Iron-Catalyzed Miyaura Borylation of Aryl Chlorides and Triflates.

Simple aryl chlorides represent challenging substrates in iron-catalyzed borylation. A combination of Li[B(Bu)pin-Bpin] as the borylating reagent and a catalyst formed in situ from iron(II) triflate and the commercially available N-heterocyclic carbene ligand, IMes, gives significantly improved activity and a much broader scope than previously reported iron-based catalysts. Iron triflate is also a good precatalyst for the borylation of aryl triflates─a previously unreported transformation─and in these cases the IMes ligand is not required.

Community-based prehabilitation before elective major surgery: the PREP-WELL quality improvement project.

Optimising health and well-being before elective major surgery via prehabilitation initiatives is important for good postoperative outcomes. In a busy tertiary centre in North East England, the lack of a formal prehabilitation service meant that opportunities were being missed to optimise patients for surgery. This quality improvement project aimed to implement and evaluate a community-based prehabilitation service for people awaiting elective major surgery: PREP-WELL.

Methylenespiro[2.3]hexanes via Nickel-Catalyzed Cyclopropanations with [1.1.1]Propellane.

[1.1.1]Propellane is a highly strained tricyclic hydrocarbon whose reactivity is dominated by addition reactions across the central inverted bond to provide bicyclo[1.

The surprisingly facile formation of Pd(i)-phosphido complexes from ortho-biphenylphosphines and palladium acetate.

The widely-used ortho-biphenylphosphine ligands SPhos and RuPhos not only undergo facile orthometallation with palladium acetate, yielding strained, four-membered dimeric palladacycles but more surprisingly, in the presence of alcoholic solvents, along with the less encumbered analogue MePhos, yield unusual dinuclear Pd(i) complexes, in which the Pd-centers are bridged by both a phosphide ligand and by the arene of a coordinated phosphine donor.

Cobalt-Catalyzed Suzuki Biaryl Coupling of Aryl Halides.

Readily accessed cobalt pre-catalysts with N-heterocyclic carbene ligands catalyze the Suzuki cross-coupling of aryl chlorides and bromides with alkyllithium-activated arylboronic pinacolate esters. Preliminary mechanistic studies indicate that the cobalt species is reduced to Co during the reaction.

Isoindolinones via Copper-Catalyzed Intramolecular Benzylic C-H Sulfamidation.

2-Benzyl-N-tosylbenzamides and related substrates undergo copper-catalyzed intramolecular sulfamidation at the benzylic methylene to give N-arylsuflonyl-1-arylisoindolinones, which can be N-deprotected using samarium iodide to generate the free 1-arylisoindolinones. Preliminary mechanistic studies indicate that the rate-determining step is not C-H bond cleavage but are instead consistent with slow oxidation of a copper π-arene intermediate.

The influence of the ligand chelate effect on iron-amine-catalysed Kumada cross-coupling.

The application of a variety of iron complexes with chelating amine ligands as pre-catalysts in the representative cross-coupling of 4-tolylmagnesium bromide with cyclohexyl bromide was investigated. The results from this study indicate the performance of the pre-catalyst is inversely proportional to the strength of the chelate or macrocyclic effect of the amine ligand, as determined by the propensity of the ligand to be displaced from the iron centre by reaction with excess benzyl magnesium chloride. The findings from this study are consistent with a catalytic cycle wherein the chelating amine ligand is not coordinated to the iron centre during turnover.

Palladium-Catalyzed Ortho-Arylation of Carbamate-Protected Estrogens.

The palladium-catalyzed ortho-arylation of diethyl carbamate-protected estrone and estriol with aryl iodides gives the 2-arylated analogues. Subsequent removal of the carbamate directing group furnishes 2-arylated estrone, estradiol, or estriol depending on the method used.

Catalyst-Switchable Regiocontrol in the Direct Arylation of Remote C-H Groups in Pyrazolo[1,5-a]pyrimidines.

The regiodivergent palladium-catalyzed C-H arylation of pyrazolo[1,5-a]pyrimidine has been achieved, wherein the switch in regioselectivity between positions C3 and C7 is under complete catalyst control. A phosphine-containing palladium catalyst promotes the direct arylation at the most acidic position (C7), whereas a phosphine-free catalyst targets the most electron-rich position (C3).

How low does iron go? Chasing the active species in fe-catalyzed cross-coupling reactions.

The catalytic cross-coupling reactions of organic halides or related substrates with organometallic nucleophiles form the cornerstone of many carbon-carbon bond-forming processes. While palladium-based catalysts typically mediate such reactions, there are increasing concerns about the long-term sustainability of palladium in synthesis. This is due to the high cost of palladium, coupled with its low natural abundance, environmentally deleterious extraction (∼6 g of metal are produced per ton of ore), toxicity, and competition for its use from the automotive and consumer electronics sectors.

Facile hydrolysis and alcoholysis of palladium acetate.

Palladium(II) acetate is readily converted into [Pd3 (μ(2) -OH)(OAc)5 ] (1) in the presence of water in a range of organic solvents and is also slowly converted in the solid state. Complex 1 can also be formed in nominally anhydrous solvents. Similarly, the analogous alkoxide complexes [Pd3 (μ(2) -OR)(OAc)5 ] (3) are easily formed in solutions of palladium(II) acetate containing a range of alcohols.

Expedient iron-catalyzed coupling of alkyl, benzyl and allyl halides with arylboronic esters.

While attractive, the iron-catalyzed coupling of arylboron reagents with alkyl halides typically requires expensive or synthetically challenging diphosphine ligands. Herein, we show that primary and secondary alkyl bromides and chlorides, as well as benzyl and allyl halides, can be coupled with arylboronic esters, activated with alkyllithium reagents, by using very simple iron-based catalysts. The catalysts used were either adducts of inexpensive and widely available diphosphines or, in a large number of cases, simply [Fe(acac)3] with no added co-ligands.

TMEDA in iron-catalyzed Kumada coupling: amine adduct versus homoleptic "ate" complex formation.

The reactions of iron chlorides with mesityl Grignard reagents and tetramethylethylenediamine (TMEDA) under catalytically relevant conditions tend to yield the homoleptic "ate" complex [Fe(mes)3 ](-) (mes=mesityl) rather than adducts of the diamine, and it is this ate complex that accounts for the catalytic activity. Both [Fe(mes)3 ](-) and the related complex [Fe(Bn)3 ](-) (Bn=benzyl) react faster with representative electrophiles than the equivalent neutral [FeR2 (TMEDA)] complexes. Fe(I) species are observed under catalytically relevant conditions with both benzyl and smaller aryl Grignard reagents.

Iron(I) in Negishi cross-coupling reactions.

Herein we demonstrate both the importance of Fe(I) in Negishi cross-coupling reactions with arylzinc reagents and the isolation of catalytically competent Fe(I) intermediates. These complexes, [FeX(dpbz)(2)] [X = 4-tolyl (7), Cl (8a), Br (8b); dpbz = 1,2-bis(diphenylphosphino)benzene], were characterized by crystallography and tested for activity in representative reactions. The complexes are low-spin with no significant spin density on the ligands.

Chiral palladacycles based on resorcinol monophosphite ligands: the role of the meta-hydroxyl in ligand C-H activation and catalysis.

The reactions of a range of chiral resorcinol monophosphite ligands with [PdCl(2)(NCMe)(2)] was investigated in order to establish whether the meta-hydroxyl function was involved in the orthometallation processes. These ligands underwent facile orthopalladation at room temperature in the presence of Et(3)N, whilst the equivalent hydroxyl-free analogues needed more forcing conditions to induce orthometallation. When the hydroxyl function was replaced by a similar sized methyl group no orthometallation occurred, even on heating.

Tuning ligand structure in chiral bis(phosphite) and mixed phosphite-phosphinite PCP-palladium pincer complexes.

A range of chiral resorcinol bis(phosphite) and phosphite-phosphinite ligands were produced and their propensity to form palladium PCP-pincer complexes examined. The ease of base-assisted C-H palladation of the ligands falls in the order bis(phosphinite) > phosphite-phosphinite > bis(phosphite). The catalytic activity of the complexes in the asymmetric allylation of benzaldehyde with allyl tributyltin was examined and it was found that, contrary to expectations, ligands with 3,3'-disubstituted BINOL residues show poorer activity and stereoselectivity than unsubstituted BINOL analogues.

Remarkably reactive dihydroindoloindoles via palladium-catalysed dearomatisation.

Palladium-catalysed dearomatisation reactions allow access to a previously unknown class of indoloindole heterocycle: 5,10b-dihydroindolo[2,3-b]indoles. The highly reactive nature of these compounds is demonstrated by their facile reactions with water and with hydride, alkyl, aryl and allyl-based organometallic nucleophiles.

Solvent-free aromatic C-H functionalisation/halogenation reactions.

The solvent-free, palladium-catalysed reaction of anilides with CuCl(2) in the presence or absence of copper acetate yields ortho-chlorinated anilides in good to excellent yields, even on a large scale (100 mmol). By contrast, the equivalent reactions with copper bromide, either solvent free or in 1,2-dichloroethane, in the presence or absence of palladium, under air or inert conditions, gave the products of simple electrophilic bromination. Mechanistic studies highlighted the involvement of palladacyclic intermediates, one of which was characterised crystallographically, which undergo subsequent reaction with copper(II) chloride to yield the chlorinated anilide products.

Solvent free catalytic C-H functionalisation.

Solvent-free reaction conditions facilitate a range of aromatic C-H functionalisations that traditionally require acidic or disfavoured solvents. These reactions include selective ortho- and meta-arylation of aryl carbamates and anilides and selective halogenation reactions.

Palladium-catalysed ortho-arylation of carbamate-protected phenols.

The carbamate (-O2CNR2) function is an excellent directing group for palladium-catalysed direct arylation reactions giving both protected or free mono- or di-substituted phenols, as well as an example of a dibenzopyranone, depending on coupling partners (aryl iodides or diaryliodonium salts) and conditions.

Simple mixed Fe-Zn catalysts for the Suzuki couplings of tetraarylborates with benzyl halides and 2-halopyridines.

Employing co-catalytic zinc reagents facilitates the iron-catalysed Suzuki cross-coupling of tetraarylborates with both benzyl and 2-heteroaryl halides.