Paul William Davies

Azophosphines can act as bridging ligands between two gold centres, and the dimer is a pre-catalyst for cyclisation reactions.

The design and tuning of new ligands is crucial for unlocking new reactivity at transition metal centers. Azophosphines have recently emerged as a new class of 1,3-P,N ligands in ruthenium piano-stool complexes. This work shows that the azophosphine synthesis can tolerate N-aryl substituents with strongly electron-donating and electron-withdrawing para-R groups and that the nature of this R group can affect the spectroscopic and structural properties of the azophosphines, as measured by NMR spectroscopy, UV-vis spectroscopy, single-crystal X-ray diffraction, and DFT studies. Azophosphines are shown to be relatively weak phosphine donors, as shown by analysis of the ¹ J _P-Se coupling constants of the corresponding azophosphine selenides, but the donor properties can be fine tuned within this area of chemical space. Monodentate and bidentate Ru-azophosphine complexes were prepared, and their first use as a catalyst was probed. The Ru-azophosphine complexes were found to promote the transfer hydrogenation of acetophenone to 1-phenylethanol without the requirement of a harsh base additive, and the bidentate complex was more active than the monodentate analogue.

Sulfenylated propargylic carboxylates were introduced to investigate the influence of sulfur substitution in gold-catalyzed alkyne activation pathways. Regiodivergent gold-catalyzed rearrangement and indole capture reactions proceed under mild conditions to give functionalized indole products bearing sulfenylated (Z)-enol carboxylate motifs. Pathways involving both 1,2- and 1,3-carboxylate migrations are achieved selectively, with indole being added in a 1,4 relationship to the sulfenyl group in each case. High levels of selectivity are influenced by the catalyst system, counterion, and carboxylate group.

The design and tuning of new ligands is crucial for unlocking new reactivity at transition metal centres. Azophosphines have recently emerged as a new class of 1,3-P,N ligands in ruthenium piano-stool complexes. This work shows that the azophosphine synthesis can tolerate N-aryl substituents with strongly electron-donating and electron-withdrawing para-R groups, and that the nature of this R group can affect the spectroscopic and structural properties of the azophosphines, as measured by NMR spectroscopy, UV-Vis spectroscopy, single crystal X-ray diffraction and DFT studies. Azophosphines are shown to be relatively weak phosphine donors, as shown by analysis of the 1JP–Se coupling constants of the corresponding azophosphine selenides, but the donor properties can be fine-tuned within this area of chemical space. Monodentate and bidentate Ru-azophosphine complexes were prepared, and their first use as catalysts was probed. The Ru-azophosphine complexes were found to promote the transfer hydrogenation of acetophenone to 1-phenylethanol without the requirement of a harsh base additive, and the bidentate complex was more active than the monodentate analogue.

The regiodivergent synthesis of 4‐ and 5‐sulfenyl oxazoles from 1,4,2‐dioxazoles and alkynyl thioethers has been achieved. Gold‐catalysed conditions are used to favour the formation of 5‐sulfenyl oxazoles via β‐selective attack of the nitrenoid relative to the sulfenyl group. In contrast, 4‐sulfenyl oxazoles are formed by α‐selective reaction under Brønsted acid conditions from the same substrates. The nature of stabilising gold‐sulfur interactions have been investigated by natural bond orbital analysis, showing that the S→Au interactions are significantly stronger in the intermediate that favours the 5‐sulfenyl oxazoles. A kinetic survey identifies catalyst inhibition processes. This study into the regiodivergent methods includes the development of telescoped annulation‐oxidation protocols for regioselective access to oxazole sulfoxides and sulfones.

A polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium framework has been accessed from a new nitrenoid reagent by a two-step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions.

Sterically congested α-tertiary primary amines are ubiquitous substructures in pharmaceutical and agrochemical agents yet are challenging to access. Herein, a straightforward photoredox-catalyzed access to structurally diverse α,α,α-trisubstituted primary amines from denitrogenative alkylarylation or dialkylation of vinyl azides with NHPI esters and cyanoarenes or aryl aldehydes has been developed. The use of vinyl azides as a precursor of primary amines was enabled by the dual role of Hantzsch ester to form electron donor-acceptor (EDA) complexes and to serve as a sacrificial reductant. This strategy provides a modular synthesis of α-tertiary primary amines, including unprotected 1,2-amino alcohols, from simple materials with excellent functional group tolerance. The synthetic applicability of this method was demonstrated by streamlined access to 2,2-disubstituted tetrahydroquinolines. Preliminary investigations support two parallel reductive photocatalytic cycles allowing for the denitrogenative alkylarylation or dialkylation of vinyl azides via decarboxylative radical addition followed by hetero-radical cross-coupling between α-amino radicals and aryl anion radicals or ketyl anion radicals.

Here we report an organophotocatalytic synthesis of α-arylated carboxylic acids, esters and amides from exhaustive defluorination of α-trifluoromethyl alkenes in the presence of alkyltrifluoroborates, water and nitrogen/oxygen nucleophiles.

The combination of a nucleophilic nitrene equivalent, a triple bond and a π‐acid catalyst has underpinned numerous efficient transformations for the preparation of azacycles. This personal account details our efforts in developing an annulation strategy. Adding a nucleophilic nitrenoid to an activated alkyne can generate carbenoid character that is then quenched by a cyclisation onto the nitrenoid substituent. The use and development of N‐acyl and N‐heterocyclic pyridinium‐N‐aminides as 1,3‐N,O and 1,3‐N,N‐dipole equivalents is discussed in the context of oxazole and heterocycle‐fused imidazole formation, respectively. The resulting processes are highly efficient, practically straightforward, and tolerate considerable structural and functional group variation. Our use of heteroatom‐substituted alkynes as enabling tools for reaction discovery is discussed. The reactivity accessed from the strong donor‐like properties of ynamides is complemented by that obtained from alkynyl thioethers, which are emerging as interesting substrates for π‐acid catalysis.

Straightforward access to [1,2]-annulated indoles, key substructures in natural products, is highly desirable yet challenging. Herein, a radical triggered fragmentary cyclization cascade reaction of ene-ynamides is presented, providing a rapid access into [1,2]-annulated indoles by an intermolecular radical addition, intramolecular cyclization, desulfonylative aryl migration, and site-selective C(sp²)-N cyclization sequence. DFT calculations support oxidation of N-centered radical species to cations prior to the C–N bond formation, followed by an unusual aza-Nazarov cyclization.