I. Total synthesis of acortatarin A using a palladium-catalyzed spiroketalization methodology II. Tandem gold-catalyzed cyclization/Diels-Alder reactions

Palladium and gold complexes have been shown to provide an efficient method for the formation of C-O and C-N bonds via activation of alkenes and alkynes towards nucleophilic attack. Of particular interest is the intramolecular cyclization of monoallylic and monopropargylic diols to afford saturated and unsaturated heterocycles respectively. The work presented in this thesis is aimed at applying these methodologies to the total synthesis of a biologically active natural product, and expanding them to a mild synthesis of diene heterocycles for Diels-Alder reactions.;Monoallylic keto-diols initially equilibrate to form a hemiketal between the non-allylic alcohol and carbonyl. The newly formed hydroxy group has been shown to attack the double bond of the allylic alcohol forming anomeric spiroketals under transition metal catalysis. This cyclization method was used to generate the spiroketal core of the natural alkaloid acortatarin A. The key hemiketal intermediate was prepared in 15 total steps, and the cyclization event proceeded under palladium(II)-catalysis to deliver the desired spiroketal in high yield. A concise end-game strategy successfully completed the natural product.;The Diels-Alder reaction is a powerful C-C bond forming technique to effect the formation of unsaturated 6-membered rings from dienes and appropriate dienophiles. Monopropargylic diols cyclize under gold-catalyzed conditions to form cyclic dienol ethers, which may further react in the capacity of dienes in the Diels-Alder reaction. Likewise, the corresponding nitrogen heterocycles may be formed from substrates containing amine derivatives. Systems comprised of 5- and 6-membered unsaturated heterocycles with pendant vinyl groups forming the dienes were prepared from propargyl alcohols using gold(I)-catalysis. These dienes were trapped as their Diels-Alder adducts with several dienophiles including N-methylmaleimide and tetracyanoethylene.;Herein we demonstrate the utility of a novel palladium-catalyzed spiroketalization in the total synthesis of the natural product acortatarin A, and report novel methods of preparing fused-ring heterocyclic systems employing a tandem gold-catalyzed cyclization / Diels-Alder methodology.