Enantioselective α-Alkylation Of Carbonyls With Alkenes And Alkynes

Enantioselective α-alkylation of carbonyl compounds is a fundamental C-C bond formation in chemical transformations.Simple alkenes and alkynes are bulk chemicals.Direct α-alkylation with these unsaturated hydrocarbons represents one of the most ideal process for α-carbonyl reactions due to high atomic economy(100%).However,to develop catalytic asymmetric version for such processes remains a great challenge.With chiral primary amine catalyst developed in our group,this dissertation intends to develop synergistic amine/metal catalysis for asymmetric α-alkylation with alkenes and alkynes.The major progresses include:(1)Synergistic chiral primary amine/Pd catalysis was developed for the asymmetricα-pentadienylation of β-ketocarbonyls and aldehydes with 1,4-nonconjugated enynes.The reaction features the construction of acylic all-carbon quaternary centers with good chemoselectivity and high diastereo-/enantio-selectivity.(2)A synergistic chiral primary amine/Pd catalyst was identified to facilitate the utilization of 1,3-enynes as atom-economic and achiral allene precursors.The synergistic catalysis enables the construction of all-carbon quaternary centers-tethered allenes bearing non-adjacent 1,3-axial central stereogenic centers in high level of diastereo-and enantio-selectivity.By switching the configurations of ligands and aminocatalysts,diastereodivergence can be achieved and any of the four diastereoisomers can be accessed in high diastereo-and enantio-selectivity.(3)We further developed an asymmetric α-pentadienylation of β-ketocarbonyls with aryl-substituted cyclopropylacetylenes by synergistic chiral primary amine/Pd catalyst.A novel ethynylcyclopropane was designed to construct chiral 1,2-substituted butadiene,a new skeleton that has not been achieved before.