Palladium-catalyzed Asymmetric Decarboxylative Cycloaddition Of Vinylethylene Carbonates: Construction Of Quaternary Setereocenters

The direct and enantioselective construction of quaternary stereocenters is a topic of great interest in organic chemistry. Many synthetic strategies in this research field offer mild conditions under which challenging and important molecular features can be reliably synthesized, including chiral all-carbon quaternary stereocenters. As a result, palladium-catalyzed asymmetric allylic substitution reactions have found significant use in total synthesis, and growing use in industry. While the general process of palladium-catalyzed asymmetric decarboxylation has been studied for decades, there have been a number of recent modifications and developments, such as asymmetric versions of decarboxylative cycloaddition procedures that are not yet well understood. The development of future implementations and improvements to palladium-catalyzed asymmetric decarboxylative cycloaddition and related methodologies is expected to be facilitated by a better understanding of these more recent developments, and thus further mechanistic investigation is required.General routes to vinyldioxolanes, multifuntionalized tetrahydrofurans and vinyloxazolidinones core structures has been developed, that incorporate the palladium-catalyzed asymmetric decarboxylative cycloaddition as a key transformation. The unique reactivity of quaternary vinylethylene carbonates(VECs) upon addition of unsaturated electrophiles reagents enables divergent access to enantioenriched tertiary vinylglycols, tertiary vinylglycinols, and tetrahydrofurans derivatives bearing all-carbon quaternary stereocenters through respective ring opening pathway. Derivatization of the resulting products provides a series of synthetically important compounds that can serve as valuable intermediates for the total synthesis of complex natural products.Herein, we reported is a set of investigations into the palladium-catalyzed asymmetric decarboxylative cycloadditions of substituted vinyl ethylene carbonates(VECs) with unsaturated electrophiles, using the chiral ligand design. By using a palladium complex generated in situ from Pd2(dba)3?CHCl3 and chiral ligands, a series of previously unidentified key intermediates is discovered. The process enabled rapid access to methylene acetal protected tertiary vinylglycols, carbonyl protected β-substituted β-vinylglycinols in high yields with high levels of enatioselectivites, and multifunctionalized tetrahydrofurans bearing continuous tertiary and vicinal all carbon quaternary stereocenters.Finally, the stereochemical outcome of the process has been explained by density functional theory(DFT) calculations for the geometry optimization of the plausible conformations of the π-allylpalladium intermediates. Moreover, the synthetic versatility of the process was demonstrated by the scale-up transformations and further elaboration of the products. Notably, via palladium-catalyzed asymmetric decarboxylative cycloaddition described here, the cycloaddition chemistry of the vinylethylene carbonates was significantly extended for the first time to unsaturated electrophiles, especially, aldehydes, isocyanates and Michael acceptors. The corresponding asymmetric decarboxylative cycloaddition process also occurred in the presence of catalytic amount of chiral ligand.Therefore, we believe that this work will open new avenues for reaction design and heterocycle synthesis based on these versatile and stable vinylethylene carbonates.