Photoredox catalysis via consecutive 2LMCT- and 3MLCT-excitation of an Fe(iii/ii)–N-heterocyclic carbene complex

Fe–N-heterocyclic carbene (NHC) complexes attract increasing attention as photosensitisers and photoredox catalysts. Such applications generally rely on sufficiently long excited state lifetimes and efficient bimolecular quenching, which leads to there being few examples of successful usage of Fe–NHC complexes to date. Here, we have employed [Fe(iii)(btz)₃]³⁺ (btz = (3,3′-dimethyl-1,1′-bis(p-tolyl)-4,4′-bis(1,2,3-triazol-5-ylidene))) in the addition of alkyl halides to alkenes and alkynes via visible light-mediated atom transfer radical addition (ATRA). Unlike other Fe–NHC complexes, [Fe(iii/ii)(btz)₃]^3+/2+ benefits from sizable charge transfer excited state lifetimes ≥0.1 ns in both oxidation states, and the Fe(iii) ²LMCT and Fe(ii) ³MLCT states are strong oxidants and reductants, respectively. The combined reactivity of both excited states enables efficient one-electron reduction of the alkyl halide substrate under green light irradiation. The two-photon mechanism proceeds via reductive quenching of the Fe(iii) ²LMCT state by a sacrificial electron donor and subsequent excitation of the Fe(ii) product to its highly reducing ³MLCT state. This route is shown to be more efficient than the alternative, where oxidative quenching of the less reducing Fe(iii) ²LMCT state by the alkyl halide drives the reaction, in the absence of a sacrificial electron donor.

An iron complex with N-heterocyclic carbene ligands engages in efficient photoredox catalysis via excited state electron transfer reactions of its Fe(ii) and Fe(iii) oxidation states.     

DFT insight into asymmetric alkyl–alkyl bond formation via nickel-catalysed enantioconvergent reductive coupling of racemic electrophiles with olefins

A DFT study has been conducted to understand the asymmetric alkyl–alkyl bond formation through nickel-catalysed reductive coupling of racemic alkyl bromide with olefin in the presence of hydrosilane and K₃PO₄. The key findings of the study include: (i) under the reductive experimental conditions, the Ni(ii) precursor is easily activated/reduced to Ni(0) species which can serve as an active species to start a Ni(0)/Ni(ii) catalytic cycle. (ii) Alternatively, the reaction may proceed via a Ni(i)/Ni(ii)/Ni(iii) catalytic cycle starting with a Ni(i) species such as Ni(i)–Br. The generation of a Ni(i) active species via comproportionation of Ni(ii) and Ni(0) species is highly unlikely, because the necessary Ni(0) species is strongly stabilized by olefin. Alternatively, a cage effect enabled generation of a Ni(i) active catalyst from the Ni(ii) species involved in the Ni(0)/Ni(ii) cycle was proposed to be a viable mechanism. (iii) In both catalytic cycles, K₃PO₄ greatly facilitates the hydrosilane hydride transfer for reducing olefin to an alkyl coupling partner. The reduction proceeds by converting a Ni–Br bond to a Ni–H bond via hydrosilane hydride transfer to a Ni–alkyl bond via olefin insertion. On the basis of two catalytic cycles, the origins for enantioconvergence and enantioselectivity control were discussed.

The enantioconvergent alkyl–alkyl coupling involves two competitive catalytic cycles with nickel(0) and nickel(i) active catalysts, respectively. K₃PO₄ plays a crucial role to enable the hydride transfer from hydrosilane to nickel–bromine species.     

Rh(i)-catalyzed dimerization of ene-vinylidenecyclopropanes for the construction of spiro[4,5]decanes and mechanistic studies

Rh(i) complex catalyzed dimerization of ene-vinylidenecyclopropanes took place smoothly to construct a series of products containing spiro[4,5]decane skeletons featuring a simple operation procedure, mild reaction conditions, and good functional group tolerance. In this paper, the combination of experimental and computational studies reveals a counterion-assisted Rh(i)–Rh(iii)–Rh(v)–Rh(iii)–Rh(i) catalytic cycle involving tandem oxidative cyclometallation/reductive elimination/selective oxidative addition/selective reductive elimination/reductive elimination steps; in addition, a pentavalent spiro-rhodium intermediate is identified as the key intermediate in this dimerization reaction upon DFT calculation.

Rh(i) complex catalyzed dimerization of ene-vinylidenecyclopropanes has been demonstrated, and its reaction mechanism is revealed based on a series of mechanistic studies.     

Hemilabile MIC^N ligands allow oxidant-free Au(i)/Au(iii) arylation-lactonization of γ-alkenoic acids

Oxidant-free Au-catalyzed reactions are emerging as a new synthetic tool for innovative organic transformations. Oxidant-free Au-catalyzed reactions are emerging as a new synthetic tool for innovative organic transformations. Still, a deeper mechanistic understanding is needed for a rational design of these processes. Here we describe the synthesis of two Au(i) complexes bearing bidentated hemilabile MIC^N ligands, [Au^I(MIC^N)Cl], and their ability to stabilize square-planar Au(iii) species (MIC = mesoionic carbene). The presence of the hemilabile N-ligand contributed to stabilize the ensuing Au(iii) species acting as a five-membered ring chelate upon its coordination to the metal center. The Au(iii) complexes can be obtained either by using external oxidants or, alternatively, by means of feasible oxidative addition with strained biphenylene C_sp²–C_sp² bonds as well as with aryl iodides. Based on the fundamental knowledge gained on the redox properties on these Au(i)/Au(iii) systems, we successfully develop a novel Au(i)-catalytic procedure for the synthesis of γ-substituted γ-butyrolactones through the arylation-lactonization reaction of the corresponding γ-alkenoic acid. The oxidative addition of the aryl iodide, which in turn is allowed by the hemilabile nature of the MIC^N ligand, is an essential step for this transformation.

A novel hemilabile MIC^N ligand-based Au(i)-catalytic procedure for the synthesis of γ-substituted γ-butyrolactones through the arylation-lactonization reaction of the corresponding γ-alkenoic acid is presented.     

Organocatalytic Synthesis of Higher‐Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d‐Glycero‐l‐galacto‐oct‐2‐ulose

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher‐carbon sugars—sedoheptulose (d‐altro‐hept‐2‐ulose) and d‐glycero‐l‐galacto‐oct‐2‐ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn‐selective aldol reaction of DHA with d‐erythrose and d‐xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn‐selective carbon–carbon‐bond‐forming aldol reactions promoted by primary‐based organocatalysts. For example, this methodology provided useful access to d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose from d‐arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1).     

Mg(ii) heterodinuclear catalysts delivering carbon dioxide derived multi-block polymers

Carbon dioxide derived polymers are emerging as useful materials for applications spanning packaging, construction, house-hold goods and automotive components. To accelerate and broaden their uptake requires both more active and selective catalysts and greater structural diversity for the carbon dioxide derived polymers. Here, highly active catalysts show controllable selectivity for the enchainment of mixtures of epoxide, anhydride, carbon dioxide and lactone. Firstly, metal dependent selectivity differences are uncovered using a series of dinuclear catalysts, Mg(ii)Mg(ii), Zn(ii)Zn(ii), Mg(ii)Zn(ii), and Mg(ii)Co(ii), each exposed to mixtures of bio-derived tricyclic anhydride, cyclohexene oxide and carbon dioxide (1 bar). Depending upon the metal combinations, different block structures are possible with Zn(ii)Zn(ii) yielding poly(ester-b-carbonate); Mg(ii)Mg(ii) or Mg(ii)Co(ii) catalysts delivering poly(carbonate-b-ester); and Mg(ii)Zn(ii) furnishing a random copolymer. These results indicate that carbon dioxide insertion reactions follow the order Co(ii) > Mg(ii) > Zn(ii). Using the most active and selective catalyst, Mg(ii)Co(ii), and exploiting reversible on/off switches between carbon dioxide/nitrogen at 1 bar delivers precision triblock (ABA), pentablock (BABAB) and heptablock (ABABABA) polymers (where A = poly(cyclohexylene oxide-alt-tricyclic anhydride), PE; B = poly(cyclohexene carbonate), PCHC). The Mg(ii)Co(ii) catalyst also selectively polymerizes a mixture of anhydride, carbon dioxide, cyclohexene oxide and ε-caprolactone to deliver a CBABC pentablock copolymer (A = PE, B = PCHC C = poly(caprolactone), PCL). The catalysts combine high activity and selectivity to deliver new polymers featuring regularly placed carbon dioxide and biomass derived linkages.

Carbon dioxide-based multiblock polymers are synthesised, in one-pot, from a mixture of monomers using a highly selective and active heterodinuclear Co(ii)Mg(ii) catalyst.     

Structure,reactivity and luminescence studies of triphenylsiloxide complexes of tetravalent lanthanides

Among the 14 lanthanide elements (Ce–Lu), until recently, the tetravalent oxidation state was readily accessible in solution only for cerium while Pr(iv), Nd(iv), Dy(iv) and Tb(iv) had only been detected in the solid state. The triphenylsiloxide ligand recently allowed the isolation of molecular complexes of Tb(iv) and Pr(iv) providing an unique opportunity of investigating the luminescent properties of Ln(iv) ions. Here we have expanded the coordination studies of the triphenylsiloxide ligand with Ln(iii) and Ln(iv) ions and we report the first observed luminescence emission spectra of Pr(iv) complexes which are assigned to a ligand-based emission on the basis of the measured lifetime and computational studies. Binding of the ligand to the Pr(iv) ion leads to an unprecedented large shift of the ligand triplet state which is relevant for future applications in materials science.

The first observed luminescence emission spectra of Pr(iv) complexes are assigned to a ligand-based emission. Binding of the triphenylsiloxide ligand to the Pr(iv) ion leads to an unprecedented large red shift of its triplet state.     

Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization

l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21–23%) and l-galactose derivatives in 12 steps (total yields: 6–8%) starting from d-mannose.     

Electrochemical oxidative N–H/P–H cross-coupling with H2 evolution towards the synthesis of tertiary phosphines

Tertiary phosphines(iii) find widespread use in many aspects of synthetic organic chemistry. Herein, we developed a facile and novel electrochemical oxidative N–H/P–H cross-coupling method, leading to a series of expected tertiary phosphines(iii) under mild conditions with excellent yields. It is worth noting that this electrochemical protocol features very good reaction selectivity, where only a 1 : 1 ratio of amine and phosphine was required in the reaction. Moreover, this electrochemical protocol proved to be practical and scalable. Mechanistic insights suggested that the P radical was involved in this reaction.

A facile and novel electrochemical oxidative N–H/P–H cross-coupling method for obtaining tertiary phosphines(iii) was developed.     

A dual catalytic strategy for carbon–phosphorus cross-coupling via gold and photoredox catalysis

A new method for the P-arylation of aryldiazonium salts with H-phosphonates via dual gold and photoredox catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or additives, and offers an efficient approach to arylphosphonates. The reaction is proposed to proceed through a photoredox-promoted generation of an electrophilic arylgold(iii) intermediate that undergoes coupling with the H-phosphonate nucleophile.     

Aptamer-modified DNA tetrahedra-gated metal–organic framework nanoparticle carriers for enhanced chemotherapy or photodynamic therapy

UiO-66 metal–organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications. Hybrid nano-carriers consisting of ATP-aptamer or VEGF-aptamer functionalized tetrahedra-gated NMOFs are loaded with the chemotherapeutic drug, doxorubicin (DOX). In the presence of ATP or VEGF, both abundant in cancer cells, the tetrahedra-gated NMOFs are unlocked to release the drug. Enhanced and selective permeation of the DOX-loaded ATP/VEGF-responsive tetrahedra-gated NMOFs into MDA-MB-231 breast cancer cells as compared to the reference ATP/VEGF-responsive duplex-gated NMOFs or non-malignant MCF-10A epithelial breast cells is observed. This results in enhanced and selective cytotoxicity of the tetrahedra-gated DOX-loaded NMOFs toward the malignant cells. Additional nano-carriers, consisting of photosensitizer Zn(ii) protoporphyrin IX (Zn(ii)-PPIX)-loaded VEGF-responsive tetrahedra-gated NMOFs, are introduced. The VEGF-triggered unlocking of the NMOFs yields separated G-quadruplex-VEGF aptamer complexes conjugated to the tetrahedra, resulting in the release of loaded Zn(ii)-PPIX. Association of the released Zn(ii)-PPIX to the G-quadruplex structures generates highly fluorescent supramolecular Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra structures. The efficient and selective generation of the highly fluorescent Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra nanostructures in malignant cells allows the light-induced photosensitized generation of reactive oxygen species (ROS), leading to high-efficacy PDT treatment of the malignant cells.

UiO-66 metal–organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications.     

Understanding the mechanism of direct visible-light-activated [2 + 2] cycloadditions mediated by Rh and Ir photocatalysts: combined computational and spectroscopic studies

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques. Experimental observations show that the Rh-based photocatalyst produces excellent yield and enantioselectivity whereas the Ir-photocatalyst yields racemates. Two different mechanistic features were found to compete with each other, namely the direct photoactivation of the catalyst–substrate complex and outer-sphere triplet energy transfer. Our integrated analysis suggests that the direct photocatalysis is the inner working of the Rh-catalyzed reaction, whereas the Ir catalyst serves as a triplet sensitizer that activates cycloaddition via an outer-sphere triplet excited state energy transfer mechanism.

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques.     

Highly efficient carbazolylgold(iii) dendrimers based on thermally activated delayed fluorescence and their application in solution-processed organic light-emitting devices

A new class of C^C^N ligand-containing carbazolylgold(iii) dendrimers has been designed and synthesized. High photoluminescence quantum yields of up to 82% in solid-state thin films and large radiative decay rate constants in the order of 10⁵ s⁻¹ are observed. These gold(iii) dendrimers are found to exhibit thermally activated delayed fluorescence (TADF), as supported by variable-temperature emission spectroscopy, time-resolved photoluminescence decay and computational studies. Solution-processed organic light-emitting diodes (OLEDs) based on these gold(iii) dendrimers have been fabricated, which exhibit a maximum current efficiency of 52.6 cd A⁻¹, maximum external quantum efficiency of 15.8% and high power efficiency of 41.3 lm W⁻¹. The operational stability of these OLEDs has also been recorded, with the devices based on zero- and second-generation dendrimers showing maximum half-lifetimes of 1305 and 322 h at 100 cd m⁻², respectively, representing the first demonstration of operationally stable solution-processed OLEDs based on gold(iii) dendrimers.

A new class of carbazolylgold(iii) C^C^N dendrimers with thermally activated delayed fluorescence properties has been designed and synthesized for the realzaqtion of operationally stable solution-processed organic light-emitting devices.     

Enhanced photoreduction of water catalyzed by a cucurbit[8]uril-secured platinum dimer

A cucurbit[8]uril (CB[8])-secured platinum terpyridyl chloride dimer was used as a photosensitizer and hydrogen-evolving catalyst for the photoreduction of water. Volumes of produced hydrogen were up to 25 and 6 times larger than those obtained with the corresponding free and cucurbit[7]uril-bound platinum monomer, respectively, at equal Pt concentration. The thermodynamics of the proton-coupled electron transfer from the Pt(ii)–Pt(ii) dimer to the corresponding Pt(ii)–Pt(iii)–H hydride key intermediate, as quantified by density functional theory, suggest that CB[8] secures the Pt(ii)–Pt(ii) dimer in a particularly reactive conformation that promotes hydrogen formation.

The cucurbit[8]uril macrocycle can secure a platinum terpyridyl complex into a particularly reactive dimer that catalyzes the photoreduction of water.     

Hydrophilic sulfonated bis-1,2,4-triazine ligands are highly effective reagents for separating actinides(iii) from lanthanides(iii) via selective formation of aqueous actinide complexes

We report the first examples of hydrophilic 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) and 2,9-bis(1,2,4-triazin-3-yl)-1,10-phenanthroline (BTPhen) ligands, and their applications as actinide(iii) selective aqueous complexing agents. The combination of a hydrophobic diamide ligand in the organic phase and a hydrophilic tetrasulfonated bis-triazine ligand in the aqueous phase is able to separate Am(iii) from Eu(iii) by selective Am(iii) complex formation across a range of nitric acid concentrations with very high selectivities, and without the use of buffers. In contrast, disulfonated bis-triazine ligands are unable to separate Am(iii) from Eu(iii) in this system. The greater ability of the tetrasulfonated ligands to retain Am(iii) selectively in the aqueous phase than the corresponding disulfonated ligands appears to be due to the higher aqueous solubilities of the complexes of the tetrasulfonated ligands with Am(iii). The selectivities for Am(iii) complexation observed with hydrophilic tetrasulfonated bis-triazine ligands are in many cases far higher than those found with the polyaminocarboxylate ligands previously used as actinide-selective complexing agents, and are comparable to those found with the parent hydrophobic bis-triazine ligands. Thus we demonstrate a feasible alternative method to separate actinides from lanthanides than the widely studied approach of selective actinide extraction with hydrophobic bis-1,2,4-triazine ligands such as CyMe₄-BTBP and CyMe₄-BTPhen.     

‘Reverse biomimetic’ synthesis of l-arogenate and its stabilized analogues from l-tyrosine

l-Arogenate (also known as l-pretyrosine) is a primary metabolite on a branch of the shikimate biosynthetic pathway to aromatic amino acids. It plays a key role in the synthesis of plant secondary metabolites including alkaloids and the phenylpropanoids that are the key to carbon fixation. Yet understanding the control of arogenate metabolism has been hampered by its extreme instability and the lack of a versatile synthetic route to arogenate and its analogues. We now report a practical synthesis of l-arogenate in seven steps from O-benzyl l-tyrosine methyl ester in an overall yield of 20%. The synthetic route also delivers the fungal metabolite spiroarogenate, as well as a range of stable saturated and substituted analogues of arogenate. The key step in the synthesis is a carboxylative dearomatization by intramolecular electrophilic capture of tyrosine''s phenolic ring using an N-chloroformylimidazolidinone moiety, generating a versatile, functionalizable spirodienone intermediate.

l-Tyrosine provides a precursor for a practical synthesis of the unstable primary metabolite l-arogenate and some stabilised arogenate analogues.     

Ruthenaelectro-catalyzed C–H acyloxylation for late-stage tyrosine and oligopeptide diversification

Ruthenaelectro(ii/iv)-catalyzed intermolecular C–H acyloxylations of phenols have been developed by guidance of experimental, CV and computational insights. The use of electricity bypassed the need for stoichiometric chemical oxidants. The sustainable electrocatalysis strategy was characterized by ample scope, and its unique robustness enabled the late-stage C–H diversification of tyrosine-derived peptides.

Ruthenaelectro(ii/iv)-catalyzed intermolecular C–H acyloxylations of oligopeptides have been developed by the guidance of key experimental, CV and computational insights.     

Unveiling ultrafast dynamics in bridged bimetallic complexes using optical and X-ray transient absorption spectroscopies

In photosynthetic systems employing multiple transition metal centers, the properties of charge-transfer states are tuned by the coupling between metal centers. Here, we use ultrafast optical and X-ray spectroscopies to elucidate the effects of metal–metal interactions in a bimetallic tetrapyridophenazine-bridged Os(ii)/Cu(i) complex. Despite having an appropriate driving force for Os-to-Cu hole transfer in the Os(ii) moiety excited state, no such charge transfer was observed. However, excited-state coupling between the metal centers is present, evidenced by variations in the Os MLCT lifetime depending on the identity of the opposite metal center. This coupling results in concerted coherent vibrations appearing in the relaxation kinetics of the MLCT states for both Cu and Os centers. These vibrations are dominated by metal–ligand contraction at the Cu/Os centers, which are in-phase and linked through the conjugated bridging ligand. This study shows how vibronic coupling between transition metal centers affects the ultrafast dynamics in bridged, multi-metallic systems from the earliest times after photoexcitation to excited-state decay, presenting avenues for tuning charge-transfer states through judicious choice of metal/ligand groups.

In photosynthetic systems employing multiple transition metal centers, the properties of charge-transfer states are tuned by the coupling between metal centers.     

Calcium ions tune the zinc-sequestering properties and antimicrobial activity of human S100A12

Human S100A12 is a host-defense protein expressed and released by neutrophils that contributes to innate immunity. Apo S100A12 is a 21 kDa antiparallel homodimer that harbors two Ca(ii)-binding EF-hand domains per subunit and exhibits two His₃Asp motifs for chelating transition metal ions at the homodimer interface. In this work, we present results from metal-binding studies and microbiology assays designed to ascertain whether Ca(ii) ions modulate the Zn(ii)-binding properties of S100A12 and further evaluate the antimicrobial properties of this protein. Our metal-depletion studies reveal that Ca(ii) ions enhance the ability of S100A12 to sequester Zn(ii) from microbial growth media. We report that human S100A12 has antifungal activity against Candida albicans, C. krusei, C. glabrata and C. tropicalis, all of which cause human disease. This antifungal activity is Ca(ii)-dependent and requires the His₃Asp metal-binding sites. We expand upon prior studies of the antibacterial activity of S100A12 and report Ca(ii)-dependent and strain-selective behavior. S100A12 exhibits in vitro growth inhibitory activity against Listeria monocytogenes. In contrast, S100A12 has negligible effect on the growth of Escherichia coli K-12 and Pseudomonas aeruginosa PAO1. Loss of functional ZnuABC, a high-affinity Zn(ii) import system, increases the susceptibility of E. coli and P. aeruginosa to S100A12, indicating that S100A12 deprives these mutant strains of Zn(ii). To evaluate the Zn(ii)-binding sites of S100A12 in solution, we present studies using Co(ii) as a spectroscopic probe and chromophoric small-molecule chelators in Zn(ii) competition titrations. We confirm that S100A12 binds Zn(ii) with a 2 : 1 stoichiometry, and our data indicate sub-nanomolar affinity binding. Taken together, these data support a model whereby S100A12 uses Ca(ii) ions to tune its Zn(ii)-chelating properties and antimicrobial activity.     

Epoc group: transformable protecting group with gold(iii)-catalyzed fluorene formation

This study presents the novel concept of a transformable protecting group, which changes its properties through structural transformation. Based on this concept, we developed a 2-(2-ethynylphenyl)-2-(5-methylfuran-2-yl)-ethoxycarbonyl (Epoc) group. The Epoc group was transformed into an Fmoc-like structure with gold(iii)-catalyzed fluorene formation and was removable under Fmoc-like mild basic conditions post-transformation even though it was originally stable under strongly basic conditions. As an application for organic synthesis, the Epoc group provides the novel orthogonality of gold(iii)-labile protecting groups in solid-phase peptide synthesis. In addition, the high turnover number of fluorene formation in aqueous media is suggestive of the applicability of the Epoc group to biological systems.

A protecting group removable with gold(iii)-catalyzed fluorene formation and the subsequent addition of piperidine was developed.