Transition metal-mediated synthesis and functionalization of macrocycles were investigated. A novel synthetic strategy was discovered to build macrocyclic enynes; vic-dibromo tetrasubstituted alkenes were utilized as highly effective protected alkyne groups in selective ene-ene ring closing metathesis reactions of (E)-dibromotrienes. Macrocyclic enynes with varied sizes and functionality were synthesized in excellent yields by facile Zn-promoted deprotection of (E)-dibromodiene rings. The new strategy circumvented high catalyst loadings and reaction condition restrictions; thus, was proven superior to traditional alkyne protection methods employing dicobalt octacarbonyl complexations. Cyclic enynes were obtained in a more step-economic and efficient manner compared to classical SN2 ring closing processes. The reactivity and utility of enyne rings were showcased by platinum(II)-catalyzed transannular cyclopropanations.

The first dicobalt hexacarbonyl-promoted transannular [4+2] cycloaddition reactions were demonstrated. Optimized cycloadditions for macrocyclic dicobalt-dienyne complexes afforded target tricyclic scaffolds in a more effective manner than thermal transannular Diels-Alder reactions of metal-free dienyne rings. Further, dicobalt hexacarbonyl complexes of unactivated dienophiles underwent intermolecular room temperature-[4+2] cycloadditions with unactivated dienes leading to products that are inaccessible by thermal Diels-Alder reactions. Cycloaddition reactions of complexes were highly selective; [4+2] reaction adducts were obtained stereospecifically and competing Pauson-Khand reactions were not detected.

Functionalizations of enyne macrocycles through intermolecular and transannular reactions of their corresponding dicobalt complexes were studied. Novel complex polycycles were prepared by intramolecular and intermolecular [2+2+2], [2+2+1+1], [2+2+1] cycloadditions. The chemoselectivity of dicobalt-promoted cycloadditions was altered by varying the promoter and solvents utilized. The first transannular Pauson-Khand reaction was discovered. The novel synthetic method was optimized and structural requirements for reaction substrates were investigated.