The acid mediated ortho-iodination of Weinreb amides using a readily available catalyst is described. The selective ortho-iodination of Weinreb amides, challenging substrates in directed C–H activations, and also of benzamides is achieved. The process works under mild conditions and tolerates air and moisture, having a great potential for industrial applications. The methodology can be applied under mechanochemical conditions maintaining the reaction outcome and selectivity. 

In this paper, we present an unprecedented and general umpolung protocol that allows the functionalization of silyl enol ethers and of 1,3-dicarbonyl compounds with a large range of heteroatom nucleophiles, including carboxylic acids, alcohols, primary and secondary amines, azide, thiols, and also anionic carbamates derived from CO₂. The scope of the reaction also extends to carbon-based nucleophiles. The reaction relies on the use of 1-bromo-3,3-dimethyl-1,3-dihydro-1λ³[d][1,2]iodaoxole, which provides a key α-brominated carbonyl intermediate. The reaction mechanism has been studied experimentally and by DFT, and we propose formation of an unusual enolonium intermediate with a halogen-bonded bromide. 

Palladium-metalated PCN-222 enables the aerobic photo-oxidative cross-condensation of anilines with benzylic amines yielding a series of linear and cyclic imines. The reaction is very efficient under mild conditions, which allows the isolation of simple, yet elusive, intermediates such as 2-(benzylideneamino)-aniline and 2-(benzylideneamino)phenols. Recyclability studies show excellent activity and selectivity after five runs. The methodology was successfully applied for the synthesis of an antitumor agent (PMX-610).

A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established. Remarkably, the method can be applied to the enantioselective synthesis of challenging chiral allylic chlorides. When the allylic halides are treated with the base triazabicyclodecene as the catalyst, a [1,3]-proton shift takes place, giving the corresponding vinyl halides in excellent yields with excellent Z:E ratios. Furthermore, the [1,3]-proton shift takes place with an outstanding level of chirality transfer from chiral allylic alcohols (<= 98%) to give chiral trifluoromethylated vinyl chlorides.

We have used experimental studies and DFT calculations to investigate the IrIII-catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination of allylic alcohols into α-chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy-barrier difference of 1.8 kcal mol−1. After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization–chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations.

A fast and operationally simple method for the aerobic homocoupling of arylboronic acids is described. The process is catalyzed by Pd(II) complexes supported on the metal-organic framework MIL-88B-NH₂(Cr). The benefits of this approach include the use of a benign oxidant/solvent mixture at room temperature with catalytic amounts of base, easy recovery of the catalyst, and easy isolation of the products. Very high conversions and good yields were achieved for a variety of substrates, and the process was also carried out on a larger scale with the same efficiency. The catalyst was found to suffer deactivation due to progressive reduction and agglomeration of palladium into inactive metal clusters/particles. An innovative procedure for the oxidative redispersion and regeneration of the active Pd(II)@MOF species is presented. 

The selective synthesis of a-functionalized ketones with two similar enolizable positions can be accomplished using allylic alcohols and iridium(III) catalysts. A formal 1,3-hydrogen shift on allylic alcohols generates catalytic iridium-enolates in a stereospecific manner, which are able to react with electrophiles to yield alpha-functionalized ketones as single constitutional isomers. However, the employment of nucleophiles to react with the nucleophilic catalytic enolates in this chemistry is still unknown. Herein, we report an umpolung strategy for the selective synthesis of alpha-alkoxy carbonyl compounds by the reaction of iridium enolates and alcohols promoted by an iodine(III) reagent. Moreover, the protocol also works in an intra-molecular fashion to synthesize 3(2H)-furanones from gamma-keto allylic alcohols. Experimental and computational investigations have been carried out, and mechanisms are proposed for both the inter- and intramolecular reactions, explaining the key role of the iodine(III) reagent in this umpolung approach.

The isomerization of dienyl alcohols and polyenyl alkyl ethers catalyzed by TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) under metal-free conditions is presented. Two reaction pathways have been observed. For dienyl alcohols, the reaction proceeds by a [1,3]-proton shift to give γ,δ-unsaturated ketones exclusively. On the other hand, the reaction with polyenyl alkyl ethers gives the corresponding conjugated vinyl ethers in good yields (up to 85%), with regioselectivities up to >20:1. Experimental and computational investigations suggest that the mechanism proceeds through consecutive “chain-walking” proton shifts (“base walk”) mediated by TBD.

A simple and quick setup for the synthesis of PCN-222 and of a variety of metalated PCN-222(Co, Ni, Cu, and Zn), using of a microwave reactor, is reported for CO2 fixation. Metalation of prophyrins by microwave heating has been evaluated through UV-vis titration. PCN-222(M) were obtained in a three-step, one-pot reaction in a remarkable 72% yield in only 30 min. The materials have been characterized using a variety of techniques. A study of CO2 fixation through cycloaddition with epoxides and azidirines using metalated PCNs as catalysts is described. Cyclic carbonates and oxazolidinones were formed using CO2 at atmospheric pressure under mild conditions. Higher activity was observed when PCN-222(Co) was used compared to that with PCN-222(Ni, Cu, Zn).

A protocol for the C-H activation/iodination of benzoic acids catalyzed by a simple iridium complex has been developed. The method described in this paper allows the ortho-selective iodination of a variety of benzoic acids under extraordinarily mild conditions in the absence of any additive or base in 1,1,1,3,3,3-hexafluoroisopropanol as the solvent. The iridium catalyst used tolerates air and moisture, and selectively gives ortho-iodobenzoic acids with high conversions. Mechanistic investigations revealed that an Ir(III)/Ir(V) catalytic cycle operates, and that the unique properties of HFIP enables the C-H iodination using the carboxylic moiety as a directing group.