A combined Lewis acid/photoredox catalyst system enabled the intramolecular umpolung addition of ketyl radicals to vinylogous carbonates in the synthesis of 2,6-dioxabicyclo[3.3.0]octan-3-ones. This reaction proceeded on a variety of aromatic ketones to provide THF rings in good yield (up to 95%). Although diastereoselectivity was found to be modest (1.4-5:1) for the C-C bond forming reaction, the minor diastereomers were converted to 2,6-dioxabicyclo[3.3.0]octan-3-ones by an efficient Lewis acid-mediated epimerization cascade in up to 90% yield.

The stereoselective synthesis of molecules bearing stereogenic phosphorus(V) centers represents an enduring challenge in organic chemistry. Although stereospecific nucleophilic substitution at P(V) provides a general strategy for elaborating optically active P(V) compounds, existing methods for accessing the requisite chiral building blocks rely almost entirely on diastereocontrol using chiral auxiliaries. Catalytic, enantioselective methods for the synthesis of synthetically versatile stereogenic P(V) building blocks offer an alternative approach to stereogenic-at-P(V) targets without requiring stoichiometric quantities of chiral control elements. Here, we report an enantioselective hydrogen-bond-donor–catalyzed synthesis of aryl chlorophosphonamidates and the development of these products as versatile chiral P(V) building blocks. We demonstrate that the two leaving groups on these chlorophosphonamidates can be displaced sequentially and stereospecifically to access a wide variety of stereogenic-at-P(V) compounds featuring diverse substitution patterns.

Photoredox catalysis has become a powerful method to generate free radical intermediates in organic synthesis. This report describes the use of photoredox catalysis to directly oxidize common nucleophilic anions to access electrophilic 1,3-dicarbonyl and amidyl radical intermediates. First, conjugate bases of 1,3-dicarbonyls were oxidized to neutral radical species for intramolecular hydro-and dialkylation of alkenes. This overall redox-neutral process provided cyclopentanone products in excellent yields (up to 96%). The scope included a variety of styrene radical acceptors and products with newly formed vicinal quaternary carbons. This process was then extended to the synthesis of pyrrolidinones by alkene amidoalkylation that proceeded via N-aryl amidyl radical intermediates in good yield (up to 85%). These reactions were characterized by their mild conditions, high atom economy, and the absence of stoichiometric byproducts. Mechanistic and computational studies supported a stepwise proton-coupled electron transfer mechanism, where an "electron borrowing" photocatalyst oxidizes an anion and reduces a benzylic radical after bond formation.

The stereoselective synthesis of molecules bearing stereogenic phosphorus(V) centers represents an enduring challenge in organic chemistry. While stereospecific nucleophilic substitution at P(V) provides a general strategy for elaborating optically active P(V) compounds, existing methods for accessing the requisite chiral building blocks rely almost entirely on diastereocontrol using chiral auxiliaries. Catalytic, enantioselective methods for the synthesis of synthetically versatile stereogenic P(V) building blocks offer an alternative approach to stereogenic-at-P(V) targets without requiring stoichiometric quantities of chiral controlling elements. Herein, we report an enantioselective hydrogen-bond-donor-catalyzed synthesis of chlorophosphonamidates, and the development of these products as versatile chiral P(V) building blocks. We demonstrate that chlorophosphonamidates possess two leaving groups that can be displaced sequentially and stereospecifically to access a wide variety of stereogenic-at-P(V) compounds featuring diverse substitution patterns.