Asymmetric allylic alkylation of ketone enolates: An asymmetric claisen surrogate

Article abstract of DOI:10.1021/ol048149t

(Chemical Equation Presented) The combination of catalytic palladium(0) and Trost ligand provides an effective catalyst for the rearrangement of allyl β-ketoesters. The mechanism of the transformation involves formation of π-allyl palladium intermediates which undergo enantioselective attack by ketone enolates. Decarboxylation of β-ketocarboxylates allows regiospecific generation of enolates under extremely mild conditions.

Full text of DOI:10.1021/ol048149t

ORGANIC
LETTERS
2004
Vol. 6, No. 22
4113-4115
Asymmetric Allylic Alkylation of Ketone
Enolates: An Asymmetric Claisen
Surrogate
Erin C. Burger and Jon A. Tunge*
Department of Chemistry, UniVersity of Kansas, Lawrence, Kansas 66045
tunge@ku.edu
Received September 13, 2004
ABSTRACT
The combination of catalytic palladium(0) and Trost ligand provides an effective catalyst for the rearrangement of allyl
mechanism of the transformation involves formation of -allyl palladium intermediates which undergo enantioselective attack by ketone enolates.
Decarboxylation of -ketocarboxylates allows regiospecific generation of enolates under extremely mild conditions.
â-ketoesters. The
π
â
Asymmetric catalysis of Claisen-type rearrangements is
currently receiving much attention. Despite the recognized
synthetic utility of Claisen rearrangements, a general asym-
metric catalytic transformation remains elusive.1,2 The major-
ity of attempts at catalysis have focused on Lewis acid
activation, despite the fact that both anionic3 and cationic4
acceleration of Claisen rearrangements are possible. Asym-
metric catalysis of Claisen rearrangements utilizing Lewis
acid activators was initially unsuccessful because the product
aldehydes are stronger Lewis bases than the allyl vinyl ether
reactants.5 This problem has been addressed by increasing
the Lewis basicity of the allyl vinyl ethers by attachment of
pendant groups capable of chelating Lewis acids.6 We
reasoned that a nucleophilic approach toward catalysis may
prove complementary to these existing methods. Recently,
we proved this concept by showing that pentamethylcyclo-
pentadienylruthenium(II) complexes efficiently catalyze the
decarboxylative rearrangement of allyl-â-keto carboxylates.7,8
These substrates are easily synthesized and readily activated
by nucleophilic catalysts, producing metal allyl complexes
and enolates which react to form γ,δ-unsaturated carbonyl
compounds.
Herein we report that high levels of asymmetric induction
can be obtained in the palladium-catalyzed decarboxylative
rearrangement of allyl-â-keto carboxylates.
Saegusa and Tsuji were the first to utilize palladium for
the rearrangement of allyl-â-ketoesters.9 The rearrangement
is thought to occur through the intermediacy of palladium
(1) (a) Hiersemann, M.; Abraham, L. Eur. J. Org. Chem. 2002, 1461-
71. (b) Ito, H.; Taguchi, T. Chem. Soc. ReV. 1999, 28, 43-50.
(2) (a) Yoon, T. P.; MacMillan, D. W. C. J. Am. Chem. Soc. 2001, 123,
2911-2912. (b) Anderson, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003,
125, 12412-12413.
(3) (a) Denmark, S. E.; Marlin, J. E. J. Org. Chem. 1987, 52, 5742-3.
(b) Denmark, S. E.; Harmata, M. A. J. Org. Chem. 1983, 48, 3369-3370.
(c) Koreeda, M.; Luengo, J. I. J. Am. Chem. Soc. 1985, 107, 5572-5573.
(4) (a) Boeckman, R. K.; Flann, C. J.; Poss, K. M. J. Am. Chem. Soc.
1985, 107, 4359-62. (b) Dhanalekshmi, S.; Venkatachalam, C. S.;
Balasubramanian, K. K. J. Chem. Soc., Chem. Commun. 1994, 511-512.
(5) Maruoka, K.; Saito, S.; Yamamoto, H. J. Am. Chem. Soc. 1995, 117,
1165-1166.
(6) (a) Abraham, L.; Czerwonka, R.; Hiersmann, M. Angew. Chem., Int.
Ed. 2001, 40, 4700-4703. (b) Trost, B. M.; Schroeder, G. M. J. Am. Chem.
Soc. 2000, 122, 3785-3786.
(7) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6, 2603-2605.
(8) (a) Carroll, M. F. J. Chem. Soc. 1940, 704-706. (b) Kimel, W.; Cope,
A. C. J. Am. Chem. Soc. 1943, 65, 1992-1998.
(9) (a) Tsuda, T.; Chujo, Y.; Nishi, S.-I.; Tawara, K.; Saegusa, T. J.
Am. Chem. Soc. 1980, 102, 6381-6384. (b) Tsuji, J. Pure Appl. Chem.
1982, 54, 197-206. (c) Tsuji, J.; Yamada, T.; Minami, I.; Yuhara, M.;
Nisar, M. Shimizu, I. J. Org. Chem. 1987, 52, 2988-2995.
10.1021/ol048149t CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/06/2004

Scheme 1
Table 1. Pd(PPh3)4-Catalyzed Rearrangements of
CH3COCH2CO2Ra
π-allyl complexes which undergo nucleophilic attack by
enolates (Scheme 1).10
Initially, we studied the rearrangement of disubstituted allyl
carboxylates because rearrangement of these substrates has
not been previously reported (Scheme 2). The rearrangement
a Reaction times and isolated yields for 0.3 M substrate and 10 mol %
Pd(PPh3)4 in C6H6 at 25 °C.
Scheme 2
Table 2. Asymmetric Palladium-Catalyzed Rearrangements of
R1COCH2CO2R2
occurred smoothly, albeit slowly, at room temperature
utilizing 10 mol % Pd(PPh3)4 in C6H6 (Table 1).
Next, we investigated the asymmetric variant using
Pd2(dba)3 and Trost’s ligand (3).11 Gratifyingly, high levels
of asymmetric induction were observed for cyclic and
methyl-substituted allyl compounds (Table 2). For instance,
treatment of 1b with 5 mol % Pd2(dba)3 and 10 mol % ligand
in C6H6 for 15 h provided a 93:7 ratio of enantiomers.
Raising the loading of ligand to 15 mol % resulted in a
significant decrease in the enantioenrichment of the product.
This behavior has been noted by others and has been
attributed to the stoichiometry of the catalyst-ligand com-
plex.12 The reaction time can be significantly reduced by
running the reactions in refluxing C6H6, with little effect on
the enantioselectivity of enolate addition. Under optimized
conditions, 1c undergoes rearrangement in the presence of
a 0.2 mol % Pd2dba3 b Reaction temperature ) 50 °C. c er is that of the
major diastereomer; dr ) 1.5.
0.2 mol % Pd2dba3 and 0.4 mol % L in refluxing benzene to
give 71% isolated yield of 2c as a 94:6 ratio of enantiomers
(>175 TOs).
A variety of terminal enolates are regiospecifically gener-
ated by decarboxylation and allylated with high enantiose-
lectivities (Table 2). Cyclic enolates are also viable partners;
however, the enolate of cyclohexanone is not very selective,
and product is formed in modest er and low dr.
The palladium-catalyzed decarboxylative rearrangement
is equivalent to the addition of nonstabilized ketone enolates
to palladium allyl complexes.13 Since the products formed
by our method can be accessed through asymmetric allylic
alkylation (AAA) utilizing sodium ethylacetoacetate as a
(10) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395-422.
(11) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc.
1992, 114, 9327-9343.
(12) Fairlamb, I. J. S.; Lloyd-Jones, G. C. Chem. Commun. 2000, 2447-
2448.
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Org. Lett., Vol. 6, No. 22, 2004

nucleophile followed by hydrolysis and decarboxylation, it
is worth comparing the two methods. Using 1c as a standard,
our yield and selectivity (85%, 93:7) can be compared to
that reported for the addition of sodium dimethylmalonate
to 2-cyclopentenyl acetate with the same ligand (77%, 69:
31).14 To assign the absolute stereochemistry of a decar-
boxylative allylation product we compared it with the
identical product derived from AAA. Thus, cyclopentenyl
acetate was treated with sodium ethylacetoacetate in THF
at 0 °C (Scheme 3).14 The resulting substitution product was
Scheme 5
a quaternary R-carbon (Scheme 5). Such a compound can
undergo the allylation reaction only if decarboxylation occurs
prior to the C-C bond-forming step. Compound 1h under-
goes Pd-catalyzed decarboxylative allylation at a similar rate
to other substrates. Thus, decarboxylation likely precedes
nucleophilic attack indicating that ketone enolates are true
intermediates. Additionally, because the product 2h cannot
be made using the traditional Tsuji-Trost reaction, these
transformations highlight the potential power of decarboxy-
lative allylation.
Scheme 3
In summary, nucleophilic Pd0 complexes are effective
catalysts for asymmetric decarboxylative allylic alkylation.
Mechanistically, the reaction involves the asymmetric ally-
lation of ketone enolates that are regiospecifically generated
in situ under base-free and tin-free conditions. Compared to
known allylations of enolates, the method described here is
superior in atom economy,15 step economy,16 and mildness
of reaction conditions. Future work will extend asymmetric
decarboxylative allylation to prochiral enolates.
decarboxylated to give R-2c as the major enantiomer (71:29
R/S). The major enantiomer resulting from the decarboxy-
lative rearrangement of 1c is also the R enantiomer. This
experiment suggests that nonstabilized ketone enolates attack
the allyl ligand from the face opposite of Pd, consistent with
the observation of complete scrambling in a crossover
experiment (Scheme 4).
Acknowledgment. E.C.B. is supported by a Madison and
Lila Self-Fellowship.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data of all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Scheme 4
OL048149T
(13) a) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Zhu, X.-Z Org. Lett. 2000,
3, 149-151. (b) Trost, B. M.; Schroeder, G. M. J. Am. Chem. Soc. 1999,
121, 6759-6760. (c) Braun, M.; Laicher, F.; Meier, T. Angew. Chem., Int.
Ed. 2000, 39, 3494-3497.
(14) (a) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089-
4090. (b) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70-79.
(15) Trost, B. M. Acc. Chem. Res. 2002, 35, 695-705.
(16) Wender, P. A.; Miller, B. L. Org. Synth.: Theory Appl. 1993, 27-
66.
To test whether decarboxylation occurs prior to the C-C
bond-forming step, we prepared an allyl â-ketoester having
Org. Lett., Vol. 6, No. 22, 2004
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