The enantioselective synthesis of isochroman motifs has been accomplished via Pd(II)-catalyzed allylic C–H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C–H oxidation reaction proceeds with the broadest scope and highest levels asymmetric induction reported to date (avg. 92% ee, 13 examples ≥90% ee)

We report the development of Pd(II)/ cis-aryl sulfoxide-oxazoline ( cis-ArSOX) catalysts for asymmetric C-H alkylation of terminal olefins with a variety of synthetically versatile nucleophiles. The modular, tunable, and oxidatively stable ArSOX scaffold is key to the unprecedented broad scope and high enantioselectivity (37 examples, avg. > 90% ee). Pd(II)/ cis-ArSOX is unique in its ability to effect high reactivity and catalyst-controlled diastereoselectivity on the alkylation of aliphatic olefins. We anticipate that this new chiral ligand class will find use in other transition metal catalyzed processes that operate under oxidative conditions.

The synthesis of chroman, isochroman, and pyran motifs has been accomplished via a combination of Pd(II)/bis-sulfoxide C–H activation and Lewis acid co-catalysis. A wide range of alcohols are found to be competent nucleophiles for the transformation under uniform conditions (catalyst, solvent, temperature). Mechanistic studies suggest that the reaction proceeds via initial C–H activation followed by a novel inner-sphere functionalization pathway. Consistent with this, the reaction shows reactivity trends orthogonal to those of traditional Pd(0)-catalyzed allylic substitutions.

Catalytic quantities of bismuth(III) triflate efficiently initiate the rearrangement of epoxides to aldehydes which subsequently react with (Z)-δ-hydroxyalkenylsilanes to afford 2,6-disubstituted-3,6-dihydro-2H-pyrans. Isolated yields of desired products using Bi(OTf)3 were compared with yields when the reactions were run with TfOH and TMSOTf in the presence and absence of several additives. These studies, as well as NMR spectroscopic analyses, indicate an initial Lewis acid/base interaction between Bi(OTf)3 and substrates providing TfOH in situ.