steps from commercial materials).5 Recently, Du has
reported the use of diene disulfonamide ligand L3, which
provides products in up to 95% ee. However, this ligand
requires six steps to prepare from 1,5-hexadiene.6 In a
similar effort, Yu has reported the successful use of a bis-
terminal diene ligand (five steps from commercial
materials) in rhodium-catalyzed conjugate additions.7
With this in mind, a more convenient synthetic approach
toward chiral dienes for use in transition metal catalysis
became the primary objective of this work. Moreover, it is
desirable to do so by implementation of a robust chemical
method on a common intermediate. In this sense, one can
rapidly produce a structurally diverse library of potential
ligands.
We recognized that our palladium-catalyzed asym-
metric allylic alkylation (Pd-AAA) of meso- and d,l-divi-
nylethylene carbonate (1)8 with suitable nucleophiles would
provide rapid access (i.e., two steps from commercial
materials) to chiral diene ligands (Scheme 1). In addition
to providing an efficient modular approach9 toward an
initial chiral diene ligand screen, it should also be noted
that either enantiomer of a respective ligand is equally
accessible using this method. This is not the case for the
previously mentioned diene diol ligand described by Du4
or the bicyclo[2.2.2]octadiene ligands synthesized in two
steps from (R)-R-phellandrene reported by Hayashi and
Rawal.10
Scheme 1. Synthesis of Chiral Diene Ligands via Pd-AAA of
meso- and d,l-1,2-Divinylethylene Carbonate
Figure 2. Ligand screen in Rh-catalyzed conjugate addition of
phenylboronic acid to 10.
previous studies with chiral terminal olefin ligands.4À6
To our delight, use of ligand 3 gave the corresponding
product (11) in 74% ee. Saturated imides 4 and 5 led to
significantly reduced yields and, in the case of 4, lowered
enantioselectivity. Incorporation of other heterocycles,
such as the isatin-derived ligand 6 or the benzoxazolidi-
none-derived ligand 7 did not provide improvement.
Known diene 88 was tested to observe the effect of het-
eroatom substitution (i.e., oxygen vs nitrogen) and led to a
reduction of yield and enantioselectivity. Compound 9,11
which is prepared from the Pd-AAA of butadiene mono-
epoxide with phthalimide, and which is structurally analo-
gous to 3 with exclusion of the second olefin, provided very
little conversion or enantioselectivity.12 This result high-
lights the requirement of a bidentate ligand (e.g., diene)
and suggests that the hydroxyl moiety is not involved in
binding with rhodium.
Several diene ligands (Figure 2, 3À9) were prepared and
evaluated with respect to conversion and enantiomeric
excess in the rhodium-catalyzed conjugate addition of
phenylboronic acid to 2-cyclopentenone (10).
At the outset we chose to evaluate 2-cyclopentenone,
a substrate which has consistently proved challenging in
Next, we examined the effect of solvent on the conjugate
addition of phenylboronic acid to 10 (Table 1). It was
found that a 2:1 ratio of dioxane and water at room
(5) Hu, X.; Cao, Z.; Liu, Z.; Wang, Y.; Du, H. Adv. Synth. Catal.
2010, 352, 651.
(6) Wang, Y.; Hu, X.; Du, H. Org. Lett. 2010, 12, 5482.
(7) Li, Q.; Dong, Z.; Yu, Z.-X. Org. Lett. 2011, 13, 1122.
(8) Trost, B. M.; Aponick, A. J. Am. Chem. Soc. 2006, 128, 3931.
(9) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc.
1992, 114, 9327.
(11) (a) Trost, B. M.; Bunt, R. C.; Lemoine, R. C.; Calkins, T. L. J.
Am. Chem. Soc. 2000, 122, 5968. (b) Trost, B. M.; Horne, D. B.;
Woltering, M. J. Chem.;Eur. J. 2006, 12, 6607.
(12) It should be noted that the absolute configurations of 8 and 9 are
opposite to that of the other ligands studied and were used arbitrarily
due to availability.
(10) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10,
4387.
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