The merger of photoredox catalysis with transition metal catalysis, termed metallaphotoredox catalysis, has become a mainstay in synthetic methodology over the past decade. Metallaphotoredox catalysis has combined the unparalleled capacity of transition metal catalysis for bond formation with the broad utility of photoinduced electron- and energy-transfer processes. Photocatalytic substrate activation has allowed the engagement of simple starting materials in metal-mediated bond-forming processes. Moreover, electron or energy transfer directly with key organometallic intermediates has provided novel activation modes entirely complementary to traditional catalytic platforms. This Review details and contextualizes the advancements in molecule construction brought forth by metallaphotocatalysis.

We describe the synthesis through visible-light photocatalysis of novel functionalized tetracyclic scaffolds that incorporate a fused azabicyclo[3.2.0]heptan-2-one motif, which are structurally interesting cores with potential in natural product synthesis and drug discovery. The synthetic approach involves an intramolecular [2 + 2] cycloaddition with concomitant dearomatization of the heterocycle via an energy transfer process promoted by an iridium-based photosensitizer, to build a complex molecular architecture with at least three stereogenic centers from relatively simple, achiral precursors. These fused azabicyclo[3.2.0]heptan-2-one-based tetracycles were obtained in high yield (generally >99%) and with excellent diastereoselectivity (>99:1). The late-stage derivatization of a bromine-substituted, tetracyclic indoline derivative with alkyl groups, employing a mild Negishi C−C bond forming protocol as a means of increasing structural diversity, provides additional modularity that will enable the delivery of valuable building blocks for medicinal chemistry. Density functional theory calculations were used to compute the T 1 −S 0 free energy gap of the olefin-tethered precursors and also to predict their reactivities based on triplet state energy transfer and transition state energy feasibility.

Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that install methyl groups onto complex molecules are highly coveted. Late-stage C–H functionalization is a particularly attractive approach, allowing chemists to bypass lengthy syntheses and facilitating the expedited synthesis of drug analogues. Herein, we disclose the direct introduction of methyl groups via C(sp 3 )–H functionalization of a broad array of saturated heterocycles, enabled by the merger of decatungstate photocatalysis and a unique nickel-mediated SH2 bond formation. To further demonstrate its synthetic utility as a tool for late-stage functionalization, this method was applied to a range of drug molecules en route to an array of methylated drug analogues.

The visible light-promoted intramolecular [2+2] cycloaddition of N-allylcinnamamines and N-allylcinnamamides in the presence of catalytic amounts of [Ir{dF(CF 3 )ppy} 2 (dtbpy)]-PF 6 is reported. Low energy visible light and a high triplet energy iridium-photosensitizer were efficient at promoting the cycloaddition reaction of N-allylcinnamamides and N-allylcinnamamines to the corresponding aryl-3-azabicyclo[3.2.0]heptanones and aryl-3-azabicyclo[3.2.0]heptanes, respectively, [a]

A class of organocatalysts that are highly active for the conversion of 2′-deoxynucleosides to furanoid glycals have been discovered. These phosphorimides, (Ph 2 PS) 2 NH and (Ph 2 PSe) 2 NH, were shown to effectively mediate persilylation of 2′-deoxynucleosides allowing the elimination of the nucleobase giving the corresponding glycal. These mild conditions were demonstrated in the syntheses of glycals with various substitution patterns while minimizing the formation of undesired byproducts and expanding the scope of this methodology.

A general and diastereoselective fluorination/glycosylation strategy for the synthesis of 2′-fluorinated nucleosides has been developed. Electrophilic fluorination of a glycal with NFSI provided the 1′,2′-difunctionalized furanoside intermediate with high diastereoselectivity. The TBS-protected 2′-deoxyfluorosulfonimide sugar was prepared on an 80 g scale and isolated as a crystalline, bench-stable single diastereomer. This intermediate was found to undergo a subsequent glycosylation reaction with a variety of heteroaryl nucleophiles with generally good diastereoselectivities.

The Cover Feature shows the [2+2] photocycloaddition of highly functionalized N‐allylcinnamamides and N‐allylcinnamamines, that could provide the corresponding aryl‐3‐azabicyclo[3.2.0]heptanones and aryl‐3‐azabicyclo[3.2.0]heptanes, respectively. Those compounds are useful as both scaffolds and fragments in drug design and discovery. We thank Dr. John Tokarski at BMS and Accdon, LLC/ LetPub for the cover design. More information can be found in the Full Paper by M. S. Oderinde et al.