Carbohydrate-Derived Ligands in Asymmetric Tsuji–Trost Reactions - Carbohydrates: Tools for Stereoselective Synthesis - page 212

10

Carbohydrate-Derived Ligands in Asymmetric
Tsuji-Trost Reactions
Montserrat Diéguez and Oscar Pàmies

10.1
Introduction

Metal-catalyzed asymmetric allylic substitution (metal Pd, Mo, Ir, Cu, Ru, Rh,

and Pt), which involves the attack of diverse nucleophiles at an allylic metal inter-
mediate or S N 2

=

-type allylic substitution, is one of the most versatile routes for
preparing optically active compounds [1]. Besides a high level of asymmetric induc-
tion, the advantages of this method are its tolerance of a wide range of functional
groups and a great flexibility in the type of bonds that can be formed. For example,
H-, C-, N-, O-, and S-centered nucleophiles can be employed. With regard to the
metal source, various transition metal complexes catalyze allylic substitutions.
However, the most widely used catalysts are palladium complexes. The catalytic
cycle for Pd-catalyzed asymmetric allylic substitution is well established and
involves olefin coordination, subsequent oxidative addition with cleavage of the
leaving group, followed by nucleophilic addition, and, finally, dissociation of the
substituted olefin (Scheme 10.1).
Except for the last step (dissociation of the olefin), the cycle of reactions offers
various possibilities for enantiodiscrimination [1]. Scheme 10.2 shows two impor-
tant classes of allylic substitutions that can be carried out enantioselectively with
chiral catalysts. Type A reactions start from a racemic substrate (linear or cyclic)
and proceed via symmetrical allyl systems. In this case, the enantioselectivity is
determined by the regioselectivity of nucleophilic attack and therefore depends on
the ability of the chiral ligand to differentiate between the two allylic termini [1].
In type B reactions, racemic or prochiral substrates possessing two identical
geminal substituents at one of the allylic termini react via a

′

π -allyl intermediate

that can isomerize via the well-established mechanism [1]. In this case,

enantioselection can occur either in the ionization step, leading to the allyl inter-
mediate, or in the nucleophilic addition step [1]. For these latter substrates, not
only does the enantioselectivity of the process need to be controlled but the regi-
oselectivity is also a problem because a mixture of regioisomers may be obtained.

π - σ - π