Mechanistic Investigations of the Pd-Catalyzed Hydrogenolysis of Ketene Heterodimer β-Lactones

Catalytic hydrogenolysis of theZ-isomer of a series of aryl-substituted ketene heterodimer beta-lactones facilitated access to deoxypropionate derivatives with adrranging from 54:46 to 86:14, favoring theanti-isomer, and with excellent transfer of chirality (91 -> 99 %eefor 13 examples). Although X = 4-F was determined to provide optimal diastereoselectivity (dr86:14), a non-linear relationship between diastereoselectivity and aryl substituent sigma values was found. For cases where apara- orortho-EWG was present on the aryl ring of the ketene heterodimer, formation of significant amounts of beta-lactone (20-44 %) as by-product was observed. The results of a number of control reactions point toanti-beta-elimination and ananti-selective hydrogenation of anE-isomer olefin intermediate being key steps in the reaction mechanism. The synthetic potential of the deoxypropionate derivative products was demonstrated by oxidative conversion into a 1,5-difunctionalized deoxypropionate motif.