Photomediated Giese reactions are at the forefront of radical chemistry, much like the classical tin‐mediated Giese reactions were nearly forty years ago. With the global recognition of organometallic photocatalysts for the mild and tunable generation of carbon‐centered radicals, chemists have developed a torrent of strategies to form previously inaccessible radical intermediates that are capable of engaging in intermolecular conjugate addition reactions. This Review summarizes advances in photoredox‐mediated Giese reactions since 2013, with a focus on the breadth of methods that provide access to crucial carbon‐centered radical intermediates that can engage in radical conjugate addition processes.
A general method for the N-arylation of sulfamides with aryl bromides is described.The protocol leverages a dual-catalytic system of nickel and a photoexcitable iridium complex and proceeds at room temperature under visible light irradiation. Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. Thereby, this method complements known Buchwald-Hartwig coupling methods for N-arylation of sulfamides.
Alcohol-anchored sulfamate esters guide the alkylation of tertiary and secondary aliphatic C(3)−H bonds. The transformation proceeds directly from N−H bonds with a catalytic oxidant, a contrast to prior methods which have required preoxidation of the reactive nitrogen center, or employed stoichiometric amounts of strong oxidants to obtain the sulfamyl radical. These sulfamyl radicals template otherwise rare 1,6-hydrogen-atom transfer (HAT) processes via seven-membered ring transition states to enable C(3)−H functionalization during Giese reactions.N itrogen-centered radicals are an important and versatile class of chemical intermediates. 1 Yet, nitrogen-centered radicals remain underutilized, as most methods for their generation rely on harsh conditions to oxidize the nitrogen center. Recently, photocatalytic strategies have been developed as mild processes to form nitrogen-centered radicals; 2−6 however, only amides, carbamates, and sulfonamides have served as precursors to neutral nitrogen-centered radicals. 4−6 These groups template position-selective C−H functionalization technologies, transforming C(4)−H bonds through 1,5-HAT processes (Scheme 1A). 7 In contrast, sulfamate esters guide functionalization to C(3)−H centers through otherwise rare 1,6-HAT processes (Scheme 1B), providing complementary positional selectivity to established processes. 8−16 As a complement to known guided methods, sulfamate esters are attractive directing groups because they derive from alcohols, which are ubiquitous in biologically active small molecules. To date, protocols templated by sulfamate ester substrates require preoxidation of the reactive nitrogen center, or the use of strong stoichiometric oxidants to access nitrogen-centered sulfamyl radicals. 14,15 As such, a strategy to facilitate sulfamyl radical formation directly from N−H bonds under mild conditions would enhance the substrate tolerance of these directing motifs, and could also enable previously unrealized synthetic disconnections. 17,18 Herein disclosed is the first catalytic process to access free sulfamyl radicals directly from N−H bonds. 19 These sulfamyl radicals have been engaged in Giese reactions, in the only examples of C(3)−H alkylation reactions guided by alcohol surrogates (Scheme 1C, 1 → 2).At the outset of these investigations, we sought conditions that would facilitate oxidation of sulfamate ester 1a to sulfamyl radical 3a. We envisioned that this could occur through an initial deprotonation to provide sulfamate ester anion 4a. Anion 4a could undergo single electron oxidation to generate sulfamyl radical 3a, with concurrent reduction of the excited iridium catalyst 6a (Scheme 2). Consistent with this proposal, in acetonitrile, sodiated 5-methylhexyl N-tert-butyl sulfamate ester anion 4a has a half-peak potential (E p/2 ) of +0.753 V
A general method is described for the coupling of (hetero)aryl bromides with O-alkyl sulfamate esters. The protocol relies on catalytic amounts of nickel and photoexcitable iridium complexes and proceeds under visible light irradiation at ambient temperature. This technology engages a broad range of simple and complex O-alkyl sulfamate ester substrates under mild conditions. Furthermore, it is possible to avoid undesirable N-alkylation, which was found to plague palladium-based protocols for N-arylation of O-alkyl sulfamate esters. These investigations represent the first use of sulfamate esters as nucleophiles in transition metal-catalyzed C–N coupling processes.
One of the first environmental cues sensed by a microbe as it enters a human host is an upshift in temperature to 37°C. In this dynamic timepoint analysis, we demonstrate that this environmental transition rapidly signals a multitude of gene expression changes in Escherichia coli . Bacteria grown at 23°C under aerobic conditions were shifted to 37°C and mRNA expression was measured at timepoints after the shift to 37°C (t=0.5, 1, and 4 hours). The first hour is characterized by a transient shift to anaerobic respiration strategies and stress responses, particularly acid resistance, indicating that temperature serves as a sentinel cue to predict and prepare for various niches within the host. The temperature effects on a subset of stress response genes were shown to be mediated by RpoS, directly correlated with RpoS, DsrA and RprA levels, and increased acid resistance was observed that was dependent on 23°C growth and RpoS. By 4 hours, gene expression shifted to aerobic respiration pathways, decreased stress responses, coupled with increases in genes associated with biosynthesis (amino acid, nucleotides), iron uptake, and host defense. ompT , a gene that confers resistance to antimicrobial peptides, was highly thermoregulated and with a pattern conserved in enteropathogenic and uropathogenic E. coli . An immediate decrease in curli gene expression concomitant with an increase in flagellar gene expression implicates temperature in this developmental decision. Together, our studies demonstrate that temperature signals a reprogramming of gene expression immediately upon an upshift that may predict, prepare, and benefit survival of the bacterium within the host. IMPORTANCE: As one of the first cues sensed by the microbe upon entry into a human host, understanding how bacteria like E. coli modulate gene expression in response to temperature improves our understanding of how bacteria immediately initiate responses beneficial to survival and colonization. For pathogens, understanding the various pathways of thermal regulation could yield valuable targets for anti-infective chemotherapeutic drugs or disinfection measures. In addition, our data provide a dynamic examination of the RpoS stress response, providing genome-wide support for how temperature impacts RpoS through changes in RpoS stability and modulation by small regulatory RNAs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.