alkyl palladium intermediates undergo â-hydride elimination
toward the vinyl/aryl group that has been added to the double
bond. In a number of cases, particularly with cyclic olefins,
this is not possible because the only â-hydride syn to the
metal is away from the newly formed carbon-carbon bond.
In these cases this results in the formation of a new chiral
carbon. Being able to control this reaction such that one
enantiomer is formed selectively would be a significant
result. Other than the excellent work of Pfaltz and Hayashi,
success with the asymmetric intermolecular version of this
reaction has been rather limited.21-30 Pfaltz has shown that
phosphine-oxazoline ligands can be used with palladium to
perform asymmetric versions of the Heck reaction on selected
substrates. The success of the Pfaltz phosphine-oxazoline
system has led us to synthesize and study the system
discussed below.
diphenylphosphine was followed by protection of the phos-
phine as its sulfide (9). Hydrolysis of the methyl ester proved
difficult, ultimately requiring a nonhydrolytic method to
obtain the desired acid.31 This reaction was followed by
conversion of the acid to an amide (10-13). Mesylation of
the alcohols 10-13 followed by sequential cyclization
provided the corresponding phosphine-oxazoline sulfides. We
have found in previous work that phosphine sulfides are good
protecting groups for what are often moderately air sensitive
phosphine groups. The free phosphine is readily generated
by reaction with Raney nickel prior to use.32-35
We also desired this type of ligand with different phos-
phine groups. The original route to the cyclohexyl derivative
of ligands 14-17 was to use the approach described in
Scheme 1. However, that route proved problematic in that
during the coupling of the amino alcohol the phosphine
sulfide was oxidized to the phosphine oxide. After comple-
tion of the synthesis, we were not able to reduce the
phosphine oxide to the phosphine. Additionally, running the
reaction with the careful exclusion of air still resulted in the
formation of the phosphine oxide. To circumvent this
problem, we decided to synthesize the oxazoline first and
then attempt the palladium-catalyzed conversion of the
ketone to the vinyl phosphine (Scheme 2). This route
The general route for the synthesis of the desired ligands
is illustrated in Scheme 1. Commercially available (S)-(+)-
Scheme 1
Scheme 2
ketopinic acid (1) was converted to its methyl ester which
was then converted to the corresponding vinyl triflate (8).
Palladium-catalyzed coupling reaction of triflate 8 and
proceeded smoothly to give the desired dicyclohexylphos-
phine. We have also used this route to synthesize the
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