Asymmetric Catalytic Palladium Allyl Alkylation Building Chiral Quaternary Carbon Center

Many natural products and drug molecule contain chiral quaternary carboncenter, and its chiral quaternary carbon center always lead to special physical andchemical properties and better in vivo biological activity. Asymmetric construction ofquaternary carbon centers is a difficult but interesting project.and has been provenparticularly challenging for organic synthesis chemists.Herein, the stabilized enolatesfrom1,3-dicarbonyl compounds and the unstabilized enolates from ketone were usedas nucleophilic reagents for Pd-catalyzed asymmetric allylic alkylation to constructquaternary carbon centers.Firstly, a series of1,3-dicarbonyl compounds are synthesized from ketones andesters with good yields from40%to87%. These1,3-dicarbonyl compounds wereutilized to form stabilized enolates as the nucleophiles of Pd-catalyzed asymmetricallylic alkylation (AAA) reaction. Optimized conditions consist of performing thereaction in the presence of BSA as base, THF as the solvent, Zn(OAc)2as additive,and a catalytic amount of a chiral palladium complex formed from π-allyl palladiumchloride dimer and (S)-BINAP. Under the optimized conditions, moderate to goodyield and enantioselectivity (up to83%ee) has been achieved.Secondly, Pd-catalyzed asymmetric allylic alkylation of nonstabilized ketoneenolates to generate quaternary carbon centers has been achieved in excellent yieldbut moderate enantioselectivity. Optimized conditions consist of performing thereaction in the presence of t-BuONa as base, toluene as the solvent, and a catalyticamount of a chiral palladium complex formed from π-allyl palladium chloride dimerand chiral ligands such as P-Phos and novel "pocket" dihosphine. Two kinds ofketone enolates are employed as nucleophiles.