Asymmetric Synthesis of Tertiary α‐Aryl Stereocentres in Tetrahydro‐4 H ‐pyran‐4‐ones Using Pd‐Catalyzed Decarboxylative Asymmetric Protonation

Pd‐catalyzed decarboxylative asymmetric protonation (DAP) has been applied to the enantioselective synthesis of a series of α‐aryl‐tetrahydro‐4 H ‐pyran‐4‐ones possessing tertiary stereocentres. This was accomplished using the corresponding α‐aryl‐β‐keto allyl esters in an achiral catalyst system with (1 R ,2 S )‐(‐)‐ephedrine as the chiral proton source. A range of α‐aryl‐β‐keto allyl esters was synthesized employing aryllead triacetate methodology to install various aryl groups. The resulting products were obtained in high yields and moderate enantioselectivities of up to 85% ee , with the best results observed for substrates containing an electron‐donating di‐ ortho ‐substitution pattern on the aryl ring, with diminished enantioselectivity observed with other substitution patterns. The observed stereochemical outcome has been rationalized, supported by the isolation and characterization of the N‐allylated derivative of (1 R ,2 S )‐(‐)‐ephedrine and the results obtained with the (1 R ,2 S )‐(‐)‐ephedrine derivatives, N‐methyl‐(1 R ,2 S )‐(‐)‐ephedrine, and (1 R ,2 S )‐1‐methoxy‐ N , N ‐dimethyl‐1‐phenylpropan‐2‐amine.