Molybdenum and palladium catalyzed asymmetric allylic alkylation of prochiral nucleophiles: Enantioselective synthesis of nonnatural alpha-amino acids and of tertiary alpha-hydroxy carboxylic acid derivatives

The complex of zerovalent molybdenum and bis-(N ,N)[carbonyl(2-pyridyl)]-1,2-diamino-cyclohexane catalyzed the asymmetric allylic alkylation (AAA) of o-bromo allylic substrates, which delivered vinylcycloalkanes in good yield and excellent enantiomeric excess after cyclization. The regioselectivity was for the more substituted terminus of the pi-allyl molybdenum intermediate.; A similar catalytic system empowered the asymmetric construction of nonnatural gamma,delta-unsaturated alpha-amino acids at low temperatures, in good yields and enantioselectivities. The molybdenum-catalyzed AAA with enolates of alpha-amino acid ester-imines preferentially afforded the product of alkylation on the less substituted allylic position. Careful exclusion of oxygen was necessary in order to accomplish the reported results. Formation of quaternary alpha,alpha-dialkylated alpha-amino acids was also achieved with interesting results.; Three methods for the preparation of 5H-5-alkyl-2-phenyl-4-oxazolones ("oxalactims"), a little known class of 5-membered oxazolones, were implemented. These oxalactims could be employed as pronucleophiles in the AAA of allylic carbonates, in the presence of catalytic quantities of the zerovalent palladium complex with chiral Trost ligand. The quaternary substituted products were obtained in excellent yields and high enantiomeric excesses. Where two contiguous stereogenic centers were installed, the diastereomeric ratios were good and strongly depended on the reaction solvent. The ability of the chiral catalyst to induce asymmetric control at the nucleophile was therefore demonstrated. The obtained 5,5-disubstituted oxalactims could be selectively hydrolyzed to primary carboxamides and to tertiary alpha-hydroxy carboxylic acids.; The same class of oxalactims could be used as pronucleophiles in the AAA reaction with allyl carbonates in the presence of the above mentioned molybdenum complex. The quaternary substituted products were obtained in good yields and excellent enantiomeric excesses. The catalytic system strongly favored the formation of the "branched" products, which contain two adjacent stereogenic centers. The diastereomeric ratio was typically very good, thus attesting the ability of the catalytic system to exert asymmetric control at the nucleophile. The obtained 5,5-disubstituted oxalactims could be selectively hydrolyzed to the corresponding primary carboxamides. The steric hindrance around the carbonyl group in combination with the sensitive monosubstituted olefin, have prevented a reproducible solvolysis of 5,5-disubstituted oxalactims to the tertiary alpha-hydroxy carboxylic acids. Finally, oxalactims generally exhibit selectivity for 1,4-addition when subjected to nucleophilic attack.