Organic Chemistry - Prof. Gooßen

Double-bond migration is often encountered as an unwanted side reaction in metal catalyzed transformations, e.g., hydrogenations, hydroformylations, olefin metatheses and Heck reactions. However, a fast double-bond migration can also open up new synthetic opportunities when combined with an irreversible reaction step that selectively removes certain double-bond isomers from the equilibrium. We investigated this concept and showed its feasibility with the following catalytic transformations:

Direct lactonization protocols starting from fatty acids are rare and usually involve large quantities of corrosive and hazardous mediators like H₂SO₄ or HClO₄. Contrarily, our reaction methodology offers the catalytic use of a non-toxic, easy-to-handle silver salt. An efficient catalytic tandem isomerization–lactonization protocol has been developed for the preparation of γ-lactones from renewable fatty acids.

The products were obtained in good yields even in the rather extreme test cases of oleic and palmitoleic acid, where only one of the numerous possible double-bond isomers could give rise to the desired γ-lactone.

Rhodium-phosphite catalysts were found to effectively mediate double-bond migrations within unsaturated esters. Once the double-bond is in conjugation with the carboxylate group, they also catalyze the Michael addition of carbon and nitrogen nucleophiles. In the presence of these catalysts, unsaturated carboxylates enter a dynamic equilibrium of positional and geometrical double-bond isomers.

The conjugated species are continuously removed via 1,4 additions with formation of β-amino esters or β-arylated products, depending on the nucleophile employed. The applicability of both protocols to a range of substrates, such as fatty esters of different chain lengths and double-bond positions, and several nucleophiles including arylborates and primary and secondary amines, is demonstrated. We believe that the applicability of isomerizing conjugate additions is in no way limited to the examples presented herein, but will soon be extended to various other nucleophiles.