57th Annual Report on Research 2012 Under Sponsorship of the ACS Petroleum Research Fund

The impact of olefin metathesis on both organic and polymer synthesis cannot be understated. Despite the success of catalysts 1 and 2 in preparing a range of increasingly complex architectures, applications to polyene systems remain rare (Figure 1). This is largely the result of problems associated with chemoselectivity, or the nonselective engagement by the metathesis catalyst of one alkene in the presence of another.

We have introduced β-acyloxysulfones (3) as a novel alkene protecting group strategy that has allowed for a metathesis approach to a variety of polyene subunits unobtainable by standard metathesis technology (Scheme 1).

Current efforts are focused on extending this strategy toward increasingly challenging targets encompassing all general types of olefin metathesis reactivity. Examples include ring-closing acyloxysulfone metathesis/elimination reactions to produce stereodefined E,Z-dienoic acids (4) and medium-ring dienyl-macrolactones (5) (Scheme 2).

This approach has provided convenient access to several important natural products including the antimicrobial alarm pheromones isopulo'upone (6) and haminol A (7) (Scheme 3).

During the course of our investigations we observed a significant substrate dependence on the rate of samarium-mediated benzoyloxysulfone eliminations. This trend has proven to be general as evidenced by extensive competition experiments and can be exploited as a selective deprotection strategy. For instance bis-benzoyloxy-sulfone 8 undergoes a highly chemoselective samarium-mediated elimination, proceeding through the presumably resonance stabilized intermediate 9, affording diene 10 containing an intact benzoyloxysulfone (Scheme 4). We have begun investigating this protocol for iterative differential alkene functionalizations. For instance Sharpless asymmetric dihydroxylation of 11, prepared by cross-metathesis of 12 and 13 followed by acylation, and chemoselective benzoyloxysulfone elimination should yield 14. This compound then contains two additional alkenes (one masked, one unmasked) for further functionalization.

Recently we have also begun exploring this general strategy for the synthesis of functionalized polymers (Scheme 5). For instance masked divinylbenzene derivative 15 can be successfully polymerized under both free radical and controlled radical conditions. Elimination then gives 16 that is poised for a variety of post-polymerization functionalizations.

This work has provided the basis for an ongoing research program aimed at the synthesis of biologically relevant and environmentally compelling small molecules and materials utilizing acyloxysulfones as masked alkenes. Results were presented by the PI and student participants at both regional and national meetings. Student researchers supported by this grant during the past year have gone on to pursue graduate degrees in chemistry at the University of North Carolina and Boston University.