Mycosporulone is a polyketide-derived fungal metabolite which was first reported in 1993 by Kaouadji. It belongs the general class of molecules known as 3-methylidene-2-oxaspiro[4.5]decan-1-ones and possesses a range a biological activities including antibacterial, anti-fungal, and cytotoxicity. In addition, it does not have toxicity towards human lung fibroblasts MRCS, up to a concentration of 100 μg/mL, suggesting there is some selectivity in its cytotoxicity. To date, no total synthesis of Mycosporulone has been reported. Our strategy towards this natural product centered on three distinct approaches. The first approach involved an intramolecular furan Diels–Alder reaction. While we were able to synthesize complex cycloadducts utilizing imide tethers, this route was abandoned due to the inability to employ ester and heteroatom tethers. The second approach was based on a masked ortho-benzoquinone strategy. We were able to solve two major problems—the first stopping self-dimerization by a Diels–Alder reaction and the second the reduction of masked ortho-benzoquinone systems by cuprate reagents. This route was ultimately was abandoned due to the propensity for our masked ortho-benzoquinone to re-aromatize and the lack of C vs. O-atom alkylation selectivity. The third approach was based on simple enone ethyl 5-methyl-3-oxocyclohexene-4-carboxylate. We developed a method to increase the reactivity of the resulting enolate by trapping the initial β-ketoester as its silyl enol ether. Subsequent ϵ-deprotination led to a highly reactive enolate that could be trapped alkyl halides and aldehydes. In addition, we were able to develop a one-pot protocol for synthesis of enol lactones from acetylenes and trimethylsilylethyl esters in the presence of Ag⁺¹. Late in this approach, we attempted to alleviate an epoxidation regioselectivity issue by changing substrates to ethyl 2-methyl-5-oxocyclohex-3-enecarboxylate. Upon α-deprotonation of its TBS enol ether and trapping with

D

-(R)-glyceraldehyde acetonide, we were able to report a kinetic resolution event involving an initial aldol, retro-aldol, and re-aldol process. The aldol product corresponding to the stereochemistry required for mycosporulone was taken forward to the proposed structure, which proved to be incorrect. Based on this information, we believe the real structure of mycosporulone corresponds to the oxidation product of 6-epi-5'-hydroxy-mycosporulone.

(+)-Fawcettimine is a Lycopodium alkaloid and is the first member of its class. It was isolated in 1959 by Burnell in the Blue Mountain range of Jamaica. While its role in biological systems is not yet known, its challenging tetracyclic structure has prompted five total syntheses. Our approach is based on work reported in the Jung laboratories concerning the Brensted acid-promoted stepwise Mukaiyama–Michael addition of hindered silyloxy dienes to hindered enones to give formal Theis–Alder cycloadducts. As an extension, we wished to augment a silyloxy diene with a cyclopropane-1,1-diester. The resulting annulation would occur by a tandem Mukaiyama–Michael homo-Michael process to give hydrinadanones. Despite experimenting with various reaction conditions, annulation products were not observed between enones and TBS enol ethers containing a cyclopropane-1,1-diester. In order to increase the reactivity of the systems, a simple Wittig methenylation was performed on the initial Mukaiyama–Michael intermediate. When this olefin is treated with scandium tris(trifluromethanesulfonate), a hydrindanone product is observed. In order to distinguish the mechanism between a "S_N1-like" and "S_N 2-like" mechanism and to synthesize Heathcock's (+)-fawcettimine intermediate, enantiopure coupling products were used. A trifluromethanesulfonimide mediated Mukaiyama–Michael reaction, a Wittig methenylation, an annulation reaction, and a Krapcho decarboxylation reaction yielded Heathcock's (+)-fawcettimine intermediate, thus completing the formal synthesis. The annulation proceeded in good yields and in a diastereospecific manner.