Cyril Ollivier

Visible-Light-Induced Photoreductive Generation of Radicals from Epoxides and Aziridines†

Epoxides are readily available and highly valuable radical precursors, as demonstrated by their omnipresence in radical transformations. Several methodologies have been reported so far for their radical ring-opening. Epoxides are particularly prone to reductive ring-opening via one-electron transfer. Lithium 4,4′-di-tert-butylbiphenylid (LDBB) has thus been widely used to generate lithiated radical anions such as 99. This latter is immediately reduced to dianion 100 which can add to various electrophiles.

Silicates as Latent Alkyl Radical Precursors: Visible‐Light Photocatalytic Oxidation of Hypervalent Bis‐Catecholato Silicon Compounds

This works introduces hypervalent bis-catecholato silicon compounds as versatile sources of alkyl radicals upon visible-light photocatalysis. Using Ir[(dF(CF3)ppy)2(bpy)](PF6) (dF(CF3)ppy = 2-(2,4-difluorophenyl)-5-trifluoromethylpyridine, bpy = bipyridine) as catalytic photooxidant, a series of alkyl radicals, including highly reactive primary ones can be generated and engaged in various intermolecular homolytic reactions. Based on cyclic voltammetry, Stern-Volmer studies, and supported by calculations, a mechanism involving a single-electron transfer from the silicate to the photoactivated iridium complex has been proposed. This oxidative photocatalyzed process can be efficiently merged with nickel-catalyzed Csp2-Csp3 cross-coupling reactions.

Expeditious synthesis of phenanthridines from benzylamines via dual palladium catalysis.

A method for the synthesis of phenanthridines from benzylamines and aryl iodides which uses a dual palladium-catalyzed process is developed. The domino sequence ends via an intramolecular amination and an oxidative dehydrogenation. No protecting group or prefunctionalization of the amine is required, and the process uses dioxygen as the terminal oxidant.

Photoredox Catalysis for the Generation of Carbon Centered Radicals

Radical chemistry has witnessed over the last decades important advances that have positioned it as a methodology of choice in synthetic chemistry. A number of great attributes such as specific reactivities, the knowledge of the kinetics of most elementary processes, the functional group tolerance, and the possibility to operate cascade sequences are clearly responsible for this craze. Nevertheless, at the end of the last century, radical chemistry appeared plagued by several hurdles to overcome such as the use of environmentally problematic mediators or the impossibility of scale up. While the concept of photocatalysis was firmly established in the coordination chemistry community, its diffusion in organic synthetic chemistry remained sporadic for decades until the end of the 2000s with the breakthrough merging of organocatalysis and photocatalysis by the MacMillan group and contemporary reports by the groups of Yoon and Stephenson. Since then, photoredox catalysis has enjoyed particularly active and intense developments. It is now the topic of a still increasing number of publications featuring various applications from asymmetric synthesis, total synthesis of natural products, and polymerization to process (flow) chemistry. In this Account, we survey our own efforts in this domain, focusing on the elaboration of new photocatalytic pathways that could lead to the efficient generation of C-centered functionalized alkyl and aryl radicals. Both reductive and oxidative manifolds are accessible through photoredox catalysis, which has guided us along these lines in our projects. Thus, we studied the photocatalytic reduction of onium salts such as sulfoniums and iodoniums for the production of the elusive aryl radical intermediates. Progressing to more relevant chemistry for synthesis, we examined the cleavage of C-O and the C-Br bonds for the generation of alkyl C-centered radicals. Activated epoxides could serve as valuable substrates of a photocatalyzed variant of the Nugent-RajanBabu-Gansäuer homolytic cleavage of epoxides. Using imidazole based carbamates, we could also devise the first photocatalyzed Barton-McCombie deoxygenation reaction. Finally, bromophenylacetate can be reduced using the [Au2(μ-dppm)2]Cl2 photocatalyst under UVA or visible-light. This was used for the initiation of the controlled atom transfer radical polymerization of methacrylates and acrylates in solution or laminate. Our next endeavors concerned the photocatalyzed oxidation of stabilized carbanions such as enolates of 1,3-dicarbonyl substrates, trifluoroborates, and more extensively bis-catecholato silicates. Because of their low oxidation potentials, the later have proved to be exquisite sources of radical entities, which can be engaged in diverse intermolecular reactions such as vinylation, alkynylation, and conjugate additions. The bis-catecholato silicates were also shown to behave as excellent partners of dual photoredox-nickel catalysis leading in an expeditious manner to libraries of cross coupling products.

Radical Synthesis of Guanidines from N‐Acyl Cyanamides

Guanidines—especially those embedded into polyclic frameworks—are an important structural unit of valuable synthetic intermediates and/or natural products. Therefore guanidines are appealing targets for total synthesis, bio-inspired molecular recognition, organocatalysis, and coordination chemistry. The development of innovative, efficient, and flexible methods to access these compounds thus remains an important goal. Radical cascade cyclization reactions have become an important tool used to construct polycyclic structures, in particular nitrogen-containing heterocycles. Our research group has introduced N-acyl cyanamides as novel radical partners for the preparation of quinazolinone systems such as luotonin A, through a radical domino sequence. Our approach to luotonin A included a retrosynthetic disconnection featuring the cyclization of a 2-quinolyl radical to an acylcyanamide A (Scheme 1). We reasoned that switching the initial carbon radical to a nitrogen-centered one (as in B) would provide an entry to cyclic guanidines after aromatic substitution of iminyl radical C, via tricyclic radical D (path a). To the best of our knowledge, a radical synthesis of guanidines is unprecedented in the literature. Iminyl radical C could also lead to a competing and unproductive b-elimination of an amidyl radical and deliver E, where the cyano group of the starting cyanamide has translocated to form a nitrogen-centered radical (path b). Nonetheless, our previous results with carbon-centered radicals made us confident that this would, at worst, be a minor path. Spagnolo and co-workers have shown that the stannylaminyl radicals obtained from reactions of tin radicals with alkyl azides add efficiently to the electrophilic cyano group. We thus decided to follow the same strategy, even though the reactivity of cyanamides may differ from that of nitriles because of the added nitrogen substituent. Substrate 1a was selected to validate our approach and was assembled in a very modular fashion from the corresponding amine, cyanogen bromide, and benzoyl chloride. We initially used the reaction conditions developed in our previous work; Bu3SnH (2 equiv) and AIBN (1.5 equiv) were slowly added (0.2 molh ) to 1a in benzene at reflux. Gratifyingly, the desired tricyclic guanidine 2a was isolated, but in a modest 41% yield (Table 1, entry 1). Replacement of benzene by toluene or tBuOH reduced the yields (Table 1, entries 2 and 3). Slow addition of Bu3SnH from a syringe pump was required and resulted in the yields increasing from 20 % (addition of Bu3SnH in one batch; Table 1, entry 4), to 41% (0.2 mmolh ; Table 1, entry 1), and then to 76 % (0.06 mmolh ; Table 1, entry 5). Lowering the amount of tin was not helpful (43 % yield with 1.2 equiv of Bu3SnH; Table 1, entry 6). Switching to [(CH3)3Si]3SiH or running the reaction at room temperature with initiation by light led to a near complete shutdown of the reaction (Table 1, entries 7 and 8). Therefore, the best yield was obtained by slowly adding Bu3SnH (0.06 molh , 2 equiv) and AIBN (1.5 equiv) to a solution of w-azido N-acyl cyanamide in benzene at reflux (Table 1, entry 5). With these optimized reaction conditions in hand, we next examined the scope for the radical synthesis of guanidine Scheme 1. Access to luotonin A and proposed route to guanidine derivatives.

Boron: A key element in radical reactions

Boron derivatives are becoming key reagents in radical chemistry. Here, we describe reactions where an organoboron derivative is used as a radical initiator, a chain-transfer reagent, and a radical precursor. For instance, B-alkylcatecholboranes, easily prepared by hydroboration of alkenes, represent a very efficient source of primary, secondary, and tertiary alkyl radicals. Their very high sensitivity toward oxygen- and heteroatom-centered radicals makes them particularly attractive for the development of radical chain processes such as conjugate addition, allylation, alkenylation, and alkynylation. Boron derivatives have also been used to develop an attractive new procedure for the reduction of radicals with alcohols and water. The selected examples presented here demonstrate that boron-containing reagents can efficiently replace tin derivatives in a wide range of radical reactions.

A dinuclear gold(I) complex as a novel photoredox catalyst for light-induced atom transfer radical polymerization

Controlled/living atom transfer radical polymerization of methacrylates and acrylates initiated by ethyl α-bromophenylacetate (EBPA) as the initiator in the presence of low loadings (1.25 mol% vs. initiator) of a dinuclear gold(I) complex based photocatalyst [Au2(μ-dppm)2]Cl2 has been accomplished in solution and in laminate under UVA and visible-light photoreductive conditions. In solution, the linear increase of molecular weights with methyl methacrylate (MMA) conversion and the low dispersity are consistent with a controlled/living process. In a film, trimethylolpropane triacrylate (TMPTA) was polymerized and the ethyl α-bromophenylacetate (EBPA)/[Au2(μ-dppm)2]Cl2 system resulted in a faster rate of polymerization compared to EBPA/Ir(ppy)3. Chain extensions of polymers were successfully conducted leading to block copolymers, which also confirms the living character of this new system. Photophysical experiments support a conventional photoredox-catalyzed ATRP mechanism. Finally, this approach utilizes a gold catalyst featuring better solubility and lower cost than the well-known Ir(ppy)3 complex.

Radical migration of substituents of aryl groups on quinazolinones derived from N-acyl cyanamides.

A newly designed radical cascade involving N-acyl cyanamides is reported. It builds on aromatic homolytic substitutions as intermediate events and leads to complex heteroaromatic structures via an unprecedented radical migration of a substituent on aryl groups of quinazolinones (hydrogen or alkyl). Mechanistic considerations are detailed, which allowed us to devise fine control over the domino processes. The latter could be predictably stopped at several stages, depending on the reaction conditions. Finally, a surgical introduction of a trifluoromethyl substituent on a quinazolinone was achieved via the reported migration.

B-Alkylcatecholboranes as a Source of Radicals for Efficient Conjugate Additions to Unsaturated Ketones and Aldehydes

Selective generation of radicals from organoboranes is reported. A simple one-pot procedure involving a hydroboration with catecholborane followed by a radical reaction has been developed (see equation).

Primary alkyl bis-catecholato silicates in dual photoredox/nickel catalysis: aryl- and heteroaryl-alkyl cross coupling reactions

Primary alkyl bis-catecholato silicates have been successfully engaged with aryl and heteroaryl bromide substrates in photoredox/nickel dual catalysis to provide aryl- and heteroaryl-alkyl cross coupling products. The scope of the transformation is wide and the process appears to be tolerant of various functional groups present. Of note, most examples rely on the challenging use of highly reactive primary radicals which constitutes a significant advance in these cross coupling reactions.