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Mechanoenzymatic reactions are described for the degradation of different PET materials using whole cell PETases.

The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high p

Suzuki–Miyaura coupling is an extremely useful way to construct Csp2–Csp2 carbon bonds. On the other hand, Csp2–Csp3 coupling reactions do not work well, and tert-alkylative Suzuki–Miyaura coupling is particularly challenging due to problematic oxidative addition and β-hydride elimination side reactions. In this short review, we will introduce recent examples of tert-alkylative Suzuki–Miyaura couplings with tert-alkyl electrophiles or -boron reagents. The review will mainly focus on catalyst and product structures and on the proposed mechanisms.1 Introduction2 Ni-Catalyzed tert-Alkylative Couplings3 Pd-Catalyzed tert-Alkylative Couplings4 Fe-Catalyzed tert-Alkylative Couplings5 tert-Alkylative Couplings with 1-Alkenyl Borons6 tert-Alkylative Couplings under Photoirradiation7 Stereospecific tert-Alkylative Couplings8 Conclusion

With an ever-growing emphasis on sustainable synthesis, aerobic C-H activation (the use of oxygen in air to activate C-H bonds) represents a highly attractive conduit for the development of novel synthetic methodologies. Herein, we report the air mediated functionalisation of various saturated heterocycles and ethers

We report the evaluation of density-functional-theory (DFT) based procedures for predicting

Pentose and hexose sugars are abundant constituents of waste biomass, making them sustainable, chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings from the pharmaceutical industry is increasing as they provide well-defined three-dimensional frameworks that show increased metabolic resistance. Through the formation of thioacetals, sugars may be manipulated in their straight-chain form and dehydrated selectively under basic conditions at C-2. This approach was applied to an array of sugars and extended to the production of useful chiral THFs via further selective dehydration reactions.

The palladium‐catalysed sp3 C−H arylation of a selection of saturated amine scaffolds was investigated using substituted picolinamide directing groups. On the bornylamine scaffold, highly selective monoarylation takes place using unsubstituted picolinamide or 3‐methylpicolinamide, whereas a double C−H arylation occurs with other substituents present, becoming a significant product with 3‐trifluoromethylpicolinamide. DFT calculations were used to help rationalise the effect of directing groups on the C−H palladation steps which were found experimentally to be irreversible. The substituted picolinamide directing groups were also examined on acyclic amine scaffolds and in many cases increased yields and selectivity could be obtained using methylpicolinamides. For a selection of other amine scaffolds, the yield of C−H arylation could be improved significantly using 3‐methylpicolinamide as the directing group and/or 3‐methylpentan‐3‐ol as the solvent.

We report the evaluation of density-functional-theory (DFT) based procedures for predicting 19F NMR chemical shifts at modest computational cost for a range of molecules with fluorine bonds, to be used as a tool for assisting the characterisation of reaction intermediates and products and as an aid to identifying mechanistic pathways. The results for a balanced learning set of molecules were then checked using two further testing sets, resulting in the recommendation of the ωB97XD/aug-cc-pvdz DFT method and basis set as having the best combination of accuracy and computational time, with a RMS error of 3.57 ppm. Cationic molecules calculated without counter-anion showed normal errors, whilst anionic molecules showed somewhat larger errors. The method was applied to the prediction of the conformationally averaged 19F chemical shifts of 2,2,3,3,4,4,5,5-octafluoropentan-1-ol, in which gauche stereoelectronic effects involving fluorine dominate and to determining the position of coordination equilibria of fluorinated boranes as an aid to verifying the relative energies of intermediate species involved in catalytic amidation reactions involving boron catalysts.

Transaminase enzymes (TAms) have been widely used for the amination of aldehydes and ketones, often resulting in optically pure products. In this work, transaminases were directly reacted with hydrazones in a novel approach to form amine products. Several substrates were investigated, including those with furan and phenyl moieties. It was determined that the amine yields increased when an additional electrophile was added to the reaction mixture, suggesting that they can sequester the hydrazine released in the reaction. Pyridoxal 5'-phosphate (PLP), a cofactor for transaminases, and polyethylene glycol (PEG)-aldehydes were both found to increase the yield of amine formed. Notably, the amination of (

A narrow substrate range is a major limitation in exploiting enzymes more widely as catalysts in synthetic organic chemistry. For enzymes using two substrates, the simultaneous optimisation of both substrate specificities is also required for the rapid expansion of accepted substrates. Transketolase (TK) catalyses the reversible transfer of a C2 -ketol unit from a donor substrate to an aldehyde acceptor and suffers the limitation of narrow substrate scope for industrial applications. Herein, TK from Escherichia coli was engineered to accept both pyruvate, as a novel donor substrate, and unnatural acceptor aldehydes, including propanal, pentanal, hexanal and 3-formylbenzoic acid (FBA). Twenty single-mutant variants were first designed and characterised experimentally. Beneficial mutations were then recombined to construct a small library. Screening of this library identified the best variant with a 9.2-fold improvement in the yield towards pyruvate and propionaldehyde, relative to wild-type (WT). Pentanal and hexanal were used as acceptors to determine stereoselectivities of the reactions, which were found to be higher than 98% enantiomeric excess (ee) for the S configuration. Three variants were identified to be active for the reaction between pyruvate and 3-FBA. The best variant was able to convert 47% of substrate into product within 24 h, whereas no conversion was observed for WT. Docking experiments suggested a cooperation between the mutations responsible for donor and acceptor recognition, which would promote the activity towards both the acceptor and donor. The variants obtained have the potential to be used for developing catalytic pathways to a diverse range of high-value products.

A transition metal catalyzed alkylation with an alkyl halide is one of the most difficult reactions to achieve, because of the difficult oxidative addition of an alkyl-halogen bond to a metal, and the tendency of the resulting alkylmetal intermediate to undergo a β-hydride elimination reaction to give an olefin. In this review, we discuss hybrid reaction systems involving Cu catalyzed combination of radicals and organometallic species, which enable facile alkylation reactions to construct C-C and C-heteroatom bonds. This paper highlights recent progress in arylation, alkenylation, alkynylation, cyclization, addition and introduction of heteroatoms via these hybrid reaction systems.

A practical method for the synthesis of phenyl enol ethers is reported. The combination of a gold(I) catalyst and potassium carbonate selectively mediates the addition of phenols to propargylic alcohols/amines in a chemo-, regio-, and stereoselective fashion in high yield. The resulting enol ethers are formed exclusively with a Z-configuration and can be obtained from a wide array of phenols and propargylic alcohols or amines with the reaction showing excellent functional group tolerance.

Carbohydrates are the major component of biomass and have unique potential as a sustainable source of building blocks for chemicals, materials, and biofuels because of their low cost, ready availability, and stereochemical diversity. With a view to upgrading carbohydrates to access valuable nitrogen‐containing sugar‐like compounds such as aminopolyols, biocatalytic aminations using transaminase enzymes (TAms) have been investigated as a sustainable alternative to traditional synthetic strategies. Demonstrated here is the reaction of TAms with sugar‐derived tetrahydrofuran (THF) aldehydes, obtained from the regioselective dehydration of biomass‐derived sugars, to provide access to cyclic aminodiols in high yields. In a preliminary study we have also established the direct transamination of sugars to give acyclic aminopolyols. Notably, the reaction of the ketose d‐fructose proceeds with complete stereoselectivity to yield valuable aminosugars in high purity.

The synthesis of amides is of widespread importance, and there has been considerable recent interest in the development of catalytic methods to access these molecules. In this Perspective, we provide an overview of the current state of the art in amide synthesis, and assess new catalytic amide formation methods in the context of efficiency and sustainability. The advantages and disadvantages of catalytic approaches are highlighted and areas for future research are identified.

Cysteine as peptide precursor and catalyst Among amino acids, cysteine is highly reactive as a nucleophile, metal ligand, and participant in redox and radical reactions. These properties make cysteine attractive as a component of prebiotic chemistry, but traditional Strecker synthesis of α-aminonitriles, which can serve as peptide precursors, cannot produce free cysteine. Foden et al. found that a simple acylation of the free amine prevented degradation of cysteine nitrile and enabled synthesis of this cysteine precursor from acetyl dehydroalanine nitrile and a sulfide donor (see the Perspective by Muchowska and Moran). When combined with other proteinogenic α-aminonitriles, acetylcysteine or derivative thiols catalyzed efficient peptide ligation in water. These results highlight how prebiotic synthesis of precursors can also generate function by creating a catalyst for polymerization. Science , this issue p. 865 ; see also p. 767

The palladium-catalysed sp3 C-H arylation of a selection of saturated amine scaffolds was investigated using substituted picolinamide directing groups. On the bornylamine scaffold, highly selective monoarylation takes place using unsubstituted picolinamide or 3-methylpicolinamide, whereas a double C-H arylation occurs with other substituents present, becoming a significant product with 3-trifluoromethylpicolinamide. DFT calculations were used to help rationalise the effect of directing groups on the C-H palladation steps which were found experimentally to be irreversible. The substituted picolinamide directing groups were also examined on acyclic amine scaffolds and in many cases increased yields and selectivity could be obtained using methylpicolinamides. For a selection of other amine scaffolds, the yield of C-H arylation could be improved significantly using 3-methylpicolinamide as the directing group and/or 3-methylpentan-3-ol as the solvent

In this paper we outline how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo‐propargylic alcohols provides a useful route to 3‐halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. Finally, a novel ring‐expansion of propargylic alcohols containing a cyclopropylalkyne provides access to halogenated alkenylcyclobutanes.

Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.

In the synthesis of bio-active compounds, fluorinated compounds play a prominent role. However, the site-selective fluorination of organic molecules is often challenging, because activation of a reaction site using a fluorinating reagent can be difficult in a substrate possessing many functional groups. This digest introduces recent examples of site-selective fluorination reactions.

A sustainable synthetic procedure to convert furfural hydrazones into functionalised phthalimides was developed. The reaction was performed in a microwave using a hydrophilic ionic liquid, [bmim][Cl], as the solvent which could be readily recovered by a simple extraction. The ionic liquid was successfully recycled with no significant loss in product yields.

Herein we report the first synthesis of protected boronocysteine. The target compound was prepared via copper-catalysed diastereoselective nucleophilic borylation of a sulfinimine. After deprotection to give the amine as the hydrochloride salt, four boronocysteine amide derivatives were prepared through reaction with a variety of different active acylating agents.

A recently developed novel recombinant influenza antigen vaccine has shown great success in preclinical studies in ferrets and mice. It provides broader protection, and is efficient to manufacture compared to the conventional trivalent influenza vaccines (TIV). Each strain of the recombinant antigen has a constant self-assembled bacterial ferritin core which, if used as a target for affinity chromatography, could lead to a universal purification method. Ferritin in silico models were used to explore potential target binding sites against ligands synthesized by the four-component Ugi reaction. Two ligands, SJ047 and SJ055, were synthesized in solution, characterized by 1H, 13C, and 2D NMR spectroscopy, and subsequently immobilized on the PEG-functionalized beads. Ligands SJ047 and SJ055 displayed apparent Kd values of 2.04 × 10–7 M and 1.91 × 10–8 M, respectively, against the ferritin. SJ047 and SJ055-functionalized resins were able to purify hemagglutinin (New Caledonia)-ferritin expressed in a crude Huma...

Furfural is recognised as an attractive platform molecule for the production of solvents, plastics, resins and fuel additives. Furfurylamines have many applications as monomers in biopolymer synthesis and for the preparation of pharmacologically active compounds, although preparation via traditional synthetic routes is not straightforward due to by-product formation and sensitivity of the furan ring to reductive conditions. In this work transaminases (TAms) have been investigated as a mild sustainable method for the amination of furfural and derivatives to access furfurylamines. Preliminary screening with a recently reported colorimetric assay highlighted that a range of furfurals were readily accepted by several transaminases and the use of different amine donors was then investigated. Multistep synthetic routes were required to synthesise furfurylamine derivatives for use as analytical standards, highlighting the benefits of using a one step biocatalytic route. To demonstrate the potential of using TAms for the production of furfurals, the amination of selected compounds was then investigated on a preparative scale.

A versatile approach to the valorization of propargylic alcohols is reported, enabling controlled access to three different products from the same starting materials. First, a general method for the hydroamination of propargylic alcohols with anilines is described using gold catalysis to give 3-hydroxyimines with complete regioselectivity. These 3-hydroxyimines can be reduced to give 1,3-amino alcohols with high syn selectivity. Alternatively, by using a catalytic quantity of aniline, 3-hydroxyketones can be obtained in high yield directly from propargylic alcohols. Further manipulation of the reaction conditions enables the selective formation of 3-aminoketones via a rearrangement/hydroamination pathway. The utility of the new chemistry was exemplified by the one-pot synthesis of a selection of N-arylpyrrolidines and N-arylpiperidines. A mechanism for the hydroamination has been proposed on the basis of experimental studies and density functional theory calculations.

B(OCH2CF3)3-catalysed direct amidations of challenging substrates (polar heteroycles, poorly nucleophilic anilines) work well in tBuOAc under Dean–Stark conditions., Catalytic direct amidation reactions have been the focus of considerable recent research effort, due to the widespread use of amide formation processes in pharmaceutical synthesis. However, the vast majority of catalytic amidations are performed in non-polar solvents (aromatic hydrocarbons, ethers) which are typically undesirable from a sustainability perspective, and are often poor at solubilising polar carboxylic acid and amine substrates. As a consequence, most catalytic amidation protocols are unsuccessful when applied to polar and/or functionalised substrates of the kind commonly used in medicinal chemistry. In this paper we report a practical and useful catalytic direct amidation reaction using tert-butyl acetate as the reaction solvent. The use of an ester solvent offers improvements in terms of safety and sustainability, but also leads to an improved reaction scope with regard to polar substrates and less nucleophilic anilines, both of which are important components of amides used in medicinal chemistry. An amidation reaction was scaled up to 100 mmol and proceeded with excellent yield and efficiency, with a measured process mass intensity of 8.

Catalytic direct amidation reactions have been the focus of considerable recent research effort, due to the widespread use of amide formation processes in pharmaceutical synthesis. However, the vast majority of catalytic amidations are performed in non-polar solvents (aromatic hydrocarbons, ethers) which are typically undesirable from a sustainability perspective, and are often poor at solubilising polar carboxylic acid and amine substrates. As a consequence, most catalytic amidation protocols are unsuccessful when applied to polar and/or functionalised substrates of the kind commonly used in medicinal chemistry. In this paper we report a practical and useful catalytic direct amidation reaction using tert-butyl acetate as the reaction solvent. The use of an ester solvent offers improvements in terms of safety and sustainability, but also leads to an improved reaction scope with regard to polar substrates and less nucleophilic anilines, both of which are important components of amides used in medicinal chemistry. An amidation reaction was scaled up to 100 mmol and proceeded with excellent yield and efficency, with a measured process mass intensity of 8.

The regioselective gold‐catalysed hydration of propargylic alcohols to β‐hydroxy ketones can be achieved by diverting the gold‐catalysed Meyer–Schuster rearrangement through the addition of a protic additive with a pK a of 7–9 such as p‐nitrophenol, boric acid or a boronic acid. This provides an interesting alternative to an aldol reaction when combined with the straightforward addition of an alkyne to an aldehyde or ketone. The gold‐catalysed reaction of an electron‐deficient, sterically hindered propargylic alcohol with a boronic acid led to the formation of an unusually stable cyclic boron enolate.

The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of

In this paper we outline how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo‐propargylic alcohols provides a useful route to 3‐halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. Finally, a novel ring expansion of propargylic alcohols containing a cyclopropylalkyne provides access to halogenated alkenylcyclobutanes.

Herein, we report a silver-free Pd(II)-catalyzed C(sp

The use of biocatalysis for the synthesis of high value added chemical building blocks derived from biomass is becoming an increasingly important application for future sustainable technologies. The synthesis of a higher value chemical from l-arabinose, the predominant monosaccharide obtained from sugar beet pulp, is demonstrated here via a transketolase and transaminase coupled reaction. Thermostable transketolases derived from Deinococcus geothermalis and Deinococcus radiodurans catalysed the synthesis of l-gluco-heptulose from l-arabinose and β-hydroxypyruvate at elevated temperatures with high conversions. β-Hydroxypyruvate, a commercially expensive compound used in the transketolase reaction, was generated in situ from l-serine and α-ketoglutaric acid via a thermostable transaminase, also from Deinococcus geothermalis. The two steps were investigated and implemented in a one-pot system for the sustainable and efficient production of l-gluco-heptulose.

The activity of HBF4 (aqueous solution) as a catalyst in propargylation reactions is presented. Diverse types of nucleophiles were employed in order to form new C–O, C–N and C–C bonds in technical acetone and in air. Good to excellent yields and good chemoselectivities were obtained using low acid loading (typically 1 mol-%) under simple reaction conditions.

Enantioenriched secondary alcohols can be prepared via a short reaction sequence involving asymmetric organocatalytic sulfenylation of an aldehyde, organometallic addition, and desulfurization. This process provides access to enantioenriched alcohols with sterically similar groups attached to the alcohol carbon atom. The intermediate β-hydroxysulfides can also serve as precursors to enantioenriched 1,2-disubstituted epoxides via alkylation of the sulfur and subsequent base-mediated ring closure.

L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducing sugars and the mechanism of the key cyclization investigated. This methodology was applied to the synthesis of a range of functionalized chiral tetrahydrofurans, as well as a formal synthesis of 3R-3-hydroxymuscarine.

The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels–Alder reaction.

The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed., The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed. We have carried out a detailed investigation of boron-catalysed amidation reactions, through study of the interaction between amines/carboxylic acids and borinic acids, boronic acids and boric acid, and have isolated and characterised by NMR/X-ray crystallography many of the likely intermediates present in catalytic amidation reactions. Rapid reaction between amines and boron compounds was observed in all cases, and it is proposed that such boron–nitrogen interactions are highly likely to take place in catalytic amidation reactions. These studies also clearly show that borinic acids are not competent catalysts for amidation, as they either form unreactive amino-carboxylate complexes, or undergo protodeboronation to give boronic acids. It therefore seems that at least three free coordination sites on the boron atom are necessary for amidation catalysis to occur. However, these observations are not consistent with the currently accepted ‘mechanism’ for boron-mediated amidation reactions involving nucleophilic attack of an amine onto a monomeric acyloxyboron intermediate, and as a result of our observations and theoretical modelling, alternative proposed mechanisms are presented for boron-mediated amidation reactions. These are likely to proceed via the formation of a dimeric B–X–B motif (X = O, NR), which is uniquely able to provide activation of the carboxylic acid, whilst orchestrating the delivery of the amine nucleophile to the carbonyl group. Quantum mechanical calculations of catalytic cycles at the B3LYP+D3/Def2-TZVPP level (solvent = CH2Cl2) support the proposal of several closely related potential pathways for amidation, all of which are likely to be lower in energy than the currently accepted mechanism.

Over 8 million tonnes of sugar beet are grown annually in the UK. Sugar beet pulp (SBP) is the main by-product of sugar beet processing which is currently dried and sold as a low value animal feed. SBP is a rich source of carbohydrates, mainly in the form of cellulose and pectin, including d-glucose (Glu), l-arabinose (Ara) and d-galacturonic acid (GalAc). This work describes the technical feasibility of an integrated biorefinery concept for the fractionation of SBP and conversion of these monosaccharides into value-added products. SBP fractionation is initially carried out by steam explosion under mild conditions to yield soluble pectin and insoluble cellulose fractions. The cellulose is readily hydrolysed by cellulases to release Glu that can then be fermented by a commercial yeast strain to produce bioethanol at a high yield. The pectin fraction can be either fully hydrolysed, using physico-chemical methods, or selectively hydrolysed, using cloned arabinases and galacturonases, to yield Ara-rich and GalAc-rich streams. These monomers can be separated using either Centrifugal Partition Chromatography (CPC) or ultrafiltration into streams suitable for subsequent enzymatic upgrading. Building on our previous experience with transketolase (TK) and transaminase (TAm) enzymes, the conversion of Ara and GalAc into higher value products was explored. In particular the conversion of Ara into l-gluco-heptulose (GluHep), that has potential therapeutic applications in hypoglycaemia and cancer, using a mutant TK is described. Preliminary studies with TAm also suggest GluHep can be selectively aminated to the corresponding chiral aminopolyol. The current work is addressing the upgrading of the remaining SBP monomer, GalAc, and the modelling of the biorefinery concept to enable economic and Life Cycle Analysis (LCA).

A commercially available borate ester catalyzes amide formation from carboxylic acids and amines with very high efficiency., Chemical reactions for the formation of amide bonds are among the most commonly used transformations in organic chemistry, yet they are often highly inefficient. A novel protocol for amidation using a simple borate ester catalyst is reported. The process presents significant improvements over other catalytic amidation methods in terms of efficiency and safety, with an unprecedented substrate scope including functionalized heterocycles and even unprotected amino acids. The method was used to access a wide range of functionalized amide derivatives, including pharmaceutically relevant targets, important synthetic intermediates, a catalyst, and a natural product.

Reaction conditions to facilitate the conversion of D-limonene selectively to p,α-dimethylstyrene (DMS) are described, in order to subsequently produce polymeric materials from biomass sourced from food waste. Limonene was dehydrogenated with several palladium catalysts and different solvents and bases, with copper chloride as oxidant at temperatures of 70–120 °C. Reaction conditions were identified using Pd(OAc)2 for the selective formation of only DMS from limonene in 2–5 hours, enabling the facile separation of DMS from unreacted starting material by vacuum distillation.

This letter describes a convenient synthesis of the six isomeric tri- and tetramethylbenzaldehydes, which are not readily available from major chemical suppliers. Formylation of readily available phenols via electrophilic aromatic substitution provides compounds containing the correct aromatic substitution pattern. ­Suzuki cross-coupling of the corresponding trifluoromethanesulfonates with methylboronic acid then provides the benzaldehydes as single isomers.

(Cyclooctadiene)(pentamethylcyclopentadiene)ruthenium chloride [Cp*RuCl(cod)] has been used to catalyze the regioselective cyclization of amide-tethered diynes with monosubstituted alkynes to give polysubstituted isoindolinones. Notably, the presence of a trimethylsilyl group on the diyne generally led to complete control over the regioselectivity of the alkyne cyclotrimerization. The cyclization reaction worked well in a sustainable non-chlorinated solvent and was tolerant of moisture. The optimized conditions were effective with a diverse range of alkynes and diynes. The 7-silylisoindolinone products could be halogenated, protodesilylated or ring opened to access a range of usefully functionalized products.

The synthesis of amides is of huge importance in a wide variety of industrial and academic fields and is of particular significance in the synthesis of pharmaceuticals. Many of the well established methods for amide synthesis involve reagents that are difficult to handle and lead to the generation of large quantities of waste products. As a consequence, there has been a considerable amount of interest in the development of new approaches to amide synthesis. Over the past few years a wide range of new reagents and catalysts for direct amidation of carboxylic acids have been reported. In addition, the interconversion of amide derivatives through transamidation is emerging as a potential alternative strategy for accessing certain amides. This microreview covers recent developments in the direct amidation of carboxylic acids and the interconversion of amides through transamidation. The advantages and disadvantages of the various methods are discussed, as well as the possible mechanisms of the reactions.

Easy as 1,2,3: Reaction of methyl carbamate, triethyl orthoformate, and readily available alkenes provides a highly practical preparation of protected aminocyclopropanes. The reaction proceeds with preferential cis addition to alkenes, and cleavage of the methyl carbamate gives the free aminocyclopropanes as their HI salts.

A commercially available borate ester, B(OCH2CF3)3, can be used to achieve protecting-group free direct amidation of α-amino acids with a range of amines in cyclopentyl methyl ether. The method can be applied to the synthesis of medicinally relevant compounds, and can be scaled up to obtain gram quantities of products.

Two new palladium-catalysed reactions have been developed for the synthesis of stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin-1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho-alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction to provide 4-allylbenzooxaborinin-1-ols.