C O M M U N I C A T I O N S
Table 2. Reaction of Various Allyl Enol Carbonatesa
to crotylated products, indicating only minor leakage from the caged
contact ion pairs in dioxane.
This alkylation was examined in a range of five-, six-, and seven-
membered ketones (Table 2, entries 1, 7-11). In all cases, good to
excellent yields of monoalkylated products were obtained. The
simplicity of the cyclohexanone substrate makes it the most
challenging, yet a respectable 78% ee was observed (Table 2, entry
1). Annealing an aromatic ring enhanced the ee to >90% (Table
2, entries 8 and 9). Using a heterocycle had no effect (Table 2,
entry 7). While the ee dropped somewhat in the case of indanone
(Table 2, entry 10), it increased to near perfect in the case of the
benzosuberone (Table 2, entry 11).
In summary, an excellent method for the asymmetric allylation
of simple ketones to create both quaternary and teriaycenters using
the Pd AAA has been developed. The success of the method stems
from the neutrality of the conditions and the tethering of the
allylating agent to the nucleophile by a CO2 unit. The excellent
results obtained in both series combined with the change in facial
selectivity compared to the use of lithium enolates in cases where
that approach is applicable raises questions as to the exact
mechanism of this reaction. Studies to elucidate the mechanism
are necessary to understand the source of the enantioselectivity,
and they are underway.
Acknowledgment. We thank the National Science Foundation
and National Institutes of Health, GM13598, for their generous
support of our programs. Mass spectra were provided by the Mass
Spectrometry Regional Center of the University of California-San
Francisco, supported by the NIH Division of Research Resources.
a Unless otherwise indicated, all reactions were performed on a 0.3 mmol
scale at 0.1 M in toluene at 23 °C for 20 h using 2.5% 2 and 5.5% ligand
L4. b The yields were isolated yields. c The ee values were determined by
chiral HPLC. d The [R]D of the product has the same sign as that reported
for the R configuration.4,12 e The ee was determined by chiral GC. f Dioxane
was used as solvent for the reaction.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds (PDF). This material is
Table 3. Selected Optimization Studies for Alkylation at
References
Secondary Carbona
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entry
T (
°
C)
solvent
eeb
yield of 6d,e
yield of 7e
yield of 8e
1
2
23
4
23
23
50
50
23
toluene
toluene
THF
THF
THF
THF
dioxane
95
95
94
94
89
89
97
62c
29c
53(52)c
51(51)c
48(48)c
46(44)c
22(18)c
81(81)c
36(39)c
25(35)c
25(32)c
13(20)c
7(10)c
6
8
5
9
19
38
<2
3
4b
5
6b
7
a Unless otherwise indicated, all reactions were performed on a 0.3 mmol
scale at 0.1 M for 20 h at 23 °C using 2.5% 2 and 5.5% ligand L4; yields
were measured by quantitative GC analysis using decane as internal
reference. b The ee values (in percent) were determined by chiral HPLC.
c The yields were for isolated compound. d The [R]D of 6 has the same sign
as that reported for the R configuration.2a e Values are in percent.
(9) Harwood, L. M.; Houminer, Y.; Manage, A.; Seeman, J. I. Tetrahedron
Lett. 1994, 35, 8027.
(10) Schroeder, G. M. Palladium Catalyzed Asymmetric Allylic Alkylation
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Erinacine A. Ph.D. Dissertation, Stanford University, Stanford, CA, 2002.
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M. J. Am. Chem. Soc. 1981, 103, 3081.
obtained. To probe our proposal, we conducted a crossover
experiment (eq 4), in which the 1:1 mixture of enol carbonate 23
and 31 was subjected to the Pd catalyst in dioxane. GC analysis of
the product mixture revealed a 10:1 mixture of 24 and 26 in addition
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