A Redox Auxiliary Strategy for Pyrrolidine Synthesis via Photocatalytic [3+2] Cycloaddition

Abstract

Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utilizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3 + 2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co-reductant. These conditions prevent the deleterious reductive ring-opening of the cyclopropyl substrates, enabling a range of less-reactive coupling partners to participate in this cycloaddition.[a] Dr.

Defluorodearomatization: A Photocatalytic Birch-Like Reduction That Enables C–C Bond Formation and Provides Access to Unnatural Cannabinoids

“…Taking the above experiments and observations, we present our working mechanistic understanding (Scheme ). After that absorption of a photon, an initial singlet photocatalyst rapidly undergoes intersystem crossing to yield the triplet excited-state photocatalyst. , Based on redox potentials, the reaction is expected to proceed through a reductive quenching cycle in which the triplet photocatalyst ( E 0 (Ir II /Ir III *) = −1.04 V) is reduced by an amine ( E ox ca. 0.5 V vs SCE).…”

“…Searching for optimal reaction conditions revealed that the mass balance for the products of the reaction, apart from several major products, consisted of a complex mixture of oligomers. Upon screening the photocatalysts (Table , entries 1–9), it was discovered that bis-4-( tert -butyl)-2-(4-( tert -butyl)­phenyl)­pyridine-4,4′-di- tert -butyl-2,2′-bipyridyl iridium­(III) hexafluorophosphate (Ir­(dtbbpy)­(dtbppy)­2PF 6 ) ( PC3 ), a somewhat oxidizing , and sterically bulky photocatalyst that has thus far been relatively underrepresented in the literature, was optimal, having a triplet-state emissive energy of 49.4 kcal/mol and energies of E 0 (Ir II /Ir III *) = −1.04 V and E 0 (Ir II /Ir III )= +1.13 V. While PC5 had a similar outcome in terms of the intended product, the reaction produced many minor side products and was therefore rejected to the simplify purification.…”

Synthesis of Chiral Amines by C–C Bond Formation with Photoredox Catalysis

“…This has also been exploited by Yoon et al in studies of [3+2] cycloaddition reactions of redox-active cyclopropyl ketones (Scheme 45). 91 In the presence of Ir(4-CF 3 -ppy) 3…”

“…This has also been exploited by Yoon et al in studies of [3+2] cycloaddition reactions of redox-active cyclopropyl ketones (Scheme 45). 91 In the presence of Ir(4-CF 3 -ppy) 3 and stoichiometric Yb(OTf) 3 , cyclopropane 4.29 underwent ring opening and radical addition to hydrazones such as 4.30 to afford N-aminopyrrolidines 4.31. The presumed mechanism involves oxidative quenching of the photocatalyst by the cyclopropyl ketone 4.29 to afford a ketyl radical 4.34, followed by cyclopropylcarbinyl radical rearrangement to distonic anion radical 4.35.…”

Ruthenium-Catalyzed Hydrodefluorination with Silane as the Directing and Reducing Group

“…Multifluorinated (partially fluorinated) arenes exhibit markedly altered properties compared to the parent nonfluorinated molecules and have potential applications in materials, pharmaceuticals, and other fields . The fluorinated arenes are not naturally occurring, and efficient methods for synthesis of multifluorinated arenes remain underdeveloped .…”