Enantioselective Reactions of Unsymmetrical Allylic Esters Catalyzed by Molybdenum, Ruthenium, Rhodium, and Iridium

Enantioselective Reactions of Unsymmetrical Allylic Esters Catalyzed by Molybdenum, Ruthenium, Rhodium, and Iridium 

As noted in Section 20.5.3, catalysts generated from metals other than palladium tend to form the product from attack at the more substituted end of a monosubstituted allylic intermediate. Molybdenum and tungsten catalysts containing nitrogen-based ligands 

The molybdenum and tungsten complexes catalyze reactions of soft nucleophiles, such as malonates, related 1,3-dicarbonyl compoimds, and nitroalkanes. Azlactones are also soft carbanions, and Trost has shown that complexes formed from molybdenum and the bis(pyridine) ligands catalyze enantioselective and diastereoselective allylation of azlactones with allylic phosphates to form quaternary amino acids (Equation 20.40). In these reactions, the nucleophile adds to the more substituted position of the allylic electrophile, and a stereocenter is formed at both the allyl carbon and the azlactone carbon. One route to the protease inhibitor tipranavir by the molybdenum-catalyzed allylation with 1,3-dicarbonyl compounds was demonstrated by Trost (Equation 20.41), and the Merck process group used related allylation chemistry with Trost s bis(pyridine) ligand to prepare the cyclopentanone precursor to various analogs of tipranavir (Equation 20.42). 

In contrast, iridium complexes of phosphoramidite ligands catalyze the enantiose-lective formation of the branched allyUc substitution products with high enantiomeric excess. Takeuchi and Helmchen - - - reported that iridium complexes, hke rhodium complexes, generate the chiral, branched product from reactions of mono-substituted aUylic acetates and carbonates with carbon and nitrogen nucleophiles (Equations 20.45-20.47). 

More recently, Hartwig and co-workers showed that iridium complexes of the phosphoramidite ligand shown in Equation 20.48 catalyzes these reactions with amines, ary-loxides, the combination of alkali metal alkoxide and Cul, the combination of alcohol and base, trifluoroacetamide, azoles, and ketone enolate equivalents with enantiomeric excess near or above 95% in most They have also shown that this irid- 

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