
isomerization to an η1-allylpalladium complex (e.g., 11) fol-
lowed by â-hydride elimination. However, kinetic isotope
effects for a number of â-hydride eliminations have been
reported, and the values are generally small, for example, in
trans-[(CD3CH2)2Pd(PMePh2)2] (1.4 ( 0.1),12 trans-[CD3CH2-
Pt (PEt3)2Cl] (2.5 ( 0.2),13,14 and n-C6H13C(H)DCH2Ir(PPh3)2-
CO (2.3 ( 0.2).15 The relatively large isotope effects that we
observe in the reactions of 1c and 6 argue against pathway A16
but would be consistent with a pathway that proceeds via a more
nearly linear C-H(D) bond cleavage transition state. Specific
base promoted elimination (pathway B) and the general base
promoted elimination (pathway C) could accommodate such a
transition state. It should be noted that Keinan11 proposed a
cyclic elimination mechanism (i.e., a specific base promoted
elimination analogous to pathway B) for the palladium-catalyzed
elimination of allyl acetates promoted by unsaturated organo-
metallic reagents. Furthermore, Andersson17 recently reported
(8) Allylic carbonate 6a was prepared in high isotopic purity via addition
of methyl-d3-magnesium iodide (Aldrich Chemicals. 99+ atom % D) to
trans-4-phenyl-3-butene-2-one (THF, -78 to 0 °C, 85%), followed by low
temperature acylation (EtOCO2Cl, THF, -78 to 25 °C, 12 h, 70%) of the
lithium alkoxide derived from the tertiary alcohol. 6a is relatively labile
and used without further purification.
(9) The ratio of 9:10 is determined by integration of the deuterium NMR
spectrum, and the result (8.6 ( 0.5:1) is the average of three independent
experiments. It should be noted that the CH3 and CD3 moieties occupy
chemically different environments in the postulated η3-allylpalladium
intermediates 7 and 8; one being exo with respect to the palladium complex
and the other being endo. Consequently, the ratio of 9:10 may be influenced
by an inherent preference for elimination from the exo (endo) position unless
7 and 8 interconvert fast relative to elimination. However, this factor alone
cannot account for the strong preference for the formation of 9 and does
not affect the arguments that follow.
To confirm the high isotope effect observed for compound
1c, we prepared the isotopically labeled allylic carbonate 6a.8
Palladium-catalyzed elimination of 6a (0.10 equiv of [Pd(OAc)2/
PBu3], THF, 25 °C, 8 h) affords a mixture of dienes 9 and 10
in the ratio of 8.6 ( 0.5:1.9 Again, in the internal competition
between loss of hydrogen versus deuterium, loss of hydrogen
is strongly preferred. Large isotope effects are also observed
in the palladium-catalyzed elimination of allylic acetate 6b under
(10) In the course of a related study, Keinan and co-workers (following
reference) reported a much lower isotope effect (kH/kD ) 2.8) for an
intermolecular competition between perhydro- and perdeutero linalyl
acetates. The competition was carried out using Pd(PPh3)4 in CDCl3, which
are not typical conditions for the palladium-catalyzed elimination. We also
observe a relatively low isotope effect for the reaction of 6b under these
conditions (0.1 equiv of Pd(PPh3)4, CDCl3, 65 °C, 9:10 ) 2.8 ( 0.2:1).
(11) Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J. J. Am. Chem. Soc.
1994, 116, 11151-2.
(1) Smutny, E. J. Am. Chem. Soc. 1967, 89, 6793.
(2) Tsuji, J.; Yamakawa, T.; Kaito, M.; Mandai, T. Tetrahedron Lett.
1978, 2075-8.
(12) Ozawa, F.; Ito, T.; Yamamoto, A. J. Am. Chem. Soc. 1980, 102,
6457-63.
(3) Trost, B. M.; Verhoeven, T. R.; Fortunak, J. M. Tetrahedron Lett.
1979, 2301-4.
(13) Brainard, R. L.; Whitesides, G. M. Organometallics 1985, 4, 1550-
7.
(4) Takahashi, T.; Nakagawa, N.; Minoshima, T.; Yamada, H.; Tsuji, J.
Tetrahedron Lett. 1990, 31, 4333-6.
(14) Romeo, R.; Alibrandi, G.; Scolaro, L. M. Inorg. Chem. 1993, 32,
4688-94.
(5) Mandai, T.; Matsumoto, T.; Tsuji, J.; Saito, S. Tetrahedron Lett. 1993,
34, 2513-16.
(15) Evans, J.; Schwartz, J.; Urquhart, P. W. J. Organomet. Chem. 1974,
81, C37-9.
(6) Mandai, T.; Matsumoto, T.; Nakao, Y.; Teramoto, H.; Kawada, M.;
Tsuji, J. Tetrahedron Lett. 1992, 33, 2549-52.
(7) Takacs, J. M.; Clement, F.; Zhu, J.; Chandramouli, S.; Gong, X. J.
Am. Chem. Soc. In press.
(16) For similar arguments in a related palladium-catalyzed reaction,
see: Chrisope, D. R.; Beak, P.; Saunders, W. H. J. Am. Chem. Soc. 1988,
110, 230-8.
(17) Andersson, P. G.; Schab, S. Organometallics 1995, 14, 1-2.
S0002-7863(96)02313-X CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 25, 1997 5957
that the palladium-catalyzed elimination of allylic acetates was
promoted by DBU and that in the presence of DBU a general
base promoted elimination (analogous to pathway C) must
constitute an important reaction pathway.
Scheme 1. The Diastereospecific Synthesis of Allylic
Carbonate 14a
a Conditions: (a) 1 equiv of BF3-OEt2, CH2Cl2, -50 °C, 48 h; (b)
excess Jones reagent, acetone, 0 °C, 1 h; (c) 1.2 equiv of TIPSCl, Et3N,
CH2Cl2, 0 °C, 3 h; (d) (1) 1.5 equiv of TBDMSCl, 1.1 equiv of
KHMDS, THF, -78 to 25 °C, 12 h (2) PhH, reflux, 12 h; (e) 2.2 equiv
of Bu4NF, THF, 25 °C, 15 min; (f) excess I2, Et2O, saturated aqueous
NaHCO3, 0 °C, 5 h; (g) 3 equiv of NaHCO3, acetone, reflux, 12 h; (h)
2.2 equiv of LAH, Et2O, 0 °C, 1 h; (i) 1 equiv of TBDMSCl, 0.1 equiv
of DMAP, 1 equiv of Et3N, CH2Cl2, 25 °C, 12 h; (j) EtOCO2Cl, 0.1
equiv of DMAP, 4 equiv of C5H5N, THF, 0-25 °C.
Figure 1. Three possible pathways for the loss of a hydrogen from a
η3-allylpalladium complex, illustrated by the conversion of 7 and/or 8
to dienes 9 and 10.
â-hydride or specific base promoted elimination (Figure 1,
pathways A and B), would have led to the isomeric cyclohexa-
diene 16.
To further distinguish between the potential pathways for the
elimination, we synthesized the cyclic allylic carbonate 14 and
examined its elimination under the Tsuji conditions. The
addition of palladium(0) to the allylic carbonate is expected to
be stereospecific and anti; that is, addition to allylic carbonate
14 should afford an intermediate η3-allyl palladium complex
with the relative stereochemistry shown in 15. Note that the
only two hydrogens in 15 can be lost to form diene products.
These methine hydrogens are essentially identical except for
the remote substitution and their disposition relative to pal-
ladium; that is, one will reside syn to palladium, the other anti.
Pathways A and B (Figure 1) require syn elimination of the
elements LnPd(X)-H, while pathway C is likely to proceed
predominantly via an anti elimination of those elements.
The diastereoselective synthesis of 14 is worthy of comment.
A number of approaches were explored, and the successful route
is shown in Scheme 1. BF3-catalyzed Diels-Alder cycload-
dition of 1-acetoxy-1,3-butadiene with crotonaldehyde20 fol-
lowed by oxidation with Jones reagent affords 18. It proved
necessary to protect the carboxylic acid as the OTIPS ester in
order to carry out the ensuing enolate Claisen rearrangement.21
After protection, stereospecific [3,3]-rearrangement via an
intermediate silyl ketene acetal followed by hydrolysis of the
silyl esters affords the diacid 19. Group selective iodolacton-
ization22,23 via the more favorable 5-exo mode affords the
intermediate cis-fused bicyclic lactone 20. Upon treatment with
base 20 undergoes a relatively little used, but facile, decar-
boxylative elimination24 to afford the unsaturated bicyclic
lactone 21. LAH reduction of the lactone, followed by selective
protection of the primary alcohol with TBDMSCl and acylation
of the remaining secondary alcohol, affords the desired allylic
carbonate 14.
In summary, the palladium-catalyzed eliminations of deuter-
ated allylic carbonates 1c and 6a proceed with a large preference
for loss of hydrogen over deuterium using Tsuji’s 1:1 Pd(OAc)2:
PBu3 catalyst. Furthermore, the deuterated allylic acetate 6b
undergoes palladium-catalyzed elimination with a similarly high
isotope effect under conditions that are typical for preparative
reactions. The palladium-catalyzed elimination of the cyclo-
hexenyl carbonate 14 affords cyclohexadiene 17 resulting from
the overall syn-elimination of the elements H-O2COR. These
results are not consistent with a commonly accepted mechanism
wherein hydrogen is lost via â-hydride elimination; instead, it
can be rationalized via stereospecific anti-addition of LnPd(0)
to the allylic carbonate followed by stereospecific base promoted
anti-elimination of the elements LnPd(X)-H (Figure 1, path C).
The major concern in carrying out such a test of stereospeci-
ficity is the potential for palladium to scramble between the
diastereomeric faces of the allyl system.18 If scrambling were
to occur, a mixture of 16 and 17 would be obtained regardless
of any stereospecificity in the elimination step. Tsuji’s observa-
tion that regioisomeric dienes are obtained from the reactions
of diastereomeric allylic carbonates in certain rigid polycyclic
ring systems6 suggested that such scrambling is slow relative
to elimination with the [Pd(OAc)2/PBu3] catalyst system.
Fortunately, this indeed turns out to be the case.
Palladium-catalyzed elimination of 14 (0.10 equiv of [Pd-
(OAc)2/PBu3], THF, 25 °C, 12 h, quantitative) affords exclu-
sively cyclohexadiene 17. We see no evidence for formation
of 16 by NMR analysis of the crude reaction mixture. The
formation of only cyclohexadiene 17 can be rationalized via
stereospecific anti-elimination of the elements LnPd(X)-H from
an intermediate such as 15.19 syn-Elimination, as required by
Acknowledgment. Financial support of this work by the National
Institutes of Health (GM34927) is gratefully acknowledged. We thank
the NIH (SIG 1-S10-RR06301) for NMR instrumentation funding, the
NSF (CHE-93000831) for GC-MS instrumentation funding, and Dr.
Richard Shoemaker for technical assistance.
Supporting Information Available: Details of the experimental
procedure and characterization data for the synthesis and elimination
of allylic carbonate 14 (26 pages). See any current masthead page for
ordering and Internet access instructions.
JA962313T
(21) Ireland, R. E.; Wipf, P.; Armstrong-III, J. D. J. Org. Chem. 1991,
56, 650-7.
(18) Keinan, E.; Roth, Z. Isr. J. Chem. 1990, 30, 305-13.
(19) While the reaction is depicted as proceeding via an η3-allyl palladium
intermediate, the conceptually related stereospecific anti-elimination of the
elements LnPd(X)-H via an η1-allyl palladium intermediate (i.e., formal
E2 or E2′ reaction) cannot be excluded by the present results.
(22) Harding, K. E.; Tiner, T. H. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 4, pp 363-421.
(23) Chuang, C.-P.; Gallucci, J. C.; Hart, D. J. J. Org. Chem. 1988, 53,
3210-8.
(20) Siegel, C.; Thorton, E. R. Tetrahedron Lett. 1988, 29, 5225-8.
(24) Cristol, S. J.; Norris, N. P. J. Am. Chem. Soc. 1953, 75, 2645-6.