Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling.

Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved

Development of Visible-Light Photoredox Catalyzed Transformations and Applications in Total Syntheses of Natural Products

In Chapter 1, alkyl oxalates are described as new bench-stable alcohol activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved. In Chapter 2, visible light photoredox-catalyzed fragmentation of methyl N-phthalimidoyl oxalates is described for the direct construction of a 1,4-dicarbonyl structural motif by a conjugate addition of the methoxycarbonyl radical to Michael acceptors. The regioselectivity of the addition of this alkoxyacyl radical species to electron-deficient olefins is found to be influenced by the electronic nature of the acceptor, behavior similar to that exhibited by nucleophilic alkyl radicals.In Chapter 3, the evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by 1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The synthetic strategy described in this chapter allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. In Chapter 4, the development of a convergent fragment-coupling strategy for the enantioselective total syntheses of a group of rearranged spongian diterpenoids that harbor the cis-2,8-dioxabicyclo[3.3.0]octan-3-one unit is described. The key bond disconnection relies on a late-stage fragment coupling between a tertiary carbon radical and an electron-deficient alkene to unite two ring systems and form two new stereocenters, one of which is quaternary, in a stereoselective and efficient manner. This strategy is applied towards 14-15 step syntheses of three diterpenoids, cheloviolenes A and B and dendrillolide C.In Chapter 5, the first total synthesis of a chromodorolide marine diterpenoid is described. The core of the natural product is constructed by a bimolecular radical addition/cyclization/fragmentation cascade that unites two complex fragments and forms two C-C bonds and four contiguous stereogenic centers of (-)-chromodorolide B in a single step. Computational studies guided the development of this transformation and provide insight into the origin of the observed stereoselectivity

Facile Preparation of Spirolactones by an Alkoxycarbonyl Radical Cyclization-Cross-Coupling Cascade.

An alkoxycarbonyl radical cyclization-cross-coupling cascade has been developed that allows functionalized γ-butyrolactones to be prepared in one step from simple tertiary alcohol-derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors

Total Synthesis of (-)-Chromodorolide B.

The first total synthesis of a chromodorolide diterpenoid is described. The synthesis features a bimolecular radical addition/cyclization/fragmentation cascade that unites butenolide and trans-hydrindane fragments while fashioning two C-C bonds and stereoselectively forming three of the ten contiguous stereocenters of chromodorolide B

Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling.

Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved

Generation of the Methoxycarbonyl Radical by Visible-Light Photoredox Catalysis and Its Conjugate Addition with Electron-Deficient Olefins

Visible-light photoredox-catalyzed fragmentation of methyl <i>N</i>-phthalimidoyl oxalate allows the direct construction of a 1,4-dicarbonyl structural motif by a conjugate addition of the methoxycarbonyl radical to reactive Michael acceptors. The regioselectivity of the addition of this alkoxyacyl radical species to electron-deficient olefins is heavily influenced by the electronic nature of the acceptor, behavior similar to that exhibited by nucleophilic alkyl radicals